The timed 25-foot walk in a large cohort of multiple sclerosis patients.

BACKGROUND: The timed 25-foot walk (T25FW) is a key clinical outcome measure in multiple sclerosis patient management and clinical research. OBJECTIVES: To evaluate T25FW performance and factors associated with its change in the Multiple Sclerosis Outcome Assessments Consortium (MSOAC) Placebo Database (n = 2465). METHODS: We created confirmed disability progression (CDP) variables for T25FW and Expanded Disability Status Scale (EDSS) outcomes. We used intraclass correlation coefficients (ICCs) and Bland Altman plots to evaluate reliability. We evaluated T25FW changes and predictive validity using a mixed-effects model, survival analysis, and nested case-control analysis. RESULTS: The mean baseline score for the T25FW in this study population was 9.2 seconds, median = 6.1 (standard deviation = 11.0, interquartile range (IQR) = 4.8, 9.0). The T25FW measure demonstrated excellent test-retest reliability (ICC = 0.98). Walk times increased with age, disability, disease type, and disease duration; relapses were not associated with an increase. Patients with T25FW progression had a faster time to EDSS-CDP compared to those without (hazards ratio (HR): 2.6; confidence interval (CI): 2.2, 3.1). Changes in the T25FW were more likely to precede changes in EDSS. CONCLUSION: This research confirms the association of the T25FW with disability and provides some evidence of predictive validity. Our findings support the continued use of the T25FW in clinical practice and clinical trials.

Cardiovascular Diseases, Medications, and ALS: A Population-Based Case-Control Study.

INTRODUCTION: We investigated the associations between antecedent all-cause CVD diagnoses, cause-specific CVD diagnosis, and CVD medication prescriptions with the risk of developing amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: We conducted a population-based case-control study of U.S. Medicare enrollees from 2006 to 2013. The final sample included 3,714 incident ALS cases and 18,570 controls (matched on age, sex, enrollment length, and county). Information was collected from Medicare Parts A, B, and D administrative claims data on hypertension, ischemic heart disease, heart failure, acute myocardial infarction, atrial fibrillation, prescriptions of angiotensin-converting enzyme inhibitors, angiotensin II receptors blockers, calcium channel blockers, beta blockers, and antiarrhythmics. Associations were evaluated using conditional logistic regression adjusting for age, sex, race/ethnicity, geographical location, alcohol and tobacco use, and socioeconomic status. RESULTS: The odds ratio (OR) for having one or more ICD-9 codes for any cardiovascular disease diagnosis at least 24 months prior to the date of ALS diagnosis was 0.85 (95% confidence interval [CI]: 0.78-0.92). Cardiovascular conditions that were inversely associated with ALS included heart failure (OR = 0.79; 95% CI 0.70-0.89), atrial fibrillation (OR = 0.81; 95% CI 0.77-0.92), and hypertension (OR = 0.91; 95% CI 0.84-0.98). Exposures to several classes of cardiovascular medications were inversely associated with ALS risk even after adjusting for confounding by indication, including ACE inhibitors (OR = 0.84, 95% CI 0.77-0.91), calcium channel blockers (OR = 0.64, 95% CI 0.59-0.70), and beta blockers (OR = 0.76, 95% CI 0.71-0.83). DISCUSSION/CONCLUSION: These findings merit additional research, including animal studies and pilot clinical trials, to further evaluate and evidence the effects of ACEIs, CCBs, and BBs on the risk of developing and clinical expression of ALS.

Evaluation of the Completeness of ALS Case Ascertainment in the US National ALS Registry: Application of the Capture-Recapture Method.

