The impact of cigarette smoking on cognitive processing speed and brain atrophy in multiple sclerosis.

BACKGROUND: Smoking is associated with an increased risk of multiple sclerosis (MS) and disability worsening. The relationship between smoking, cognitive processing speed, and brain atrophy remains uncertain. OBJECTIVE: To quantify the impact of smoking on processing speed and brain volume in MS and to explore the longitudinal relationship between smoking and changes in processing speed. METHODS: A retrospective study of MS patients who completed the processing speed test (PST) between September 2015 and March 2020. Demographics, disease characteristics, smoking history, and quantitative magnetic resonance imaging (MRI) were collected. Cross-sectional associations between smoking, PST performance, whole-brain fraction (WBF), gray matter fraction (GMF), and thalamic fraction (TF) were assessed using multivariable linear regression. The longitudinal relationship between smoking and PST performance was assessed by linear mixed modeling. RESULTS: The analysis included 5536 subjects of whom 1314 had quantitative MRI within 90 days of PST assessment. Current smokers had lower PST scores than never smokers at baseline, and this difference persisted over time. Smoking was associated with reduced GMF but not with WBF or TF. CONCLUSION: Smoking has an adverse relationship with cognition and GMF. Although causality is not demonstrated, these observations support the importance of smoking cessation counseling in MS management.

Association of socioeconomic disadvantage and neighborhood disparities with clinical outcomes in multiple sclerosis patients.

BACKGROUND: Socioeconomic disadvantage may be an important contributor to clinical outcomes in MS but is not well understood. Our objective was to examine the associations between Area Deprivation Index (ADI), a validated measure of neighborhood-level disadvantage, with clinical outcomes. METHODS: We assessed the longitudinal association between MS Performance Test (MSPT) and quality of life in Neurological Disorders (Neuro-QoL) measures with ADI quartiles (Q1: lowest deprivation - Q4 highest deprivation) in relapsing remitting MS (RRMS) and progressive MS cohorts. RESULTS: Our study included 2,921 patients (65.8% RRMS and 34.1% progressive MS) with 13,715 visits. Patients living in the most disadvantaged areas had almost universal worsening on baseline MSPT and Neuro-QoL scores (p < 0.05) when compared to patients living in areas of lowest deprivation. Manual Dexterity Test (MDT) illustrated particular disparity as RRMS patients living in the greatest area of deprivation had MDT score which averaged 2.9 seconds longer than someone living in areas of least deprivation. Longitudinal analysis illustrated less favorable MSPT and Neuro-QoL outcomes across visits between Q1 versus Q4 ADI quartiles within in the RRMS cohort but not within the progressive MS cohort. After adjustment, linearly increasing area deprivation scores reflected less favorable Processing Speed Test (PST) and six Neuro-QoL outcomes among the RRMS cohort. Within the progressive cohort, higher deprivation was associated less favorable MDT, PST and 11 of 12 Neuro-QoL outcome measures. CONCLUSIONS: This study provides evidence for socioeconomic disadvantage as a risk factor for disability accrual in MS and may be targeted to improve care while informing resource allocation.

Clinical features and outcomes of COVID-19 despite SARS-CoV-2 vaccination in people with multiple sclerosis.

BACKGROUND: Several studies have demonstrated reduced serological response to vaccines in patients treated with anti-CD20 agents. However, limited data exist surrounding the clinical effect of disease modifying therapy (DMT) use on vaccine efficacy. OBJECTIVES: To investigate breakthrough coronavirus disease 2019 (COVID-19) in vaccinated people with multiple sclerosis (PwMS) on DMT. METHODS: PwMS on DMT diagnosed with COVID-19 after full vaccination were identified from an existing Cleveland Clinic COVID-19 registry, supplemented by provider-identified cases. Demographics, disease history, DMTs, comorbidities, exposures, vaccination status, and COVID-19 outcomes were confirmed by review of the electronic medical record. RESULTS: Thirteen (3.8%) of 344 fully vaccinated people with multiple sclerosis on disease modifying therapy were diagnosed with COVID-19 after vaccination. Ten patients (76.9%) were on an anti-CD20 therapy, the remaining 3 (23.1%) on fingolimod. Only 2 patients (15.4%), both on anti-CD20 therapy, required hospitalization and steroid treatment. Neither required Intensive Care Unit admission. CONCLUSION: Patients treated with anti-CD20 agents and sphingosine 1-phosphate receptor modulators may still be at risk for COVID-19 despite vaccination. While still at risk for hospitalization, intubation and death from COVID-19 appear rare. Larger studies analyzing how this may differ in the setting of emerging variants are needed.

