Adjusting Incidence Estimates with Laboratory Test Performances: A Pragmatic Maximum Likelihood Estimation-Based Approach.

Understanding the incidence of disease is often crucial for public policy decision-making, as observed during the COVID-19 pandemic. Estimating incidence is challenging, however, when the definition of incidence relies on tests that imperfectly measure disease, as in the case when assays with variable performance are used to detect the SARS-CoV-2 virus. To our knowledge, there are no pragmatic methods to address the bias introduced by the performance of labs in testing for the virus. In the setting of a longitudinal study, we developed a maximum likelihood estimation-based approach to estimate laboratory performance-adjusted incidence using the expectation-maximization algorithm. We constructed confidence intervals (CIs) using both bootstrapped-based and large-sample interval estimator approaches. We evaluated our methods through extensive simulation and applied them to a real-world study (TrackCOVID), where the primary goal was to determine the incidence of and risk factors for SARS-CoV-2 infection in the San Francisco Bay Area from July 2020 to March 2021. Our simulations demonstrated that our method converged rapidly with accurate estimates under a variety of scenarios. Bootstrapped-based CIs were comparable to the large-sample estimator CIs with a reasonable number of incident cases, shown via a simulation scenario based on the real TrackCOVID study. In more extreme simulated scenarios, the coverage of large-sample interval estimation outperformed the bootstrapped-based approach. Results from the application to the TrackCOVID study suggested that assuming perfect laboratory test performance can lead to an inaccurate inference of the incidence. Our flexible, pragmatic method can be extended to a variety of disease and study settings.

Application of cell-free DNA fungal polymerase chain reaction for invasive fungal disease evaluation in pediatric oncology and stem cell transplant patients.

BACKGROUND: Molecular diagnostics may enable early, noninvasive detection of invasive fungal disease (IFD) in immunocompromised patients. Cell-free deoxyribonucleic acid (cfDNA) fungal polymerase chain reaction (PCR) assays were recently incorporated into institutional prolonged febrile neutropenia pathways. We aimed to evaluate the performance of plasma cfDNA PCR panels (mold and Candida panels) in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients with clinical concern for IFD. METHODS: This single-center, observational study assessed plasma cfDNA fungal PCR performance for noninvasive IFD detection in hospitalized pediatric oncology and HSCT patients. The primary outcome was IFD diagnosis per published consensus definitions within 1 month. Positive and negative agreement between plasma cfDNA fungal PCR and consensus definitions were calculated. We also described test turnaround time and patient survival. RESULTS: From October 2021 to 2022, 54 patients underwent 60 evaluations with 11 proven/probable IFD cases. Comparing plasma cfDNA fungal PCRs to consensus definitions for proven/probable IFD, there was 73% positive agreement and 96% negative agreement. Two proven/probable cases with negative PCRs were caused by organisms not included on either panel. Median time to cfDNA fungal PCR result was 35 hours (interquartile range: 19-69) in eight proven/probable cases detected by cfDNA fungal PCR. There were 17 deaths among 54 patients, and IFD contributed to 45% of deaths in patients with proven/probable IFD. CONCLUSIONS: Plasma cfDNA fungal PCRs detected relevant molds or yeast in most cases classified as proven/probable IFD. However, this targeted approach missed some cases. More studies are required to determine optimal utilization of molecular diagnostics in pediatric patients.

Acute kidney injury in neonates with hypoxic ischemic encephalopathy based on serum creatinine decline compared to KDIGO criteria.