INTRODUCTION: The Centers for Disease Control and Prevention (CDC) National Amyotrophic Lateral Sclerosis (ALS) Registry is the first national registry for a chronic neurologic disease in the USA and uses a combination of case-finding methods including administrative healthcare data and patient self-registration. METHODS: We applied capture-recapture methodology to estimate the completeness of the Registry for ascertaining patients with ALS for the first full year and the fourth year of the Registry (2011, 2014). The Registry uses the combination of two national administrative claims databases (Medicare and Veterans Affairs) with a self-register option at the registry portal. We conducted descriptive analyses of the demographic and clinical characteristics of the ALS cases identified by each of the sources and estimated the completeness of case ascertainment for each of the three ALS Registry sources individually, pairwise, and in all combinations. RESULTS: Case-finding completeness was 54% in 2011 and improved to 56% in 2014. A smaller proportion of ALS patients under age 65 were ascertained than those 65 or older, and ascertainment was also lower for nonwhite than white patients. The uncorrected ALS prevalence was 4.3/100,000 in 2011 (in 2014, 5.0/100,000), but after correction for underascertainment, annual prevalence in 2011 was 7.9/100,000 (95% CI: 7.6-8.2) (in 2014 was 8.9/100,000 [95% CI: 8.7-9.2]). DISCUSSION/CONCLUSION: Our findings indicate that administrative healthcare databases are a very efficient method for identifying the majority of ALS prevalent cases in the National ALS Registry and that the inclusion of a web registry portal for patients to self-register is important to ensure a more representative population for estimating ALS prevalence. Nonetheless, more than 40% of ALS cases were not ascertained by the Registry, with individuals younger than age 65 and people of color underrepresented. Recommendations are provided for additional methods that can be considered to improve the completeness of case ascertainment.

Cervical dystonia incidence and diagnostic delay in a multiethnic population.

BACKGROUND: Current cervical dystonia (CD) incidence estimates are based on small numbers in relatively ethnically homogenous populations. The frequency and consequences of delayed CD diagnosis is poorly characterized. OBJECTIVES: To determine CD incidence and characterize CD diagnostic delay within a large, multiethnic integrated health maintenance organization. METHODS: We identified incident CD cases using electronic medical records and multistage screening of more than 3 million Kaiser Permanente Northern California members from January 1, 2003, to December 31, 2007. A final diagnosis was made by movement disorders specialist consensus. Diagnostic delay was measured by questionnaire and health utilization data. Incidence rates were estimated assuming a Poisson distribution of cases and directly standardized to the 2000 U.S. census. Multivariate logistic regression models were employed to assess diagnoses and behaviors preceding CD compared with matched controls, adjusting for age, sex, and membership duration. RESULTS: CD incidence was 1.18/100,000 person-years (95% confidence interval [CI], 0.35-2.0; women, 1.81; men, 0.52) based on 200 cases over 15.4 million person-years. Incidence increased with age. Half of the CD patients interviewed reported diagnostic delay. Diagnoses more common in CD patients before the index date included essential tremor (odds ratio [OR] 68.1; 95% CI, 28.2-164.5), cervical disc disease (OR 3.83; 95% CI, 2.8-5.2), neck sprain/strain (OR 2.77; 95% CI, 1.99-3.62), anxiety (OR 2.24; 95% CI, 1.63-3.11) and depression (OR 1.94; 95% CI, 1.4-2.68). CONCLUSIONS: CD incidence is greater in women and increases with age. Diagnostic delay is common and associated with adverse effects. © 2019 International Parkinson and Movement Disorder Society.

Feasibility of Using a Nationally Representative Telephone Survey to Monitor Multiple Sclerosis Prevalence in the United States.

BACKGROUND: Multiple sclerosis (MS) is the most common chronic neurologic disease of young adults, placing a heavy burden on patients, families, and the healthcare system. Ongoing surveillance of the incidence and prevalence of MS is critical for health policy and research, but feasible options are limited in the United States and many other countries. We investigated the feasibility of monitoring the prevalence of MS using a large national telephone survey of the adult US population. METHODS: We developed questions to estimate the lifetime prevalence and age of onset of MS using the US-based Behavioral Risk Factor Surveillance System (BRFSS) and piloted these questions in 4 states (MN, RI, MD, and TX). There was a total of 45,198 respondents aged 18 years and above. Analyses investigated individual state and combined prevalence estimates along with health-related comorbidities and limitations. MS prevalence estimates from the BRFSS were compared to estimates from multi-source administrative claims and traditional population-based methods. RESULTS: The estimated lifetime prevalence of self-reported MS (per 100,000 adults) was 682 (95% CI 528-836); 384 (95% CI 239-529) among males and 957 (95% CI 694-1,220) among females. Estimates were consistent across the 4 states but much higher than recently published estimates using population-based administrative claims data. This was observed for both national results and for MS prevalence estimates from other studies within specific states (MN, RI, and TX). Prevalence estimates for Caucasian, African American, and Hispanic respondents were 824, 741, and 349 per 100,000 respectively. Age and sex distributions were consistent with prior epidemiologic reports. Comorbidity and functional limitations were more pronounced among female than male respondents. CONCLUSIONS: While yielding higher overall MS prevalence estimates compared to recent studies, this large-scale self-report telephone method yielded relative prevalence estimates (e.g., prevalence patterns of MS by sex, age, and race-ethnicity) that were generally comparable to other surveillance approaches. With certain caveats, population-based telephone surveys may eventually offer the ability to investigate novel disease correlates and are relatively feasible, and affordable. Further work is needed to create a valid question set and methodology for case ascertainment before this approach could be adopted to accurately estimate MS prevalence.

