Effects of cannabidiol and Δ9-tetrahydrocannabinol on cytochrome P450 enzymes: a systematic review.

Due to legal, political, and cultural changes, the use of cannabis has rapidly increased in recent years. Research has demonstrated that the cannabinoids cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) inhibit and induce cytochrome P450 (CYP450) enzymes. The objective of this review is to evaluate the effect of CBD and THC on the activity of CYP450 enzymes and the implications for drug-drug interactions (DDIs) with psychotropic agents that are CYP substrates. A systematic search was conducted using PubMed, Scopus, Scientific Electronic Library Online (SciELO) and PsychINFO. Search terms included 'cannabidiol', 'tetrahydrocannabinol', and 'cytochrome P450'. A total of seven studies evaluating the interaction of THC and CBD with CYP450 enzymes and psychotropic drugs were included. Both preclinical and clinical studies were included. Results from the included studies indicate that both CBD and THC inhibit several CYP450 enzymes including, but not limited to, CYP1A2, CYP3C19, and CYP2B6. While there are a few known CYP450 enzymes that are induced by THC and CBD, the induction of CYP450 enzymes is an understudied area of research and lacks clinical data. The inhibitory effects observed by CBD and THC on CYP450 enzymes vary in magnitude and may decrease the metabolism of psychotropic agents, cause changes in plasma levels of psychotropic medications, and increase adverse effects. Our findings clearly present interactions between THC and CBD and several CYP450 enzymes, providing clinicians evidence of a high risk of DDIs for patients who consume both cannabis and psychotropic medication. However, more clinical research is necessary before results are applied to clinical settings.

Impacts of metabolic disruption, body mass index and inflammation on cognitive function in post-COVID-19 condition: a randomized controlled trial on vortioxetine.

BACKGROUND: Post-COVID-19 Condition (PCC), as defined by the World Health Organization (WHO), currently lacks any regulatory-approved treatments and is characterized by persistent and debilitating cognitive impairment and mood symptoms. Additionally, metabolic dysfunction, chronic inflammation and the associated risks of elevated body mass index (BMI) have been reported. In this study, we aim to investigate the efficacy of vortioxetine in improving cognitive deficits in individuals with PCC, accounting for the interaction of metabolic dysfunction, elevated inflammation and BMI. METHODS: This is a post-hoc analysis of an 8-week randomized, double-blind, placebo-controlled trial that was conducted among adults aged 18 years and older living in Canada who were experiencing WHO-defined PCC symptoms. The recruitment of participants began in November 2021 and concluded in January 2023. A total of 200 individuals were enrolled, where 147 were randomized in a 1:1 ratio to receive either vortioxetine (5-20 mg, n = 73) or placebo (n = 74) for daily treatment under double-blind conditions. The primary outcome measure was the change in the Digit Symbol Substitution Test (DSST) score from baseline to endpoint. RESULTS: Our findings showed significant effects for time (χ2 = 7.771, p = 0.005), treatment (χ2 = 7.583, p = 0.006) and the treatment x time x CRP x TG-HDL x BMI interaction (χ2 = 11.967, p = 0.018) on cognitive function. Moreover, the between-group analysis showed a significant improvement with vortioxetine at endpoint (mean difference = 0.621, SEM = 0.313, p = 0.047). CONCLUSION: Overall, vortioxetine demonstrated significant improvements in cognitive deficits among individuals with baseline markers of metabolic dysfunction, elevated inflammation and higher BMI at endpoint as compared to placebo. TRIAL REGISTRATION: NCT05047952 (ClinicalTrials.gov; Registration Date: September 17, 2021).

Impact of elevated body mass index (BMI) on cognitive functioning and inflammation in persons with post-COVID-19 condition: a secondary analysis.

