Effects of the Million Hearts Model on Myocardial Infarctions, Strokes, and Medicare Spending: A Randomized Clinical Trial.

Importance: The Million Hearts Model paid health care organizations to assess and reduce cardiovascular disease (CVD) risk. Model effects on long-term outcomes are unknown. Objective: To estimate model effects on first-time myocardial infarctions (MIs) and strokes and Medicare spending over a period up to 5 years. Design, Setting, and Participants: This pragmatic cluster-randomized trial ran from 2017 to 2021, with organizations assigned to a model intervention group or standard care control group. Randomized organizations included 516 US-based primary care and specialty practices, health centers, and hospital-based outpatient clinics participating voluntarily. Of these organizations, 342 entered patients into the study population, which included Medicare fee-for-service beneficiaries aged 40 to 79 years with no previous MI or stroke and with high or medium CVD risk (a 10-year predicted probability of MI or stroke [ie, CVD risk score] ≥15%) in 2017-2018. Intervention: Organizations agreed to perform guideline-concordant care, including routine CVD risk assessment and cardiovascular care management for high-risk patients. The Centers for Medicare & Medicaid Services paid organizations to calculate CVD risk scores for Medicare fee-for-service beneficiaries. CMS further rewarded organizations for reducing risk among high-risk beneficiaries (CVD risk score ≥30%). Main Outcomes and Measures: Outcomes included first-time CVD events (MIs, strokes, and transient ischemic attacks) identified in Medicare claims, combined first-time CVD events from claims and CVD deaths (coronary heart disease or cerebrovascular disease deaths) identified using the National Death Index, and Medicare Parts A and B spending for CVD events and overall. Outcomes were measured through 2021. Results: High- and medium-risk model intervention beneficiaries (n = 130 578) and standard care control beneficiaries (n = 88 286) were similar in age (median age, 72-73 y), sex (58%-59% men), race (7%-8% Black), and baseline CVD risk score (median, 24%). The probability of a first-time CVD event within 5 years was 0.3 percentage points lower for intervention beneficiaries than control beneficiaries (3.3% relative effect; adjusted hazard ratio [HR], 0.97 [90% CI, 0.93-1.00]; P = .09). The 5-year probability of combined first-time CVD events and CVD deaths was 0.4 percentage points lower in the intervention group (4.2% relative effect; HR, 0.96 [90% CI, 0.93-0.99]; P = .02). Medicare spending for CVD events was similar between the groups (effect estimate, -$1.83 per beneficiary per month [90% CI, -$3.97 to -$0.30]; P = .16), as was overall Medicare spending including model payments (effect estimate, $2.11 per beneficiary per month [90% CI, -$16.66 to $20.89]; P = .85). Conclusions and Relevance: The Million Hearts Model, which encouraged and paid for CVD risk assessment and reduction, reduced first-time MIs and strokes. Results support guidelines to use risk scores for CVD primary prevention. Trial Registration: ClinicalTrials.gov Identifier: NCT04047147.

Stroke risk following implantation of current generation centrifugal flow left ventricular assist devices.

BACKGROUND AND AIM: Stroke remains a significant complication of left ventricular assist device (LVAD) therapy. We performed a single-center retrospective study evaluating patients undergoing first-time HeartWare HVAD (Medtronic Inc) or HeartMate 3 (Abbott Inc) implantation from September 2009-February 2018. METHODS: Exclusion criteria were age <18 and preoperative ECMO. The primary endpoint was stroke-free survival. Stroke was defined as new neurological deficits persisting >24 hours with corresponding radiographic evidence. Risk factors evaluated included demographics, medical comorbidities, heart failure etiology, LVAD indication, INTERMACS profile, and device type. Univariate predictors (P < .15) and variables clinically suspected to raise stroke risk were entered in a multivariate hazard regression model, specified using backward selection of covariates and accounting for competing risks of transplant/LVAD exchange. RESULTS: A total of 163 HVAD and 84 HM3 patients were analyzed. Median follow up (until death, censoring for transplant/LVAD removal, or end of follow up) was 1.2 years in HVAD patients and 1.4 years in HM3 patients. Stroke occurred in 24 HVAD patients (15 ischemic, 9 hemorrhagic) and 6 HM3 patients (4 ischemic, 2 hemorrhagic). One-year stroke-free survival was 76.8% for HVAD and 84.3% for HM3. Thirty-day mortality following stroke was 41.7% for HVAD and 66.7% for HM3; 54.2% of HVAD strokes were disabling compared to 83.3% of HM3 strokes. Age, LVAD indication, and device type were associated (P < .15) with stroke on univariate analysis. On multivariate analysis, the HVAD was associated with significantly higher stroke risk (hazard ratio, 2.57; 95% confidence interval, 1.02-6.44; P = .045). CONCLUSIONS: Different LVAD models appear to be associated with significantly different stroke risks.

