Adverse Events in Studies of Classic Psychedelics: A Systematic Review and Meta-Analysis.

Importance: A clear and comprehensive understanding of risks associated with psychedelic-assisted therapy is necessary as investigators extend its application to new populations and indications. Objective: To assess adverse events (AEs) associated with classic psychedelics, particularly serious AEs (SAEs) and nonserious AEs (NSAEs) requiring medical or psychiatric evaluation. Data Sources: The search for potentially eligible studies was conducted in the Scopus, MEDLINE, PsycINFO, and Web of Science databases from inception through February 8, 2024. Study Selection: Two independent reviewers screened articles of classic psychedelics (lysergic acid diethylamide [LSD], psilocybin, dimethyltryptamine [DMT], and 5-methoxy-N,N-dimethyltryptamine [5-MeO-DMT]) involving administration in clinical or research contexts. Data Extraction and Synthesis: AE data were extracted and synthesized by 2 reviewers and were used for random-effects meta-analysis of AE frequency and heterogeneity. Risk of bias assessment focused on AE ascertainment (eg, systematic assessment and quality of follow-up). Main Outcomes and Measures: A hybrid approach was used for capture of all reported AEs following high-dose classic psychedelic exposure and confirmatory capture of AEs of special interest, including suicidality, psychotic disorder, manic symptoms, cardiovascular events, and hallucinogen persisting perception disorder. AEs were stratified by timescale and study population type. Forest plots of common AEs were generated, and the proportions of participants affected by SAEs or NSAEs requiring medical intervention were summarized descriptively. Results: A total of 214 unique studies were included, of which 114 (53.3%) reported analyzable AE data for 3504 total participants. SAEs were reported for no healthy participants and for approximately 4% of participants with preexisting neuropsychiatric disorders; among these SAEs were worsening depression, suicidal behavior, psychosis, and convulsive episodes. NSAEs requiring medical intervention (eg, paranoia, headache) were similarly rare. In contemporary research settings, there were no reports of deaths by suicide, persistent psychotic disorders, or hallucinogen persisting perception disorders following administration of high-dose classic psychedelics. However, there was significant heterogeneity in the quality of AE monitoring and reporting. Of 68 analyzed studies published since 2005, only 16 (23.5%) described systematic approaches to AE assessment, and 20 studies (29.4%) reported all AEs, as opposed to only adverse drug reactions. Meta-analyses of prevalence for common AEs (eg, headache, anxiety, nausea, fatigue, and dizziness) yielded comparable results for psilocybin and LSD. Conclusions and Relevance: In this systematic review and meta-analysis, classic psychedelics were generally well tolerated in clinical or research settings according to the existing literature, although SAEs did occur. These results provide estimates of common AE frequencies and indicate that certain catastrophic events reported in recreational or nonclinical contexts have yet to be reported in contemporary trial participants. Careful, ongoing, and improved pharmacovigilance is required to understand the risk and benefit profiles of these substances and to communicate such risks to prospective study participants and the public.

Cardiovascular and all-cause mortality outcomes of adrenalectomy versus medical treatment in primary aldosteronism: an umbrella review.

BACKGROUND: Primary aldosteronism (PA) is now recognized as the most prevalent form of secondary hypertension globally, contributing significantly to cardiovascular morbidity and mortality. This umbrella review aims to systematically compare cardiovascular outcomes and all-cause mortality in PA patients undergoing adrenalectomy versus mineralocorticoid receptor antagonist (MRA) treatment, aiming to inform optimal management strategies. METHOD: Following PRISMA guidelines, Supplemental Digital Content 1, http://links.lww.com/JS9/D386, Supplemental Digital Content 2, http://links.lww.com/JS9/D387, a comprehensive search strategy was employed across multiple databases. Meta-analyses focusing on cardiovascular outcomes or all-cause mortality, comparing adrenalectomy and MRAs treatment in PA patients, were included. Studies were independently screened and assessed for quality using AMSTAR 2, Supplemental Digital Content 3, http://links.lww.com/JS9/D388 and GRADE checklists. RESULTS: A total of 8 studies met the inclusion criteria. Adrenalectomy showed potential benefits over MRAs in reducing the risk of arrhythmias (OR=2.17; 95% CI: 1.25-3.76) and major adverse cardiovascular events (OR=1.81; 95% CI: 1.33-2.46). Patients treated with MRAs exhibited a higher risk of cardiovascular events (OR=1.23; 95% CI: 1.05-1.44), hypertension (OR=3.22; 95% CI: 1.15-8.97), and all-cause mortality (OR=3.03; 95% CI: 1.36-6.70) compared to adrenalectomy. CONCLUSION: Adrenalectomy appears to offer favorable outcomes compared to MRAs treatment in PA patients, particularly in reducing the risk of major adverse cardiovascular events and all-cause mortality. These findings suggest the importance of considering surgical intervention as a primary treatment modality for PA.

