EMDR v. other psychological therapies for PTSD: a systematic review and individual participant data meta-analysis.

BACKGROUND: This systematic review and individual participant data meta-analysis (IPDMA) examined the overall effectiveness of eye movement desensitization and reprocessing (EMDR) in reducing posttraumatic stress disorder (PTSD) symptoms, achieving response and remission, and reducing treatment dropout among adults with PTSD compared to other psychological treatments. Additionally, we examined available participant-level moderators of the efficacy of EMDR. METHODS: This study included randomized controlled trials. Eligible studies were identified by a systematic search in PubMed, Embase, PsyclNFO, PTSDpubs, and CENTRAL. The target population was adults with above-threshold baseline PTSD symptoms. Trials were eligible if at least 70% of study participants had been diagnosed with PTSD using a structured clinical interview. Primary outcomes included PTSD symptom severity, treatment response, and PTSD remission. Treatment dropout was a secondary outcome. The systematic search retrieved 15 eligible randomized controlled trials (RCTs); 8 of these 15 were able to be included in this IPDMA (346 patients). Comparator treatments included relaxation therapy, emotional freedom technique, trauma-focused cognitive behavioral psychotherapies, and REM-desensitization. RESULTS: One-stage IPDMA found no significant difference between EMDR and other psychological treatments in reducing PTSD symptom severity (ß = -0.24), achieving response (ß = 0.86), attaining remission (ß = 1.05), or reducing treatment dropout rates (ß = -0.25). Moderator analyses found unemployed participants receiving EMDR had higher PTSD symptom severity at the post-test, and males were more likely to drop out of EMDR treatment than females. CONCLUSION: The current study found no significant difference between EMDR and other psychological treatments. We found some indication of the moderating effects of gender and employment status.

Early pharmacological interventions for prevention of post-traumatic stress disorder (PTSD) in individuals experiencing acute traumatic stress symptoms.

BACKGROUND: Acute traumatic stress symptoms may develop in people who have been exposed to a traumatic event. Although they are usually self-limiting in time, some people develop post-traumatic stress disorder (PTSD), a severe and debilitating condition. Pharmacological interventions have been proposed for acute symptoms to act as an indicated prevention measure for PTSD development. As many individuals will spontaneously remit, these interventions should balance efficacy and tolerability. OBJECTIVES: To assess the efficacy and acceptability of early pharmacological interventions for prevention of PTSD in adults experiencing acute traumatic stress symptoms. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trial Register (CCMDCTR), CENTRAL, MEDLINE, Embase and two other databases. We checked the reference lists of all included studies and relevant systematic reviews. The search was last updated on 23 January 2023. SELECTION CRITERIA: We included randomised controlled trials on adults exposed to any kind of traumatic event and presenting acute traumatic stress symptoms, without restriction on their severity. We considered comparisons of any medication with placebo, or with another medication. We excluded trials that investigated medications as an augmentation to psychotherapy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Using a random-effects model, we analysed dichotomous data as risk ratios (RR) and calculated the number needed to treat for an additional beneficial/harmful outcome (NNTB/NNTH). We analysed continuous data as mean differences (MD) or standardised mean differences (SMD). Our primary outcomes were PTSD severity and dropouts due to adverse events. Secondary outcomes included PTSD rate, functional disability and quality of life. MAIN RESULTS: We included eight studies that considered four interventions (escitalopram, hydrocortisone, intranasal oxytocin, temazepam) and involved a total of 779 participants. The largest trial contributed 353 participants and the next largest, 120 and 118 participants respectively. The trials enrolled participants admitted to trauma centres or emergency departments. The risk of bias in the included studies was generally low except for attrition rate, which we rated as high-risk. We could meta-analyse data for two comparisons: escitalopram versus placebo (but limited to secondary outcomes) and hydrocortisone versus placebo. One study compared escitalopram to placebo at our primary time point of three months after the traumatic event. There was inconclusive evidence of any difference in terms of PTSD severity (mean difference (MD) on the Clinician-Administered PTSD Scale (CAPS, score range 0 to 136) -11.35, 95% confidence interval (CI) -24.56 to 1.86; 1 study, 23 participants; very low-certainty evidence), dropouts due to adverse events (no participant left the study early due to adverse events; 1 study, 31 participants; very low-certainty evidence) and PTSD rates (RR 0.59, 95% CI 0.03 to 13.08; NNTB 37, 95% CI NNTB 15 to NNTH 1; 1 study, 23 participants; very low-certainty evidence). The study did not assess functional disability or quality of life. Three studies compared hydrocortisone to placebo at our primary time point of three months after the traumatic event. We found inconclusive evidence on whether hydrocortisone was more effective in reducing the severity of PTSD symptoms compared to placebo (MD on CAPS -7.53, 95% CI -25.20 to 10.13; I2 = 85%; 3 studies, 136 participants; very low-certainty evidence) and whether it reduced the risk of developing PTSD (RR 0.47, 95% CI 0.09 to 2.38; NNTB 14, 95% CI NNTB 8 to NNTH 5; I2 = 36%; 3 studies, 136 participants; very low-certainty evidence). Evidence on the risk of dropping out due to adverse events is inconclusive (RR 3.19, 95% CI 0.13 to 75.43; 2 studies, 182 participants; low-certainty evidence) and it is unclear whether hydrocortisone might improve quality of life (MD on the SF-36 (score range 0 to 136, higher is better) 19.70, 95% CI -1.10 to 40.50; 1 study, 43 participants; very low-certainty evidence). No study assessed functional disability. AUTHORS' CONCLUSIONS: This review provides uncertain evidence regarding the use of escitalopram, hydrocortisone, intranasal oxytocin and temazepam for people with acute stress symptoms. It is therefore unclear whether these pharmacological interventions exert a positive or negative effect in this population. It is important to note that acute traumatic stress symptoms are often limited in time, and that the lack of data prevents the careful assessment of expected benefits against side effects that is therefore required. To yield stronger conclusions regarding both positive and negative outcomes, larger sample sizes are required. A common operational framework of criteria for inclusion and baseline assessment might help in better understanding who, if anyone, benefits from an intervention. As symptom severity alone does not provide the full picture of the impact of exposure to trauma, assessment of quality of life and functional impairment would provide a more comprehensive picture of the effects of the interventions. The assessment and reporting of side effects may facilitate a more comprehensive understanding of tolerability.