Comorbidities and the decision to undergo or forego destination therapy left ventricular assist device implantation: An analysis from the Trial of a Shared Decision Support Intervention for Patients and their Caregivers Offered Destination Therapy for End-Stage Heart Failure (DECIDE-LVAD) study.

BACKGROUND: Patients considering destination therapy left ventricular assist devices (DT LVAD) often have high comorbid burden but the association between these comorbidities and post-decision outcomes is unknown. METHODS: We included subjects in DECIDE-LVAD (NCT02344576), a stepped-wedge multicenter trial of patients considering LVADs, recording comorbidities per INTERMACS protocol. We compared decisional conflict, regret, perceived stress, quality of life (EQ-VAS), depression (PHQ-2), struggle with- and acceptance of illness by comorbid burden and amongst the most common comorbidities. RESULTS: Of 239 patients, LVAD recipients (n = 164) and non-recipients (n = 75) had a similar proportion with ≥1 comorbidity (70% v. 80%, P = .09). Patients with comorbidities were younger regardless of LVAD implantation status. After adjusting for age, overall and amongst LVAD recipients, patients with ≥1 comorbidity had higher mean decision conflict at baseline (23.2 ±â€¯1.5 vs. 17.4 ±â€¯2.2), and at 6 months, higher stress (13.0 ±â€¯0.6 vs. 10.4 ±â€¯1.0) and struggle with illness (13.3 ±â€¯0.4 vs. 11.1 ±â€¯0.6) than those without comorbidities (P < .05). No difference was noted in decision regret, PHQ-2, EQ-VAS, acceptance of illness and survival overall and amongst LVAD recipients. Of the three most common comorbidities, while patients with pulmonary hypertension had worse decision regret, depression, stress and acceptance of illness at 6-month follow-up than those who did not have pulmonary hypertension, no difference was noted in patients with chronic renal disease or high body mass index. CONCLUSION: Patients considering LVAD implantation with comorbidities experience increased decision conflict, stress and struggle with illness. These findings provide insights in the role comorbidities play in patient decision-making and decisional outcomes.

The Impact of a Health Information Technology-Focused Patient-centered Medical Neighborhood Program Among Medicare Beneficiaries in Primary Care Practices: The Effect on Patient Outcomes and Spending.

BACKGROUND: The Center for Medicare & Medicaid Innovation (CMMI) tests new models of paying for or delivering health care services and expands models that improve health outcomes while lowering medical spending. CMMI gave TransforMED, a national learning and dissemination contractor, a 3-year Health Care Innovation Award (HCIA) to integrate health information technology systems into physician practices. This paper estimates impacts of TransforMED's HCIA-funded program on patient outcomes and Medicare parts A and B spending. RESEARCH DESIGN: We compared outcomes for Medicare fee-for-service (FFS) beneficiaries served by 87 treatment practices to outcomes for Medicare FFS beneficiaries served by 286 matched comparison practices, adjusting for differences in outcomes between the 2 groups during a 1-year baseline period. We estimated impacts in 3 evaluation outcome domains: quality-of-care processes, service use, and spending. RESULTS: We estimated the program led to a 7.1% reduction in inpatient admissions and a 5.7% decrease in the outpatient emergency department visits. However, there was no evidence of statistically significant effects in outcomes in either the quality-of-care processes or spending domains. CONCLUSIONS: These results indicate that TransforMED's program reduced service use for Medicare FFS beneficiaries, but also show that the program did not have statistically significant favorable impacts in the quality-of-care processes or spending domains. These results suggest that providing practices with population health management and cost-reporting software-along with technical assistance for how to use them-can complement practices' own patient-centered medical home transformation efforts and add meaningfully to their impacts on service use.

