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.

A randomized controlled trial of graded exposure treatment (GET living) for adolescents with chronic pain.

ABSTRACT: Graded exposure treatment (GET) is a theory-driven pain treatment that aims to improve functioning by exposing patients to activities previously feared and avoided. Combining key elements of GET with acceptance-based exposure, GET Living (GL) was developed for adolescents with chronic pain (GL). Based on robust treatment effects observed in our single-case experimental design pilot trial of GL (NCT01974791), we conducted a 2-arm randomized clinical trial comparing GL with multidisciplinary pain management (MPM) comprised of cognitive behavioral therapy and physical therapy for pain management (NCT03699007). A cohort of 68 youth with chronic musculoskeletal pain (M age 14.2 years; 81% female) were randomized to GL or MPM. Owing to COVID-19 restrictions, 54% of participants received zoom video delivered care. Assessments were collected at baseline, discharge, as well as at 3-month and 6-month follow-up. Primary outcomes were self-reported pain-related fear and avoidance. Secondary outcomes were child functional disability and parent protective responses to child pain. As hypothesized, GL improved in primary and secondary outcomes at 3-month follow-up. Contrary to our superiority hypothesis, there was no significant difference between GL and MPM. Patients reported both GL and MPM (in person and video) as credible and were highly satisfied with the treatment experience. Next steps will involve examining the single-case experimental design data embedded in this trial to facilitate an understanding of individual differences in treatment responses (eg, when effects occurred, what processes changed during treatment within the treatment arm). The current findings support GET Living and MPM for youth with chronic pain.

The EMBER trial for weight management engagement: A hybrid type 1 randomized controlled trial protocol.

BACKGROUND: Almost 40% of Veterans Health Administration (VHA) users have obesity. VHA's national weight management program is associated with weight loss and improved health. However, while 94% of eligible VHA users are offered weight management programs, <8% use them. We developed EMBER - a novel, Motivational Interviewing-based, self-help tool - with the goal of Enhancing Motivation for Better Engagement and Reach for weight management. EMBER is not a weight management program; instead it engages people in existing programs by informing and guiding choices about weight management. METHODS: The EMBER Trial is a randomized hybrid type 1 effectiveness implementation trial. Participants are Palo Alto or Houston VA Health Care System users with obesity who have not used a VHA weight management program in the past two years (target N = 470). Participants are randomly assigned to EMBER or an information-only control condition, after which they receive materials on paper or digitally, per their preference. The trial's primary goal is to determine whether participants randomized to EMBER are more likely to have any weight management engagement at two-month follow-up compared to those in the control condition. Secondary outcomes include 6-month retention in weight management, weight management behaviors, weight loss, quality of life, and implementation outcomes (e.g., reach, appropriateness). CONCLUSION: EMBER is the first self-directed, Motivational Interviewing-based intervention designed to increase weight management program engagement. The study takes a low-touch, population health approach that could be modified for other programs if effective. The Hybrid Type 1 design will ensure results can be scaled and sustained.

Virtual Reality-Augmented Physiotherapy for Chronic Pain in Youth: Protocol for a Randomized Controlled Trial Enhanced With a Single-Case Experimental Design.

