Search

Samuel N Rodgers-Melnick,1,2 Robert J Trager,1 Thomas E Love,2– 4 Jeffery A Dusek5 1Connor Whole Health, University Hospitals of Cleveland, Cleveland, OH, USA; 2Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA; 3Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA; 4Population Health and Equity Research Institute, The MetroHealth System, Cleveland, OH, USA; 5Department of Family Medicine and Community Health, Case Western Reserve University School of Medicine, Cleveland, OH, USACorrespondence: Samuel N Rodgers-Melnick, University Hospitals Connor Whole Health, 11100 Euclid Avenue, Wearn 548A, Cleveland, OH, 44106, USA, Tel +1 216 844 7727, Fax +1 216 201 6220, Email Samuel.RodgersMelnick@UHhospitals.orgObjective: To examine variables associated with engagement in (1) integrative health and medicine (IHM) and (2) nonpharmacologic modalities rather than opioids among United States adults with chronic pain.Methods: Using the 2019 National Health Interview Survey, we examined sociodemographic, pain, and mental health predictors of (1) the sum of IHM modalities (ie, chiropractic care, yoga/Tai Chi, massage, or meditation/guided imagery) used to manage pain and (2) exclusive engagement in nonpharmacologic pain management modalities (ie, IHM, a chronic pain self-management program, support groups, or physical, rehabilitative, occupational, or talk therapy) or opioids in the past 3 months.Results: Metropolitan residency, higher family income, higher education levels, increased number of pain locations, and increased frequency of pain limiting life/work activities were associated with increased odds of IHM engagement. Older age, male sex, non-Hispanic Black/African American race/ethnicity, and daily opioid use were associated with decreased odds of IHM engagement. Older age, male sex, and increased depressive symptoms were associated with decreases in the count of IHM modalities used to manage pain. Metropolitan residency, higher family income, and higher education levels were associated with increased odds of exclusive nonpharmacologic modality engagement. Older age and increasing frequency of pain limiting life/work activities were associated with decreased odds of exclusive nonpharmacologic modality engagement.Conclusions: We identified several contrasts between factors prevalent among individuals with chronic pain and factors associated with engagement in nonpharmacologic and IHM modalities. These results support efforts to address barriers to accessing these modalities among subpopulations of adults with chronic pain (eg, older adults, individuals identifying as Black/African American, rural residents, and those with lower levels of education and income).Plain Language Summary: This study examined factors influencing the use of integrative health and non-drug treatments for chronic pain in the United States. Results revealed that metropolitan residence, higher income, and education were associated with increased use of these treatments, while older age, male sex, daily opioid use, and non-Hispanic Black/African American ethnicity were associated with decreased use. The findings emphasize the importance of addressing barriers to these forms of care, especially among older adults, Black/African American individuals, and those with higher depressive symptoms and lower education and income levels, who are more likely to have chronic pain.Keywords: integrative medicine, chronic pain, nonpharmacologic, opioids

Aims: To examine the clinical effectiveness of angiotensin receptor blockers (ARBs) in older patients with heart failure and preserved ejection fraction (HF-PEF).Methods and Results: Of the 10 570 hospitalized HF-PEF patients, aged ≥ 65 years, EF ≥ 40%, in OPTIMIZE-HF (2003-2004), linked to Medicare data (up to 31 December 2008), 3806 were not receiving angiotensin-converting enzyme inhibitors or prior ARB therapy. Of these, 303 (8%) patients received new discharge prescriptions for ARBs. Propensity scores for the receipt of ARBs, estimated for each of the 3806 patients, were used to assemble a cohort of 296 pairs of patients receiving and not receiving ARBs, who were balanced on 114 baseline characteristics. Patients had a mean age of 80 years, mean EF of 55%, 69% were women, and 12% were African American. During 6 years of follow-up, the primary composite endpoint of all-cause mortality or HF hospitalization occurred in 79% (235/296) and 81% (241/296) of patients receiving and not receiving ARBs, respectively [hazard ratio (HR) associated with ARB use 0.88, 95% confidence interval (CI) 0.74-1.06; P = 0.179]. ARB use had no association with individual endpoints of all-cause mortality (HR 0.93, 95% CI 0.76-1.14; P = 0.509), HF hospitalization (HR 0.90, 95% CI, 0.72-1.14; P = 0.389), or all-cause hospitalization (HR 0.91, 95% CI 0.77-1.08; P = 0.265). These associations remained unchanged when we compared any (prevalent and new prescriptions) ARB use vs. non-use in a separately assembled propensity-matched cohort of 1137 pairs of HF-PEF patients.Conclusions: In real-world older HF-PEF patients, ARB use was not associated with improved clinical outcomes. [ABSTRACT FROM AUTHOR]

Context: High dietary phosphorus intake has deleterious consequences for renal patients and is possibly harmful for the general public as well. To prevent hyperphosphatemia, patients with end-stage renal disease limit their intake of foods that are naturally high in phosphorus. However, phosphorus-containing additives are increasingly being added to processed and fast foods. The effect of such additives on serum phosphorus levels is unclear.Objective: To determine the effect of limiting the intake of phosphorus-containing food additives on serum phosphorus levels among patients with end-stage renal disease.Design, Setting, and Participants: Cluster randomized controlled trial at 14 long-term hemodialysis facilities in northeast Ohio. Two hundred seventy-nine patients with elevated baseline serum phosphorus levels (>5.5 mg/dL) were recruited between May and October 2007. Two shifts at each of 12 large facilities and 1 shift at each of 2 small facilities were randomly assigned to an intervention or control group.Intervention: Intervention participants (n=145) received education on avoiding foods with phosphorus additives when purchasing groceries or visiting fast food restaurants. Control participants (n=134) continued to receive usual care.Main Outcome Measure: Change in serum phosphorus level after 3 months.Results: At baseline, there was no significant difference in serum phosphorus levels between the 2 groups. After 3 months, the decline in serum phosphorus levels was 0.6 mg/dL larger among intervention vs control participants (95% confidence interval, -1.0 to -0.1 mg/dL). Intervention participants also had statistically significant increases in reading ingredient lists (P<.001) and nutrition facts labels (P = .04) but no significant increase in food knowledge scores (P = .13).Conclusion: Educating end-stage renal disease patients to avoid phosphorus-containing food additives resulted in modest improvements in hyperphosphatemia.Trial Registration: clinicaltrials.gov Identifier: NCT00583570. [ABSTRACT FROM AUTHOR]

Background: Among advanced-stage cancer patients, age is an important determinant of decision making about medical care. We examined age-related differences in patient well-being, care perspectives, and preferences, and the relationship between these patient characteristics and subsequent care practices including care communication, pain management, and acute care utilization during the early treatment phase of late-stage cancer.Methods: Patient demographics, well-being, and care perspectives were assessed during patient and physician baseline interviews. Care practices were measured using outpatient and inpatient records for the 30-day period after baseline assessment. Multivariate regression models were used to examine the patterns of association of age and other patient characteristics with care practices.Results: A total of 174 middle-aged and 149 older patients with recently diagnosed late-stage cancer were included. Older patients had more comorbidities but lower levels of depression, anxiety, and symptom distress. Older patients preferred pain relief/comfort as a treatment goal, but received fewer prescriptions for opioids. Whereas provider-initiated communication with patients/families was positively associated with severity of illness, patient/family-initiated communication was associated with patient psychosocial attributes and care perspectives. Satisfaction with care was inversely associated with reports of pain. Symptom distress was positively associated with subsequent opioid prescriptions and hospitalizations.Conclusions: Our results help to explain the role of patients' psychosocial attributes, care perspectives, and preferences in subsequent care practices during the early treatment phase for late-stage cancer. Age-related differences in patient well-being and care perspectives suggest a role for age-sensitive interventions in the treatment of advanced cancer patients. [ABSTRACT FROM AUTHOR]