BACKGROUND: Neonates with hypoxic ischemic encephalopathy receiving therapeutic hypothermia (HIE + TH) are at risk for acute kidney injury (AKI). The standardized Kidney Disease Improving Global Outcomes (KDIGO) criteria identifies AKI based on a rise in serum creatinine (SCr) or reduced urine output. This definition is challenging to apply in neonates given the physiologic decline in SCr during the first week of life. Gupta et al. proposed alternative neonatal criteria centered on rate of SCr decline. This study aimed to compare the rate of AKI based on KDIGO and Gupta in neonates with HIE and to examine associations with mortality and morbidity. METHODS: A retrospective review was performed of neonates with moderate to severe HIE + TH from 2008 to 2020 at a single center. AKI was assessed in the first 7 days after birth by KDIGO and Gupta criteria. Mortality, brain MRI severity of injury, length of stay, and duration of respiratory support were compared between AKI groups. RESULTS: Among 225 neonates, 64 (28%) met KDIGO, 69 (31%) neonates met Gupta but not KDIGO, and 92 (41%) did not meet either definition. Both KDIGO-AKI and GuptaOnly-AKI groups had an increased risk of the composite mortality and/or moderate/severe brain MRI injury along with longer length of stay and prolonged duration of respiratory support compared to those without AKI. CONCLUSIONS: AKI in neonates with HIE + TH was common and varied by definition. The Gupta definition based on rate of SCr decline identified additional neonates not captured by KDIGO criteria who are at increased risk for adverse outcomes. Incorporating the rate of SCr decline into the neonatal AKI definition may increase identification of clinically relevant kidney injury in neonates with HIE + TH.

Stress Symptoms Among Children and Their Parents After ICU Hospitalization.

Objective: Child survival after intensive care unit (ICU) hospitalization has increased, yet many children experience acute stress that may precipitate mental/behavioral health comorbidities. Parents report stress after their child's hospitalization. Little is known about the individual and family characteristics that may moderate intergenerational relationships of acute stress. Design: Following ICU admission at a large academic medical center, a prospective cross-sectional cohort study assessed the associations between intergenerational characteristics and acute stress among children and families. Patients: Parent-child dyads (N = 88) were recruited from the pediatric ICU and pediatric cardiovascular ICU (CVICU) following ICU discharge. Eligible children were between 8 and 18 years old with ICU stays longer than 24 hours. Children with developmental delays were excluded. Caregivers were proficient in English or Spanish. Surveys were collected before hospital discharge. Measurements/Main Results: The primary outcome was "child stress" defined as a score≥17, measured by the Children's Revised Impact of Events Scale (CRIES-8). "Parent stress" was defined as an elevated composite score on the Stanford Acute Stress Reaction Questionnaire. We used validated scales to assess the child's clinical and family social characteristics. Acute stress was identified in 34 (39.8%) children and 50 (56.8%) parents. In multivariate linear regression analyses adjusting for social characteristics, parent stress was associated with increased risk of child stress (adjusted odds ratio 2.58, 95% confidence interval 0.69, 4.46, p < .01). In unadjusted analyses, Hispanic ethnicity was associated with greater child stress. In adjusted analyses, race, income, ICU length of stay, and language were not associated with child stress and did not moderate the parent-child stress relationship. Conclusions: Parent stress is closely correlated with child stress during ICU hospitalization. Hispanic ethnicity may be associated with increased risk for child stress, but further studies are required to define the roles of other social and clinical measures.

Activated 4-Factor Prothrombin Complex Concentrate as a Hemostatic Adjunct for Neonatal Cardiac Surgery: A Propensity Score-Matched Cohort Study.

