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Abstract Little attention was given to heparanase 2 (Hpa2) over the last two decades, possibly because it lacks a heparan sulfate (HS)-degrading activity typical of heparanase. Emerging results suggest, nonetheless, that Hpa2 plays a role in human pathologies, including cancer progression where it functions as a tumor suppressor. Here, we examined the role of Hpa2 in cervical carcinoma. We report that high levels of Hpa2 correlate with prolonged survival of cervical carcinoma patients. Strong staining intensity of Hpa2 also correlates with low tumor grade. Overexpression of Hpa2 in SiHa cervical carcinoma cells resulted in tumor xenografts that were two-fold smaller than control tumors. Interestingly, even smaller tumor xenografts were developed by SiHa cells overexpressing the Pro140Arg and Asn543Ile Hpa2 missense mutations that were identified in patients diagnosed with urofacial syndrome (UFS). Utilizing the Ras recruitment system, we identified bromodomain-containing protein 7 (BRD7) to interact with Hpa2 and found that both BRD7 and the Hpa2 mutants are translocated to the cell nucleus in tumors developed by the Pro140Arg and Asn543Ile Hpa2 mutants. Utilizing our newly developed conditional Hpa2-KO mice, we further show that Hpa2 plays a critical role in macrophage polarization; in the absence of Hpa2, macrophages are shifted towards pro-tumorigenic, M2 phenotype. Notably, implanting SiHa cervical carcinoma cells together with Hpa2-KO macrophages promoted tumor growth. These results support, and further expand, the notion that Hpa2 functions as a tumor suppressor, co-operating with another tumor suppressor, BRD7.

Rare early-onset lower urinary tract disorders include defects of functional maturation of the bladder. Current treatments do not target the primary pathobiology of these diseases. Some have a monogenic basis, such as urofacial, or Ochoa, syndrome (UFS). Here, the bladder does not empty fully because of incomplete relaxation of its outflow tract, and subsequent urosepsis can cause kidney failure. UFS is associated with biallelic variants of HPSE2, encoding heparanase-2. This protein is detected in pelvic ganglia, autonomic relay stations that innervate the bladder and control voiding. Bladder outflow tracts of Hpse2 mutant mice display impaired neurogenic relaxation. We hypothesized that HPSE2 gene transfer soon after birth would ameliorate this defect and explored an adeno-associated viral (AAV) vector-based approach. AAV9/HPSE2, carrying human HPSE2 driven by CAG, was administered intravenously into neonatal mice. In the third postnatal week, transgene transduction and expression were sought, and ex vivo myography was undertaken to measure bladder function. In mice administered AAV9/HPSE2, the viral genome was detected in pelvic ganglia. Human HPSE2 was expressed and heparanase-2 became detectable in pelvic ganglia of treated mutant mice. On autopsy, wild-type mice had empty bladders, whereas bladders were uniformly distended in mutant mice, a defect ameliorated by AAV9/HPSE2 treatment. Therapeutically, AAV9/HPSE2 significantly ameliorated impaired neurogenic relaxation of Hpse2 mutant bladder outflow tracts. Impaired neurogenic contractility of mutant detrusor smooth muscle was also significantly improved. These results constitute first steps towards curing UFS, a clinically devastating genetic disease featuring a bladder autonomic neuropathy.

Background: Guided internet-based, cognitive behavioural therapy with a trauma-focus (i-CBT-TF) is recommended in guidelines for post-traumatic stress disorder (PTSD). There is limited evidence regarding its acceptability, with significant dropout from individual face-to-face CBT-TF, suggesting non-acceptability at least in some cases. Objective: To determine the acceptability of a guided internet-based CBT-TF intervention, ‘Spring’, in comparison with face-to-face CBT-TF for mild to moderate PTSD. Method: Treatment adherence, satisfaction, and therapeutic alliance were measured quantitatively for participants receiving ‘Spring’ or face-to-face CBT-TF as part of a Randomised Controlled Trial. Qualitative interviews were conducted with a purposive sample of therapists and participants. Results: ‘Spring’ guided internet-based CBT-TF was found to be acceptable, with over 89% participants fully or partially completing the programme. Therapy adherence and alliance for ‘Spring’ and face-to-face CBT-TF did not differ significantly, apart from post-treatment participant-reported alliance, which was in favour of face-to-face CBT-TF. Treatment satisfaction was high for both treatments, in favour of face-to-face CBT-TF. Interviews with participants receiving, and therapists delivering ‘Spring’ corroborated its acceptability. Conclusions: Guided internet-based CBT-TF is acceptable for many people with mild to moderate PTSD. Findings provide insights into future implementation, highlighting the importance of personalising guided self-help, depending on an individual’s presentation, and preferences.

ABSTRACTBackground: Post-traumatic stress disorder (PTSD) and substance use disorder (SUD) are often comorbid and difficult to treat. The availability of evidence-based treatment guidelines is very limited and there is significant uncertainty about what best practice looks like.Objective: This paper describes the methodology used to develop expert recommendations for the assessment and psychological treatment of PTSD and comorbid SUD and presents the final recommendations.Methodology: A small committee of experts in the field of PTSD and SUD was formed on behalf of the European Society for Traumatic Stress Studies (ESTSS) Board. The committee developed recommendations based on a two-stage process. In the first stage a systematic review of randomised controlled trials of psychological interventions aimed at treating PTSD-SUD comorbidity was completed, and other recent relevant reviews systematic were also considered. To complement the recommendations based on systematic review, the second stage involved the review and collation of existing guidance, good practice and consensus recommendations made in methodologically rigorous clinical practice guidelines.Results: The two-stage process resulted in 9 recommendations related to assessment and 21 recommendations related to treatment planning and delivery.Conclusions: To our knowledge, this is the first attempt to provide expert recommendations based on a systematic review of the literature and through collation of guidance provided in other authoritative and reliable sources. These expert recommendations will provide helpful guidance to clinicians and service providers in both addiction and mental health settings about appropriate clinical care for those with PTSD SUD comorbidity.

ABSTRACTBackground: ICD-11 Posttraumatic Stress Disorder (PTSD) and Complex PTSD (CPTSD) are stress-related disorders. The International Trauma Questionnaire (ITQ) is a widely used instrument to assess PTSD and CPTSD. To date, there is no evidence of the psychometric characteristics of the ITQ in Latin American countries.Objective: The aim of this study was to assess the construct and concurrent validity of the Latin American Spanish adaptation of the ITQ in a sample of Chilean adults.Methods: A sample of 275 Chilean young adults completed the ITQ, a traumatic life events checklist, the Adverse Childhood Experiences Questionnaire, the Depression Anxiety Stress Scales-21, and the Columbia-Suicide Severity Rating Scale short version. Four alternative confirmatory factor analysis models were tested. Correlation analyses were performed to determine concurrent validity with associated measures (number of reported traumatic events, number of adverse childhood experiences, anxiety, depression, and suicidal risk).Results: The second-order two-factor (PTSD and DSO) and the correlated first-order six-factor model provided acceptable fit; however, the first model showed a better fit based on the BIC difference. The PTSD and DSO dimensions, as well as the six ITQ clusters showed positive correlations with reported number of traumatic life-events, reported number of adverse childhood experiences, levels of anxiety, depression, and suicidal risk.Conclusions: The ITQ Latin American Spanish adaptation provides acceptable psychometric evidence to assess PTSD and CPTSD in accordance with the ICD-11.