Disease and weight loss: a prospective study of middle-aged and older adults in Costa Rica and England.

OBJECTIVE: To determine whether disease predicts weight loss in population-based studies, as this may confound the relationship between weight and mortality. MATERIALS AND METHODS: We used longitudinal data from the Costa Rican Longevity and Healthy Aging Study (CRELES) and the English Longitudinal Study of Ageing (ELSA). We defined two overlapping outcomes of measured weight loss between waves: >1.0 point of body mass index (BMI) and >2.0 BMI points. Logistic regression models estimated the associations with disease, adjusting for age (range 52-79), sex, smoking, and initial BMI. RESULTS: In ELSA, onset of diabetes, cancer, or lung disease is associated with loss >2.0 points (respectively, OR=2.25 [95%CI: 1.34-3.80]; OR=2.70 [95%CI: 1.49-4.89]; OR=1.82 [95%CI: 1.02-3.26]). In CRELES, disease-onset reports are not associated with weight loss at 5% significance, but statistical power to detect associations is poor. CONCLUSION: Although it is known that some diseases cause weight loss, at the population level these associations vary considerably across samples.

Thrombolytic therapy for thrombosis of continuous flow ventricular assist devices.

BACKGROUND: Despite chronic systemic anticoagulation, advanced heart failure patients treated with a continuous-flow left ventricular assist device (LVAD) remain at risk for pump thrombosis. Pump thrombosis may initially be suspected in the setting of clinical and biochemical evidence for intravascular hemolysis, putatively related to shear stress on red blood cells propelled through a partially occluded pump. Limited data exist to guide management in these patients. METHODS AND RESULTS: We present a series of 8 LVAD patients who presented with intravascular hemolysis secondary to pump thrombosis who were treated with intraventricular thrombolytic therapy. In 3 patients, thrombolytic therapy led to complete and lasting resolution of hemolysis, suggesting successful dissolution of pump thrombus. In the remaining 5 patients, thrombolytic therapy ultimately failed to halt or reverse pump thrombosis and hemolysis: 1 patient required emergent pump exchange, 2 patients progressed to cardiogenic shock and died, 1 patient suffered a debilitating stroke after which care was withdrawn, and 1 patient underwent cardiac transplantation. CONCLUSIONS: In the setting of LVAD thrombosis, thrombolytic therapy is an alternate treatment strategy in a subset of patients. Candidacy for this alternate procedure must carefully weigh the risks of complications, including hemorrhage and thromboembolism.

Critical Aspects of pH Measurement for Bacteriostatic Water for Injection.

Bacteriostatic water for injection (bWFI) is a common diluent for parenteral pharmaceutical products. bWFI is sterile water for injection containing one or more suitable antimicrobial agents to suppress the growth of microbial contaminants. United States Pharmacopeia (USP) monograph describes bWFI with pH ranging from pH 4.5 to 7.0. Lacking buffering reagents, bWFI has very low ionic strength, no buffering capacity and is prone to sample contamination. These characteristics pose a challenge for accurate bWFI pH measurements which are characterized by long response times and noisy signals, resulting in inconsistent results. The challenging nature of bWFI pH measurement, however, is not fully recognized as pH is generally considered a routine analytical technique. Even with the addition of KCl to increase ionic strength as recommended by the USP bWFI monograph, variability in pH results is still observed without careful consideration of other critical measurement factors. To bring awareness to the challenges associated with bWFI pH measurement, we present a comprehensive characterization of the bWFI pH measurement process that includes an evaluation of probe suitability, measurement stabilization time, and pH meter settings. While these factors may be non-critical and sometimes overlooked when developing pH methods for buffered samples, they can have a significant impact on bWFI pH measurement. We present recommendations that can help reliable bWFI pH measurements for routine execution in a controlled environment. These recommendations also apply to other pharmaceutical solutions or water samples with low ionic strength.

Morphology and separation efficiency of low-aspect-ratio capillary ultrahigh pressure liquid chromatography columns.

