Novel OX40 and 4-1BB Derived Spacers Enhance CD30 CAR Activity and Safety in CD30 Positive Lymphoma Models.

The chimeric antigen receptor (CAR) derived from the CD30 specific murine antibody, HRS-3, has produced promising clinical efficacy with a favorable safety profile in the treatment of relapsed or refractory CD30-positive lymphomas. However, persistence of the autologous CAR T cells was brief, and many patients relapsed a year after treatment. The lack of persistence may be attributed to the use of a wildtype IgG1 spacer that can associate with Fc receptors. We first identified the cysteine rich domain (CRD) 5 of CD30 as the primary binding epitope of HRS-3 and armed with this insight, attempted to improve the HRS-3 CAR functionality with a panel of novel spacer designs. We demonstrate that HRS-3 CARs with OX40 and 4-1BB derived spacers exhibited similar anti-tumor efficacy, circumvented interactions with Fc receptors and secreted lower levels of cytokines in vitro than a CAR employing the IgG1 spacer. Humanization of the HRS-3 scFv coupled with the 4-1BB spacer preserved potent on-target, on-tumor efficacy, and on-target, off-tumor safety. In a lymphoma mouse model of high tumor burden, T cells expressing a humanized HRS-3 CD30.CARs with the 4-1BB spacer potently killed tumors with low levels of circulating inflammatory cytokines, providing a promising candidate for future clinical development in the treatment of CD30-positive malignancies.

Phenotypic screening in Organ-on-a-Chip systems: a 1537 kinase inhibitor library screen on a 3D angiogenesis assay.

Modern drug development increasingly requires comprehensive models that can be utilized in the earliest stages of compound and target discovery. Here we report a phenotypic screening exercise in a high-throughput Organ-on-a-Chip setup. We assessed the inhibitory effect of 1537 protein kinase inhibitors in an angiogenesis assay. Over 4000 micro-vessels were grown under perfusion flow in microfluidic chips, exposed to a cocktail of pro-angiogenic factors and subsequently exposed to the respective kinase inhibitors. Efficacy of compounds was evaluated by reduced angiogenic sprouting, whereas reduced integrity of the main micro-vessel was taken as a measure for toxicity. The screen yielded 53 hits with high anti-angiogenicity and low toxicity, of which 44 were previously unassociated with angiogenic pathways. This study demonstrates that Organ-on-a-Chip models can be screened in high numbers to identify novel compounds and targets. This will ultimately reduce bias in early-stage drug development and increases probability to identify first in class compounds and targets for today's intractable diseases.

Pain trajectories and their associations with cognition among older adults: a 10-year cohort study from network perspective.

BACKGROUND: Few studies have examined the associations between pain trajectories and cognitive function in older adults. This study explored the associations between pain trajectories and different cognitive domains in older adults from a network perspective. METHODS: Data on pain trajectories were derived from the Health and Retirement Study between 2010 and 2020 using latent class growth analyses. Measurements of key cognition domains, including memory, attention, calculation, orientation and language, were included. Linear regression and network analysis were performed to evaluate the associations between different pain trajectories and cognition. RESULTS: A total of 9,551 older adults were included in this study and three trajectories of pain were identified. After controlling for the covariates, persistent severe pain trajectory was associated with poorer overall cognition, memory and calculation ability when compared to mild or non-persistent pain trajectory. In the pain and cognition network model, memory (expected influence (EI) = 0.62), language (EI = 0.58) and calculation (EI = 0.41) were the most central domains. CONCLUSIONS: Pain trajectories appeared stable over time among older adults in this study. Severity of persistent pain was an important risk factor for poor cognition, especially in relation to memory and calculation domains. Interventions targeting memory, language and calculation domains might be useful in addressing cognitive decline in older adults with persistent pain.

The Influence of Personality Disorder Symptoms on Treatment Outcomes in Bipolar Disorder: A Secondary Analysis of a Randomised Controlled Trial: L'influence des symptômes du trouble de la personnalité sur les résultats du traitement dans le trouble bipolaire : Une analyse secondaire d'un essai randomisé contrôlé.