BACKGROUND: Chronic musculoskeletal (MSK) pain is a prominent health concern, resulting in pain-related disability, loss of functioning, and high health care costs. Physiotherapy rehabilitation is a gold-standard treatment for improving functioning in youth with chronic MSK pain. However, increasing physical activity can feel unattainable for many adolescents because of pain-related fear and movement avoidance. Virtual reality (VR) offers an immersive experience that can interrupt the fear-avoidance cycle and improve engagement in physiotherapy. Despite promising initial findings, data are limited and often lack the rigor required to establish VR as an evidence-based treatment for MSK pain. OBJECTIVE: This trial evaluates physiorehabilitation with VR in adolescents with MSK pain. This protocol outlines the rationale, design, and implementation of a randomized controlled trial enhanced with a single-case experimental design. METHODS: This study is a 2-group randomized controlled trial assessing the use of physiorehabilitation with VR in adolescents with MSK pain. The authors will collaborate with physical therapists to integrate VR into their standard clinical care. For participants enrolled in standard physiotherapy, there will be no VR integrated into their physical therapy program. Primary outcomes include physical function and engagement in VR. Secondary outcomes include pain-related fear and treatment adherence. Moreover, we will obtain clinician perspectives regarding the feasibility of integrating the intervention into the flow of clinical practice. RESULTS: The pilot study implementing physiorehabilitation with VR demonstrated that high engagement and use of physiorehabilitation with VR were associated with improvements in pain, fear, avoidance, and function. Coupled with qualitative feedback from patients, families, and clinicians, the pilot study results provide support for this trial to evaluate physiorehabilitation with VR for youth with chronic MSK pain. Analysis of results from the main clinical trial will begin as recruitment progresses, and results are expected in early 2024. CONCLUSIONS: Significant breakthroughs for treating MSK pain require mechanistically informed innovative approaches. Physiorehabilitation with VR provides exposure to progressive challenges, real-time feedback, and reinforcement for movement and can include activities that are difficult to achieve in the real world. It has the added benefit of sustaining patient motivation and adherence while enabling clinicians to use objective benchmarks to influence progression. These findings will inform the decision of whether to proceed with a hybrid effectiveness-dissemination trial of physiorehabilitation with VR, serving as the basis for potential large-scale implementation of physiorehabilitation with VR. TRIAL REGISTRATION: ClinicalTrials.gov NCT04636177; https://clinicaltrials.gov/ct2/show/NCT04636177. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40705.

Role of left atrial hypertension in pulmonary hypertension associated with bronchopulmonary dysplasia.

Left atrial hypertension (LAH) may contribute to pulmonary hypertension (PH) in premature infants with bronchopulmonary dysplasia (BPD). Primary causes of LAH in infants with BPD include left ventricular diastolic dysfunction or hemodynamically significant left to right shunt. The incidence of LAH, which is definitively diagnosed by cardiac catheterization, and its contribution to PH is unknown in patients with BPD-PH. We report the prevalence of LAH in an institutional cohort with BPD-PH with careful examination of hemodynamic contributors and impact on patient outcomes. This single-center, retrospective cohort study examined children <2 years of age with BPD-PH who underwent cardiac catheterization at Lucile Packard Children's Hospital Stanford. Patients with unrepaired simple shunt congenital heart disease (CHD) and pulmonary vein stenosis (only 1 or 2 vessel disease) were included. Patients with complex CHD were excluded. From April 2010 to December 2021, 34 patients with BPD-PH underwent cardiac catheterization. We define LAH as pulmonary capillary wedge pressure (PCWP) or left atrial pressure (LAP) of at least 10 mmHg. In this cohort, median PCWP was 8 mmHg, with LAH present in 32% (n = 11) of the total cohort. A majority (88%, n = 30) of the cohort had severe BPD. Most patients had some form of underlying CHD and/or pulmonary vein stenosis: 62% (n = 21) with an atrial septal defect or patent foramen ovale, 62% (n = 21) with patent ductus arteriosus, 12% (n = 4) with ventricular septal defect, and 12% (n = 4) with pulmonary vein stenosis. Using an unadjusted logistic regression model, baseline requirement for positive pressure ventilation at time of cardiac catheterization was associated with increased risk for LAH (odds ratio 8.44, 95% CI 1.46-48.85, p = 0.02). Small for gestational age birthweight, sildenafil use, and CHD were not associated with increased risk for LAH. LAH was associated with increased risk for the composite outcome of tracheostomy and/or death, with a hazard ratio of 6.32 (95% CI 1.72, 22.96; p = 0.005). While the etiology of BPD-PH is multifactorial, LAH is associated with PH in some cases and may play a role in clinical management and patient outcomes.

End-of-Life Cost Trajectories in Cancer Patients Treated by Medicare versus the Veterans Health Administration.