Global Prevalence of Nonalcoholic Fatty Liver Disease: An Updated Review Meta-Analysis comprising a Population of 78 million from 38 Countries.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a global health challenge, with a rising rate in line with other metabolic diseases. We aimed to assess the global prevalence of NAFLD in adult and pediatric populations. METHODS: PubMed, Scopus and Web of Science databases were systematically searched up to May 2023. Heterogeneity was assessed using Cochran's Q test and I2 statistics, and random-effects model was used for meta-analysis. Analyses were performed using STATA version 18. RESULTS: A total of 479 studies with 78,001,755 participants from 38 countries were finally included. The global prevalence of NAFLD was estimated to be 30.2% (95% CI: 28.7-31.7%). Regionally, the prevalence of NAFLD was as follows: Asia 30.9% (95% CI: 29.2-32.6%), Australia 16.1% (95% CI: 9.0-24.8%), Europe 30.2% (95% CI: 25.6-35.0%), North America 29% (95% CI: 25.8-32.3%), and South America 34% (95% CI: 16.9-53.5%). Countries with a higher human development index (HDI) had significantly lower prevalence of NAFLD (coefficient = -0.523, p = 0.005). Globally, the prevalence of NAFLD in men and women was 36.6% (95% CI: 34.7-38.4%) and 25.5% (95% CI: 23.9-27.1%), respectively. The prevalence of NAFLD in adults, adults with obesity, children, and children with obesity was 30.2% (95% CI: 28.8-31.7%), 57.5% (95% CI: 43.6-70.9%), 14.3% (95% CI: 10.3-18.8%), and 38.0% (95% CI: 31.5-44.7%), respectively. CONCLUSION: The prevalence of NAFLD is remarkably high, particularly in countries with lower HDI. This substantial prevalence in both adults and children underscores the need for disease management protocols to reduce the burden.

Diagnostic and prognostic value of triglyceride glucose index: a comprehensive evaluation of meta-analysis.

OBJECTIVE: The present umbrella review aims to collate and summarize the findings from previous meta-analyses on the Triglyceride and Glucose (TyG) Index, providing insights to clinicians, researchers, and policymakers regarding the usefulness of this biomarker in various clinical settings. METHODS: A comprehensive search was conducted in PubMed, Scopus, and Web of Science up to April 14, 2024, without language restrictions. The AMSTAR2 checklist assessed the methodological quality of the included meta-analyses. Statistical analyses were performed using Comprehensive Meta-Analysis (CMA) software. RESULTS: A total of 32 studies were finally included. The results revealed significant associations between the TyG index and various health outcomes. For kidney outcomes, a high TyG index was significantly associated with an increased risk of contrast-induced nephropathy (CIN) (OR = 2.24, 95% CI: 1.82-2.77) and chronic kidney disease (CKD) (RR = 1.46, 95% CI: 1.32-1.63). High TyG index was significantly associated with an increased risk of type 2 diabetes mellitus (T2DM) (RR = 3.53, 95% CI: 2.74-4.54), gestational diabetes mellitus (GDM) (OR = 2.41, 95% CI: 1.48-3.91), and diabetic retinopathy (DR) (OR = 2.34, 95% CI: 1.31-4.19). Regarding metabolic diseases, the TyG index was significantly higher in patients with obstructive sleep apnea (OSA) (SMD = 0.86, 95% CI: 0.57-1.15), metabolic syndrome (MD = 0.83, 95% CI: 0.74-0.93), and non-alcoholic fatty liver disease (NAFLD) (OR = 2.36, 95% CI: 1.88-2.97) compared to those without these conditions. In cerebrovascular diseases, a higher TyG index was significantly associated with an increased risk of dementia (OR = 1.14, 95% CI: 1.12-1.16), cognitive impairment (OR = 2.31, 95% CI: 1.38-3.86), and ischemic stroke (OR = 1.37, 95% CI: 1.22-1.54). For cardiovascular outcomes, the TyG index showed significant associations with an increased risk of heart failure (HF) (HR = 1.21, 95% CI: 1.12-1.30), atrial fibrillation (AF) (SMD = 1.22, 95% CI: 0.57-1.87), and hypertension (HTN) (RR = 1.52, 95% CI: 1.25-1.85). CONCLUSION: The TyG index is a promising biomarker for screening and predicting various medical conditions, particularly those related to insulin resistance and metabolic disorders. However, the heterogeneity and methodological quality of the included studies suggest the need for further high-quality research to confirm these findings and refine the clinical utility of the TyG index.

