Cost-effectiveness of bevacizumab therapy in the care of patients with hereditary hemorrhagic telangiectasia.

ABSTRACT: No US Food and Drug Administration- or European Medicines Agency-approved therapies exist for bleeding due to hereditary hemorrhagic telangiectasia (HHT), the second-most common inherited bleeding disorder worldwide. The current standard of care (SOC) includes iron and red cell supplementation, alongside the necessary hemostatic procedures, none of which target underlying disease pathogenesis. Recent evidence has demonstrated that bleeding pathophysiology is amenable to systemic antiangiogenic therapy with the anti-vascular endothelial growth factor bevacizumab. Despite its high cost, the addition of longitudinal bevacizumab to the current SOC may reduce overall health care resource use and improve patient quality of life. We conducted, to our knowledge, the first cost-effectiveness analysis of IV bevacizumab in patients with HHT with the moderate-to-severe phenotype, comparing bevacizumab added to SOC vs SOC alone. The primary outcome was the incremental net monetary benefit (iNMB) reported over a lifetime time horizon and across accepted willingness-to-pay thresholds, in US dollar per quality-adjusted life year (QALY). Bevacizumab therapy accrued 9.3 QALYs while generating $428 000 in costs, compared with 8.3 QALYs and $699 000 in costs accrued in the SOC strategy. The iNMB of bevacizumab therapy vs the SOC was $433 000. No parameter variation and no scenario analysis, including choice of iron supplementation product, changed the outcome of bevacizumab being a cost-saving strategy. Bevacizumab therapy also saved patients an average of 133 hours spent receiving HHT-specific care per year of life. In probabilistic sensitivity analysis, bevacizumab was favored in 100% of all 10 000 Monte Carlo iterations across base-case and all scenario analyses. Bevacizumab should be considered for more favorable formulary placement in the care of patients with moderate-to-severe HHT.

Investigating Lipid-Modulating Agents for Prevention or Treatment of COVID-19: JACC State-of-the-Art Review.

Coronavirus disease-2019 (COVID-19) is associated with systemic inflammation, endothelial activation, and multiorgan manifestations. Lipid-modulating agents may be useful in treating patients with COVID-19. These agents may inhibit viral entry by lipid raft disruption or ameliorate the inflammatory response and endothelial activation. In addition, dyslipidemia with lower high-density lipoprotein cholesterol and higher triglyceride levels portend worse outcomes in patients with COVID-19. Upon a systematic search, 40 randomized controlled trials (RCTs) with lipid-modulating agents were identified, including 17 statin trials, 14 omega-3 fatty acids RCTs, 3 fibrate RCTs, 5 niacin RCTs, and 1 dalcetrapib RCT for the management or prevention of COVID-19. From these 40 RCTs, only 2 have reported preliminary results, and most others are ongoing. This paper summarizes the ongoing or completed RCTs of lipid-modulating agents in COVID-19 and the implications of these trials for patient management.

Trends and geographical variation in population thriving, struggling and suffering across the USA, 2008-2017: a retrospective repeated cross-sectional study.

OBJECTIVES: Well-being is a holistic, positively framed conception of health, integrating physical, emotional, social, financial, community and spiritual aspects of life. High well-being is an intrinsically worthy goal for individuals, communities and nations. Multiple measures of well-being exist, yet we lack information to identify benchmarks, geographical disparities and targets for intervention to improve population life evaluation in the USA. DESIGN: Using data from the Gallup National Health and Well-Being Index, we conducted retrospective analyses of a series of cross-sectional samples. SETTING/PARTICIPANTS: We summarised select well-being outcomes nationally for each year, and by county (n=599) over two time periods, 2008-2012 and 2013-2017. MAIN OUTCOME MEASURES: We report percentages of people thriving, struggling and suffering using the Cantril Self-Anchoring Scale, percentages reporting high or low current life satisfaction, percentages reporting high or low future life optimism, and changes in these percentages over time. RESULTS: Nationally, the percentage of people that report thriving increased from 48.9% in 2008 to 56.3% in 2017 (p<0.05). The percentage suffering was not significantly different over time, ranging from 4.4% to 3.2%. In 2013-2017, counties with the highest life evaluation had a mean 63.6% thriving and 2.3% suffering while counties with the lowest life evaluation had a mean 49.5% thriving and 6.5% suffering, with counties experiencing up to 10% suffering, threefold the national average. Changes in county-level life evaluation also varied. While counties with the greatest improvements experienced 10%-15% increase in the absolute percentage thriving or 3%-5% decrease in absolute percentage suffering, most counties experienced no change and some experienced declines in life evaluation. CONCLUSIONS: The percentage of the US population thriving increased from 2008 to 2017 while the percentage suffering remained unchanged. Marked geographical variation exists indicating priority areas for intervention.

The Promise of Big Data and Digital Solutions in Building a Cardiovascular Learning System: Opportunities and Barriers.

The learning health system is a conceptual model for continuous learning and knowledge generation rooted in the daily practice of medicine. While companies such as Google and Amazon use dynamic learning systems that learn iteratively through every customer interaction, this efficiency has not materialized on a comparable scale in health systems. An ideal learning health system would learn from every patient interaction to benefit the care for the next patient. Notable advances include the greater use of data generated in the course of clinical care, Common Data Models, and advanced analytics. However, many remaining barriers limit the most effective use of large and growing health care data assets. In this review, we explore the accomplishments, opportunities, and barriers to realizing the learning health system.

