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Objective Methods Results Interpretation Given the high disease and cost burden of ischemic stroke, evaluating the clinical efficacy and cost‐effectiveness of new approaches to prevent and treat ischemic stroke is critical. Effective ischemic stroke management depends on timely administration of thrombolytics after stroke onset. This study evaluates the cost‐effectiveness associated with the use of mobile stroke units (MSUs) to expedite tissue plasminogen activator (tPA) administration, as compared with standard management through emergency medical services (EMS).This study is a prospective, multicenter, alternating‐week, cluster‐controlled trial of MSU versus EMS. One‐year and life‐time cost‐effectiveness analyses, using the incremental cost‐effectiveness ratio (ICER) method, were performed from the perspective of CMS's Medicare. Quality‐adjusted life years (QALYs) estimated using patient‐reported EQ‐5D‐5L data were used as the effectiveness measure. Health care utilizations were converted to costs using average national Medicare reimbursements. ICERs excluding patients with pre‐existing disability, and limited to stroke‐related costs were also calculated.The first‐year ICER for all tPA‐eligible patients using total cost differences between MSU and EMS groups was $238,873/QALY; for patients without pre‐existing disability was $61,199/QALY. The lifetime ICERs for all tPA‐eligible patients and for those without pre‐existing disability were $94,710 and $31,259/QALY, respectively. All ICERs were lower when restricted to stroke‐related costs and were highly dependent on the number of patients treated per year in an MSU.MSUs' cost‐effectiveness is borderline if we consider total first‐year costs and outcomes in all tPA‐eligible patients. MSUs are cost‐effective to highly cost‐effective when calculations are based on patients without pre‐existing disability, patients' lifetime horizon, stroke‐related costs, and more patients treated per year in an MSU. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Background: Whole blood trauma resuscitation is conceptually appealing and increasingly used but lacks evidence. A randomized controlled trial is needed but challenging to design. A Bayesian approach might be more efficient and more interpretable than a conventional frequentist design. We report the results on an elicitation meeting to create prior probability distributions to help develop such a trial.Methods: In-person expert elicitation meeting, based on Sheffield Elicitation Framework methodology. We used an interactive graphical tool to elicit the quantities of interest (24-hour mortality and certainty required). Two rounds were conducted, with an intervening discussion of deidentified responses. Individual responses were aggregated into probability distributions.Results: Fifteen experts participated. The pooled belief was that the median 24-hour mortality of trauma patients with hemorrhagic shock treated with component therapy (the current standard of care) was 19% (95% credible interval [CrI], 6%-45%), and the median 24-hour mortality of those treated with whole blood, 16% (95% CrI, 5%-39%). The pooled prior distribution for the relative risk had a median of 0.84 (95% CrI, 0.26-3.1), indicating that the expert group had a 64% prior belief that whole blood decreases 24-hour mortality compared to component therapy.Conclusions: Experts had moderately strong beliefs that whole blood reduces the 24-hour mortality of trauma patients with hemorrhagic shock. These data will assist with the design and planning of a Bayesian trial of whole blood resuscitation, which will help to answer a key question in contemporary transfusion practice. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The use of co-primary endpoints in drug development allows investigators to capture an experimental intervention's multidimensional effect more comprehensively than a single primary endpoint. We propose the theoretical basis and development of an adaptive population enrichment design with co-primary endpoints, provide stage-wise boundary values for futility and efficacy, and discuss power under different efficacy configurations, subgroup prevalence, and analysis times using a pre-specified decision criterion. We considered a two-arm, two-stage, parallel group design where population enrichment occurs at the interim analysis by dropping any non-responsive subgroups. A test for efficacy is conducted only in the enriched population. Two binary endpoints are evaluated as co-primary endpoints. Our trial objective is to determine whether the experimental intervention is superior to the control intervention, with superiority required in both endpoints. We define the stopping boundary using alpha spending functions. Using a 0.025 significance level for each endpoint, we obtain the stage I threshold boundary values for futility and efficacy as -0.1040 and 2.2761, respectively, and the stage II boundary value for futility and efficacy is 2.2419. We show that in the presence of substantial heterogeneity of treatment effect, we gain more power to observe an effect in the subgroup where the benefits are greater. By allowing the dropping of non-responsive subgroups at an early stage, our design reduces the likelihood of obtaining false-negative results due to inclusion of the heterogeneous treatment effects of both subgroups, which would dilute the responsive subgroup's results. [ABSTRACT FROM AUTHOR]

Background: The mortality of trauma patients requiring massive transfusion to treat hemorrhagic shock approaches 17% at 24 hours and 26% at 30 days. The use of stored RBCs is limited to less than 42 days, so older RBCs are delivered first to rapidly bleeding trauma patients. Patients who receive a greater quantity of older RBCs may have a higher risk for mortality.Methods and Materials: Characterizing blood age exposure requires accounting for the age of each RBC unit and the quantity of transfused units. To address this challenge, a novel Scalar Age of Blood Index (SBI) that represents the relative distribution of RBCs received is introduced and applied to a secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) randomized controlled trial (NCT01545232, https://clinicaltrials.gov/ct2/show/NCT01545232). The effect of the SBI is assessed on the primary PROPPR outcome, 24-hour and 30-day mortality.Results: The distributions of blood storage ages successfully maps to a parameter (SBI) that fully defines the blood age curve for each patient. SBI was a significant predictor of 24-hour and 30-day mortality in an adjusted model that had strong predictive ability (odds ratio, 1.15 [1.01-1.29], p = 0.029, C-statistic, 0.81; odds ratio, 1.14 [1.02-1.28], p = 0.019, C-statistic, 0.88, respectively).Conclusion: SBI is a simple scalar metric of blood age that accounts for the relative distribution of RBCs among age categories. Transfusion of older RBCs is associated with 24-hour and 30-day mortality, after adjustment for total units and clinical covariates. [ABSTRACT FROM AUTHOR]