We derive a quantitative relationship between the bed morphology and the chromatographic separation efficiency of capillary columns packed with sub-2 µm particles, covering capillary inner diameters from 10 to 75 µm. Our study focuses on wall effects and their impact on band broadening at increasing column-to-particle diameter (aspect) ratios. We approach these complex effects by a morphological analysis of reconstructed column segments composed of several thousand particles that were imaged by confocal laser scanning microscopy. Radial interparticle porosity profiles including wall effects are quantified through an integral porosity deviation, a scalar measure that proves to be a general descriptor of transcolumn porosity heterogeneity. It correlates with the associated transcolumn eddy dispersion, which dominates band broadening in the capillaries and is visualized in the plate height curves by a simple velocity-proportional term. Our comprehensive approach identifies the packing structure features that contribute to decreased efficiency as reflected, e.g., in subtle variations of the wall effect at different aspect ratios, or a particle size-segregation effect in larger-diameter columns as a result of an increased number of packing voids near the wall-bed interface.

State-of-the-art and emerging trends in analytical approaches to pharmaceutical-product commercialization.

The biopharmaceutical landscape continues to evolve rapidly, and associated modality complexity and the need to improve molecular understanding require concomitant advances in analytical approaches used to characterize and release the product. The Product Quality Attribute Assessment (PQAA) and Quality Target Product Profile (QTPP) frameworks help catalog and translate molecular understanding to process and product-design targets, thereby enabling reliable manufacturing of high-quality product. The analytical target profile forms the basis of identifying best-fit analytical methods for attribute measurement and continues to be successfully used to develop robust analytical methods for detailed product characterization as well as release and stability testing. Despite maturity across multiple testing platforms, advances continue to be made, several with the potential to alter testing paradigms. There is an increasing role for mass spectrometry beyond product characterization and into routine release testing as seen by the progress in multi-attribute methods and technologies, applications to aggregate measurement, the development of capillary zone electrophoresis (CZE) coupled with mass spectrometry (MS) and capillary isoelectric focusing (CIEF) with MS for measurement of glycans and charged species, respectively, and increased application to host cell protein measurement. Multitarget engaging multispecific modalities will drive advances in bioassay platforms and recent advances both in 1- and 2-D NMR approaches could make it the method of choice for characterizing higher-order structures. Additionally, rigorous understanding of raw material and container attributes is necessary to complement product understanding, and these collectively can enable robust supply of high-quality product to patients.

Development of claims-based measures of unplanned acute care with superior power for assessing the effectiveness of interventions following acute care.

OBJECTIVE: To develop outcome measures that are more sensitive than current measures for evaluating primary or transitional care after hospitalizations, emergency department (ED) visits, or observation stays. DATA SOURCES: Medicare claims data from January 1, 2015, to October 31, 2017, for 1 261 707 Medicare fee-for-service beneficiaries served by (a) primary care practices participating in Track 1 of the Comprehensive Primary Care Plus (CPC+) initiative, and (b) their matched comparison practices. STUDY DESIGN: Given the poor statistical power in many studies to detect effects on readmissions, we developed two novel claims-based measures of unplanned acute care (UAC) following an index acute care event. The first measure assesses the proportion of hospitalizations followed by an unplanned readmission, ED visit, or observation stay within 30 days of discharge; the second assesses the proportion of ED visits and observation stays followed by a hospitalization, ED visit, or observation stay within 30 days. We calculate minimum detectable effects (MDEs) for both measures and for a conventional measure of 30-day unplanned readmissions, using CPC+ data. PRINCIPAL FINDINGS: Repeat UAC events are common among Medicare beneficiaries served by the CPC+ practices. In 2017, 22% of discharges and 21% of ED visits and observation stays had a UAC event within 30 days. Readmissions were the most common UAC event following discharge, whereas ED visits were most common following index ED visits or observation stays. MDEs are 25%-40% lower for the new measures than for the standard 30-day readmissions measure, indicating better statistical power to detect impacts of primary or transitional care interventions. CONCLUSIONS: This study introduces two new claims-based measures to assess quality of care during a patient's vulnerable period following acute care. The new measures complement existing measures, covering a broader range of UAC events than the standard 30-day readmissions measure, and yielding greater statistical power.

