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.

Provision of online eye movement and desensitisation therapy (EMDR) for people with post-traumatic stress disorder (PTSD): a multi-method service evaluation.

Background: The evidence for the effectiveness of online EMDR for PTSD is scarce.Objective: This service evaluation aimed to assess how online EMDR compared to in-person EMDR, in terms of its potential effectiveness and acceptability to therapists and patients.Method: The evaluation was carried out in the Cardiff and Vale University Health Board Traumatic Stress Service. We compared the outcome of therapy (PTSD scores at end of treatment), number of sessions, drop-out rate, and adverse events using linear/logistic regression in those receiving online EMDR over a 12-month period with those who had received in-person therapy in the year previous to that. Interviews with therapists and clients who had provided or undertaken online EMDR explored their views and experiences of treatment. Interviews were analysed thematically.Results: 33 people received in-person EMDR (15.3 sessions, SD = 1.4), and 45 received online EMDR (12.4 sessions, SD = 0.9). 24 individuals completed therapy in-person, and 32 online. There was no evidence of a difference in therapy completion, drop-out rates or adverse events between the two delivery modes. There was weak evidence that those who completed EMDR online and had available data (N = 29), had slightly lower PTSD scores at the end of therapy compared to those who received in-person EMDR (N = 24) (17.1 (SD = 3.2) versus 24.5 (SD = 3.0), mean difference = 7.8, 95% CI -0.3, 15.9, p = .06). However, groups were not randomised and only those who completed treatment were analysed, so estimates may be biased. 11 patients and five therapists were interviewed. Overall, both therapists and clients viewed online EMDR as safe and effective. Benefits mentioned by clients included feeling more in control and not having to travel. Clients' concerns related to lack of privacy and 'transition time/space' between therapy and their daily lives.Conclusion: Results suggest that online EMDR is an acceptable, safe and effective alternative to in-person EMDR for PTSD in this service.

This service evaluation assessed how online Eye Movement Desensitisation and Reprocessing (EMDR) compared to in-person EMDR in people with PTSD.Individuals receiving online EMDR had lower PTSD scores at the end of therapy, but the evidence for this was weak and as this was not a randomised trial we do not know whether this was due to the mode of therapy or other characteristics of clients receiving online therapy.Clients and therapists generally viewed online EMDR as being safe and effective, and supported the availability of online EMDR for PTSD.

Do Certain Flavonoid IMPS Have a Vital Function?

Flavonoids are a vast group of metabolites that are essential for vascular plant physiology and, thus, occur ubiquitously in plant-based/-derived foods. The solitary designation of thousands of known flavonoids hides the fact that their metabolomes are structurally highly diverse, consist of disparate subgroups, yet undergo a certain degree of metabolic interconversion. Unsurprisingly, flavonoids have been an important theme in nutrition research. Already in the 1930s, it was discovered that the ability of synthetic Vitamin C to treat scurvy was inferior to that of plant extracts containing Vitamin C. Subsequent experimental evidence led to the proposal of Vitamin P (permeability) as an essential phytochemical nutrient. However, attempts to isolate and characterize Vitamin P gave confusing and sometimes irreproducible results, which today can be interpreted as rooted in the unrecognized (residual) complexity of the intervention materials. Over the years, primarily flavonoids (and some coumarins) were known as having Vitamin P-like activity. More recently, in a NAPRALERT meta-analysis, essentially all of these Vitamin P candidates were identified as IMPs (Invalid/Improbable/Interfering Metabolic Panaceas). While the historic inability to define a single compound and specific mode of action led to general skepticism about the Vitamin P proposition for "bioflavonoids," the more logical conclusion is that several abundant and metabolically labile plant constituents fill this essential role in human nutrition at the interface of vitamins, cofactors, and micronutrients. Reviewing 100+ years of the multilingual Vitamin P and C literature provides the rationales for this conclusion and new perspectives for future research.

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.

The Essential Medicinal Chemistry of Cannabidiol (CBD).