Gut microbiota interventions in type 2 diabetes mellitus: An umbrella review of glycemic indices.

BACKGROUND: We aimed to explore how probiotics, prebiotics, or synbiotics impact glycemic indices in patients with diabetes mellitus. METHOD: A comprehensive search was conducted on PubMed, Scopus, and Web of Science from inception up to April 2023. The random-effects model was employed for the study analysis. Furthermore, sensitivity and subgroup analyses were conducted to investigate potential sources of heterogeneity. AMSTAR2 checklist was used to determine the quality of studies. Comprehensive meta-analysis version 3 was used for the study analysis. RESULT: A total of 31 studies were included in the final analysis. Based on the results of the meta-analysis, gut microbial therapy could significantly decrease serum fasting blood glucose levels in patients with type 2 diabetes mellitus (effect size: -0.211; 95 % CI: -0.257, -0.164; P < 0.001). Additionally, significant associations were also found between gut microbial therapy and improved serum levels of fasting insulin, glycated hemoglobin, and homeostatic model assessment for insulin resistance (effect size: -0.087; 95 % confidence interval: -0.120, -0.053; P < 0.001; effect size: -0.166; 95 % confidence interval: -0.200, -0.132; P < 0.001; effect size: -0.230; 95 % confidence interval: -0.288, -0.172; P < 0.001, respectively). CONCLUSION: Our results revealed promising effects of gut microbiota modulation on glycemic profile of patients with type 2 diabetes mellitus. The use of these agents as additional treatments can be considered.

The Ability of ChatGPT in Paraphrasing Texts and Reducing Plagiarism: A Descriptive Analysis.

Background: The introduction of ChatGPT by OpenAI has garnered significant attention. Among its capabilities, paraphrasing stands out. Objective: This study aims to investigate the satisfactory levels of plagiarism in the paraphrased text produced by this chatbot. Methods: Three texts of varying lengths were presented to ChatGPT. ChatGPT was then instructed to paraphrase the provided texts using five different prompts. In the subsequent stage of the study, the texts were divided into separate paragraphs, and ChatGPT was requested to paraphrase each paragraph individually. Lastly, in the third stage, ChatGPT was asked to paraphrase the texts it had previously generated. Results: The average plagiarism rate in the texts generated by ChatGPT was 45% (SD 10%). ChatGPT exhibited a substantial reduction in plagiarism for the provided texts (mean difference -0.51, 95% CI -0.54 to -0.48; P<.001). Furthermore, when comparing the second attempt with the initial attempt, a significant decrease in the plagiarism rate was observed (mean difference -0.06, 95% CI -0.08 to -0.03; P<.001). The number of paragraphs in the texts demonstrated a noteworthy association with the percentage of plagiarism, with texts consisting of a single paragraph exhibiting the lowest plagiarism rate (P<.001). Conclusions: Although ChatGPT demonstrates a notable reduction of plagiarism within texts, the existing levels of plagiarism remain relatively high. This underscores a crucial caution for researchers when incorporating this chatbot into their work.

Efficacy of Radiofrequency Ablation in Autonomous Functioning Thyroid Nodules: A Comprehensive Systematic Review and Meta-analysis.

