The Impact of Non-Fiscal Mandatory and Voluntary Policies and Interventions on the Reformulation of Food and Beverage Products: A Systematic Review.

Background/Objectives: Low quality diets are a risk factor for non-communicable diseases; therefore, improving diet quality is a public health and policy priority in the UK and elsewhere. Reformulating food/beverage products to make them healthier may be an effective approach. Evidence suggests that fiscal interventions, notably taxes/levies on soft drinks, can lead to reformulation but the evidence for voluntary or mandated non-fiscal interventions is less clear. We aimed to review and synthesise contemporary evidence to determine whether non-fiscal policies/interventions result in the reformulation of food/beverage products Methods: In April 2023, we systematically searched ten international academic and nine grey literature databases. We included real-world study designs, all nutrients, in- and out-of-home sectors, and studies published from 2013, to ensure policy relevancy. We excluded modelling studies. Using the Synthesis Without Meta-Analysis method we conducted vote counting of studies based on the direction of effect and narrative synthesis by intervention type. Risk of bias was assessed using a tool developed by the EPPI-Centre and quality was assessed using GRADE. Results: We included 77 real-world studies from 19 countries, reporting 100 non-fiscal policies/interventions. Most commonly, these were reduction targets (n = 44), front-of-pack labels (n = 23), and advertising standards (n = 9). Most interventions were voluntary (n = 67), compared to mandatory (n = 33), and focused on the in-home sector (n = 63). The vote counting results showed non-fiscal policies/interventions overall led to improvements in reformulation in 60/63 studies with a valid direction of effect (95%, 95% CI 0.869, 0.984, p < 0.001). Mandatory implementations were more successful than voluntary implementations with 15/15 showing an improvement (100%, 95% CI 0.796, 1], p < 0.001), compared 40/43 showing an improvement (93%, 95% CI 0.814, 0.976, p < 0.001). Most of the studies were of low quality, due to the observational nature of the studies. Sodium was the most commonly targeted nutrient (n = 56) and was found to be reformulated in most studies. Causation is difficult to establish from real-world studies, but evidence suggests that regulatory and multi-component strategies may be effective at driving reformulation. Conclusions: Non-fiscal policies/interventions can play an important role in driving reformulation, alongside fiscal measures. This work was funded by the National Institute for Health and Care Research PRP-PRU-02-15-Healthy Weight and registered on Open Science Framework.

Progressing "Positive epidemiology": A cross-national analysis of adolescents' positive mental health and outcomes during the COVID-19 pandemic.

PURPOSE: "Positive epidemiology" emphasizes strengths and assets that protect the health of populations. Positive mental health refers to a range of social and emotional capabilities that may support adaptation to challenging circumstances. We examine the role of positive mental health in promoting adolescent health during the crisis phase of the COVID-19 pandemic. METHODS: We used four long-running Australian and UK longitudinal cohorts: Childhood to Adolescence Transition Study (CATS; analyzed N=809; Australia); Longitudinal Study of Australian Children (LSAC) - Baby (analyzed N=1,534) and Kindergarten (analyzed N=1,300) cohorts; Millennium Cohort Study (MCS; analyzed N=2,490; UK). Measures included: (Pre-pandemic exposure): Positive mental health (parent-reported, 13-15 years) including regulating emotions, interacting well with peers, and caring for others; and pandemic outcomes: psychological distress, life satisfaction, and sleep and alcohol use outside of recommendations (16-21 years; 2020). We used two-stage meta-analysis to estimate associations between positive mental health and outcomes across cohorts, accounting for potential confounders. RESULTS: Estimates suggest meaningful effects of positive mental health on psychosocial outcomes during the pandemic, including lower risk of psychological distress (Risk Ratio [RR]=0.83 95%CI=0.71, 0.97) and higher life satisfaction (RR=1.1, 95%CI=1.0, 1.2). The estimated effects for health behaviors were smaller in magnitude (sleep: RR=0.95, 95%CI=0.86, 1.1; alcohol use: RR=0.97, 95%CI=0.85, 1.1). CONCLUSIONS: Our results are consistent with the hypothesis that adolescents' positive mental health supports better psychosocial outcomes during challenges such as the COVID-19 pandemic, but relevance for health behaviors is less clear. These findings reinforce the value of extending evidence to include positive health states and assets.

COVID-19 vaccine effectiveness and uptake in a national cohort of English children and young people with life-limiting neurodisability.