Development and Internal Validation of a Multivariable Prediction Model for Individual Episodic Migraine Attacks Based on Daily Trigger Exposures.

OBJECTIVE: To develop and internally validate a multivariable predictive model for days with new-onset migraine headaches based on patient self-prediction and exposure to common trigger factors. BACKGROUND: Accurate real-time forecasting of one's daily risk of migraine attack could help episodic migraine patients to target preventive medications for susceptible time periods and help decrease the burden of disease. Little is known about the predictive utility of common migraine trigger factors. METHODS: We recruited adults with episodic migraine through online forums to participate in a 90-day prospective daily-diary cohort study conducted through a custom research application for iPhone. Every evening, participants answered questions about migraine occurrence and potential predictors including stress, sleep, caffeine and alcohol consumption, menstruation, and self-prediction. We developed and estimated multivariable multilevel logistic regression models for the risk of a new-onset migraine day vs a healthy day and internally validated the models using repeated cross-validation. RESULTS: We had 178 participants complete the study and qualify for the primary analysis which included 1870 migraine events. We found that a decrease in caffeine consumption, higher self-predicted probability of headache, a higher level of stress, and times within 2 days of the onset of menstruation were positively associated with next-day migraine risk. The multivariable model predicted migraine risk only slightly better than chance (within-person C-statistic: 0.56, 95% CI: 0.54, 0.58). CONCLUSIONS: In this study, episodic migraine attacks were not predictable based on self-prediction or on self-reported exposure to common trigger factors. Improvements in accuracy and breadth of data collection are needed to build clinically useful migraine prediction models.

Estimation of the Prevalence of Amyotrophic Lateral Sclerosis in the United States Using National Administrative Healthcare Data from 2002 to 2004 and Capture-Recapture Methodology.

BACKGROUND: National administrative healthcare data may be used as a case-finding method for prevalence studies of chronic disease in the United States, but the completeness of ascertainment likely varies depending on the disease under study. METHODS: We used 3 case-finding sources (Medicare, Medicaid, and Veterans Administration data) to estimate the prevalence of amyotrophic lateral sclerosis (ALS) in the United States for 2002-2004, and applied the capture-recapture methodology to estimate the degree of under-ascertainment when relying solely on these sources for case identification. RESULTS: Case-finding completeness was 76% overall and did not vary by race, but was lower for males (77%) than for females (88%), and lower for patients under age 65 (66%) than patients over age 65 (79%). The uncorrected ALS prevalence ratio was 2.8/100,000 in 2002, 3.3/100,000 in 2003, and 3.7/100,000 in 2004. After correcting for under-ascertainment, the annual prevalence increased by approximately 1 per 100,000 to 3.7/100,000 in 2002 (95% CI 3.66-3.80), 4.4/100,000 in 2003 (95% CI 4.34-4.50), and 4.8/100,000 in 2004 (95% CI 4.76-4.91). CONCLUSIONS: Federal healthcare claims databases ascertained are a very efficient method for identifying the majority of ALS-prevalent cases in the National ALS Registry, and may be enhanced by having patients self-register through the registry web portal.

Risk Factors for Severe Postpartum Hemorrhage After Cesarean Delivery: Case-Control Studies.