BACKGROUND: Individuals who have recovered from the acute stage of SARS-CoV-2 infection may be at risk of developing post-COVID-19 condition (PCC), characterised by a spectrum of persisting, non-specific, and functionally impairing symptoms across multiple organ systems. Obesity has been implicated as a risk factor for PCC, mediated by chronic systemic inflammation. The foregoing has also been separately reported to mediate cognitive dysfunction in PCC. METHODS: This is a post-hoc analysis of a randomised, double-blinded, placebo-controlled clinical trial evaluating vortioxetine treatment for cognitive impairments in persons with PCC who received vortioxetine or placebo for eight weeks. This analysis comprises baseline data, examining the impact of BMI on cognitive functioning measured by the Digit Symbol Substitution Test (DSST) and Trails Making Tests (TMT)-A/B, as well as inflammation, via serum c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). RESULTS: Complete data from 70 participants were statistically analysed and adjusted for age and sex. BMI was negatively correlated with performance on the DSST (ß = -0.003, p = 0.047), TMT-A (ß = -0.006, p = 0.025), and TMT-B (ß = -0.006, p = 0.002). BMI was positively correlated with serum CRP (unstandardized ß = 0.193, standardized ß = 0.612, p < 0.001) and ESR (ß = 0.039, p < 0.001) levels. CONCLUSION: We observed a significant negative correlation between BMI and cognitive functioning, and a significant positive correlation between BMI and inflammation in persons with PCC, suggesting a bidirectional interplay between BMI, PCC, and cognitive function; individuals with an elevated BMI may be at a greater risk of developing PCC and/or presenting with greater cognitive deficits mediated by chronic systemic inflammation.

How to treat subsyndromal anxiety disorder - practical recommendations for implementation in primary care.

BACKGROUND: Anxiety is a common and disabling condition that significantly impacts quality of life. Subsyndromal anxiety (SSA) refers to anxiety symptoms that do not meet the full diagnostic criteria for an anxiety disorder but pose a risk for developing such disorders. We aimed to provide practical recommendations for the treatment of SSA in primary care settings. METHODS: A narrative review was conducted to identify strategies for recognizing and treating patients with SSA. RESULTS: The recommendations for treating SSA include lifestyle modifications such as exercise and stress reduction techniques, psychotherapy, and pharmacological treatments, including natural compounds like the lavender oil extract Silexan. Regular follow-up care is essential to monitor treatment response and address ongoing symptoms. Additionally, the use of the GAD-7 tool is recommended for accurately identifying patients with SSA. CONCLUSION: Implementing these recommendations in primary care can lead to effective treatment of SSA, preventing the development of more severe anxiety disorders. An integrative approach, combining lifestyle modifications, psychotherapy, and pharmacotherapy, including natural compounds, offers significant benefits for managing anxiety.

Anxiety is prevalent and disablingSubsyndromal anxiety is a risk factor for anxiety disordersSubsyndromal anxiety can be assessed with the GAD-7 (Generalised Anxiety Disorder-7 scale)Subsyndromal anxiety can be treated with life-style modification, psychotherapy and pharmacological treatment, including silexan, a natural compound.

Psychological Health of Surgeons in a Time of COVID-19: A Global Survey.

OBJECTIVE: To assess the degree of psychological impact among surgical providers during the COVID-19 pandemic. SUMMARY OF BACKGROUND DATA: The COVID-19 pandemic has extensively impacted global healthcare systems. We hypothesized that the degree of psychological impact would be higher for surgical providers deployed for COVID-19 work, certain surgical specialties, and for those who knew of someone diagnosed with, or who died, of COVID-19. METHODS: We conducted a global web-based survey to investigate the psychological impact of COVID-19. The primary outcomes were the depression anxiety stress scale-21 and Impact of Event Scale-Revised scores. RESULTS: A total of 4283 participants from 101 countries responded. 32.8%, 30.8%, 25.9%, and 24.0% screened positive for depression, anxiety, stress, and PTSD respectively. Respondents who knew someone who died of COVID-19 were more likely to screen positive for depression, anxiety, stress, and PTSD (OR 1.3, 1.6, 1.4, 1.7 respectively, all P < 0.05). Respondents who knew of someone diagnosed with COVID-19 were more likely to screen positive for depression, stress, and PTSD (OR 1.2, 1.2, and 1.3 respectively, all P < 0.05). Surgical specialties that operated in the head and neck region had higher psychological distress among its surgeons. Deployment for COVID- 19-related work was not associated with increased psychological distress. CONCLUSIONS: The COVID-19 pandemic may have a mental health legacy outlasting its course. The long-term impact of this ongoing traumatic event underscores the importance of longitudinal mental health care for healthcare personnel, with particular attention to those who know of someone diagnosed with, or who died of COVID-19.

