Lifetime Traumatic Brain Injury and Risk of Post-Concussive Symptoms in the Millennium Cohort Study.

Traumatic brain injury (TBI) is prevalent among active duty military service members, with studies reporting up to 23% experiencing at least one TBI, with 10-60% of service members reporting at least one subsequent repeat TBI. A TBI has been associated with an increased risk of cumulative effects and long-term neurobehavioral symptoms, impacting operational readiness in the short-term and overall health in the long term. The association between multiple TBI and post-concussive symptoms (PCS), however, defined as symptoms that follow a concussion or TBI, in the military has not been adequately examined. Previous studies in military populations are limited by methodological issues including small sample sizes, the use of non-probability sampling, or failure to include the total number of TBI. To overcome these limitations, we examined the association between the total lifetime number of TBI and total number of PCS among U.S. active duty military service members who participated in the Millennium Cohort Study. A secondary data analysis was conducted using the Millennium Cohort Study's 2014 survey (n = 28,263) responses on self-reported TBI and PCS (e.g., fatigue, restlessness, sleep disturbances, poor concentration, or memory loss). Zero-inflated negative binomial models calculated prevalence ratios (PRs) and 95% confidence intervals (CIs) for the unadjusted and adjusted associations between lifetime TBIs and PCS. A third of military participants reported experiencing one or more TBIs during their lifetime with 72% reporting at least one PCS. As the mean number of PCS increased, mean lifetime TBIs increased. The mean number of PCS by those with four or more TBI (4.63) was more than twice that of those with no lifetime TBI (2.28). One, two, three, and four or more TBI had 1.10 (95% CI: 1.06-1.15), 1.19 (95% CI: 1.14-1.25), 1.23 (95% CI: 1.17-1.30), and 1.30 times (95% CI: 1.24-1.37) higher prevalence of PCS, respectively. The prevalence of PCS was 2.4 (95% CI: 2.32-2.48) times higher in those with post-traumatic stress disorder than their counterparts. Active duty military service members with a history of TBI are more likely to have PCS than those with no history of TBI. These results suggest an elevated prevalence of PCS as the number of TBI increased. This highlights the need for robust, longitudinal studies that can establish a temporal relationship between repetitive TBI and incidence of PCS. These findings have practical relevance for designing both workplace safety prevention measures and treatment options regarding the effect on and from TBI among military personnel.

Strokes Averted by Intravenous Thrombolysis: A Secondary Analysis of a Prospective, Multicenter, Controlled Trial of Mobile Stroke Units.

OBJECTIVE: This study was undertaken to examine averted stroke in optimized stroke systems. METHODS: This secondary analysis of a multicenter trial from 2014 to 2020 compared patients treated by mobile stroke unit (MSU) versus standard management. The analytical cohort consisted of participants with suspected stroke treated with intravenous thrombolysis. The main outcome was a tissue-defined averted stroke, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis and no acute infarction/hemorrhage on imaging. An additional outcome was stroke with early symptom resolution, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis. RESULTS: Among 1,009 patients with a median last known well to thrombolysis time of 87 minutes, 159 (16%) had tissue-defined averted stroke and 276 (27%) had stroke with early symptom resolution. Compared with standard management, MSU care was associated with more tissue-defined averted stroke (18% vs 11%, adjusted odds ratio [aOR] = 1.82, 95% confidence interval [CI] = 1.13-2.98) and stroke with early symptom resolution (31% vs 21%, aOR = 1.74, 95% CI = 1.12-2.61). The relationships between thrombolysis treatment time and averted/early recovered stroke appeared nonlinear. Most models indicated increased odds for stroke with early symptom resolution but not tissue-defined averted stroke with earlier treatment. Additionally, younger age, female gender, hyperlipidemia, lower National Institutes of Health Stroke Scale, lower blood pressure, and no large vessel occlusion were associated with both tissue-defined averted stroke and stroke with early symptom resolution. INTERPRETATION: In optimized stroke systems, 1 in 4 patients treated with thrombolysis recovered within 24 hours and 1 in 6 had no demonstrable brain injury on imaging. ANN NEUROL 2024;95:347-361.

The 18-year risk of cancer, angioedema, insomnia, depression, and erectile dysfunction in association with antihypertensive drugs: post-trial analyses from ALLHAT-Medicare linked data.

