Retrospective analysis of acute ischemic stroke shows timing of antidepressant use associated with short-term recovery and functional independence at 90-days.

BACKGROUND: Little is known about how the timing of antidepressant use influences stroke outcomes. Previous research shows conflicting results on the impact of a new antidepressant prescription on stroke recovery. OBJECTIVE: The objective of this exploratory, retrospective analysis is to examine stroke outcomes by timing of antidepressant use among patients who received stroke treatment. METHODS: 12,590 eligible patients were treated for a primary or secondary diagnosis of ischemic stroke. The outcome variables were a change in ambulation or modified Rankin scale (mRs) from pre-stroke to discharge; and a change in mRS from pre-stroke to 90-days post-discharge. The independent variable of interest was timing of antidepressant treatment. Logistic regression with generalized estimating equations was used, controlling for covariates. RESULTS: Our model predicted that a new antidepressant prescription at discharge was associated with a ∼7% decrease in the likelihood of returning to baseline functional independence at 90-days compared to patients currently using an antidepressant (AOR:0.510, CI:0.277-0.938, p = 0.03). CONCLUSION: These results suggest that use of antidepressants was associated with stroke recovery, but the effects are moderated by sex. Further study is needed to determine if this relationship is causal and the mechanisms between timing of antidepressant treatment and outcomes.

A Retrospective Analysis of Ischemic Stroke Patients Supports That Very Early Mobilization Within 24 Hours After Intravenous Alteplase Is Safe and Possibly Beneficial.

ABSTRACT: BACKGROUND: Stroke care guidelines recommend early mobilization of acute ischemic stroke patients, but there are sparse data regarding early mobilization of stroke patients receiving thrombolytic therapy. We developed the Providence Early Mobility for Stroke (PEMS) protocol to mobilize patients to their highest individual tolerance within 24 hours of stroke admission in 2010, and it has been in continuous use at our primary and comprehensive stroke centers for over a decade. In this study, we evaluated the PEMS protocol in all patients treated with intravenous alteplase without endovascular treatment. METHODS : This retrospective study includes 318 acute ischemic stroke patients treated with alteplase who were admitted to 2 urban stroke centers between January 2013 and December of 2017 and were mobilized with the PEMS protocol within 24 hours of receiving alteplase. Safety of PEMS was assessed by change in National Institutes of Health Stroke Scale at 24 hours by time first mobilized. Using multivariate and logistic regression models, we analyzed time first mobilized and 90-day modified Rankin scale (mRS). RESULTS : Median time first mobilized was 9 hours from administration of alteplase. For every hour delay in mobilization, the odds of being slightly or moderately disabled (mRS, 2-3) at 90 days increased by 7% (adjusted odds ratio, 1.07; P = .004), and the odds of being severely disabled or dead (mRS, 4-6) at 90 days increased by 7% (adjusted odds ratio, 1.07; P = .02). In addition, for every hour delay in mobilization, 24-hour National Institutes of Health Stroke Scale increased by 1.8%. DISCUSSION: Our results support that the PEMS protocol is safe, and possibly beneficial, for acute ischemic stroke patients treated with intravenous alteplase. Our protocol differs from other very early mobility protocols because it does not prescribe a "dose" of activity. Instead, each patient was mobilized to his/her individual highest degree as soon as it was safe to do so.

Advancing Care and Outcomes for African American Patients With Multiple Sclerosis.

Multiple sclerosis (MS) has historically been underdiagnosed and undertreated among African Americans. Recent evidence suggests that African Americans with MS have a different clinical presentation, increased disease incidence and burden, and worse long-term outcomes vs their White counterparts. Due to limited data available for African Americans in MS clinical trials, it is difficult to make informed, generalizable conclusions about the natural history, prognosis, and therapeutic response in this population. In this narrative review, we highlight the nature and magnitude of the health disparities experienced by African Americans with MS and underscore the pressing need to increase knowledge about and understanding of MS disease manifestations in this group. In addition, we describe the mission and objectives of the recently established National African Americans with Multiple Sclerosis Registry, which is intended to be a platform to advance the care of African Americans with MS and address health disparities they may experience.

