Precision Health Analytics With Predictive Analytics and Implementation Research: JACC State-of-the-Art Review.

Emerging data science techniques of predictive analytics expand the quality and quantity of complex data relevant to human health and provide opportunities for understanding and control of conditions such as heart, lung, blood, and sleep disorders. To realize these opportunities, the information sources, the data science tools that use the information, and the application of resulting analytics to health and health care issues will require implementation research methods to define benefits, harms, reach, and sustainability; and to understand related resource utilization implications to inform policymakers. This JACC State-of-the-Art Review is based on a workshop convened by the National Heart, Lung, and Blood Institute to explore predictive analytics in the context of implementation science. It highlights precision medicine and precision public health as complementary and compelling applications of predictive analytics, and addresses future research and training endeavors that might further foster the application of predictive analytics in clinical medicine and public health.

Practice-Based Research Networks: Strategic Opportunities to Advance Implementation Research for Health Equity.

While the vast majority of people receive their medical care in community primary and specialty care clinics, most clinical research is performed in academic tertiary care hospitals and hospital clinics. Practice-based research networks are most commonly collections of primary care practices that work together to ask and answer health questions for their patients and communities and are an integral part of the translational pathway from discovery to practice to community health. Community primary care practices are at the front line of health equity issues; equity in clinical care, equity in community health, equity in social determinants of health, and equity in health outcomes. Practice-based research networks can gather and combine data from dozens of communities, hundreds of practices and thousands of patients to address health equity and disparities across the full spectrum of community and public health to clinical and primary care. This article will briefly outline the history of PBRNs, types of PBRNs, locations, topics, and patient outcomes over the past 25 years. Current PBRN efforts to address health disparities and improve health equity will be described. New PBRN opportunities to address health disparities and approaches to advance implementation research for health equity in the practice and community will be described. Readers will be challenged to consider ways to engage practice-based research networks in their health equity efforts.

Pharmacokinetics, safety and efficacy of maraviroc in treatment-experienced pediatric patients Infected with CCR5-tropic HIV-1

BACKGROUND: Maraviroc is a CC-chemokine receptor 5 antagonist approved to treat adults infected with CC-chemokine receptor 5-tropic (R5) HIV-1. Study A4001031 was conducted to evaluate the pharmacokinetics, safety and efficacy of maraviroc in combination with optimized background therapy in treatment-experienced pediatric patients infected with R5 HIV-1 and support registration of maraviroc for pediatric use. METHODS: This is an open-label, 2-stage, age-stratified, noncomparative multicenter study. One-hundred and three participants were enrolled into 4 age/formulation cohorts and dosed twice daily. Initial doses were determined by body surface area and optimized background therapy, based on drug interactions with maraviroc in adults. Dose adjustment and pharmacokinetic reevaluation occurred if the average concentrations (Cavg) at Week 2 were <100 ng/mL (Stage 1-dose finding). RESULTS: Data from the Week 48 analysis demonstrated that 49/50 Stage 1 participants rolling over into Stage 2 (safety and efficacy) achieved Cavg ≥100 ng/mL. Doses were identified that achieved similar concentration ranges to those seen in adults. The majority (90/103) received optimized background therapy containing potent cytochrome P450 3A inhibitors. Maraviroc was well tolerated and the safety and efficacy were comparable to those of adults. All cohorts had a mean decrease from baseline in HIV-1 RNA of >1 log10. Increases from baseline in the median CD4+ cell count and percentage were seen for all age groups. CONCLUSIONS: The maraviroc dosing strategy resulted in participants achieving the target Cavg, with exposure ranges similar to those observed in adults on approved doses. The safety and efficacy of maraviroc in this pediatric population were comparable to those seen in adults

Reducing Cardiovascular Disparities Through Community-Engaged Implementation Research: A National Heart, Lung, and Blood Institute Workshop Report.

Cardiovascular disparities remain pervasive in the United States. Unequal disease burden is evident among population groups based on sex, race, ethnicity, socioeconomic status, educational attainment, nativity, or geography. Despite the significant declines in cardiovascular disease mortality rates in all demographic groups during the last 50 years, large disparities remain by sex, race, ethnicity, and geography. Recent data from modeling studies, linked micromap plots, and small-area analyses also demonstrate prominent variation in cardiovascular disease mortality rates across states and counties, with an especially high disease burden in the southeastern United States and Appalachia. Despite these continued disparities, few large-scale intervention studies have been conducted in these high-burden populations to examine the feasibility of reducing or eliminating cardiovascular disparities. To address this challenge, on June 22 and 23, 2017, the National Heart, Lung, and Blood Institute convened experts from a broad range of biomedical, behavioral, environmental, implementation, and social science backgrounds to summarize the current state of knowledge of cardiovascular disease disparities and propose intervention strategies aligned with the National Heart, Lung, and Blood Institute mission. This report presents the themes, challenges, opportunities, available resources, and recommended actions discussed at the workshop.

Pharmacokinetics, Safety and Efficacy of Maraviroc in Treatment-experienced Pediatric Patients Infected With CCR5-Tropic HIV-1.