Purpose: This study aimed to determine the 18-year risk of cancer, angioedema, insomnia, depression, and erectile dysfunction in association with antihypertensive drug use. Methods: This is a post-trial passive follow-up study of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants between 1994 and 1998 that was conducted by linking their follow-up data with Medicare claims data until 2017 of subjects who were free of outcomes at baseline on 1 January 1999. The main outcomes were the occurrence of cancer (among n = 17,332), angioedema (among n = 17,340), insomnia (among n = 17,340), depression (among n = 17,330), and erectile dysfunction (among n = 7,444 men) over 18 years of follow-up. Results: The 18-year cumulative incidence rate of cancer other than non-melanoma skin cancer from Medicare inpatient claims was 23.9% for chlorthalidone, 23.4% for amlodipine, and 25.3% for lisinopril. There were no statistically significant differences in the 18-year risk of cancer, depression, and erectile dysfunction among the three drugs based on the adjusted hazard ratios. The adjusted 18-year risk of angioedema was elevated in those receiving lisinopril than in those receiving amlodipine (hazard ratio: 1.63, 95% CI: 1.14-2.33) or in those receiving chlorthalidone (1.33, 1.00-1.79), whereas the adjusted 18-year risk of insomnia was statistically significantly decreased in those receiving lisinopril than in those receiving amlodipine (0.90, 0.81-1.00). Conclusions: The 18-year risk of angioedema was significantly higher in patients receiving lisinopril than in those receiving amlodipine or chlorthalidone; the risk of insomnia was significantly lower in patients receiving lisinopril than in those receiving amlodipine; and the risk of cancer, depression, and erectile dysfunction (in men) was not statistically significantly different among the three drug groups.

Mortality and Morbidity Among Individuals With Hypertension Receiving a Diuretic, ACE Inhibitor, or Calcium Channel Blocker: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The long-term relative risk of antihypertensive treatments with regard to mortality and morbidity is not well understood. Objective: To determine the long-term posttrial risk of primary and secondary outcomes among trial participants who were randomized to either a thiazide-type diuretic, calcium channel blocker (CCB), or angiotensin-converting enzyme (ACE) inhibitor with up to 23 years of follow-up. Design, Setting, and Participants: This prespecified secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a multicenter randomized, double-blind, active-controlled clinical trial, followed up with participants aged 55 years or older with a diagnosis of hypertension and at least 1 other coronary heart disease risk factor for up to 23 years, from February 23, 1994, to December 31, 2017. Trial participants were linked with administrative databases for posttrial mortality (N = 32 804) and morbidity outcomes (n = 22 754). Statistical analysis was performed from January 2022 to October 2023. Interventions: Participants were randomly assigned to receive a thiazide-type diuretic (n = 15 002), a CCB (n = 8898), or an ACE inhibitor (n = 8904) for planned in-trial follow-up of approximately 4 to 8 years and posttrial passive follow-up for up to 23 years. Main Outcomes and Measures: The primary end point was mortality due to cardiovascular disease (CVD). Secondary outcomes included all-cause mortality, combined fatal and nonfatal (morbidity) CVD, and both mortality and morbidity for coronary heart disease, stroke, heart failure, end-stage renal disease, and cancer. Results: A total of 32 804 participants (mean [SD] age, 66.9 [7.7] years; 17 411 men [53.1%]; and 11 772 Black participants [35.9%]) were followed up for all-cause mortality and a subgroup of 22 754 participants (mean [SD] age, 68.7 [7.2] years; 12 772 women [56.1%]; and 8199 Black participants [36.0%]) were followed up for fatal or nonfatal CVD through 2017 (mean [SD] follow-up, 13.7 [6.7] years; maximum follow-up, 23.9 years). Cardiovascular disease mortality rates per 100 persons were 23.7, 21.6, and 23.8 in the diuretic, CCB, and ACE inhibitor groups, respectively, at 23 years after randomization (adjusted hazard ratio [AHR], 0.97 [95% CI, 0.89-1.05] for CCB vs diuretic; AHR, 1.06 [95% CI, 0.97-1.15] for ACE inhibitor vs diuretic). The long-term risks of most secondary outcomes were similar among the 3 groups. Compared with the diuretic group, the ACE inhibitor group had a 19% increased risk of stroke mortality (AHR, 1.19 [95% CI, 1.03-1.37]) and an 11% increased risk of combined fatal and nonfatal hospitalized stroke (AHR, 1.11 [95% CI, 1.03-1.20]). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial in an adult population with hypertension and coronary heart disease risk factors, CVD mortality was similar between all 3 groups. ACE inhibitors increased the risk of stroke outcomes by 11% compared with diuretics, and this effect persisted well beyond the trial period. Trial Registration: ClinicalTrials.gov Identifier: NCT00000542.

Outcomes of patients with pre-existing disability managed by mobile stroke units: A sub-analysis of the BEST-MSU study.