Objective: Hospitalization for worsening heart failure (HF) is common and associated with high mortality. However, the effect of incident HF hospitalization (compared with no HF hospitalization) on subsequent mortality has not been studied in a propensity-matched population of chronic HF patients.Methods: In the Digitalis Investigation Group trial, 5501 patients had no HF hospitalizations (4512 alive at 2 years after randomization) and 1732 patients had HF hospitalizations during the first 2 years (1091 alive at 2 years). Propensity scores for incident HF hospitalization during the first 2 years after randomization were calculated for each patient and used to match 1057 patients (97%) who had 2-year HF hospitalization with 1057 patients who had no HF hospitalization. We used matched Cox regression analysis to estimate the effect of incident HF hospitalization during the first 2 years after randomization on post-2-year mortality.Results: Compared with 153 deaths (rate, 420/10,000 person-years) in the no HF hospitalization group, 334 deaths (rate, 964/10,000 person-years) occurred in the HF hospitalization group (hazard ratio 2.49; 95% confidence interval 1.97-3.13; P < .0001). The hazard ratios (95% confidence intervals) for cardiovascular and HF mortality were 2.88 (2.23-3.74; P < .0001) and 5.22 (3.34-8.15; P < .0001), respectively.Conclusions: Hospitalization for worsening HF was associated with increased risk of subsequent mortality in ambulatory patients with chronic HF. These results highlight the importance of HF hospitalization as a marker of disease progression and poor outcomes in chronic HF, reinforcing the need for prevention of HF hospitalizations and strategies to improve postdischarge outcomes. [ABSTRACT FROM AUTHOR]

Background: Poor prognosis in heart failure (HF) patients with diabetes is often attributed to increased co-morbidity and advanced disease. Further, this effect may be worse in women.Objective: To determine whether the effect of diabetes on outcomes and the sex-related variation persisted in a propensity score-matched HF population, and whether the sex-related variation was a function of age.Methods: Of the 7788 HF patients in the Digitalis Investigation Group trial, 2218 had a history of diabetes. Propensity score for diabetes was calculated for each patient using a non-parsimonious logistic regression model incorporating all measured baseline covariates, and was used to match 2056 (93%) diabetic patients with 2056 non-diabetic patients.Results: All-cause mortality occurred in 135 (25%) and 216 (39%) women without and with diabetes (adjusted HR = 1.67; 95% CI = 1.34 to 2.08; p<0.001). Among men, 535 (36%) and 609 (41%) patients without and with diabetes died from all causes (adjusted HR = 1.21; 95% CI = 1.07 to 1.36; p = 0.002). Sex-diabetes interaction (overall adjusted p<0.001) was only significant in patients > or = 65 years (15% absolute risk increase in women; multivariable p for interaction = 0.005), but not in younger patients (2% increase in women; p for interaction = 0.173). Risk-adjusted HR (95% CI) for all-cause hospitalisation for women and men were 1.49 (1.28 to 1.72) and 1.21 (1.11 to 1.32), respectively, also with significant sex-diabetes interaction (p = 0.011).Conclusions: Diabetes-associated increases in morbidity and mortality in chronic HF were more pronounced in women, and theses sex-related differences in outcomes were primarily observed in elderly patients. [ABSTRACT FROM AUTHOR]

Background: The prospective payment system (PPS) for nursing homes was designed to curtail the rapid expansion of Medicare costs for skilled nursing care. This study examines the changes that occurred in nursing home patients and rehabilitation services following the PPS.Setting: Free-standing Medicare and/or Medicaid certified nursing homes in Ohio.Primary Outcomes: The percent of new admissions receiving therapy and the amount of rehabilitation therapy provided.Sample: A total of 7006 first admissions in 1994-6 (pre-PPS) and 61,569 first admissions in 2000-1 (post-PPS).Methods: A logistic model predicting likelihood of rehabilitation was developed and validated in pre-PPS admissions and applied to the post-PPS patients. Rehabilitation services were compared in the pre-PPS and post-PPS cohorts overall, stratified by quintile of predicted score, diagnosis group, and by nursing home profit status.Results: Post-PPS patients had less cognitive impairment, more depression, and more family support. The amount of rehabilitation services declined the most in the higher quintiles of predicted likelihood of rehabilitation and among patients with stroke. The percent of patients receiving rehabilitation services increased the most in the lowest quintile and among patients with medical conditions. These changes were greater in for-profit nursing homes.Conclusions: The implementation of the PPS in nursing homes has been associated with a decrease in the amount of rehabilitation services, targeted at those predicted to receive higher amounts and an increased frequency of providing services targeted at those predicted to be less likely to receive them. The outcomes of the changes deserve further study. [ABSTRACT FROM AUTHOR]

A high cardiothoracic ratio (CTR) is a marker of an enlarged heart and is associated with poor outcomes in patients with heart failure (HF). To what extent this association is independent of other confounders is not well known. However, to study this, propensity score matching was used to design a study in which HF patients with normal (0.50) CTRs were well balanced on all measured baseline covariates. In the Digitalis Investigation Group trial (n=7,788), 4,690 patients had high (>0.50) CTRs. Propensity scores for high CTR were calculated for each patient and were then used to match 2,586 pairs of patients with normal and high CTRs. Matched Cox regression analyses were used to estimate associations of high CTR with mortality and hospitalization during 37 months of median follow-up. All-cause mortality occurred in 28.5% (rate 919 per 10,000 patient-years of follow-up) of patients with normal CTRs and 34.3% (rate 1,185 per 10,000 patient-years) of patients with high CTRs (hazard ratio 1.35, 95% confidence interval [CI] 1.21 to 1.51, p<0.0001). All-cause hospitalization occurred in 64.8% (rate 3,513 per 10,000 patient-years) of patients with normal CTRs and 66.2% (rate 3,932 per 10,000 patient-years) of patients with high CTRs (hazard ratio 1.10, 95% CI 1.01 to 1.20, p=0.032). Respective hazard ratios for other outcomes were 1.48 (95% CI 1.30 to 1.68, p<0.0001) for cardiovascular mortality, 1.57 (95% CI 1.28 to 1.92, p<0.0001) for HF mortality, 1.18 (95% CI 1.08 to 1.30, p=0.001) for cardiovascular hospitalization, and 1.27 (95% CI 1.13 to 1.44, p<0.0001) for HF hospitalization. In conclusion, a baseline CTR>0.50 was associated with increased mortality and morbidity in ambulatory patients with chronic HF. [ABSTRACT FROM AUTHOR]

