Ethnicity and deprivation negatively impact the access to disease-modifying therapy for relapsing-remitting multiple sclerosis: a retrospective, single-centre study.

BACKGROUND: A growing body of evidence suggests inequitable access to disease-modifying therapies (DMTs) for multiple sclerosis (MS) in publicly funded healthcare systems. This retrospective study examined the impact of ethnicity and deprivation on the access to DMTs. METHODS: All adults diagnosed with relapsing-remitting MS between 2010 and 2020 were included. The impact of ethnicity and deprivation on being offered and starting any DMTs and high-efficacy DMTs were measured using binary, multinomial logistic and Cox regression models. These analyses were adjusted for sex, age at diagnosis and year of diagnosis. RESULTS: 164/1648 people with MS (PwMS) were from non-white ethnicities. 461/1648 who were living in the most deprived areas, were less likely to be offered DMTs, with an OR of 0.66 (95% CI 0.47 to 0.93), less likely to start high-efficacy DMTs with an OR of 0.67 (95% CI 0.48 to 0.93) and more likely to experience a delay in starting high-efficacy DMTs with an HR of 0.76 (95% CI 0.63 to 0.92), when also adjusted for ethnicity. Although the offer of DMTs did not depend on ethnicity, PwMS from non-white ethnicities were more likely to decline DMTs, less likely to start any DMTs and high-efficacy DMTs with ORs of 0.60 (95% CI 0.39 to 0.93) and 0.61 (95% CI 0.38 to 0.98), respectively, and more likely to experience a delay in starting DMTs with an HR of 0.79 (95% CI 0.66 to 0.95), when also adjusted for deprivation. CONCLUSIONS: In a publicly funded healthcare system, the access to DMTs varied depending on ethnicities and levels of deprivation.

Therapeutic plasma exchange in neurological disorders: Experience from a tertiary neuroscience centre.

Therapeutic plasma exchange (TPE) involves the extracorporeal separation of plasma from the cellular components of blood with replacement fluid, such as human albumin or fresh frozen plasma. A number of studies across the world revealed that more than one third of TPE procedures were performed for neurological disorders. Myasthenia gravis (MG), Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) were the most frequently cited indications for TPE, followed by multiple sclerosis (MS). However, treatments of these conditions have evolved over the years and it is likely that this has impacted on clinical practice. Here we present our experience of using TPE to treat neurological disorders. We reviewed the medical records of all 63 patients who received 349 procedures over 70 therapeutic cycles between 2012 and 2015 in a tertiary neurology centre. In total only 2 patients with GBS and MG were treated with TPE. The commonest indication was voltage gated potassium channel (VGKC) complex antibody associated disorders followed by CIDP and MS. There were 11 patients with limbic encephalitis. Nine of them had antibodies against VGKC complex and two had N-methyl-D-aspartate (NMDA) receptor antibodies. Sixty four percent of patients with limbic encephalitis and overall 78% of patients responded to TPE. The complication rate associated with this procedure was 8.6 per 100 therapeutic cycle. There was no treatment related mortality. We observed a change in indications of TPE compared to historical studies. It was less frequently used to treated GBS and MG. It was found to be safe and effective.

Acute respiratory distress syndrome following alemtuzumab therapy for relapsing multiple sclerosis.

We present the case of a 54 year old woman with known relapsing-remitting multiple sclerosis who presented with acute respiratory deterioration five weeks after a first course of alemtuzumab. Imaging showed bilateral ground glass changes and extensive investigations confirmed chest infection with dual pathogens - Pneumocystis jirovecii and Cytomegalovirus. She responded to standard anti-PJP and CMV therapy and was discharged on oral prophylaxis. Opportunistic infections in the weeks immediately following alemtuzumab therapy remain an uncommon complication but one that requires clinical vigilance, careful monitoring and appropriate prophylactic therapy.

Long-range DNA interactions at the IL-1/IL-36/IL-37 gene cluster (2q13) are induced by activation of monocytes.

The interleukin-1 gene cluster occupies a 360kb region of chromosome 2q13 and contains nine homologous genes. These include agonists and antagonists of the parallel IL-1 and IL-36 systems, and IL1F7, the gene encoding IL-37. As the genes of the cluster are structurally and functionally related and have similar mRNA kinetics, we have sought evidence for gene induction-specific looping of chromatin in the IL-1 cluster by chromatin conformation capture (3C). We show here that IL1A, IL1B and IL1F7 regulatory regions come in close proximity in LPS stimulated cells but not in resting human monocytes. This suggests that IL1A, IL1B and IL1F7 are likely transcribed by the same transcription factory. One cardinal function of transcriptional Locus Control Region (LCR) is bringing map-distant activated genes into close physical proximity within the transcription factory. Our data show distant intergenic DNA segments are also in close proximity to the regulatory regions of the three genes. This may indicate that they are co-regulated and raise the possibility of a LCR within the cluster.