BACKGROUND: Prothrombin complex concentrates are an emerging "off-label" therapy to augment hemostasis after cardiopulmonary bypass (CPB), but data supporting their use for neonatal cardiac surgery are limited. METHODS: We retrospectively reviewed neonates undergoing open heart surgery with first-time sternotomy between May 2014 and December 2018 from a hospital electronic health record database. Neonates who received activated 4-factor prothrombin complex concentrate (a4FPCC) after CPB were propensity score matched (PSM) to neonates who did not receive a4FPCC (control group). The primary efficacy outcome was total volume (mL/kg) of blood products transfused after CPB, including the first 24 hours on the cardiovascular intensive care unit (CVICU). The primary safety outcome was the incidence of 7- and 30-day postoperative thromboembolism. Secondary outcomes included 24 hours postoperative chest tube output, time to extubation, duration of CVICU stay, duration of hospital stay, 30-day mortality, and incidence of acute kidney injury on postoperative day 3. We used linear regression modeling on PSM data for the primary efficacy outcome. For the primary safety outcome, we tested for differences using McNemar test on PSM data. For secondary outcomes, we used linear regression, Fisher exact test, or survival analyses as appropriate, with false discovery rate-adjusted P values. RESULTS: A total of 165 neonates were included in the final data analysis: 86 in the control group and 79 in the a4FPCC group. After PSM, there were 43 patients in the control group and 43 in the a4FPCC group. We found a statistically significant difference in mean total blood products transfused for the a4FPCC group (47.5 mL/kg) compared with the control group (63.7 mL/kg) for PSM patients (adjusted difference, 15.3; 95% CI, 29.4-1.3; P = .032). We did not find a statistically significant difference in 7- or 30-day thromboembolic rate, postoperative chest tube output, time to extubation, incidence of postoperative acute kidney injury (AKI), or 30-day mortality between the groups. The a4FPCC group had a significantly longer length of intensive care unit stay (32.9 vs 13.3 days; adjusted P = .049) and hospital stay (44.6 vs 24.1 days; adjusted P = .049) compared with the control group. CONCLUSIONS: We found that the use of a4FPCC as a hemostatic adjunct for post-CPB bleeding in neonatal cardiac surgery was associated with a decrease in mean total blood products transfused after CPB without an increased rate of 7- or 30-day postoperative thromboembolism. Our findings suggest that a4FPCCs can be considered as part of a hemostasis pathway for refractory bleeding in neonatal cardiac surgery.

Community Urgent Care Use Following Implementation of the Veterans Affairs Maintaining Internal Systems and Strengthening Integrated Outside Networks Act.

BACKGROUND: Effective June 6, 2019, Veterans Affairs (VA) began offering a new urgent care (UC) benefit that provides eligible Veterans with greater choice and access to care for the treatment of minor injuries and illnesses in their local communities. OBJECTIVES: The aim was to describe trends in UC use, identify predictors of UC benefit use, and understand the factors associated with community UC use versus VA emergency department (ED) or urgent care center (UCC) use. STUDY DESIGN: Using VA administrative data, this was a retrospective cross-sectional study of Veterans that were enrolled in VA in FY19. Veterans were classified into 3 groups: UC benefit users, benefit non-users, and VA ED/UCC users. METHODS: We used summary statistics to compare population characteristics across user groups. To determine whether predisposing, enabling, and need factors predicted UC benefit use and setting choice (community UCC vs. VA ED/UCC), 2 logistic regression models were fitted to assess odds of UC use. RESULTS: From June 6, 2019 through February 29, 2020, 138,305 Veterans made 175,821 community UC visits. The majority of visits were made by White males who were not subject to co-pays. The average cost to VA for UC visits was $132 (SD=$135). Upper respiratory infections were the most common reason for UC use. Being younger, female, and living farther from a VA ED/UCC was associated with greater UC benefit use compared with both benefit non-users and VA ED/UCC users. CONCLUSIONS: The new benefit expands Veteran access to UC services for low-acuity conditions.

Comorbidity Assessment Is Uneven Across Veterans Health Administration and Medicare for the Same Patient: Implications for Risk Adjustment.

OBJECTIVE: Compare comorbidity identification in Medicare and Veterans Health Administration (VA) data for the purposes of risk adjustment. DATA SOURCES: Analysis of Medicare and VA datasets for dually-enrolled Veterans receiving care in both settings, fiscal years 2010-2014. STUDY DESIGN: A retrospective analysis of administrative data for a national sample of cancer decedents. DATA EXTRACTION METHODS: Comorbidities were evaluated using Elixhauser and Charlson coding algorithms. PRINCIPAL FINDINGS: Clinical comorbidities were more likely to be recorded in Medicare than in VA datasets. Of 42 comorbidities, 36 (86%) were recorded at a different frequency. For example, congestive heart failure was recorded for 22.0% of patients in Medicare data and for 11.3% of patients in VA data (P<0.001). CONCLUSION: There are large differences in comorbidity assessment across VA and Medicare administrative data for the same patient, posing challenges for risk adjustment.