The comparative effectiveness of angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II type 1 receptor blockers (ARBs) in real-world older heart failure (HF) patients remains unclear. Of the 8,049 hospitalized HF patients aged ≥ 65 years discharged alive from 106 Alabama hospitals, 4,044 received discharge prescriptions of either ACE inhibitors (n = 3,383) or ARBs (n = 661). Propensity scores for ARB use, calculated for each of 4,044 patients, were used to match 655 (99% of 661) patients receiving ARBs with 661 patients receiving ACE inhibitors. The assembled cohort of 655 pairs of patients was well balanced on 56 baseline characteristics. During >8 years of follow-up, all-cause mortality occurred in 63% and 68% of matched patients receiving ARBs and ACE inhibitors, respectively (hazard ratio [HR] associated with ARB use 0.86, 95% confidence interval [CI] 0.75 to 0.99, p = 0.031). Among the 956 matched patients with data on the left ventricular ejection fraction (LVEF), the association between ARB (vs ACE inhibitor) use was significant in only 419 patients with LVEFs ≥ 45% (HR 0.65, 95% CI 0.51 to 0.84, p = 0.001) but not in the 537 patients with LVEFs < 45% (HR 1.00, 95% CI 0.81 to 1.23, p = 0.999; p for interaction = 0.012). HRs for HF hospitalization associated with ARB use were 0.99 (95% CI 0.86 to 1.14, p = 0.876) overall, 0.80 (95% CI 0.63 to 1.03, p = 0.080) in those with LVEFs ≥45%, and 1.14 (95% CI 0.91 to 1.43, p = 0.246) in those with LVEFs <45% (p for interaction = 0.060). In conclusion, in older HF patients with preserved LVEFs, discharge prescriptions of ARBs (vs ACE inhibitors) were associated with lower mortality and a trend toward lower HF hospitalization, findings that need replication in other HF populations. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is common and is associated with increased mortality in heart failure (HF). However, it is unknown whether the effect of CKD on mortality varies by left ventricular ejection fraction (LVEF). We evaluated the effect of CKD on mortality in patients with systolic (LVEF 45%) HF. Of the 7,788 patients in the Digitalis Investigation Group trial, 3,527 (45%) had CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2). We calculated the propensity score for CKD for each patient, using a multivariate logistic regression model (c statistic 0.76, postmatch absolute standardized differences <5% for all 32 co-variates). We matched 2,399 pairs of patients with and without CKD with similar propensity scores. There were 757 (rate 1,049/10,000 person-years) and 882 (rate 1,282/10,000 person-years) deaths, respectively, in patients without and with CKD (hazard ratio 1.22, 95% confidence interval 1.09 to 1.36, p <0.0001). CKD-associated mortality was higher in those with diastolic HF (371 extra deaths/10,000 person-years, hazard ratio 1.71, 95% confidence interval 1.21 to 2.41, p = 0.002) than in systolic HF (214 extra deaths/10,000 person-years, hazard ratio 1.19, 95% confidence interval 1.07 to 1.32, p = 0.001), which was significant (adjusted p for interaction = 0.034). A graded association was found between CKD-related deaths and LVEF. The hazard ratios for CKD-associated mortality for the LVEF subgroups of <35%, 35% to 55%, and >55% were 1.15 (95% confidence interval 1.02 to 1.29), 1.35 (95% confidence interval 1.11 to 1.64), and 2.33 (95% confidence interval 1.34 to 4.06). In conclusion, CKD-associated mortality was higher in those with diastolic than systolic HF. Patients with diastolic HF should be evaluated for CKD, and the role of inhibitors of the renin-angiotensin system in these patients needs to be investigated. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the Ohio Diabetes Quality Improvement Project (QIP) equity aim to reduce the percentage of Non-Hispanic Black (NHB) and Hispanic patients with A1C >9% by ≥20% over 2 years., Research Design and Methods: The Ohio Department of Medicaid, Ohio Colleges of Medicine Government Resource Center, Ohio Medicaid managed care plans, and seven medical schools in Ohio formed the Diabetes QIP collaborative using the collective impact model to improve diabetes outcomes and equity in 20 practices across 11 health systems. The quality improvement (QI) strategies included data audit and feedback, peer-to-peer learning, QI coaching/practice facilitation, and subject matter expert consultation through coaching calls, monthly webinars, and annual virtual learning sessions. Electronic health record data were collected for preintervention (2019-2020) and intervention (2020-2022) periods. Assessments of improvements in A1C were based on prevalence of A1C >9% from preintervention, year 1, and year 2 with stratification by race and ethnicity., Results: The Diabetes QIP included 7,689 (54% female) sociodemographically diverse patients, self-identifying as non-Hispanic White (NHW) (42%), NHB (43%), Hispanic (8%), non-Hispanic Asian (4%), or other (3%). In year 2 compared with baseline, there were decreases in the proportion of patients with A1C >9% among NHW, NHB, and Hispanic patients (NHW from 19% to 12% [37% reduction], NHB 23% to 18% [22% reduction], and Hispanic 29% to 23% [20% reduction])., Conclusions: The Ohio Diabetes QIP, focused on multisector collaborative approaches, reduced the percentage of patients with A1C >9% by ≥20% among NHW, NHB, and Hispanic populations. Given the persistence of disparities, further equity-focused refinements are warranted to address disparities in diabetes control., (© 2024 by the American Diabetes Association.)

Objective: Owing to perceived additional costs, patients may avoid integrative health and medicine (IHM) treatments, while insurers may not cover IHM. We hypothesized that adult beneficiaries of a health system's employee insurance plan with musculoskeletal (MSK) conditions receiving covered outpatient IHM would have reduced total allowed costs over the 1-year follow-up compared with matched controls, secondarily exploring medical and pharmaceutical cost subsets. Methods: We queried medical records and claims spanning 2018-2023 for beneficiaries aged 18-89 years with a new MSK episode. Patients were divided into cohorts: (1) IHM within 3 months after MSK diagnosis and (2) no IHM after initial primary care. After inflation adjustment and trimming, propensity score matching was used to balance cohorts on demographics, comorbidity, health care utilization, and prior 12-month spend. Least-squares mean total, medical, and pharmaceutical allowed costs (United States Dollar) over the 1-year follow-up were analyzed using a linear mixed model. Findings were compared with a generalized linear model without trimming. Results: There were 251 patients per matched cohort, with adequate covariate balance. There was no meaningful between-cohort difference (IHM minus No IHM) in least-squares mean total cost (+703 [95% CI: -314, 1720]). Secondary outcomes included medical cost (+878 [95% CI: 61, 1695]) and pharmaceutical cost (+6 [95% CI: -71, 83]). A generalized linear model revealed no meaningful difference in estimated mean total medical costs (-2561 [95% CI: -7346, +2224]). Conclusions: IHM use among adult health system beneficiaries with MSK conditions was not associated with meaningful differences in 1-year follow-up total health care costs compared with matched controls. Our study was underpowered for secondary outcomes, which should be interpreted with caution. Future research should include a larger sample of patients and examine longitudinal changes in patient-reported outcomes.

Introduction: Gardening has been found to increase vegetable intake and reduce BMI; this suggests that it may improve diets by lowering inflammatory content. The goal of this study goal was to evaluate the effect of gardening on Dietary Inflammatory Index scores., Methods: Longitudinal data were collected annually between 2015 and 2018 from adults in low-income, urban neighborhoods of Cleveland and Columbus, Ohio. The authors measured the association between gardening and Dietary Inflammatory Index in the full data set using multivariable mixed-effect models with a random intercept for participant (Model 1; n =409). To further explore potential causation, the author used propensity score analyses in a subset of the data by building a 1-to-1 matched model (Model 2; n =339)., Results: Of 409 adults, 30.3% were gardeners with Dietary Inflammatory Index scores ranging from -6.228 to +6.225. Participating in gardening was associated with lower Dietary Inflammatory Index scores in the mixed-effects model (-0.45; 95% CI= -0.85, -0.04; Model 1) and the 1-to-1 matched model (-0.77; 95% CI= -1.40, -0.14; Model 2)., Conclusions: The analyses indicate that gardeners had lower Dietary Inflammatory Index scores than nongardeners, implying lower diet-driven inflammation. These findings highlight the potential for a causal relationship between gardening and Dietary Inflammatory Index, which should be confirmed in future studies. If this relationship is validated, strategies to increase gardening may be worth testing as primary prevention tools for diet-driven chronic disease., (© 2024 The Authors.)

We used a collective impact model to form a statewide diabetes quality improvement collaborative to improve diabetes outcomes and advance diabetes health equity. Between 2020 and 2022, in collaboration with the Ohio Department of Medicaid, Medicaid Managed Care Plans, and Ohio's seven medical schools, we recruited 20 primary care practices across the state. The percentage of patients with hemoglobin A1c greater than 9% improved from 25% to 20% over two years. Applying our model more broadly could accelerate improvement in diabetes outcomes. ( Am J Public Health. 2023;113(12):1254-1257. https://doi.org/10.2105/AJPH.2023.307410).

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.