Background Guided self-help has been shown to be effective for other mental conditions and, if effective for post-traumatic stress disorder, would offer a time-efficient and accessible treatment option, with the potential to reduce waiting times and costs. Objective To determine if trauma-focused guided self-help is non-inferior to individual, face-to-face cognitive-behavioural therapy with a trauma focus for mild to moderate post-traumatic stress disorder to a single traumatic event. Design Multicentre pragmatic randomised controlled non-inferiority trial with economic evaluation to determine cost-effectiveness and nested process evaluation to assess fidelity and adherence, dose and factors that influence outcome (including context, acceptability, facilitators and barriers, measured qualitatively). Participants were randomised in a 1 : 1 ratio. The primary analysis was intention to treat using multilevel analysis of covariance. Setting Primary and secondary mental health settings across the United Kingdom’s National Health Service. Participants One hundred and ninety-six adults with a primary diagnosis of mild to moderate post-traumatic stress disorder were randomised with 82% retention at 16 weeks and 71% at 52 weeks. Nineteen participants and ten therapists were interviewed for the process evaluation. Interventions Up to 12 face-to-face, manualised, individual cognitive-behavioural therapy with a trauma focus sessions, each lasting 60–90 minutes, or to guided self-help using Spring, an eight-step online guided self-help programme based on cognitive-behavioural therapy with a trauma focus, with up to five face-to-face meetings of up to 3 hours in total and four brief telephone calls or e-mail contacts between sessions. Main outcome measures Primary outcome: the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, at 16 weeks post-randomisation. Secondary outcomes: included severity of post-traumatic stress disorder symptoms at 52 weeks, and functioning, symptoms of depression, symptoms of anxiety, alcohol use and perceived social support at both 16 and 52 weeks post-randomisation. Those assessing outcomes were blinded to group assignment. Results Non-inferiority was demonstrated at the primary end point of 16 weeks on the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [mean difference 1.01 (one-sided 95% CI −∞ to 3.90, non-inferiority p = 0.012)]. Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, score improvements of over 60% in both groups were maintained at 52 weeks but the non-inferiority results were inconclusive in favour of cognitive-behavioural therapy with a trauma focus at this timepoint [mean difference 3.20 (one-sided 95% confidence interval −∞ to 6.00, non-inferiority p = 0.15)]. Guided self-help using Spring was not shown to be more cost-effective than face-to-face cognitive-behavioural therapy with a trauma focus although there was no significant difference in accruing quality-adjusted life-years, incremental quality-adjusted life-years −0.04 (95% confidence interval −0.10 to 0.01) and guided self-help using Spring was significantly cheaper to deliver [£277 (95% confidence interval £253 to £301) vs. £729 (95% CI £671 to £788)]. Guided self-help using Spring appeared to be acceptable and well tolerated by participants. No important adverse events or side effects were identified. Limitations The results are not generalisable to people with post-traumatic stress disorder to more than one traumatic event. Conclusions Guided self-help using Spring for mild to moderate post-traumatic stress disorder to a single traumatic event appears to be non-inferior to individual face-to-face cognitive-behavioural therapy with a trauma focus and the results suggest it should be considered a first-line treatment for people with this condition. Future work Work is now needed to determine how best to effectively disseminate and implement guided self-help using Spring at scale. Trial registration This trial is registered as ISRCTN13697710. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/192/97) and is published in full in Health Technology Assessment; Vol. 27, No. 26. See the NIHR Funding and Awards website for further award information. Plain language summary Post-traumatic stress disorder is a common, disabling condition that can occur following major traumatic events. Typical symptoms include distressing reliving, avoidance of reminders and feeling a current sense of threat. First-choice treatments for post-traumatic stress disorder are individual, face-to-face talking treatments, of 12–16 hours duration, including cognitive behavioural therapy with a trauma focus. If equally effective treatments could be developed that take less time and can be largely undertaken in a flexible manner at home, this would improve accessibility, reduce waiting times and hence the burden of disease. RAPID was a randomised controlled trial using a web-based programme called Spring. The aim was to determine if trauma-focused guided self-help provided a faster and cheaper treatment for post-traumatic stress disorder than first-choice face-to-face therapy, while being equally effective. Guided self-help using Spring is delivered through eight steps. A therapist provides a 1-hour introductory meeting followed by four further, fortnightly sessions of 30 minutes each and four brief (around 5 minutes) telephone calls or e-mail contacts between sessions. At each session, the therapist reviews progress and guides the client through the programme, offering continued support, monitoring, motivation and problem-solving. One hundred and ninety-six people with post-traumatic stress disorder to a single traumatic event took part in the study. Guided self-help using Spring was found to be equally effective to first-choice face-to-face therapy at reducing post-traumatic stress disorder symptoms at 16 weeks. Very noticeable improvements were maintained at 52 weeks post-randomisation in both groups, when most results were inconclusive but in favour of face-to-face therapy. Guided self-help using Spring was significantly cheaper to deliver and appeared to be well-tolerated. It is noteworthy that not everyone benefitted from guided self-help using Spring, highlighting the importance of considering it on a person-by-person basis, and personalising interventions. But, the RAPID trial has demonstrated that guided self-help using Spring provides a low-intensity treatment option for people with post-traumatic stress disorder that is ready to be implemented in the National Health Service. Scientific summary Background Post-traumatic stress disorder (PTSD) is a common mental health condition that may develop following exposure to traumatic events that involve threatened or actual death, serious injury or sexual violence. PTSD causes significant distress to those affected by it, often co-occurs with other physical and mental health conditions and is associated with a large economic burden. Face-to-face, trauma-focused psychological treatments (TFPT) have been found to be the most effective currently available treatments for PTSD and are recommended first line by treatment guidelines across the world. Unfortunately, the limited number of suitably trained therapists available to deliver TFPT in the National Health Service often prevents timely access to treatment and some people find accessing and fully engaging with face-to-face TFPT difficult for other reasons, including work commitments, travel and childcare. Guided self-help (GSH) provides an alternative approach to the delivery of treatment by combining the use of self-help materials with regular guidance from a trained professional and requires less therapist time than recommended face-to-face TFPT. GSH has been shown to be effective for other mental conditions and, if effective for PTSD, GSH would offer a time-efficient and accessible treatment option, with the potential to reduce waiting times and intervention costs. Objectives The main aim of the RAPID trial was to determine the likely clinical and cost-effectiveness of GSH using Spring, an internet-based programme based on cognitive behavioural therapies with a trauma focus (CBT-TF), for mild to moderate PTSD. RAPID also aimed to describe the experience of receiving GSH using Spring from the recipient’s perspective, and the delivery of GSH using Spring from the therapist’s perspective. The objectives were to determine if: GSH using Spring was at least equivalent in effectiveness and cost-effective relative to individual face-to-face CBT-TF for people with PTSD, as judged by reduced symptoms of PTSD and improved quality of life. GSH using Spring improved functioning and reduced symptoms of depression, symptoms of anxiety, alcohol use and perceived social support. Specific factors may impact effectiveness and successful roll-out of GSH for PTSD in the NHS. Methods RAPID was a multicentre pragmatic randomised controlled non-inferiority trial with assessors masked to treatment allocation. Individual randomisation was used. Economic evaluation was undertaken to determine cost-effectiveness and nested process evaluation to assess fidelity and adherence, dose and factors that may influence outcome (including context, acceptability, and facilitators and barriers, measured qualitatively). GSH using Spring was not expected to be more effective than face-to-face CBT-TF, and therefore, a non-inferiority design was chosen. Participants were recruited from NHS Improving Access to Psychological Therapy services based in primary care in England, and NHS psychological treatment settings based in primary and secondary care in Scotland and Wales. Wide eligibility criteria were used to ensure good external validity. Participants were aged 18 or over, had mild to moderate PTSD as their primary diagnosis, had regular access to the internet and gave informed consent to take part. Exclusion criteria were inability to read and write fluently in English, previous completion of a course of TFPT for PTSD, current PTSD symptoms to more than one traumatic event, current engagement in psychological therapy, psychosis, substance dependence, active suicide risk and change in psychotropic medication in the past 4 weeks. Participants were randomised to receive up to 12 face-to-face, manualised, individual CBT-TF sessions, each lasting 60–90 minutes, or to GSH using Spring. Spring is a manualised, eight-step online GSH programme based on CBT-TF. An initial meeting of 1 hour between the therapist and the person with PTSD is followed by four subsequent fortnightly meetings of 30 minutes, with four brief telephone calls or e-mail contacts between sessions. The primary outcome was the severity of symptoms of PTSD over the previous week as measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) at 16 weeks post-randomisation. Secondary outcomes included severity of PTSD symptoms at 52 weeks, and functioning, symptoms of depression, symptoms of anxiety, alcohol use, and perceived social support at both 16 and 52 weeks post-randomisation. Resource use was also collected to support the health economic evaluation. Semistructured interviews were conducted with 19 participants and 10 therapists as part of the process evaluation, to gather perspectives of receiving and delivering the interventions, to examine underlying mechanisms and factors influencing future implementation. Results One hundred and ninety-six participants were randomised with 82% retention at 16 weeks and 71% at 52 weeks. There were no serious imbalances observed in the baseline data between the two groups. Non-inferiority (margin of 5 points) was demonstrated at the primary endpoint of 16 weeks on the CAPS-5 using the intention to treat principle [mean difference 1.0, 95% one-sided confidence interval (CI) (−∞, 3.9, non-inferiority p = 0.012)]. This was also the case for all secondary outcomes at this time point, except for client satisfaction that was inconclusive but in favour of CBT-TF. At 52 weeks post-randomisation, non-inferiority was shown for Multidimensional Scale for Perceived Social Support (MSPSS), Alcohol Use Disorders Test and GSES; non-inferiority was not shown for the other outcomes but the results, which were inconclusive, were in favour of CBT-TF. Further examination of the Impact of Event Scale-Revised (IES-R) longitudinal measurements indicated that while the GSH group maintained their reduction (improvement) in IES-R scores between the 16- and 52-week assessments, the CBT-TF group continued to improve at a slow rate over the same period. There were no subgroup effects that showed any evidence of difference between the interventions including gender (pre-specified), mode of data collection or assessments conducted after the introduction of the COVID-19 lockdown. Spring was cheaper to deliver than face-to-face CBT TF [£277 (95% CI £253 to £301) vs. £729 (95% CI £671 to £788)]. When total costs were included, Spring was £572 (95% CI £64.96 to £1080.14) cheaper and produced but derived fewer quality-adjusted life-years (QALYs) compared to CBT-TF, −0.04 (95% CI −0.10 to 0.01). At a willingness-to-pay threshold of £30,000 per QALY gained, the probability of GSH being cost-effective was 29.74%. The process data provided evidence of acceptability of the overall trial methodology, although key points were identified for consideration in future randomised controlled design, especially concerning burden and impact of outcome measures on participants and how they are delivered and explained. Intervention acceptability was indicated for both GSH and CBT-TF interventions, although there was a preference for face-to-face treatment. Therapeutic relationship was an important factor highlighted in the acceptability of the interventions. Flexibility identified with GSH was seen as positive and some activities within Spring were described as more helpful than others. Conclusions Implications for health care GSH using Spring was found to be non-inferior to face-to-face CBT-TF at treating people with mild to moderate PTSD. Significant gains were maintained in the GSH using Spring group at 52 weeks but some ongoing improvements in the CBT-TF group appeared to result in largely inconclusive findings with respect to non-inferiority at 52 weeks. The additional benefits of GSH using Spring with respect to time, cost and convenience, and having another evidence-based treatment option could be argued as outweighing what appear to be minor differences at 52 weeks. The results of the RAPID trial should herald a step change in the approach of services to the provision of evidence-based treatment to people with mild to moderate PTSD. There is now an urgent need to make GSH using Spring available as a low-intensity treatment option for people with PTSD. Future research implications How best to effectively disseminate and implement GSH using Spring at scale, to maximise its impact, is a key research question. This includes identification of the specific skill set and competencies required by a guiding clinician to foster effective alliance and engagement, and the optimal level of training and supervision required for the provision of GSH using Spring. The optimal amount of guidance is unclear. The quantitative and qualitative results strongly suggest that the current number of facilitation sessions is right for most people but that some people could probably benefit with more. Research into the impact of increased flexibility in delivery and more personalised adaptations is desirable. Research is also required to understand the extent to which individuals may or may not be excluded from internet-based treatments due to language and literacy issues, and online access issues, and how best to address these. Trial registration This trial is registered as ISRCTN13697710. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/192/97) and is published in full in Health Technology Assessment; Vol. 27, No. 26. See the NIHR Funding and Awards website for further award information.

