Targeting danger molecules in tendinopathy: the HMGB1/TLR4 axis

Objectives: To seek evidence of the danger molecule, high-mobility group protein B1 (HMGB1) expression in human tendinopathy and thereafter, to explore mechanisms where HMGB1 may regulate inflammatory mediators and matrix regulation in human tendinopathy. Methods: Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing ‘early pathology’) biopsies were collected from patients undergoing arthroscopic shoulder surgery. Control samples of subscapularis tendon were collected from patients undergoing arthroscopic stabilisation surgery. Markers of inflammation and HMGB1 were quantified by reverse transcriptase PCR (RT-PCR) and immunohistochemistry. Human tendon-derived primary cells were derived from hamstring tendon tissue obtained during hamstring tendon anterior cruciate ligament reconstruction and used through passage 3. In vitro effects of recombinant HMGB1 on tenocyte matrix and inflammatory potential were measured using quantitative RT-PCR, ELISA and immunohistochemistry staining. Results: Tendinopathic tissues demonstrated significantly increased levels of the danger molecule HMGB1 compared with control tissues with early tendinopathy tissue showing the greatest expression. The addition of recombinant human HMGB1 to tenocytes led to significant increase in expression of a number of inflammatory mediators, including interleukin 1 beta (IL-1β), IL-6, IL-33, CCL2 and CXCL12, in vitro. Further analysis demonstrated rhHMGB1 treatment resulted in increased expression of genes involved in matrix remodelling. Significant increases were observed in Col3, Tenascin-C and Decorin. Moreover, blocking HMGB1 signalling via toll-like receptor 4 (TLR4) silencing reversed these key inflammatory and matrix changes. Conclusion: HMGB1 is present in human tendinopathy and can regulate inflammatory cytokines and matrix changes. We propose HMGB1 as a mediator driving the inflammatory/matrix crosstalk and manipulation of the HMGB1/TLR4 axis may offer novel therapeutic approaches targeting inflammatory mechanisms in the management of human tendon disorders

Achieving integrated treatment:a realist synthesis of service models and systems for co-existing serious mental health and substance use conditions

Approximately 30-50% of people with serious mental illness have co-existing drug/alcohol problems (COSMHAD), associated with adverse health/social care outcomes. UK guidelines advocate both co-occurring needs being met within mental health services but uncertainty remains about how to operationalise this to improve outcomes. Various unevaluated service configurations exist in the UK. A realist synthesis was undertaken to identify, test and refine programme theories (PTs) explaining how context shapes the mechanisms through which UK service models for COSMHAD work, for whom, and in what circumstances. Structured and iterative realist searches of 7 databases identified 5,099 records. A two-stage screening process identified 132 papers. Three broad contextual factors shaped COMSHAD services across 11 PTs: committed leadership; clear expectations regarding COSMAHD from mental health and substance use workforces; and clear care coordination processes. These contextual factors led to increased staff empathy, confidence, legitimisation and multidisciplinary ethos which improved care coordination, and increased people with COSMHAD’s motivations to work towards their goals. Our synthesis highlights that integrating COSMHAD care is complex and both individual and cultural behavioural shifts in leadership, workforce and service delivery is essential to ensure people with COSMHAD receive compassionate, trauma informed care that meets their needs

Comparing transgender and cisgender experiences of being taken advantage of sexually while under the influence of alcohol and/or other drugs

A small body of literature suggests that transgender people are more frequently exposed to sexual violence while they are under the influence of alcohol than cisgender counterparts. The goal of this study was to report any differences between transgender (n=1,136) and cisgender (n=74,277) respondents to the Global Drug Survey on their experiences of being taken advantage of sexually while under the influence of alcohol and/or other drugs. We found that transgender people were more likely than cisgender people to have experienced being taken advantage of in the last year (9.3% vs 4.2%) and more than 12 months preceding the survey (24.9% vs 14.3%). Non-binary participants were more likely than binary transgender participants (27.7% vs 17.8%) to report being taken advantage of sexually more than a year preceding the survey. Similarly, trans respondents assigned female at birth were more likely than trans respondents assigned male at birth to report this (30.0% vs 19.7%). Non-specialist services for survivors of sexual violence should be adequately prepared for and accommodating towards transgender clients. Future research should explore their unique needs. Moreover, clinicians who assess transgender people should remain mindful of their increased likelihood of being taken advantage of sexually while under the influence of alcohol and other drugs and consider trauma-informed interventions

Psychiatric Symptoms and Proinflammatory Cytokines in Pregnancy

Clinical studies suggest that psychiatric symptoms, particularly depression, anxiety and trauma, may be associated with inflammation, as indexed by proinflammatory cytokines. Such a link may be especially significant in pregnancy, and may shed additional light on the etiology of perinatal mood disorders

Pandemic-related changes in alcohol use among LGB+ people with and without mental health and neurodevelopmental conditions: a multinational cross-sectional study

