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Before the COVID-19 pandemic, the prevalence and severity of psychiatric disorders among sexual and gender diverse (SGD) young people was greater than in their heterosexual/cisgender peers. We systematically reviewed literature examining the prevalence, severity, and risk factors for psychiatric disorders among SGD young people aged 25 and under during the pandemic. Four databases (MEDLINE, PsycInfo, Scopus and Web of Science) were searched. Eligibility criteria were studies assessing prevalence rates, mean symptomology scores and risk factors of psychiatric disorders using contemporaneous screening measures or diagnosis. Thirteen studies of mixed quality were identified. Most studies indicated SGD young people were at high risk of experiencing several psychiatric disorders including depressive and generalised anxiety disorder compared to the general population. This group also experienced more severe symptomology of various psychiatric disorders compared to their heterosexual/cisgender peers. Risk factors included those specific to the pandemic along with factors that led to greater risk before the pandemic. This systematic review has indicated evidence of heightened risk of psychiatric disorders among SGD young people during the COVID-19 pandemic. It is important for clinicians to acknowledge the needs of SGD young people, working with them to co-develop more inclusive care as they deal with the pandemic's fallout. Plain language summary: Why was the study done? Before the COVID-19 pandemic, the prevalence and severity of psychiatric disorders in sexual and gender diverse (SGD) young people was greater than in their heterosexual/cisgender peers, based on several risk factors. Research using validated screening measures assessed whether this continued during the pandemic. Yet, these studies have not been brought together in an organised fashion to provide a comprehensive summary of this evidence. What did the researchers do? We reviewed literature examining the prevalence, severity, and risk factors for psychiatric disorders among SGD young people aged 25 and under during the pandemic. Eligibility criteria were studies assessing prevalence rates, mean symptomology scores or risk factors of psychiatric disorders using contemporaneous screening measures or diagnosis. What did the researchers find? Thirteen studies of mixed quality were identified. Most studies indicated SGD young people were more likely to report experiencing several psychiatric disorders including depressive and generalised anxiety disorders compared to the general population. SGD young people also experienced more severe symptomology of various psychiatric disorders compared to their heterosexual/cisgender peers. Risk factors included those specific to the pandemic along with factors that existed before the pandemic. What do the findings mean? This review suggests SGD young people were at greater risk of psychiatric disorders during the COVID-19 pandemic. Clinicians should acknowledge the needs of SGD young people, working with them to co-develop more inclusive care as they deal with the pandemic's fallout. [ABSTRACT FROM AUTHOR]

Conjugation of small interfering RNA (siRNA) to an asialoglycoprotein receptor ligand derived from N-acetylgalactosamine (GalNAc) facilitates targeted delivery of the siRNA to hepatocytes in vitro and in vivo. The ligands derived from GalNAc are compatible with solid-phase oligonucleotide synthesis and deprotection conditions, with synthesis yields comparable to those of standard oligonucleotides. Subcutaneous (SC) administration of siRNA-GalNAc conjugates resulted in robust RNAi-mediated gene silencing in liver. Refinement of the siRNA chemistry achieved a 5-fold improvement in efficacy over the parent design in vivo with a median effective dose (ED50) of 1 mg/kg following a single dose. This enabled the SC administration of siRNA-GalNAc conjugates at therapeutically relevant doses and, importantly, at dose volumes of ≤1 mL. Chronic weekly dosing resulted in sustained dose-dependent gene silencing for over 9 months with no adverse effects in rodents. The optimally chemically modified siRNA-GalNAc conjugates are hepatotropic and long-acting and have the potential to treat a wide range of diseases involving liver-expressed genes.

Evidence suggests heightened prevalence and severity of mental disorders among sexual minority (SM) and gender minority (GM) young people. Several risk factors have been associated with these disparities. A systematic review of systematic reviews and meta-analysis was conducted to provide a comprehensive overview of the literature and to determine the field's current position. MEDLINE, PsycInfo, Scopus and Web of Science were searched in March 2022 and updated January 2024. Eligibility criteria were systematic reviews or meta-analyses assessing contemporaneous prevalence, severity and/or risk factors of mental disorders among SM or GM young people aged 25 and under. 42 reviews were included, all of which were low quality. The prevalence of depression among SM was 26% (95% CI 21-32%), and among GM was 46% (95% CI 36-56%). Greater depression severity was found among SM compared to heterosexual young people, with a significant albeit small effect size (Hedges' g = 0.38, 95% CI = 0.25 to 0.50); effect sizes were similar when separating by gender. GM also reported greater symptom severity compared to cisgender young people. Other mental disorders were more prevalent compared to those reported in the general population, and of greater severity compared to heterosexual/cisgender young people. Several proximal and distal risk factors were focused upon within the systematic reviews identified. Past systematic reviews consistently indicate a heightened risk of mental disorders among SM and GM young people. Services need to be aware of these disparities and adapt their care accordingly., (© 2024. The Author(s).)

Background: Avoidant restrictive food intake disorder (ARFID) is a feeding and eating disorder with known acute and longstanding physical health complications in children and young people (CYP) and commonly presents to paediatricians., Objective: To systematically review the published literature on physical health complications in CYP with ARFID using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines., Methods: A systematic search of PubMed, Embase, Web of Science, PsycINFO and Cochrane Library was performed on 14 February 2024. Studies reporting physical health complications in CYP ≤25 years with ARFID were included. We pooled studies for meta-analysis comparing ARFID with healthy controls or anorexia nervosa (AN)., Results: Of 9058 studies found in searches, we included 132 studies. We found evidence for low weight, nutritional deficiencies and low bone mineral density. CYP with ARFID can present across the weight spectrum; however, the majority of CYP with ARFID were within the healthy weight to underweight range. Most studies reported normal range heart rates and blood pressures in ARFID, but some CYP with ARFID do experience bradycardia and hypotension. CYP with ARFID had higher heart rates than AN (weighted mean difference: 12.93 bpm; 95% CI: 8.65 to 17.21; n=685); heterogeneity was high (I 2 : 81.33%)., Conclusion: There is a broad range of physical health complications associated with ARFID requiring clinical consideration. Many CYP with ARFID are not underweight yet still have complications. Less cardiovascular complications found in ARFID compared with AN may be related to chronicity., Prospero Registration Number: CRD42022376866., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)