Comorbidity effect on processing speed test and MRI measures in multiple sclerosis patients.

BACKGROUND: Comorbid conditions are known to affect the clinical course of multiple sclerosis (MS). Our objective was to determine the impact of comorbidities on the processing speed test (PST). METHODS: We conducted a retrospective, longitudinal analysis of all patients who completed PST testing from June 2015 - August 2019 at our center. Our electronic medical record was queried to determine the presence of the following comorbidities: diabetes mellitus (DM), hypertension (HTN), hyperlipidemia (HLD), coronary artery disease, and depression. To help address baseline PST performance and practice effect, patients were also divided into four quartiles by baseline PST scores. Brain MRIs obtained within a 90-day window from the initial clinical assessment were quantitatively analyzed via fully-automated methods to calculate whole brain fraction (WBF), T2 lesion volume (T2LV), gray matter fraction (GMF), and thalamic volume (TV). Univariable and multivariable linear regression models were used to determine the relationship between the comorbidities, PST performance and MRI metrics over time. RESULTS: A total of 4,344 patients (mean age 49.5 ± 12.4 years, 72.3% female, and 63.7% relapsing remitting MS) were included in the analysis with 13,375 individual patient encounters. Over half the cohort (52.4%) suffered from at least one comorbidity with the most common being depression (37.4%), HLD (20.9%), HTN (19.6%), and DM (6.4%). Patients with one or more comorbidity had lower baseline PST scores. Longitudinally, patients with two comorbidities lost 1.46 points on the PST per year relative to those with no comorbidities (95% CI -2.46 - -0.46, p = 0.004). Individuals with depression had lower PST scores than those without, and this difference persisted over time (ß = -2.40, 95% CI -3.08 - -1.73, p < 0.001). At baseline, HLD patients had higher PST scores than non-HLD patients (ß = 1.10, 95% CI 0.15 - 2.05, p = 0.022), but this difference did not remain over time. Individuals in the highest PST performance quartile were negatively impacted when diagnosed with depression, HTN, and DM relative to those without the comorbidities. There were no other correlations with PST scores and the remaining comorbidities. Depression was associated with lower baseline WBF (ß = -0.0043, 95% CI -0.0084 - -0.0003, p = 0.033) and GMF (ß = -0.0046, 95% CI -0.0078 - -0.0015, p = 0.004) along with larger T2LV (ß = 0.1605, 95% CI 0.0082 - 0.3128, p = 0.039). HLD patients had more favorable baseline MRI measures, including higher WBF (ß = 0.0076, 95% CI 0.0017 - 0.0135, p = 0.012) and TV (ß = 0.0002, 95% CI 0.0000 - 0.0005, p = 0.041), with a lower T2LV (ß = -0.2963, 95% CI -0.5219 - -0.0706, p = 0.010). CONCLUSIONS: Comorbidities are common within a MS cohort and adversely impact processing speed. Depression adversely impacted PST scores with worse MRI outcomes. HLD was associated with lower longitudinal PST measures but favorable quantitative MRI metrics. MS patients with faster baseline processing speeds were most sensitive to comorbid conditions. Our findings suggest a complex interplay between cognition and comorbid conditions in MS patients.

Multiple sclerosis management during the COVID-19 pandemic.

BACKGROUND: People with multiple sclerosis (MS) may be at higher risk for complications from the 2019 coronavirus (COVID-19) pandemic due to use of immunomodulatory disease modifying therapies (DMTs) and greater need for medical services. OBJECTIVES: To evaluate risk factors for COVID-19 susceptibility and describe the pandemic's impact on healthcare delivery. METHODS: Surveys sent to MS patients at Cleveland Clinic, Johns Hopkins, and Vall d'Hebron-Centre d'Esclerosi Múltiple de Catalunya in April and May 2020 collected information about comorbidities, DMTs, exposures, COVID-19 testing/outcomes, health behaviors, and disruptions to MS care. RESULTS: There were 3028/10,816 responders. Suspected or confirmed COVID-19 cases were more likely to have a known COVID-19 contact (odds ratio (OR): 4.38; 95% confidence interval (CI): 1.04, 18.54). In multivariable-adjusted models, people who were younger, had to work on site, had a lower education level, and resided in socioeconomically disadvantaged areas were less likely to follow social distancing guidelines. 4.4% reported changes to therapy plans, primarily delays in infusions, and 15.5% a disruption to rehabilitative services. CONCLUSION: Younger people with lower socioeconomic status required to work on site may be at higher exposure risk and are potential targets for educational intervention and work restrictions to limit exposure. Providers should be mindful of potential infusion delays and MS care disruption.