OBJECTIVES: Many people who are diagnosed with bipolar disorder also have comorbid personality disorder. Few studies have explored how personality disorder may influence pharmacological treatment outcomes. The aim of this study was to conduct a secondary analysis of data from a clinical trial of adjunctive nutraceutical treatments for bipolar depression, to determine whether maladaptive personality traits influence treatment outcomes. METHODS: Scores on the Standardised Assessment of Personality - Abbreviated Scale screener were used to classify participants as having bipolar disorder with (n = 119) and without (n = 29) above threshold personality disorder symptoms (personality disorder). Outcome measures included: The Montgomery Åsberg Depression Rating Scale, Clinical Global Impressions and Improvement Severity Scales, Patient Global Impressions-Improvement scale, Bipolar Depression Rating Scale, Range of Impaired Functioning Tool, Social and Occupational Functioning Assessment Scale and Quality of Life and Enjoyment Scale (Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form). Generalised estimated equations examined the two-way interactions of personality disorder by time or treatment and investigated personality disorder as a non-specified predictor of outcomes. RESULTS: Over time, the Patient Global Impressions-Improvement scores were significantly higher in those in the personality disorder group. No other significant differences in the two-way interactions of personality disorder by treatment group or personality disorder by time were found. Personality disorder was a significant but non-specific predictor of poorer outcomes on the Bipolar Depression Rating Scale, Range of Impaired Functioning Tool, and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form, regardless of time or treatment group. CONCLUSIONS: This study highlights the potential impact of maladaptive personality traits on treatment outcomes and suggests that the presence of comorbid personality disorder may confer additional burden and compromise treatment outcomes. This warrants further investigation as does the corroboration of these exploratory findings. This is important because understanding the impact of comorbid personality disorder on bipolar disorder may enable the development of effective psychological and pharmacotherapeutic options for personalised treatments.

COVID-19 and Sleep Problems: A Perspective from Bibliometric Analysis.

OBJECTIVES: The Coronavirus Disease 2019 (COVID-19) pandemic and the containment measures for COVID-19 have affected sleep quality in the population. This study explored sleep-related research from a bibliometric perspective to provide an overview of the research outputs in this field. METHODS: Original and review articles were retrieved from the Web of Science Core Collection (WOSCC) database from December 2019 to 7 Aug 2023. R package "bibliometrix" was used to summarize the number of articles of authors, institutions, and countries; count the citations of the articles, and generate a Three-Fields Plot. VOSviewer software was applied to visualize the collaboration network among authors and institutions, and to conduct a co-occurrence analysis of keywords. RESULTS: A total of 4,499 articles on COVID-19 and sleep, and 25,883 articles on non-COVID-19 and sleep were included. Sleep related articles were mainly published by authors from China, the USA, and Italy. For COVID-19 and sleep research, Huazhong University of Science was the most productive institution. The Psychiatry Research was the most influential journal across the different subject categories of this field. "Mental health", "anxiety", and "depression" were the most common keywords, while "sleep quality" and "quality of life" were the likely topic areas in terms of future research directions. CONCLUSIONS: Our findings provide a comprehensive perspective for researchers to understand the wider landscape of both COVID-19 and non-COVID-19 sleep-related research area.

Target-mediated drug disposition model for drugs with N > 2 binding sites that bind to a target with one binding site.

The paper extended the TMDD model to drugs with more than two (N > 2) identical binding sites (N-to-one TMDD). The quasi-steady-state (N-to-one QSS), quasi-equilibrium (N-to-one QE), irreversible binding (N-to-one IB), and Michaelis-Menten (N-to-one MM) approximations of the model were derived. To illustrate properties of new equations and approximations, N = 4 case was investigated numerically. Using simulations, the N-to-one QSS approximation was compared with the full N-to-one TMDD model. As expected, and similarly to the standard TMDD for monoclonal antibodies (mAb), N-to-one QSS predictions were nearly identical to N-to-one TMDD predictions, except for times of fast changes following initiation of dosing, when equilibrium has not yet been reached. Predictions for mAbs with soluble targets (slow elimination of the complex) were simulated from the full 4-to-one TMDD model and were fitted to the 4-to-one TMDD model and to its QSS approximation. It was demonstrated that the 4-to-one QSS model provided nearly identical description of not only the observed (simulated) total drug and total target concentrations, but also unobserved concentrations of the free drug, free target, and drug-target complexes. For mAb with a membrane-bound target, the 4-to-one MM approximation adequately described the data. The 4-to-one QSS approximation converged 8 times faster than the full 4-to-one TMDD.