Distinguishing between ICD-11 complex post-traumatic stress disorder and borderline personality disorder: clinical guide and recommendations for future research.

Although complex post-traumatic stress disorder and borderline personality disorder are distinct disorders, there is confusion in clinical practice regarding the similarities between the diagnostic profiles of these conditions. We summarise the differences in the diagnostic criteria that are clinically informative and we illustrate these with case studies to enable diagnostic accuracy in clinical practice.

Rare copy number variation in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24-71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta = 0.029, SE = 0.005, P = 6.3 × 10-8). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta = 0.0206, SE = 0.0056, P = 0.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR q < 0.05), but these associations were not significant once NDD regions were removed. A larger sample size, better detection methods, and annotated resources of CNV are needed to explore this relationship further.

Associations among psychosis, mood, anxiety, and posttraumatic stress symptoms: A network analysis.

The associations among psychotic experiences (i.e., hallucinations and delusions), trauma exposure, and posttraumatic stress symptoms are complex and multidirectional. Using network analysis to understand how psychotic experiences and symptoms of posttraumatic stress disorder (PTSD) relate to one another may identify new interventional targets to treat comorbidity and its underlying pathological processes. This study aimed to use network analysis to examine the associations among psychotic experiences; negative symptoms of psychosis; and symptoms of PTSD, anxiety, and depression. In this population-based cohort study, 4,472 participants (36.7% male) were assessed for psychotic experiences, negative symptoms of psychosis, PTSD, anxiety, and depression at age 23 (M = 23.86 years, SD = 0.520) or 24 years (M = 24.03, SD = 0.848). Associations among symptoms were assessed via network analysis. Exploratory graph analysis identified three clusters of densely connected symptoms within the overall network: psychotic experiences; PTSD symptoms; and depressive and anxiety symptoms and negative symptoms of psychosis. Psychotic experiences had the strongest associations with other symptoms in the network, and symptoms of anxiety played a key role in bridging psychotic experiences, symptoms of PTSD, and depressive symptoms. Consistent with the stress reactivity and affective models for psychotic experiences, the results suggest that symptoms of anxiety and emotional distress (e.g., hyperarousal, panic) may have a key role in the development and maintenance of psychotic experiences and symptoms of PTSD. Targeting these symptoms may ameliorate symptom burden transdiagnostically.

