New Evidence for the Role of the Blood-Brain Barrier and Inflammation in Stress-Associated Depression: A Gene-Environment Analysis Covering 19,296 Genes in 109,360 Humans.

Mounting evidence supports the key role of the disrupted integrity of the blood-brain barrier (BBB) in stress- and inflammation-associated depression. We assumed that variations in genes regulating the expression and coding proteins constructing and maintaining this barrier, along with those involved in inflammation, have a predisposing or protecting role in the development of depressive symptoms after experiencing severe stress. To prove this, genome-by-environment (GxE) interaction analyses were conducted on 6.

The role of nutrient sensing dysregulation in anorexia of ageing: The little we know and the much we don't.

The age-related decline in appetite and food intake - termed "anorexia of ageing" - is implicated in undernutrition in later life and hence provides a public health challenge for our ageing population. Eating behaviour is controlled, in part, by homeostatic mechanisms which sense nutrient status and provide feedback to appetite control regions of the brain. Such feedback signals, propagated by episodic gut hormones, are dysregulated in some older adults.

Percutaneous tibial nerve stimulation versus sacral nerve stimulation for the treatment of faecal incontinence.

Introduction: Faecal incontinence (FI) is a common condition with a significant impact on quality of life (QoL). Neuromodulation treatments delivered by members of the multidisciplinary team including sacral nerve stimulation (SNS) and percutaneous tibial nerve stimulation (PTNS) are options for FI refractory to conservative management. The aim of this study was to assess whether a successful treatment with one neuromodulation modality corresponds with success in the other.

Habit training versus habit training with direct visual biofeedback in adults with chronic constipation: A randomized controlled trial.

Aim: The aim was to determine whether specialist-led habit training using Habit Training with Biofeedback (HTBF) is more effective than specialist-led habit training alone (HT) for chronic constipation and whether outcomes of interventions are improved by stratification to HTBF or HT based on diagnosis (functional defaecation disorder vs. no functional defaecation disorder) by radio-physiological investigations (INVEST).

Method: This was a parallel three-arm randomized single-blinded controlled trial, permitting two randomized comparisons: HTBF versus HT alone; INVEST- versus no-INVEST-guided intervention.

Exploring the delivery of remote physiotherapy during the COVID-19 pandemic: UK wide service evaluation.

Introduction: During the Coronavirus (Covid-19) pandemic, physiotherapists changed rapidly to working remotely. Research demonstrates the benefits of remote physiotherapy, but little is known about its implementation in practice.

Purpose: Explore the take-up and delivery of remote physiotherapy during the pandemic in the United Kingdom.

Surgery versus radiosurgery for vestibular schwannoma: Shared decision making in a multidisciplinary clinic.

Background: Our neurosurgical unit adopted a model of shared decision-making (SDM) based on multidisciplinary clinics for vestibular schwannoma (VS). A unique feature of this clinic is the interdisciplinary counseling process with a surgeon presenting the option of surgery, an oncologist radiosurgery or radiotherapy, and a specialist nurse advocating for the patient.

Methods: This is a retrospective cohort study.

Inflammation and Blood-Brain Barrier in Depression: Interaction of CLDN5 and IL6 Gene Variants in Stress-Induced Depression.

Background: Evidence from rodents indicated that after recent stress, reduced expression of tight junction protein claudin-5 may weaken the blood-brain barrier and allow interleukin-6 to induce depressive symptoms. Our aims were to prove this pathomechanism in humans.

Methods: We used a large population genetic database (UK Biobank, n = 277 501) to test whether variation in the CLDN5 gene could modulate effects of the IL6 gene variant in stress-induced depression.

Management of anxiety disorders among children and adolescents in UK primary care: A cohort study.

Background: Anxiety disorders are common in childhood and adolescence but evidence-based guidance on their management is limited in the UK. In the absence of guidelines, we examined what treatment young people with anxiety disorders receive in primary care in the year following diagnosis.

Method: We delineated a cohort of individuals diagnosed with anxiety disorders aged 10-18 using the Clinical Practice Research Datalink (CPRD).

Hybrid model of compounded and multichamber bag parenteral nutrition for adults with chronic intestinal failure.

Background: Although international guidelines support the use of commercially available multichamber bags (MCBs), the majority of home parenteral nutrition (HPN) in the United Kingdom has been compounded PN, tailored to the patient. However, national capacity limitations in aseptic facilities have necessitated the increased use of MCBs. There are no studies evaluating the appropriateness or benefits of using a "hybrid" regimen incorporating both MCBs and compounded PN in patients already established on compounded HPN.

Excess years of life lost to COVID-19 and other causes of death by sex, neighbourhood deprivation, and region in England and Wales during 2020: A registry-based study.

Background: Deaths in the first year of the Coronavirus Disease 2019 (COVID-19) pandemic in England and Wales were unevenly distributed socioeconomically and geographically. However, the full scale of inequalities may have been underestimated to date, as most measures of excess mortality do not adequately account for varying age profiles of deaths between social groups. We measured years of life lost (YLL) attributable to the pandemic, directly or indirectly, comparing mortality across geographic and socioeconomic groups.