COVID-19 vaccination for the prevention and treatment of long COVID: A systematic review and meta-analysis.

Empirical evidence addressing the association between SARS-CoV-2 vaccination and long COVID would guide public health priorities and inform personal health decisions. Herein, the co-primary objectives are to determine the differential risk of long COVID in vaccinated versus unvaccinated patients, and the trajectory of long COVID following vaccination. Of 2775 articles identified via systematic search, 17 were included, and 6 were meta-analyzed. Meta-analytic results determined that at least one vaccine dose was associated with a protective effect against long COVID (OR 0.539, 95% CI 0.295-0.987, p = 0.045, N = 257 817). Qualitative analysis revealed that trajectories of pre-existing long COVID following vaccination were mixed, with most patients reporting no changes. The evidence herein supports SARS-CoV-2 vaccination for the prevention of long COVID, and recommends long COVID patients adhere to standard SARS-CoV-2 vaccination schedules.

Mapping Studies of Alcohol Use Among People Living with HIV/AIDS During 1990-2019 (GAPRESEARCH).

Alcohol drinking has long been reported to be common in people living with HIV/AIDS, having biological and behavioral impacts on the transmission, progression, and prevention of HIV/AIDS. A total of 7059 eligible articles and reviews published in English from 1990 to 2019 were extracted from the WOS. Results show an increase in publication volume, while citations peak for papers published in 2006. Content analysis reveals a wide-ranging coverage of topics, with the most popular being effects of alcohol consumption on ART adherence and outcomes, alcohol-related sexual behaviors, TB co-infection, and psycho-socio-cultural considerations in examining and designing measures targeting alcohol use and interventions to reduce alcohol dependence in PLWHA. This calls for more active engagement of governments in research and in designing and implementing interventions, as well as collaborations and knowledge transfer from high-income countries to developing counterparts, to effectively address alcohol use-related issues in PLWHA, moving toward the HIV/AIDS eradication target.

Changes in Quality of life Outcomes of Patients with HIV/AIDS Under a Theory-based Mobile Health Intervention.

This study examined the effectiveness of a theory-based mHealth intervention on the quality of life (QOL) of people living with HIV. A randomized controlled trial was performed at two outpatient clinics in Hanoi, Vietnam. There were 428 patients with HIV/AIDs in selected clinics and were divided into the intervention arm (receiving HIV-assisted smartphone application and usual care) and the control arm (receiving only usual care). The WHOQOLHIV-BREF instrument was utilized to measure QOL. An intention-to-treat approach using Generalized Linear Mixed Model analysis was performed. The trial showed significant improvements in Physical health, Psychological health, and Level of Dependence among patients in the intervention arm compared to the control arm. However, the Environment and Spirituality/Personal beliefs improvements would require additional interventions, both individual, organizational, or governmental. This study explored the utility of a smartphone mobile application for individuals with HIV, and how the resultant application could improve the overall QOL.

Impact of interventions on the quality of life of cancer patients: a systematic review and meta-analysis of longitudinal research.