The results of a 24-month controlled, prospective study of relapsing multiple sclerosis patients at risk for progressive multifocal encephalopathy, who switched from prolonged use of natalizumab to teriflunomide.

BACKGROUND: Natalizumab (NTZ) is a highly effective disease modifying treatment for relapsing multiple sclerosis (RMS), but it increases risk of progressive multifocal leukoencephalopathy (PML) in patients with serum anti- John Cunningham virus (JCV) antibodies. OBJECTIVE: To assess the safety and efficacy of rapid transition, from NTZ to teriflunomide (TFM) in RMS patients. METHODS: Clinically stable NTZ-treated, anti-JCV antibody positive RMS patients were switched to TFM 28 ± 7 days after their last dose of NTZ. The primary endpoint was proportion of relapse free patients at 24 months. RESULTS: Median [IQR] age of the 55 enrolled patients was 47 [40.7, 56.3] years, 76% were female. The median [IQR] number of prior NTZ treatments was 34 [18, 64]. annualized relapse rate (ARR) was 0.07 and 77% of the patients were relapse free at 24 months. Mean time to first GAD + lesion was 19.6 months, and to new/enlarging T2 lesion was 19.2 months. Mean time to 3 month sustained disability worsening (SDW) was 22 months and proportion free of 3-month SDW was 0.87. There were no cases of PML. CONCLUSIONS: The washout-free transition of NTZ to TFM was an efficacious and safe strategy for patients at risk of developing PML.ClinicalTrials.gov Identifier: NCT01970410.

Healthcare utilization and cost outcomes for a multicenter first seizure and new onset epilepsy clinic.

RATIONALE: A First Seizure/New Onset Epilepsy (FS/NOE) protocol was implemented to ensure proper evaluation by an epileptologist and improve overall care for patients. We compared healthcare utilization and cost incurred by patients pre and post protocol implementation. METHODS: Clinical data were retrospectively collected from the EMR and cost data from the financial database. Patients were identified by FS event and grouped into either the pre-implementation (pre-FSC) or post-implementation cohort (post-FSC). Pre-FSC patients were seen between January 2014-December 2015 and post-FSC between March 2016-January 2018. Utilization outcomes include time from FS to neurology appointment, MRI, and electroencephalogram (EEG). Cost outcomes included the annualized median difference in pre versus post costs for ER, inpatient, outpatient or ambulatory, and total hospital services. Cost and utilization outcomes were collected within 90 days or 6 months post first-seizure event. Pre and post cohorts were compared using Kaplan-Meier analysis and Cox proportional hazard models for time-to-event outcomes, multivariable median regression models for cost differences and negative binomial regression models for utilization analyses. Models were adjusted for age, sex, health insurance, and comorbidities. RESULTS: One-hundred and fifty six patients were included with 84 (53.8%) pre- and 72 (46.2%) post-FSC patients. Kaplan-Meier and Cox regression results indicated post-FSC patients had significantly faster time-to-first neurology appointment (5.0 vs. 20.9 days, p < .001; Adjusted Hazard Ratio (HR) = 5.98, p < .001), time-to-MRI (9.0 vs. 27.0 days; p = 0.005; HR = 1.88, p = .021) and EEG (3.6 vs. 48.6 days, p < .001; HR = 9.01, p < .001). A total of 138 patients had at least one cost in the financial database. For 6-month follow-up period, post-FSC patients had higher adjusted all-cause total median costs (+$830, p = 0.009) and outpatient costs (+$1203, p < .001) but lower ED costs (-245, p = 0.073), not significant. Results were similar for seizure-related costs. Similarly, Post-FSC patients had a significantly higher likelihood of all-cause (Adjusted Rate Ratio (ARR) = 1.41, p = .029) and outpatient utilization (ARR = 1.72, p = .008) but lower ED utilization (ARR = 0.54, p < .001). CONCLUSIONS: Implementation of the FSC decreased time to evaluation by a neurologist and time to diagnostic workup. Ultimately, total healthcare costs and ambulatory costs increased but ED costs and utilization were reduced. It is our hypothesis that faster access to initial care and diagnosis would result in better control of seizures and reduce long-term costs and utilization. Further research over a longer duration of time across a broader population is needed to evaluate the full implications of an epilepsy specialist-populated FSC.

