"There are still broken or fragmented systems": Qualitative assessment of needs to strengthen adolescent mental health services in American Samoa.

Mental health challenges appear common among adolescents in American Samoa. There is a community-identified need to better understand the health burden and identify opportunities to strengthen the mental health system to better meet adolescent mental health needs. The goal of this qualitative study was to gather community stakeholders' perceptions of common mental health problems among adolescents in American Samoa, identify existing services for adolescent mental health, and highlight strength-based opportunities to enhance care. Using the Fa'afaletui research framework, semi-structured in-depth interviews (n = 28) were conducted between October 2020 and February 2021 using Zoom. Key informants were adults living in American Samoa, sampled for diversity in profession, age, gender, education, and region of residence. Transcripts were coded in duplicate and analysed using deductive thematic analysis. Participants reported that suicide, depression, anxiety, and post-traumatic stress disorder are the conditions of highest burden. Participants identified an impressive amount of infrastructure and community mobilization, but also limitations in these services in addressing adolescents' health needs. Four themes arose related to the need to: (1) strengthen existing infrastructure; (2) reduce barriers to treatment access; (3) improve sustainability; and (4) encourage collaboration among leaders. Policymakers should prioritize the allocation of resources to strengthen infrastructure, public education, and stakeholder collaboration to improve adolescent mental health in American Samoa.

Validating the portal population of the United Kingdom Multiple Sclerosis Register.

The UK Multiple Sclerosis Register (UKMSR) is a large cohort study designed to capture 'real world' information about living with multiple sclerosis (MS) in the UK from diverse sources. The primary source of data is directly from people with Multiple Sclerosis (pwMS) captured by longitudinal questionnaires via an internet portal. This population's diagnosis of MS is self-reported and therefore unverified. The second data source is clinical data which is captured from MS Specialist Treatment centres across the UK. This includes a clinically confirmed diagnosis of MS (by Macdonald criteria) for consented patients. A proportion of the internet population have also been consented at their hospital making comparisons possible. This dataset is called the 'linked dataset'. The purpose of this paper is to examine the characteristics of the three datasets: the self-reported portal data, clinical data and linked data, in order to assess the validity of the self-reported portal data. The internet (n = 11,021) and clinical (n = 3,003) populations were studied for key shared characteristics. We found them to be closely matched for mean age at diagnosis (clinical = 37.39, portal = 39.28) and gender ratio (female %, portal = 73.1, clinical = 75.2). The Two Sample Kolmogorov-Smirnov test was for the continuous variables to examine is they were drawn from the same distribution. The null hypothesis was rejected only for age at diagnosis (D = 0.078, p < 0.01). The populations therefore, were drawn from different distributions, as there are more patients with relapsing disease in the clinical cohort. In all other analyses performed, the populations were shown to be drawn from the same distribution. Our analysis has shown that the UKMSR portal population is highly analogous to the entirely clinical (validated) population. This supports the validity of the self-reported diagnosis and therefore that the portal population can be utilised as a viable and valid cohort of people with Multiple Sclerosis for study.

Haemoglobin scavenging after subarachnoid haemorrhage.

Rapid and effective clearance of cell-free haemoglobin after subarachnoid haemorrhage (SAH) is important to prevent vasospasm and neurotoxicity and improve long-term outcome. Haemoglobin is avidly bound by haptoglobin, and the complex is cleared by CD163 expressed on the membrane surface of macrophages. We studied the kinetics of haemoglobin and haptoglobin in cerebrospinal fluid after SAH. We show that haemoglobin levels rise gradually after SAH. Haptoglobin levels rise acutely with aneurysmal rupture as a result of injection of blood into the subarachnoid space. Although levels decline as haemoglobin scavenging occurs, complete depletion of haptoglobin does not occur and levels start rising again, indicating saturation of CD163 sites available for haptoglobin-haemoglobin clearance. In a preliminary neuropathological study we demonstrate that meningeal CD163 expression is upregulated after SAH, in keeping with a proinflammatory state. However, loss of CD163 occurs in meningeal areas with overlying blood compared with areas without overlying blood. Becauses ADAM17 is the enzyme responsible for shedding membrane-bound CD163, its inhibition may be a potential therapeutic strategy after SAH.