The impact of cancer interventions has been conducted in several research due to the significant burden of this non-communicable disease. The interventions that played an important role in the improvement of the patient's quality of life (QoL) and health-related quality of life (HRQL) can be classified into two main groups: pharmaceutical and non-pharmacological methods. However, studies so far often analyze a specific group of interventions for specific types of cancer. Thus, in this systematic review and meta-analysis, we synthesized the overall impact of cancer interventions on patients' quality of life in several cancers.In this research, we followed the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) to search the longitudinal original research on the Web of Science (WOS) database. After that, the Newcastle-Ottawa Scale (NOS) and Jadad Scale were used to assess the quality of non-randomized control trials and randomized control trials, respectively. Then, the characteristics of the included studies were described in the six main fields table and the random effect model with robust estimation was applied to analyze the impact of interventions on the health utility of patients.From the database, 122 longitudinal original research were included in the meta-regression, with most of them having high or fair quality. The European Organization for the research and treatment of cancer scale for quality of life (EORTC-QLQ) was the most used health utility measurement at 65.15%. In the adjusted effect models, the Visual Analogue Scale (VAS) had significant statistics in all models when we compared it with the EQ-5D Scale (p < 0.05) and several types of cancer such as breast, lung, and prostate cancer had significant statistics when comparing with hematological cancer in the model types of cancer (p < 0.01). Moreover, radiotherapy, screening, and a combination of chemotherapy and best supportive care also had significant statistics (p < 0.01) in the model of interventions when compared with radiotherapy applied only. Our research can suggest a vital combination of both pharmaceutical and non-pharmacological interventions to improve the quality of life of some common types of cancer patients.

The bidirectional association of nonalcoholic fatty liver disease with depression, bipolar disorder, and schizophrenia.

Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic-inflammatory disease associated with poor outcomes and decreased quality of life. NAFLD is overrepresented in patients with psychiatric disorders like depression, bipolar disorder, and schizophrenia; however, a comprehensive review on NAFLD and psychiatric disorders remains to be delineated. This review endeavors to investigate the association of NAFLD with psychiatric disorders, including shared pathogenesis and future clinical derivatives. Extant literature suggests that patients with psychiatric disorders (in particular, mood disorders) are more susceptible to the development of NAFLD due to multiple reasons, including but not limited to hypothalamic-pituitary-adrenal axis dysregulation, metabolic syndrome, and chronic perceived stress. Moreover, the clinical manifestations of mood disorders (e.g., anhedonia, psychomotor retardation, lifestyle modification, etc.), and potentially long-term treatment with weight-gaining agents, differentially affect these patients, making them more prone to NAFLD. Considering the increased morbidity associated with both mood disorders and NAFLD, our review recommends regular screenings for NAFLD in select patients with mood disorders exhibiting signs of increased risk (i.e., obesity, metabolic syndrome, diabetes, or family history of NAFLD) for better diagnosis and holistic care of both potentially interrelated conditions.

Toward sustainable development goals in gender inequality: an analysis of gender preferences among urban pregnant women in a Southeast Asian country.

BACKGROUND: Gender-biased discrimination and preferences are global phenomena, particularly son preferences. However, updated evidence about this issue in Vietnam has not yet been provided. Therefore, this study aimed to examine the gender preferences among pregnant women and identify associated factors of such preferences. METHODS: A cross-sectional survey was conducted in two hospitals in Vietnam with 732 pregnant women. Gender preferences for their child were asked, along with socio-demographic (e.g., education, occupation) and pregnancy characteristics (e.g., pressure to have a son, gender of first child, the importance to have a son of family members, and information sources on pregnancy care) by using face-to-face interviews and a structured questionnaire. Multinomial logistic regression was performed to determine factors associated with gender preferences. RESULTS: About 51.9% of the participants had no gender preference, while, among those who had a gender preference, 26.5% preferred sons, and 21.6% preferred daughters. Only 6.2% had pressure to have a son. Having the first child who was female (OR = 4.16, 95%CI = 1.54-11.25), having the pressure to have a son (OR = 6.77, 95%CI = 2.06-22.26), and higher self-perceived importance to have a son (OR = 3.05, 95%CI = 1.85-5.02) were positively associated with son preference. Otherwise, women having partners with high school education or above (OR = 2.04, 95%CI = 1.06-3.91), living with parents-in-law (OR = 2.33; 95%CI = 1.25-4.34), the higher number of pregnancies, and a higher degree of importance in having a son regarding parents-in-law (OR = 2.15, 95%CI = 1.38-3.35) associated with higher odds of preferring daughter. CONCLUSION: This study showed that gender preference was common among pregnant women, but the pressure to have a son was low. Further education programs and legal institutions should be implemented to improve gender inequality and gender preference in society.

