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.

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.

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.

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.

Impact of drug-eluting stents on the comparative effectiveness of coronary artery bypass surgery and percutaneous coronary intervention.

BACKGROUND: Drug-eluting stents (DES) have largely replaced bare-metal stents (BMS) for percutaneous coronary intervention (PCI). It is uncertain, however, whether introduction of DES had a significant impact on the comparative effectiveness of PCI versus coronary artery bypass graft surgery (CABG) for death and myocardial infarction (MI). METHODS: We identified Medicare beneficiaries aged ≥66 years who underwent multivessel CABG or multivessel PCI and matched PCI and CABG patients on propensity score. We defined the BMS era as January 1999 to April 2003 and the DES era as May 2003 to December 2006. We compared 5-year outcomes of CABG and PCI using Cox proportional hazards models, adjusting for baseline characteristics and year of procedure and tested for a statistically significant interaction (P(int)) of DES era with treatment (CABG or PCI). RESULTS: Five-year survival improved from the BMS era to the DES era by 1.2% for PCI and by 1.1% for CABG, and the CABG:PCI hazard ratio was unchanged (0.90 vs 0.90; P(int) = .96). Five-year MI-free survival improved by 1.4% for PCI and 1.1% for CABG, with no change in the CABG:PCI hazard ratio (0.81 vs 0.82; P(int) = .63). By contrast, survival-free of MI or repeat coronary revascularization improved from the BMS era to the DES era by 5.7% for PCI and 0.9% for CABG, and the CABG:PCI hazard ratio changed significantly (0.50 vs 0.57, P(int) ≤ .0001). CONCLUSIONS: The introduction of DES did not alter the comparative effectiveness of CABG and PCI with respect to hard cardiac outcomes.

Cost-effectiveness of genotype-guided and dual antiplatelet therapies in acute coronary syndrome.

BACKGROUND: The choice of antiplatelet therapy after acute coronary syndrome (ACS) is complicated: Ticagrelor and prasugrel are novel alternatives to clopidogrel, patients with some genotypes may not respond to clopidogrel, and low-cost generic formulations of clopidogrel are available. OBJECTIVE: To determine the most cost-effective strategy for dual antiplatelet therapy after percutaneous coronary intervention for ACS. DESIGN: Decision-analytic model. DATA SOURCES: Published literature, Medicare claims, and life tables. TARGET POPULATION: Patients having percutaneous coronary intervention for ACS. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Five strategies were examined: generic clopidogrel, prasugrel, ticagrelor, and genotyping for polymorphisms of CYP2C19 with carriers of loss-of-function alleles receiving either ticagrelor (genotyping with ticagrelor) or prasugrel (genotyping with prasugrel) and noncarriers receiving clopidogrel. OUTCOME MEASURES: Direct medical costs, quality-adjusted life years(QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: The clopidogrel strategy produced$179 301 in costs and 9.428 QALYs. Genotyping with prasugrel was superior to prasugrel alone, with an ICER of $35 800 per QALY relative to clopidogrel. Genotyping with ticagrelor was more effective than genotyping with prasugrel ($30 200 per QALY relative to clopidogrel). Ticagrelor was the most effective strategy($52 600 per QALY relative to genotyping with ticagrelor). RESULTS OF SENSITIVITY ANALYSIS: Stronger associations between genotype and thrombotic outcomes rendered ticagrelor substantially less cost-effective ($104 800 per QALY). Genotyping with prasugrel was the preferred therapy among patients who could not tolerate ticagrelor. LIMITATION: No randomized trials have directly compared genotyping strategies or prasugrel with ticagrelor. CONCLUSION: Genotype-guided personalization may improve the cost-effectiveness of prasugrel and ticagrelor after percutaneous coronary intervention for ACS, but ticagrelor for all patients may bean economically reasonable alternative in some settings.

Cost-effectiveness of percutaneous coronary intervention in patients with stable coronary artery disease and abnormal fractional flow reserve.

BACKGROUND: The Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) 2 trial demonstrated a significant reduction in subsequent coronary revascularization among patients with stable angina and at least 1 coronary lesion with a fractional flow reserve ≤0.80 who were randomized to percutaneous coronary intervention (PCI) compared with best medical therapy. The economic and quality-of-life implications of PCI in the setting of an abnormal fractional flow reserve are unknown. METHODS AND RESULTS: We calculated the cost of the index hospitalization based on initial resource use and follow-up costs based on Medicare reimbursements. We assessed patient utility using the EQ-5D health survey with US weights at baseline and 1 month and projected quality-adjusted life-years assuming a linear decline over 3 years in the 1-month utility improvements. We calculated the incremental cost-effectiveness ratio based on cumulative costs over 12 months. Initial costs were significantly higher for PCI in the setting of an abnormal fractional flow reserve than with medical therapy ($9927 versus $3900, P<0.001), but the $6027 difference narrowed over 1-year follow-up to $2883 (P<0.001), mostly because of the cost of subsequent revascularization procedures. Patient utility was improved more at 1 month with PCI than with medical therapy (0.054 versus 0.001 units, P<0.001). The incremental cost-effectiveness ratio of PCI was $36 000 per quality-adjusted life-year, which was robust in bootstrap replications and in sensitivity analyses. CONCLUSIONS: PCI of coronary lesions with reduced fractional flow reserve improves outcomes and appears economically attractive compared with best medical therapy among patients with stable angina.

Comparative effectiveness of multivessel coronary bypass surgery and multivessel percutaneous coronary intervention: a cohort study.