The Brain Economy: Advancing Brain Science to Better Understand the Modern Economy.

The coming years are likely to be turbulent due to a myriad of factors or polycrisis, including an escalation in climate extremes, emerging public health threats, weak productivity, increases in global economic instability and further weakening in the integrity of global democracy. These formidable challenges are not exogenous to the economy but are in some cases generated by the system itself. They can be overcome, but only with far-reaching changes to global economics. Our current socio-economic paradigm is insufficient for addressing these complex challenges, let alone sustaining human development, well-being and happiness. To support the flourishing of the global population in the age of polycrisis, we need a novel, person-centred and collective paradigm. The brain economy leverages insights from neuroscience to provide a novel way of centralising the human contribution to the economy, how the economy in turn shapes our lives and positive feedbacks between the two. The brain economy is primarily based on Brain Capital, an economic asset integrating brain health and brain skills, the social, emotional, and the diversity of cognitive brain resources of individuals and communities. People with healthy brains are essential to navigate increasingly complex systems. Policies and investments that improve brain health and hence citizens' cognitive functions and boost brain performance can increase productivity, stimulate greater creativity and economic dynamism, utilise often underdeveloped intellectual resources, afford social cohesion, and create a more resilient, adaptable and sustainability-engaged population.

Prevalence of insomnia and its association with quality of life in caregivers of psychiatric inpatients during the COVID-19 pandemic: a network analysis.

BACKGROUND: Studies on sleep problems among caregivers of psychiatric patients, especially during the COVID-19 pandemic, are limited. This study examined the prevalence and correlates of insomnia symptoms (insomnia hereafter) among caregivers of psychiatric inpatients during the COVID-19 pandemic as well as the association with quality of life (QoL) from a network analysis perspective. METHODS: A multi-center cross-sectional study was conducted on caregivers of inpatients across seven tertiary psychiatric hospitals and psychiatric units of general hospitals. Network analysis explored the structure of insomnia using the R program. The centrality index of "Expected influence" was used to identify central symptoms in the network, and the "flow" function was adopted to identify specific symptoms that were directly associated with QoL. RESULTS: A total of 1,101 caregivers were included. The overall prevalence of insomnia was 18.9% (n = 208; 95% CI = 16.7-21.3%). Severe depressive (OR = 1.185; P < 0.001) and anxiety symptoms (OR = 1.099; P = 0.003), and severe fatigue (OR = 1.320; P < 0.001) were associated with more severe insomnia. The most central nodes included ISI2 ("Sleep maintenance"), ISI7 ("Distress caused by the sleep difficulties") and ISI1 ("Severity of sleep onset"), while "Sleep dissatisfaction" (ISI4), "Distress caused by the sleep difficulties" (ISI7) and "Interference with daytime functioning" (ISI5) had the strongest negative associations with QoL. CONCLUSION: The insomnia prevalence was high among caregivers of psychiatric inpatients during the COVID-19 pandemic, particularly in those with depression, anxiety and fatigue. Considering the negative impact of insomnia on QoL, effective interventions that address insomnia and alteration of sleep dissatisfaction should be developed.

Hikikomori: A perspective from bibliometric analysis.

AIMS: Hikikomori is a common phenomenon reported in Japan and many other countries. However, the broad trends of the research publications on hikikomori are unclear. Therefore, this study examined the patterns of research on hikikomori using bibliometric analysis. METHODS: Relevant publications were searched in Web of Science. Bibliometric analyses were performed with CiteSpace, R and VOSviewer. RESULTS: In total, 297 publications on hikikomori met the eligibility criteria. The International Journal of Social Psychiatry (IF = 10.461) published the most papers (K = 17, or 5.7%) on hikikomori. Takahiro A. Kato from Kyushu University (41; 13.8%; H-index = 18) was the most influential author, while Takahiro A. Kato (total link strength [TLS]: 235), Alan R. Teo (TLS: 157), and Masaru Tateno (TLS: 153) separately had the strongest research collaboration with other researchers. Of all countries that published on hikikomori, Japan had the highest number of publications (K = 91). The keywords "United States" and "psychiatric diagnosis" received the most attention between 2013 and 2015, whereas "health" and "autism spectrum disorder" received the most attention in 2021 and 2022. CONCLUSIONS: Peer-reviewed research publications on hikikomori are growing rapidly and the research trends in this field are also changing.