OBJECTIVE: To investigate SARS-CoV-2 vaccine uptake and effectiveness in children and young people (CYP) with life-limiting neurodisability. DESIGN: We undertook a retrospective cohort study using national hospital data in England from 21 December 2020 to 2 September 2022 to describe SARS-CoV-2 vaccination uptake, and then examined COVID-19 hospitalisation, paediatric intensive care unit (PICU) admission and death following SARS-CoV-2 infection by vaccination status using Cox regression models. PATIENTS: CYP aged 5-17 with life-limiting neurodisability. RESULTS: We identified 38 067 CYP with life-limiting neurodisability; 13 311 (35.0%) received at least one SARS-CoV-2 vaccine, with uptake higher among older, white CYP, from less deprived neighbourhoods. Of 8134 CYP followed up after a positive SARS-CoV-2 test, 1547 (19%) were vaccinated. Within 28 days of infection, 309 (4.7%) unvaccinated CYP were hospitalised with COVID-19 compared with 75 (4.8%) vaccinated CYP. 46 (0.7%) unvaccinated CYP were admitted to PICU compared with 10 (0.6%) vaccinated CYP. 20 CYP died within 28 days of SARS-CoV-2 infection, of which 13 were unvaccinated. Overall, adjusted hazard of hospitalisation for COVID-19 or admission to PICU did not vary by vaccination status. When the Alpha-Delta SARS-CoV-2 variants were dominant, hazard of hospitalisation with COVID-19 was significantly lower among vaccinated CYP (HR 0.26 (0.09 to 0.74)), with no difference seen during Omicron (HR 1.16 (0.74 to 1.81)). CONCLUSIONS: SARS-CoV-2 vaccination was protective of COVID-19 hospitalisation among CYP with life-limiting neurodisability during Alpha-Delta, but not for other SARS-CoV-2 variants. Vaccine uptake was low and varied by ethnicity and deprivation.

The Impact of COVID-19 on Acute Surgeries in England Among the Under-25s: A Retrospective Study of 61,360 Appendicitis and 15,850 Testicular Torsion Admissions.

BACKGROUND: Little is known about how COVID-19 impacted acute surgical activity for children and young people (CYP) across England. Appendicitis and testicular torsion are common surgical conditions where treatment delays can lead to avoidable complications. We undertook a retrospective national cohort study. PRIMARY AIM: To describe monthly acute surgical activity in CYP during the COVID-19 pandemic. Secondary aim: To investigate evidence of delayed diagnosis and adverse outcomes, describing variations by age and socioeconomic deprivation. METHODS: Acute hospital admissions with appendicitis or testicular pain for those under 18 were extracted using Hospital Episode Statistics. Interrupted time series modelling, Mann-Whitney and Pearson's Chi-Squared tests compared the first 14 pandemic months with the previous five years. Results were stratified by age (0-4s, 5-9s and 10-17s) and appendicitis type (all, simple and complex). RESULTS: Admissions for appendicitis and testicular torsion fell significantly early in the COVID-19 pandemic. The proportion of children with complex appendicitis also increased during this time. Orchidectomy rates rose in April 2020 for the 0-4s (+15.6% (95% CI 7.9-23.3)) and 10-17s (+11.5% (4.9-18.2)), but when the pre-pandemic period was compared with the pandemic period as a whole, there were no overall statistically significant differences in orchidectomy rates between the study periods. Overall, there was a statistically significant rise in the orchidopexy rate during the pandemic period for the 10-17s when compared with the pre-pandemic period (Pre-pandemic: 17.0% vs Pandemic: 20.9%, p < 0.0001). CONCLUSION: A consistent reduction in activity, with short-lived periods of delayed presentations during COVID-19 pandemic peaks, occurred without persisting overall increased complication rates. These results provide useful national context for smaller sized studies that reported complications due to delays in surgery. Future research could examine how reduced activity impacted other healthcare settings and treatment pathways. LEVEL OF EVIDENCE: II.

Clinical implications of head trauma in frontotemporal dementia and primary progressive aphasia.