Observational Study of the Downstream Consequences of Inappropriate MRI of the Lumbar Spine.

BACKGROUND: Contrary to guidelines, magnetic resonance imaging (MRI) is often ordered in the first 6 weeks of new episodes of uncomplicated non-specific low back pain. OBJECTIVE: To determine the downstream consequences of early imaging. DESIGN: Retrospective matched cohort study using data from electronic health records of primary care clinics of the U.S. Department of Veterans Affairs. PARTICIPANTS: Patients seeking primary care for non-specific low back pain without a red flag condition or an encounter for low back pain in the prior 6 months (N = 405,965). EXPOSURE: MRI of the lumbar spine within 6 weeks of the initial primary care visit. MAIN MEASURES: Covariates included patient demographics, health history in the prior year, and baseline pain. Outcomes were lumbar surgery, prescription opioid use, acute health care costs, and last pain score recorded within 1 year of the index visit. KEY RESULTS: Early MRI was associated with more back surgery (1.48% vs. 0.12% in episodes without early MRI), greater use of prescription opioids (35.1% vs. 28.6%), a higher final pain score (3.99 vs. 3.87), and greater acute care costs ($8082 vs. $5560), p < 0.001 for all comparisons. LIMITATIONS: Reliance on data gathered in normal clinical care and the potential for residual confounding despite the use of coarsened exact matching weights to adjust for baseline differences. CONCLUSIONS: The association between early imaging and increased utilization was apparent even in a setting largely unaffected by incentives of fee-for-service care. Reduced imaging cost is only part of the motivation to improve adherence with guidelines for the use of MRI. Early scans are associated with excess surgery, higher costs for other care, and worse outcomes, including potential harms from prescription opioids.

Neonatal genetic epilepsies display convergent white matter microstructural abnormalities.

White matter undergoes rapid development in the neonatal period. Its structure during and after development is influenced by neuronal activity. Pathological neuronal activity, as in seizures, might alter white matter, which in turn may contribute to network dysfunction. Neonatal epilepsy presents an opportunity to investigate seizures and early white matter development. Our objective was to determine whether neonatal seizures in the absence of brain injury or congenital anomalies are associated with altered white matter microstructure. In this retrospective case-control study of term neonates, cases had confirmed or suspected genetic epilepsy and normal brain magnetic resonance imaging (MRI) and no other conditions independently impacting white matter. Controls were healthy neonates with normal MRI results. White matter microstructure was assessed via quantitative mean diffusivity (MD). In 22 cases, MD was significantly lower in the genu of the corpus callosum, compared to 22 controls, controlling for gestational age and postmenstrual age at MRI. This finding suggests convergent abnormal corpus callosum microstructure in neonatal epilepsies with diverse suspected genetic causes. Further study is needed to determine the specific nature, causes, and functional impact of seizure-associated abnormal white matter in neonates, a potential pathogenic mechanism.

Collateral Status in Ischemic Stroke: A Comparison of Computed Tomography Angiography, Computed Tomography Perfusion, and Digital Subtraction Angiography.