Using the Theoretical Domains Framework to Inform the Implementation of Therapeutic Virtual Reality into Mental Healthcare.

Evidence supporting the efficacy of therapeutic virtual reality (VR) for mental health conditions is rapidly growing. However, little is known about how best to implement VR, or the challenges perceived by treatment providers. This study aimed to (1) synthesis perspectives of staff working in private mental healthcare and (2) use the Theoretical Domains Framework (TDF) and Behaviour Change Wheel (BCW) to identify mechanisms of change targets and intervention functions to facilitate its clinical implementation. Semi-structured interviews were conducted with clinicians (n = 14) and service managers (n = 5) working in a major private mental health hospital in Victoria, Australia. Transcripts were coded using framework analysis to identify relevant TDF domains. Specific belief statements were generated and coded as a barrier and/or facilitator and thematically organised within domains. Domains were ranked for importance based on frequency, elaboration, and evidence of conflicting beliefs. Using the BCW, domains were mapped to their respective COM-B components and indicated intervention functions. A total of 11 TDF domains were identified as relevant to early-stage implementation of therapeutic VR. Three domains were judged as highly important (beliefs about consequences; environmental context and resources; knowledge), while seven domains were judged as moderately important (social/professional role and identity; emotions; skills; memory, attention, and decision processes; intentions; beliefs about capabilities; social influences). Based on current data, we propose a theory-informed roadmap to promote VR uptake in mental healthcare services. A priority for intervention development should be addressing knowledge gaps and attitudinal barriers (e.g., safety concerns) with education and training.

A Systematic Review and Meta-Analysis of the Association Between Periodontal Disease and Severe Mental Illness.

BACKGROUND: Periodontal disease represents a global public health concern, with a disproportionate burden being borne by vulnerable populations. One such group is people with severe mental illness (SMI), and this study examined whether periodontal health is poorer in people with SMI than the general population. METHODS: We conducted a systematic search for studies published before March 2021 on the periodontal health of people with SMI using the following databases: PubMed, PsycINFO, EMBASE, China National Knowledge Infrastructure, and Chongqing VIP. Outcomes were periodontitis, periodontal disease, and shallow and deep periodontal pockets. Results were compared with the general population. RESULTS: Seventeen studies had sufficient data for a random-effects meta-analysis, consisting of 4404 psychiatric patients and 95,411 controls. SMI was associated with an increased prevalence of periodontitis (odds ratio = 1.97, 95% confidence interval [CI] = 1.15-3.35) compared with the general population. People with SMI had 4.28 the odds of having periodontal disease compared with controls (95% CI = 2.54-7.21). They also had 3.65 the odds of shallow pockets (95% CI = 1.80-7.42) and 2.76 the odds of deep pockets (95% CI = 1.10-6.93). CONCLUSIONS: Our findings highlight the increased prevalence and severity of periodontal disease in people with SMI. Oral health is often considered the gateway to overall health and should be a public health priority for this population.

Minimal Physiologically-based Pharmacokinetic Model to Investigate the Effect of Charge on the Pharmacokinetics of Humanized anti-HCV-E2 IgG Antibodies in Sprague-Dawley Rats.

PURPOSE: To develop a minimal physiologically-based pharmacokinetic (mPBPK) model in quantifying the relationships between the charge and pharmacokinetics (PK) of therapeutic monoclonal IgG antibody (TMAb). METHODS: PK data used in this study were native IgG and five humanized anti-HCVE2-IgG antibodies in rats. Different models that related the effect of charge on interstitial distribution, transcapillary transport, and cellular uptake for FcRn-mediated metabolism were tested. External validation was conducted to assess if the charge-parameter relationships derived from rats could be used to predict the PK of TMAbs in mice. The final mPBPK model was used to construct the relationships between the FcRn binding and charge on the PK of TMAbs. RESULTS: Increasing the isoelectric point (pI) of IgG was associated with higher interstitial space distribution and cellular uptake. The transcapillary transport of IgG from plasma to interstitial space remains constant with pI values below 7.96 and then increased linearly with pI. The model-based simulation results suggested that improving the FcRn binding affinity can overcome the problems of low plasma/interstitial space exposures associated with TMAbs with higher pI values by reducing the FcRn-mediated metabolism and hence increasing drug exposure in the interstitial space that has close contact with many solid tumors. CONCLUSIONS: The final mPBPK model was developed and used to construct complex quantitative relationships between the pI/FcRn binding affinity and PK of TMAbs and such relationships are useful to select the discovery of a "sweet spot" of designing future generation of TMAbs with optimal PK properties to achieve desirable plasma and tissue drug exposures.