This Perspective of the published essential medicinal chemistry of cannabidiol (CBD) provides evidence that the popularization of CBD-fortified or CBD-labeled health products and CBD-associated health claims lacks a rigorous scientific foundation. CBD's reputation as a cure-all puts it in the same class as other "natural" panaceas, where valid ethnobotanicals are reduced to single, purportedly active ingredients. Such reductionist approaches oversimplify useful, chemically complex mixtures in an attempt to rationalize the commercial utility of natural compounds and exploit the "natural" label. Literature evidence associates CBD with certain semiubiquitous, broadly screened, primarily plant-based substances of undocumented purity that interfere with bioassays and have a low likelihood of becoming therapeutic agents. Widespread health challenges and pandemic crises such as SARS-CoV-2 create circumstances under which scientists must be particularly vigilant about healing claims that lack solid foundational data. Herein, we offer a critical review of the published medicinal chemistry properties of CBD, as well as precise definitions of CBD-containing substances and products, distilled to reveal the essential factors that impact its development as a therapeutic agent.

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.

Psychological therapies for post-traumatic stress disorder in adults: systematic review and meta-analysis.

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.

Objetivo: determinar los tamaños del efecto de las terapias manualizadas para el TEPT.Métodos: Realizamos una revisión sistemática siguiendo las guías de la Colaboración Cochrane. Se aplicó una definición predeterminada de importancia clínica a los resultados y se evaluó la calidad de la evidencia utilizando el enfoque de calificación de recomendaciones, evaluación, desarrollo y evaluaciones (GRADE).Resultados: se incluyeron 114 ensayos controlados aleatorizados (ECA) de 8.171 participantes. Hubo evidencia robusta de que las terapias ampliamente definidas como TCC con un enfoque de trauma (TCC-T), así como la desensibilización y reprocesamiento POR movimientos oculares (EMDR), tuvieron un efecto clínicamente importante. Las CBT-Ts manualizados con la mayor evidencia de efecto fueron la terapia de procesamiento cognitivo (CPT); Terapia cognitiva (CT); y exposición prolongada (PE). También hubo alguna evidencia que apoya la TCC sin un enfoque traumático; TCC grupal con enfoque en trauma; TCC basada en Internet guiada; y terapia centrada en el presente (PCT). Hubo evidencia emergente para una serie de otras terapias.Conclusiones: Un aumento reciente en ECA de terapias psicológicas para el TEPT, da como resultado una recomendación más confiable de CBT-T y EMDR como los tratamientos de primera línea. Entre los CBT-Ts considerados por la revisión CPT, CT y PE deberían ser los tratamientos de elección. Los hallazgos deben guiar la toma de decisiones compartida informada por la evidencia entre el paciente y el médico.

Pharmacological prevention and early treatment of post-traumatic stress disorder and acute stress disorder: a systematic review and meta-analysis.

Post-traumatic stress disorder (PTSD) is a common mental disorder associated with significant distress and reduced functioning. Its occurrence after a severe traumatic event and association with characteristic neurobiological changes make PTSD a good candidate for pharmacological prevention and early treatment. The primary aim for this systematic review and meta-analysis was to assess whether pharmacological interventions when compared to placebo, or other pharmacological/psychosocial interventions resulted in a clinically significant reduction or prevention of symptoms, improved functioning or quality of life, presence of disorder, or adverse effects. A systematic search was undertaken to identify RCTs, which used early pharmacotherapy (within three months of a traumatic event) to prevent and treat PTSD and acute stress disorder (ASD) in children and adults. Using Cochrane Collaboration methodology, RCTs were identified and rated for risk of bias. Available data was pooled to calculate risk ratios (RR) for PTSD prevalence and standardised mean differences (SMD) for PTSD severity. 19 RCTs met the inclusion criteria; 16 studies with adult participants and three with children. The methodological quality of most trials was low. Only hydrocortisone in adults was found to be superior to placebo (3 studies, n = 88, RR: 0.21 (CI 0.05 to 0.89)) although this was in populations with severe physical illness, raising concerns about generalisability. No significant effects were found for the other pharmacotherapies investigated (propranolol, oxytocin, gabapentin, fish oil (1470 mg DHA/147 mg EPA), fish oil (224 mg DHA/22.4 mg EPA), dexamethasone, escitalopram, imipramine and chloral hydrate). Hydrocortisone shows the most promise, of pharmacotherapies subjected to RCTs, as an emerging intervention in the prevention of PTSD within three months after trauma and should be a target for further investigation. The limited evidence for hydrocortisone and its adverse effects mean it cannot be recommended for routine use, but, it could be considered as a preventative intervention for people with severe physical illness or injury, shortly after a traumatic event, as long as there are no contraindications. More research is needed using larger, high quality RCTs to establish the most efficacious use of hydrocortisone in different populations and optimal dosing, dosing window and route. There is currently a lack of evidence to suggest that other pharmacological agents are likely to be effective.