Preference and willingness to pay for reproductive health services among adults in Urban-Rural transition settings of a developing country: evidence from a cross-sectional study in a rural district of Hanoi, Vietnam.

BACKGROUND: Since the introduction of fee-for-service models in public hospitals and the legalization of private health services in Vietnam in 1989, the price of reproductive health services has risen. These changes have exacerbated inequities in accessing reproductive health services. This study examines potential disparities in willingness to pay for reproductive health services among adults in a rural district of Hanoi. METHODS: A cross-sectional study was conducted at 9 communes in Thanh Oai district, a rural district of Hanoi, Vietnam, in July 2019. Face-to-face interviews were conducted using a structured questionnaire to collect self-reported data. The contingent valuation was used to examine willingness to pay for reproductive health services with a starting price of 2 million VND (~ US$86.2, July 2019 exchange rate), which is the average price of all RHS in public facilities in Vietnam. Multiple Logistic regression and Multiple Interval regression models were used to identify factors associated with willingness to pay and the amount that people were willing to pay for reproductive health services. RESULTS: Among 883 participants, this study found 59.1% of them willing to pay for reproductive health services at an average maximum amount of US$36.2, significantly less than the current average price of US$86.2. Occupation, number of sex partners, perception towards the necessity of reproductive health services, and prior use of reproductive health services were found to significantly influence willingness to pay for reproductive health services, while age, income level, gender, occupation, perception towards the necessity of reproductive health services and prior use of reproductive health services were reportedly correlated with the amount participants were willing to pay for reproductive health services. CONCLUSION: Lower willingness to pay for reproductive health services compared to the current prices (US$36.2 vs. US$86.2) is likely related to an overall low awareness of the necessity of reproductive health services, and future education campaigns should specifically target those from lower-income backgrounds. Financial subsidization should also be provided, especially for those from the low-income group, to ensure equitable access to reproductive health services. Given the heterogeneity of reproductive health services, further studies should examine the willingness to pay for each type of service independently.

Efficacy of a Mobile Phone-Based Intervention on Health Behaviors and HIV/AIDS Treatment Management: Randomized Controlled Trial.

BACKGROUND: Antiretroviral therapy (ART) is considered the most important intervention for HIV-positive patients; thus, encouraging the use of and adherence to ART are vital to HIV treatment outcomes. Advances in web and mobile technologies hold potential in supporting HIV treatment management. OBJECTIVE: The aim of this study was to evaluate the feasibility and efficacy of a theory-based mobile health (mHealth) intervention on health behaviors and HIV treatment adherence among patients with HIV/AIDS in Vietnam. METHODS: We performed a randomized controlled trial on 425 HIV patients in two of the largest HIV clinics in Hanoi, Vietnam. Both the intervention group (238 patients) and the control group (187 patients) received regular consultations with doctors and then participated in 1-month and 3-month follow-up visits. Patients in the intervention group received a theory-driven smartphone app to facilitate medication adherence and self-efficacy in HIV patients. Measurements were developed based on the Health Belief Model, which included the visual analog scale of ART Adherence, HIV Treatment Adherence Self-Efficacy Scale, and HIV Symptom Management Self-Efficacy Scale. We also included the 9-item Patient Health Questionnaire (PHQ-9) to assess patients' mental health throughout treatment. RESULTS: In the intervention group, the adherence score increased significantly (ß=1.07, 95% CI .24-1.90) after 1 month, whereas the HIV adherence self-efficacy was significantly higher after 3 months (ß=2.17, 95% CI 2.07-2.27) compared to the control group. There was a positive but low level of change in risk behaviors such as drinking, smoking, and drug use. Factors related to positive change in adherence were being employed and having stable mental well-being (lower PHQ-9 scores). Factors associated with self-efficacy in treatment adherence and symptom management were gender, occupation, younger age, and having no other underlying conditions. A longer duration of ART increased treatment adherence but decreased self-efficacy in symptom management. CONCLUSIONS: Our study demonstrated that the mHealth app could improve the overall ART adherence self-efficacy of patients. Further studies with larger sample sizes and longer follow-up periods are needed to support our findings. TRIAL REGISTRATION: Thai Clinical Trials Registry TCTR20220928003; https://www.thaiclinicaltrials.org/show/TCTR20220928003.