Network Analysis of Depression, Anxiety, Posttraumatic Stress Symptoms, Insomnia, Pain, and Fatigue in Clinically Stable Older Patients With Psychiatric Disorders During the COVID-19 Outbreak.

OBJECTIVES: The Coronavirus Disease 2019 (COVID-19) pandemic has profound negative effects on the mental health of clinically stable older patients with psychiatric disorders. This study examined the influential nodes of psychiatric problems and their associations in this population using network analysis. METHODS: Clinically stable older patients with psychiatric disorders were consecutively recruited from four major psychiatric hospitals in China from May 22 to July 15, 2020. Depressive and anxiety syndromes (depression and anxiety hereafter), insomnia, posttraumatic stress symptoms (PTSS), pain, and fatigue were measured using the Patient Health Questionnaire, General Anxiety Disorder, Insomnia Severity Index, Posttraumatic Stress Disorder Checklist - Civilian Version, and Numeric Rating Scales for pain and fatigue, respectively. RESULTS: A total of 1063 participants were included. The network analysis revealed that depression was the most influential node followed by anxiety as indicated by the centrality index of strength. In contrast, the edge connecting depression and anxiety was the strongest edge, followed by the edge connecting depression and insomnia, and the edge connecting depression and fatigue as indicated by edge-weights. The network structure was invariant by gender based on the network structure invariance test (M = .14, P = .20) and global strength invariance tests (S = .08, P = .30). CONCLUSIONS: Attention should be paid to depression and its associations with anxiety, insomnia, and fatigue in the screening and treatment of mental health problems in clinically stable older psychiatric patients affected by the COVID-19 pandemic.

Prevalence of Suicidality and its Association with Quality of Life in Older Patients with Clinically Stable Psychiatric Disorders in China During the COVID-19 Pandemic.

AIMS: The pattern of suicidality in older patients with psychiatric disorders during the COVID-19 pandemic is not clear. This study examined the prevalence of suicidality and its association with quality of life (QOL) among older clinically stable patients with psychiatric disorders during the COVID-19 pandemic. METHODS: A multicenter, cross-sectional study was conducted from May 22 to July 15, 2020, among four major tertiary psychiatric hospitals in China. Suicidality was assessed by asking 3 standardized questions. Depressive symptoms, pain, and QOL were assessed with the 9-item Patient Health Questionnaire (PHQ-9), the numeric pain rating scale (NPRS), and the World Health Organization Quality of Life Questionnaire-brief version, respectively. RESULTS: A total of 1063 clinically stable patients participated and completed the assessment. The prevalence of suicidality was 11.8% (95% CI: 9.9%-13.7%) during the COVID-19 pandemic. Multiple logistic regression analysis revealed that poor treatment adherence (P = .009, OR = 1.86, 95% CI: 1.17-2.96) and perceived illness worsening during the COVID-19 outbreak (P = .02, OR = 2.07, 95% CI: 1.15-3.73), being diagnosed with major depressive disorder (P < .001, OR = 2.79, 95% CI: 1.68-4.64), PHQ-9 total score (P < .001, OR = 1.20, 95% CI: 1.15-1.24) and NPRS total score (P = .002, OR = 1.17, 95% CI: 1.06-1.29) were associated with higher risk of suicidality. After controlling for covariates, older psychiatric patients with suicidality had lower QOL compared to those without (F(1, 1063) =16.5, P<.001). CONCLUSIONS: Suicidality was common in older patients with clinically stable psychiatric disorders during the COVID-19 pandemic. Considering its negative impact on QOL and personal suffering, routine screening and preventive suicide measures should be implemented for older psychiatric patients.

Treatment of refractory obsessive-compulsive disorder with nutraceuticals (TRON): a 20-week, open label pilot study.