Early psychological intervention following recent trauma: A systematic review and meta-analysis.

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.

Antecedentes: El Trastorno de Estrés Postraumático (TEPT) es un trastorno frecuente y debilitante que tiene un impacto significativo en las vidas de los que lo padecen. Se han desarrollado una serie de intervenciones psicológicas tempranas para tratar de prevenir dificultades crónicas.Objetivo: El objetivo de este estudio fue establecer la evidencia actual para la eficacia de intervenciones psicológicas tempranas con múltiples sesiones con el objetivo de prevenir o tratar síntomas de estrés traumático que comenzaron en los tres meses posteriores a la exposición al trauma.Métodos: Se realizó una búsqueda bibliográfica basada en la base de datos de Cochrane de Estudios Clínicos de Trastornos Mentales Frecuentes, en el registro de ensayos controlados de Cochrane, MEDLINE, Embase, PsycINFO y PILOTS, para identificar ensayos controlados randomizados de intervenciones psicológicas tempranas de múltiples sesiones que tenían el objetivo de prevenir o reducir síntomas de estrés traumático en individuos expuestos a un evento traumático, y que cumplían los criterios de TEPT según la CIE o el DSM. Dos autores independientes extrajeron los detalles e información del estudio y completaron una evaluación de riesgo de sesgo. Se llevaron a cabo análisis usando el software Review Manager. La calidad de los hallazgos fue puntuada según los 'Grados de Recomendación, Valoración, Desarrollo y Evaluación' (GRADE pos sus siglas en inglés) y evaluada por su importancia clínica.Resultados: Se identificaron sesenta y un estudios que evaluaban una variedad de intervenciones. Para aquellos individuos que estuvieron expuestos a un trauma que no tuvieron una pre-evaluación de síntomas de estrés traumático no hubo una diferencia clínica importante entre cualquier intervención y cuidado usual. Para los individuos que reportaron síntomas de estrés traumático encontramos evidencia clínicamente significativa de los beneficios de la terapia cognitiva focalizada en el trauma (CBT-T por sus siglas en inglés), terapia cognitiva sin exposición y desensibilización y reprocesamiento a través de movimientos oculares (EMDR por sus siglas en inglés). Las diferencias fueron mayores para aquellos diagnosticados con trastornos de estrés agudo (ASD por sus siglas en inglés) y TEPT.Conclusiones: Existe evidencia para la eficacia de varias intervenciones psicológicas tempranas para individuos con síntomas de estrés traumático posterior a la exposición a un trauma, especialmente para aquellos que cumplen con los criterios para un diagnóstico completo de ASD o TEPT. La evidencia es más fuerte para la CBT-T.

Active duty and ex-serving military personnel with post-traumatic stress disorder treated with psychological therapies: systematic review and meta-analysis.

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.