BACKGROUND: Few data exist on acute stroke treatment in patients with pre-existing disability (PD) since they are usually excluded from clinical trials. A recent trial of mobile stroke units (MSUs) demonstrated faster treatment and improved outcomes, and included PD patients. AIM: To determine outcomes with tissue plasminogen activator (tPA), and benefit of MSU versus management by emergency medical services (EMS), for PD patients. METHODS: Primary outcomes were utility-weighted modified Rankin Scale (uw-mRS). Linear and logistic regression models compared outcomes in patients with versus without PD, and PD patients treated by MSU versus standard management by EMS. Time metrics, safety, quality of life, and health-care utilization were compared. RESULTS: Of the 1047 tPA-eligible ischemic stroke patients, 254 were with PD (baseline mRS 2-5) and 793 were without PD (baseline mRS 0-1). Although PD patients had worse 90-day uw-mRS, higher mortality, more health-care utilization, and worse quality of life than non-disabled patients, 53% returned to at least their baseline mRS, those treated faster had better outcome, and there was no increased bleeding risk. Comparing PD patients treated by MSU versus EMS, 90-day uw-mRS was 0.42 versus 0.36 (p = 0.07) and 57% versus 46% returned to at least their baseline mRS. There was no interaction between disability status and MSU versus EMS group assignment (p = 0.67) for 90-day uw-mRS. CONCLUSION: PD did not prevent the benefit of faster treatment with tPA in the BEST-MSU study. Our data support inclusion of PD patients in the MSU management paradigm.

Integrating, Harmonizing, and Curating Studies With High-Frequency and Hourly Physiological Data: Proof of Concept from Seven Traumatic Brain Injury Data Sets.

Research in severe traumatic brain injury (TBI) has historically been limited by studies with relatively small sample sizes that result in low power to detect small, yet clinically meaningful outcomes. Data sharing and integration from existing sources hold promise to yield larger more robust sample sizes that improve the potential signal and generalizability of important research questions. However, curation and harmonization of data of different types and of disparate provenance is challenging. We report our approach and experience integrating multiple TBI data sets containing collected physiological data, including both expected and unexpected challenges encountered in the integration process. Our harmonized data set included data on 1536 patients from the Citicoline Brain Injury Treatment Trial (COBRIT), Effect of erythropoietin and transfusion threshold on neurological recovery after traumatic brain injury: a randomized clinical trial (EPO Severe TBI), BEST-TRIP, Progesterone for the Treatment of Traumatic Brain Injury III Clinical Trial (ProTECT III), Transforming Research and Clinical Knowledge in Traumatic brain Injury (TRACK-TBI), Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase-II (BOOST-2), and Ben Taub General Hospital (BTGH) Research Database studies. We conclude with process recommendations for data acquisition for future prospective studies to aid integration of these data with existing studies. These recommendations include using common data elements whenever possible, a standardized recording system for labeling and timing of high-frequency physiological data, and secondary use of studies in systems such as Federal Interagency Traumatic Brain Injury Research Informatics System (FITBIR), to engage investigators who collected the original data.

Golden Hour Treatment With tPA (Tissue-Type Plasminogen Activator) in the BEST-MSU Study.

BACKGROUND: Treatment of patients with acute ischemic stroke on mobile stroke units (MSUs) improves outcomes compared with management by standard emergency medical services ambulances and is associated with more patients treated with intravenous tPA (tissue-type plasminogen activator) in the first golden hour after last known normal. We explored the predictors and outcomes of first-hour treatment (FHT) compared with later treatment in an alternating-week cluster-controlled trial of MSUs. METHODS: We analyzed all patients treated with intravenous tPA in the BEST-MSU Study (Benefits of Stroke Treatment Delivered by a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services). After stratifying by treatment timeframe, we identified factors associated with FHT. We performed adjusted analyses of the association between FHT and clinical outcome and modeled the shape of the relationship between last known normal-to-treatment time and excellent outcome. RESULTS: Among 941 tPA-treated patients, 206 (21.8%) had lytic started within 60 minutes. Treatment on the MSU, older age, male sex, alert by 911, faster arrival on-scene and imaging, more severe stroke, atrial fibrillation, and absence of heart failure and pretreatment antihypertensive treatment were associated with FHT. Compared with later treatment, FHT was associated with higher adjusted odds ratio for 90-day modified Rankin Scale score of 0 to 1 (odds ratio, 1.87 [95% CI, 1.25-2.84]; P=0.003). Among FHT patients, 68% achieved a 90-day modified Rankin Scale of 0 or 1 or returned to their baseline status. FHT was not associated with higher risk of hemorrhage and was associated with reduced risk of treating neurovascular mimics. CONCLUSIONS: FHT almost doubles the odds of excellent clinical outcome without increased risk compared with later treatment, which supports the use of MSUs.

Occupation and Risk of Traumatic Brain Injury in the Millennium Cohort Study.