Importance: Tobacco 21 (T21) policies raise the minimum legal age to purchase tobacco from 18 to 21 years to curb youth access to tobacco products. While some studies have found that T21 is associated with reducing prevalence of youth tobacco use, little is known about the impact it may have on youth of different racial and ethnic identities., Objective: To evaluate the association of T21 policy with the prevalence of high school youth tobacco use across sex, race, and ethnicity., Design, Setting, and Participants: This survey study used representative survey data collected from the local biennial Youth Risk Behavior Survey from 2013 to 2017 comparing Cleveland, Ohio (which has a T21 policy), to proximal jurisdictions in the first-ring suburbs in Cuyahoga County (which do not have T21 policies). Within-Cleveland demographic information was also collected for 2013 to 2019. Overall high school youth tobacco use rates were compared between Cleveland and the first-ring suburbs and then examined within Cleveland among Hispanic, non-Hispanic Black, and non-Hispanic White high school students. Percentage data were adjusted to more closely align with local population demographics. Data were analyzed from January to June 2022., Exposures: T21 was implemented in Cleveland in 2016 and not adopted in proximal jurisdictions or at the state and federal level until at least 1 year later., Main Outcomes and Measures: The main outcomes were prevalence of past 30-day cigarette, cigar product, or e-cigarette use, measured using geographically representative high school youth survey data from 2013 to 2015 (prelegislation) and 2017 to 2019 (postlegislation) and compared using a difference-in-differences analysis., Results: The unweighted sample included 12 616 high school students (27.0% [95% CI, 26.9%-28.0%] in 10th grade; 50.9% [95% CI, 50.3%-51.6%] females) participating in 1 or more Youth Risk Behavior Surveys from 2013 to 2019, including 7064 students in Cleveland and 5552 students in the first-ring suburbs. Compared with the first-ring suburbs, Cleveland had a greater proportion of younger students (1623 [28.5%] ninth grade students vs 2179 [34.0%] ninth grade students) and Hispanic students (436 students [1.1%] vs 1433 students [12.6%]) and non-Hispanic Black students (2000 students [53.1%] vs 3971 students [75.1%]). Cigars were the most commonly used tobacco product in Cleveland, with use reported by 6201 students (19.8%) in 2013, 5877 students (21.3%) in 2015, and 5784 students (16.8%) in 2019. Compared with the first-ring suburbs, there was a greater decline in prevalence of use of cigars in Cleveland (β = 0.18 [SE, 0.05]; P < .001). The disparity across race, ethnicity, and sex decreased for all current tobacco product use. For example, the maximum difference between demographic subpopulations in current cigarette use was 11.6 (95% CI, 9.5-13.7) percentage points in 2013 between White females (16.1% [95% CI, 11.3%-20.8%]) and Black males (4.5% [95% CI, 3.5%-5.4%]). This maximum difference in current cigarette use decreased significantly to 5.1 (95% CI, 3.5-6.7) percentage points in 2019 between White females (6.9% [95% CI, 3.4%-10.3%]) and Black females (1.8% [95% CI, 0.7%-2.8%])., Conclusions and Relevance: This survey study found that there was a decline in youth-reported tobacco use across every tobacco product category from 2013 to 2019. This decline changed the trajectory of use among several demographic groups and brought the youth populations with the highest tobacco product use to similar rates of others.

Objective: The aim was to compare the outcomes of subdural electrode (SDE) implantations versus stereotactic electroencephalography (SEEG), the 2 predominant methods of intracranial electroencephalography (iEEG) performed in difficult-to-localize drug-resistant focal epilepsy., Methods: The Surgical Therapies Commission of the International League Against Epilepsy created an international registry of iEEG patients implanted between 2005 and 2019 with ≥1 year of follow-up. We used propensity score matching to control exposure selection bias and generate comparable cohorts. Study endpoints were: (1) likelihood of resection after iEEG; (2) seizure freedom at last follow-up; and (3) complications (composite of postoperative infection, symptomatic intracranial hemorrhage, or permanent neurological deficit)., Results: Ten study sites from 7 countries and 3 continents contributed 2,012 patients, including 1,468 (73%) eligible for analysis (526 SDE and 942 SEEG), of whom 988 (67%) underwent subsequent resection. Propensity score matching improved covariate balance between exposure groups for all analyses. Propensity-matched patients who underwent SDE had higher odds of subsequent resective surgery (odds ratio [OR] = 1.4, 95% confidence interval [CI] 1.05, 1.84) and higher odds of complications (OR = 2.24, 95% CI 1.34, 3.74; unadjusted: 9.6% after SDE vs 3.3% after SEEG). Odds of seizure freedom in propensity-matched resected patients were 1.66 times higher (95% CI 1.21, 2.26) for SEEG compared with SDE (unadjusted: 55% seizure free after SEEG-guided resections vs 41% after SDE)., Interpretation: In comparison to SEEG, SDE evaluations are more likely to lead to brain surgery in patients with drug-resistant epilepsy but have more surgical complications and lower probability of seizure freedom. This comparative-effectiveness study provides the highest feasible evidence level to guide decisions on iEEG. ANN NEUROL 2021;90:927-939., (© 2021 American Neurological Association.)

Animals with elodont dentition and unfused mandible symphyses are hypothesized to have symmetric incisor morphology. Since these animals maintain their teeth by gnawing, they may provide physiologic feedback on mechanical function when unilateral mandible defects are created that manifest as ipsilateral changes in tooth structure. This defect model would potentially generate important information on the functional/mechanical properties of implants. Rats' and rabbits' mandibles and teeth are analyzed with µCT at baseline and post-intervention ( n = 8 for each). Baseline incisors were compared. In a unilateral mandible pilot study, defects-ranging from critical size defect to complete ramus osteotomies-were created to assess effect on dentition (rats, n = 7; rabbits, n = 6). Within 90% confidence intervals, animals showed no baseline left/right differences in their incisors. There are apparent dental changes associated with unilateral defect type and location. Thus, at baseline, animals exhibit statistically significant incisor symmetry and there is an apparent relationship between mandible defect and incisor growth. The baseline symmetry proven here sets the stage to study the degree to which hemi-mandible destabilizing procedures result in measurable & reproducible disruption of dental asymmetry. In a validated model, an implant designed to function under load that prevents incisor asymmetry would provide supporting evidence that the implant has clinically useful load-bearing function.

Background: Accountable care organizations (ACOs), patient-centered medical homes (PCMHs), and the meaningful use of electronic health records (EHRs) generated particular attention during the last decade. Translating these reforms into meaningful increases in population health depends on improving the quality and clinical integration of primary care providers (PCPs). However, if these innovations spread more quickly among PCPs in urban and wealthier areas, then they could potentially worsen existing geographic disparities in health outcomes., Objective: To determine the market penetration of Medicare Shared Savings Program (MSSP) ACOs, PCMHs, and the meaningful use of EHRs among PCPs across urban and rural counties in Ohio., Design: Retrospective, observational study of the percent of PCPs in a county who are affiliated with PCMH, ACO, and meaningful use (MU) of EHR., Participants: PCPs in all of Ohio's 88 counties from 2011 to 2015., Main Measures: Primary care market penetration of ACO, PCMH, and meaningful use of EHR KEY RESULTS: In 2015, the Ohio primary care market penetration of PCMH was 23.4%, ACO was 27.7%, MU stage 1 was 55.8%, and MU stage 2 was 26.6%. During the study period, PCMH and ACO market penetration increased faster in urban counties relative to rural counties, and market penetration of meaningful use of EHR increased faster in rural counties., Conclusions: Market penetration of PCMH and ACOs increased faster in urban markets compared to rural markets. However, the adoption of EHRs increased faster in rural markets. The results are a cause for optimism as well as a call to action: although recent efforts to increase PCMH and ACO adoption were less effective among the rural population in Ohio, federal programs to accelerate adoption of EHRs were overwhelmingly successful in rural areas.