OBJECTIVE: To compare assessment of collaterals by single-phase computed tomography (CT) angiography (CTA) and CT perfusion-derived 3-phase CTA, multiphase CTA and temporal maximum-intensity projection (tMIP) images to digital subtraction angiography (DSA), and relate collateral assessments to clinical outcome in patients with acute ischemic stroke. METHODS: Consecutive acute ischemic stroke patients who underwent CT perfusion, CTA, and DSA before thrombectomy with occlusion of the internal carotid artery, the M1 or the M2 segments were included. Two observers assessed all CT images and one separate observer assessed DSA (reference standard) with static and dynamic (modified American Society of Interventional and Therapeutic Neuroradiology) collateral grading methods. Interobserver agreement and concordance were quantified with Cohen-weighted κ and concordance correlation coefficient, respectively. Imaging assessments were related to clinical outcome (modified Rankin Scale, ≤ 2). RESULTS: Interobserver agreement (n = 101) was 0.46 (tMIP), 0.58 (3-phase CTA), 0.67 (multiphase CTA), and 0.69 (single-phase CTA) for static assessments and 0.52 (3-phase CTA) and 0.54 (multiphase CTA) for dynamic assessments. Concordance correlation coefficient (n = 80) was 0.08 (3-phase CTA), 0.09 (single-phase CTA), and 0.23 (multiphase CTA) for static assessments and 0.10 (3-phase CTA) and 0.27 (multiphase CTA) for dynamic assessments. Higher static collateral scores on multiphase CTA (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.1-2.7) and tMIP images (OR, 2.0; 95% CI, 1.1-3.4) were associated with modified Rankin Scale of 2 or less as were higher modified American Society of Interventional and Therapeutic Neuroradiology scores on 3-phase CTA (OR, 1.5; 95% CI, 1.1-2.2) and multiphase CTA (OR, 1.7; 95% CI, 1.1-2.6). CONCLUSIONS: Concordance between assessments on CT and DSA was poor. Collateral status evaluated on 3-phase CTA and multiphase CTA, but not on DSA, was associated with clinical outcome.

Clinical Outcomes and Cost-Effectiveness of Fractional Flow Reserve-Guided Percutaneous Coronary Intervention in Patients With Stable Coronary Artery Disease: Three-Year Follow-Up of the FAME 2 Trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation).

BACKGROUND: Previous studies found that percutaneous coronary intervention (PCI) does not improve outcome compared with medical therapy (MT) in patients with stable coronary artery disease, but PCI was guided by angiography alone. FAME 2 trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) compared PCI guided by fractional flow reserve with best MT in patients with stable coronary artery disease to assess clinical outcomes and cost-effectiveness. METHODS: A total of 888 patients with stable single-vessel or multivessel coronary artery disease with reduced fractional flow reserve were randomly assigned to PCI plus MT (n=447) or MT alone (n=441). Major adverse cardiac events included death, myocardial infarction, and urgent revascularization. Costs were calculated on the basis of resource use and Medicare reimbursement rates. Changes in quality-adjusted life-years were assessed with utilities determined by the European Quality of Life-5 Dimensions health survey at baseline and over follow-up. RESULTS: Major adverse cardiac events at 3 years were significantly lower in the PCI group compared with the MT group (10.1% versus 22.0%; P<0.001), primarily as a result of a lower rate of urgent revascularization (4.3% versus 17.2%; P<0.001). Death and myocardial infarction were numerically lower in the PCI group (8.3% versus 10.4%; P=0.28). Angina was significantly less severe in the PCI group at all follow-up points to 3 years. Mean initial costs were higher in the PCI group ($9944 versus $4440; P<0.001) but by 3 years were similar between the 2 groups ($16 792 versus $16 737; P=0.94). The incremental cost-effectiveness ratio for PCI compared with MT was $17 300 per quality-adjusted life-year at 2 years and $1600 per quality-adjusted life-year at 3 years. The above findings were robust in sensitivity analyses. CONCLUSIONS: PCI of lesions with reduced fractional flow reserve improves long-term outcome and is economically attractive compared with MT alone in patients with stable coronary artery disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01132495.

High-Need Patients' Goals and Goal Progress in a Veterans Affairs Intensive Outpatient Care Program.