Antecedentes: el trastorno de estrés postraumático (TEPT) es una causa importante de morbilidad entre el personal militar activo y en retiro. En los últimos años se han realizado esfuerzos crecientes para desarrollar tratamientos más efectivos.Objetivo: determinar qué terapias psicológicas son eficaces en el tratamiento del personal militar en servicio activo y en retiro con trastorno de estrés postraumático (TEPT).Método: se realizó una revisión sistemática de acuerdo con las Pautas de la Colaboración Cochrane. La medida de resultado primaria fue la reducción de los síntomas de TEPT y la secundaria los abandonos al tratamiento.Resultados: se incluyeron 24 estudios con 2386 participantes. La evidencia demostró que la Terapia cognitivo conductual centrada en el trauma (TCC-CT) se asoció con la mayor evidencia de efecto en comparación con la lista de espera/atención habitual en la reducción de los síntomas de TEPT después del tratamiento (10 estudios; n = 524; DME -1.22, -1.78 a - 0,66). La TCC-CT grupal fue menos efectivo en comparación con el TCC-CT individual para reducir los síntomas de TEPT después del tratamiento (1 estudio; n = 268; SMD -0.35, -0.11 a -0.59). La terapia de desensibilización y reprocesamiento por movimiento ocular (EMDR) no fue efectiva en comparación con la lista de espera/atención habitual para reducir los síntomas de TEPT después del tratamiento (4 estudios; n = 92; SMD -0.83, -1.75 a 0.10). Hubo evidencia de un mayor abandono de las terapias TCC-CT en comparación con la lista de espera y la terapia centrada en el presente.Conclusiones: La evidencia, aunque limitada, respalda la TCC-CT individual como el tratamiento psicológico de primera línea del TEPT en el personal militar en servicio activo y en retiro. Existe evidencia de TCC-CT grupal, pero esta no es tan consistente como para TCC-CT individual. No se puede recomendar EMDR como terapia de primera línea en la actualidad y requiere urgentemente una evaluación adicional. Los tamaños de efecto más bajos que para otras poblaciones con TEPT y altos niveles de abandono sugieren que TCC-TC en sus formatos actuales no es óptimamente aceptable y se requiere más investigación para desarrollar y evaluar tratamientos más efectivos para TEPT y TEPT complejo en personal militar en servicio activo y en retiro.

Psychological interventions for ICD-11 complex PTSD symptoms: systematic review and meta-analysis.

BACKGROUND: The 11th revision to the WHO International Classification of Diseases (ICD-11) identified complex post-traumatic stress disorder (CPTSD) as a new condition. There is a pressing need to identify effective CPTSD interventions. METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of psychological interventions for post-traumatic stress disorder (PTSD), where participants were likely to have clinically significant baseline levels of one or more CPTSD symptom clusters (affect dysregulation, negative self-concept and/or disturbed relationships). We searched MEDLINE, PsycINFO, EMBASE and PILOTS databases (January 2018), and examined study and outcome quality. RESULTS: Fifty-one RCTs met inclusion criteria. Cognitive behavioural therapy (CBT), exposure alone (EA) and eye movement desensitisation and reprocessing (EMDR) were superior to usual care for PTSD symptoms, with effects ranging from g = -0.90 (CBT; k = 27, 95% CI -1.11 to -0.68; moderate quality) to g = -1.26 (EMDR; k = 4, 95% CI -2.01 to -0.51; low quality). CBT and EA each had moderate-large or large effects on negative self-concept, but only one trial of EMDR provided useable data. CBT, EA and EMDR each had moderate or moderate-large effects on disturbed relationships. Few RCTs reported affect dysregulation data. The benefits of all interventions were smaller when compared with non-specific interventions (e.g. befriending). Multivariate meta-regression suggested childhood-onset trauma was associated with a poorer outcome. CONCLUSIONS: The development of effective interventions for CPTSD can build upon the success of PTSD interventions. Further research should assess the benefits of flexibility in intervention selection, sequencing and delivery, based on clinical need and patient preferences.

Pharmacognosy in the digital era: shifting to contextualized metabolomics.

Humans have co-evolved alongside numerous other organisms, some having a profound effect on health and nutrition. As the earliest pharmaceutical subject, pharmacognosy has evolved into a meta-discipline devoted to natural biomedical agents and their functional properties. While the acquisition of expanding data volumes is ongoing, contextualization is lagging. Thus, we assert that the establishment of an integrated and open databases ecosystem will nurture the discipline. After proposing an epistemological framework of knowledge acquisition in pharmacognosy, this study focuses on recent computational and analytical approaches. It then elaborates on the flux of research data, where good practices could foster the implementation of more integrated systems, which will in turn help shaping the future of pharmacognosy and determine its constitutional societal relevance.

The Essential Medicinal Chemistry of Curcumin.