Background: Accelerated translation of real-world interventions for hypertension management is critical to improving cardiovascular outcomes and reducing disparities., Objective: To determine whether a positive deviance approach would improve blood pressure (BP) control across diverse health systems., Design: Quality improvement study using 1-year cross sections of electronic health record data over 5 years (2013-2017)., Participants: Adults ≥ 18 with hypertension with two visits in 2 years with at least one primary care visit in the last year (N = 114,950 at baseline) to a primary care practice in Better Health Partnership, a regional health improvement collaborative., Interventions: Identification of a "positive deviant" and dissemination of this system's best practices for control of hypertension (i.e., accurate/repeat BP measurement; timely follow-up; outreach; standard treatment algorithm; and communication curriculum) using 3 different intensities (low: Learning Collaborative events describing the best practices; moderate: Learning Collaborative events plus consultation when requested; and high: Learning Collaborative events plus practice coaching)., Main Measures: We used a weighted linear model to estimate the pre- to post-intervention average change in BP control (< 140/90 mmHg) for 35 continuously participating clinics., Key Results: BP control post-intervention improved by 7.6% [95% confidence interval (CI) 6.0-9.1], from 67% in 2013 to 74% in 2017. Subgroups with the greatest absolute improvement in BP control included Medicaid (12.0%, CI 10.5-13.5), Hispanic (10.5%, 95% CI 8.4-12.5), and African American (9.0%, 95% CI 7.7-10.4). Implementation intensity was associated with improvement in BP control (high: 14.9%, 95% CI 0.2-19.5; moderate: 5.2%, 95% CI 0.8-9.5; low: 0.2%, 95% CI-3.9 to 4.3)., Conclusions: Employing a positive deviance approach can accelerate translation of real-world best practices into care across diverse health systems in the context of a regional health improvement collaborative (RHIC). Using this approach within RHICs nationwide could translate to meaningful improvements in cardiovascular morbidity and mortality.

Introduction: This study examines the uptake of a clinician-focused teachable moment communication process (TMCP) and its impact on patient receipt of tobacco cessation support. The TMCP is a counseling method that uses patient concerns to help clinicians guide behavior change discussions about tobacco. We evaluate the added value of the TMCP training in a health system that implemented an Ask-Advise-Connect (AAC) systems-based approach., Methods: A stepped wedge cluster randomized trial included eight community health centers. Training involved a web module and onsite skill development with standardized patients and coaching. Main outcome measures included contact and enrollment in cessation services among patients referred for counseling, prescription of cessation medications and quit attempts., Results: Forty-four of 60 eligible clinicians received the TMCP training. Among TMCP-trained clinicians 68% used a TMCP approach (documented by flowsheet use) one or more times, with the median number of uses being 15 (IQR 2-33). Overall, the TMCP was used in 661 out of 8198 visits by smokers (8%). There was no improvement in any of the tobacco cessation assistance outcomes for the AAC + TMCP vs. the AAC only period. Visits where clinicians used the TMCP approach were associated with increased ordering of tobacco cessation medications, (OR = 2.6; 95% CI = 1.9, 3.5) and providing advice to quit OR 3.2 (95% CI 2.2, 4.7)., Conclusions: Despite high fidelity to the training, uptake of the TMCP approach in routine practice was poor, making it difficult to evaluate the impact on patient outcomes. When the TMCP approach was used, ordering tobacco cessation medications increased., Implications: Tobacco cessation strategies in primary care have the potential to reach a large portion of the population and deliver advice tailored to the patient. The poor uptake of the approach despite high training fidelity suggests that additional implementation support strategies, are needed to increase sustainable adoption of the TMCP approach., Trial Registration: clinicaltrials.gov #NCT02764385 , registration date 06/05/2016.

Within the aphasia literature, it is common to link location of lesioned brain tissue to specific patterns of language impairment. This has provided valuable insight into the relationship between brain structure and function, but it does not capture important underlying alterations in function of regions that remain structurally intact. Research has demonstrated that in the chronic stage of aphasia, variable patterns of reduced cerebral blood flow (CBF; hypoperfusion) in structurally intact regions of the brain contribute to persisting language impairments. However, one consistent issue in this literature is a lack of clear consensus on how to define hypoperfusion, which may lead to over- or underestimation of tissue functionality. In the current study, we conducted an exploratory analysis in six individuals with chronic aphasia (>1 year post-onset) using perfusion imaging to (1) suggest a new, individualized metric for defining hypoperfusion; (2) identify the extent of hypoperfused tissue in perilesional bands; and (3) explore the relationship between hypoperfusion and language impairment. Results indicated that our individualized metric for defining hypoperfusion provided greater precision when identifying functionally impaired tissue and its effects on language function in chronic aphasia. These results have important implications for intervention approaches that target intact (or impaired) brain tissue.

Significance: Guidelines urge primary care practices to routinely provide tobacco cessation care (i.e., assess tobacco use, provide brief cessation advice, and refer to cessation support). This study evaluates the impact of a systems-based strategy to provide tobacco cessation care in eight primary care clinics serving low-income patients., Methods: A non-randomized stepped wedge study design was used to implement an intervention consisting of (1) changes to the electronic health record (EHR) referral functionality and (2) expansion of staff roles to provide brief advice to quit; assess readiness to quit; offer a referral to tobacco cessation counseling; and sign the referral order. Outcomes assessed from the EHR include performance of tobacco cessation care tasks, referral contact, and enrollment rates for the quitline (QL) and in-house Freedom from Smoking (FFS) program. Generalized estimating equations (GEE) methods were used to compute odds ratios contrasting the pre-implementation vs. 1-, 3-, 6-, and 12-month post-implementation periods., Results: Of the 176,061 visits, 26.1% were by identified tobacco users. All indicators significantly increased at each time period evaluated post-implementation. In comparison with the pre-intervention period, assessing smoking status (26.6% vs. 55.7%; OR = 3.7, CI = 3.6-3.9), providing advice (44.8% vs. 88.7%; OR = 7.8, CI = 6.6-9.1), assessing readiness to quit (15.8% vs. 55.0%; OR = 6.2, CI = 5.4-7.0), and acceptance of a referral to tobacco cessation counseling (0.5% vs. 30.9%; OR = 81.0, CI = 11.4-575.8) remained significantly higher 12 months post-intervention. For the QL and FFS, respectively, there were 1223 and 532 referrals; 324 (31.1%) and 103 (24.7%) were contacted; 241 (74.4%) and 72 (69.6%) enrolled; and 195 (80.9%) and 14 (19.4%) received at least one counseling session., Conclusions: This system change intervention that includes an EHR-supported role expansion substantially increased the provision of tobacco cessation care and improvements were sustained beyond 1 year. This approach has the potential to greatly increase the number of individuals referred for tobacco cessation counseling.