Abstract Background The 11th revision of the International Classification of Diseases (ICD-11) includes a new diagnosis of complex posttraumatic stress disorder (CPTSD). There has been very little research investigating associations between CPTSD symptoms and suicide risk following sexual abuse. This and questions concerning similarities and differences between CPTSD and borderline personality disorder (BPD), led to the current study that aimed to explore indirect associations between sexual abuse and suicide risk through the symptoms of CPTSD and borderline traits. Methods The study sample comprised 103 adults with a history of traumatic experiences (M age = 32.64, SD age = 9.36; 83.5% female). In total, 26.3% of the participants reported experiencing sexual abuse during their lifetime. The clinician-administered International Trauma Interview (ITI) was used for the assessment of ICD-11 CPTSD symptoms. Self-report measures were used for the evaluation of borderline pattern (BP) symptoms and suicide risk. Mediation analyses were performed to evaluate the mediating effects of CPTSD and BP symptoms for the association between sexual trauma and suicide risk. Results In a parallel mediation model, CPTSD and BP symptoms mediated the association between sexual abuse and suicide risk, following adjustment for the covariates of age, gender, and whether the traumatic experience occurred in childhood or adulthood. Around 73% of participants who met diagnostic criteria for CPTSD reported previous suicide attempt(s). Conclusions Suicide risk assessment and intervention should be an important part of the management of victims of sexual abuse with CPTSD and BP symptoms.

Background Current psychiatric diagnoses, although heritable, have not been clearly mapped onto distinct underlying pathogenic processes. The same symptoms often occur in multiple disorders, and a substantial proportion of both genetic and environmental risk factors are shared across disorders. However, the relationship between shared symptoms and shared genetic liability is still poorly understood. Aims Well-characterised, cross-disorder samples are needed to investigate this matter, but few currently exist. Our aim is to develop procedures to purposely curate and aggregate genotypic and phenotypic data in psychiatric research. Method As part of the Cardiff MRC Mental Health Data Pathfinder initiative, we have curated and harmonised phenotypic and genetic information from 15 studies to create a new data repository, DRAGON-Data. To date, DRAGON-Data includes over 45 000 individuals: adults and children with neurodevelopmental or psychiatric diagnoses, affected probands within collected families and individuals who carry a known neurodevelopmental risk copy number variant. Results We have processed the available phenotype information to derive core variables that can be reliably analysed across groups. In addition, all data-sets with genotype information have undergone rigorous quality control, imputation, copy number variant calling and polygenic score generation. Conclusions DRAGON-Data combines genetic and non-genetic information, and is available as a resource for research across traditional psychiatric diagnostic categories. Algorithms and pipelines used for data harmonisation are currently publicly available for the scientific community, and an appropriate data-sharing protocol will be developed as part of ongoing projects (DATAMIND) in partnership with Health Data Research UK.

