How do children's hospitals address health inequalities: a grey literature scoping review.

OBJECTIVES: Health inequalities are systematic differences in health between people, which are avoidable and unfair. Globally, more political strategies are required to address health inequalities, which have increased since the global SARS-CoV-2/COVID-19 pandemic, with a disproportionate impact on children. This scoping review aimed to identify and collate information on how hospitals around the world that deliver care to children have addressed health inequalities. DESIGN: Scoping review focused solely on grey literature. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Following Joanna Briggs Institute guidelines, a four-step approach to identifying literature was adopted. DATA SOURCES: Overton, OpenGrey, OpenMD, Trip Database, DuckDuckGo, Google, targeted websites and children's hospital websites were searched on March 2023 for items published since 2010. DATA EXTRACTION AND SYNTHESIS: Retrieved items were screened against clear inclusion and exclusion criteria before data were extracted by two independent reviewers using a data extraction tool. Studies were tabulated by a hospital. A meta-analysis was not conducted due to the varied nature of studies and approaches. RESULTS: Our study identified 26 approaches to reduction of health inequalities, from 17 children's hospitals. Approaches were categorised based on their size and scope. Seven approaches were defined as macro, including hospital-wide inequality strategies. Ten approaches were classed as meso, including the establishment of new departments and research centres. Micro approaches (n=9) included one-off projects or interventions offered to specific groups/services. Almost half of the reported approaches did not discuss the evaluation of impact. CONCLUSIONS: Children's hospitals provide a suitable location to conduct public health interventions. This scoping review provides examples of approaches on three scales delivered at hospitals across high-income countries. Hospitals with the most comprehensive and extensive range of approaches employ dedicated staff within the hospital and community. This review indicates the value of recruitment of both public health-trained staff and culturally similar staff to deliver community-based interventions.

How do hospitals address health inequalities experienced by children and young people: a grey literature scoping review protocol.

INTRODUCTION: Health inequalities are unfair, systematic differences in health between people. In the UK, the Health and Social Care Act 2012 recognised health inequalities as a responsibility of the National Health Service (NHS). Health inequalities were foregrounded in the publication of 2019 NHS Long Term Plan and during the SARS-CoV-2/COVID-19 pandemic. Hospitals are well placed to address health inequalities through their role as anchor institutions. While many hospitals have begun to address inequalities, children are often overlooked or assumed to have the same needs as adult populations. This grey literature scoping review aims to identify, collate and present approaches taken by hospitals to address health inequalities in children and young people. METHODS AND ANALYSIS: This scoping review will follow Joanna Briggs Institute guidance. A four-step approach to identifying grey literature will be used. Literature will be examined to identify approaches that aim to address health inequalities. Literature must describe the health inequality they aim to address and be initiated by the hospital. It will exclude literature not available in English and published before 2010. Two reviewers will independently review the results of the searches using the inclusion and exclusion criteria. Data will be extracted using a data extraction tool. Study findings will be presented in tabular form detailing the interventions identified. DISSEMINATION: The review will synthesise information on worldwide hospital approaches to addressing child health inequalities. The findings will be used to inform guidelines for children's hospitals in the UK and will be disseminated through national and international professional bodies, conferences and research papers.

What Have We Learnt About the Treatment of Juvenile-Onset Systemic Lupus Erythematous Since Development of the SHARE Recommendations 2012?

Introduction: Juvenile-onset systemic lupus erythematous (JSLE) is a rare multisystem autoimmune disorder. In 2012, the Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) initiative developed recommendations for the diagnosis/management of JSLE, lupus nephritis (LN) and childhood-onset anti-phospholipid syndrome (APS). These recommendations were based upon available evidence informing international expert consensus meetings. Objective: To review new evidence published since 2012 relating to the management of JSLE, LN and APS in children, since the original literature searches informing the SHARE recommendations were performed. Method: MEDLINE, EMBASE and CINAHL were systematically searched for relevant literature (2012-2021) using the following criteria: (1) English language studies; (2) original research studies regarding management of JSLE, LN, APS in children; (3) adult studies with 3 or more patients <18-years old, or where the lower limit of age range ≤16-years and the mean/median age is ≤30-years; (4) randomized controlled trials (RCTs), cohort studies, case control studies, observational studies, case-series with >3 patients. Three reviewers independently screened all titles/abstracts against predefined inclusion/exclusion criteria. All relevant manuscripts were reviewed independently by at least two reviewers. Data extraction, assessment of the level of evidence/methodological quality of the manuscripts was undertaken in-line with the original SHARE processes. Specific PUBMED literature searches were also performed to identify new evidence relating to each existing SHARE treatment recommendation. Results: Six publications met the inclusion/exclusion criteria for JSLE: three RCTs, one feasibility trial, one case series. For LN, 16 publications met the inclusion/exclusion criteria: eight randomized trials, three open label prospective clinical trials, five observational/cohort studies. For APS, no publications met the inclusion criteria. The study with the highest evidence was an RCT comparing belimumab vs. placebo, including 93 JSLE patients. Whilst the primary-endpoint was not met, a significantly higher proportion of belimumab-treated patients met the PRINTO/ACR cSLE response to therapy criteria. New evidence specifically addressing each SHARE recommendation remains limited. Conclusion: Since the original SHARE literature searches, undertaken >10-years ago, the main advance in JSLE treatment evidence relates to belimumab. Additional studies are urgently needed to test new/existing agents, and assess their long-term safety profile in JSLE, to facilitate evidence-based practice.