BACKGROUND: Obsessive-compulsive disorder (OCD) is often challenging to treat and resistant to psychological interventions and prescribed medications. The adjunctive use of nutraceuticals with potential neuromodulatory effects on underpinning pathways such as the glutamatergic and serotonergic systems is one novel approach. OBJECTIVE: To assess the effectiveness and safety of a purpose-formulated combination of nutraceuticals in treating OCD: N-acetyl cysteine, L-theanine, zinc, magnesium, pyridoxal-5' phosphate, and selenium. METHODS: A 20-week open label proof-of-concept study was undertaken involving 28 participants with treatment-resistant DSM-5-diagnosed OCD, during 2017 to 2020. The primary outcome measure was the Yale-Brown Obsessive-Compulsive Scale (YBOCS), administered every 4 weeks. RESULTS: An intention-to-treat analysis revealed an estimated mean reduction across time (baseline to week-20) on the YBOCS total score of -7.13 (95% confidence interval = -9.24, -5.01), with a mean reduction of -1.21 points per post-baseline visit (P ≤ .001). At 20-weeks, 23% of the participants were considered "responders" (YBOCS ≥35% reduction and "very much" or "much improved" on the Clinical Global Impression-Improvement scale). Statistically significant improvements were also revealed on all secondary outcomes (eg, mood, anxiety, and quality of life). Notably, treatment response on OCD outcome scales (eg, YBOCS) was greatest in those with lower baseline symptom levels, while response was limited in those with relatively more severe OCD. CONCLUSIONS: While this pilot study lacks placebo-control, the significant time effect in this treatment-resistant OCD population is encouraging and suggests potential utility especially for those with lower symptom levels. Our findings need to be confirmed or refuted via a follow-up placebo-controlled study.

An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels.

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.

Exploring interleukin-6, lipopolysaccharide-binding protein and brain-derived neurotrophic factor following 12 weeks of adjunctive minocycline treatment for depression.

This study aimed to explore effects of adjunctive minocycline treatment on inflammatory and neurogenesis markers in major depressive disorder (MDD). Serum samples were collected from a randomised, placebo-controlled 12-week clinical trial of minocycline (200 mg/day, added to treatment as usual) for adults (n = 71) experiencing MDD to determine changes in interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP) and brain derived neurotrophic factor (BDNF). General Estimate Equation modelling explored moderation effects of baseline markers and exploratory analyses investigated associations between markers and clinical outcomes. There was no difference between adjunctive minocycline or placebo groups at baseline or week 12 in the levels of IL-6 (week 12; placebo 2.06 ± 1.35 pg/ml; minocycline 1.77 ± 0.79 pg/ml; p = 0.317), LBP (week 12; placebo 3.74 ± 0.95 µg/ml; minocycline 3.93 ± 1.33 µg/ml; p = 0.525) or BDNF (week 12; placebo 24.28 ± 6.69 ng/ml; minocycline 26.56 ± 5.45 ng/ml; p = 0.161). Higher IL-6 levels at baseline were a predictor of greater clinical improvement. Exploratory analyses suggested that the change in IL-6 levels were significantly associated with anxiety symptoms (HAMA; p = 0.021) and quality of life (Q-LES-Q-SF; p = 0.023) scale scores. No other clinical outcomes were shown to have this mediation effect, nor did the other markers (LBP or BDNF) moderate clinical outcomes. There were no overall changes in IL-6, LBP or BDNF following adjunctive minocycline treatment. Exploratory analyses suggest a potential role of IL-6 on mediating anxiety symptoms with MDD. Future trials may consider enrichment of recruitment by identifying several markers or a panel of factors to better represent an inflammatory phenotype in MDD with larger sample size.

Prevalence of Depressive Symptoms Among Pregnant and Postpartum Women in China During the COVID-19 Pandemic.

OBJECTIVE: According to recent studies, the COVID-19 pandemic has been associated with an increased risk of mental health problems across many subpopulations including pregnant and postnatal women. This study examined the prevalence and correlates of depressive symptoms (depression hereafter) in Chinese pregnant and postpartum women during the COVID-19 pandemic. METHODS: This was a multicenter, cross-sectional study comprising 1309 pregnant and postpartum women across 12 provinces in China during the COVID-19 pandemic. Depression was assessed using the nine-item Patient Health Questionnaire. Univariate analyses and multivariate logistic regression analyses were conducted. RESULTS: The prevalence of depression in pregnant and postpartum women was 27.43% (95% confidence interval [CI] = 25.01%-29.85%). Women who were worried about themselves or their babies being infected with COVID-19 (odds ratio [OR] = 2.562, 95% CI = 1.670-3.929), and those who had delayed regular medical checkups (OR = 2.434, 95% CI = 1.580-3.750) were at higher risk of depression. Compared with those living in central and western parts of China, women living in northern (OR = 0.513, 95% CI = 0.326-0.807) and southeastern parts of China (OR = 0.626, 95% CI = 0.463-0.846) were less likely to have depression. CONCLUSIONS: The COVID-19 pandemic was associated with an increased likelihood of mental health problems among pregnant and postnatal women. Over a quarter of the pregnant and postpartum women in China had depression during the COVID-19 pandemic. Considering the negative health impact of depression, preventive measures, regular mental health screening, and medical checkups are needed with the goal to reduce the risk of depression in this vulnerable population during a pandemic.