BACKGROUND: Traumatic brain injury (TBI) and repetitive head impacts (RHI) have been linked to increased risk for multiple types of neurodegenerative disease, higher dementia risk, and earlier age of dementia symptom onset, suggesting transdiagnostic implications for later-life brain health. Frontotemporal dementia (FTD) and primary progressive aphasia (PPA) represent a spectrum of clinical phenotypes that are neuropathologically diverse. FTD/PPA diagnoses bring unique challenges due to complex cognitive and behavioral symptoms that disproportionately present as an early-onset dementia (before age 65). We performed a detailed characterization of lifetime head trauma exposure in individuals with FTD and PPA compared to healthy controls to examine frequency of lifetime TBI and RHI and associated clinical implications. METHODS: We studied 132 FTD/PPA (age 68.9 ± 8.1, 65% male) and 132 sex-matched healthy controls (HC; age 73.4 ± 7.6). We compared rates of prior TBI and RHI (contact/collision sports) between FTD/PPA and HC (chi-square, logistic regression, analysis of variance). Within FTD/PPA, we evaluated associations with age of symptom onset (analysis of variance). Within behavioral variant FTD, we evaluated associations with cognitive function and neuropsychiatric symptoms (linear regression controlling for age, sex, and years of education). RESULTS: Years of participation were greater in FTD/PPA than HC for any contact/collision sport (8.5 ± 6.7yrs vs. 5.3 ± 4.5yrs, p = .008) and for American football (6.2yrs ± 4.3yrs vs. 3.1 ± 2.4yrs; p = .003). Within FTD/PPA, there were dose-dependent associations with earlier age of symptom onset for TBI (0 TBI: 62.1 ± 8.1, 1 TBI: 59.9 ± 6.9, 2 + TBI: 57.3 ± 8.4; p = .03) and years of American football (0yrs: 62.2 ± 8.7, 1-4yrs: 59.7 ± 7.0, 5 + yrs: 55.9 ± 6.3; p = .009). Within bvFTD, those who played American football had worse memory (z-score: -2.4 ± 1.2 vs. -1.4 ± 1.6, p = .02, d = 1.1). CONCLUSIONS: Lifetime head trauma may represent a preventable environmental risk factor for FTD/PPA. Dose-dependent exposure to TBI or RHI influences FTD/PPA symptom onset and memory function in bvFTD. Clinico-pathological studies are needed to better understand the neuropathological correlates linking RHI or TBI to FTD/PPA onset and symptoms.

3D-Mapping and Manipulation of Photocurrent in an Optoelectronic Diamond Device.

Establishing connections between material impurities and charge transport properties in emerging electronic and quantum materials, such as wide-bandgap semiconductors, demands new diagnostic methods tailored to these unique systems. Many such materials host optically-active defect centers which offer a powerful in situ characterization system, but one that typically relies on the weak spin-electric field coupling to measure electronic phenomena. In this work, charge-state sensitive optical microscopy is combined with photoelectric detection of an array of nitrogen-vacancy (NV) centers to directly image the flow of charge carriers inside a diamond optoelectronic device, in 3D and with temporal resolution. Optical control is used to change the charge state of background impurities inside the diamond on-demand, resulting in drastically different current flow such as filamentary channels nucleating from specific, defective regions of the device. Conducting channels that control carrier flow, key steps toward optically reconfigurable, wide-bandgap optoelectronics are then engineered using light. This work might be extended to probe other wide-bandgap semiconductors (SiC, GaN) relevant to present and emerging electronic and quantum technologies.

Reduced Expression of Oligodendrocyte Linage-Enriched Transcripts During the Endoplasmic Reticulum Stress/Integrated Stress Response.

Endoplasmic reticulum (ER) stress in oligodendrocyte (OL) linage cells contributes to several CNS pathologies including traumatic spinal cord injury (SCI) and multiple sclerosis. Therefore, primary rat OL precursor cell (OPC) transcriptomes were analyzed using RNASeq after treatments with two ER stress-inducing drugs, thapsigargin (TG) or tunicamycin (TM). Gene ontology term (GO) enrichment showed that both drugs upregulated mRNAs associated with the general stress response. The GOs related to ER stress were only enriched for TM-upregulated mRNAs, suggesting greater ER stress selectivity of TM. Both TG and TM downregulated cell cycle/cell proliferation-associated transcripts, indicating the anti-proliferative effects of ER stress. Interestingly, many OL lineage-enriched mRNAs were downregulated, including those for transcription factors that drive OL identity such as Olig2. Moreover, ER stress-associated decreases of OL-specific gene expression were found in mature OLs from mouse models of white matter pathologies including contusive SCI, toxin-induced demyelination, and Alzheimer's disease-like neurodegeneration. Taken together, the disrupted transcriptomic fingerprint of OL lineage cells may facilitate myelin degeneration and/or dysfunction when pathological ER stress persists in OL lineage cells.

The ER stress response compromises the transcriptomic identity of the OL lineage. Therefore, persistent, pathological ER stress may have a negative impact on structural and/or functional integrity of the white matter.

Morphological and Mechanical Tube Feet Plasticity among Populations of Sea Urchin (Strongylocentrotus purpuratus).