A replication study separates polymorphisms behind migraine with and without depression.

The largest migraine genome-wide association study identified 38 candidate loci. In this study we assessed whether these results replicate on a gene level in our European cohort and whether effects are altered by lifetime depression. We tested SNPs of the loci and their vicinity with or without interaction with depression in regression models.

A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials.

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification.

Excess deaths from COVID-19 and other causes by region, neighbourhood deprivation level and place of death during the first 30 weeks of the pandemic in England and Wales: A retrospective registry study.

Background: Excess deaths during the COVID-19 pandemic compared with those expected from historical trends have been unequally distributed, both geographically and socioeconomically. Not all excess deaths have been directly related to COVID-19 infection. We investigated geographical and socioeconomic patterns in excess deaths for major groups of underlying causes during the pandemic.

Catheter-related infection rates in patients receiving customized home parenteral nutrition compared with multichamber bags.

Background: The risk of bloodstream infections may be increased in hospitalized patients receiving ready-made parenteral nutrition (PN) multichamber bags (MCBs) compared with customized PN; however, as highlighted in recent international guidelines, there are no comparable data relating to home PN (HPN).

Methods: Data from a prospectively maintained database were analyzed to compare incidence rates of catheter-related bloodstream infections (CRBSIs) between patients receiving customized HPN compared with MCB HPN at a national UK referral center between May 2018 and August 2020.

Results: Sixty patients with chronic intestinal failure were commenced on MCBs and 45 received customized HPN for a total of 5914 and 7641 catheter days, respectively.

P2RX7 gene variation mediates the effect of childhood adversity and recent stress on the severity of depressive symptoms.

The P2X purinoceptor 7 (P2RX7) mediates inflammatory microglial responses and is implicated in neuroimmune mechanisms of depression and neurodegenerative disorders. A number of studies suggest that psychosocial stress may precipitate depression through immune activation. Genetic association studies of P2RX7 variants with depression have been inconclusive.

"I was Confused … and Still am" Barriers Impacting the Help-Seeking Pathway for an Autism Diagnosis in Urban North India: A Mixed Methods Study.

Timely recognition of autism in children is integral to improve developmental outcomes. This study used mixed-methods (84 case-registers and 20 in-depth interviews with caregivers of children with a diagnosis of autism) to explore the extent to which the nature of parental concerns and prior knowledge of developmental disorders impact the time between symptom recognition and autism diagnosis, and the contextual family, societal and health-system related factors that impede the autism help-seeking pathway. Lack of awareness of age-appropriate child developmental milestones, apparent amongst the community and health professionals, contributed to a 1.

Temporal trends in annual incidence rates for psychiatric disorders and self-harm among children and adolescents in the UK, 2003-2018.

Background: There has been growing concern in the UK over recent years that a perceived mental health crisis is affecting children and adolescents, although published epidemiological evidence is limited.

Methods: Two population-based UK primary care cohorts were delineated in the Aurum and GOLD datasets of the Clinical Practice Research Datalink (CPRD). We included data from 9,133,246 individuals aged 1-20 who contributed 117,682,651 person-years of observation time.

Annual Research Review: Achieving universal health coverage for young children with autism spectrum disorder in low- and middle-income countries: a review of reviews.

Background: Autism presents with similar prevalence and core impairments in diverse populations. We conducted a scoping review of reviews to determine key barriers and innovative strategies which can contribute to attaining universal health coverage (UHC), from early detection to effective interventions for autism in low- and middle-income countries (LAMIC).

Methods: A systematic literature search of review articles was conducted.

The relationship between language difficulties, psychosocial difficulties and speech-language pathology service access in the community.

Background: A range of factors may impact whether children access speech-language pathology (SLP) services, beyond their communication difficulties. For instance, co-occurring psychosocial difficulties may amplify children's observable difficulties, leading to greater access. It is important to examine such associations because they may reflect inherent differences between children with language difficulties who access services and those who do not, indicating under-servicing for subgroups in the community.

COVID-19 infection in patients with intestinal failure: UK experience.

Background: The direct effect of the coronavirus disease 2019 (COVID-19) pandemic on patients with intestinal failure (IF) has not been described.

Methods: We conducted a nationwide study of UK IF centers to evaluate the infection rates, presentations, and outcomes in patients with types 2 and 3 IF.

Results: A total of 45 patients with IF contracted COVID-19 between March and August 2020; this included 26 of 2191 (1.

An International Survey of Clinicians' Experience Caring for Patients Receiving Home Parenteral Nutrition for Chronic Intestinal Failure During the COVID-19 Pandemic.

Background: This survey of centers caring for patients receiving home parenteral nutrition (HPN) was conducted to assess the impact of the coronavirus disease 2019 (COVID-19) crisis on the management of these patients regarding provision of care, monitoring, regular follow-up, and any changes to service infrastructure.

Methods: A survey was devised and publically published on the Research Electronic Data Capture database management system, with individual centers responding to a public link.

Results: A total of 78 adult and pediatric centers worldwide contributed to the survey, representing ≥3500 patients' experiences.