Early depressive symptoms and disability accrual in Multiple Sclerosis: a UK MS Register study.

Understanding the associations and potential drivers of long-term disability in Multiple Sclerosis (MS) is of clinical and prognostic value. Previous data have suggested a link between depression and disability accrual in MS. We aimed to determine whether depression in early MS predicts subsequent accrual of disability. Using data from the UK MS Register, we identified individuals with and without symptoms of depression and anxiety close to disease onset. We used Cox proportional hazards regression to evaluate whether early depressive or anxiety symptoms predict subsequent physical disability worsening, measured using the Expanded Disability Status Scale (EDSS). We analysed data from 862 people with MS of whom 134 (15.5%) reached an EDSS of ≥ 6.0. Early depressive symptoms were associated with an increased risk of reaching an EDSS of 6.0 (HR 2.42, 95% CI 1.49-3.95, p < 0.001), however this effect dissipated when adjusting for baseline EDSS (HR 1.40, 95% CI 0.84-2.32, p = 0.2). These data suggest that early depressive symptoms in MS are associated with subsequent disability accrual, but are likely the result of disability rather than its cause.

Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis.

BACKGROUND: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear. OBJECTIVE: To determine whether early non-disabling relapses predict disability accumulation in RRMS. METHODS: We redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up. RESULTS: People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated (n = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00-1.68) or given platform DMTs (n = 1074 vs 7262; HR = 1.33, 95% CI = 1.15-1.54), but not if given high-efficacy DMTs (n = 572 vs 3534; HR = 0.90, 95% CI = 0.71-1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically. CONCLUSION: This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.

INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR PHARMACEUTICAL UTILIZATION AND FINANCIAL IMPACT IN A VALUE-BASED CARE PROGRAM.

PURPOSE: To investigate trends and the potential impact of the COVID-19 pandemic on the utilization of intravitreal antivascular endothelial growth factor (anti-VEGF) pharmaceuticals in an accountable care organization (ACO). METHODS: We retrospectively analyzed the Centers for Medicare and Medicaid Services beneficiary claims for all patients in the Houston Methodist Coordinated Care ACO registry during the years 2018, 2019, and 2020. RESULTS: Across the 3 years studied, a mean of 708 patients received anti-VEGF injections per year. The percentage of patients who received anti-VEGF injections decreased in each sequential year, with a steeper decline during the COVID-19 pandemic in the year 2020 (decrease by 0.4% from 2019 to 2020, P < 0.001; decrease by 0.2% from 2018 to 2019, P = 0.1453). The percentage of patients receiving bevacizumab of the total number of patients receiving any anti-VEGF treatment decreased (bevacizumab decreased by 6% from 2019 to 2020, P = 0.0174; decreased by 7% from 2018 to 2019, P = 0.0074). The COVID-19 pandemic did not seem to correlate with a change in the distribution of the specific anti-VEGF injection used. CONCLUSION: Despite the lower price which may correlate with value-based care, bevacizumab was the least used anti-VEGF treatment. COVID-19 correlated with a larger decrease in the utilization of all three anti-VEGF drugs.

A rare presentation of rapidly progressing myopathy in an adolescent.

We present a case of severe juvenile dermatomyositis with limited response to steroids in an adolescent who developed symptoms within hours after receiving Pfizer BNT162b2 coronavirus disease 2019 vaccine. The patient presented with severe weakness of proximal muscles, dyspnoea, and tachycardia. His muscle enzymes were raised, and he was diagnosed with severe juvenile dermatomyositis following magnetic resonance imaging and muscle biopsy. His management was challenging, requiring multidisciplinary input, and difficult decisions with regard to the appropriate immunomodulatory treatments. The patient had to undergo escalating immunosuppressive treatments before he began to recover clinically and biochemically. To our knowledge, this is the first case in an adolescent although a few cases of similar presentations following coronavirus disease 2019 vaccination have been reported in adults. Elucidating the potential relationship of the vaccine with this severe myopathy in an adolescent is important for global vaccination policies, but avoiding the conflation of association with causation is also crucial in the context of the pandemic.

Remyelination varies between and within lesions in multiple sclerosis following bexarotene.

OBJECTIVE: In multiple sclerosis chronic demyelination is associated with axonal loss, and ultimately contributes to irreversible progressive disability. Enhancing remyelination may slow, or even reverse, disability. We recently trialled bexarotene versus placebo in 49 people with multiple sclerosis. While the primary MRI outcome was negative, there was converging neurophysiological and MRI evidence of efficacy. Multiple factors influence lesion remyelination. In this study we undertook a systematic exploratory analysis to determine whether treatment response - measured by change in magnetisation transfer ratio - is influenced by location (tissue type and proximity to CSF) or the degree of abnormality (using baseline magnetisation transfer ratio and T1 values). METHODS: We examined treatment effects at the whole lesion level, the lesion component level (core, rim and perilesional tissues) and at the individual lesion voxel level. RESULTS: At the whole lesion level, significant treatment effects were seen in GM but not WM lesions. Voxel-level analyses detected significant treatment effects in WM lesion voxels with the lowest baseline MTR, and uncovered gradients of treatment effect in both WM and CGM lesional voxels, suggesting that treatment effects were lower near CSF spaces. Finally, larger treatment effects were seen in the outer and surrounding components of GM lesions compared to inner cores. INTERPRETATION: Remyelination varies markedly within and between lesions. The greater remyelinating effect in GM lesions is congruent with neuropathological observations. For future remyelination trials, whole GM lesion measures require less complex post-processing compared to WM lesions (which require voxel level analyses) and markedly reduce sample sizes.

A virtual COVID-19 ophthalmology rotation.

The coronavirus (COVID-19) pandemic temporarily suspended medical student involvement in clinical rotations, resulting in the need to develop virtual clinical experiences. The cancellation of clinical ophthalmology electives and away rotations reduces opportunities for exposure to the field, to network with faculty, conduct research, and prepare for residency applications. We review the literature and discuss the impact and consequences of COVID-19 on undergraduate medical education with an emphasis on ophthalmic undergraduate medical education. We also discuss innovative learning modalities used from medical schools around the world during the COVID-19 pandemic such as virtual didactics, online cases, and telehealth. Finally, we describe a novel, virtual neuro-ophthalmology elective created to educate medical students on neuro-ophthalmology foundational principles, provide research and presentation opportunities, and build relationships with faculty members. These innovative approaches represent a step forward in further improving medical education in ophthalmology during COVID-19 pandemic and beyond.