Abstract Diabetes mellitus (DM) is the leading cause of chronic kidney disease and diabetic nephropathy is widely studied. In contrast, the pathobiology of diabetic urinary bladder disease is less understood despite dysfunctional voiding being common in DM. We hypothesised that diabetic cystopathy has a characteristic molecular signature. We therefore studied bladders of hyperglycaemic and polyuric rats with streptozotocin (STZ)-induced DM. Sixteen weeks after induction of DM, as assessed by RNA arrays, wide-ranging changes of gene expression occurred in DM bladders over and above those induced in bladders of non-hyperglycaemic rats with sucrose-induced polyuria. The altered transcripts included those coding for extracellular matrix regulators and neural molecules. Changes in key genes deregulated in DM rat bladders were also detected in db/db mouse bladders. In DM rat bladders there was reduced birefringent collagen between detrusor muscle bundles, and atomic force microscopy showed a significant reduction in tissue stiffness; neither change was found in bladders of sucrose-treated rats. Thus, altered extracellular matrix with reduced tissue rigidity may contribute to voiding dysfunction in people with long-term DM. These results serve as an informative stepping stone towards understanding the complex pathobiology of diabetic cystopathy.

Background The psychological treatment of comorbid post-traumatic stress disorder (PTSD) and substance use disorder (SUD) is clinically challenging, and outcomes are often poor. Objective This paper describes a systematic review and meta-analysis which sought to establish the current efficacy for a number of established psychological approaches for adults and adolescents, in comparison to interventions for SUD alone, or other active approaches, following a pre-registered protocol. Method This review followed PRISMA and Cochrane Collaboration guidelines. Data extraction and risk of bias judgements using Cochrane criteria were undertaken by all authors. Primary outcomes were PTSD severity and substance use post-treatment. The quality of findings was assessed using GRADE. Following a comprehensive search, conducted to 13 September 2021, 27 studies were included. Results We found a relatively high level of dropout across studies. In our main comparisons, we found no benefits for present-focused treatment approaches aimed at improving coping skills beyond those for SUD-only interventions. We found modest benefits for trauma-focused intervention plus SUD intervention post-treatment for PTSD (standardized mean difference (SMD) = −0.36, 95% confidence interval (CI) −0.64, −0.08), and at 6–13 months for PTSD (SMD = −0.48, 95% CI −0.81, −0.15) and alcohol use (SMD = −0.23, 95% CI −0.44, −0.02). There were no benefits for cognitive restructuring interventions as a group, but we found a modest effect for integrated cognitive behavioural therapy (ICBT) for PTSD post-treatment (SMD = −0.33, 95% CI −0.62, −0.04). There was evidence of some benefit for trauma-focused intervention over present-focused intervention for PTSD from a single study and for reduction in dropout for incentivized attendance for trauma-focused intervention from another single study. Most findings were of very low quality. Conclusion There is evidence that trauma-focused therapy and ICBT can improve PTSD for some individuals, but many patients do not fully engage with treatment and average treatment effects are modest. HIGHLIGHTS For PTSD, evidence was strongest for trauma-focused CBT-based approaches, but effects were modest. There was little evidence of any added benefit on substance use, beyond that of standard addiction treatments, for any included intervention. Dropout from treatment was high

Background The 11th revision of the International Classification of Diseases (ICD-11) includes a new diagnosis of complex posttraumatic stress disorder (CPTSD). The International Trauma Interview (ITI) is a novel clinician-administered diagnostic interview for the assessment of ICD-11 PTSD and CPTSD. Objective The aim of this study was to evaluate the psychometric properties of the ITI in a Lithuanian sample in relation to interrater agreement, latent structure, internal reliability, as well as convergent and discriminant validity. Method In total, 103 adults with a history of various traumatic experiences participated in the study. The sample was predominantly female (83.5%), with a mean age of 32.64 years (SD = 9.36). For the assessment of ICD-11 PTSD and CPTSD, the ITI and the self-report International Trauma Questionnaire (ITQ) were used. Mental health indicators, such as depression, anxiety, and dissociation, were measured using self-report questionnaires. The latent structure of the ITI was evaluated using confirmatory factor analysis (CFA). In order to test the convergent and discriminant validity of the ITI we conducted a structural equation model (SEM). Results Overall, based on the ITI, 18.4% of participants fulfilled diagnostic criteria for PTSD and 21.4% for CPTSD. A second-order two-factor CFA model of the ITI PTSD and disturbances in self-organization (DSO) symptoms demonstrated a good fit. The associations with various mental health indicators supported the convergent and discriminant validity of the ITI. The clinician-administered ITI and self-report ITQ had poor to moderate diagnostic agreement across different symptom clusters. Conclusion The ITI is a reliable and valid tool for assessing and diagnosing ICD-11 PTSD and CPTSD.

Urofacial (also called Ochoa) syndrome (UFS) is an autosomal recessive congenital disorder of the urinary bladder featuring voiding dysfunction and a grimace upon smiling. Biallelic variants in HPSE2, coding for the secreted protein heparanase-2, are described in around half of families genetically studied. Hpse2 mutant mice have aberrant bladder nerves. We sought to expand the genotypic spectrum of UFS and make insights into its pathobiology. Sanger sequencing, next generation sequencing and microarray analysis were performed in four previously unreported families with urinary tract disease and grimacing. In one, the proband had kidney failure and was homozygous for the previously described pathogenic variant c.429T>A, p.(Tyr143*). Three other families each carried a different novel HPSE2 variant. One had homozygous triplication of exons 8 and 9; another had homozygous deletion of exon 4; and another carried a novel c.419C>G variant encoding the missense p.Pro140Arg in trans with c.1099-1G>A, a previously reported pathogenic splice variant. Expressing the missense heparanase-2 variant in vitro showed that it was secreted as normal, suggesting that 140Arg has aberrant functionality after secretion. Bladder autonomic neurons emanate from pelvic ganglia where resident neural cell bodies derive from migrating neural crest cells. We demonstrated that, in normal human embryos, neuronal precursors near the developing hindgut and lower urinary tract were positive for both heparanase-2 and leucine rich repeats and immunoglobulin like domains 2 (LRIG2). Indeed, biallelic variants of LRIG2 have been implicated in rare UFS families. The study expands the genotypic spectrum in HPSE2 in UFS and supports a developmental neuronal pathobiology.

Background ICD-11 includes a new diagnosis of complex post-traumatic stress disorder (CPTSD), resulting predominantly from reoccurring or prolonged trauma. Previous studies showed that lack of social support is among the strongest predictors of PTSD, but social factors have been sparsely studied in the context of the ICD-11 definition of PTSD and CPTSD. Aims To analyse the factor structure of the International Trauma Questionnaire (ITQ) in a Lithuanian clinical sample and to evaluate the mediating role of social and interpersonal factors in the relationship between trauma exposure and ICD-11 PTSD and CPTSD. Method The sample comprised 280 adults from out-patient mental health centres (age, years: mean 39.48 (s.d. = 13.35); 77.5% female). Trauma-related stress symptoms were measured with the ITQ. Social disapproval was measured with the Social Acknowledgment Questionnaire (SAQ) and trauma disclosure using the Disclosure of Trauma Questionnaire (DTQ). Results ICD-11 PTSD and CPTSD prevalence among the participants in this study was 13.9% and 10.0% respectively. Results indicated that avoidance of trauma disclosure mediated the relationship between trauma exposure and PTSD as well as CPTSD, whereas social disapproval mediated only the relationship between trauma exposure and CPTSD. Conclusions The findings suggest that disclosure of traumatic experiences and support from closest friends and family members might mitigate the effects of traumatic experiences, potentially reducing the risk of developing CPTSD.