BACKGROUND/OBJECTIVES: To evaluate differences in end-of-life cost trajectories for cancer patients treated through Medicare versus by the Veterans Health Administration (VA). DESIGN: A retrospective analysis of VA and Medicare administrative data from FY 2010 to 2014. We employed three-level generalized estimating equations to evaluate monthly cost trajectories experienced by patients in their last year of life, with patients nested within hospital referral region. SETTING: Care received at VA facilities or by Medicare-reimbursed providers nationwide. PARTICIPANTS: A total of 36,401 patients dying from cancer and dually enrolled in VA and Medicare. MEASUREMENTS: We evaluated trajectories for total, inpatient, outpatient, and drug costs, using the last 12 months of life. Cost trajectories were prioritized as costs are not directly comparable across Medicare and VA. Patients were assigned to be VA-reliant, Medicare-reliant or Mixed-reliant based on their healthcare utilization in the last year of life. RESULTS: All three groups experienced significantly different cost trajectories for total costs in the last year of life. Inpatient cost trajectories were significantly different between Medicare-reliant and VA-reliant patients, but did not differ between VA-reliant and Mixed-reliant patients. Outpatient and drug cost trajectories exhibited the inverse pattern: they were significantly different between VA-reliant and Mixed-reliant patients, but not between VA-reliant and Medicare-reliant patients. However, visual examination of cost trajectories revealed similar cost patterns in the last year of life among all three groups; there was a sharp rise in costs as patients approach death, largely due to inpatient care. CONCLUSION: Despite substantially different financial incentives and organization, VA- and Medicare-treated patients exhibit similar patterns of increasing end-of-life costs, largely driven by inpatient costs. Both systems require improvement to ensure quality of end-of-life care is aligned with recommended practice.

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.

Graded exposure treatment for adolescents with chronic pain (GET Living): Protocol for a randomized controlled trial enhanced with single case experimental design.

Chronic musculoskeletal pain in adolescence is a significant public health concern with 3-5% of adolescents suffering from significant pain-related disability. Pain-related fear and avoidance of activities has been found to have a significant influence on pain outcomes in children and adolescents and is a risk factor for less favorable response to treatment. To address this need, we developed graded exposure treatment for youth with chronic pain (GET Living). We describe the rationale, design, and implementation of a two-group randomized controlled trial (RCT) enhanced with single-case experimental design (SCED) methodology with a sample of 74 adolescents with chronic musculosketal pain and their parent caregivers. GET Living includes education, behavioral exposures, and parent intervention jointly delivered by pain psychology and physical therapy providers. The multidisciplinary pain management control group includes pain psychology delivered education and pain self-management skills training (e.g., relaxation, cognitive skills) and separate physical therapy. Assessments include brief daily diaries (baseline to discharge, 7-days at 3-month and 6-month follow-up), comprehensive in-person evaluations at baseline and discharge, and questionnaire across all time points (baseline, discharge, 3-month and 6-month follow-up). Primary outcome is pain-related fear avoidance. Secondary outcome is functional disability. We also outline all additional outcomes, exploratory outcomes, covariates, and implementation measures. The objective is to offer a mechanism-based, targeted intervention to youth with musculoskeletal pain to enhance likelihood of return to function.

Years of Potential Life Lost Because of Cardiovascular Disease in Asian-American Subgroups, 2003-2012.

Background Asian-American subgroups (Asian-Indian, Chinese, Filipino, Korean, Japanese, and Vietnamese) display varied cardiovascular disease mortality patterns, especially at younger ages. This study aims to examine the years of potential life lost because of ischemic heart disease and cerebrovascular disease among the 6 largest Asian-American subgroups compared with non-Hispanic whites. Methods and Results We used National Center for Health Statistics Multiple Causes of Death mortality files from 2003 to 2012 to calculate race-specific life expectancy, mean years of potential life lost, and years of potential life lost per 100 000 population for each Asian subgroup and non-Hispanic whites. Asian-American subgroups display heterogeneity in cardiovascular disease burden. Asian-Indians had a high burden of ischemic heart disease; Asian-Indian men lost 724 years per 100 000 population in 2012 and a mean of 17 years to ischemic heart disease. Respectively, Vietnamese and Filipino men and women lost a mean of 17 and 16 years of life to cerebrovascular disease; Filipino men lost 352 years per 100 000 population in 2012. All Asian subgroups for both sexes had higher years of life lost to cerebrovascular disease compared with non-Hispanic whites. Conclusions Cardiovascular disease burden varies among Asian subgroups, and contributes to greater premature mortality in certain subgroups. Asian-Indian and Filipino populations have the highest years of life lost because of ischemic heart disease and Filipino and Vietnamese have the highest years of life lost because of cerebrovascular disease. Analysis of risk factors and development of subgroup-specific interventions are required to address these health disparities.