Electronic medical record-assisted design of a cluster-randomized trial to improve diabetes care and outcomes.

BACKGROUND: Electronic medical records (EMRs) have the potential to facilitate the design of large cluster-randomized trials (CRTs). OBJECTIVE: To describe the design of a CRT of clinical decision support to improve diabetes care and outcomes. METHODS: In the Diabetes Improvement Group-Intervention Trial (DIG-IT), we identified and balanced preassignment characteristics of 12,675 diabetic patients cared for by 147 physicians in 24 practices of 2 systems using the same vendor's EMR. EMR-facilitated disease management was system A's experimental intervention; system B interventions involved patient empowerment, with or without disease management. For our sample, we: (1) identified characteristics associated with response to interventions or outcomes; (2) summarized feasible partitions of 10 system A practices (2 groups) and 14 system B practices (3 groups) using intra-cluster correlation coefficients (ICCs) and standardized differences; (3) selected (blinded) partitions to effectively balance the characteristics; and (4) randomly assigned groups of practices to interventions. RESULTS: In System A, 4,306 patients, were assigned to 2 groups of practices; 8,369 patients in system B were assigned to 3 groups of practices. Nearly all baseline outcome variables and covariates were well-balanced, including several not included in the initial design. DIG-IT's balance was superior to alternative partitions based on volume, geography or demographics alone. CONCLUSIONS: EMRs facilitated rigorous CRT design by identifying large numbers of patients with diabetes and enabling fair comparisons through preassignment balancing of practice sites. Our methods can be replicated in other settings and for other conditions, enhancing the power of other translational investigations.

Trends in postdischarge mortality and readmissions: has length of stay declined too far?

BACKGROUND: Length of hospital stay continues to decline, but the effect on postdischarge outcomes is unclear. METHODS: We determined trends in risk-adjusted mortality rates and readmission rates for 83,445 Medicare patients discharged alive after hospitalization for myocardial infarction, heart failure, gastrointestinal hemorrhage, chronic obstructive pulmonary disease, pneumonia, or stroke. Patients were stratified into deciles of observed/expected length of stay to determine whether patients whose length of stay was much shorter than expected had higher risk-adjusted mortality and readmission rates. Analyses were stratified by whether a do-not-resuscitate (DNR) order was written within 2 days of admission (early) or later. RESULTS: From 1991 through 1997, risk-adjusted postdischarge mortality generally remained stable for patients without a DNR order. Postdischarge mortality increased by 21% to 72% for patients with early DNR orders and increased for 2 of 6 diagnoses for patients with late DNR orders. Markedly shorter than expected length of stay was associated with higher than expected risk-adjusted mortality for patients with early DNR orders but not for others (no DNR and late DNR). Risk-adjusted readmission rates remained stable from 1991 through 1997, except for a 15% (95% confidence interval, 3%-30%) increase for patients with congestive heart failure. Short observed/expected length of stay was not associated with higher readmission rates. CONCLUSIONS: The dramatic decline in length of stay from 1991 through 1997 was not associated with worse postdischarge outcomes for patients without DNR orders. However, postdischarge mortality increased among patients with early DNR orders, and some of this trend may be due to patients being discharged more rapidly than previously.

Changes in the use of do-not-resuscitate orders after implementation of the Patient Self-Determination Act.

OBJECTIVE: To determine changes in the use of do-not-resuscitate (DNR) orders and mortality rates following a DNR order after the Patient Self-determination Act (PSDA) was implemented in December 1991. DESIGN: Time-series. SETTING: Twenty-nine hospitals in Northeast Ohio. PATIENTS/PARTICIPANTS: Medicare patients (N = 91,539) hospitalized with myocardial infarction, heart failure, gastrointestinal hemorrhage, chronic obstructive pulmonary disease, pneumonia, or stroke. MEASUREMENTS AND MAIN RESULTS: The use of "early" (first 2 hospital days) and "late" DNR orders was determined from chart abstractions. Deaths within 30 days after a DNR order were identified from Medicare Provider Analysis and Review files. Risk-adjusted rates of early DNR orders increased by 34% to 66% between 1991 and 1992 for 4 of the 6 conditions and then remained flat or declined slightly between 1992 and 1997. Use of late DNR orders declined by 29% to 53% for 4 of the 6 conditions between 1991 and 1997. Risk-adjusted mortality during the 30 days after a DNR order was written did not change between 1991 and 1997 for 5 conditions, but risk-adjusted mortality increased by 21% and 25% for stroke patients with early DNR and late DNR orders, respectively. CONCLUSIONS: Overall use of DNR orders changed relatively little after passage of the PSDA, because the increase in the use of early DNR orders between 1991 and 1992 was counteracted by decreasing use of late DNR orders. Risk-adjusted mortality rates after a DNR order generally remained stable, suggesting that there were no dramatic changes in quality of care or aggressiveness of care for patients with DNR orders. However, the increasing mortality for stroke patients warrants further examination.