Social support as a predictor of outcomes of cognitive behavioral therapy with a trauma focus delivered face-to-face and via guided internet-based self-help.

There is mounting evidence that cognitive behavioral therapy with a trauma focus (CBT-TF) delivered via guided internet-based self-help is noninferior to CBT-TF delivered face-to-face for individuals with posttraumatic stress disorder (PTSD) of mild-to-moderate severity. The availability of multiple evidence-based treatment options creates a need to determine predictors of outcome to enable clinicians to make informed treatment recommendations. We examined perceived social support as a predictor of treatment adherence and response among 196 adults with PTSD enrolled in a multicenter pragmatic randomized controlled noninferiority trial. Perceived social support was measured using the Multidimensional Scale of Perceived Social Support and PTSD was assessed using the Clinician-Administered PTSD Scale for DSM-5. Linear regression was used to explore the associations between different dimensions of perceived social support (i.e., from friends, family, and significant others) and posttraumatic stress symptoms (PTSS) at baseline. Linear and logistic regression were used to determine whether these dimensions of support predicted treatment adherence or response for either treatment modality. Lower baseline perceived social support from family was associated with higher levels of PTSS, B = -0.24, 95% CI [-0.39, -0.08], p = .003, but the same did not apply to social support from friends or significant others. We did not find evidence that any dimension of social support predicted treatment adherence or response for either treatment. This work does not indicate that social support is a factor that can help predict the suitability of psychological therapy for PTSD delivered via guided internet-based self-help versus face-to-face.

Evaluation of an adapted version of the International Trauma Questionnaire for use by people with intellectual disabilities.

AIMS: The International Trauma Questionnaire (ITQ) is a novel assessment instrument that is aligned to the ICD-11 diagnoses of post-traumatic stress disorder (PTSD) and complex PTSD (CPTSD). The purpose of this study was to develop and evaluate an adapted version of the ITQ suitable for use by people with intellectual disabilities. METHODS: The ITQ-ID follows the original ITQ, using wording developed in collaboration with a focus group of people with intellectual disabilities The ITQ-ID was administered to 40 people with intellectual disabilities recruited from learning disability forensic and community settings, alongside a Trauma Information Form and the Impact of Event Scale-Intellectual Disabilities (IES-IDs). RESULTS: Most participants reported multiple traumatizing events. Around half of the participants met strict criteria for a diagnosis of PTSD, and around three quarters met looser criteria. Depending on definitions, between 66% and 93% of those who met criteria for PTSD also met criteria for a diagnosis of CPTSD. The ITQ-ID showed a single-component structure, with very good-to-excellent internal consistency, excellent test-retest reliability, and evidence of concurrent, discriminant, and content validity. SIGNIFICANCE: The results support the potential of the ITQ-ID for assessment of PTSD and CPTSD in people with intellectual disabilities in both clinical and research contexts and highlight the need for further validation work.

Trauma exposure and co-occurring ICD-11 post-traumatic stress disorder and complex post-traumatic stress disorder in adults with lived experience of psychiatric disorder.

OBJECTIVE: To establish factors associated with ICD-11 post-traumatic stress disorder (PTSD) and complex PTSD (CPTSD) in a large sample of adults with lived experience of psychiatric disorder and examine the psychiatric burden associated with the two disorders. METHODS: One thousand three hundred and five adults were recruited from the National Centre for Mental Health (NCMH) cohort. ICD-11 PTSD/CPTSD were assessed with the International Trauma Questionnaire (ITQ). Binary logistic regression was used to determine factors associated with both PTSD and CPTSD. One-way between-groups analysis of variance was conducted to examine the burden associated with the two disorders in terms of symptoms of anxiety, depression, and psychological wellbeing. For post-hoc pairwise comparisons, the Tukey HSD test was used, and the magnitude of between-group differences assessed using Cohen's d. RESULTS: Probable ICD-11 CPTSD was more common than PTSD within the sample (PTSD 2.68%; CPTSD 12.72%). We found evidence that PTSD was associated with interpersonal trauma and household income under £20,000 a year. CPTSD was also associated with interpersonal trauma, higher rates of personality disorder, and lower rates of bipolar disorder. Those with probable-CPTSD had higher levels of current anxiety and depressive symptoms and lower psychological wellbeing in comparison to those with probable-PTSD and those with neither disorder. CONCLUSIONS: CPTSD was more prevalent than PTSD in our sample of people with lived experience of psychiatric disorder. Our findings indicate a need for routine screening for trauma histories and PTSD/CPTSD in clinical settings and a greater focus on the need for interventions to treat CPTSD.