Assessment of the socio-economic and health impact of COVID-19 in the NGO intervention areas of Gujarat.

Background and Aim: By this time, the world has already witnessed catastrophic effects of the pandemic on economic and healthcare services infrastructure, from India the scientific publications documenting this effect are quite sparse. The current report aims to compile the socio-economic, demographic and healthcare services transactions among the population in the non-governmental organization (NGO) supported areas of Gujarat state. Methods: The data were collected by human research of the NGO from Sanand, Mundra and Ahmedabad sites at three different time intervals - pre-lockdown, during lockdown and post-lockdown. Results: The findings of the study reported a clear increase in availing of healthcare services in all three study sites covered under the programmes of the NGO. It was clearly evident that the impact of lockdown on the livelihood of the population in all three sites was devastating with a significant proportion of individuals losing their jobs. However, the majority of the people were able to rejoin the jobs (though with lower average income) in all three sites. During the lockdown, people heavily relied on stored food sources such as grains and pulses and consumption of fresh vegetables and fruits reduced significantly. Lockdown has severely hampered essential maternal and child care services which were remarkably improved in the months of post-lockdown. A considerable number of the family had to mortgage their assets during the lockdown. The mortgage proportion varied widely (3-58%) among all the study sites. Conclusion: It was observed that in the unprecedented time, the national lockdown was a challenging time, where there was a drastic shift in the livelihood profile of the population due to significant loss of jobs. Lockdown has also severely affected the essential healthcare services coverage; however, with efforts from the government and the NGO, it was restored to a near pre-lockdown situation in all three sites.

A Population-Based Intervention to Improve Care Cascades of Patients With Hepatitis C Virus Infection.

Hepatitis C virus (HCV) infection is common in the United States and leads to significant morbidity, mortality, and economic costs. Simplified screening recommendations and highly effective direct-acting antivirals for HCV present an opportunity to eliminate HCV. The objective of this study was to increase testing, linkage to care, treatment, and cure of HCV. This was an observational, prospective, population-based intervention program carried out between September 2014 and September 2018 and performed in three community health centers, three large multiclinic health care systems, and an HCV patient education and advocacy group in King County, WA. There were 232,214 patients included based on criteria of documented HCV-related diagnosis code, positive HCV laboratory test or prescription of HCV medication, and seen at least once at a participating clinical site in the prior year. Electronic health record (EHR) prompts and reports were created. Case management linked patients to care. Primary care providers received training through classroom didactics, an online curriculum, specialty clinic shadowing, and a telemedicine program. The proportion of baby boomer patients with documentation of HCV testing increased from 18% to 54% during the project period. Of 77,577 baby boomer patients screened at 87 partner clinics, 2,401 (3%) were newly identified HCV antibody positive. The number of patients staged for treatment increased by 391%, and those treated increased by 1,263%. Among the 79% of patients tested after treatment, 95% achieved sustained virologic response. Conclusion: A combination of EHR-based health care system interventions, active linkage to care, and clinician training contributed to a tripling in the number of patients screened and a more than 10-fold increase of those treated. The interventions are scalable and foundational to the goal of HCV elimination.

A degradatory fate for CCR4 suggests a primary role in Th2 inflammation.

CCR4 is the sole receptor for the chemokines CCL22 and CCL17. Clinical studies of asthmatic airways have shown levels of both ligands and CCR4+ Th2 cells to be elevated, suggestive of a role in disease. Consequently, CCR4 has aroused much interest as a potential therapeutic target and an understanding of how its cell surface expression is regulated is highly desirable. To this end, receptor expression, receptor endocytosis, and chemotaxis were assessed using transfectants expressing CCR4, CCR4+ human T cell lines, and human Th2 cells polarized in vitro. CCL17 and CCL22 drove rapid endocytosis of CCR4 in a dose-dependent manner. Replenishment at the cell surface was slow and sensitive to cycloheximide, suggestive of de novo synthesis of CCR4. Constitutive CCR4 endocytosis was also observed, with the internalized CCR4 found to be significantly degraded over a 6-h incubation. Truncation of the CCR4 C-terminus by 40 amino acids had no effect on cell surface expression, but resulted in significant impairment of ligand-induced endocytosis. Consequently, migration to both CCL17 and CCL22 was significantly enhanced. In contrast, truncation of CCR4 did not impair constitutive endocytosis or degradation, suggesting the use of alternative receptor motifs in these processes. We conclude that CCR4 cell surface levels are tightly regulated, with a degradative fate for endocytosed receptor. We postulate that this strict control is desirable, given that Th2 cells recruited by CCR4 can induce the further expression of CCR4 ligands in a positive feedback loop, thereby enhancing allergic inflammation.