Quality of life among injectable and oral disease-modifying therapy users in the Pacific Northwest Multiple Sclerosis Registry.

BACKGROUND: Nine oral disease-modifying therapies (DMTs) have been approved for the treatment of multiple sclerosis (MS) in the United States. Few studies have examined self-reported quality of life (QoL) and functional status outcomes among patients who switch to oral medications from injectable MS therapies. This study compares self-reported QoL and disability status between participants switching from injectable to oral DMTs, to those who stay on injectable DMTs continuously for the same time period. METHODS: Longitudinal data were assessed from relapsing MS participants in the Pacific Northwest MS Registry completing a minimum of two surveys between 2012 and 2018 with a maximum of 36 months between surveys. Stayers were defined as those who remained on injectable DMTs continuously from Time 1 to Time 2; switchers were those who switched from injectable to either fingolimod, teriflunomide or dimethyl fumarate during the same time interval. Outcomes of interest were physical and psychological QoL, measured by the Multiple Sclerosis Impact Scale (MSIS-29), and disability, measured by the Patient Determined Disease Steps (PDDS). To analyze the effect of switching to oral DMT on outcomes at Time 2, a one-to-two propensity score matching (PSM) was used to match switchers to stayers. Outcomes at Time 2 were analyzed using paired t-test for QoL scores, and Stuart Maxwell test for PDDS as a categorical variable. RESULTS: Among 2385 participants who returned consecutive yearly surveys, 413 met the inclusion criteria for stayers and 66 for switchers. After one-to-two PSM, 124 stayers were matched to 62 switchers. Paired t-test showed no differences between switchers and stayers for physical (mean difference: - 0.41; [95% confidence interval CI: - 3.3-2.4]; p = 0.78) or psychological (mean difference: - 0.23; [95% CI, - 1.6- 1.1]; p = 0.74) QoL. Additionally, no differences were seen between switchers and stayers in self-reported disability status. CONCLUSIONS: MS registry participants who switched to an oral DMT from injectable showed no significant differences in QoL or self-reported disability status compared to those remaining on injectable DMT continuously in the same time period.

Three-year clinical outcomes of relapsing multiple sclerosis patients treated with dimethyl fumarate in a United States community health center.

BACKGROUND: Following approval of dimethyl fumarate (DMF), we established a registry of relapsing multiple sclerosis (RMS) patients taking DMF at our community MS center. OBJECTIVE: To track DMF patients' tolerability, disease progression, and lymphopenia. METHODS: Patients prescribed DMF for RMS from March 2013 to March 2016 were prospectively enrolled ( N = 412). Baseline data, clinical relapses, magnetic resonance imaging (MRI) activity, discontinuation, and lymphocyte counts were captured through chart review. RESULTS: The mean age of patients starting DMF was 49.4 ± 12.0 years and 70% transitioned from a previous disease-modifying therapy (DMT). Of the patients, 38% discontinued DMF, 76% of whom discontinued due to side effects. Clinical relapse and MRI activity were low. Comparing patients who transitioned from interferon-ß (IFN), glatiramer acetate (GA), or natalizumab (NTZ), patients previously on NTZ had higher rates of relapse than those previously on GA (annualized relapse rate p = 0.039, percent relapse p = 0.021). Grade III lymphopenia developed in 11% of patients. Lymphopenia was associated with older age ( p < 0.001) and longer disease duration ( p < 0.001). CONCLUSION: Given the high rates of lymphopenia and discontinuation, it has become our clinical practice to more closely scrutinize older patients and those with a longer disease duration who are potential candidates for initiating DMF therapy.

MRI utility in the detection of disease activity in clinically stable patients with multiple sclerosis: a retrospective analysis of a community based cohort.