INTRODUCTION: Traumatic brain injury (TBI) is an occupational health hazard of military service. Few studies have examined differences in military occupational categories (MOC) which take into consideration the physical demands and job requirements across occupational groups. METHODS: This study was approved by the University of Texas Health Science Center at Houston Institutional Review Board. Data for this cross-sectional study were obtained from the Naval Health Research Center's Millennium Cohort Study, an ongoing DoD study. Univariate analyses were employed to calculate frequencies and proportions for all variables. Bivariate analyses included unadjusted odds ratios (OR) and 95% CI for the association between all variables and TBI. Multivariable logistic regression was used to calculate adjusted ORs and 95% CIs to assess the association between MOC and TBI, adjusted for potential confounders: sex, race/ethnicity, rank, military status, branch of service, before-service TBI, and panel. Logistic regression models estimated odds of TBI for each MOC, and stratified models estimated odds separately for enlisted and officer MOCs. RESULTS: Approximately 27% of all participants reported experiencing a service-related TBI. All MOCs were statistically significantly associated with increased odds of service-related TBI, with a range of 16 to 45%, except for "Health Care" MOCs (OR: 1.01, 95% CI 0.91-1.13). Service members in "Infantry/Tactical Operations" had the highest odds (OR: 1.45, 95% CI 1.31-1.61) of service-related TBI as compared to "Administration & Executives." Among enlisted service members, approximately 28% reported experiencing a service-related TBI. Among enlisted-specific MOCs, the odds of TBI were elevated for those serving in "Infantry, Gun Crews, Seamanship (OR: 1.79, 95% CI 1.58-2.02)," followed by "Electrical/Mechanical Equipment Repairers (OR: 1.23, 95% CI 1.09-1.38)," "Service & Supply Handlers (OR 1.21, 95% CI 1.08-1.37)," "Other Technical & Allied Specialists (OR 1.21, 95% CI 1.02-1.43)," "Health Care Specialists (OR 1.19, 95% CI 1.04-1.36)," and "Communications & Intelligence (OR: 1.16, 95% CI 1.02-1.31)," compared to "Functional Support & Administration." Among officer service members, approximately 24% reported experiencing a service-related TBI. After adjustment the odds of TBI were found to be significant for those serving as "Health Care Officers" (OR: 0.65, 95% CI: 0.52-0.80) and "Intelligence Officers" (OR: 1.27, 95% CI: 1.01-1.61). CONCLUSIONS: A strength of this analysis is the breakdown of MOC associations with TBI stratified by enlisted and officer ranks, which has been previously unreported. Given the significantly increased odds of service-related TBI reporting within enlisted ranks, further exploration into the location (deployed versus non-deployed) and mechanism (e.g., blast, training, sports, etc.) for these injuries is needed. Understanding injury patterns within these military occupations is necessary to increase TBI identification, treatment, and foremost, prevention.Results highlight the importance of examining specific occupational categories rather than relying on gross categorizations, which do not account for shared knowledge, skills, and abilities within occupations. The quantification of risk among enlisted MOCs suggests a need for further research into the causes of TBI.

Design for a cluster randomized controlled trial to evaluate the effects of the CATCH Healthy Smiles school-based oral health promotion intervention among elementary school children.

Background: The top two oral diseases (tooth decay and gum disease) are preventable, yet dental caries is the most common childhood disease with 68% of children entering kindergarten having tooth decay. CATCH Healthy Smiles is a coordinated school health program to prevent cavities for students in kindergarten, 1st, and 2nd grade, and is based on the framework of Coordinated Approach to Child Health (CATCH), an evidence-based coordinated school health program. CATCH has undergone several cluster-randomized controlled trials (CRCT) demonstrating sustainable long-term effectiveness in incorporating the factors surrounding children, in improving eating and physical activity behaviors, and reductions in obesity prevalence among low-income, ethnically diverse children. The aim of this paper is to describe the design of the CATCH Healthy Smiles CRCT to determine the effectiveness of an oral health school-based behavioral intervention in reducing incidence of dental caries among children. Methods: In this CRCT, 30 schools serving low-income, ethnically-diverse children in greater Houston area are recruited and randomized into intervention and comparison groups. From which, 1020 kindergarten children (n = 510 children from 15 schools for each group) will be recruited and followed through 2nd grade. The intervention consists of four components (classroom curriculum, toothbrushing routine, family outreach, and schoolwide coordinated activities) will be implemented for three years in the intervention schools, whereas the control schools will be offered free trainings and materials to implement a sun safety curriculum in the meantime. Outcome evaluation will be conducted at four time points throughout the study period, each consists of three components: dental assessment, child anthropometric measures, and parent survey. The dental assessment will use International Caries Detection and Assessment System (ICDAS) to measures the primary outcome of this study: incidence of dental caries in primary teeth as measured at the tooth surface level (dfs). The parent self-report survey measures secondary outcomes of this study, such as oral health related behavioral and psychosocial factors. A modified crude caries increment (mCCI) will be used to calculate the primary outcome of the CATCH Healthy Smiles CRCT, and a two-tailed test of the null hypothesis will be conducted to evaluate the intervention effect, while considering between- and within-cluster variances through computing the weighted-average of the mCCI ratios by cluster. Conclusion: If found to be effective, a platform for scalability, sustainability and dissemination of CATCH already exists, and opens a new line of research in school oral health. Clinical trials identifier: At ClinicalTrials.gov - NCT04632667.