Background: PTSD and substance use disorder (SUD) frequently co-occur. Estimates of life time PTSD amongst SUD patients range from 26% to 52%, with estimates of current PTSD between 15% and 42%. Amongst individual diagnosed with PTSD estimates of comorbid substance abuse range from 19% to 35% and comorbid alcohol abuse from 36% to 52% (Roberts, Roberts, Jones, & Bisson, ). PTSD-SUD comorbidity presents many clinical challenges for treating clinicians. Individuals with PTSD-SUD present with a more severe clinical profile, tend to have poorer functioning and wellbeing, and inferior treatment outcomes. Clinicians view this comorbidity to be substantially more difficult to treat than either disorder alone (Schäfer & Lotzin, ). There are now a number of well-established psychological therapies for PTSD. These include prolonged exposure, cognitive therapy, cognitive processing therapy and EMDR (Bisson et al., ). However, patients with PTSD-SUD comorbidity are often excluded from clinical trials of psychological intervention. Clinicians are therefore often uncertain about how best to implement effective treatment, and traditionally, patients with this comorbidity have been offered treatment sequentially. This normally involves referral for to PTSD treatment only after completion of treatment for addiction (Roberts, Back, Mueser, & Murray, ). However, there are concerns about whether this approach causes some patients to ‘fall through the cracks’ between services and there is debate about whether integrated or simultaneous approaches might be more effective. A number of integrated treatment approaches have been developed. These are often grouped into past focused treatments, which include components of exposure-based trauma processing; and present focused treatments, which focus more on improving current coping skills (see Roberts et al., ). Recent reviews have tended to report more support for exposure-based approaches, particularly in relation to PTSD outcomes (Roberts et al., ), although findings have been based on a small number of studies and high drop-out from treatment has been noted as a problem across different approaches. Most recent guidelines (e.g. ISTSS 2018 – see NICE ; Bisson et al., ) have not included scoping questions to address issues of comorbidity, and there are no widely accepted guidelines about how to deliver optimal care and treatment for such individuals. Objectives and methodology: To describe the work of a task force which has been established to develop expert recommendations for the psychological treatment of this comorbidity for ESTSS, following principles used in guideline development through two stages. Stage 1. Update of a systematic review and meta-analysis (Roberts et al., ) of RCTs of psychological interventions aimed at treating comorbid PTSD and SUD, with the aim of establishing the current evidence base for a number of approaches including: Trauma focused CBT trauma focused treatments plus treatment as usual for SUD, such as COPE Present focused treatments such as Seeking Safety plus treatment as usual for SUD Integrated cognitive restructuring-based interventions plus treatment as usual for SUD EMDR plus treatment as usual for SUD. The working group also seeks to investigate whether there is evidence for different models of treatment delivery: i.e. sequential treatments, vs. integrated treatments delivered by the same therapist vs simultaneous treatments delivered by different therapists. Treatment recommendations will be based on the strength and quality of the findings addressing which will be evaluated through the GRADE approach. Stage 2. It is anticipated that many of the challenges faced in clinical practice are unlikely to be addressed through the Stage 1 process, where there is limited high-quality evidence to make evidence-based recommendations. Stage 2 will involve the collation good practice/consensus point recommendations made in trusted methodologically rigorous treatment guidelines and expert guidance publications. Findings and Recommendations: This project is currently ongoing. The presentation will provide an update of the progress of the working group, share preliminary findings where these are available and make recommendations for future research.

Background: Pharmacological-assisted psychotherapies, using conventional and novel drug agents, are increasingly being used both in clinical and experimental research settings, respectively. Objective: To determine the efficacy of conventional and novel pharmacological-assisted psychotherapies in reducing PTSD symptom severity. Method: A systematic review and meta-analysis of randomised-controlled trials were undertaken; 21 studies were included. Results: MDMA-assisted therapy was found to statistically superior to active and inactive placebo-assisted therapy in reduction of PTSD symptoms (standardised mean difference −1.09, 95% CI −1.60 to −0.58). There was no evidence of superiority over placebo for any other intervention. Conclusions: MDMA-assisted therapy demonstrated an impressive effect size; however, it is difficult to have confidence at this stage in this intervention due to the small numbers of participants included, and more research in this area is needed. There was no evidence to support the efficacy of any other drug-assisted interventions.

Background: PTSD self-report measures are frequently used in mental health services but very few have been evaluated in clinical samples that include civilians. The PCL-5 was developed to assess for DSM-5 PTSD. Objective: The aim of this study was to evaluate the psychometric properties of the PCL-5 in a sample of trauma-exposed mental health service users who were evidencing symptoms of PTSD. Method: Reliability and validity of the PCL-5 were investigated in a sample of 273 participants who reported past diagnosis for PTSD or who had screened positively for traumatic stress symptoms. Diagnostic utility was evaluated in comparison to the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Results: The PCL-5 demonstrated high internal consistency, good convergent and divergent validity, acceptable stability and good diagnostic utility. However, operating characteristics differed from those found in other samples. Scores of 43–44 provided optimal efficiency for diagnosing PTSD. A post hoc regression analysis showed that depression explained more of the variance in PCL-5 total score than the CAPS-5. Conclusion: Whilst the PCL-5 is psychometrically sound it appears to have difficulty differentiating self-reported depression and anxiety symptoms from PTSD in trauma-exposed mental health service users and clinicians should take care to assess full symptomatology when individuals screen positively on the PCL-5. Clinicians and researchers should also take care not to assume that operating characteristics of self-report PTSD measures are valid for mental health service users, when these have been established in other populations.

Background: An increasing body of research highlights reconsolidation-based therapies as emerging treatments for post-traumatic stress disorder (PTSD). The Rewind Technique is a non-pharmacological reconsolidation-based therapy with promising early results, which now requires evaluation through an RCT. Objectives: This is a preliminary efficacy RCT to determine if the Rewind Technique is likely to be a good candidate to test against usual care in a future pragmatic efficacy RCT. Methods: 40 participants will be randomised to receive either the Rewind Technique immediately, or after an 8 week wait. The primary outcome will be PTSD symptom severity as measured by the Clinician-Administered PTSD Scale for DSM5 (CAPS-5) at 8 and 16 weeks post-randomisation. Secondary outcome measures include the PTSD Checklist (PCL-5), International Trauma Questionnaire (ITQ), Patient Health Questionnaire (PHQ-9), the General Anxiety Disorder-7 (GAD-7), Insomnia Severity Index, the Euro-Qol-5D (EQ5D-5 L), the prominence of re-experiencing specific symptoms (CAPS-5) and an intervention acceptability questionnaire to measure tolerability of the intervention. Conclusions: This study will be the first RCT to assess the Rewind Technique. Using a cross-over methodology we hope to rigorously assess the efficacy and tolerability of Rewind using pragmatic inclusion criteria. Potential challenges include participant recruitment and retention. Trial registration: ISRCTN91345822

Background: Pharmacological approaches are widely used for post-traumatic stress disorder (PTSD) despite uncertainty over efficacy. Objectives: To determine the efficacy of all pharmacological approaches, including monotherapy, augmentation and head-to-head approaches (drug versus drug, drug versus psychotherapy), in reducing PTSD symptom severity. Method: A systematic review and meta-analysis of randomised controlled trials were undertaken; 115 studies were included. Results: Selective serotonin reuptake inhibitors (SSRIs) were found to be statistically superior to placebo in reduction of PTSD symptoms but the effect size was small (standardised mean difference −0.28, 95% CI −0.39 to −0.17). For individual monotherapy agents compared to placebo in two or more studies, we found small statistically significant evidence for the antidepressants fluoxetine, paroxetine, sertraline, venlafaxine and the antipsychotic quetiapine. For pharmacological augmentation, we found small statistically significant evidence for prazosin and risperidone. Conclusions: Some medications have a small positive effect on reducing PTSD symptom severity and can be considered as potential monotherapy treatments; these include fluoxetine, paroxetine, sertraline, venlafaxine and quetiapine. Two medications, prazosin and risperidone, also have a small positive effect when used to augment pharmacological monotherapy. There was no evidence of superiority for one intervention over another in the small number of head-to-head comparison studies.