BACKGROUND: Women who undergo intrapartum caesarean delivery (CD) are at increased risk of postpartum hemorrhage (PPH) compared with those undergoing prelabor CD. To determine whether the presence and strength of the associations between individual risk factors and severe PPH vary among women undergoing prelabor CD or intrapartum CD, stratified analyses are needed according to CD subtype. METHODS: To identify risk factors for severe PPH within 2 distinct CD populations, prelabor CD and intrapartum CD, we performed 2 case-control studies. Women in each study cohort delivered at a tertiary obstetric center in the United States between 2002 and 2012. For each study, cases were women who had a blood loss ≥1500 mL or who received an intraoperative or postoperative transfusion up to 48 hours after delivery. Risk factors for severe PPH among women undergoing prelabor CD or intrapartum CD were examined in separate logistic regression models. RESULTS: For prelabor CD, we identified 269 cases and 550 controls. Clinical factors with the highest adjusted odds for severe PPH during prelabor CD were general anesthesia (adjusted odds ratio [aOR] = 22.3; 95% confidence interval [CI], 4.9-99.9; reference group = spinal anesthesia), multiple pregnancies (aOR = 8.0; 95% CI, 4.2-15.0; reference group = singleton pregnancy), and placenta previa (aOR = 6.3; 95% CI, 3.4-11.8). For intrapartum CD, we identified 278 cases and 572 controls. Clinical factors with the highest adjusted odds for severe PPH during intrapartum CD were general anesthesia (aOR = 5.4; 95% CI, 1.7-17.1), multiple pregnancies (aOR = 3.2; 95% CI, 1.7-6.3), and a predelivery hemoglobin ≤ 9.9 g/dL (aOR = 3.0; 95% CI, 1.3-6.9; reference group = predelivery hemoglobin ≥ 11 g/dL). CONCLUSIONS: Women who undergo prelabor CD and intrapartum CD have several shared risk factors for severe PPH (general anesthesia and multiple pregnancies). However, the risk factor profiles for severe PPH differed between these CD cohorts. Recognizing these differences may be important when planning resources and interventions for high-risk patients undergoing either prelabor or intrapartum CD.

Racial and Ethnic Disparities in Mode of Anesthesia for Cesarean Delivery.

BACKGROUND: Racial and ethnic disparities have been identified in the provision of neuraxial labor analgesia. These disparities may exist in other key aspects of obstetric anesthesia care. We sought to determine whether racial/ethnic disparities exist in mode of anesthesia for cesarean delivery (CD). METHODS: Women who underwent CD between 1999 and 2002 at 19 different obstetric centers in the United States were identified from the Maternal-Fetal Medicine Units Network Cesarean Registry. Race/ethnicity was categorized as: Caucasian, African American, Hispanic, and Non-Hispanic Others (NHOs). Mode of anesthesia was classified as neuraxial anesthesia (spinal, epidural, or combined spinal-epidural anesthesia) or general anesthesia. To account for obstetric and non-obstetric covariates that may have influenced mode of anesthesia, multiple logistic regression analyses were performed by using sequential sets of covariates. RESULTS: The study cohort comprised 50,974 women who underwent CD. Rates of general anesthesia among racial/ethnic groups were as follows: 5.2% for Caucasians, 11.3% for African Americans, 5.8% for Hispanics, and 6.6% for NHOs. After adjustment for obstetric and non-obstetric covariates, African Americans had the highest odds of receiving general anesthesia compared with Caucasians (adjusted odds ratio [aOR] = 1.7; 95% confidence interval [CI], 1.5-1.8; P < 0.001). The odds of receiving general anesthesia were also higher among Hispanics (aOR = 1.1; 95% CI, 1.0-1.3; P = 0.02) and NHOs (aOR = 1.2; 95% CI, 1.0-1.4; P = 0.03) compared with Caucasians, respectively. In our sensitivity analysis, we reconstructed the models after excluding women who underwent neuraxial anesthesia before general anesthesia. The adjusted odds of receiving general anesthesia were similar to those in the main analysis: African Americans (aOR = 1.7; 95% CI, 1.5-1.9; P < 0.001); Hispanics (aOR = 1.2; 95% CI, 1.1-1.4; P = 0.006); and NHOs (aOR = 1.2; 95% CI, 1.0-1.5; P = 0.05). CONCLUSIONS: Based on data from the Cesarean Registry, African American women had the highest odds of undergoing general anesthesia for CD compared with Caucasian women. It is uncertain whether this disparity exists in current obstetric practice.

Second-line uterotonics and the risk of hemorrhage-related morbidity.