Case growth analysis to inform local response to COVID-19 epidemic in a diverse U.S community.

Early detection of new outbreak waves is critical for effective and sustained response to the COVID-19 pandemic. We conducted a growth rate analysis using local community and inpatient records from seven hospital systems to characterize distinct phases in SARS-CoV-2 outbreak waves in the Greater Houston area. We determined the transition times from rapid spread of infection in the community to surge in the number of inpatients in local hospitals. We identified 193,237 residents who tested positive for SARS-CoV-2 via molecular testing from April 8, 2020 to June 30, 2021, and 30,031 residents admitted within local healthcare institutions with a positive SARS-CoV-2 test, including emergency cases. We detected two distinct COVID-19 waves: May 12, 2020-September 6, 2020 and September 27, 2020-May 15, 2021; each encompassed four growth phases: lagging, exponential/rapid growth, deceleration, and stationary/linear. Our findings showed that, during early stages of the pandemic, the surge in the number of daily cases in the community preceded that of inpatients admitted to local hospitals by 12-36 days. Rapid decline in hospitalized cases was an early indicator of transition to deceleration in the community. Our real-time analysis informed local pandemic response in one of the largest U.S. metropolitan areas, providing an operationalized framework to support robust real-world surveillance for outbreak preparedness.

Trends and Correlates of Breakthrough Infections With SARS-CoV-2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta variant has been hypothesized to decrease the efficacy of COVID-19 vaccines. Factors associated with infections with SARS-CoV-2 after vaccination are unknown. In this observational cohort study, we examined two groups in Harris County, Texas: (1) individuals with positive Nucleic Acid Amplification test between 12/14/2020 and 9/30/2021 and (2) the subset of individuals fully vaccinated in the same time period. Infected individuals were classified as a breakthrough if their infection occurred 14 days after their vaccination had been completed. Among fully vaccinated individuals, demographic and vaccine factors associated with breakthrough infections were assessed. Of 146,731 positive SARS-CoV-2 tests, 7.5% were breakthrough infections. Correlates of breakthrough infection included young adult age, female, White race, and receiving the Janssen vaccine, after adjustments including the amount of community spread at the time of infection. Vaccines remained effective in decreasing the probability of testing positive for SARS-CoV-2. The data indicate that increased vaccine booster uptake would help decrease new infections.

How Frequent is the One-Hour tPA Infusion Interrupted or Delayed?

BACKGROUND AND PURPOSE: Tissue plasminogen activator (tPA) requires a one-hour infusion after the bolus. The frequency of delay or interruption of the tPA infusion may be useful in weighing the advantages of Tenecteplase (TNKase, TNK) which does not require an infusion. METHODS: Utilizing the Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services study database, we calculated the frequency and magnitude of tPA infusion delay or interruption. RESULTS: Of 497 patients treated with tPA on the Houston Mobile Stroke Unit (MSU), 41 (8.3%) had delay or interruption of the infusion for reasons that did not reflect a side effect of, or contraindication to, tPA. Nine received less than 90% of their calculated dose (median 62%, range 28-88%), and eleven had more than a 10% prolongation of their infusion (median 19 min, range 7-210 min). Six patients (1.2%) had infusion stopped for a valid concern for tPA side effect or contraindication. CONCLUSIONS: Interruption or discontinuation of the tPA infusion occurs in 8% of patients treated on a MSU providing an opportunity for more complete and faster treatment with TNK.

Hemorrhage Enlargement Is More Frequent in the First 2 Hours: A Prehospital Mobile Stroke Unit Study.