Background: Despite the established efficacy of psychological therapies for post-traumatic stress disorder (PTSD) there has been little systematic exploration of dropout rates. Objective: To ascertain rates of dropout across different modalities of psychological therapy for PTSD and to explore potential sources of heterogeneity. Method: A systematic review of dropout rates from randomized controlled trials (RCTs) of psychological therapies was conducted. The pooled rate of dropout from psychological therapies was estimated and reasons for heterogeneity explored using meta-regression. Results:: The pooled rate of dropout from RCTs of psychological therapies for PTSD was 16% (95% CI 14–18%). There was evidence of substantial heterogeneity across studies. We found evidence that psychological therapies with a trauma-focus were significantly associated with greater dropout. There was no evidence of greater dropout from therapies delivered in a group format; from studies that recruited participants from clinical services rather than via advertisements; that included only military personnel/veterans; that were limited to participants traumatized by sexual traumas; that included a higher proportion of female participants; or from studies with a lower proportion of participants who were university educated. Conclusions: Dropout rates from recommended psychological therapies for PTSD are high and this appears to be particularly true of interventions with a trauma focus. There is a need to further explore the reasons for dropout and to look at ways of increasing treatment retention.

Background Non-pharmacological and non-psychological approaches to the treatment of post-traumatic stress disorder (PTSD) have often been excluded from systematic reviews and meta-analyses. Consequently, we know little regarding their efficacy. Objective To determine the effect sizes of non-pharmacological and non-psychological treatment approaches for PTSD. Method We undertook a systematic review and meta-analyses following Cochrane Collaboration guidelines. A pre-determined definition of clinical importance was applied to the results and the quality of evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Results 30 randomised controlled trials (RCTs) of a range of heterogeneous non-psychological and non-pharmacological interventions (28 in adults, two in children and adolescents) were included. There was emerging evidence for six different approaches (acupuncture, neurofeedback, saikokeishikankyoto (a herbal preparation), somatic experiencing, transcranial magnetic stimulation, and yoga). Conclusions Given the level of evidence available, it would be premature to offer non-pharmacological and non-psychological interventions routinely, but those with evidence of efficacy provide alternatives for people who do not respond to, do not tolerate or do not want more conventional evidence-based interventions. This review should stimulate further research in this area.

Background: Psychological therapies are the recommended first-line treatment for post-traumatic stress disorder (PTSD). Previous systematic reviews have grouped theoretically similar interventions to determine differences between broadly distinct approaches. Consequently, we know little regarding the relative efficacy of the specific manualized therapies commonly applied to the treatment of PTSD. Objective: To determine the effect sizes of manualized therapies for PTSD. Methods: We undertook a systematic review following Cochrane Collaboration guidelines. A pre-determined definition of clinical importance was applied to the results and the quality of evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Results: 114 randomized-controlled trials (RCTs) of 8171 participants were included. There was robust evidence that the therapies broadly defined as CBT with a trauma focus (CBT-T), as well as Eye Movement Desensitization and Reprocessing (EMDR), had a clinically important effect. The manualized CBT-Ts with the strongest evidence of effect were Cognitive Processing Therapy (CPT); Cognitive Therapy (CT); and Prolonged Exposure (PE). There was also some evidence supporting CBT without a trauma focus; group CBT with a trauma focus; guided internet-based CBT; and Present Centred Therapy (PCT). There was emerging evidence for a number of other therapies. Conclusions: A recent increase in RCTs of psychological therapies for PTSD, results in a more confident recommendation of CBT-T and EMDR as the first-line treatments. Among the CBT-Ts considered by the review CPT, CT and PE should be the treatments of choice. The findings should guide evidence informed shared decision-making between patient and clinician.

This letter to the editor responds to a recent EJPT editorial and following commentary which express concerns about the validity of the ICD-11 complex PTSD (CPTSD) diagnosis. Achterhof and colleagues caution that latent profile analyses and latent class analyses, which have been frequently used to demonstrate the discriminative validity of the ICD-11 PTSD and CPTSD constructs, have limitations and cannot be relied on to definitively determine the validity of the diagnosis. Ford takes a broader perspective and introduces the concept of ‘cPTSD’ which describes a wide ranging set of symptoms identified from studies related to DSM-IV, DSM-V and ICD-11 and proposes that the validity of the ICD-11 CPTSD is in question as it does not address the multiple symptoms identified from previous trauma-related disorders. We argue that ICD-11 CPTSD is a theory-driven, empirically supported construct that has internal consistency and conceptual coherence and that it need not explain nor resolve the inconsistencies of past formulations to demonstrate its validity. We do agree with Ford and with Achterhof and colleagues that no one single statistical process can definitively answer the question of whether CPTSD is a valid construct. We reference several studies utilizing many different statistical approaches implemented across several countries, the overwhelming majority of which have supported the validity of ICD-11 as a unique construct. We conclude with our own cautions about ICD-11 CPTSD research to date and identify important next steps.

BackgroundComplex traumatic events associated with armed conflict, forcible displacement, childhood sexual abuse, and domestic violence are increasingly prevalent. People exposed to complex traumatic events are at risk of not only posttraumatic stress disorder (PTSD) but also other mental health comorbidities. Whereas evidence-based psychological and pharmacological treatments are effective for single-event PTSD, it is not known if people who have experienced complex traumatic events can benefit and tolerate these commonly available treatments. Furthermore, it is not known which components of psychological interventions are most effective for managing PTSD in this population. We performed a systematic review and component network meta-analysis to assess the effectiveness of psychological and pharmacological interventions for managing mental health problems in people exposed to complex traumatic events.Methods and findingsWe searched CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Published International Literature on Traumatic Stress, PsycINFO, and Science Citation Index for randomised controlled trials (RCTs) and non-RCTs of psychological and pharmacological treatments for PTSD symptoms in people exposed to complex traumatic events, published up to 25 October 2019. We adopted a nondiagnostic approach and included studies of adults who have experienced complex trauma. Complex-trauma subgroups included veterans; childhood sexual abuse; war-affected; refugees; and domestic violence. The primary outcome was reduction in PTSD symptoms. Secondary outcomes were depressive and anxiety symptoms, quality of life, sleep quality, and positive and negative affect. We included 116 studies, of which 50 were conducted in hospital settings, 24 were delivered in community settings, seven were delivered in military clinics for veterans or active military personnel, five were conducted in refugee camps, four used remote delivery via web-based or telephone platforms, four were conducted in specialist trauma clinics, two were delivered in home settings, and two were delivered in primary care clinics; clinical setting was not reported in 17 studies. Ninety-four RCTs, for a total of 6,158 participants, were included in meta-analyses across the primary and secondary outcomes; 18 RCTs for a total of 933 participants were included in the component network meta-analysis. The mean age of participants in the included RCTs was 42.6 ± 9.3 years, and 42% were male. Nine non-RCTs were included. The mean age of participants in the non-RCTs was 40.6 ± 9.4 years, and 47% were male. The average length of follow-up across all included studies at posttreatment for the primary outcome was 11.5 weeks. The pairwise meta-analysis showed that psychological interventions reduce PTSD symptoms more than inactive control (k = 46; n = 3,389; standardised mean difference [SMD] = -0.82, 95% confidence interval [CI] -1.02 to -0.63) and active control (k-9; n = 662; SMD = -0.35, 95% CI -0.56 to -0.14) at posttreatment and also compared with inactive control at 6-month follow-up (k = 10; n = 738; SMD = -0.45, 95% CI -0.82 to -0.08). Psychological interventions reduced depressive symptoms (k = 31; n = 2,075; SMD = -0.87, 95% CI -1.11 to -0.63; I2 = 82.7%, p = 0.000) and anxiety (k = 15; n = 1,395; SMD = -1.03, 95% CI -1.44 to -0.61; p = 0.000) at posttreatment compared with inactive control. Sleep quality was significantly improved at posttreatment by psychological interventions compared with inactive control (k = 3; n = 111; SMD = -1.00, 95% CI -1.49 to -0.51; p = 0.245). There were no significant differences between psychological interventions and inactive control group at posttreatment for quality of life (k = 6; n = 401; SMD = 0.33, 95% CI -0.01 to 0.66; p = 0.021). Antipsychotic medicine (k = 5; n = 364; SMD = -0.45; -0.85 to -0.05; p = 0.085) and prazosin (k = 3; n = 110; SMD = -0.52; -1.03 to -0.02; p = 0.182) were effective in reducing PTSD symptoms. Phase-based psychological interventions that included skills-based strategies along with trauma-focused strategies were the most promising interventions for emotional dysregulation and interpersonal problems. Compared with pharmacological interventions, we observed that psychological interventions were associated with greater reductions in PTSD and depression symptoms and improved sleep quality. Sensitivity analysis showed that psychological interventions were acceptable with lower dropout, even in studies rated at low risk of attrition bias. Trauma-focused psychological interventions were superior to non-trauma-focused interventions across trauma subgroups for PTSD symptoms, but effects among veterans and war-affected populations were significantly reduced. The network meta-analysis showed that multicomponent interventions that included cognitive restructuring and imaginal exposure were the most effective for reducing PTSD symptoms (k = 17; n = 1,077; mean difference = -37.95, 95% CI -60.84 to -15.16). Our use of a non-diagnostic inclusion strategy may have overlooked certain complex-trauma populations with severe and enduring mental health comorbidities. Additionally, the relative contribution of skills-based intervention components was not feasibly evaluated in the network meta-analysis.ConclusionsIn this systematic review and meta-analysis, we observed that trauma-focused psychological interventions are effective for managing mental health problems and comorbidities in people exposed to complex trauma. Multicomponent interventions, which can include phase-based approaches, were the most effective treatment package for managing PTSD in complex trauma. Establishing optimal ways to deliver multicomponent psychological interventions for people exposed to complex traumatic events is a research and clinical priority.