OBJECTIVE: Uterine atony is a leading cause of postpartum hemorrhage. Although most cases of postpartum hemorrhage respond to first-line therapy with uterine massage and oxytocin administration, second-line uterotonics including methylergonovine and carboprost are integral for the management of refractory uterine atony. Despite their ubiquitous use, it is uncertain whether the risk of hemorrhage-related morbidity differs in women exposed to methylergonovine or carboprost at cesarean delivery. STUDY DESIGN: We performed a secondary analysis using the Maternal-Fetal Medicine Units Network Cesarean Registry. We identified women who underwent cesarean delivery and received either methylergonovine or carboprost for refractory uterine atony. The primary outcome was hemorrhage-related morbidity defined as intraoperative or postoperative red blood cell transfusion or the need for additional surgical interventions including uterine artery ligation, hypogastric artery ligation, or peripartum hysterectomy for atony. We compared the risk of hemorrhage-related morbidity in those exposed to methylergonovine vs carboprost. Propensity-score matching was used to account for potential confounders. RESULTS: The study cohort comprised 1335 women; 870 (65.2%) women received methylergonovine and 465 (34.8%) women received carboprost. After accounting for potential confounders, the risk of hemorrhage-related morbidity was higher in the carboprost group than the methylergonovine group (relative risk, 1.7; 95% confidence interval, 1.2-2.6). CONCLUSION: In this propensity score-matched analysis, methylergonovine was associated with reduced risk of hemorrhage-related morbidity during cesarean delivery compared to carboprost. Based on these results, methylergonovine may be a more effective second-line uterotonic.

Risk Factors for Prolonged Postpartum Length of Stay Following Cesarean Delivery.

OBJECTIVE: This study aims to identify risk factors for prolonged postpartum length of stays (LOS) after cesarean delivery (CD). STUDY DESIGN: Patients undergoing CD were sourced from a multicenter registry of 19 academic centers between 1999 and 2002 (n = 57,067). Prolonged postpartum LOS was defined as a hospitalization duration ≥ 90th centile. Maternal, antepartum, perioperative, and neonatal variables were compared between women with and without prolonged postpartum LOS. RESULTS: The 90th centile for postpartum LOS was 4 days, with 14,954 women experiencing prolonged postpartum LOS. Women with perioperative complications had the highest independent risk for a prolonged postpartum LOS: ileus (adjusted odds ratio [aOR] = 12.28; 95% confidence interval CI = 8.98-16.8); endometritis (aOR = 10.45; 95% CI = 9.51-11.5), and wound complications (aOR = 5.49; 95% CI = 4.54-6.63). Several antepartum, perioperative, and neonatal variables were associated with a prolonged postpartum LOS. CONCLUSION: Perioperative complications had the highest risk for prolonged LOS after CD. Strategies to reduce perioperative complications are needed to decrease the health care burden of prolonged post-CD LOS.

Prevalence, Demographic, and Clinical Factors Associated With Cognitive Dysfunction in Patients With Neuromyelitis Optica Spectrum Disorder.

BACKGROUND AND OBJECTIVES: Neuromyelitis optica spectrum disorder (NMOSD) is a chronic CNS demyelinating autoimmune disorder targeting the astrocyte antigen aquaporin-4 (AQP4), typically presenting with optic neuritis, transverse myelitis, and brain syndromes. Cognitive dysfunction (CD) in NMOSD is under-recognized and poorly understood. The purpose of this study was to evaluate the prevalence and clinical variables associated with CD in NMOSD. METHODS: This observational retrospective study with longitudinal follow-up describes a clinical cohort seen in the Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD. Serial Montreal Cognitive Assessments (MoCAs) were performed upon enrollment and at 6-month intervals to evaluate longitudinal cognitive function relative to demographic and disease-related factors. We used 2-tailed t test, analysis of variance, the χ2 test, linear regression for univariable and adjusted analyses and simultaneous linear regression and mixed-effects model for multivariable analyses. RESULTS: Thirty-four percent (75/219) of patients met criteria for CD (MoCA <26); 29% (64/219) showed mild dysfunction (MoCA 20-26/30), and 5% (11/219) showed moderate (MoCA <20/30) dysfunction. Patients with less neurologic disability and lower pain scores had higher MoCA scores (95% CI 0.24-0.65 and 95% CI 0.09-0.42, respectively). Patients with at least high school education scored higher on the MoCA (95% CI 2.2-5). When comparing patients dichotomized for CD, patients never on rituximab scored higher than patients only treated with rituximab (p < 0.029). There was no significant association between annualized relapse rate, age, sex, disease duration, AQP4 serostatus or brain lesions, and CD. CD was more pronounced among Black than White patients (95% CI -2.7 to -0.7). Multivariable analysis of serial MoCA did not indicate change (p = 0.715). Descriptive analysis of serial MoCA showed 30% (45/150) of patients with worsening MoCA performance had impaired language and verbal recall. DISCUSSION: To our knowledge, this is the largest study of diverse cohort to investigate CD in patients with NMOSD. Our findings demonstrate 34% of patients with NMOSD experience mild-to-moderate CD, while 30% of patients demonstrated decline on serial testing. The substantial prevalence of CD in this pilot report highlights the need for improved and validated screening tools and comprehensive measures to investigate CD in NMOSD.