COVID-19-related posttraumatic stress disorder in adults with lived experience of psychiatric disorder.

BACKGROUND: Prevalence estimates of COVID-19-related posttraumatic stress disorder (PTSD) have ranged from 1% to over 60% in the general population. Individuals with lived experience of a psychiatric disorder may be particularly vulnerable to COVID-19-related PTSD but this has received inadequate attention. METHODS: Participants were 1571 adults with lived experience of psychiatric disorder who took part in a longitudinal study of mental health during the COVID-19 pandemic. PTSD was assessed by the International Trauma Questionnaire (ITQ) anchored to the participant's most troubling COVID-19-related experiencevent. Factors hypothesised to be associated with traumatic stress symptoms were investigated by linear regression. RESULTS: 40.10% of participants perceived some aspect of the pandemic as traumatic. 5.28% reported an ICD-11 PTSD qualifying COVID-19 related traumatic exposure and 0.83% met criteria for probable ICD-11 COVID-19-related PTSD. Traumatic stress symptoms were associated with younger age, lower income, lower social support, and financial worries, and lived experience of PTSD/complex PTSD. Depression and anxiety measured in June 2020 predicted traumatic stress symptoms at follow-up approximately 20 weeks later in November 2020. CONCLUSIONS: We did not find evidence of widespread COVID-19-related PTSD among individuals with lived experience of a psychiatric disorder. There is a need for future research to derive valid prevalence estimates of COVID-19-related PTSD.

Early pharmacological interventions for universal prevention of post-traumatic stress disorder (PTSD).

BACKGROUND: Post-traumatic stress disorder (PTSD) is a severe and debilitating condition. Several pharmacological interventions have been proposed with the aim to prevent or mitigate it. These interventions should balance efficacy and tolerability, given that not all individuals exposed to a traumatic event will develop PTSD. There are different possible approaches to preventing PTSD; universal prevention is aimed at individuals at risk of developing PTSD on the basis of having been exposed to a traumatic event, irrespective of whether they are showing signs of psychological difficulties. OBJECTIVES: To assess the efficacy and acceptability of pharmacological interventions for universal prevention of PTSD in adults exposed to a traumatic event. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trial Register (CCMDCTR), CENTRAL, MEDLINE, Embase, two other databases and two trials registers (November 2020). We checked the reference lists of all included studies and relevant systematic reviews. The search was last updated on 13 November 2020. SELECTION CRITERIA: We included randomised clinical trials on adults exposed to any kind of traumatic event. We considered comparisons of any medication with placebo or with another medication. We excluded trials that investigated medications as an augmentation to psychotherapy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. In a random-effects model, we analysed dichotomous data as risk ratios (RR) and number needed to treat for an additional beneficial/harmful outcome (NNTB/NNTH). We analysed continuous data as mean differences (MD) or standardised mean differences (SMD). MAIN RESULTS: We included 13 studies which considered eight interventions (hydrocortisone, propranolol, dexamethasone, omega-3 fatty acids, gabapentin, paroxetine, PulmoCare enteral formula, Oxepa enteral formula and 5-hydroxytryptophan) and involved 2023 participants, with a single trial contributing 1244 participants. Eight studies enrolled participants from emergency departments or trauma centres or similar settings. Participants were exposed to a range of both intentional and unintentional traumatic events. Five studies considered participants in the context of intensive care units with traumatic events consisting of severe physical illness. Our concerns about risk of bias in the included studies were mostly due to high attrition and possible selective reporting. We could meta-analyse data for two comparisons: hydrocortisone versus placebo, but limited to secondary outcomes; and propranolol versus placebo. No study compared hydrocortisone to placebo at the primary endpoint of three months after the traumatic event. The evidence on whether propranolol was more effective in reducing the severity of PTSD symptoms compared to placebo at three months after the traumatic event is inconclusive, because of serious risk of bias amongst the included studies, serious inconsistency amongst the studies' results, and very serious imprecision of the estimate of effect (SMD -0.51, 95% confidence interval (CI) -1.61 to 0.59; I2 = 83%; 3 studies, 86 participants; very low-certainty evidence). No study provided data on dropout rates due to side effects at three months post-traumatic event. The evidence on whether propranolol was more effective than placebo in reducing the probability of experiencing PTSD at three months after the traumatic event is inconclusive, because of serious risk of bias amongst the included studies, and very serious imprecision of the estimate of effect (RR 0.77, 95% CI 0.31 to 1.92; 3 studies, 88 participants; very low-certainty evidence). No study assessed functional disability or quality of life.  Only one study compared gabapentin to placebo at the primary endpoint of three months after the traumatic event, with inconclusive evidence in terms of both PTSD severity and probability of experiencing PTSD, because of imprecision of the effect estimate, serious risk of bias and serious imprecision (very low-certainty evidence). We found no data on dropout rates due to side effects, functional disability or quality of life. For the remaining comparisons, the available data are inconclusive or missing in terms of PTSD severity reduction and dropout rates due to adverse events. No study assessed functional disability. AUTHORS' CONCLUSIONS: This review provides uncertain evidence only regarding the use of hydrocortisone, propranolol, dexamethasone, omega-3 fatty acids, gabapentin, paroxetine, PulmoCare formula, Oxepa formula, or 5-hydroxytryptophan as universal PTSD prevention strategies. Future research might benefit from larger samples, better reporting of side effects and inclusion of quality of life and functioning measures.