Background: Perceived social support (PSS) is one of the most important risk factors for the onset and maintenance of posttraumatic stress disorder (PTSD) symptoms, however the relationship between PSS and Complex PTSD (CPTSD) is unknown. The evidence-base for CPTSD treatment is currently lacking, though increasingly important given the recent publication of the ICD-11, which now allows for a formal diagnosis of CPTSD. Objective: This research aims to develop understanding of the relationship between PSS and CPTSD with a view to informing the development of new and existing treatments. Method: A cross-sectional study was undertaken with 246 individuals recruited to the National Centre for Mental Health (NCMH) cohort. Measures of PSS and PTSD/CPTSD were undertaken with this clinical sample and linear and logistic regression were conducted to assess for associations between PSS and the PTSD symptom clusters of DSM-5 and ICD-11, and to explore the predictive utility of any PSS association on the likelihood of a CPTSD presentation. Results: It was found that individuals with a presentation of CPTSD tend to exhibit lower levels of PSS, compared with individuals not presenting with CPTSD, and lower PSS had a statistically significant unique association with the likelihood of presenting with CPTSD. Conclusions: Intervention aiming to improve PSS could be particularly helpful for some individuals with CPTSD, especially those with disturbances in relationships, and there is opportunity to develop skills training within a phase-based approach to treatment that targets factors related to PSS.

Background: Post-traumatic stress disorder (PTSD) is a major cause of morbidity amongst active duty and ex-serving military personnel. In recent years increasing efforts have been made to develop more effective treatments. Objective: To determine which psychological therapies are efficacious in treating active duty and ex-serving military personnel with post-traumatic stress disorder (PTSD). Method: A systematic review was undertaken according to Cochrane Collaboration Guidelines. The primary outcome measure was reduction in PTSD symptoms and the secondary outcome dropout. Results: Twenty-four studies with 2386 participants were included. Evidence demonstrated that CBT with a trauma focus (CBT-TF) was associated with the largest evidence of effect when compared to waitlist/usual care in reducing PTSD symptoms post treatment (10 studies; n = 524; SMD −1.22, −1.78 to −0.66). Group CBT-TF was less effective when compared to individual CBT-TF at reducing PTSD symptoms post treatment (1 study; n = 268; SMD −0.35, −0.11 to −0.59). Eye Movement Desensitization and Reprocessing (EMDR) therapy was not effective when compared to waitlist/usual care at reducing PTSD symptoms post treatment (4 studies; n = 92; SMD −0.83, −1.75 to 0.10). There was evidence of greater dropout from CBT-TF therapies compared to waitlist and Present Centred Therapy. Conclusions: The evidence, albeit limited, supports individual CBT-TF as the first-line psychological treatment of PTSD in active duty and ex-serving personnel. There is evidence for Group CBT-TF, but this is not as strong as for individual CBT-TF. EMDR cannot be recommended as a first line therapy at present and urgently requires further evaluation. Lower effect sizes than for other populations with PTSD and high levels of drop-out suggest that CBT-TF in its current formats is not optimally acceptable and further research is required to develop and evaluate more effective treatments for PTSD and complex PTSD in active duty and ex-serving military personnel.

Background: The recently published ICD-11 includes substantial changes to the diagnosis of posttraumatic stress disorder (PTSD) and introduces the diagnosis of Complex PTSD (CPTSD). The International Trauma Interview (ITI) has been developed for clinicians to assess these new diagnoses but has not yet been evaluated. Objectives: To evaluate the psychometric properties of the Swedish translation of the ITI by examining the interrater agreement, latent structure, internal consistency, and convergent and discriminant validity. Methods: In a prospective study, 186 adults who had experienced a potentially traumatic event were assessed with the ITI and answered questionnaires for symptoms of posttraumatic stress, other psychiatric disorders, functional disability, and quality of life (QoL). Results: The diagnostic rate was 16% for PTSD and 6% for CPTSD. Interrater agreement was satisfactory (α = .76), and confirmatory factor analysis indicated that a two-factor second-20 order model consistent with the ICD-11 model of CPTSD provided acceptable fit to the data. Composite reliability analysis demonstrated that the ITI possessed acceptable internal reliability, and associations with measures of other psychiatric disorders, insomnia, functional disability, and QoL supported the concurrent validity of the ITI. Conclusion: Swedish ITI shows promise as a clinician-administered instrument to assess and diagnose ICD-11 PTSD and CPTSD.

Background: Internet-delivered Cognitive Behavioural Therapy (i-CBT) offers potential as an alternative, accessible, clinically and cost-effective treatment for post-traumatic stress disorder (PTSD), but little is known about its acceptability. Objective: To review the available evidence to understand the acceptability of i-CBT for PTSD. Method: We undertook a mixed-methods systematic review according to Cochrane Collaboration Guidelines, of randomised controlled trials (RCTs) of i-CBT for adults with PTSD. We examined included studies for measures of acceptability, and possible proxy indicators of acceptability, including dropout rates, which were meta-analysed as risk ratios (RRs). Results: Ten studies with 720 participants were included. We found i-CBT to be acceptable according to specific acceptability measures, and suggestions for acceptability according to some proxy measures of i-CBT programme usage. There was, however, evidence of greater dropout from i-CBT than waitlist (RR 1.39, CI 1.03–1.88; 8 studies; participants = 585) and no evidence of a difference in dropout between i-CBT and i-non-CBT (RR 2.14, CI 0.97–4.73; participants = 132; 2 studies). Conclusion: i-CBT appears a potentially acceptable intervention for adults with PTSD. We identified clinical and research questions, including the status of proxy indicators, and call for standardised, consistent treatment acceptability measurement.