Chip-Based Capillary Zone Electrophoresis Mass Spectrometry for Rapid Resolution and Quantitation of Critical Quality Attributes in Protein Biotherapeutics.

The aspiration of the multi-attribute method (MAM) is to utilize a single mass spectrometry-based method that can measure multiple attributes simultaneously, thus enabling data-driven decisions more quickly and efficiently. However, challenges associated with identifying and quantitating critical quality attributes such as asparagine deamidation and isoaspartic acid using conventional ultrahigh-pressure liquid chromatography (UHPLC) coupled to mass spectrometry have necessitated long gradients to ensure sufficient separation for quantitation. Microfluidic chip-based capillary zone electrophoresis mass spectrometry (CZE-MS) shows potential to enable rapid charge-based separation of peptide mixtures, and this approach was evaluated using multipeptide mixtures of synthetic peptides as well as digested protein therapeutics. In these experiments, repeatability, linearity, and peak-to-peak resolution of several peptide families containing asparagine deamidation and/or isoaspartic acid were demonstrated. In addition, a comparison of peptide map results acquired with both UHPLC-MS and CZE-MS for two enzymatically digested biological therapeutics showed comparable sequence coverage and quantitation results between the two approaches. As MAM becomes increasingly utilized for analysis of biological therapeutics, MS instrument demand will rapidly increase, resulting in a bottleneck. A CZE-based separation shows potential to alleviate this bottleneck by drastically increasing MAM throughput while providing results comparable to those acquired using conventional UHPLC separations.

Measuring physician practice site characteristics: A comparison of data from SK&A and a practice site survey.

OBJECTIVE: To evaluate the comparability of commercially available practice site data from SK&A with survey data to understand the implications of using SK&A data for health services research. DATA SOURCES: Responses to the Comprehensive Primary Care Plus (CPC+) Practice Survey and SK&A data. STUDY DESIGN: Comparison of CPC + Practice Survey responses to SK&A information for 2698 primary care practice sites. DATA COLLECTION: CPC + Practice Survey data collected through a web-only survey from April through September 2017, and SK&A data purchased in November 2016. PRINCIPAL FINDINGS: Information was similar across data sources, although some discrepancies were common. For example, 56% of practice sites had differences in the reported number of practitioners, and larger sites tended to have larger differences. Among practice sites with 1 practitioner in the survey, only 1.3% had a difference of 3 or more practitioners between the data sources, whereas 63% of practice sites with 11 or more practitioners had a difference of 3 or more practitioners. CONCLUSIONS: Discrepancies between data sources could reflect differences of interpretation when defining practice site characteristics, changes over time in those characteristics, or data errors in either SK&A or the survey. Researchers using SK&A data should consider possible ramifications for their studies.

Characteristics of strokes associated with centrifugal flow left ventricular assist devices.

Stroke is a devastating complication of left ventricular assist device (LVAD) therapy. Understanding the characteristics, risk factors and outcomes of strokes associated with the centrifugal flow LVADs is important to devise better strategies for management and prevention. This is a retrospective cohort study at a single US academic medical center. The cohort includes patients who received a first time Heartmate 3 (HM3) or Heartware (HVAD) LVAD between September 2009 through February 2018 and had a stroke while the LVAD was in place. Descriptive statistics were used when appropriate. A logistic regression analysis was used to determine predictors of poor outcome. Out of a total of 247 patients, 12.1% (N = 30, 24 HVAD and 6 HM3) had a stroke (63% ischemic) and 3 of these patients had pump thrombosis. Events per patient year (EPPY) were similar for HVAD and HM3 patients (0.3 ± 0.1). INR was subtherapeutic in 47.4% of ischemic stroke patients and supratherapeutic in 18.2% of hemorrhagic stroke patients. Concurrent infections were more common in the setting of hemorrhagic stroke than ischemic stroke (45.4% vs 5.3%, p = 0.008). Strokes were severe in most cases, with initial NIH stroke scale (NIHSS) higher in HM3 patients compared to HVAD patients (mean 24.6 vs 16) and associated with high in-patient mortality (21.1% of ischemic stroke vs. 88.8% of hemorrhagic stroke). Predictors of death within 30 days and disability at 90 days included creatinine at stroke onset, concurrent infection, hemorrhaghic stroke, and initial stroke severity (NIHSS). A score derived from these variables predicted with 100% certainty mortality at 30 days and mRS ≥ 4 at 90 days. For patients with centrifugal flow LVADs, ischemic strokes were more common but hemorrhagic strokes were associated with higher in-patient mortality and more frequently seen in the setting of concurrent infections. Infections, sub or supratherapeutic INR range, and comorbid cardiovascular risk factors may all be contributing to the stroke burden. These findings may inform future strategies for stroke prevention in this population.