Background: No studies have investigated whether race/ethnicity is associated with the recommended use of preoperative chemotherapy or subsequent outcomes in gastric cancer. To determine whether there is such an association, analyses of patients with gastric cancer in the National Cancer Data Base (NCDB) were performed.Methods: Patients with clinical T2-4bN0-1M0 gastric adenocarcinoma, as defined by the eighth edition of the American Joint Committee on Cancer staging manual, who underwent gastrectomy from 2006 to 2014 were identified from the NCDB. Multiple logistic regression was conducted to examine factors associated with preoperative chemotherapy use.Results: This study identified 16,945 patients who met the criteria, and 8286 of these patients (49%) underwent preoperative chemotherapy. The use of preoperative chemotherapy remarkably increased over the study period, from 34% in 2006 to 65% in 2014. Preoperative chemotherapy was more commonly used for cardia tumors than noncardia tumors (83% vs 44% in 2014). In a multivariable analysis, races and ethnicities other than non-Hispanic (NH) white race were associated with less frequent use of preoperative chemotherapy in comparison with NH whites after adjustments for social, tumor, and hospital factors. The insurance status and the education level mediated an enhanced effect of racial/ethnic disparities in preoperative chemotherapy use. The use of preoperative chemotherapy and radiation therapy was associated with reduced racial/ethnic disparities in overall survival.Conclusions: Racial/ethnic disparities in the use of preoperative chemotherapy and in outcomes exist among patients with gastric cancer in the United States. Efforts to improve the access to high-quality cancer care in minority groups may reduce racial disparities in gastric cancer in the United States. Cancer 2018;124:998-1007. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

The use of longitudinal measurements to predict a categorical outcome is an increasingly common goal in research studies. Joint models are commonly used to describe two or more models simultaneously by considering the correlated nature of their outcomes and the random error present in the longitudinal measurements. However, there is limited research on joint models with longitudinal predictors and categorical cross-sectional outcomes. Perhaps the most challenging task is how to model the longitudinal predictor process such that it represents the true biological mechanism that dictates the association with the categorical response. We propose a joint logistic regression and Markov chain model to describe a binary cross-sectional response, where the unobserved transition rates of a two-state continuous-time Markov chain are included as covariates. We use the method of maximum likelihood to estimate the parameters of our model. In a simulation study, coverage probabilities of about 95%, standard deviations close to standard errors, and low biases for the parameter values show that our estimation method is adequate. We apply the proposed joint model to a dataset of patients with traumatic brain injury to describe and predict a 6-month outcome based on physiological data collected post-injury and admission characteristics. Our analysis indicates that the information provided by physiological changes over time may help improve prediction of long-term functional status of these severely ill subjects. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Although the Papanicolaou smear has been successful in decreasing cervical cancer incidence in the developed world, there exist many challenges for implementation in the developing world. Quantitative cytology, a semi-automated method that quantifies cellular image features, is a promising screening test candidate. The nested structure of its data (measurements of multiple cells within a patient) provides challenges to the usual classification problem. Here we perform a comparative study of three main approaches for problems with this general data structure: (i) extract patient-level features from the cell-level data, (ii) use a statistical model that accounts for the hierarchical data structure, and (iii) classify at the cellular level and use an ad hoc approach to classify at the patient level. We apply these methods to a dataset of 1728 patients, with an average of 2600 cells collected per patient and 133 features measured per cell, predicting whether a patient had a positive biopsy result. The best approach we found was to classify at the cellular level and count the number of cells that had a posterior probability greater than a threshold value, with estimated 61% sensitivity and 89% specificity on independent data. Recent statistical learning developments allowed us to achieve high accuracy. [ABSTRACT FROM AUTHOR]

Testing emerging technologies involves the evaluation of biologic plausibility, technical efficacy, clinical effectiveness, patient satisfaction, and cost-effectiveness. The objective of this study was to select an effective classification algorithm for optical spectroscopy as an adjunct to colposcopy and obtain preliminary estimates of its accuracy for the detection of CIN 2 or worse. We recruited 1,000 patients from screening and prevention clinics and 850 patients from colposcopy clinics at two comprehensive cancer centers and a community hospital. Optical spectroscopy was performed, and 4,864 biopsies were obtained from the sites measured, including abnormal and normal colposcopic areas. The gold standard was the histologic report of biopsies, read 2 to 3 times by histopathologists blinded to the cytologic, histopathologic, and spectroscopic results. We calculated sensitivities, specificities, receiver operating characteristic (ROC) curves, and areas under the ROC curves. We identified a cutpoint for an algorithm based on optical spectroscopy that yielded an estimated sensitivity of 1.00 [95% confidence interval (CI) = 0.92-1.00] and an estimated specificity of 0.71 [95% CI = 0.62-0.79] in a combined screening and diagnostic population. The positive and negative predictive values were 0.58 and 1.00, respectively. The area under the ROC curve was 0.85 (95% CI = 0.81-0.89). The per-patient and per-site performance were similar in the diagnostic and poorer in the screening settings. Like colposcopy, the device performs best in a diagnostic population. Alternative statistical approaches demonstrate that the analysis is robust and that spectroscopy works as well as or slightly better than colposcopy for the detection of CIN 2 to cancer. [ABSTRACT FROM AUTHOR]