BACKGROUND: Hematoma enlargement (HE) after intracerebral hemorrhage (ICH) is a therapeutic target for improving outcomes. Hemostatic therapies to prevent HE may be more effective the earlier they are attempted. An understanding of HE in first 1 to 2 hours specifically in the prehospital setting would help guide future treatment interventions in this time frame and setting. METHODS: Patients with spontaneous ICH within 4 hours of symptom onset were prospectively evaluated between May 2014 and April 2020 as a prespecified substudy within a multicenter trial of prehospital mobile stroke unit versus standard management. Baseline computed tomography scans obtained <1, 1 to 2, and 2 to 4 hours postsymptom onset on the mobile stroke unit in the prehospital setting were compared with computed tomography scans repeated 1 hour later and at 24 hours in the hospital. HE was defined as >6 mL if baseline ICH volume was <20 mL and 33% increase if baseline volume >20 mL. The association between time from symptom onset to baseline computed tomography (hours) and HE was investigated using Wilcoxon rank-sum test when time was treated as a continuous variable and using Fisher exact test when time was categorized. Kruskal-Wallis and Wilcoxon rank-sum tests evaluated differences in baseline volumes and HE. Univariable and multivariable logistic regression analyses were conducted to identify factors associated with HE and variable selection was performed using cross-validated L1-regularized (Lasso regression). This study adhered to STROBE guidelines (Strengthening the Reporting of Observational Studies in Epidemiology) for cohort studies. RESULTS: One hundred thirty-nine patients were included. There was no difference between baseline ICH volumes obtained <1 hour (n=43) versus 1 to 2 hour (n=51) versus >2 hours (n=45) from symptom onset (median [interquartile range], 13 mL [6-24] versus 14 mL [6-30] versus 12 mL [4-19]; P=0.65). However, within the same 3 time epochs, initial hematoma growth (volume/time from onset) was greater with earlier baseline scanning (median [interquartile range], 17 mL/hour [9-35] versus 9 mL/hour [5-23]) versus 4 mL/hour [2-7]; P<0.001). Forty-nine patients had repeat scans 1 hour after baseline imaging (median, 2.3 hours [interquartile range. 1.9-3.1] after symptom onset). Eight patients (16%) had HE during that 1-hour interval; all of these occurred in patients with baseline imaging within 2 hours of onset (5/18=28% with baseline imaging within 1 hour, 3/18=17% within 1-2 hour, 0/13=0% >2 hours; P=0.02). HE did not occur between the scans repeated at 1 hour and 24 hours. No association between baseline variables and HE was detected in multivariable analyses. CONCLUSIONS: HE in the next hour occurs in 28% of ICH patients with baseline imaging within the first hour after symptom onset, and in 17% of those with baseline imaging between 1 and 2 hours. These patients would be a target for ultraearly hemostatic intervention.

Association of Gulf War Illness-Related Symptoms with Military Exposures among 1990-1991 Gulf War Veterans Evaluated at the War-Related Illness and Injury Study Center (WRIISC).

Veterans with difficult-to-diagnose conditions who receive care in the Department of Veterans Affairs (VA) healthcare system can be referred for evaluation at one of three specialty VA War-Related Illness and Injury Study Centers (WRIISC). Veterans of the 1990−1991 Gulf War have long experienced excess rates of chronic symptoms associated with the condition known as Gulf War Illness (GWI), with hundreds evaluated at the WRIISC. Here we provide the first report from a cohort of 608 Gulf War Veterans seen at the WRIISC who completed questionnaires on chronic symptoms (>6 months) consistent with GWI as well as prominent exposures during Gulf War deployment. These included veterans' reports of hearing chemical alarms/donning Military-Ordered Protective Posture Level 4 (MOPP4) gear, pesticide use, and use of pyridostigmine bromide (PB) pills as prophylaxis against the effects of nerve agents. Overall, veterans in the cohort were highly symptomatic and reported a high degree of exposures. In multivariable models, these exposures were significantly associated with moderate-to-severe chronic symptoms in neurocognitive/mood, fatigue/sleep, and pain domains. Specifically, exposure to pesticides was associated with problems with concentration and memory, problems sleeping, unrefreshing sleep, and joint pain. Use of MOPP4 was associated with light sensitivity and unrefreshing sleep and use of PB was associated with depression. We also evaluated the association of exposures with symptom summary scores based on veterans' severity of symptoms in four domains and overall. In multivariable modeling, the pain symptom severity score was significantly associated with pesticide use (Odds ratio (OR): 4.13, 95% confidence intervals (CI): 1.78−9.57) and taking PB pills (OR: 2.28, 95% CI: 1.02−5.09), and overall symptom severity was significantly associated with use of PB pills (OR: 2.41, 95% CI: 1.01−5.75). Conclusion: Decades after deployment, Gulf War veterans referred to a VA tertiary evaluation center report a high burden of chronic symptoms, many of which were associated with reported neurotoxicant exposures during the war.

Comparison of Mobile Stroke Unit With Usual Care for Acute Ischemic Stroke Management: A Systematic Review and Meta-analysis.