Utility of capture-recapture methodology to assess completeness of amyotrophic lateral sclerosis case ascertainment.

BACKGROUND: With the establishment of a national amyotrophic lateral sclerosis (ALS) registry in the United States, methods are needed to ascertain the completeness of case ascertainment, especially in view of the proposal to rely largely on existing data sources. METHODS: Data about ALS patients residing in the 5-county metropolitan Atlanta area (within the State of Georgia) from 2001 to 2005 were categorized according to their source--ALS Association, clinical (Emory Healthcare, community neurologist, Veterans Health Administration, Veterans Benefits Administration), Medicare and death certificates. ALS diagnoses were verified using chart review. Capture-recapture analyses were carried out using log-linear modeling, stratified by age and race. RESULTS: The final model (based on 798 cases), which included the 4 main sources and 3 two-way interaction terms, yielded an estimated total population of 880 (95% CI 816-965), indicating that the combination of case-finding methods identified about 90.7% of cases. The estimated 5-year period prevalence is 38.5/100,000 (95% CI 35.66-42.19). CONCLUSION: This study highlights gaps in data based on existing data sources and illustrates a method for combining data from multiple sources to help facilitate the successful establishment of a US national ALS registry.

Prevalence of amyotrophic lateral sclerosis in the United States using established and novel methodologies, 2017.

Objective:To estimate the prevalence of amyotrophic lateral sclerosis (ALS) in the United States for 2017 using data from the National ALS Registry (Registry) as well as capture-recapture methodology to account for under-ascertainment. Established in 2010, the Registry collects and examines data on ALS patients in the US to better describe the epidemiology of ALS (i.e. risk factor exposures, demographics).Methods: The Registry compiled data from national administrative databases (from the Centers for Medicare and Medicaid Services, the Veterans Health Administration, and the Veterans Benefits Administration) and a voluntary enrollment data through a web portal (www.cdc.gov/als). To estimate the number of missing cases, capture-recapture methodology was utilized.Results: The Registry conservatively identified 17,800 adult persons (lower-bound estimate) who met the Registry definition of ALS for an age-adjusted prevalence of 5.5 per 100,000 US population. Using capture-recapture methodology, we obtained a "mean case count" of 24,821 ALS cases (prevalence of 7.7 per 100,000 U.S. population) and estimated the upper-bound estimate to be 31,843 cases (prevalence of 9.9 per 100,000 U.S. population). The pattern of patient characteristics (e.g. age, sex, and race/ethnicity) remained unchanged from previous Registry reports. Overall, ALS was most common among whites, males, and persons aged 60-69 years. The age groups with the lowest number of cases were persons aged 18-39 years. Males had a higher prevalence than females overall and across all data sources.Conclusions: Existing Registry methodology, along with capture-recapture methodology, are being used to better describe the epidemiology and demographics of ALS in the US.

Bringing Micro to the Macro: How Citizen Science Data Enrich Geospatial Visualizations to Advance Health Equity.

Social and spatial contexts affect health, and understanding nuances of context is key to informing successful interventions for health equity. Layering mixed methods and mixed scale data sources to visualize patterns of health outcomes facilitates analysis of both broad trends and person-level experiences across time and space. We used micro-scale citizen scientist-collected data from four Bay Area communities along with aggregate epidemiologic and population-level data sets to illustrate barriers to, and facilitators of, physical activity in low-income aging adults. These data integrations highlight the synergistic value added by combining data sources, and what might be missed by relying on either a micro- or macro-level data source alone. Mixed methods and granularity data integration can generate a deeper understanding of environmental context, which in turn can inform more relevant and attainable community, advocacy, and policy improvements.