Parasitic infections during pregnancy need not affect infant antibody responses to early vaccination against Streptococcus pneumoniae, diphtheria, or Haemophilus influenzae type B.

BACKGROUND: Globally, vaccine-preventable diseases remain a significant cause of early childhood mortality despite concerted efforts to improve vaccine coverage. One reason for impaired protection may be the influence of prenatal exposure to parasitic antigens on the developing immune system. Prior research had shown a decrease in infant vaccine response after in utero parasite exposure among a maternal cohort without aggressive preventive treatment. This study investigated the effect of maternal parasitic infections on infant vaccination in a more recent setting of active anti-parasitic therapy. METHODOLOGY/PRINCIPAL FINDINGS: From 2013-2015, 576 Kenyan women were tested in pregnancy for malaria, soil-transmitted helminths, filaria, and S. haematobium, with both acute and prophylactic antiparasitic therapies given. After birth, 567 infants received 10-valent S. pneumoniae conjugate vaccine and pentavalent vaccine for hepatitis B, pertussis, tetanus, H. influenzae type B (Hib) and C. diphtheriae toxoid (Dp-t) at 6, 10, and 14 weeks. Infant serum samples from birth, 10 and 14 weeks, and every six months until age three years, were analyzed using a multiplex bead assay to quantify IgG for Hib, Dp-t, and the ten pneumococcal serotypes. Antenatal parasitic prevalence was high; 461 women (80%) had at least one and 252 (43.6%) had two or more infections during their pregnancy, with the most common being malaria (44.6%), S. haematobium (43.9%), and hookworm (29.2%). Mixed models comparing influence of infection on antibody concentration revealed no effect of prenatal infection status for most vaccine outcomes. Prevalences of protective antibody concentrations after vaccination were similar among the prenatal exposure groups. CONCLUSIONS/SIGNIFICANCE: These findings are in contrast with results from our prior cohort study performed when preventive anti-parasite treatment was less frequently given. The results suggest that the treatment of maternal infections in pregnancy may be able to moderate the previously observed effect of antenatal maternal infections on infant vaccine responses.

Acute Flavivirus and Alphavirus Infections among Children in Two Different Areas of Kenya, 2015.

Alphaviruses and flaviviruses are known to be endemic in Eastern Africa, but few data are available to evaluate the prevalence of these infections. This leads to missed opportunities for prevention against future outbreaks. This cohort study investigated the frequency of alphavirus and flavivirus incident infections in two regions of Kenya and identified potential risk factors. Seroconversions for alphavirus and flavivirus infections were identified by immunoglobulin G enzyme-linked immunosorbent assay (IgG-ELISA) in a cohort of 1,604 acutely ill children over the year 2015. The annual incidence was 0.5% (0.2-1.2%) for alphaviruses and 1.2% (0.7-2.2%) for flaviviruses. Overall, seroprevalence was significantly higher for alphaviruses in western Kenya than on the coast (P = 0.014), whereas flavivirus seroprevalence was higher on the coast (P = 0.044). Poverty indicators did not emerge as risk factors, but reliance on household water storage was associated with increased exposure to both alphaviruses and flaviviruses (odds ratio = 2.3).

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.

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.

Thiazolidinediones and Risk of Atrial Fibrillation Among Patients with Diabetes and Coronary Disease.