A web-based tool for personalized prediction of long-term disease course in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: The Evidence-Based Decision Support Tool in Multiple Sclerosis (EBDiMS) is the first web-based prognostic calculator in multiple sclerosis (MS) capable of delivering individualized estimates of disease progression. It has recently been extended to provide long-term predictions based on the data from a large natural history cohort. METHODS: We compared the predictive accuracy and consistency of EBDiMS with that of 17 neurologists highly specialized in MS. RESULTS: We show that whilst the predictive accuracy was similar, neurologists showed a significant intra-rater and inter-rater variability. CONCLUSIONS: Because EBDiMS was consistent, it is of superior utility in a specialist setting. Further field testing of EBDiMS in non-specialist settings, and investigation of its usefulness for counselling patients in treatment decisions, is warranted.

Pathophysiology of the lymphatic drainage of the central nervous system: Implications for pathogenesis and therapy of multiple sclerosis.

In most organs of the body, immunological reactions involve the drainage of antigens and antigen presenting cells (APCs) along defined lymphatic channels to regional lymph nodes. The CNS is considered to be an immunologically privileged organ with no conventional lymphatics. However, immunological reactions do occur in the CNS in response to infections and in immune-mediated disorders such as multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). Here, we review evidence that cervical lymph nodes play a role in B and T cell mediated immune reactions in the CNS. Then we define the separate pathways by which interstitial fluid (ISF) and CSF drain to cervical lymph nodes. ISF and solutes drain from the brain along the 100-150nm-wide basement membranes in the walls of capillaries and arteries. In humans, this perivascular pathway is outlined by the deposition of insoluble amyloid (Abeta) in capillary and artery walls in cerebral amyloid angiopathy in Alzheimer's disease. The failure of APCs to migrate to lymph nodes along perivascular lymphatic drainage pathways may be a major factor in immunological privilege of the brain. Lymphatic drainage of CSF is predominantly through the cribriform plate into nasal lymphatics. Lymphatic drainage of ISF and CSF and the specialised cervical lymph nodes to which they drain play significant roles in the induction of immunological tolerance and of adaptive immunological responses in the CNS. Understanding the afferent and efferent arms of the CNS lymphatic system will be valuable for the development of therapeutic strategies for diseases such as MS.

Corticosteroids for the long-term treatment in multiple sclerosis.

BACKGROUND: Short term high dose corticosteroid treatment improves symptoms and short term disability after an acute exacerbation of multiple sclerosis (MS) but it is unknown whether its long-term use can reduce the accumulation of disability. OBJECTIVES: To determine the efficacy and safety of long-term corticosteroid use in MS. SEARCH STRATEGY: We searched the following bibliographic databases: CENTRAL (Issue 1, 2007), MEDLINE (1966 to February 2007) and EMBASE (1980 to February 2007). In an effort to identify further published, unpublished and ongoing trials we searched reference lists and contacted trial authors and one pharmaceutical company. SELECTION CRITERIA: We considered controlled, randomised trials (RCTs), with or without blinding, of long term treatment (i.e. longer than 6 months) of any type of corticosteroid in MS, irrespective of disease course. DATA COLLECTION AND ANALYSIS: Reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: Three trials, all classified at high risk of bias, contributed to this review (Miller 1961; BPSM 1995; Zivadinov 2001) resulting in a total of 183 participants (91 treated). Corticosteroid therapy did not reduce the risk of being worse at the end of follow-up (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.26 to 1.02) but there was a substantial heterogeneity between studies (I(2): 78.4%). I. v. periodic high dose methylprednisolone (MP) was associated with a significant reduction in the risk of disability progression at 5 years in relapsing-remitting (RR) MS (OR 0.26, 95% CI 0.10 to 0.66), while oral continuous low dose prednisolone was not associated with any risk reduction in disability progression at 18 months (OR 1.23, 95% CI 0.43 to 3.56). Risk of experiencing at least one exacerbation at end of follow-up was not significantly reduced with corticosteroid treatment (OR 0.36; 95% CI 0.10 to 1.25). Only one study recorded adverse events: in one patient i. v. MP was discontinued after the fourth pulse when he developed acute glomerulonephritis; a second patient was removed from the study after the fifth i. v. MP pulse because of severe osteoporosis. AUTHORS' CONCLUSIONS: There is no enough evidence that long-term corticosteroid treatment delays progression of long term disability in patients with MS. Since one study at high risk of bias showed that the administration of pulsed high dose i. v. MP is associated with a significant reduction in the risk of long term disability progression in patients with RR MS, an adequately powered, high quality RCT is needed to investigate this finding.