BACKGROUND: Healthcare systems nationwide are implementing intensive outpatient care programs to optimize care for high-need patients; however, little is known about these patients' personal goals and factors associated with goal progress. OBJECTIVE: To describe high-need patients' goals, and to identify factors associated with their goal progress DESIGN: Retrospective cohort study PARTICIPANTS: A total of 113 high-need patients participated in a single-site Veterans Affairs intensive outpatient care program. MAIN MEASURES: Two independent reviewers examined patients' goals recorded in the electronic health record, categorized each goal into one of three domains (medical, behavioral, or social), and determined whether patients attained goal progress during program participation. Logistic regression was used to determine factors associated with goal progress. RESULTS: The majority (n = 72, 64%) of the 113 patients attained goal progress. Among the 100 (88%) patients with at least one identified goal, 58 set goal(s) in the medical domain; 60 in the behavioral domain; and 52 in the social domain. Within each respective domain, 41 (71%) attained medical goal progress; 34 (57%) attained behavioral goal progress; and 32 (62%) attained social goal progress. Patients with mental health condition(s) (aOR 0.3; 95% CI 0.1-0.9; p = 0.03) and those living alone (aOR 0.4; 95% CI 0.1-1.0; p = 0.05) were less likely to attain goal progress. Those with mental health condition(s) and those who were living alone were least likely to attain goal progress (interaction aOR 0.1 compared to those with neither characteristic; 95% CI 0.0-0.7; p = 0.02). CONCLUSIONS: Among high-need patients participating in an intensive outpatient care program, patient goals were fairly evenly distributed across medical, behavioral, and social domains. Notably, individuals living alone with mental health conditions were least likely to attain progress. Future care coordination interventions might incorporate strategies to address this gap, e.g., broader integration of behavioral and social service components.

Carotid Artery Imaging Is More Strongly Associated With the 10-Year Atherosclerotic Cardiovascular Disease Score Than Coronary Artery Imaging.

PURPOSE: The aim of this study was to compare coronary and carotid artery imaging and determine which one shows the strongest association with atherosclerotic cardiovascular disease (ASCVD) score. PATIENTS AND METHODS: Two separate series patients who underwent either coronary computed tomography angiography (CTA) or carotid CTA were included. We recorded the ASCVD scores and assessed the CTA imaging. Two thirds were used to build predictive models, and the remaining one third generated predicted ASCVD scores. The Bland-Altman analysis analyzed the concordance. RESULTS: A total of 110 patients were included in each group. There was no significant difference between clinical characteristics. Three imaging variables were included in the carotid model. Two coronary models (presence of calcium or Agatston score) were created. The bias between true and predicted ASCVD scores was 0.37 ± 5.72% on the carotid model, and 2.07 ± 7.18% and 2.47 ± 7.82% on coronary artery models, respectively. CONCLUSIONS: Both carotid and coronary artery imaging features can predict ASCVD score. The carotid artery was more associated to the ASCVD score than the coronary artery.

Validation of the NeuroImaging Radiological Interpretation System for Acute Traumatic Brain Injury.

PURPOSE: The aim of the study was to refine and validate the NeuroImaging Radiological Interpretation System (NIRIS), which was developed to predict management and clinical outcome based on noncontrast head computerized tomography findings in patients suspected of acute traumatic brain injury (TBI). METHODS: We assessed the performance of the NIRIS score in a prospective, single-center cohort of patients suspected of TBI (n = 648) and compared the performance of NIRIS with that of the Marshall and Rotterdam scoring systems. We also revised components of the NIRIS scoring system using decision tree methodologies implemented on pooled data from the retrospective and prospective studies (N = 1190). RESULTS: The NIRIS performed similarly to the Marshall and Rotterdam scoring systems in predicting mortality and markedly better in terms of predicting more granular elements of disposition and management of TBI patients, such as admission, follow-up imaging, intensive care unit stay, and neurosurgical procedures. The revised NIRIS classification correctly predicted disposition and outcome in 91.2% (331/363) after excluding patients with other major extracranial traumatic injuries or intracranial nontraumatic injuries. CONCLUSIONS: The present study further demonstrates the predictive value of NIRIS in guiding standardized clinical management and decision-making regarding treatment options for TBI patients.