Multiple Sclerosis (MS) is a common cause of neurological disability among young adults and has a high economic burden. Currently there are 18 disease modifying agents for relapsing MS, which were tested in clinical trials versus placebo or an active comparator in a pairwise manner. However, there is currently no consensus on the fundamental principles of treatment approach and initial therapy selection. These factors result in variable use of disease modifying therapies. Here we describe the study protocol for Determining the Effectiveness of earLy Intensive Versus Escalation approaches for the Treatment of Relapsing-remitting Multiple Sclerosis (DELIVER-MS). The main objective of the study is to determine whether an early highly effective treatment approach, defined as use of one of four monoclonal antibodies as initial therapy, is more effective than an escalation treatment approach (any other approved medication as initial therapy with subsequent escalation to higher efficacy treatments guided by radiological and clinical evaluation). The primary endpoint of the study is reduction in normalized brain volume loss from baseline visit to month 36 visit using MRI. Brain volume loss was selected as the best short-term predictor of long-term clinical disability. A total of 400 participants will be randomized 1:1 using minimization to account for age and sex by site, and 400 will be enrolled into a parallel observational cohort. The study results will help guide overall treatment philosophy and will have important implications for patient choice, clinical practice, and treatment access., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Guidelines urge primary care practices to routinely provide tobacco cessation care, but quality indicators for the provision of advice and assistance to quit smoking lag. This study evaluated the implementation of a systems-based strategy to improve performance of tobacco cessation care in primary care clinics., Methods: Changes to the electronic health record (EHR) facilitated staff to document when they ask about tobacco use, advise the patient to quit, offer to connect the patient to a quitline (QL) counselor, and refer interested patients to receive a call from a QL. Medical assistants (MAs) were trained to use the new sections of the EHR, and their roles were expanded to include the provision of brief cessation advice and activation of the QL referral. Primary outcomes were change in tobacco cessation processes preimplementation vs. one, three, and six months postimplementation of the strategy., Results: The increase in performance of tobacco cessation care was significant and sustained at six months postimplementation for assessing smoking status (50.9% vs. 76.3%; odds ratio [OR] = 3.04; 95% confidence interval [CI] = 2.80-3.31), providing advice (15.1% vs. 92.7%; OR = 69.3; 95% CI = 51.88-92.60), assessing readiness to quit (22.8% vs. 76.6%; OR = 10.80; 95% CI = 8.92-13.08), and accepting a referral to the QL (1.3% vs. 21.7%; OR = 20.31; 95% CI = 4.91-84.05)., Conclusion: Key stakeholder engagement informed a system change intervention that includes an EHR-supported role expansion of MAs for QL referrals; these changes substantially increased the provision of tobacco cessation care., (Copyright © 2019 The Joint Commission. Published by Elsevier Inc. All rights reserved.)

Objectives: The high prevalence of tobacco use at primary care safety-net clinics represents an opportunity to offer assistance with cessation. Documentation of smoking status, offering advice and medications, and referral to cessation services are important steps in supporting cessation attempts and are required elements by payors and accrediting agencies to demonstrate care quality. This study examines tobacco cessation support rates and patient characteristics using electronic medical record (EMR) data., Methods: This cross-sectional study engaged eight community health centers affiliated with a county hospital system in NE Ohio where adult tobacco use rates exceed 30%. EMR data from June 2014 through May 2016 were analysed to assess rates of tobacco cessation counselling, order of cessation medications, or both. The association of tobacco cessation support with patient characteristics and quit attempts was assessed using multivariable logistic regression models., Results: Among 21 702 current tobacco users, 74% had no intervention documented; 15.4% had counselling documented, 6.4% were prescribed tobacco cessation medication, and 4.2% had both documented. Males, those aged 18 to 34, and African Americans were more likely to have no documented intervention. Of current tobacco users with at least two visits, 5.6% had a quit attempt. Medication alone was associated with a greater likelihood of a quit attempt (AOR: 1.72 [95% CI: 1.36-2.17]) as well as counselling and medication combined (AOR: 1.95 [95% CI: 1.48-2.56])., Conclusions: Tobacco cessation support was lacking for 74% of current smokers and was less likely in subgroups including males, younger adults, and African Americans. Ordering tobacco cessation medication combined with counselling nearly doubled the likelihood of a quit attempt., (© 2018 John Wiley & Sons, Ltd.)

Background: Lower pH after out-of-hospital cardiac arrest (OHCA) has been associated with worsening neurologic outcome, with <7.2 identified as an "unfavorable resuscitation feature" in consensus treatment algorithms despite conflicting data. This study aimed to describe the relationship between decremental post-resuscitation pH and neurologic outcomes after OHCA., Methods: Consecutive OHCA patients treated with targeted temperature management (TTM) at multiple US centers from 2008 to 2017 were evaluated. Poor neurologic outcome at hospital discharge was defined as cerebral performance category ≥3. The exposure was initial arterial pH after return of spontaneous circulation (ROSC) analyzed in decremental 0.05 thresholds. Potential confounders (demographics, history, resuscitation characteristics, initial studies) were defined a priori and controlled for via ATT-weighting on the inverse propensity score plus direct adjustment for the linear propensity score., Results: Of 723 patients, 589 (80%) experienced poor neurologic outcome at hospital discharge. After propensity-adjustment with excellent covariate balance, the adjusted odds ratios for poor neurologic outcome by pH threshold were: ≤7.3: 2.0 (1.0-4.0); ≤7.25: 1.9 (1.2-3.1); ≤7.2: 2.1 (1.3-3.3); ≤7.15: 1.9 (1.2-3.1); ≤7.1: 2.4 (1.4-4.1); ≤7.05: 3.1 (1.5-6.3); ≤7.0: 4.5 (1.8-12)., Conclusions: No increased hazard of progressively poor neurologic outcomes was observed in resuscitated OHCA patients treated with TTM until the initial post-ROSC arterial pH was at least ≤7.1. This threshold is more acidic than in current guidelines, suggesting the possibility that post-arrest pH may be utilized presently as an inappropriately-pessimistic prognosticator., (Copyright © 2019. Published by Elsevier B.V.)

Background: Our primary aim was to evaluate the effects of 2 family-based obesity management interventions compared with a control group on BMI in low-income adolescents with overweight or obesity., Methods: In this randomized clinical trial, 360 urban-residing youth and a parent were randomly assigned to 1 of 2 behaviorally distinct family interventions or an education-only control group. Eligible children were entering the sixth grade with a BMI ≥85th percentile. Interventions were 3 years in length; data were collected annually for 3 years. Effects of the interventions on BMI slope (primary outcome) over 3 years and a set of secondary outcomes were assessed., Results: Participants were primarily African American (77%), had a family income of <25 000 per year, and obese at enrollment (68%). BMI increased over time in all study groups, with group increases ranging from 0.95 to 1.08. In an intent-to-treat analysis, no significant differences were found in adjusted BMI slopes between either of the family-based interventions and the control group ( P = .35). No differences were found between the experimental and control groups on secondary outcomes of diet, physical activity, sleep, perceived stress, or cardiometabolic factors. No evidence of effect modification of the study arms by sex, race and/or ethnicity, household income, baseline levels of child and parent obesity, or exposure to a school fitness program were found., Conclusions: In this low-income, adolescent population, neither of the family-based interventions improved BMI or health-related secondary outcomes. Future interventions should more fully address poverty and other social issues contributing to childhood obesity., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Background: A lower heart rate is associated with better outcomes in patients with heart failure (HF) with reduced ejection fraction (EF). Less is known about this association in patients with HF with preserved ejection fraction (HFpEF)., Objectives: The aims of this study were to examine associations of discharge heart rate with outcomes in hospitalized patients with HFpEF., Methods: Of the 8,873 hospitalized patients with HFpEF (EF ≥50%) in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 6,286 had a stable heart rate, defined as ≤20 beats/min variation between admission and discharge. Of these, 2,369 (38%) had a discharge heart rate of <70 beats/min. Propensity scores for discharge heart rate <70 beats/min, estimated for each of the 6,286 patients, were used to assemble a cohort of 2,031 pairs of patients with heart rate <70 versus ≥70 beats/min, balanced on 58 baseline characteristics., Results: The 4,062 matched patients had a mean age of 79 ± 10 years, 66% were women, and 10% were African American. During 6 years (median 2.8 years) of follow-up, all-cause mortality was 65% versus 70% for matched patients with a discharge heart rate <70 versus ≥70 beats/min, respectively (hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.80 to 0.93; p < 0.001). A heart rate <70 beats/min was also associated with a lower risk for the combined endpoint of HF readmission or all-cause mortality (HR: 0.90; 95% CI: 0.84 to 0.96; p = 0.002), but not with HF readmission (HR: 0.93; 95% CI: 0.85 to 1.01) or all-cause readmission (HR: 1.01; 95% CI: 0.95 to 1.08). Similar associations were observed regardless of heart rhythm or receipt of beta-blockers., Conclusions: Among hospitalized patients with HFpEF, a lower discharge heart rate was independently associated with a lower risk of all-cause mortality, but not readmission., (Published by Elsevier Inc.)