Needs, gaps and opportunities for standard and e-mental health care among at-risk populations in the Asia Pacific in the context of COVID-19: a rapid scoping review.

BACKGROUND: The COVID-19 pandemic is expected to have profound mental health impact, including in the Asia Pacific Economic Cooperation (APEC) region. Some populations might be at higher risk of experiencing negative mental health impacts and may encounter increased barriers to accessing mental health care. The pandemic and related restrictions have led to changes in care delivery, including a rapid shift to the use of e-mental health and digital technologies. It is therefore essential to consider needs and opportunities for equitable mental health care delivery to the most at-risk populations. This rapid scoping review: 1) identifies populations in the APEC region that are at higher risk of the negative mental health impacts of COVID-19, 2) identifies needs and gaps in access to standard and e-mental health care among these populations, and 3) explores the potential of e-mental health to address these needs. METHODS: We conducted a rapid scoping review following the PRISMA Extension for Scoping Reviews (PRISMA-ScR). We searched Medline, Embase and PsychInfo databases and Google Scholar using a search strategy developed in consultation with a biomedical librarian. We included records related to mental health or psychosocial risk factors and COVID-19 among at-risk groups; that referred to one or more APEC member economies or had a global, thus generalizable, scope; English language papers, and papers with full text available. RESULTS: A total of 132 records published between December 2019 and August 2020 were included in the final analysis. Several priority at-risk populations, risk factors, challenges and recommendations for standard and e-mental health care were identified. Results demonstrate that e-mental health care can be a viable option for care delivery but that specific accessibility and acceptability considerations must be considered. Options for in-person, hybrid or "low-tech" care must also remain available. CONCLUSIONS: The COVID-19 pandemic has highlighted the urgent need for equitable standard and e-mental health care. It has also highlighted the persistent social and structural inequities that contribute to poor mental health. The APEC region is vast and diverse; findings from the region can guide policy and practice in the delivery of equitable mental health care in the region and beyond.

Comparison between TightRail rotating dilator sheath and GlideLight laser sheath for transvenous lead extraction.

BACKGROUND: There are limited data on the comparative analyses of TightRail rotating dilator sheath (Philips) and laser sheath for lead extraction. OBJECTIVE: To evaluate the effectiveness and safety of the TightRail sheath as a primary or secondary tool for transvenous lead extraction (TLE). METHODS: Retrospective cohort analysis of 202 consecutive patients who underwent TLE using either TightRail sheath and/or GlideLight laser sheath (Philips) in our hospital. The study population was divided into three groups: Group A underwent TLE with laser sheath only (N = 157), Group B with TightRail sheath only (N = 22), and Group C with both sheaths (N = 23). RESULTS: During this period, 375 leads in 202 patients were extracted, including 297 leads extracted by laser sheath alone, 45 leads by TightRail sheath alone, and 33 by both TightRail sheath and laser sheaths. The most common indications included device infection (44.6%) and lead-related complications (44.1%). The median age of leads was 8.9 years. TightRail sheath (Group B) achieved similar efficacy as a primary extraction tool compared with laser sheath (Group A), with complete procedure success rate of 93.3% (vs. 96.6%, P = .263) and clinical success rate of 100.0% (vs. 98.1%, P = .513). Among 32 leads in which Tightrail was used after laser had failed (Group C), the complete procedure success rate was 75.8%. No significant difference in procedural adverse events was observed. CONCLUSION: Our single-center experience confirms that the TightRail system is an effective first-line and second-line method for TLE. Further investigation is required to guide the selection of mechanical and laser sheaths in lead extraction cases.