BACKGROUND: We sought to determine whether insulin-sensitizing therapy (thiazolidinediones or metformin) decreased the risk of developing atrial fibrillation compared with insulin-providing therapy (insulin, sulfonylurea, or a meglitinide). Thiazolidinediones are insulin sensitizers that also decrease the inflammatory response. Because inflammation is a risk factor for atrial fibrillation, we hypothesized that treating diabetes with thiazolidinediones might decrease the risk of developing atrial fibrillation. METHODS: The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial enrolled patients with type 2 diabetes and documented coronary artery disease. All patients were randomized to insulin-sensitizing therapy or insulin-providing therapy. RESULTS: A total of 2319 patients entered the study, with 1160 assigned to the insulin-sensitization strategy and 1159 assigned to the insulin-provision strategy. Over a median follow-up of 4.2 years, 90 patients (3.9%) developed new-onset atrial fibrillation. In the intention-to-treat analysis, the incidence of atrial fibrillation was 8.7 per 1000 person-years in patients assigned to insulin sensitization compared with 9.5 in patients assigned to insulin provision with a hazard ratio (HR) of 0.91 (95% confidence interval [CI], 0.60-1.38, P = .66). In a time-varying exposure analysis, the incidence rate per 1000 person-years was 7.2 while exposed to thiazolidinediones and 9.7 while not exposed to thiazolidinediones with an adjusted HR of 0.80 (95% CI, 0.33-1.94, P = .62). In a subset of patients matched on propensity to receive a thiazolidinediones, the HR was 0.75 (95% CI, 0.43-1.30, P = .30). CONCLUSIONS: We did not find a significant reduction of atrial fibrillation incidence with use of thiazolidinediones.

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.

The Identification of Risk Factors for Chronic Chikungunya Arthralgia in Grenada, West Indies: A Cross-Sectional Cohort Study.

BACKGROUND: Chikungunya virus (CHIKV) is a re-emerging arboviral pathogen. In 2014, an explosive CHIKV outbreak occurred in Grenada, West Indies, infecting approximately 60% of the population. In approximately 50% of cases, CHIKV infection transitions to painful arthralgia that can persist for years. Elucidation of the risk factors for chronic disease is imperative to the development of effective risk management strategies and specific therapeutics. METHODS: We conducted a cross-sectional study of 240 people who were tested for CHIKV during the outbreak. We administered questionnaires to examine demographic, behavioral, psychological, social, and environmental factors to identify associations with chronic disease. Physical examinations were performed and persistent symptoms were recorded. RESULTS: Ethnicity and socioeconomic status were not associated with risk of chronic joint pain. Female sex increased risk, and age was demonstrated to be predictive of chronic CHIKV sequelae. Mosquito avoidance behaviors did not reduce risk. Patients suffering joint pains, generalized body ache, and weakness in the extremities during acute infection were more likely to develop chronic arthralgia, and an increased duration of acute disease also increased risk. CONCLUSIONS: These data demonstrate that chronic CHIKV affects people across the ethnic and socioeconomic spectrum, and it is not reduced by vector avoidance activity. Increased duration of acute symptoms, in particular acute joint pain, was strongly correlated with the risk of persistent arthralgia, thus effective clinical management of acute CHIKV disease could reduce burden of chronic CHIKV.

Quality Of End-Of-Life Care Is Higher In The VA Compared To Care Paid For By Traditional Medicare.

Congressional and Veterans Affairs (VA) leaders have recommended the VA become more of a purchaser than a provider of health care. Fee-for-service Medicare provides an example of how purchased care differs from the VA's directly provided care. Using established indicators of overly intensive end-of-life care, we compared the quality of care provided through the two systems to veterans dying of cancer in fiscal years 2010-14. The Medicare-reliant veterans were significantly more likely to receive high-intensity care, in the form of chemotherapy, hospital stays, admission to the intensive care unit, more days spent in the hospital, and death in the hospital. However, they were significantly less likely than VA-reliant patients to have multiple emergency department visits. Higher-intensity end-of-life care may be driven by financial incentives present in fee-for-service Medicare but not in the VA's integrated system. To avoid putting VA-reliant veterans at risk of receiving lower-quality care, VA care-purchasing programs should develop coordination and quality monitoring programs to guard against overly intensive end-of-life care.

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.