BACKGROUND: Radiofrequency ablation (RFA) is a minimally invasive outpatient procedure that has recently emerged as a treatment option for autonomous functioning thyroid nodules (AFTNs), offering a less invasive alternative to surgery. The objective of this systematic review and meta-analysis is to evaluate the efficacy of RFA for AFTNs. METHOD: Global databases of PubMed, Scopus, Embase, Web of Science, and Cochrane Library were systematically searched from 1990 until January 5, 2024, for studies on AFTNs undergoing RFA that presented volume reduction ratio (VRR) for at least one of 1, 3, 6 or 12 months post-operative follow-up with the results presented as means. The primary outcomes were VRR and TSH normalization rate, and the secondary outcomes were the cosmetic score, symptom score, and post-procedure complications. Heterogeneity was assessed by Cochrane and I2 statistics, and a random-effects model was used for meta-analysis. The study protocol was registered on PROSPERO (CRD42024499932). RESULTS: A total of 10 eligible studies with a total sample size of 254 were included. The pooled VRR after 1, 3, 6, and 12 months of follow-up post-treatment with RFA was 46.6% (95% CI: 40.3-52.9%), 62% (95% CI: 57.6-66.4%), 67.4% (95% CI:62.3-72.6%), and 77.2% (95% CI: 79.2-81.5%), respectively. The overall rate of TSH normalization was 76.4% (95% CI: 58.1-88.4%). Based on included studies the overall rate of subclinical hypothyroidism as one of the most important side effects of this method was 4% (95% CI: 1.9%-8.1%). CONCLUSION: RFA emerges as a promising non-surgical treatment for AFTNs, showing high rates of TSH normalization, tumor size reduction, and improved cosmetic and symptom scores. However, further research is needed to compare RFA with surgical methods and assess long-term outcomes.

Simultaneous surgical management of malignancy and coronary heart disease.

Coronary heart disease and cancer are the most common causes of mortality across the globe. It has been a dilemma for the surgical team to decide which surgical procedure should be done first when a patient needs surgery for both. This is a single-center retrospective observational study. Six patients who underwent simultaneous coronary artery bypass graft (CABG) and oncological surgeries between January 2018 and July 2021 were included in the study. One patient underwent lung bilobectomy via the same sternotomy incision; one underwent surgery for breast cancer, stomach cancer, and colon cancer; and one patient each of buccal mucosa carcinoma and tongue carcinoma. The median age was 65 years (59-70). Median blood loss was 550 ml (400-800). The median intensive care unit (ICU) stay was 60 h (46-130) and hospital stay was 7.5 days (6-14). The median follow-up of the present study was 31.5 months (6-38). One patient with lung carcinoma developed recurrence after 6 months and the patient is in remission after a follow-up of 32 months. Simultaneous CABG and oncological resection can be performed effectively and safely by an experienced team of cardiothoracic surgeons, surgical oncologists, and anesthetists after good patient selection.

Psychedelic Experiences Increase Mind Perception but do not Change Atheist-Believer Status: A Prospective Longitudinal Study.

Recent studies suggest psychedelic use may be associated with changes in a variety of beliefs or belief-like states, including increased 1) mind perception, 2) non-naturalistic beliefs, and 3) Atheist-Believer status (e.g. believer, agnostic, or nonbeliever). We conducted a prospective longitudinal study among participants (N = 657) who planned to have a psilocybin experience outside a laboratory setting. We asked participants about their beliefs concerning mind perception of various entities, specific metaphysical positions, and Atheist-Believer status both before (and after their experience. Replicating previous findings, we observed increases in mind perception across a variety of living and non-living targets (e.g. plants, rocks). However, we found little to no change in metaphysical beliefs (e.g. dualism) or Atheist-Believer status. Taken together, these findings contrast with those from cross-sectional studies that psilocybin experiences result in changes to Atheist-Believer status and non-naturalistic beliefs but support the relevance of mind perception and mentalization.

Can modulation of gut microbiota affect anthropometric indices in patients with non-alcoholic fatty liver disease? An umbrella meta-analysis of randomized controlled trials.