Posttraumatic growth related to the COVID-19 pandemic among individuals with lived experience of psychiatric disorder.

Although the COVID-19 pandemic has been shown to be detrimental to mental health, it may hold a parallel potential for positive change. Little is known about posttraumatic growth (PTG) as a potential outcome for individuals with lived experience of psychiatric disorders following trauma exposure, especially in the context of the COVID-19 pandemic. Participants were 1,424 adults with lived experience of a psychiatric disorder who took part in a longitudinal study of mental health during the COVID-19 pandemic conducted by the National Centre for Mental Health. PTG was measured using the Posttraumatic Growth Inventory-Short Form (PTGI-SF). Factors hypothesized to be associated with PTG were investigated using linear regression. The mean participant PTGI score was 12.64 (SD = 11.01). On average, participants reported the highest scores on items related to appreciation of life and lowest on those related to spiritual change subscale. We found the strongest evidence of associations between higher levels of PTG and higher scores on assessment items related to perceived social support, B = 2.86; perceptions of the pandemic as traumatic, B = 4.89; and higher psychological well-being, B = 0.40. Taken together, we did not observe evidence of widespread PTG related to the COVID-19 pandemic among individuals with lived experiences of psychiatric disorders.

Prenylated Coumaric Acids from Artemisia scoparia Beneficially Modulate Adipogenesis.

Two new diprenylated coumaric acid isomers (1a and 1b) and two known congeners, capillartemisin A (2) and B (3), were isolated from Artemisia scoparia as bioactive markers using bioactivity-guided HPLC fractionation. Their structures were determined by spectroscopic means, including 1D and 2D NMR methods and LC-MS, with their purity assessed by 1D 1H pure shift qNMR spectroscopic analysis. The bioactivity of compounds was evaluated by enhanced accumulation of lipids, as measured using Oil Red O staining, and by increased expression of several adipocyte marker genes, including adiponectin in 3T3-L1 adipocytes relative to untreated negative controls. Compared to the plant's 80% EtOH extract, these purified compounds showed significant but still weaker inhibition of TNFα-induced lipolysis in 3T3-L1 adipocytes. This suggests that additional bioactive substances are responsible for the multiple metabolically favorable effects on adipocytes observed with Artemisia scoparia extract.

The Untargeted Capability of NMR Helps Recognizing Nefarious Adulteration in Natural Products.