Background: Digoxin use has been shown to be associated with a lower risk of 30-day all-cause hospital readmissions in older patients with heart failure (HF). In the current study, we examined this association among long-term care (LTC) residents hospitalized for HF., Methods: Of the 8049 Medicare beneficiaries discharged alive after hospitalization for HF from 106 Alabama hospitals, 545 (7%) were LTC residents, of which 227 (42%) received discharge prescriptions for digoxin. Propensity scores for digoxin use, estimated for each of the 545 patients, were used to assemble a matched cohort of 158 pairs of patients receiving and not receiving digoxin who were balanced on 29 baseline characteristics. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with digoxin among matched patients were estimated using Cox regression models., Results: Matched patients (n = 316) had a mean age of 83 years, 74% were women, and 18% African American. Thirty-day all-cause readmission occurred in 21% and 20% of patients receiving and not receiving digoxin, respectively (HR, 1.02; 95% CI, 0.63-1.66). Digoxin had no association with all-cause mortality (HR, 0.90; 95% CI, 0.48-1.70), HF readmission (HR, 0.90; 95% CI, 0.38-2.12), or a combined endpoint of all-cause readmission or all-cause mortality (HR, 0.97; 95% CI, 0.65-1.45) at 30 days. These associations remained unchanged at 1 year postdischarge., Conclusions: The lack of an association between digoxin and 30-day all-cause readmission in older nursing home residents hospitalized for HF is intriguing and needs to be interpreted with caution given the small sample size., (Published by Elsevier Inc.)

Background: Dimethyl fumarate and fingolimod are oral disease-modifying therapies approved to treat relapsing multiple sclerosis. Prior observational studies and our previous 12-month investigation showed comparable clinical efficacy., Objective: The purpose of this study was to assess real-world efficacy and discontinuation of dimethyl fumarate and fingolimod over 24 months in patients with multiple sclerosis., Methods: Patients treated with dimethyl fumarate ( n  = 395) or fingolimod ( n  = 264) completed 24-month follow-up in a large academic multiple sclerosis center. Discontinuation rates and measures of disease activity were compared after propensity score weighting. The primary outcome was on-treatment annualized relapse rate ratio. Other measures included rate of drug discontinuation and brain magnetic resonance imaging activity defined as new T2 and/or gadolinium-enhancing lesions., Results: Propensity score weighting showed excellent covariate balance. At 24 months, dimethyl fumarate demonstrated comparable annualized relapse rate (rate ratio = 1.45, 95% confidence interval 0.53-3.99) and brain magnetic resonance imaging activity (odds ratio = 1.38, 95% confidence interval 0.83-2.32). Dimethyl fumarate patients discontinued therapy earlier compared to fingolimod (hazard ratio = 1.40, 95% confidence interval 1.11-1.77) and were more likely to discontinue therapy due to intolerability (odds ratio = 1.98, 95% confidence interval 1.18-3.23)., Conclusion: Dimethyl fumarate and fingolimod had similar reductions in annualized relapse rate in clinical trials, and our real-world experience supports this observation. Dimethyl fumarate-treated patients had higher likelihood of early discontinuation, and this was mostly due to intolerability.

Background: Therapy with evidence-based heart failure (HF) medications has been shown to be associated with lower risk of 30-day all-cause readmission in patients with HF and reduced ejection fraction (HFrEF)., Methods: We examined the association of aldosterone antagonist use with 30-day all-cause readmission in this population. Of the 2443 Medicare beneficiaries with HF and left ventricular EF ≤35% discharged home from 106 Alabama hospitals during 1998-2001, 2060 were eligible for spironolactone therapy (serum creatinine ≤2.5 for men and ≤2mg/dl for women, and serum potassium <5mEq/L). After excluding 186 patients already receiving spironolactone on admission, the inception cohort consisted of 1874 patients eligible for a new discharge prescription for spironolactone, of which 329 received one. Using propensity scores for initiation of spironolactone therapy, we assembled a matched cohort of 324 pairs of patients receiving and not receiving spironolactone balanced on 34 baseline characteristics (mean age 72years, 42% women, 33% African American)., Results: Thirty-day all-cause readmission occurred in 17% and 19% of matched patients receiving and not receiving spironolactone, respectively (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.64-1.32; p=0.650). Spironolactone had no association with 30-day all-cause mortality (HR, 0.84; 95% CI, 0.38-1.88; p=0.678) or HF readmission (HR, 0.74; 95% CI, 0.41 1.31; p=0.301). These associations remained unchanged during 12months of post-discharge follow-up., Conclusion: A discharge prescription for spironolactone had no association with 30-day all-cause readmission among older, hospitalized Medicare beneficiaries with HFrEF eligible for spironolactone therapy., Competing Interests: Disclosures: None, (Published by Elsevier Ireland Ltd.)

Background: Heart failure is the leading cause for 30-day all-cause readmission. We examined the impact of 30-day all-cause readmission on long-term outcomes and cost in a propensity score-matched study of hospitalized patients with heart failure., Methods: Of the 7578 Medicare beneficiaries discharged with a primary diagnosis of heart failure from 106 Alabama hospitals (1998-2001) and alive at 30 days after discharge, 1519 had a 30-day all-cause readmission. Using propensity scores for 30-day all-cause readmission, we assembled a matched cohort of 1516 pairs of patients with and without a 30-day all-cause readmission, balanced on 34 baseline characteristics (mean age 75 years, 56% women, 24% African American)., Results: During 2-12 months of follow-up after discharge from index hospitalization, all-cause mortality occurred in 41% and 27% of matched patients with and without a 30-day all-cause readmission, respectively (hazard ratio 1.68; 95% confidence interval 1.48-1.90; P <.001). This harmful association of 30-day all-cause readmission with mortality persisted during an average follow-up of 3.1 (maximum, 8.7) years (hazard ratio 1.33; 95% confidence interval 1.22-1.45; P <.001). Patients with a 30-day all-cause readmission had higher cumulative all-cause readmission (mean, 6.9 vs 5.1; P <.001), a longer cumulative length of stay (mean, 51 vs 43 days; P <.001), and a higher cumulative cost (mean, $38,972 vs $34,025; P = .001) during 8.7 years of follow-up., Conclusions: Among Medicare beneficiaries hospitalized for heart failure, 30-day all-cause readmission was associated with a higher risk of subsequent all-cause mortality, higher number of cumulative all-cause readmission, longer cumulative length of stay, and higher cumulative cost., (Published by Elsevier Inc.)