Sea urchins rely on an adhesive secreted by their tube feet to cope with the hydrodynamic forces of dislodgement common in nearshore, high wave-energy environments. Tube feet adhere strongly to the substrate and detach voluntarily for locomotion. In the purple sea urchin, Strongylocentrotus purpuratus, adhesive performance depends on both the type of substrate and the population of origin, where some substrates and populations are more adhesive than others. To explore the source of this variation, we evaluated tube foot morphology (disc surface area) and mechanical properties (maximum disc tenacity and stem breaking force) of populations native to substrates with different lithologies: sandstone, mudstone, and granite. We found differences among populations, where sea urchins native to mudstone substrates had higher disc surface area and maximum disc tenacity than sea urchins native to sandstone substrates. In a lab-based reciprocal transplant experiment, we attempted to induce a plastic response in tube foot morphology. We placed sea urchins on nonnative substrates (i.e., mudstone sea urchins were placed on sandstone and vice versa), while keeping a subgroup of both populations on their original substrates as a control. Instead of a reciprocal morphological response, we found that all treatments, including the control, reduced their disc area in laboratory conditions. The results of this study show differences in morphology and mechanical properties among populations, which explains population differences in adhesive performance. Additionally, this work highlights the importance of considering the impact of phenotypic plasticity in response to captivity when interpreting the results of laboratory studies.

Los erizos de mar utilizan una secreción adhesiva en sus pies ambulacrales para adherirse al sustrato y resistir fuerzas hidrodinámicas. Los pies ambulacrales se adhieren fuertemente, pero pueden despegarse voluntariamente para moverse. En el erizo morado, Strongylocentrotus purpuratus, el desempeño del sistema de adhesión depende del tipo de sustrato y la población de origen donde algunas poblaciones y sustratos tienen mejor desempeño adhesivo que otros. Para explicar el origen de esta variación, evaluamos la morfología (área del disco) del pie ambulacral y las propiedades mecánicas (tenacidad máxima del disco y fuerza necesaria para romper el tubo que conecta el disco con el animal) de poblaciones que se encuentran adheridas a sustratos con diferentes litologías: arenisca, lodolitas, y granito. Encontramos diferencias entre las poblaciones donde erizos de la población que vive en lodolitas tienen tenacidad del disco más alta y discos más grandes que erizos que viven en arenisca. En un experimento de laboratorio, intentamos inducir una respuesta plástica en la morfología del pie ambulacral. Para esto, pusimos erizos en sustratos diferentes a los que normalmente se adhieren (erizos que en encuentran en lodolita los pusimos en arenisca y viceversa) y dejamos erizos en su sustrato original como control. Sin embargo, en lugar de una respuesta plástica en la morfología del pie ambulacral, encontramos que todos los tratamientos, incluido los controles, redujeron el área del disco en condiciones de laboratorio. Los resultados de este estudio muestran diferencias en morfología y propiedades mecánicas entre las poblaciones, lo que explica diferencias en el desempeño del sistema de adhesión. Además, este estudio demuestra la importancia de considerar el impacto de plasticidad fenotípica al momento de interpretar estudios de laboratorio.

Changing patterns of health risk in adolescence: implications for health policy.

Adolescence is a time of physical, cognitive, social, and emotional development. This period is a very sensitive developmental window; environmental exposures, the development of health behaviours (eg, smoking and physical activity), and illness during adolescence can have implications for lifelong health. In the UK and other high-income countries, the experience of adolescence has changed profoundly over the past 20 years. Smoking, drug use, and alcohol consumption have all been in long-term decline. At the same time, obesity and mental ill health have increased and are now common among adolescents, with new risks (ie, vaping, psychoactive substances, and online harms) emerging. In this Viewpoint, we describe these and related trends in England and the UK. Although previous work has explored these changes in isolation, in this Viewpoint we consider them collectively. We explore what might be driving the changes and consider the implications for practice, policy, and research.

Rising Unscheduled Healthcare Utilisation of Children and Young People: How Does the Rise Vary Across Deprivation Quintiles in UK Nations?

This retrospective population-based analysis assessed variations in urgent healthcare use by children and young people (CYP) across UK nations (England, Scotland and Wales) between 2007 and 2017. The study focused on urgent hospital admissions, short stay urgent admissions (SSUA) and Emergency Department (ED) attendances among CYP aged <25 years, stratified by age groups and Index of Multiple Deprivation (IMD) quintile groups. A linear mixed model was used to assess trends in healthcare activity over time and across deprivation quintiles. Urgent admissions, SSUA and ED attendances increased across all deprivation quintiles in all studied nations. Increasing deprivation was consistently associated with higher urgent healthcare utilisation. In England, the rise in urgent admissions and SSUA for CYP was slower for CYP from the quintile of greatest deprivation compared those from the least deprived quintile (respective mean differences 0.69/1000/y [95% CI 0.53, 0.85] and 0.25/1000/y [0.07, 0.42]), leading to a narrowing in health inequality. Conversely, in Scotland, urgent admissions and SSUA increased more rapidly for CYP from all deprivation quintiles, widening health inequality. Understanding the differences we describe here could inform changes to NHS pathways of care across the UK which slow the rise in urgent healthcare use for CYP.

The impact of the COVID-19 pandemic on 397 631 elective dental admissions among the under-25s in England: a retrospective study.