Background and aim: Modulating the gut microbiota population by administration of probiotics, prebiotics, and synbiotics has shown to have a variety of health benefits in different populations, particularly those with metabolic disorders. Although the promising effects of these compounds have been observed in the management of patients with non-alcoholic fatty liver disease (NAFLD), the exact effects and the mechanisms of action are yet to be understood. In the present study, we aimed to evaluate how gut microbiota modulation affects anthropometric indices of NAFLD patients to achieve a comprehensive summary of current evidence-based knowledge. Methods: Two researchers independently searched international databases, including PubMed, Scopus, and Web of Science, from inception to June 2023. Meta-analysis studies that evaluated the effects of probiotics, prebiotics, and synbiotics on patients with NAFLD were entered into our umbrella review. The data regarding anthropometric indices, including body mass index, weight, waist circumference (WC), and waist-to-hip ratio (WHR), were extracted by the investigators. The authors used random effect model for conducting the meta-analysis. Subgroup analysis and sensitivity analysis were also performed. Results: A total number of 13 studies were finally included in our study. Based on the final results, BMI was significantly decreased in NAFLD patients by modulation of gut microbiota [effect size (ES): -0.18, 05% CI: -0.25, -0.11, P<0.001]; however, no significant alteration was observed in weight and WC (ES: -1.72, 05% CI: -3.48, 0.03, P=0.055, and ES: -0.24, 05% CI: -0.75, 0.26, P=0.353, respectively). The results of subgroup analysis showed probiotics had the most substantial effect on decreasing BMI (ES: -0.77, 95% CI: -1.16, -0.38, P<0.001) followed by prebiotics (ES: -0.51, 95% CI: -0.76, -0.27, P<0.001) and synbiotics (ES: -0.12, 95% CI: -0.20, -0.04, P=0.001). Conclusion: In conclusion, the present umbrella meta-analysis showed that although modulation of gut microbiota by administration of probiotics, prebiotics, and synbiotics had promising effects on BMI, no significant change was observed in the WC and weight of the patients. No sufficient data were available for other anthropometric indices including waist-to-hip ratio and waist-to-height ratio and future meta-analyses should be done in this regard.

The effects of gut microbiome manipulation on glycemic indices in patients with non-alcoholic fatty liver disease: a comprehensive umbrella review.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a significant risk factor for non-alcoholic fatty liver disease (NAFLD). Increased fasting blood sugar (FBS), fasting insulin (FI), and insulin resistance (HOMA-IR) are observed in patients with NAFLD. Gut microbial modulation using prebiotics, probiotics, and synbiotics has shown promise in NAFLD treatment. This meta-umbrella study aimed to investigate the effects of gut microbial modulation on glycemic indices in patients with NAFLD and discuss potential mechanisms of action. METHODS: A systematic search was conducted in PubMed, Web of Science, Scopus, and Cochrane Library until March 2023 for meta-analyses evaluating the effects of probiotics, prebiotics, and synbiotics on patients with NAFLD. Random-effect models, sensitivity analysis, and subgroup analysis were employed. RESULTS: Gut microbial therapy significantly decreased HOMA-IR (ES: -0.41; 95%CI: -0.52, -0.31; P < 0.001) and FI (ES: -0.59; 95%CI: -0.77, -0.41; P < 0.001). However, no significant effect was observed on FBS (ES: -0.17; 95%CI: -0.36, 0.02; P = 0.082). Subgroup analysis revealed prebiotics had the most potent effect on HOMA-IR, followed by probiotics and synbiotics. For FI, synbiotics had the most substantial effect, followed by prebiotics and probiotics. CONCLUSION: Probiotics, prebiotics, and synbiotics administration significantly reduced FI and HOMA-IR, but no significant effect was observed on FBS.

The impact of pre-stroke metformin use on clinical outcomes after acute ischemic stroke: A systematic review and meta-analysis.

OBJECTIVES: Stroke is a leading cause of mortality and disability globally, with limited treatment options available for acute ischemic stroke (AIS) patients. Type 2 diabetes mellitus (T2DM) is not only widespread but also a known risk factor for stroke. Our meta-analysis aims to assess the influence of pre-stroke metformin use on the clinical outcomes in AIS patients with T2DM. MATERIALS AND METHODS: We conducted this study following PRISMA guidelines, searching the following databases: Medline, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials up to February 29, 2024. All studies providing separate data on AIS patients using metformin were included, and statistical analysis was conducted using R software to pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI). RESULTS: Out of 1051 studies, 7 met the inclusion criteria for our meta-analysis with a total of 11589 diabetic patients, including 5445 patients taking metformin and 6144 diabetic patients in the non-metformin group. Compared to the non-metformin group, the metformin group had a significantly higher rate of mRS 0-2 score at discharge (OR 1.56; 95% CI 1.25:1.95; p=< 0.01) and a lower rate of 90-day mortality (OR 0.51; 95% CI 0.42:0.61; p=< 0.01), with no significant difference in sICH (OR 0.88; 95% CI 0.47:1.64; p= 0.68) between the two groups. CONCLUSIONS: Our meta-analysis demonstrated that pre-stroke metformin use is associated with higher functional independence and lower mortality in AIS patients with T2DM.

