The Effectiveness of Trauma-Focused Psychotherapy for Complex Post-Traumatic Stress Disorder: A Retrospective Study

Objective We retrospectively evaluated the effectiveness of trauma-focused psychotherapy (TF-P) versus stabilization and waiting in a civilian cohort of patients with an 11th version of the international classification of disease (ICD-11) diagnosis of complex post-traumatic stress disorder (CPTSD). Methods We identified patients with CPTSD treated at a specialist trauma service over a 3-year period by triangulating evidence from self-report questionnaires, file review, and expert-clinician opinion. Patients completed a phase-based treatment: stabilization consisting of symptom management and establishing safety, followed by waiting for treatment (phase 1); individual TF-P in the form of trauma-focused cognitive behavioral therapy (TF-CBT), or eye movement desensitization and reprocessing (EMDR) or TF-CBT plus EMDR (phase 2). Our primary outcome was PTSD symptoms during phase 2 versus phase 1. Secondary outcomes included depressive symptoms, functional impairment, and a proxy CPTSD measure. Exploratory analysis compared outcomes between treatments. Adverse outcomes were recorded. Results Fifty-nine patients were included. Compared to receiving only phase 1, patients completing TF-P showed statistically significant reductions in PTSD [t(58) = −3.99, p < 0.001], depressive symptoms [t(58) = −4.41, p < 0.001], functional impairment [t(58) = −2.26, p = 0.028], and proxy scores for CPTSD [t(58) = 4.69, p < 0.001]. There were no significant differences in outcomes between different treatments offered during phase 2. Baseline depressive symptoms were associated with higher PTSD symptoms and functional impairment. Conclusions This study suggests that TF-P effectively improves symptoms of CPTSD. However, prospective research with validated measurements is necessary to evaluate current and new treatments and identify personal markers of treatment effectiveness for CPTSD.</p

Understanding and modelling wildfire regimes: An ecological perspective

© 2021 The Author(s).Recent extreme wildfire seasons in several regions have been associated with exceptionally hot, dry conditions, made more probable by climate change. Much research has focused on extreme fire weather and its drivers, but natural wildfire regimes—and their interactions with human activities—are far from being comprehensively understood. There is a lack of clarity about the 'causes' of wildfire, and about how ecosystems could be managed for the co-existence of wildfire and people. We present evidence supporting an ecosystem-centred framework for improved understanding and modelling of wildfire. Wildfire has a long geological history and is a pervasive natural process in contemporary plant communities. In some biomes, wildfire would be more frequent without human settlement; in others they would be unchanged or less frequent. A world without fire would have greater forest cover, especially in present-day savannas. Many species would be missing, because fire regimes have co-evolved with plant traits that resist, adapt to or promote wildfire. Certain plant traits are favoured by different fire frequencies, and may be missing in ecosystems that are normally fire-free. For example, post-fire resprouting is more common among woody plants in high-frequency fire regimes than where fire is infrequent. The impact of habitat fragmentation on wildfire crucially depends on whether the ecosystem is fire-adapted. In normally fire-free ecosystems, fragmentation facilitates wildfire starts and is detrimental to biodiversity. In fire-adapted ecosystems, fragmentation inhibits fires from spreading and fire suppression is detrimental to biodiversity. This interpretation explains observed, counterintuitive patterns of spatial correlation between wildfire and potential ignition sources. Lightning correlates positively with burnt area only in open ecosystems with frequent fire. Human population correlates positively with burnt area only in densely forested regions. Models for vegetation-fire interactions must be informed by insights from fire ecology to make credible future projections in a changing climate.We gratefully acknowledge support from the Leverhulme Centre for Wildfires, Environment and Society, who organized the virtual mini-workshop which initiated the writing of this paper. RKN is supported by the Leverhulme Centre. SPH and YS acknowledge support from the ERC-funded project GC2.0 (Global Change 2.0: Unlocking the past for a clearer future, Grant Number 694481). ICP, KJB and ND acknowledge support from the ERC-funded project REALM (Re-inventing Ecosystem And Land-surface Models, Grant Number 787203). JCH acknowledges funding from the ERC project SCATAPNUT (Grant Number 681885). This work is a contribution to the LEMONTREE (Land Ecosystem Models based On New Theory, obseRvations and ExperimEnts) project, funded through the generosity of Eric and Wendy Schmidt by recommendation of the Schmidt Futures program (SPH, YS and ICP)

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The effectiveness of trauma-focused psychotherapy for complex post-traumatic stress disorder: A retrospective study