Curcuma longa (turmeric) has an extensive history of ethnomedical use for common ailments, and "curcumin"-containing dietary supplements (CDS) are a highly visible portion of today's self-medication market. Owing to raw material cost pressure, CDS products are affected by economically motivated, nefarious adulteration with synthetic curcumin ("syncumin"), possibly leading to unexpected toxicological issues due to "residual" impurities. Using a combination of targeted and untargeted (phyto)chemical analysis, this study investigated the botanical integrity of two commercial "turmeric" CDS with vitamin and other additives that were associated with reported clinical cases of hepatotoxicity. Analyzing multisolvent extracts of the CDS by 100% quantitative 1H NMR (qHNMR), alone and in combination with countercurrent separation (CCS), provided chemical fingerprints that allowed both the targeted identification and quantification of declared components and the untargeted recognition of adulteration. While confirming the presence of curcumin as a major constituent, the universal detection capability of NMR spectroscopy identification of significant residual impurities, including potentially toxic components. While the loss-free nature of CCS captured a wide polarity range of declared and unwanted chemical components, and also increased the dynamic range of the analysis, (q)HNMR determined their mass proportions and chemical constitutions. The results demonstrate that NMR spectroscopy can recognize undeclared constituents even if they represent only a fraction of the mass balance of a dietary supplement product. The chemical information associated with the missing 4.8% and 7.4% (m/m) in the two commercial samples, exhibiting an otherwise adequate curcumin content of 95.2% and 92.6%, respectively, pointed to a product integrity issue and adulteration with undeclared synthetic curcumin. Impurities from synthesis are most plausibly the cause of the observed adverse clinical effects. The study exemplifies how the simultaneously targeted and untargeted analytical principle of the 100% qHNMR method, performed with entry-level high-field instrumentation (400 MHz), can enhance the safety of dietary supplements by identifying adulterated, non-natural "natural" products.

Internet-based cognitive and behavioural therapies for post-traumatic stress disorder (PTSD) in adults.