Curcumin is a constituent (up to ∼5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double-blinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed.

Inhibitory activity of plant stilbenoids against nitric oxide production by lipopolysaccharide-activated microglia.

Microglia-driven inflammatory processes are thought to play an important role in ageing and several neurological disorders. Since consumption of a diet rich in polyphenols has been associated with anti-inflammatory and neuroprotective effects, we studied the effects of twenty-five stilbenoids isolated from Milicia excelsa, Morus alba, Gnetum africanum, and Vitis vinifera. These compounds were tested at 5 and 10 µM on BV-2 microglial cells stimulated with bacterial lipopolysaccharide. Ten stilbenoids reduced lipopolysaccharide-induced nitric oxide production at 5 and/or 10 µM. Two tetramers, E-vitisin A and E-vitisin B, were the most effective molecules. Moreover, they attenuated the expression of the inducible NO synthase protein and gene.

Development of hybrid elution systems for efficient purification of stilbenoids using centrifugal partition chromatography coupled to mass spectrometry.

The phytochemical study of the root extract of the stilbenoid-rich Vitis riparia×Vitis berlandieri grapevine was carried out by centrifugal partition chromatography (CPC). For this reason, we developed a new elution mode we named back-step, which allowed us to obtain cleaner fractions and a more efficient separation process when used in conjunction with a classical elution approach. Three hydroxystilbenes: (E)-resveratrol, (E)-ɛ-viniferin and (E)-vitisin C, with greater than 90% purity were thus obtained through such process, with minimal sample handling and purification steps. Online coupling of CPC to ESI mass spectrometry was used for optimization of the separation parameters and to facilitate the characterization of the stilbenoids. This study details the first phytochemical investigation of stilbenoids from the hybrid species together with a new elution mode able to widen the range of ARIZONA biphasic systems.

Do all psychological treatments really work the same in posttraumatic stress disorder?

A recent meta-analysis by Benish, Imel, and Wampold (2008, Clinical Psychology Review, 28, 746-758) concluded that all bona fide treatments are equally effective in posttraumatic stress disorder (PTSD). In contrast, seven other meta-analyses or systematic reviews concluded that there is good evidence that trauma-focused psychological treatments (trauma-focused cognitive behavior therapy and eye movement desensitization and reprocessing) are effective in PTSD; but that treatments that do not focus on the patients' trauma memories or their meanings are either less effective or not yet sufficiently studied. International treatment guidelines therefore recommend trauma-focused psychological treatments as first-line treatments for PTSD. We examine possible reasons for the discrepant conclusions and argue that (1) the selection procedure of the available evidence used in Benish et al.'s (2008)meta-analysis introduces bias, and (2) the analysis and conclusions fail to take into account the need to demonstrate that treatments for PTSD are more effective than natural recovery. Furthermore, significant increases in effect sizes of trauma-focused cognitive behavior therapies over the past two decades contradict the conclusion that content of treatment does not matter. To advance understanding of the optimal treatment for PTSD, we recommend further research into the active mechanisms of therapeutic change, including treatment elements commonly considered to be non-specific. We also recommend transparency in reporting exclusions in meta-analyses and suggest that bona fide treatments should be defined on empirical and theoretical grounds rather than by judgments of the investigators' intent.

Post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is an increasingly recognized and potentially preventable condition. Certain factors, especially the severity of the trauma, perceived lack of social support and peri-traumatic dissociation have been associated with its development. In recent years, a more robust evidence base regarding the management of individuals involved in traumatic events has emerged. Immediately after a traumatic event, simple practical, pragmatic support provided in a sympathetic manner by non-mental health professionals seems most likely to help. For individuals who develop persisting PTSD, trauma-focused cognitive behavioural therapy (TFCBT) may be beneficial within a few months of the trauma. For those who develop chronic PTSD, TFCBT and eye movement desensitization and reprocessing are best supported by the current evidence. Some anti-depressants appear to have a modest beneficial effect and are recommended as a second-line treatment. The current evidence base has allowed the development of guidelines that now require implementation. This has major implications in terms of planning and developing services that allow appropriately qualified and trained individuals to be available to cater adequately for the needs of survivors of traumatic events.