BACKGROUND: Maraviroc is a CC-chemokine receptor 5 antagonist approved to treat adults infected with CC-chemokine receptor 5-tropic (R5) HIV-1. Study A4001031 was conducted to evaluate the pharmacokinetics, safety and efficacy of maraviroc in combination with optimized background therapy in treatment-experienced pediatric patients infected with R5 HIV-1 and support registration of maraviroc for pediatric use. METHODS: This is an open-label, 2-stage, age-stratified, noncomparative multicenter study. One-hundred and three participants were enrolled into 4 age/formulation cohorts and dosed twice daily. Initial doses were determined by body surface area and optimized background therapy, based on drug interactions with maraviroc in adults. Dose adjustment and pharmacokinetic reevaluation occurred if the average concentrations (Cavg) at Week 2 were <100 ng/mL (Stage 1-dose finding). RESULTS: Data from the Week 48 analysis demonstrated that 49/50 Stage 1 participants rolling over into Stage 2 (safety and efficacy) achieved Cavg ≥100 ng/mL. Doses were identified that achieved similar concentration ranges to those seen in adults. The majority (90/103) received optimized background therapy containing potent cytochrome P450 3A inhibitors. Maraviroc was well tolerated and the safety and efficacy were comparable to those of adults. All cohorts had a mean decrease from baseline in HIV-1 RNA of >1 log10. Increases from baseline in the median CD4+ cell count and percentage were seen for all age groups. CONCLUSIONS: The maraviroc dosing strategy resulted in participants achieving the target Cavg, with exposure ranges similar to those observed in adults on approved doses. The safety and efficacy of maraviroc in this pediatric population were comparable to those seen in adults.

Hepatic safety of maraviroc in patients with HIV-1 and hepatitis C and/or B virus: 144-week results from a randomized, placebo-controlled trial.

BACKGROUND: In the primary 48-week analysis of a hepatic safety trial in patients with HIV-1 coinfected with HBV and/or HCV, maraviroc-containing treatment regimens were not associated with increased hepatotoxicity. METHODS: In this randomized, double-blind, placebo-controlled, multicentre study, patients received maraviroc twice daily (n=70) or placebo (n=67) with concomitant antiretroviral therapy for 144 weeks (Clinicaltrials.gov identifier, NCT01327547). The primary end point was the proportion of patients with protocol-defined Grade 3/4 alanine aminotransferase (ALT) abnormalities through week 48. Key secondary end points included 144-week analysis of Grade 3/4 ALT abnormalities and liver fibrosis by enhanced liver fibrosis (ELF) testing, hepatic elastography and an optional biopsy substudy. RESULTS: Through 144 weeks of treatment, two (maraviroc) and three (placebo) patients met the protocol-defined Grade 3/4 ALT end point. Similar to the 48-week results, there were no statistically significant differences between groups in change from baseline in ELF or hepatic elastography. However, decreased elastography scores were noted in the maraviroc group. Blinded pathologist review suggested that 2 of 11 paired biopsies (both on maraviroc) showed signs of decreased fibrosis. One (maraviroc) and two (placebo) patients experienced treatment-related hepatobiliary adverse events (AEs). Five patients in the maraviroc group discontinued because of treatment-related AEs versus three in the placebo group. One death in the maraviroc group and two deaths in the placebo group were reported. CONCLUSIONS: Use of maraviroc did not increase hepatotoxicity in this population through 144 weeks. Further investigation regarding possible beneficial effects of maraviroc on liver fibrosis may be warranted.

Special issue on primary care practice-based research networks: insights on innovative strategies for harnessing health information technology to help individuals, teams.

This issue of the Journal highlights the problem-solving perspectives of primary care practices, including practice-based research networks. Informed, dedicated primary care teams are seeking incremental insight on how to use health information technology to support holistic enhancements in primary care, including how health information technology can support individual patients and how it can support care teams. Practice-based research networks comprise groups of primary care clinicians, their diversified practice teams, and skilled researchers, all of whom work together to answer community-based health care questions, seek practical solutions, and translate research findings into practice.

Health information technology and hospital patient safety: a conceptual model to guide research.

BACKGROUND: The literature indicates that health information technology (IT) use may lead to some gains in the quality and safety of care in some situations but provides little insight into this variability in the results that has been found. The inconsistent findings point to the need for a conceptual model that will guide research in sorting out the complex relationships between health IT and the quality and safety of care. METHODS: A conceptual model was developed that describes how specific health IT functions could affect different types of inpatient safety errors and that include contextual factors that influence successful health IT implementation. The model was applied to a readily available patient safety measure and nationwide data (2009 AHA Annual Survey Information Technology Supplement and 2009 Healthcare Cost and Utilization Project State Inpatient Databases). FINDINGS: The model was difficult to operationalize because (1) available health IT adoption data did not characterize health IT features and extent of usage, and (2) patient safety measures did not elucidate the process failures leading to safety-related outcomes. The sample patient safety measure--Postoperative Physiologic and Metabolic Derangement Rate--was not significantly related to self-reported health IT capabilities when adjusted for hospital structural characteristics. CONCLUSION: These findings illustrate the critical need for collecting data that are germane to health IT and the possible mechanisms by which health IT may affect inpatient safety. Well-defined and sufficiently granular measures of provider's correct use of health IT functions, the contextual factors surrounding health IT use, and patient safety errors leading to health care-associated conditions are needed to illuminate the impact of health IT on patient safety.