BACKGROUND: COVID-19 caused widespread disruptions to health services worldwide, including reductions in elective surgery. Tooth extractions are among the most common reasons for elective surgery among children and young people (CYP). It is unclear how COVID-19 affected elective dental surgeries in hospitals over multiple pandemic waves at a national level. METHODS: Elective dental tooth extraction admissions were selected using Hospital Episode Statistics. Admission trends for the first 14 pandemic months were compared with the previous five years and results were stratified by age (under-11s, 11-16s, 17-24s). RESULTS: The most socioeconomically deprived CYP comprised the largest proportion of elective dental tooth extraction admissions. In April 2020, admissions dropped by >95%. In absolute terms, the biggest reduction was in April (11-16s: -1339 admissions, 95% CI -1411 to -1267; 17-24s: -1600, -1678 to -1521) and May 2020 (under-11s: -2857, -2962 to -2752). Admissions differed by socioeconomic deprivation for the under-11s (P < 0.0001), driven by fewer admissions than expected by the most deprived and more by the most affluent during the pandemic. CONCLUSION: Elective tooth extractions dropped most in April 2020, remaining below pre-pandemic levels throughout the study. Despite being the most likely to be admitted, the most deprived under-11s had the largest reductions in admissions relative to other groups.

Assessing the impact of obesity interventions in the early years: a systematic review of UK-based studies.

OBJECTIVES: Childhood obesity rates in the UK are high. The early years of childhood are critical for establishing healthy behaviours and offer interventional opportunities. We aimed to identify studies evaluating the impact of UK-based obesity interventions in early childhood. DESIGN: Systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: Nine databases were searched in March 2023. ELIGIBILITY CRITERIA: We included UK-based obesity intervention studies delivered to children aged 6 months to 5 years that had diet and/or physical activity components and reported anthropometric outcomes. The primary outcome of interest was z-score Body Mass Index (zBMI) change (within and between subjects). Studies evaluating the effects of breastfeeding interventions were not included as obesity prevention interventions, given that best-practice formula feeding is also likely to encourage healthy growth. The publication date for studies was limited to the previous 12 years (2011-23), as earlier reviews found few evaluations of interventions in the UK. DATA EXTRACTION AND SYNTHESIS: The reviewers worked independently using standardised approach to search, screen and code the included studies. Risk of bias was assessed using Cochrane tools (ROB 2 or ROBINS-I). RESULTS: Six trials (five studies) were identified, including two randomised controlled trials (RCT), one cluster randomised trial (CRT), two feasibility CRTs and one impact assessment. The total number of participants was 566. Three trials focused on disadvantaged families and two included high-risk children categorised as having overweight or obesity. Compared with baseline, five interventions reported reductions in zBMI, three of which were statistically significant (p<0.05). Compared with control, five interventions showed zBMI reductions, one of which was significant. Only two trials were followed up beyond 12 months. All studies were found to have a high risk of bias. Meta-analysis was not possible due to the heterogeneity of studies. CONCLUSION: UK evidence was limited but some interventions showed promising results in promoting healthy growth. As part of a programme of policies, interventions in the early years may have an important role in reducing the risk of childhood obesity. PROSPERO REGISTRATION NUMBER: CRD42021290676.

Oligodendrocyte-selective deletion of the eIF2α kinase Perk/Eif2ak3 limits functional recovery after spinal cord injury.

After spinal cord injury (SCI), re-establishing cellular homeostasis is critical to optimize functional recovery. Central to that response is PERK signaling, which ultimately initiates a pro-apoptotic response if cellular homeostasis cannot be restored. Oligodendrocyte (OL) loss and white matter damage drive functional consequences and determine recovery potential after thoracic contusive SCI. We examined acute (<48 h post-SCI) and chronic (6 weeks post-SCI) effects of conditionally deleting Perk from OLs prior to SCI. While Perk transcript is expressed in many types of cells in the adult spinal cord, its levels are disproportionately high in OL lineage cells. Deletion of OL-Perk prior to SCI resulted in: (1) enhanced acute phosphorylation of eIF2α, a major PERK substrate and the critical mediator of the integrated stress response (ISR), (2) enhanced acute expression of the downstream ISR genes Atf4, Ddit3/Chop, and Tnfrsf10b/Dr5, (3) reduced acute OL lineage-specific Olig2 mRNA, but not neuronal or astrocytic mRNAs, (4) chronically decreased OL content in the spared white matter at the injury epicenter, (5) impaired hindlimb locomotor recovery, and (6) reduced chronic epicenter white matter sparing. Cultured primary OL precursor cells with reduced PERK expression and activated ER stress response showed: (1) unaffected phosphorylation of eIF2α, (2) enhanced ISR gene induction, and (3) increased cytotoxicity. Therefore, OL-Perk deficiency exacerbates ISR signaling and potentiates white matter damage after SCI. The latter effect is likely mediated by increased loss of Perk-/- OLs.