BACKGROUND: Randomized trials of coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI) suggest that patient characteristics modify the effect of treatment on mortality. OBJECTIVE: To assess whether clinical characteristics modify the comparative effectiveness of CABG versus PCI in an unselected, general patient population. DESIGN: Observational treatment comparison using propensity score matching and Cox proportional hazards models. SETTING: United States, 1992 to 2008. PATIENTS: Medicare beneficiaries aged 66 years or older. INTERVENTION: Multivessel CABG or multivessel PCI. MEASUREMENTS: The CABG-PCI hazard ratio (HR) for all-cause mortality, with prespecified treatment-by-covariate interaction tests, and the absolute difference in life-years of survival in clinical subgroups after CABG or PCI, both over 5 years of follow-up. RESULTS: Among 105 156 propensity score-matched patients, CABG was associated with lower mortality than PCI (HR, 0.92 [95% CI, 0.90 to 0.95]; P < 0.001). Association of CABG with lower mortality was significantly greater (interaction P ≤ 0.002 for each) among patients with diabetes (HR, 0.88), a history of tobacco use (HR, 0.82), heart failure (HR, 0.84), and peripheral arterial disease (HR, 0.85). The overall predicted difference in survival between CABG and PCI treatment over 5 years was 0.053 life-years (range, -0.017 to 0.579 life-years). Patients with diabetes, heart failure, peripheral arterial disease, or tobacco use had the largest predicted differences in survival after CABG, whereas those with none of these factors had slightly better survival after PCI. LIMITATION: Treatments were chosen by patients and physicians rather than being randomly assigned. CONCLUSION: Multivessel CABG is associated with lower long-term mortality than multivessel PCI in the community setting. This association is substantially modified by patient characteristics, with improvement in survival concentrated among patients with diabetes, tobacco use, heart failure, or peripheral arterial disease. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

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.

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.

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.

A sustained virologic response reduces risk of all-cause mortality in patients with hepatitis C.

BACKGROUND & AIMS: The effectiveness of hepatitis C virus (HCV) treatment with pegylated interferon and ribavirin usually is evaluated by the surrogate end point of sustained virologic response (SVR), although the ultimate goal of antiviral treatment is to reduce mortality. The impact of SVR on all-cause mortality is not well documented by HCV genotype or in populations in routine medical practice with substantial comorbidities. METHODS: From the US Department of Veterans Affairs (VA), we identified all patients infected with HCV genotypes 1, 2, or 3, without human immunodeficiency virus co-infection or hepatocellular carcinoma before HCV treatment with pegylated interferon and ribavirin, who started HCV treatment from January 2001 to June 2007, stopped treatment by June 2008, and had a posttreatment HCV RNA test result of SVR or no SVR. Mortality data from VA and non-VA sources were available through 2009. RESULTS: HCV genotypes 1, 2, or 3 cohorts consisted of 12,166, 2904, and 1794 patients, respectively, with SVR rates of 35%, 72%, and 62%, respectively. Each cohort had high rates of comorbidities. During a median follow-up period of approximately 3.8 years, 1119 genotype-1, 220 genotype-2, and 196 genotype-3 patients died. In genotype-specific multivariate survival models that controlled for demographic factors, comorbidities, laboratory characteristics, and treatment characteristics, an SVR was associated with substantially reduced mortality risk for each genotype (genotype-1 hazard ratio, 0.70; P < .0001; genotype-2 hazard ratio, 0.64; P = .006; genotype-3 hazard ratio, 0.51; P = .0002). CONCLUSIONS: An SVR reduced mortality among patients infected with HCV of genotypes 1, 2, or 3 who were being treated by routine medical practice and had substantial comorbidities.

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.

Economic outcomes of treatment strategies for type 2 diabetes mellitus and coronary artery disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial.

BACKGROUND: The economic outcomes of clinical management strategies are important in assessing their value to patients. METHODS AND RESULTS: Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) randomized patients with type 2 diabetes mellitus and angiographically documented, stable coronary disease to strategies of (1) prompt revascularization versus medical therapy with delayed revascularization as needed to relieve symptoms and (2) insulin sensitization versus insulin provision. Before randomization, the physician declared whether coronary artery bypass grafting or percutaneous coronary intervention would be used if the patient were assigned to revascularization. We followed 2005 patients for medical utilization and costs and assessed the cost-effectiveness of these management strategies. Medical costs were higher for revascularization than medical therapy, with a significant interaction with the intended method of revascularization (P<0.0001). In the coronary artery bypass grafting stratum, 4-year costs were $80 900 for revascularization versus $60 600 for medical therapy (P<0.0001). In the percutaneous coronary intervention stratum, costs were $73 400 for revascularization versus $67 800 for medical therapy (P<0.02). Costs also were higher for insulin sensitization ($71 300) versus insulin provision ($70 200). Other factors that significantly (P<0.05) and independently increased cost included insulin use and dose at baseline, female sex, white race, body mass index > or =30, and albuminuria. Cost-effectiveness based on 4-year data favored the strategy of medical therapy over prompt revascularization and the strategy of insulin provision over insulin sensitization. Lifetime projections of cost-effectiveness showed that medical therapy was cost-effective compared with revascularization in the percutaneous coronary intervention stratum ($600 per life-year added) with high confidence. Lifetime projections suggest that revascularization may be cost-effective in the coronary artery bypass grafting stratum ($47 000 per life-year added) but with lower confidence. CONCLUSIONS: Prompt coronary revascularization significantly increases costs among patients with type 2 diabetes mellitus and stable coronary disease. The strategy of medical therapy (with delayed revascularization as needed) appears to be cost-effective compared with the strategy of prompt coronary revascularization among patients identified a priori as suitable for percutaneous coronary intervention.