Effect of the Million Hearts Cardiovascular Disease Risk Reduction Model on Initiating and Intensifying Medications: A Prespecified Secondary Analysis of a Randomized Clinical Trial.

Importance: The Million Hearts Cardiovascular Disease (CVD) Risk Reduction Model pays provider organizations for measuring and reducing Medicare patients' cardiovascular risk. Objective: To assess whether the model increases the initiation or intensification of antihypertensive medications or statins among patients with blood pressure or low-density lipoprotein (LDL) cholesterol levels above guideline thresholds for treatment intensification. Design, Setting, and Participants: This prespecified secondary analysis of a cluster-randomized, pragmatic trial included primary care and cardiology practices, health care centers, and hospital-based outpatient departments across the US. Participants included Medicare patients who were enrolled into the model in 2017 by participating organizations and who were at high risk and at medium risk of a myocardial infarction or stroke in 10 years. Patient outcomes were analyzed for 1 year postenrollment (through December 2018) using an intent-to-treat design. Analysis began November 2019. Interventions: US Centers for Medicare & Medicaid Services paid organizations for risk stratifying Medicare patients and reducing CVD risk among high-risk patients through discussing risk scores, developing individualized risk reduction plans, and following up with patients twice yearly. Main Outcomes and Measures: Initiating or intensifying statin or antihypertensive therapy within 1 year of enrollment, measured in Medicare Part D claims, and LDL cholesterol and systolic blood pressure levels approximately 1 year after enrollment, measured in usual care and reported to Centers for Medicare & Medicaid Services via a data registry (data complete for 51% of high-risk enrollees). The study's primary outcome (incidence of first-time myocardial infarction and stroke) is not reported because the trial is ongoing. Results: A total of 330 primary care and cardiology practices, health care centers, and hospital-based outpatient departments and 125 436 Medicare patients were included in this analysis. High-risk patients in the intervention group had a mean (SD) age of 74 (4.1), 15 213 (63%) were male, 21 657 (90%) were receiving antihypertensive medication at baseline, and 16 558 (69%) were receiving statins. Almost all (21 791 [91%]) high-risk intervention group patients had above-threshold systolic blood pressure level (>130 mm Hg), LDL cholesterol level (>70 mg/dL), or both. Patients in the intervention group with these risk factors were more likely than control patients (8127 [37.3%] vs 4753 [32.4%]; adjusted difference in percentage points, 4.8; 95% CI, 2.9-6.7; P < .001) to initiate or intensify statins or antihypertensive medication. Centers for Medicare & Medicaid Services did not pay for CVD risk reduction for medium-risk enrollees, but initiation or intensification rates for these enrollees were also higher in the intervention vs control groups (12 668 [27.9%] vs 7544 [24.8%]; adjusted difference in percentage points, 3.1; 95% CI, 1.9-4.3; P < .001). Among high-risk enrollees with clinical data approximately 1 year after enrollment, LDL cholesterol level was slightly lower in the intervention vs control groups (mean [SD], 89 [31.8] vs 91 [32.1] mg/dL; adjusted difference in percentage points, -1.8; 95% CI, -2.9 to -0.6; P = .002), as was systolic blood pressure (mean [SD], 133 [15.7] vs 135 [16.4] mm Hg; adjusted difference in percentage points, -1.7; 95% CI, -2.8 to -0.6; P = .003). Conclusions and Relevance: In this study, a pay-for-performance model led to modest increases in the use of CVD medications in a range of organizations, despite high medication use at baseline.

Decision Aid Implementation among Left Ventricular Assist Device Programs Participating in the DECIDE-LVAD Stepped-Wedge Trial.