Psychological Constructs From the Fear Avoidance Model and Beyond as Predictors for Persisting Symptoms After Concussion: An Integrative Review.

OBJECTIVES: To identify the range of evidence for relationships between psychological factors using the Fear Avoidance Model (FAM) as a guiding framework and relevant clinical outcomes in adult patients with persisting symptoms after concussion (PSaC), develop a comprehensive understanding of psychological factors that have been identified as predictors of clinical outcomes for PSaC, and contribute to the theoretical framework of the FAM for PSaC. DATA SOURCES: Six databases (CINAHL, Embase, PsycINFO, PubMed, SportDiscus, and Web of Science) were searched by a librarian for empirical and theoretical publications and experimental and quasi-experimental study designs. The literature search was not limited by publication date restrictions. Gray literature, with the exception of doctoral dissertations, was excluded. STUDY SELECTION: We included studies in the English language consisting of human participants aged ≥18 years. Articles must have included both outcomes pertaining to PSaC (≥3mo after injury) and psychological constructs. DATA EXTRACTION: One reviewer extracted data from the resulting studies using a standardized data extraction form designed for this review. Two reviewers independently assessed risk of bias using the Quality in Prognosis Studies tool. DATA SYNTHESIS: This review found numerous psychological constructs, some directly linked to the FAM, that have potential prognostic relationships with PSaC. However, research remains limited and some psychological factors central to FAM were only identified in a small number of studies (catastrophizing, cogniphobia, and avoidance), whereas other psychological factors were studied more extensively (anxiety and depression). CONCLUSIONS: There is the need for additional evidence, and this integrative review provides an adaptation of the FAM for PSaC to be used as a guiding preliminary framework for future research. Future research should aim to include psychological factors proposed in this modified FAM to fully understand PSaC.

Childhood attention-deficit hyperactivity disorder: socioeconomic inequalities in symptoms, impact, diagnosis and medication.

BACKGROUND: Children from disadvantaged backgrounds are at greater risk of attention-deficit hyperactivity disorder (ADHD)-related symptoms, being diagnosed with ADHD, and being prescribed ADHD medications. We aimed to examine how inequalities manifest across the 'patient journey', from perceptions of impacts of ADHD symptoms on daily life, to the propensity to seek and receive a diagnosis and treatment. METHODS: We investigated four 'stages': (1) symptoms, (2) caregiver perception of impact, (3) diagnosis and (4) medication, in two data sets: UK Millennium Cohort Study (MCS, analytic n ~ 9,000), with relevant (parent-reported) information on all four stages (until 14 years); and a population-wide 'administrative cohort', which includes symptoms (child health checks) and prescriptions (dispensing records), born in Scotland, 2010-2012 (analytic n ~ 100,000), until ~6 years. We described inequalities according to maternal occupational status, with percentages and relative indices of inequality (RII). RESULTS: The prevalence of ADHD symptoms and medication receipt was considerably higher in the least compared to the most advantaged children in the administrative cohort (RIIs of 5.9 [5.5-6.4] and 8.1 [4.2-15.6]) and the MCS (3.08 [2.68-3.55], 3.75 [2.21-6.36]). MCS analyses highlighted complexities between these two stages, however, those from least advantaged backgrounds, with ADHD symptoms, were the least likely to perceive impacts on daily life (15.7% vs. average 19.5%) and to progress from diagnosis to medication (44.1% vs. average 72.5%). CONCLUSIONS: Despite large inequalities in ADHD symptoms and medication, parents from the least advantaged backgrounds were less likely to report impacts of ADHD symptoms on daily life, and their children were less likely to have received medication postdiagnosis, highlighting how patient journeys differed according to socioeconomic circumstances.

Oritavancin Versus Daptomycin for Osteomyelitis Treatment After Surgical Debridement.