Impacts of COVID-19 on career choices in health professionals and medical students.

BACKGROUNDS: The COVID-19 pandemic has resulted in not only significant mortalities in Vietnam but has had an impact on its economy. Previous studies have highlighted how the pandemic has had a marginal impact on Vietnamese healthcare workers working at the frontlines. To date, there have been several other studies examining the impact of COVID-19 on intentions to transition between jobs among healthcare professionals, but this has yet to be explored amongst Vietnamese healthcare workers. METHODS: To achieve the study's objectives an online cross-sectional study was conducted between September to November 2021. Snowball sampling methodology was adopted for the recruitment of participants. The questionnaire that was used for this study comprised of the following sections: (a) socio-demographic information; (b) impact of COVID-19 on work; (c) risk of exposure to COVID-19; (d) career choices/intentions to change job, and (e) motivation at work. RESULTS: There were 5727 completed the entire survey. 17.2% of the respondents have had increased job satisfaction, 26.4% reported increased motivation to work, and 40.9% reported decreased motivation to work. Whilst there were changes in the daily work intensity and the level of work-related stress, more than 60% of respondents we sampled did not intend to switch careers. Demographic variables like gender, whether one was a student or an existing healthcare worker, and income related to work motivation. The community's stigma was a negative factor that declined intrinsic motivation as well as decreased work retention. CONCLUSIONS: Our study is instrumental in identifying the impact of COVID-19 on career choices amongst Vietnamese healthcare workers. The factors identified have clear implications for policymaking.

Depressive symptoms are associated with immunological failure among HIV-positive patients in Vietnam.

As the lives of people living with HIV (PLWH) become increasingly normalized, more focus is being given to the associated comorbidities of HIV, including those related to mental health such as depression. This study aims to evaluate the correlation between depressive symptoms and HIV outcomes in Vietnam through the measurement of CD4 cell count. A mixed design was utilized, in which both a longitudinal assessment of CD4 cell counts and a cross-sectional survey of depressive symptoms were conducted on 481 patients in the Bach Mai and Ha Dong HIV clinics (Hanoi, Vietnam). CD4 cell count data was extracted from the medical records of participants, and depressive symptoms were screened using the Patient Health Questionnaire (PHQ-9). The results illustrate that the presence of moderately severe to severe depressive symptoms is associated with lower CD4 cell counts, indicating poorer HIV outcomes resulting from comorbid depression. This correlation was especially noticeable in the PHQ-9 items for psychomotor agitation/retardation (p < 0.05) and suicidal ideation (p < 0.05). Future policy and treatment options for HIV in Vietnam should consider the presence of comorbid mental health conditions in order to provide more suitable and effective treatment in the goal of providing a higher quality of life for PLWH.

Repetitive Transcranial Magnetic Stimulation for Fibromyalgia: An Updated Systematic Review and Meta-Analysis.

OBJECTIVE: Meta-analysis was performed to evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in fibromyalgia on the domains of pain, depression, anxiety and quality of life. METHOD: Publications were searched with the keywords "repetitive transcranial magnetic stimulation" and "fibromyalgia" for randomized controlled trials that compare rTMS with sham stimulation for treating pain, depression, anxiety, and quality of life. Trials available until April 2021 were searched through PubMed, Scopus, Web of Science, and Cochrane Controlled Trials Register. The postintervention scores after 4 weeks for pain, depression, anxiety, and quality of life were extracted to compare the effects of rTMS and sham. Subgroup analysis was conducted based on the stimulation site. RESULTS: From 265 screened articles, 11 eligible randomized controlled trials involving 303 patients were included. The results show that rTMS is more effective than sham stimulation in improving pain (standardized mean difference [SMD] = -0.35; 95% confidence interval [CI] = -0.62 to -0.08; p = .01) and quality of life (SMD = -0.51; 95% CI = -0.78 to -0.23; p = .0003). It is not more effective than sham stimulation for depression, and anxiety. After sensitivity analysis, subgroup analysis revealed that primary motor cortex stimulation was more effective than sham for improving pain (SMD = -0.57; 95% CI = -0.91 to -0.23; p = <0.01). Neither dorsolateral prefrontal cortex nor primary motor cortex stimulation was more effective than sham in improving depression and anxiety. CONCLUSIONS: rTMS is more effective than sham in improving pain and quality of life, but it does not demonstrate reduction in depression or anxiety.

Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis.

IMPORTANCE: COVID-19 is associated with clinically significant symptoms despite resolution of the acute infection (i.e., post-COVID-19 syndrome). Fatigue and cognitive impairment are amongst the most common and debilitating symptoms of post-COVID-19 syndrome. OBJECTIVE: To quantify the proportion of individuals experiencing fatigue and cognitive impairment 12 or more weeks following COVID-19 diagnosis, and to characterize the inflammatory correlates and functional consequences of post-COVID-19 syndrome. DATA SOURCES: Systematic searches were conducted without language restrictions from database inception to June 8, 2021 on PubMed/MEDLINE, The Cochrane Library, PsycInfo, Embase, Web of Science, Google/Google Scholar, and select reference lists. STUDY SELECTION: Primary research articles which evaluated individuals at least 12 weeks after confirmed COVID-19 diagnosis and specifically reported on fatigue, cognitive impairment, inflammatory parameters, and/or functional outcomes were selected. DATA EXTRACTION & SYNTHESIS: Two reviewers independently extracted published summary data and assessed methodological quality and risk of bias. A meta-analysis of proportions was conducted to pool Freeman-Tukey double arcsine transformed proportions using the random-effects restricted maximum-likelihood model. MAIN OUTCOMES & MEASURES: The co-primary outcomes were the proportions of individuals reporting fatigue and cognitive impairment, respectively, 12 or more weeks following COVID-19 infection. The secondary outcomes were inflammatory correlates and functional consequences associated with post-COVID-19 syndrome. RESULTS: The literature search yielded 10,979 studies, and 81 studies were selected for inclusion. The fatigue meta-analysis comprised 68 studies, the cognitive impairment meta-analysis comprised 43 studies, and 48 studies were included in the narrative synthesis. Meta-analysis revealed that the proportion of individuals experiencing fatigue 12 or more weeks following COVID-19 diagnosis was 0.32 (95% CI, 0.27, 0.37; p < 0.001; n = 25,268; I2 = 99.1%). The proportion of individuals exhibiting cognitive impairment was 0.22 (95% CI, 0.17, 0.28; p < 0.001; n = 13,232; I2 = 98.0). Moreover, narrative synthesis revealed elevations in proinflammatory markers and considerable functional impairment in a subset of individuals. CONCLUSIONS & RELEVANCE: A significant proportion of individuals experience persistent fatigue and/or cognitive impairment following resolution of acute COVID-19. The frequency and debilitating nature of the foregoing symptoms provides the impetus to characterize the underlying neurobiological substrates and how to best treat these phenomena. STUDY REGISTRATION: PROSPERO (CRD42021256965).

Peripheral inflammatory biomarkers define biotypes of bipolar depression.

We identified biologically relevant moderators of response to tumor necrosis factor (TNF)-α inhibitor, infliximab, among 60 individuals with bipolar depression. Data were derived from a 12-week, randomized, placebo-controlled clinical trial secondarily evaluating the efficacy of infliximab on a measure of anhedonia (i.e., Snaith-Hamilton Pleasure Scale). Three inflammatory biotypes were derived from peripheral cytokine measurements using an iterative, machine learning-based approach. Infliximab-randomized participants classified as biotype 3 exhibited lower baseline concentrations of pro- and anti-inflammatory cytokines and soluble TNF receptor-1 and reported greater pro-hedonic improvements, relative to those classified as biotype 1 or 2. Pretreatment biotypes also moderated changes in neuroinflammatory substrates relevant to infliximab's hypothesized mechanism of action. Neuronal origin-enriched extracellular vesicle (NEV) protein concentrations were reduced to two factors using principal axis factoring: phosphorylated nuclear factorκB (p-NFκB), Fas-associated death domain (p-FADD), and IκB kinase (p-IKKα/ß) and TNF receptor-1 (TNFR1) comprised factor "NEV1," whereas phosphorylated insulin receptor substrate-1 (p-IRS1), p38 mitogen-activated protein kinase (p-p38), and c-Jun N-terminal kinase (p-JNK) constituted "NEV2". Among infliximab-randomized subjects classified as biotype 3, NEV1 scores were decreased at weeks 2 and 6 and increased at week 12, relative to baseline, and NEV2 scores increased over time. Decreases in NEV1 scores and increases in NEV2 scores were associated with greater reductions in anhedonic symptoms in our classification and regression tree model (r2 = 0.22, RMSE = 0.08). Our findings provide preliminary evidence supporting the hypothesis that the pro-hedonic effects of infliximab require modulation of multiple TNF-α signaling pathways, including NF-κB, IRS1, and MAPK.