BACKGROUND: Since the application of MRI scanning to the diagnosis and treatment of multiple sclerosis, it has been recognized that only a small fraction of lesions seen on MRI scans produce recognizable symptoms or neurological findings. Because new lesions may occur without clinical detection, the recommendation has been made that MRI scanning be performed on a routine scheduled basis, usually yearly, even in patients who are clinically stable. METHODS: A retrospective chart review study was conducted on MS patients who had MRI scans of the central nervous system between 2009 and 2012 at Providence Multiple Sclerosis Center. Inclusion criteria were patients with relapsing MS who had been treated with interferon beta or glatiramer acetate for 6 months or longer. Information on type, indication, and result of MRI and whether a change in disease modifying therapy occurred as a result of the scan was collected. RESULTS: Of the 436 clinically stable patients who had routine MRI, 16.7 % of subjects had scans revealing new, enlarged or active lesions, yet in only 4.4 % patients was there a change in therapy based upon MRI results. Subjects who had MRI changes were found to be younger (50.15 vs 53.43, p = 0.02) but there was no significant difference in other demographic or clinical characteristics when compared with the subjects who did not have MRI changes. Thirty-six percent of patients with MRI changes did not change DMT due to patient request. CONCLUSIONS: This study provides data on the likelihood of detecting MRI-documented disease activity, in patients demonstrating longer term sustained clinical stability while receiving DMTs. These results may materially assist in the decision whether or not to perform yearly MRI scanning of such patients. The potential clinical impact of the results of routine MRI scanning must be weighed against the consideration of considerable expense of frequent MRI scanning, and the yet unknown adverse impact of retained gadolinium in patients repeatedly receiving this contrast agent. The long-term clinical impact of not changing DMTs in patients in whom MRI changes were observed will be addressed in future studies of this cohort.

Patients with Low National Institutes of Health Stroke Scale Scores Have Longer Door-to-Needle Times: Analysis of a Telestroke Network.

BACKGROUND: The benefits of intravenous tissue-type plasminogen activator (IV-tPA) in acute ischemic stroke (AIS) are time dependent. Because emergency rooms quickly initiate a stroke alert with more severe symptoms, we hypothesized that patients with lower National Institutes of Health Stroke Scale (NIHSS) scores, indicating a less severe stroke, would have longer door-to-needle (DTN) times compared to patients with higher NIHSS scores. METHODS: Data obtained from the 19-hospital Providence Stroke Registry were used to identify AIS patients who received IV-tPA within 4.5 hours of last-known-well. NIHSS scores were obtained prior to tPA administration at the time of emergency department presentation and categorized as low-NIHSS (score = 0-5) or high-NIHSS (score = 6-42) strokes. Median DTN times were collected for both groups as the primary outcome variable. Linear mixed-effects regression models were used to assess the effect of NIHSS scores on DTN and its 2 components: door-to-CT (DCT) and CT-to-needle (CTN) times. RESULTS: We identified 692 AIS patients who received IV-tPA within 4.5 hours of last-known-well, with 198 patients presenting with low-NIHSS strokes and 494 patients with high-NIHSS strokes. In multivariable analysis, median DTN time was estimated to be 18% higher for low-NIHSS strokes than high-NIHSS strokes after adjusting for covariates (P < .001). Median DCT times were also higher for low-NIHSS (19 minutes) compared to high-NIHSS (11 minutes) strokes after adjusting for covariates (P < .001), whereas CTN times were unchanged (P = .055). CONCLUSION: In AIS patients receiving IV-tPA in a telestroke network, lower NIHSS scores were associated with longer DTN and DCT times.

The cost-effectiveness of telestroke in the Pacific Northwest region of the USA.