IMPORTANCE: So far, uncertainty remains as to whether there is sufficient cumulative evidence that mobile stroke unit (MSU; specialized ambulance equipped with computed tomography scanner, point-of-care laboratory, and neurological expertise) use leads to better functional outcomes compared with usual care. OBJECTIVE: To determine with a systematic review and meta-analysis of the literature whether MSU use is associated with better functional outcomes in patients with acute ischemic stroke (AIS). DATA SOURCES: MEDLINE, Cochrane Library, and Embase from 1960 to 2021. STUDY SELECTION: Studies comparing MSU deployment and usual care for patients with suspected stroke were eligible for analysis, excluding case series and case-control studies. DATA EXTRACTION AND SYNTHESIS: Independent data extraction by 2 observers, following the PRISMA and MOOSE reporting guidelines. The risk of bias in each study was determined using the ROBINS-I and RoB2 tools. In the case of articles with partially overlapping study populations, unpublished disentangled results were obtained. Data were pooled in random-effects meta-analyses. MAIN OUTCOMES AND MEASURES: The primary outcome was excellent outcome as measured with the modified Rankin Scale (mRS; score of 0 to 1 at 90 days). RESULTS: Compared with usual care, MSU use was associated with excellent outcome (adjusted odds ratio [OR], 1.64; 95% CI, 1.27-2.13; P < .001; 5 studies; n = 3228), reduced disability over the full range of the mRS (adjusted common OR, 1.39; 95% CI, 1.14-1.70; P = .001; 3 studies; n = 1563), good outcome (mRS score of 0 to 2: crude OR, 1.25; 95% CI, 1.09-1.44; P = .001; 6 studies; n = 3266), shorter onset-to-intravenous thrombolysis (IVT) times (median reduction, 31 minutes [95% CI, 23-39]; P < .001; 13 studies; n = 3322), delivery of IVT (crude OR, 1.83; 95% CI, 1.58-2.12; P < .001; 7 studies; n = 4790), and IVT within 60 minutes of symptom onset (crude OR, 7.71; 95% CI, 4.17-14.25; P < .001; 8 studies; n = 3351). MSU use was not associated with an increased risk of all-cause mortality at 7 days or at 90 days or with higher proportions of symptomatic intracranial hemorrhage after IVT. CONCLUSIONS AND RELEVANCE: Compared with usual care, MSU use was associated with an approximately 65% increase in the odds of excellent outcome and a 30-minute reduction in onset-to-IVT times, without safety concerns. These results should help guideline writing committees and policy makers.

Prevalence and Financial Burden of Digestive Diseases in a Commercially Insured Population.

BACKGROUND & AIMS: Digestive diseases represent a diverse group of clinical conditions that impact the population. Their heterogeneity in classification, presentation, acuity, chronicity, and need for drug therapy presents a challenge when comparing and contrasting the burden associated with these conditions. Prior studies use an outdated classification system and aggregate costs at the population level or focus on specific diseases, limiting the ability to characterize the overall landscape. Our aim was to provide the most up-to-date assessment of cost, utilization, and prevalence associated with digestive diseases. METHODS: We examined digestive disease claims and payment data for a commercially insured adult population between 2016 and 2018 to provide a comprehensive summary of costs, utilization, and prevalence across 38 conditions. Outcome variables included point prevalence and relative prevalence, annualized all-cause medical and drug costs, digestive disease-specific average medical cost, digestive disease-specific cost per fill, and utilization by clinical setting and by clinical condition. RESULTS: A total of 7,297,435 individuals with a digestive disease diagnosis were included in the study. The point prevalence of having a digestive disease in the total population was 24%. Annualized total costs by clinical category ranged from $10,038 (eosinophilic esophagitis) to $107,007 (hepatitis C), with medical costs accounting for most of the expenditures in a majority of conditions. Annualized total costs for common conditions included $39,653 for alcoholic liver disease, $42,554 for acute pancreatitis, $62,735 for Crohn's disease, $13,948 for functional gastrointestinal disorders, $53,214 for nonalcoholic cirrhosis, and $36,441 for ulcerative colitis. Average cost of inpatient stays ranged from $12,218 (noninfectious gastroenteritis/colitis) to $78,259 (nonalcoholic steatohepatitis). Outpatient visits ranged from $784 (gastrointestinal infection) to $4629 (gallbladder and biliary tract disease). Average drug cost per fill ranged from $83 (gastroesophageal reflux disease) to $1458 (hepatitis C). A total of 27,429,046 clinical encounters occurred across all conditions during the study period, with 90% taking place as outpatient visits. Abdominal pain was the single largest contributor to outpatient visits and emergency department to home encounters. Inpatient stays were considerably more heterogeneous, with no condition accounting for more than 12% (gallbladder and biliary tract disease) of the total. CONCLUSIONS: The results demonstrate digestive diseases are common, heterogeneous in cost and utilization, and collectively exact a significant financial burden on the U.S. adult population.

Development and Feasibility Testing of CATCH Healthy Smiles, an Oral Health Promotion Intervention for Prevention of Dental Caries Among Elementary School Children.