Purpose: Using data from 36,981 respondents to the Global Drug Survey (GDS) COVID-19 Special Edition, this study aims to compare changes, following the first “lockdown,” in alcohol consumption between lesbian, gay, bisexual and other sexual minority (LGB+) and heterosexual respondents with and without lifetime mental health and neurodevelopmental (MHND) conditions. Design/methodology/approach: Characteristics and drinking behavior of respondents to GDS who disclosed their sexual orientation and past 30-day alcohol use were described and compared. LGB+ participants with and without MHND conditions were compared, and logistic regression models identified correlates of increased drinking among LGB+ people. The impact of changed drinking on the lives of LGB+ participants with and without MHND conditions was assessed. Findings: LGB+ participants who reported that they were “not coping well at all” with the pandemic had twofold greater odds of reporting increased binge drinking. LGB+ participants with MHND conditions were significantly more likely than those without to report increased drinking frequency (18.7% vs 12.4%), quantity (13.8% vs 8.8%) and that changed drinking had impacted their lives. Originality/value: This study, which has a uniquely large and international sample, explores aspects of alcohol use not considered in other COVID-19 alcohol use research with LGB+ people; and to the best of the authors’ knowledge, this is the first study to explore alcohol use among LGB+ people with MHND conditions

Achieving integrated treatment: a realist synthesis of service models and systems for co-existing serious mental health and substance use conditions.

Approximately 30-50% of people with serious mental illness have co-existing drug or alcohol problems (COSMHAD), associated with adverse health and social care outcomes. UK guidelines advocate both co-occurring needs being met within mental health services, but uncertainty remains about how to operationalise this to improve outcomes. Various unevaluated service configurations exist in the UK. A realist synthesis was done to identify, test, and refine programme theories of how context shapes the mechanisms through which UK service models for COSMHAD work, for whom, and in what circumstances. Structured and iterative realist searches of seven databases identified 5099 records. A two-stage screening process identified 132 papers. Three broad contextual factors shaped COSMHAD services across 11 programme theories: committed leadership, clear expectations regarding COSMHAD from mental health and substance use workforces, and clear care-coordination processes. These contextual factors led to increased staff empathy, confidence, legitimisation, and multidisciplinary ethos, which improved care coordination and increased the motivation of people with COSMHAD to work towards their goals. Our synthesis highlights that integrating COSMHAD care is complex, and both individual and cultural behavioural shifts in leadership, workforce, and service delivery are essential to ensure people with COSMHAD receive compassionate, trauma-informed care that meets their needs

Achieving integrated treatment: a realist synthesis of service models and systems for co-existing serious mental health and substance use conditions

Approximately 30–50% of people with serious mental illness have co-existing drug or alcohol problems (COSMHAD), associated with adverse health and social care outcomes. UK guidelines advocate both co-occurring needs being met within mental health services, but uncertainty remains about how to operationalise this to improve outcomes. Various unevaluated service configurations exist in the UK. A realist synthesis was done to identify, test, and refine programme theories of how context shapes the mechanisms through which UK service models for COSMHAD work, for whom, and in what circumstances. Structured and iterative realist searches of seven databases identified 5099 records. A two-stage screening process identified 132 papers. Three broad contextual factors shaped COSMHAD services across 11 programme theories: committed leadership, clear expectations regarding COSMHAD from mental health and substance use workforces, and clear care-coordination processes. These contextual factors led to increased staff empathy, confidence, legitimisation, and multidisciplinary ethos, which improved care coordination and increased the motivation of people with COSMHAD to work towards their goals. Our synthesis highlights that integrating COSMHAD care is complex, and both individual and cultural behavioural shifts in leadership, workforce, and service delivery are essential to ensure people with COSMHAD receive compassionate, trauma-informed care that meets their needs

Fiction Fix 12

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The Effects of Trauma History and Prenatal Affective Symptoms on Obstetric Outcomes: Trauma, Anxiety, and Birthweight

Prenatal maternal mood may explain the adverse obstetric outcomes seen in disadvantaged populations yet the effects of trauma history are not well studied. We examined the impact of trauma exposure and mood symptoms on obstetric outcomes in 358 women. Women with antecedent trauma were more likely to have a history of depression χ2(1, N = 358) = 19.2, p =.001; OR = 2.83, 95% CI [1.81, 4.42], were younger at their first pregnancy t(356) = −2.97, p = .003 and had a higher number of previous pregnancies t(356) = 2.77, p = .011 compared to those with no trauma exposure. Women with prenatal anxiety had significantly smaller babies than nonanxious women F(1, 322) = 5.32, p = .024. Trauma history magnified the effects of maternal prenatal mood on birth weight; the moderating effect was limited to those who first experienced a trauma under 18 years of age F(14, 320) = 2.44, p =.005. Childhood trauma exposure increases vulnerability for low birthweight delivery associated with prenatal mood disturbance. Screening pregnant women for trauma history and current mood symptoms is indicated