Background: Dimethyl fumarate (DMF) and fingolimod (FTY) are approved oral disease modifying therapies (DMT) for relapsing multiple sclerosis (MS). Phase 3 trials established these agents as effective and generally well tolerated, though comparative efficacy and discontinuation remain unknown., Objective: To assess real-world efficacy and discontinuation of DMF and FTY over 12 months in patients with MS., Methods: We identified 458 DMF-treated and 317 FTY-treated patients in a large academic MS center. Measures of disease activity and discontinuation were compared using propensity score (PS) weighting. Covariates in the PS model included demographics and baseline clinical and MRI characteristics within 12 months of DMT initiation. The primary outcome measure was on-treatment annualized relapse rate (ARR) ratio, which was analyzed using a Poisson regression model. Other measures included time to first relapse, drug discontinuation, time to discontinuation, and new brain MRI lesions at 12 months., Results: The on-treatment ARR for DMF was 0.16 (95% CI (0.12, 0.18)) and 0.13 (95% CI (0.08, 0.16)) for FTY. PS weighting, which demonstrated excellent covariate balance, showed no differences between groups on ARR (rate ratio=1.56, 95% CI (0.78, 3.14)), overall brain MRI activity defined as new T2 and/or gadolinium enhancing (GdE) lesions (OR=1.38, 95% CI (0.78, 2.42)), new T2 lesions (OR=1.33, 95% CI (0.71, 2.49)), and discontinuation (OR=1.30, 95% CI (0.84, 1.99)). DMF had higher odds of GdE lesions (OR=2.19, 95% CI (1.10, 4.35)), earlier time to discontinuation (HR=1.35, 95% CI (1.05, 1.74)), and earlier relapses (HR=1.64, 95% CI (1.10, 2.46)) compared to FTY., Conclusion: Assessment in our clinical practice cohort showed comparable clinical efficacy, overall brain MRI activity, and discontinuation between DMF and FTY at 12 months. DMF had increased GdE lesions and intolerability early after treatment initiation., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Heart failure is the leading cause for 30-day all-cause readmission, the reduction of which is a goal of the Affordable Care Act. There is a growing interest in understanding the impact of evidence-based heart failure therapy on 30-day all-cause readmission. In the current study, we examined the impact of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI-ARBs) on 30-day all-cause readmission in heart failure., Methods: Of the 1384 hospitalized Medicare beneficiaries with heart failure and left ventricular ejection fraction <45% discharged alive from 106 Alabama hospitals (1998-2001) without prior ACEI-ARB use and without known contraindications to ACEI-ARB use; 734 received new predischarge prescriptions for these drugs. Using propensity scores for ACEI-ARB initiation, we assembled a matched cohort of 477 pairs of patients balanced on 32 baseline characteristics (mean age 75 years, 46% women, 26% African American)., Results: Thirty-day all-cause readmissions occurred in 18% and 24% of matched patients receiving and not receiving ACEI-ARBs, respectively (hazard ratio [HR] 0.74; 95% confidence interval [CI], 0.56-0.97; P = .030). ACEI-ARB use was also associated with lower risk of 30-day all-cause mortality (HR 0.56; 95% CI, 0.33-0.98; P = .041) and of the combined endpoint of 30-day all-cause readmission or 30-day all-cause mortality (HR 0.73; 95% CI, 0.56-0.94; P = .017). All associations remained significant at 1 year post discharge., Conclusions: Among hospitalized patients with heart failure and reduced ejection fraction, the use of ACEI-ARBs was associated with a significantly lower risk of 30-day all-cause readmission and 30-day all-cause mortality; both beneficial associations persisted during long-term follow-up., Competing Interests: None, (Published by Elsevier Inc.)

Objective: To assess long-term direct medical costs, health care utilization, and mortality following resective surgery in persons with uncontrolled epilepsy., Methods: Retrospective longitudinal cohort study of Medicaid beneficiaries with epilepsy from 2000 to 2008. The study population included 7,835 persons with uncontrolled focal epilepsy ages 18-64 years, with an average follow-up time of 5 years. Of these, 135 received surgery during the study period. To account for selection bias, we used risk-set optimal pairwise matching on a time-varying propensity score, and inverse probability of treatment weighting. Repeated measures generalized linear models were used to model utilization and cost outcomes. Cox proportional hazard was used to model survival., Results: The mean direct medical cost difference between the surgical group and control group was $6,806 after risk-set matching. The incidence rate ratio of inpatient, emergency room, and outpatient utilization was lower among the surgical group in both unadjusted and adjusted analyses. There was no significant difference in mortality after adjustment. Among surgical cases, mean annual costs per subject were on average $6,484 lower, and all utilization measures were lower after surgery compared to before., Significance: Subjects that underwent epilepsy surgery had lower direct medical care costs and health care utilization. These findings support that epilepsy surgery yields substantial health care cost savings., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)

Randomized trials provide strong evidence regarding efficacy of interventions but are limited in their capacity to address potential heterogeneity in effectiveness within broad clinical populations. For example, a treatment that on average is superior may be distinctly worse in certain patients. We propose a technique for using large electronic health registries to develop and validate decision models that measure-for distinct combinations of covariate values-the difference in predicted outcomes among 2 alternative treatments. We demonstrate the methodology in a prototype analysis of in-hospital mortality under alternative revascularization treatments. First, we developed prediction models for a binary outcome of interest for each treatment. Decision criteria were then defined based on the treatment-specific model predictions. Patients were then classified as receiving concordant or discordant care (in relation to the model recommendation), and the association between discordance and outcomes was evaluated. We then present alternative decision criteria and validation methodologies, as well as sensitivity analyses that investigate 1) the imbalance between treatments on observed covariates and 2) the aggregate impact of unobserved covariates. Our methodology supplements population-average clinical trial results by modeling heterogeneity in outcomes according to specific covariate values. It thus allows for assessment of current practice, from which cogent hypotheses for improved care can be derived. Newly emerging large population registries will allow for accurate predictions of outcome risk under competing treatments, as complex functions of predictor variables. Whether or not the models might be used to inform decision making depends on the extent to which important predictors are available. Further work is needed to understand the strengths and limitations of this approach, particularly in relation to those based on randomized trials., (© The Author(s) 2015.)

Objectives: The objective of this cohort study was to compare neuropsychological outcomes following left temporal lobe resection (TLR) in patients with epilepsy who had or had not undergone prior invasive monitoring., Methods: Data were obtained from an institutional review board-approved, neuropsychology registry for patients who underwent epilepsy surgery at Cleveland Clinic between 1997 and 2013. A total of 176 patients (45 with and 131 without invasive EEG) met inclusion criteria. Primary outcome measures were verbal memory and language scores. Other cognitive outcomes were also examined. Outcomes were assessed using difference in scores from before to after surgery and by presence/absence of clinically meaningful decline using reliable change indices (RCIs). Effect of invasive EEG on cognitive outcomes was estimated using weighting and propensity score adjustment to account for differences in baseline characteristics. Linear and logistic regression models compared surgical groups on all cognitive outcomes., Results: Patients with invasive monitoring showed greater declines in confrontation naming; however, when RCIs were used to assess clinically meaningful change, there was no significant treatment effect on naming performance. No difference in verbal memory was observed, regardless of how the outcome was measured. In secondary outcomes, patients with invasive monitoring showed greater declines in working memory, which were no longer apparent using RCIs to define change. There were no outcome differences on other cognitive measures., Conclusions: Results suggest that invasive EEG monitoring conducted prior to left TLR is not associated with greater cognitive morbidity than left TLR alone. This information is important when counseling patients regarding cognitive risks associated with this elective surgery., (© 2015 American Academy of Neurology.)

Background: Severe asthma occurs more often in older adult patients. We hypothesized that the greater risk for severe asthma in older individuals is due to aging, and is independent of asthma duration., Methods: This is a cross-sectional study of prospectively collected data from adult participants (N=1130; 454 with severe asthma) enrolled from 2002 - 2011 in the Severe Asthma Research Program., Results: The association between age and the probability of severe asthma, which was performed by applying a Locally Weighted Scatterplot Smoother, revealed an inflection point at age 45 for risk of severe asthma. The probability of severe asthma increased with each year of life until 45 years and thereafter increased at a much slower rate. Asthma duration also increased the probability of severe asthma but had less effect than aging. After adjustment for most comorbidities of aging and for asthma duration using logistic regression, asthmatics older than 45 maintained the greater probability of severe asthma [OR: 2.73 (95 CI: 1.96; 3.81)]. After 45, the age-related risk of severe asthma continued to increase in men, but not in women., Conclusions: Overall, the impact of age and asthma duration on risk for asthma severity in men and women is greatest over times of 18-45 years of age; age has a greater effect than asthma duration on risk of severe asthma.