BACKGROUND: Therapist-delivered trauma-focused psychological therapies are effective for post-traumatic stress disorder (PTSD) and have become the accepted first-line treatments. Despite the established evidence-base for these therapies, they are not always widely available or accessible. Many barriers limit treatment uptake, such as the number of qualified therapists available to deliver the interventions; cost; and compliance issues, such as time off work, childcare, and transportation, associated with the need to attend weekly appointments. Delivering Internet-based cognitive and behavioural therapy (I-C/BT) is an effective and acceptable alternative to therapist-delivered treatments for anxiety and depression. OBJECTIVES: To assess the effects of I-C/BT for PTSD in adults. SEARCH METHODS: We searched MEDLINE, Embase, PsycINFO and the Cochrane Central Register of Controlled Trials to June 2020. We also searched online clinical trial registries and reference lists of included studies and contacted the authors of included studies and other researchers in the field to identify additional and ongoing studies. SELECTION CRITERIA: We searched for RCTs of I-C/BT compared to face-to-face or Internet-based psychological treatment, psychoeducation, wait list, or care as usual. We included studies of adults (aged over 16 years), in which at least 70% of the participants met the diagnostic criteria for PTSD, according to the Diagnostic and Statistical Manual (DSM) or the International Classification of Diseases (ICD). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed abstracts, extracted data, and entered data into Review Manager 5. The primary outcomes were severity of PTSD symptoms and dropouts. Secondary outcomes included diagnosis of PTSD after treatment, severity of depressive and anxiety symptoms, cost-effectiveness, adverse events, treatment acceptability, and quality of life. We analysed categorical outcomes as risk ratios (RRs), and continuous outcomes as mean differences (MD) or standardised mean differences (SMDs), with 95% confidence intervals (CI). We pooled data using a fixed-effect meta-analysis, except where heterogeneity was present, in which case we used a random-effects model. We independently assessed the included studies for risk of bias and we evaluated the certainty of available evidence using the GRADE approach; we discussed any conflicts with at least one other review author, with the aim of reaching a unanimous decision. MAIN RESULTS: We included 13 studies with 808 participants. Ten studies compared I-C/BT delivered with therapist guidance to a wait list control. Two studies compared guided I-C/BT with I-non-C/BT. One study compared guided I-C/BT with face-to-face non-C/BT. There was substantial heterogeneity among the included studies. I-C/BT compared with face-to-face non-CBT Very low-certainty evidence based on one small study suggested face-to-face non-CBT may be more effective than I-C/BT at reducing PTSD symptoms post-treatment (MD 10.90, 95% CI 6.57 to 15.23; studies = 1, participants = 40). There may be no evidence of a difference in dropout rates between treatments (RR 2.49, 95% CI 0.91 to 6.77; studies = 1, participants = 40; very low-certainty evidence). The study did not measure diagnosis of PTSD, severity of depressive or anxiety symptoms, cost-effectiveness, or adverse events. I-C/BT compared with wait list Very low-certainty evidence showed that, compared with wait list, I-C/BT may be associated with a clinically important reduction in PTSD post-treatment (SMD -0.61, 95% CI -0.93 to -0.29; studies = 10, participants = 608). There may be no evidence of a difference in dropout rates between the I-C/BT and wait list groups (RR 1.25, 95% CI 0.97 to 1.60; studies = 9, participants = 634; low-certainty evidence). I-C/BT may be no more effective than wait list at reducing the risk of a diagnosis of PTSD after treatment (RR 0.53, 95% CI 0.28 to 1.00; studies = 1, participants = 62; very low-certainty evidence). I-C/BT may be associated with a clinically important reduction in symptoms of depression post-treatment (SMD -0.51, 95% CI -0.97 to -0.06; studies = 7, participants = 473; very low-certainty evidence). Very low-certainty evidence also suggested that I-C/BT may be associated with a clinically important reduction in symptoms of anxiety post-treatment (SMD -0.61, 95% CI -0.89 to -0.33; studies = 5, participants = 345). There were no data regarding cost-effectiveness. Data regarding adverse events were uncertain, as only one study reported an absence of adverse events. I-C/BT compared with I-non-C/BT There may be no evidence of a difference in PTSD symptoms post-treatment between the I-C/BT and I-non-C/BT groups (SMD -0.08, 95% CI -0.52 to 0.35; studies = 2, participants = 82; very low-certainty evidence). There may be no evidence of a difference between dropout rates from the I-C/BT and I-non-C/BT groups (RR 2.14, 95% CI 0.97 to 4.73; studies = 2, participants = 132; I² = 0%; very low-certainty evidence). Two studies found no evidence of a difference in post-treatment depressive symptoms between the I-C/BT and I-non-C/BT groups (SMD -0.12, 95% CI -0.78 to 0.54; studies = 2, participants = 84; very low-certainty evidence). Two studies found no evidence of a difference in post-treatment symptoms of anxiety between the I-C/BT and I-non-C/BT groups (SMD 0.08, 95% CI -0.78 to 0.95; studies = 2, participants = 74; very low-certainty evidence). There were no data regarding cost-effectiveness. Data regarding adverse effects were uncertain, as it was not discernible whether adverse effects reported were attributable to the intervention. AUTHORS' CONCLUSIONS: While the review found some beneficial effects of I-C/BT for PTSD, the certainty of the evidence was very low due to the small number of included trials. This review update found many planned and ongoing studies, which is encouraging since further work is required to establish non-inferiority to current first-line interventions, explore mechanisms of change, establish optimal levels of guidance, explore cost-effectiveness, measure adverse events, and determine predictors of efficacy and dropout.

Disturbed Sleep Connects Symptoms of Posttraumatic Stress Disorder and Somatization: A Network Analysis Approach.

Posttraumatic stress disorder (PTSD) and physical health problems, particularly somatic symptom disorder, are highly comorbid. Studies have only examined this co-occurrence at the disorder level rather than assessing the associations between specific symptoms. Using network analysis to identify symptoms that act as bridges between these disorders may allow for the development of interventions to specifically target this comorbidity. We examined the association between somatization and PTSD symptoms via network analysis. This included 349 trauma-exposed individuals recruited through the National Centre for Mental Health PTSD cohort who completed the Clinician-Administered PTSD Scale for DSM-5 and the Patient Health Questionnaire-15. A total of 215 (61.6%) individuals met the DSM-5 diagnostic criteria for PTSD. An exploratory graph analysis identified four clusters of densely connected symptoms within the overall network: PTSD, chronic pain, gastrointestinal issues, and more general somatic complaints. Sleep difficulties played a key role in bridging PTSD and somatic symptoms. Our network analysis demonstrates the distinct nature of PTSD and somatization symptoms, with this association connected by disturbed sleep.