Background. Despite demonstrated efficacy, patient decision aids (DAs) are rarely used in clinical practice in the absence of coverage mandates. Deciding whether to pursue a left ventricular assist device (LVAD) is a major, preference-sensitive decision-ideal for exploring implementation of a DA. Methods. We conducted a type II effectiveness-implementation hybrid trial at 6 LVAD programs using a stepped-wedge cluster-randomized design. Using the RE-AIM framework, we collected both quantitative and qualitative outcomes, including a checklist collected by study staff for each enrolled patient regarding DA use and interviews with LVAD program clinicians preintervention, 6 months postintervention, and at the conclusion of the study. Results. From June 2015 to January 2017, 248 patients and their caregivers were enrolled. A total of 69 interviews were conducted with 48 clinicians at 3 time points. The DA reached 95% of eligible patients. Adoption was 100%, as all sites approached agreed to participate in the trial. Interviews revealed several themes related to the implementation of the DA: clinicians had a strong desire to ensure patients were informed and embraced the DA. Despite this, they reported communication challenges among their team that impeded implementation. Five of the 6 sites have maintained use of the DA following the trial; 1 site reported concerns about decreased procedural volume with use of the DA as a reason for discontinuation. Conclusions. In this hybrid trial, a DA for patients considering LVADs and their caregivers demonstrated high reach. Adoption and implementation were facilitated by a strong desire to ensure that patients were well informed. Future dissemination research and practice should attend to concerns about procedure volume and coverage mandates and facilitate ongoing communication at sites using the DA.

Left ventricular assist systems and infection-related outcomes: A comprehensive analysis of the MOMENTUM 3 trial.

BACKGROUND: In a randomized controlled trial (MOMENTUM 3), the HeartMate 3 (HM3) fully magnetically levitated centrifugal-flow left ventricular assist device (LVAD) demonstrated superiority over the HeartMate II (HMII) axial-flow LVAD. These findings were driven by hemocompatibility-related outcomes, but infection-related outcomes were not altered by device choice. In this trial-level analysis, we analyzed the clinical patterns of infection-related outcomes over 2 years of support. METHODS: In MOMENTUM 3, 1,020 patients were implanted with either the HM3 (n = 515) or HMII (n = 505) pump. Clinical characteristics and morbidity- and mortality-related outcomes were evaluated to identify predictors associated with major infectious complications, using univariable and multivariable models. RESULTS: The cumulative number of infections at 2 years was 1,213 (634 HM3 and 579 HMII), and major infection occurred in 58% of patients with the HM3 and 56% of patients with the HMII (p = 0.57). Infections of a local nature unrelated to pump components were most common (n = 681/1,213; 56%), followed by driveline-associated infection (n = 329/1,213; 27%), sepsis (n = 194/1,213; 16%), and other events (n = 9/1,213; 0.7%). Bacterial pathogens were implicated in 806 of 1,213 events (66%); significant predictors of infection included sex (women vs men; hazard ratio [HR]: 1.38, p = 0.003), pre-implant use of intra-aortic balloon pump (HR: 1.33, p = 0.02), pre-implant history of cardiac surgery (HR: 1.28, p = 0.01), and body mass index ≥ 30 (HR: 1.40, p < 0.0001). Most deaths in those with infection occurred owing to non-infectious causes. CONCLUSION: Infection is the most common adverse effect in patients implanted with contemporary continuous-flow LVADs, with most such events unrelated to the pump or its peripheral components. Whether chronic mechanical circulatory devices confer an immunomodulatory effect pre-disposing to infection warrants closer scrutiny to understand and ameliorate this morbidity.

Predicting Receipt of Social Security Administration Disability Benefits Using Biomarkers and Other Physiological Measures: Evidence From the Health and Retirement Study.

OBJECTIVES: The objective of this study was to assess how well physiological measures, including biomarkers and genetic indicators, predict receipt of Social Security Administration (SSA) disability benefits among U.S. adults aged 51 to 65 years. METHOD: We used data from the 2006 to 2012 waves of the Health and Retirement Study (HRS), linked to SSA administrative data. Using logistic regression, we predicted benefit receipt (either Social Security Disability Insurance or Supplemental Security Income) using 19 distinct physiological markers, adjusting for age, sex, race, and select medication use. We then calculated the propensity (i.e., predicted probability) that each HRS respondent received benefits and assessed how well propensity score-based classifications could identify beneficiaries and nonbeneficiaries. RESULTS: Thirteen percent of respondents received benefits. Using the propensity score cut point that maximized the sum of sensitivity and specificity, the model correctly predicted 75.9% of beneficiaries and 73.5% of nonbeneficiaries. DISCUSSION: Physiological measures have moderate power to predict SSA disability benefit receipt.