Improving Adolescent Health: Learnings from an Interventional Study in Gujarat, India.

BACKGROUND: There are multiple risk factors during adolescence, which become precursors of various diseases and injuries inflicting high morbidity, mortality, and disability. There are several gaps in adolescent health research in India; one among them is that programs targeting adolescent health are constrained by the absence of rigorous interventional research informing interventions for improving adolescent health. This study aims to document the effectiveness of intervention on adolescent health and knowledge change on the risk factors among adolescents in one of the selected districts in Gujarat, India. METHODS: This was an interventional study with quasi-experimental design executed in one of the blocks of Gujarat. Baseline was conducted in 2013-2014 followed by intervention and the end line during 2016-2017. A structured validated questionnaire after pilot testing was executed to collect information on sociodemographic profile, nutrition status, menstrual hygiene practices, reproductive and sexual health, substance abuse, program awareness and utilization, and empowerment through life skills of adolescents in baseline and end line survey. Data analysis was carried out using IBM SPSS Statistics for Windows, Version 20.0. (Armonk, NY: IBM Corp). RESULTS: This study documented increased awareness regarding anemia, knowledge about STD and HIV/AIDS, reduced addiction to tobacco, improved practices during menstrual hygiene and engagement with adolescent services/schemes in the intervention site. CONCLUSION: This study concludes that evidence-based interventions lead to increase in knowledge and practices; however, some improvements have also been documented in the nonintervention site. Therefore, changes due to interventions could not be attributed completely for improving adolescent health. Further long term interventional studies are required to develop a robust evidence on improving health of adolescents in India.

Misdiagnosis of narcolepsy.

BACKGROUND: Narcolepsy is a chronic primary sleep disorder, characterized by excessive daytime sleepiness and sleep dysfunction with or without cataplexy. Narcolepsy is uncommon, with a low prevalence rate which makes it difficult to diagnose definitively without a complex series of tests and a detailed history. The aim of this study was to review patients referred to a tertiary sleep centre who had been labelled with a diagnosis of narcolepsy prior to referral in order to assess if the diagnosis was accurate, and if not, to determine the cause of diagnostic misattribution. METHODS: All patients seen at a sleep centre from 2007-2013 (n = 551) who underwent detailed objective testing including an MSLT PSG, as well as wearing an actigraphy watch and completing a sleep diary for 2 weeks, were assessed for a pre-referral and final diagnosis of narcolepsy. RESULTS: Of the 41 directly referred patients with a diagnostic label of narcolepsy, 19 (46 %) were subsequently confirmed to have narcolepsy on objective testing and assessment by a sleep physician using ICSD-2 criteria. CONCLUSIONS: The diagnosis of narcolepsy was incorrectly attributed to almost 50 % of patients labelled with a diagnosis of narcolepsy who were referred for further opinion by a variety of specialists and generalists. Accurate diagnosis of narcolepsy is critical for many reasons, such as the impact it has on quality of life, driving, employment, insurance and pregnancy in women as well as medication management.

Distinct conformations of the chemokine receptor CCR4 with implications for its targeting in allergy.

CC chemokine receptor 4 (CCR4) is expressed by Th2 and regulatory T cells and directs their migration along gradients of the chemokines CCL17 and CCL22. Both chemokines and receptor are upregulated in allergic disease, making CCR4 a therapeutic target for the treatment of allergy. We set out to assess the mechanisms underlying a previous report that CCL22 is a dominant ligand of CCR4, which may have implications for its therapeutic targeting. Human T cells expressing endogenous CCR4 and transfectants engineered to express CCR4 were assessed for receptor function, using assays of calcium release, chemotaxis, receptor endocytosis, and ligand binding. Despite the two ligands having equal potency in calcium flux and chemotaxis assays, CCL22 showed dominance in both receptor endocytosis assays and heterologous competitive binding assays. Using two different CCR4-specific Abs, we showed that CCR4 exists in at least two distinct conformations, which are differentially activated by ligand. A major population is activated by both CCL17 and CCL22, whereas a minor population is activated only by CCL22. Mutation of a single C-terminal residue K310 within a putative CCR4 antagonist binding site ablated activation of CCR4 by CCL17, but not by CCL22, despite having no effect on the binding of either ligand. We conclude that CCL17 and CCL22 are conformationally selective ligands of CCR4 and interact with the receptor by substantially different mechanisms. This finding suggests that the selective blockade of CCR4 in allergy may be feasible when one CCR4 ligand dominates, allowing the inhibition of Th2 signaling via one ligand while sparing regulatory T cell recruitment via another.