Hybrid Controlled Clinical Trials Using Concurrent Registries in Amyotrophic Lateral Sclerosis: A Feasibility Study.

Hybrid designs with both randomized arms and an external control cohort preserve key features of randomization and utilize external information to augment clinical trials. In this study, we propose to leverage high-quality, patient-level concurrent registries to enhance clinical trials and illustrate the impact on trial design for amyotrophic lateral sclerosis. The proposed methodology was evaluated in a randomized, placebo-controlled clinical trial. We used patient-level information from a well-defined, population-based registry, that was running parallel to the randomized clinical trial, to identify concurrently nonparticipating, eligible patients who could be matched with trial participants, and integrate them into the statistical analysis. We assessed the impact of the addition of the external controls on the treatment effect estimate, precision, and time to reach a conclusion. During the runtime of the trial, a total of 1,141 registry patients were alive; 473 (41.5%) of them fulfilled the eligibility criteria and 133 (11.7%) were enrolled in the study. A matched control population could be identified among the nonparticipating patients. Augmenting the randomized controls with matched external controls could have avoided unnecessary randomization of 17 patients (-12.8%) as well as reducing the study duration from 30.1 months to 22.6 months (-25.0%). Matching eligible external controls from a different calendar period led to bias in the treatment effect estimate. Hybrid trial designs utilizing a concurrent registry with rigorous matching can minimize bias due to a mismatch in calendar time and differences in standard of care, and may accelerate the development of new treatments.

Population-Based Estimates for the Prevalence of Multiple Sclerosis in the United States by Race, Ethnicity, Age, Sex, and Geographic Region.

Importance: Racial, ethnic, and geographic differences in multiple sclerosis (MS) are important factors to assess when determining the disease burden and allocating health care resources. Objective: To calculate the US prevalence of MS in Hispanic, non-Hispanic Black (hereafter referred to as Black), and non-Hispanic White individuals (hereafter referred to as White) stratified by age, sex, and region. Design, Setting, and Participants: A validated algorithm was applied to private, military, and public (Medicaid and Medicare) administrative health claims data sets to identify adult cases of MS between 2008 and 2010. Data analysis took place between 2019 and 2022. The 3-year cumulative prevalence overall was determined in each data set and stratified by age, sex, race, ethnicity, and geography. The insurance pools included 96 million persons from 2008 to 2010. Insurance and stratum-specific estimates were applied to the 2010 US Census data and the findings combined to calculate the 2010 prevalence of MS cumulated over 10 years. No exclusions were made if a person met the algorithm criteria. Main Outcomes and Measurements: Prevalence of MS per 100 000 US adults stratified by demographic group and geography. The 95% CIs were approximated using a binomial distribution. Results: A total of 744 781 persons 18 years and older were identified with MS with 564 426 cases (76%) in females and 180 355 (24%) in males. The median age group was 45 to 54 years, which included 229 216 individuals (31%), with 101 271 aged 18 to 24 years (14%), 158 997 aged 35 to 44 years (21%), 186 758 aged 55 to 64 years (25%), and 68 539 individuals (9%) who were 65 years or older. White individuals were the largest group, comprising 577 725 cases (77%), with 80 276 Black individuals (10%), 53 456 Hispanic individuals (7%), and 33 324 individuals (4%) in the non-Hispanic other category. The estimated 2010 prevalence of MS per 100 000 US adults cumulated over 10 years was 161.2 (95% CI, 159.8-162.5) for Hispanic individuals (regardless of race), 298.4 (95% CI, 296.4-300.5) for Black individuals, 374.8 (95% CI, 373.8-375.8) for White individuals, and 197.7 (95% CI, 195.6-199.9) for individuals from non-Hispanic other racial and ethnic groups. During the same time period, the female to male ratio was 2.9 overall. Age stratification in each of the racial and ethnic groups revealed the highest prevalence of MS in the 45- to 64-year-old age group, regardless of racial and ethnic classification. With each degree of latitude, MS prevalence increased by 16.3 cases per 100 000 (95% CI, 12.7-19.8; P < .001) in the unadjusted prevalence estimates, and 11.7 cases per 100 000 (95% CI, 7.4-16.1; P < .001) in the direct adjusted estimates. The association of latitude with prevalence was strongest in women, Black individuals, and older individuals. Conclusions and Relevance: This study found that White individuals had the highest MS prevalence followed by Black individuals, individuals from other non-Hispanic racial and ethnic groups, and Hispanic individuals. Inconsistent racial and ethnic classifications created heterogeneity within groups. In the United States, MS affects diverse racial and ethnic groups. Prevalence of MS increases significantly and nonuniformly with latitude in the United States, even when adjusted for race, ethnicity, age, and sex. These findings are important for clinicians, researchers, and policy makers.