Managing COVID-19 related distress in primary care: principles of assessment and management.

COVID-19 will cause normal feelings of worry and stress and many of those who experience higher levels of distress will experience resolution of their symptoms as society returns to pre-COVID-19 functioning. Only a minority are likely to develop a psychiatric disorder. Certain individuals may be vulnerable to experiencing persisting symptoms, such as those with pre-existing comorbidity. Management approaches could centre around using collaborative approaches to provide and build on already existing socioeconomic support structures, the avoidance of over-medicalisation, watchful waiting and finally treating those who do meet the criteria for psychiatric diagnosis. Primary care clinicians are likely be the first healthcare point of contact for most COVID-19 related distress and it is important that they are able to provide evidence based and evidence informed responses, which includes social, psychological and pharmacological approaches. This expert opinion paper serves to summarise some approaches, based primarily on indirect extrapolation of evidence concerning the general management of psychological distress, in the absence of COVID-19 specific evidence, to assist primary care clinicians in their assessment and management of COVID-19 related distress.

Psychological and pharmacological interventions for posttraumatic stress disorder and comorbid mental health problems following complex traumatic events: Systematic review and component network meta-analysis.

BACKGROUND: Complex 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 FINDINGS: We 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. CONCLUSIONS: In 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.

Evidence-based prescribing for post-traumatic stress disorder.

There is strong research evidence to support the pharmacological treatment of post-traumatic stress disorder (PTSD) as a second line to trauma-focused psychological interventions. Fluoxetine, paroxetine, sertraline and venlafaxine are the best-evidenced drugs, with lower-level evidence for other medications. It is important that prescribing for PTSD is evidence-based.

Selective Chlorophyll Removal Method to "Degreen" Botanical Extracts.

Chlorophylls are present in all extracts from the aerial parts of green plant materials. Chlorophylls may act as in vitro bioassay nuisance compounds, possibly preventing the reproducibility and accurate measurement of readouts due to their UV/vis absorbance, fluorescence properties, and tendency to precipitate in aqueous media. Despite the diversity of methods used traditionally to remove chlorophylls, details about their mode of operation, specificity, and reproducibility are scarce. Herein, we report a selective and efficient 45 min liquid-liquid/countercurrent chlorophyll cleanup method using Centrifugal Partition Chromatography (CPC) with a solvent system composed of hexanes-EtOAc-MeOH-water (5:5:5:5, v/v) in elution-extrusion mode. The broader utility of the method was assessed with four different extracts prepared from three well-characterized plant materials: Epimedium sagittatum (leaves), Senna alexandrina (leaves), and Trifolium pratense (aerial parts). The reproducibility of the method, the selectivity of the chlorophyll removal, as well as the preservation of the phytochemical integrity of the resulting chlorophyll-free ("degreened") extracts were evaluated using HPTLC, UHPLC-UV, 1H NMR spectroscopy, and LC-MS as orthogonal phytochemical methods. The cleanup process adequately preserves the metabolomic diversity as well as the integrity of the original extracts. This method was found to be sufficiently rapid for the "degreening" of botanical extracts in higher-throughput sample preparation for further biological screening.

Antimycobacterial Rufomycin Analogues from Streptomyces atratus Strain MJM3502.

This study represents a systematic chemical and biological study of the rufomycin (RUF) class of cyclic heptapeptides, which our anti-TB drug discovery efforts have identified as potentially promising anti-TB agents that newly target the caseinolytic protein C1, ClpC1. Eight new RUF analogues, rufomycins NBZ1-NBZ8 (1-8), as well as five known peptides (9-13) were isolated and characterized from the Streptomyces atratus strain MJM3502. Advanced Marfey's and X-ray crystallographic analysis led to the assignment of the absolute configuration of the RUFs. Several isolates exhibited potent activity against both pathogens M. tuberculosis H37Rv and M. abscessus, paired with favorable selectivity (selectivity index >60), which collectively underscores the promise of the rufomycins as potential anti-TB drug leads.