INTRODUCTION: Weekly intravenous (IV) oritavancin and daily daptomycin were compared in an outpatient setting following extensive surgical debridement for treating patients with osteomyelitis. METHODS: This was a retrospective, observational study of patients diagnosed with acute osteomyelitis. Exclusion criteria were the use of Gram-negative antibiotic therapy, use of antibiotics for more than 48 h prior to oritavancin or daptomycin or prior use of > 2 doses of oritavancin or more than 4 weeks of daptomycin. Clinical success was resolution or improvement of symptoms and no further treatment. Data were analyzed with Chi-square test or Fisher's exact test. RESULTS: Consecutive outpatients (n = 150) with acute osteomyelitis who were treated with oritavancin or daptomycin (1:1) following extensive surgical debridement were identified. Staphylococcus aureus was the most common pathogen (n = 117). No patient in either group received prior antibiotic therapy (previous 30 days) or was hospitalized within 90 days prior to surgical debridement. Twenty-one (28%) patients prescribed oritavancin had chronic kidney disease, seven of whom were receiving hemodialysis or peritoneal dialysis. Compared to oritavancin, patients prescribed daptomycin had higher rates of all-cause readmission [odds ratio (OR) 2.89; p < 0.001], more infection-related readmission (OR 3.19; p < 0.001), and greater likelihood of receiving antibiotics post-discontinuation of initial therapy (OR 2.13; p < 0.001). Repeat surgical debridement was required for 68.0% with daptomycin vs. 23.1% with oritavancin (p < 0.001). CONCLUSIONS: Oritavancin demonstrated a significantly higher rate of clinical success compared to daptomycin, with lower all-cause and infection-related readmissions, reduced need for repeat surgical debridement, and fewer additional antibiotic requirements.

Admissions to paediatric medical wards with a primary mental health diagnosis: a systematic review of the literature.

OBJECTIVE: To systematically review the literature describing children and young people (CYP) admissions to paediatric general wards because of primary mental health (MH) reasons, particularly in MH crisis. DESIGN: PubMed, Embase, PsycINFO, Web of Science and Google Scholar were searched, with no restriction on country or language. We addressed five search questions to inform: trends and/or the number of admissions, the risk factors for adverse care, the experiences of CYP, families/carers and healthcare professionals (HCPs) and the evidence of interventions aimed at improving the care during admissions.Two reviewers independently assessed the relevance of abstracts identified, extracted data and undertook quality assessment. This review was registered with PROSPERO (CRD42022350655). RESULTS: Thirty-two studies met the inclusion criteria. Eighteen addressed trends and/or numbers/proportions of admissions, 12 provided data about the views/experiences of HCPs, two provided data about CYP's experiences and four explored improving care. We were unable to identify studies examining risk factors for harm during admissions, but studies did report the length of stay in general paediatric/adult settings while waiting for specialised care, which could be considered a risk factor while caring for this group. CONCLUSIONS: MH admissions to children's wards are a long-standing issue and are increasing. CYP will continue to need to be admitted in crisis, with paediatric wards a common location while waiting for assessment. For services to be delivered effectively and for CYP and their families/carers to feel supported and HCPs to feel confident, we need to facilitate more integrated physical and MH pathways of care. PROSPERO REGISTRATION NUMBER: CRD42022350655.

Impact of the COVID-19 pandemic on the clinical management trends for acute appendicitis among the under-25s: a retrospective study.

OBJECTIVE: To describe the COVID-19 pandemic's impact on acute appendicitis management on children and young people (CYP). DESIGN: Retrospective cohort study. SETTING: All English National Health Service hospitals. PATIENTS: Acute appendicitis admissions (all, simple, complex) by CYP (under-5s, 5-9s, 10-24s). EXPOSURE: Study pandemic period: February 2020-March 2021. Comparator pre-pandemic period: February 2015-January 2020. MAIN OUTCOME MEASURES: Monthly appendicectomy and laparoscopic appendicectomy rate trends and absolute differences between pandemic month and the pre-pandemic average. Proportions of appendicitis admissions comprising complex appendicitis by hospital with or without specialist paediatric centres were compared. RESULTS: 101 462 acute appendicitis admissions were analysed. Appendicectomy rates fell most in April 2020 for the 5-9s (-18.4% (95% CI -26.8% to -10.0%)) and 10-24s (-28.4% (-38.9% to -18.0%)), driven by reductions in appendicectomies for simple appendicitis. This was equivalent to -54 procedures (-68.4 to -39.6) and -512 (-555.9 to -467.3) for the 5-9s and 10-24s, respectively. Laparoscopic appendicectomies fell in April 2020 for the 5-9s (-15.5% (-23.2% to -7.8%)) and 10-24s (-44.8% (-57.9% to -31.6%) across all types, which was equivalent to -43 (-56.1 to 30.3) and -643 (-692.5 to -593.1) procedures for the 5-9s and 10-24s, respectively. A larger proportion of complex appendicitis admissions were treated within trusts with specialist paediatric centres during the pandemic. CONCLUSIONS: For CYP across English hospitals, a sharp recovery followed a steep reduction in appendicectomy rates in April 2020, due to concerns with COVID-19 transmission. This builds on smaller-sized studies reporting the immediate short-term impacts.

Effect of vitamin E-enhanced highly cross-linked polyethylene on wear rate and particle debris in anatomic total shoulder arthroplasty: a biomechanical comparison to ultrahigh-molecular-weight polyethylene.