Evaluating biomarkers for contrast-induced nephropathy following coronary interventions: an umbrella review on meta-analyses.

BACKGROUND: Contrast-induced nephropathy (CIN) is a form of acute kidney injury (AKI) occurring in patients undergoing cardiac catheterization, such as coronary angiography (CAG) or percutaneous coronary intervention (PCI). Although the conventional criterion for CIN detection involves a rise in creatinine levels within 72 h after contrast media injection, several limitations exist in this definition. Up to now, various meta-analyses have been undertaken to assess the accuracy of different biomarkers of CIN prediction. However, the existing body of research lacks a cohesive overview. To address this gap, a comprehensive umbrella review was necessary to consolidate and summarize the outcomes of prior meta-analyses. This umbrella study aimed to offer a current, evidence-based understanding of the prognostic value of biomarkers in predicting CIN. METHODS: A systematic search of international databases, including PubMed, Scopus, and Web of Science, from inception to December 12, 2023, was conducted to identify meta-analyses assessing biomarkers for CIN prediction. Our own meta-analysis was performed by extracting data from the included studies. Sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were assessed using Meta-Disc and CMA softwares. RESULTS: Twelve studies were ultimately included in the umbrella review. The results revealed that neutrophil gelatinase-associated lipocalin (NGAL) exhibited the highest area under the curve (AUC), followed by cystatin-C, urinary kidney injury molecule-1 (uKIM-1), and brain natriuretic peptide (BNP) with AUCs of 0.91, 0.89, 0.85, and 0.80, respectively. NGAL also demonstrated the highest positive likelihood ratio [effect size (ES): 6.02, 95% CI 3.86-9.40], followed by cystatin-C, uKIM-1, and BNP [ES: 4.35 (95% CI 2.85-6.65), 3.58 (95% CI 2.75-4.66), and 2.85 (95% CI 2.13-3.82), respectively]. uKIM-1 and cystatin-C had the lowest negative likelihood ratio, followed by NGAL and BNP [ES: 0.25 (95% CI 0.17-0.37), ES: 0.25 (95% CI 0.13-0.50), ES: 0.26 (95% CI 0.17-0.41), and ES: 0.39 (0.28-0.53) respectively]. NGAL emerged as the biomarker with the highest diagnostic odds ratio for CIN, followed by cystatin-C, uKIM-1, BNP, gamma-glutamyl transferase, hypoalbuminemia, contrast media volume to creatinine clearance ratio, preprocedural hyperglycemia, red cell distribution width (RDW), hyperuricemia, neutrophil-to-lymphocyte ratio, C-reactive protein (CRP), high-sensitivity CRP, and low hematocrit (P < 0.05). CONCLUSION: NGAL demonstrated superior diagnostic performance, exhibiting the highest AUC, positive likelihood ratio, and diagnostic odds ratio among biomarkers for CIN, followed by cystatin-C, and uKIM-1. These findings underscore the potential clinical utility of NGAL, cystatin-C and uKIM-1 in predicting and assessing CIN.

The therapeutic alliance between study participants and intervention facilitators is associated with acute effects and clinical outcomes in a psilocybin-assisted therapy trial for major depressive disorder.