INTRODUCTION: Using real-world data from the Providence Oregon Telestroke Network, we examined the cost-effectiveness of telestroke from both the spoke and hub perspectives by level of financial responsibility for these costs and by patient stroke severity. METHODS: We constructed a decision analytic model using patient-level clinical and financial data from before and after telestroke implementation. Effectiveness was measured as quality-adjusted life years (QALYs) and was combined with cost per patient outcomes to calculate incremental cost effectiveness ratios (ICERs). Outcomes were generated (a) overall; (b) by stroke severity, via the National Institute of Health Stroke Scale (NIHSS) at time of arrival, defined as low (<5), medium (5-14) and high (>15); and (c) by percentage of implementation costs paid by spokes (0%, 50%, 100%). RESULTS: Data for 864 patients, 98 pre- and 766 post-implementation, were used to parameterize our model. From the spoke perspective, telestroke had ICERs of US$1322/QALY, US$25,991/QALY and US$50,687/QALY when responsible for 0%, 50%, and 100% of these costs, respectively. Overall, the ICER ranged from US$22,363/QALY to US$71,703/QALY from the hub perspective. CONCLUSIONS: Our results support previous models showing good value, overall. However, costs and ICERs varied by stroke severity, with telestroke being most cost-effective for severe strokes. Telestroke was least cost effective for the spokes if spokes paid for more than half of implementation costs.

Results of sustained long-term use of interferon beta-1a in a community-based cohort of patients with relapsing multiple sclerosis.

BACKGROUND: Few studies have evaluated long-term efficacy of interferon beta-1a in large community-based cohorts. OBJECTIVE: Evaluate time to relapse, relapse rate, and disability progression in patients treated with intramuscular interferon beta-1a. METHODS: A retrospective review of medical records from 2000-2010 was performed. Adult patients with relapsing-remitting MS or clinically isolated syndrome treated with interferon beta-1a were included. Primary outcomes were time to relapse, annualized relapse rate, and changes in Expanded Disability Status Scale score. Other outcomes included factors associated with time to first relapse, risk of having a relapse while receiving interferon beta-1a, and discontinuation of therapy. RESULTS: In total, 364 of 696 patients screened were enrolled, with a mean age of 51 ± 12.1 years, disease duration of 9.39 ± 7.02 years, and duration of therapy of 4.03 ± 2.56 years. Mean time to first on-therapy relapse was 5.58 ± 0.26 years, annualized relapse rate was 0.30 ± 0.55 years, and mean increase in sustained Expanded Disability Status Scale score was 0.018. Relapse risk was associated with higher baseline Expanded Disability Status Scale score, age at disease onset, and number of relapses in the 12 months prior to therapy initiation. CONCLUSIONS: This study demonstrates favorable clinical outcomes observed in a large community-based cohort, and serves to emphasize the continued therapeutic importance of interferon beta-1a, despite the development of newer agents with greater convenience of use, but also more potential risk of serious morbidity.

Increasing prevalence of gestational diabetes and pregnancy-related hypertension in Los Angeles County, California, 1991-2003.

INTRODUCTION: Gestational diabetes and pregnancy-related hypertension can lead to adverse health effects in mothers and infants. We assessed recent trends in the rates of these conditions in Los Angeles County, California. METHODS: Hospital discharge data were used to identify all women aged 15-54 years who resided in the county, had a singleton delivery from 1991 through 2003, and had gestational diabetes or pregnancy-related hypertension listed as a discharge diagnosis at the time of delivery. The prevalence of each condition was calculated by calendar year, race/ethnicity, and age group. Temporal trends in the rates were assessed by using negative binomial regression models, controlling for race/ethnicity and age. Separate models were run for each racial/ethnic and age group. RESULTS: The age-adjusted prevalence of gestational diabetes increased more than threefold (from 14.5 cases per 1000 women in 1991 to 47.9 cases per 1000 in 2003). The age-adjusted prevalence of pregnancy-related hypertension also increased (from 40.5 cases per 1000 in 1991 to 54.4 cases per 1000 in 2003). In the multivariable regression analysis, the annual rate increase for gestational diabetes was 8.3% overall and was highest among Hispanics (9.9%). The annual rate increase for pregnancy-related hypertension was 2.8% overall and was highest among blacks (4.8%). CONCLUSION: The rates of gestational diabetes and pregnancy-related hypertension are increasing in Los Angeles County. Further research is needed to determine the causes of the observed increases and the growing racial/ethnic disparities in those rates.