BACKGROUND: We present results of the development and feasibility testing of CATCH Healthy Smiles, a school-based oral health program, among children in grades K-2 in Houston, Texas. METHODS: Study design was cross-sectional (N = 2 schools; N = 125 parent-child dyads; 31 kindergarteners, 42 first graders, and 52 second graders). CATCH Healthy Smiles program was implemented by trained school teachers in the 2016-2017 school year. Trained dentists conducted dental assessments to measure dental caries increment score (d3mfs). Parent-reported 24-hour dietary recalls and surveys assessed child and parent behavioral, environmental, and psychosocial factors. Logistic regression analysis assessed factors associated with caries experience adjusting for covariates. RESULTS: Of the 113 children with complete dental assessments, 54% children in grade K, 62% in first grade, and 73% in second grade had caries experience. Children with caries experience had a higher body weight (AdjOR = 1.13, 95% confidence interval [CI]: 1.02-1.29), were less likely to be girls (AdjOR = 0.22, 95% CI: 0.05-0.82), had greater odds of difficulty drinking hot or cold beverages because of dental problems (AdjOR = 13.13, 95% CI: 1.09-275.14), greater frequency of consuming sugar-sweetened beverages (AdjOR = 11.53, 95% CI: 2.10-87.19), greater odds of receiving government assistance (AdjOR = 14.62, 95% CI: 2.74-119.81), and lower odds of seeing a dental provider (AdjOR = 0.11, 95% CI: 0.02-0.45). Process evaluation showed that 100% of the CATCH Healthy Smiles lessons and activities were taught in the two schools with a high degree of program fidelity and acceptability across the schools, children, and parents. CONCLUSIONS: These data will be used to conduct a subsequent fully powered cluster randomized controlled trial.

Machine Learning Automated Detection of Large Vessel Occlusion From Mobile Stroke Unit Computed Tomography Angiography.

BACKGROUND: Prehospital automated large vessel occlusion (LVO) detection in Mobile Stroke Units (MSUs) could accelerate identification and treatment of patients with LVO acute ischemic stroke. Here, we evaluate the performance of a machine learning (ML) model on CT angiograms (CTAs) obtained from 2 MSUs to detect LVO. METHODS: Patients evaluated on MSUs in Houston and Los Angeles with out-of-hospital CTAs were identified. Anterior circulation LVO was defined as an occlusion of the intracranial internal carotid artery, middle cerebral artery (M1 or M2), or anterior cerebral artery vessels and determined by an expert human reader. A ML model to detect LVO was trained and tested on independent data sets consisting of in-hospital CTAs and then tested on MSU CTA images. Model performance was determined using area under the receiver-operator curve statistics. RESULTS: Among 68 patients with out-of-hospital MSU CTAs, 40% had an LVO. The most common occlusion location was the middle cerebral artery M1 segment (59%), followed by the internal carotid artery (30%), and middle cerebral artery M2 (11%). Median time from last known well to CTA imaging was 88.0 (interquartile range, 59.5-196.0) minutes. After training on 870 in-hospital CTAs, the ML model performed well in identifying LVO in a separate in-hospital data set of 441 images with area under receiver-operator curve of 0.84 (95% CI, 0.80-0.87). ML algorithm analysis time was under 1 minute. The performance of the ML model on the MSU CTA images was comparable with area under receiver-operator curve 0.80 (95% CI, 0.71-0.89). There was no significant difference in performance between the Houston and Los Angeles MSU CTA cohorts. CONCLUSIONS: In this study of patients evaluated on MSUs in 2 cities, a ML algorithm was able to accurately and rapidly detect LVO using prehospital CTA acquisitions.

Retrospectively Collected EQ-5D-5L Data as Valid Proxies for Imputing Missing Information in Longitudinal Studies.

OBJECTIVES: Studies face challenges with missing 5-level EQ-5D (EQ-5D-5L) data, often because of the need for longitudinal EQ-5D-5L data collection. There is a dearth of validated methodologies for dealing with missing EQ-5D-5L data in the literature. This study, for the first time, examined the possibility of using retrospectively collected EQ-5D-5L data as proxies for the missing data. METHODS: Participants who had prospectively completed a 3rd month postdischarge EQ-5D-5L instrument (in-the-moment collection) were randomly interviewed to respond to a 2nd "retrospective collection" of their 3rd month EQ-5D-5L at 6th, 9th, or 12th month after hospital discharge. A longitudinal single imputation was also used to assess the relative performance of retrospective collection compared with the longitudinal single imputation. Concordances between the in-the-moment, retrospective, and imputed measures were assessed using intraclass correlation coefficients and weighted kappa statistics. RESULTS: Considerable agreement was observed on the basis of weighted kappa (range 0.72-0.95) between the mobility, self-care, and usual activities dimensions of EQ-5D-5L collected in-the-moment and retrospectively. Concordance based on intraclass correlation coefficients was good to excellent (range 0.79-0.81) for utility indices computed, and excellent (range 0.93-0.96) for quality-adjusted life-years computed using in-the-moment compared with retrospective EQ-5D-5L. The longitudinal single imputation did not perform as well as the retrospective collection method. CONCLUSIONS: This study demonstrates that retrospective collection of EQ-5D-5L has high concordance with "in-the-moment" EQ-5D-5L and could be a valid and attractive alternative for data imputation when longitudinally collected EQ-5D-5L data are missing. Future studies examining this method for other disease areas and populations are required to provide more generalizable evidence.