Objective We retrospectively evaluated the effectiveness of trauma-focused psychotherapy (TF-P) versus stabilization and waiting in a civilian cohort of patients with an 11th version of the international classification of disease (ICD-11) diagnosis of complex post-traumatic stress disorder (CPTSD). Methods We identified patients with CPTSD treated at a specialist trauma service over a 3-year period by triangulating evidence from self-report questionnaires, file review, and expert-clinician opinion. Patients completed a phase-based treatment: stabilization consisting of symptom management and establishing safety, followed by waiting for treatment (phase 1); individual TF-P in the form of trauma-focused cognitive behavioral therapy (TF-CBT), or eye movement desensitization and reprocessing (EMDR) or TF-CBT plus EMDR (phase 2). Our primary outcome was PTSD symptoms during phase 2 versus phase 1. Secondary outcomes included depressive symptoms, functional impairment, and a proxy CPTSD measure. Exploratory analysis compared outcomes between treatments. Adverse outcomes were recorded. Results Fifty-nine patients were included. Compared to receiving only phase 1, patients completing TF-P showed statistically significant reductions in PTSD [t(58) = −3.99, p < 0.001], depressive symptoms [t(58) = −4.41, p < 0.001], functional impairment [t(58) = −2.26, p = 0.028], and proxy scores for CPTSD [t(58) = 4.69, p < 0.001]. There were no significant differences in outcomes between different treatments offered during phase 2. Baseline depressive symptoms were associated with higher PTSD symptoms and functional impairment. Conclusions This study suggests that TF-P effectively improves symptoms of CPTSD. However, prospective research with validated measurements is necessary to evaluate current and new treatments and identify personal markers of treatment effectiveness for CPTSD.</p

Multistudy Research Operations in the ICU: An Interprofessional Pandemic-Informed Approach

OBJECTIVES:. Proliferation of COVID-19 research underscored the need for improved awareness among investigators, research staff and bedside clinicians of the operational details of clinical studies. The objective was to describe the genesis, goals, participation, procedures, and outcomes of two research operations committees in an academic ICU during the COVID-19 pandemic. DESIGN:. Two-phase, single-center multistudy cohort. SETTING:. University-affiliated ICU in Hamilton, ON, Canada. PATIENTS:. Adult patients in the ICU, medical stepdown unit, or COVID-19 ward. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. An interprofessional COVID Collaborative was convened at the pandemic onset within our department, to proactively coordinate studies, help navigate multiple authentic consent encounters by different research staff, and determine which studies would be suitable for coenrollment. From March 2020 to May 2021, five non-COVID trials continued, two were paused then restarted, and five were launched. Over 15 months, 161 patients were involved in 215 trial enrollments, 110 (51.1%) of which were into a COVID treatment trial. The overall informed consent rate (proportion agreed of those eligible and approached including a priori and deferred consent models) was 83% (215/259). The informed consent rate was lower for COVID-19 trials (110/142, 77.5%) than other trials (105/117, 89.7%; p = 0.01). Patients with COVID-19 were significantly more likely to be coenrolled in two or more studies (29/77, 37.7%) compared with other patients (13/84, 15.5%; p = 0.002). Review items for each new study were collated, refined, and evolved into a modifiable checklist template to set up each study for success. The COVID Collaborative expanded to a more formal Department of Critical Care Research Operations Committee in June 2021, supporting sustainable research operations during and beyond the pandemic. CONCLUSIONS:. Structured coordination and increased communication about research operations among diverse research stakeholders cultivated a sense of shared purpose and enhanced the integrity of clinical research operations

Glycogen Synthase Kinase-3 Is Required for Efficient Dictyostelium Chemotaxis

We present a new role for glycogen synthase kinase (GSK) in the regulation of aggregation and chemotaxis in Dictyostelium. GSK regulates two chemotactic pathways, PIP3 and TORC2; hence, a loss of function of GSK leads to poor chemotaxis, an observation not previously seen when only one chemotactic pathway was targeted

Identification of seven new prostate cancer susceptibility loci through a genome-wide association study

Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. To identify common PrCa susceptibility alleles, we have previously conducted a genome-wide association study in which 541, 129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and 1,894 controls. We have now evaluated promising associations in a second stage, in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls, and a third stage, involving an additional 16,229 cases and 14,821 controls from 21 studies. In addition to previously identified loci, we identified a further seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8, 11, and 22 (P=1.6×10−8 to P=2.7×10−33)