Deficits of social cognition in bipolar disorder: Systematic review and meta-analysis.

BACKGROUND: The association between impaired social cognition and bipolar disorder (BD) is well established. However, to our knowledge, there has not been a recent systematic review that characterizes disparate dimensions of social cognition in BD. Herein, this systematic review and meta-analysis aimed to synthesize the literature on core aspects of social cognition (i.e., Theory of Mind, emotion recognition, and social judgment) to identify potential areas of impairment. METHODS: Online databases (i.e., PubMed, Cochrane Libraries, PsycINFO) and Google Scholar were searched from inception to May 2021. Studies with populations ages ≥16 with DSM-IV or DSM-5 defined BD (I or II) either in a euthymic or symptomatic state were included. The risk of bias was measured using the ROBINS-1 tool, and the quality of the sources was evaluated using GRADE criteria. The results of the studies were quantitatively measured by synthesizing Hedge's g effect sizes through a random effects meta-analytic approach. RESULTS: A total of 29 studies were included in the final review (i.e., 12 studies on the Theory of Mind, 11 on emotion recognition, and 6 on social judgment). Overall, results demonstrated social cognition to be moderately impaired in individuals with BD (d = 0.59). The individual domains ranged in effect size (0.38 < d < 0.70), providing evidence for variation in impairment within social cognition. DISCUSSION: Individuals with BD exhibit clinically significant deficits in social cognition during euthymic and symptomatic states. Social cognition impairments in individuals with BD are an important therapeutic target for treatment discovery and development.

Do sleep changes mediate the anti-depressive and anti-suicidal response of intravenous ketamine in treatment-resistant depression?

Sleep disturbances are commonly reported in patients with treatment-resistant depression (TRD). Available data have shown that intravenous (IV) ketamine is an effective treatment for patients with TRD and growing data suggest ketamine may improve overall sleep architecture. In the present study, we evaluated whether changes in sleep symptoms mediated the anti-depressive and/or anti-suicidal effects of IV ketamine and whether improvement in sleep correlated with a higher likelihood of achieving response or remission. Adults with TRD received four infusions of IV ketamine at a community-based clinic. Total depressive symptom severity was measured with the Quick Inventory Depressive Symptoms Self-Report 16-Item (QIDS-SR16 ) at baseline and was repeated across four infusions. Suicidal ideation (SI) and four sleep symptoms were measured using the SI item and the five sleep items on the QIDS-SR16 . A total of 323 patients with TRD received IV ketamine. Self-reported improvements in insomnia, night-time restlessness, hypersomnia, early morning waking, and total sleep were significant partial mediators to the improvements observed in depression severity. Similarly, insomnia, night-time restlessness, early morning waking and total sleep improvements mediated the reduction of IV ketamine on SI. All sleep items, except for hypersomnia, were associated with an increased likelihood of achieving response or remission. Notably, each point improvement in total sleep score was significantly associated with achieving responder/remitter status (odds ratio 3.29, 95% confidence interval 2.00-5.41). Insomnia, sleep restlessness, early morning waking and total sleep improvements were significant mediators of antidepressant and anti-suicidal improvements in patients with TRD receiving IV ketamine.