Socioeconomic Differences in the Epidemiologic Transition From Heart Disease to Cancer as the Leading Cause of Death in the United States, 2003 to 2015: An Observational Study.

Background: Recent data suggest that the United States is in the midst of an epidemiologic transition in the leading cause of death. Objective: To examine county-level sociodemographic differences in the transition from heart disease to cancer as the leading cause of death in the United States. Design: Observational study. Setting: U.S. death records, 2003 to 2015. Participants: Decedents aged 25 years or older, classified by racial/ethnic group. Measurements: All-cause, heart disease, and cancer mortality stratified by quintiles of county median household income. Age- and sex-adjusted mortality rates and average annual percentage of change were calculated. Results: Heart disease was the leading cause of death in 79% of counties in 2003 and 59% in 2015. Cancer was the leading cause of death in 21% of counties in 2003 and 41% in 2015. The shift to cancer as the leading cause of death was greatest in the highest-income counties. Overall, heart disease mortality rates decreased by 28% (30% in high-income counties vs. 22% in low-income counties) from 2003 to 2015, and cancer mortality rates decreased by 16% (18% in high-income counties vs. 11% in low-income counties). In the lowest-income counties, heart disease remained the leading cause of death among all racial/ethnic groups, and improvements were smaller for both heart disease and cancer. Limitation: Use of county median household income as a proxy for socioeconomic status. Conclusion: Data show that heart disease is more likely to be the leading cause of death in low-income counties. Low-income counties have not experienced the same decrease in mortality rates as high-income counties, which suggests a later transition to cancer as the leading cause of death in low-income counties. Primary Funding Source: National Institute on Minority Health and Health Disparities.

A Multiple-Imputation "Forward Bridging" Approach to Address Changes in the Classification of Asian Race/Ethnicity on the US Death Certificate.

The incomparability of old and new classification systems for describing the same data can be seen as a missing-data problem, and, under certain assumptions, multiple imputation may be used to "bridge" 2 classification systems. One example of such a change is the introduction of detailed Asian-American race/ethnicity classifications on the 2003 version of the US national death certificate, which was adopted for use by 38 states between 2003 and 2011. Using county- and decedent-level data from 3 different national sources for pre- and postadoption years, we fitted within-state multiple-imputation models to impute ethnicities for decedents classified as "other Asian" during preadoption years. We present mortality rates derived using 3 different methods of calculation: 1) including all states but ignoring the gradual adoption of the new death certificate over time, 2) including only the 7 states with complete reporting of all ethnicities, and 3) including all states and applying multiple imputation. Estimates from our imputation model were consistently in the middle of the other 2 estimates, and trend results demonstrated that the year-by-year estimates of the imputation model were more similar to those of the 7-state model. This work demonstrates how multiple imputation can provide a "forward bridging" approach to make more accurate estimates over time in newly categorized populations.

Weekly Docetaxel, Cisplatin, and Cetuximab in Palliative Treatment of Patients with Squamous Cell Carcinoma of the Head and Neck.

LESSONS LEARNED: Chemotherapy for recurrent, metastatic squamous cell carcinoma of the head and neck need not be known for extreme toxicity.The weekly regimen studied here has been demonstrated to be tolerable and effective. BACKGROUND: The objective of this study was to establish the response rate, progression-free survival (PFS) and overall survival (OS), and safety profile of weekly docetaxel, platinum, and cetuximab (TPC) in patients with relapsed or metastatic squamous cell carcinoma of the head and neck (SCCHN). MATERIALS AND METHODS: Twenty-nine patients with metastatic or recurrent SCCHN with an Eastern Cooperative Oncology Group (ECOG) performance status <3 were enrolled in an institutional review board-approved phase II trial. This study permitted prior chemoradiation, radiation, and/or surgery, provided that 3 months had elapsed since the end of the potentially curative treatment. Patients received cisplatin 30 mg/m2 or carboplatin area under the curve (AUC) 2, docetaxel 30 mg/m2, and cetuximab 250 mg/m2 weekly for 3 weeks, followed by a break during the fourth week, for a 28-day cycle. Planned intrapatient dose modifications were based on individual toxicity. RESULTS: Twenty-seven patients received TPC and were evaluable for response and toxicity. Rates of complete response (CR), partial response (PR), and confirmed PR were 3%, 52%, and 30%, respectively. The overall objective response rate was 56%. Estimated median PFS and OS were 4.8 and 14.7 months, respectively. The rates of grade 3 and 4 worst-grade adverse events (AEs) per patient were 85% and 7%, respectively. Dose density through cycle 4 was preserved for all patients; however, treatment beyond cycle 6 with the TPC regimen proved unfeasible. CONCLUSION: Weekly docetaxel, cisplatin, and cetuximab is an effective regimen for patients with metastatic or recurrent SCCHN. Response rates, PFS, and OS compare favorably with other combination chemotherapy treatments. Grade 4 toxicity rates observed in this study were substantially lower than those described with regimens using less frequent, higher-dose chemotherapy schedules.