We examined if the therapeutic alliance between study participants and intervention facilitators in a psilocybin-assisted therapy (PAT) trial changed over time and whether there were relationships between alliance, acute psilocybin experiences, and depression outcomes. In a randomized, waiting list-controlled clinical trial for major depressive disorder in adults (N = 24), participants were randomized to an immediate (N = 13) or delayed (N = 11) condition with two oral doses of psilocybin (20mg/70kg and 30mg/70kg). Ratings of therapeutic alliance significantly increased from the final preparation session to one-week post-intervention (p = .03, d = .43). A stronger total alliance at the final preparation session predicted depression scores at 4 weeks (r = -.65, p = .002), 6 months (r = -.47, p = .036), and 12 months (r = -.54, p = .014) post-intervention. A stronger total alliance in the final preparation session was correlated with higher peak ratings of mystical experiences (r = .49, p = .027) and psychological insight (r = .52, p = .040), and peak ratings of mystical experience and psychological insight were correlated with depression scores at 4 weeks (r = -.45, p = .030 for mystical; r = -.75, p < .001 for insight). Stronger total alliance one week after the final psilocybin session predicted depression scores at 4 weeks (r = -.85, p < .001), 3 months (r = -.52, p = .010), 6 months (r = -.77, p < .001), and 12 months (r = -.61, p = .001) post-intervention. These findings highlight the importance of the therapeutic relationship in PAT. Future research should explore therapist and participant characteristics which maximize the therapeutic alliance and evaluate its relationship to treatment outcomes. Trial registration: Registration: Clinicaltrials.gov NCT03181529. https://classic.clinicaltrials.gov/ct2/show/NCT03181529.

Intensive vs Conventional Blood Pressure Control After Thrombectomy in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Importance: Endovascular thrombectomy (EVT) is standard treatment for acute ischemic stroke (AIS) due to large-vessel occlusion (LVO), but optimal post-EVT blood pressure (BP) control remains debated. Objective: To assess the association of different systolic BP targets following EVT with functional outcomes, mortality, and complications in patients with AIS due to LVO. Data Sources: Systematic review and meta-analysis of databases (PubMed, Embase, Web of Science, Scopus, and Cochrane Library) to September 8, 2023. Study Selection: Inclusion criteria consisted of randomized clinical trials examining post-EVT management of systolic BP in patients with AIS and LVO comparing intensive vs conventional targets. Nonrandomized studies, observational studies, noninterventional trials, meeting abstracts, duplicate studies, studies with overlapping data, and non-English language studies were excluded. Two authors independently applied these criteria through a blinded review, with discrepancies resolved through consensus. The risk of bias in the included studies was assessed using the revised tool for assessing risk of bias in randomized trials. Data Extraction and Synthesis: This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Three authors extracted data regarding study characteristics, baseline patient data, and outcomes of interest. The pooled data were analyzed using a random-effects meta-analysis. Main Outcomes and Measures: Rates of functional independence, 90-day mortality, symptomatic intracranial hemorrhage, and hypotensive events. Results: A total of 4 randomized clinical trials with 1571 initially enrolled patients were included in the analysis. Lower functional independence rates were observed in the intensive control group (relative risk [RR], 0.81 [95% CI, 0.67-0.98]). No significant differences were found in 90-day mortality (RR, 1.18 [95% CI, 0.92-1.52]), symptomatic intracranial hemorrhage (RR, 1.12 [95% CI, 0.75-1.67]), or hypotensive events (RR, 1.80 [95% CI, 0.37-8.76]). There was minimal heterogeneity among the studies included in the functional independence outcome (I2 = 13% and τ2 = 0.003), which was absent among other outcomes (I2 = 0 and τ2 = 0). Conclusions and Relevance: These findings suggest that intensive post-EVT BP reduction does not yield benefits and may carry risks. While awaiting the results of additional ongoing trials, a conservative BP management strategy after endovascular recanalization is favored in daily practice.

IUPHAR-review: The integration of classic psychedelics into current substance use disorder treatment models.

Substance use disorders (SUDs) have an enormous impact on public health. With classic psychedelic-assisted therapies showing initial promise in treating multiple SUDs, it is possible that these treatments will become legally available options for patients with SUDs in the future. This article highlights how classic psychedelic-assisted therapies might be integrated into current clinical practice. We first describe contemporary evidence-based treatments for SUDs and highlight how classic psychedelic-assisted therapies might fit within each treatment. We suggest that classic psychedelic-assisted therapies can be integrated into most mainstream evidence-based SUD treatments that are currently used in clinical settings, indicating broad compatibility of classic psychedelics with contemporary SUD treatment paradigms.