Cost-effectiveness of modern radiotherapy techniques in locally advanced pancreatic cancer.

BACKGROUND: Radiotherapy may improve the outcome of patients with pancreatic cancer but at an increased cost. In this study, the authors evaluated the cost-effectiveness of modern radiotherapy techniques in the treatment of locally advanced pancreatic cancer. METHODS: A Markov decision-analytic model was constructed to compare the cost-effectiveness of 4 treatment regimens: gemcitabine alone, gemcitabine plus conventional radiotherapy, gemcitabine plus intensity-modulated radiotherapy (IMRT); and gemcitabine with stereotactic body radiotherapy (SBRT). Patients transitioned between the following 5 health states: stable disease, local progression, distant failure, local and distant failure, and death. Health utility tolls were assessed for radiotherapy and chemotherapy treatments and for radiation toxicity. RESULTS: SBRT increased life expectancy by 0.20 quality-adjusted life years (QALY) at an increased cost of $13,700 compared with gemcitabine alone (incremental cost-effectiveness ratio [ICER] = $69,500 per QALY). SBRT was more effective and less costly than conventional radiotherapy and IMRT. An analysis that excluded SBRT demonstrated that conventional radiotherapy had an ICER of $126,800 per QALY compared with gemcitabine alone, and IMRT had an ICER of $1,584,100 per QALY compared with conventional radiotherapy. A probabilistic sensitivity analysis demonstrated that the probability of cost-effectiveness at a willingness to pay of $50,000 per QALY was 78% for gemcitabine alone, 21% for SBRT, 1.4% for conventional radiotherapy, and 0.01% for IMRT. At a willingness to pay of $200,000 per QALY, the probability of cost-effectiveness was 73% for SBRT, 20% for conventional radiotherapy, 7% for gemcitabine alone, and 0.7% for IMRT. CONCLUSIONS: The current results indicated that IMRT in locally advanced pancreatic cancer exceeds what society considers cost-effective. In contrast, combining gemcitabine with SBRT increased clinical effectiveness beyond that of gemcitabine alone at a cost potentially acceptable by today's standards.

Epidemiology of environmental exposures and human autoimmune diseases: findings from a National Institute of Environmental Health Sciences Expert Panel Workshop.

Autoimmune diseases (AID) are a collection of many complex disorders of unknown etiology resulting in immune responses to self-antigens and are thought to result from interactions between genetic and environmental factors. Here we review the epidemiologic evidence for the role of environmental factors in the development of human AID, the conclusions that can be drawn from the existing data, critical knowledge gaps, and research needed to fill these gaps and to resolve uncertainties. We specifically summarize the state of knowledge and our levels of confidence in the role of specific agents in the development of autoimmune diseases, and we define the areas of greatest impact for future investigations. Among our consensus findings we are confident that: 1) crystalline silica exposure can contribute to the development of several AID; 2) solvent exposure can contribute to the development of systemic sclerosis; 3) smoking can contribute to the development of seropositive rheumatoid arthritis; and 4) an inverse association exists between ultraviolet radiation exposure and the risk of development of multiple sclerosis. We suggest that more studies of phenotypes, genotypes, and multiple exposures are needed. Additional knowledge gaps needing investigation include: defining important windows in the timing of exposures and latencies relating to age, developmental state, and hormonal changes; understanding dose-response relationships; and elucidating mechanisms for disease development. Addressing these essential issues will require more resources to support research, particularly of rare AID, but knowledge of the risks conferred by environmental factors in specific genetic contexts could pave the way for prevention of AID in the future.