Patient Activation Changes as a Potential Signal for Changes in Health Care Costs: Cohort Study of US High-Cost Patients.

BACKGROUND: Programs to improve quality of care and lower costs for the highest utilizers of health services are proliferating, yet such programs have difficulty demonstrating cost savings. OBJECTIVE: In this study, we explore the degree to which changes in Patient Activation Measure (PAM) levels predict health care costs among high-risk patients. PARTICIPANTS: De-identified claims, demographic data, and serial PAM scores were analyzed on 2155 patients from multiple medical groups engaged in an existing Center for Medicare and Medicaid Innovation-funded intervention over 3 years designed to activate and improve care coordination for high-risk patients. DESIGN: In this prospective cohort study, four levels of PAM (from low to high) were used as the main predictor variable. We fit mixed linear models for log10 of allowed charges in follow-up periods in relation to change in PAM, controlling for baseline PAM, baseline costs, age, sex, income, and baseline risk score. MAIN MEASURES: Total allowed charges were derived from claims data for the cohort. PAM scores were from a separate database managed by the local practices. KEY RESULTS: A single PAM level increase was associated with 8.3% lower follow-up costs (95% confidence interval 2.5-13.2%). CONCLUSIONS: These findings contribute to a growing evidence base that the change in PAM score could serve as an early signal indicating the impact of interventions designed for high-cost, high-needs patients.

A Behavior-Based Intervention That Prevents Sexual Assault: the Results of a Matched-Pairs, Cluster-Randomized Study in Nairobi, Kenya.

DESIGN: The study's design was a cluster-randomized, matched-pairs, parallel trial of a behavior-based sexual assault prevention intervention in the informal settlements. METHODS: The participants were primary school girls aged 10-16. Classroom-based interventions for girls and boys were delivered by instructors from the same settlements, at the same time, over six 2-h sessions. The girls' program had components of empowerment, gender relations, and self-defense. The boys' program promotes healthy gender norms. The control arm of the study received a health and hygiene curriculum. The primary outcome was the rate of sexual assault in the prior 12 months at the cluster level (school level). Secondary outcomes included the generalized self-efficacy scale, the distribution of number of times victims were sexually assaulted in the prior period, skills used, disclosure rates, and distribution of perpetrators. Difference-in-differences estimates are reported with bootstrapped confidence intervals. RESULTS: Fourteen schools with 3147 girls from the intervention group and 14 schools with 2539 girls from the control group were included in the analysis. We estimate a 3.7 % decrease, p = 0.03 and 95 % CI = (0.4, 8.0), in risk of sexual assault in the intervention group due to the intervention (initially 7.3 % at baseline). We estimate an increase in mean generalized self-efficacy score of 0.19 (baseline average 3.1, on a 1-4 scale), p = 0.0004 and 95 % CI = (0.08, 0.39). INTERPRETATION: This innovative intervention that combined parallel training for young adolescent girls and boys in school settings showed significant reduction in the rate of sexual assault among girls in this population.