BACKGROUND: Particle-induced osteolysis resulting from polyethylene wear remains a source of implant failure in anatomic total shoulder designs. Modern polyethylene components are irradiated in an oxygen-free environment to induce cross-linking, but reducing the resulting free radicals with melting or heat annealing can compromise the component's mechanical properties. Vitamin E has been introduced as an adjuvant to thermal treatments. Anatomic shoulder arthroplasty models with a ceramic head component have demonstrated that vitamin E-enhanced polyethylene show improved wear compared with highly cross-linked polyethylene (HXLPE). This study aimed to assess the biomechanical wear properties and particle size characteristics of a novel vitamin E-enhanced highly cross-linked polyethylene (VEXPE) glenoid compared to a conventional ultrahigh-molecular-weight polyethylene (UHMWPE) glenoid against a cobalt chromium molybdenum (CoCrMo) head component. METHODS: Biomechanical wear testing was performed to compare the VEXPE glenoid to UHMWPE glenoid with regard to pristine polyethylene wear and abrasive endurance against a polished CoCrMo alloy humeral head in an anatomic shoulder wear-simulation model. Cumulative mass loss (milligrams) was recorded, and wear rate calculated (milligrams per megacycle [Mc]). Under pristine wear conditions, particle analysis was performed, and functional biologic activity (FBA) was calculated to estimate particle debris osteolytic potential. In addition, 95% confidence intervals for all testing conditions were calculated. RESULTS: The average pristine wear rate was statistically significantly lower for the VEXPE glenoid compared with the HXLPE glenoid (0.81 ± 0.64 mg/Mc vs. 7.00 ± 0.45 mg/Mc) (P < .05). Under abrasive wear conditions, the VEXPE glenoid had a statistically significant lower average wear rate compared with the UHMWPE glenoid comparator device (18.93 ± 5.80 mg/Mc vs. 40.47 ± 2.63 mg/Mc) (P < .05). The VEXPE glenoid demonstrated a statistically significant improvement in FBA compared with the HXLPE glenoid (0.21 ± 0.21 vs. 1.54 ± 0.49 (P < .05). CONCLUSIONS: A new anatomic glenoid component with VEXPE demonstrated significantly improved pristine and abrasive wear properties with lower osteolytic particle debris potential compared with a conventional UHMWPE glenoid component. Vitamin E-enhanced polyethylene shows early promise in shoulder arthroplasty components. Long-term clinical and radiographic investigation needs to be performed to verify if these biomechanical wear properties translate to diminished long-term wear, osteolysis, and loosening.

Effect of Bamlanivimab as Monotherapy or in Combination with Etesevimab or Sotrovimab on Persistently High Viral Load in Patients with Mild-to-Moderate COVID-19: A Randomized, Phase 2 BLAZE-4 Trial.

INTRODUCTION: Treatment with monoclonal antibodies provides rapid, passive immunity and may stop COVID-19 disease progression. The study evaluated the effect of bamlanivimab (BAM) or BAM + etesevimab (ETE)/sotrovimab compared to placebo on SARS-CoV-2 viral load in patients with COVID-19. METHODS: The phase 2, randomized, single-dose study included patients aged between ≥ 18 and < 65 years, not hospitalized at the time of randomization, and had ≥ 1 mild or moderate COVID-19 symptoms. Study included arms 1-6 (placebo, BAM 175 mg + ETE 350 mg, BAM 700 mg + ETE 1400 mg, BAM 2800 mg + ETE 2800 mg, BAM 700 mg alone, and BAM 350 mg + ETE 700 mg, respectively), BAM 700 mg + ETE 700 mg unintentional dosing; and arms 7 and 8 (BAM 700 mg + sotrovimab 500 mg and placebo, respectively). The primary endpoint was proportion of patients with SARS-CoV-2 log viral load > 5.27 on day 7 (persistently high viral load [PHVL]) who received BAM or BAM + (ETE or sotrovimab). RESULTS: A total of 725 patients, mean age 39.6 years (range 18-75 years), 50.2% male were randomized and infused with study drug in arms 1-6; and a total 202 patients, mean age 38 years (range 18-63 years), 53.5% female were randomized and infused with study drug in arms 7 and 8. A significantly lower proportion of patients in arms 2-6 and arm 7 experienced PHVL on day 7 compared to placebo. On day 7, patients in arms 2, 3, and 6 consistently experienced significantly greater reduction in viral load than placebo. Significant improvement was observed in time to viral load clearance and time to symptom improvement by day 29 in some arms compared to placebo. No new safety concerns were observed with drug combinations. CONCLUSION: The study demonstrated that a significantly lower proportion of patients with mild-to-moderate COVID-19 treated with BAM or BAM + (ETE or sotrovimab) experienced a PHVL at day 7. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04634409.