Background: Post-traumatic stress disorder (PTSD) is a common and debilitating disorder which has a significant impact on the lives of sufferers. A number of early psychological interventions have been developed to try to prevent chronic difficulties. Objective: The objective of this study was to establish the current evidence for the effectiveness of multiple session early psychological interventions aimed at preventing or treating traumatic stress symptoms beginning within three months of trauma exposure. Methods: Randomized controlled trials of early multiple session psychological interventions aimed at preventing or reducing traumatic stress symptoms of individuals exposed to a traumatic event, fulfiling trauma criteria for an ICD or DSM diagnosis of PTSD were identified through a search of the Cochrane Common Mental Disorders Group Clinical Trials Registers database, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO and PILOTS. Two authors independently extracted study details and data and completed risk of bias assessments. Analyses were undertaken using Review Manager software. Quality of findings were rated according to ‘Grades of Recommendation, Assessment, Development, and Evaluation’ (GRADE) and appraised for clinical importance. Results: Sixty-one studies evaluating a variety of interventions were identified. For individuals exposed to a trauma who were not pre-screened for traumatic stress symptoms there were no clinically important differences between any intervention and usual care. For individuals reporting traumatic stress symptoms we found clinically important evidence of benefits for trauma-focused cognitive-behavioural therapy (CBT-T), cognitive therapy without exposure and eye movement desensitization and reprocessing (EMDR). Differences were greatest for those diagnosed with acute stress disorder (ASD) and PTSD. Conclusions: There is evidence for the effectiveness of several early psychological interventions for individuals with traumatic stress symptoms following trauma exposure, especially for those meeting the diagnostic threshold for ASD or PTSD. Evidence is strongest for trauma-focused CBT.

The urinary tract comprises the renal pelvis, the ureter, the urinary bladder, and the urethra. The tract acts as a functional unit, first propelling urine from the kidney to the bladder, then storing it at low pressure inside the bladder which intermittently and completely voids urine through the urethra. Congenital diseases of these structures can lead to a range of diseases sometimes associated with fetal losses or kidney failure in childhood and later in life. In some of these disorders, parts of the urinary tract are severely malformed. In other cases, the organs appear grossly intact yet they have functional deficits that compromise health. Human studies are beginning to indicate monogenic causes for some of these diseases. Here, the implicated genes can encode smooth muscle, neural or urothelial molecules, or transcription factors that regulate their expression. Furthermore, certain animal models are informative about how such molecules control the development and functional differentiation of the urinary tract. In future, novel therapies, including those based on gene transfer and stem cell technologies, may be used to treat these diseases to complement conventional pharmacological and surgical clinical therapies.

Background: Two ‘sibling disorders’ have been proposed for the 11th version of the International Classification of Diseases (ICD-11): Posttraumatic Stress Disorder (PTSD) and Complex PTSD (CPTSD). To date, no research has attempted to identify the optimal symptom indicators for the ‘Disturbances in Self-Organization’ (DSO) symptom cluster. Objective: The aim of the current study was to assess the psychometric performance of scores of 16 potential DSO symptom indicators from the International Trauma Questionnaire (ITQ). Criteria relating to score variability and their ability to discriminate were employed. Method: Participants (N = 1839) were a nationally representative household sample of non-institutionalized adults currently residing in the US. Item scores from the ITQ were examined in relation to basic criteria associated with interpretability, variability, homogeneity, and association with functional impairment. The performance of the DSO symptoms was also assessed using 1- and 2-parameter item response theory (IRT) models. Results: The distribution of responses for all DSO indicators met the criteria associated with interpretability, variability, homogeneity, and association with functional impairment. The 1-parameter graded response model was considered the best model and indicated that each set of indictors performed very similarly. Conclusions: The ITQ contains 16 DSO symptom indicators and they perform well in measuring their respective symptom cluster. There was no evidence that particular indicators were ‘better’ than others, and it was concluded that the indicators are essentially interchangeable.

The 11th revision to the World Health Organization’s International Classification of Diseases (ICD-11) proposes two distinct sibling conditions: Posttraumatic Stress Disorder (PTSD) and Complex PTSD (CPTSD). In this paper, we aim to provide an update on the latest research regarding the conceptual structure and measurement of PTSD and CPTSD using the International Trauma Questionnaire (ITQ) as per ICD-11 proposals in the USA, UK, Germany and Lithuania. Preliminary findings suggest that CPTSD is common in clinical and population samples, although there may be variations across countries in prevalence rates. In clinical samples, preliminary evidence suggests that CPTSD is a more commonly observed condition than PTSD. Preliminary evidence also suggests that the ITQ scores are reliable and valid and can adequately distinguish between PTSD and CPTSD. Further cross-cultural work is proposed to explore differences in PTSD and CPTSD across different countries with regard to prevalence, incidence, and predictors of PTSD and CPTSD.

Background: The International Trauma Interview (ITI) is a clinician-administered assessment that has been newly developed for the International Classification of Diseases (ICD-11) diagnoses of posttraumatic stress disorder (PTSD) and complex PTSD (CPTSD).Objective: The current study evaluated the psychometric properties of the ITI for treatment-seeking people with adverse childhood experiences (ACE) in South Korea, with the aims of verifying the validity and reliability of ITI as well as examining the differentiation of ICD-11 CPTSD and borderline personality disorder (BPD).Methods: In total, data of 103 people were analysed. Clinical psychologists conducted the ITI and the structured interview for BPD. Along with the International Trauma Questionnaire (ITQ), self-report measurements on ACE, adulthood trauma, emotion dysregulation, dissociation, depression, adult attachment, BPD symptoms, self-harm, self-compassion, and quality of life were collected. A confirmatory factor analysis (CFA) was conducted to examine the factorial validity and a structural equation model (SEM) was used to evaluate the convergent and discriminant validity.Results: The CFA supported the second-order two-factor model of ICD-11 CPTSD. However, we determined that the alternatively suggested second-order two-factor model of reexperience avoidance combined PTSD and DSO described the data the best. As was hypothesized, ITI PTSD and DSO showed convergent and discriminant validity, and ITI DSO also showed distinctive features with BPD. Interrater reliability and composite reliability were both found to be acceptable. Agreement and consistency between ITQ and ITI were also fair although tentative.Conclusions: The ITI is determined to be a valid and reliable method for the assessment and diagnosis of ICD-11 PTSD and CPTSD, and it is considered to be promising for the differential diagnosis of BPD in South Korean treatment-seeking people with ACE. Future research should aim to assess the agreement between ITI and ITQ while also seeking alternative criteria for ITI PTSD across variant trauma memory features.

Background: The efficacy of psychosocial therapies for common mental health disorders in veterans is unclear and requires further examination. Method: Systematic review and meta-analyses of randomised controlled trials (RCTs). Twenty databases were searched. Studies were included if they reported a psychosocial intervention designed to treat or reduce common mental health symptoms in veterans identified as being symptomatic at the time they entered the study. Studies of substance dependency disorders and psychosis were excluded. Eligible studies were assessed against methodological quality criteria and data were extracted and analysed. Results: Twenty-nine RCTs were identified. There was evidence for the use of trauma-focused therapies for post-traumatic stress disorder (PTSD) and some evidence for psychological interventions in the treatment of borderline personality disorder, depression, insomnia, and panic disorder co-morbid to PTSD. However, methodological quality of many of the studies was less than optimal. Conclusions: Trauma-focused psychological therapies are likely to be effective for combat-related PTSD but there is a need for more research to determine the efficacy of psychological treatments for other mental health disorders in veterans.