Parent Partners: Evaluation of a Novel Peer-Support Intervention for the Caregivers of Children Hospitalized for Behavioral Health Conditions.

OBJECTIVE: Nearly 10% of all hospitalized children have a primary behavioral health diagnosis, but the effectiveness of treatment can be limited by caregivers' challenges navigating the behavioral health system. In this study, we assessed a novel peer-support intervention ("parent partners") designed for the caregivers of children admitted to an inpatient psychiatric unit. METHODS: We used a mixed-methods approach including 1) document review and interviews to assess implementation and 2) a difference-in-differences analysis using claims for Medicaid-enrolled children admitted to the intervention inpatient psychiatric unit and matched comparison children admitted to other inpatient psychiatric units to assess the impacts on health care use after discharge. RESULTS: Ninety-six percent of caregivers who were offered the intervention engaged with a parent partner. The primary challenges to implementation were accommodating the needs of parent partners to address behavioral health crises among their own children and initial limited engagement from behavioral health clinicians. The intervention leaders reported success in addressing these through adjustments to staffing policies, training parent partners in engagement with clinicians, and incorporating parent partners into team rounds. We did not find a statistically significant difference in follow-up outpatient behavioral health visits (adjusted treatment to comparison difference +3% [90% CI = -2%, +9%]), readmissions (+5% [-33%, +43%]), or behavioral health ED visits (-15% [-44%, +14%]). CONCLUSIONS: This novel intervention was implemented successfully, and although our study did not find statistically significant impacts on health care use after discharge, the findings for ED visits are suggestive of benefits. Parent peer support in inpatient settings warrants additional investigation.

Effects of a Behavioral Health and Chronic Illness Care Intervention on Patient Outcomes in Primary Care Practices in the Dakotas.

From 2012 to 2015, Sanford Health, a large health care system, integrated behavioral health services and chronic condition care management in some of its primary care practices in the Dakotas and rural Minnesota. Using difference-in-differences analyses for fee-for-service Medicare beneficiaries attributed to 22 participating practices and 91 matched comparison practices, we found that the program increased the receipt of four recommended diabetes care processes by 8.6% (p=.048) and, by slowing the increase in emergency department (ED) visits, reduced them by 4.9% (p=.07) relative to the comparison group. However, the findings are mixed: the program did not affect hospital admissions, readmissions, or Medicare spending. In addition, the program increased admissions for ambulatory care-sensitive conditions by 13.6% (p=.07) relative to the comparison group. Sanford's program provides a concrete example of how to incorporate behavioral health services in primary care in underserved areas with some positive results on quality-of-care processes and ED utilization.

Separation and quantitation of eight isomers in a molecule with three stereogenic centers by normal phase liquid chromatography.

A normal phase liquid chromatography method was developed for the separation and detection of eight stereoisomers of the key intermediate, CORE + OMe, having three chiral centers. The stereochemistry of this intermediate dictates the stereochemistry of the active pharmaceutical ingredient generated by an additional six synthetic steps. Multiple columns and mobile phases were screened during the development based on a platform approach. The use of dichloromethane as mobile phase additive and adjustment of flow rate and column temperature contributed in achieving resolution of these eight stereoisomers. The separation and detection of these stereoisomers was achieved using a Chiralcel OD-H, 4.6 × 250 mm, 5 µm dp column with heptane: ethanol: dichloromethane in a ratio of 95:3:2 (v:v:v) as mobile phase at a flow rate of 0.7 mL/min. UV detection was carried out at 245 nm and the column temperature was maintained at 15 °C. The analytical method was phase appropriately validated. The limit of detection and limit of quantification were found to be 0.035 and 0.07 µg, respectively. The newly developed method has been implemented for routine utilization to monitor the chiral control during process development and used as the quality control method for chiral purity of the desired compound.