The effect of publicly reporting hospital performance on market share and risk-adjusted mortality at high-mortality hospitals.

BACKGROUND: It is unclear whether publicly reporting hospitals' risk-adjusted mortality affects market share and mortality at outlier hospitals. OBJECTIVES: To examine hospitals' market share and risk-adjusted mortality from 1991 to 1997 at hospitals participating in Cleveland Health Quality Choice (CHQC). RESEARCH DESIGN: Time series. SUBJECTS: Changes in market share were examined for all patients hospitalized with acute myocardial infarction, heart failure, gastrointestinal hemorrhage, obstructive pulmonary disease, pneumonia, or stroke at all 30 nonfederal hospitals in Northeast Ohio. Patients insured by Medicare were used to examine changes in mortality. MEASURES: Trends in market share (proportion of patients with the target conditions discharged from a given hospital) and risk-adjusted 30-day mortality. RESULTS: CHQC identified several hospitals with consistently higher than expected mortality. The five hospitals with the highest mortality tended to lose market share (mean change -0.6%, 95% CI -1.9-0.6), but this was not significant. The only outlier hospital with a large decline in market share had declining volume for 2 years before being declared an outlier. Risk-adjusted mortality declined only slightly at hospitals classified by us as "below average" (-0.8%; 95% CI, 2.9-1.8%) or "worst" (-0.4%; 95% CI -2.3-1.7). However, risk-adjusted mortality at one hospital changed from consistently above expected to consistently below expected shortly after first being declared an outlier. CONCLUSION: Despite CHQC's strengths, identifying hospitals with higher than expected mortality did not adversely affect their market share or, with one exception, lead to improved outcomes. This failure may have resulted from consumer disinterest or difficulty interpreting CHQC reports, unwillingness of businesses to create incentives targeted to hospitals' performance, and hospitals' inability to develop effective quality improvement programs.

Mortality trends during a program that publicly reported hospital performance.

BACKGROUND: It is unclear whether publicly reporting hospitals' risk-adjusted mortality leads to improvements in outcomes. OBJECTIVES: To examine mortality trends during a period (1991-1997) when the Cleveland Health Quality Choice program was operational. RESEARCH DESIGN: Time series. SUBJECTS: Medicare patients hospitalized with acute myocardial infarction (AMI; n = 10,439), congestive heart failure (CHF; n = 23,505), gastrointestinal hemorrhage (GIH; n = 11,088), chronic obstructive pulmonary disease (COPD; n = 8495), pneumonia (n = 23,719), or stroke (n = 14,293). MEASURES: Risk-adjusted in-hospital mortality, early postdischarge mortality (between discharge and 30 days after admission), and 30-day mortality. RESULTS: Risk-adjusted in-hospital mortality declined significantly for all conditions except stroke and GIH, with absolute declines ranging from -2.1% for COPD to -4.8% for pneumonia. However, the mortality rate in the early postdischarge period rose significantly for all conditions except COPD, with increases ranging from 1.4% for GIH to 3.8% for stroke. As a consequence, the 30-day mortality declined significantly only for CHF (absolute decline 1.4%, 95% CI, -2.5 to -0.1%) and COPD (absolute decline 1.6%, 95% CI, -2.8-0.0%). For stroke, risk-adjusted 30-day mortality actually increased by 4.3% (95% CI, 1.8-7.1%). CONCLUSION: During Cleveland's experiment with hospital report cards, deaths shifted from in hospital to the period immediately after discharge with little or no net reduction in 30-day mortality for most conditions. Hospital profiling remains an unproven strategy for improving outcomes of care for medical conditions. Using in-hospital mortality rates to monitor trends in outcomes for hospitalized patients may lead to spurious conclusions.