Characteristics, Management, and Outcomes of Patients Hospitalized for Heart Failure in China: The China PEACE Retrospective Heart Failure Study.

Background Heart failure (HF) is an emerging epidemic in China and accounts for significant healthcare resource utilization in the inpatient setting. To create evidence-based, life-saving, and cost-saving hospitalization systems, the first step is to characterize the contemporary national landscape of inpatient HF care. Methods and Results In the China PEACE 5r-HF study (China Patient-centered evaluative Assessment of Cardiac Events Retrospective Study of Heart Failure), we used 2-stage random sampling to create a nationally representative cohort of 10 004 admissions for HF from 189 hospitals in 2015 in China. Data on patient characteristics, management, and outcomes were obtained through centralized medical record abstraction. The median age of the cohort was 73 years (interquartile range, 65-80), and 48.9% were women. More than half (56.2%) of the patients were hospitalized in rural areas. Prevalence of ejection fraction ≥50%, 40% to 50%, and <40% was 60.3%, 17.7%, and 22.0%, respectively. We identified substantial gaps in care, including underutilization of diagnostic tests such as echocardiograms (63.6%), chest imaging (75.2%), and biomarker testing (56.4%), low prescription rates of guideline-recommended medications during hospitalization and at discharge, suboptimal rates of follow-up appointments (24.3%), and widespread utilization of traditional Chinese medicine (74.8%). The combined rate of in-hospital mortality and treatment withdrawal in our study was 3.5%, and median length-of-stay was 9 days (interquartile range, 7-13). Conclusions Patients admitted with acute HF in China have distinctive epidemiology and receive substandard care, but have low inpatient mortality despite long length of stay. These findings provide opportunities for streamlining efficiencies while improving quality of inpatient HF care in China. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02877914.

Traditional Chinese Medicine Use in the Treatment of Acute Heart Failure in Western Medicine Hospitals in China: Analysis From the China PEACE Retrospective Heart Failure Study.

Background Traditional Chinese medicine (TCM) is used in the treatment of many conditions, including heart failure (HF), although it is not well characterized. Methods and Results We conducted a retrospective analysis of TCM use in a random sample of hospitalizations for HF within a random sample of Western medicine hospitals in China in 2015 using data from the China PEACE 5r-HF (China Patient-Centered Evaluative Assessment of Cardiac Events 5 Retrospective Heart Failure Study). We describe the frequency of TCM use and its association with patient characteristics, in-hospital use of evidence-based therapies, and hospital characteristics using hierarchical logistic regression models. Finally, we assessed risk-adjusted in-hospital bleeding and mortality. Among 10 004 patients hospitalized with HF (median age, 73 years; 48.9% women) from 189 hospitals, 74.7% received TCM (83.3% administered intravenously). The most commonly used agent was Salvia miltiorrhiza (51.2%). Patients with coronary artery disease (odds ratio [OR], 1.73; 95% CI, 1.53-1.95) or stroke (OR, 1.32; 95% CI, 1.15-1.51) were more likely to receive TCM; there was no correlation with evidence-based therapy use. Nearly all hospitals (99.4%) used TCM, with substantial variation across hospitals (median OR, 3.29; 95% CI, 2.82-3.76). In-patient bleeding (OR, 1.39; 95% CI, 1.03-1.88) and mortality (OR, 1.36; 95% CI, 1.04-1.79) were higher with Salvia miltiorrhiza, although not with other TCMs. Conclusions In a nationally representative sample of patients hospitalized with acute HF in China, three fourths received TCM. Nearly all hospitals used TCM, although use varied substantially by hospital. Although TCM was not used in lieu of evidence-based therapies for HF, we found a signal for harm with the most commonly used TCM. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02877914.

Traditional Chinese Medicine for Acute Myocardial Infarction in Western Medicine Hospitals in China.

BACKGROUND: Amid national efforts to improve the quality of care for people with cardiovascular disease in China, the use of traditional Chinese medicine (TCM) is increasing, yet little is known about its use in the early management of acute myocardial infarction (AMI). METHODS AND RESULTS: We aimed to examine intravenous use of TCM within the first 24 hours of hospitalization (early IV TCM) for AMI. Data come from the China Patient-centered Evaluative Assessment of Cardiac Events Retrospective Study of Acute Myocardial Infarction, restricted to a large, representative sample of Western medicine hospitals throughout China (n=162). We conducted a chart review of randomly sampled patients with AMI in 2001, 2006, and 2011, comparing early intravenous TCM use across years, predictors of any early intravenous TCM use, and association with in-hospital bleeding and mortality. From 2001 to 2011, early intravenous TCM use increased (2001: 38.2% versus 2006: 49.1% versus 2011: 56.1%; P<0.01). Nearly all (99%) hospitals used early intravenous TCM. Salvia miltiorrhiza was most commonly prescribed, used in one third (35.5%) of all patients admitted with AMI. Patients receiving any early intravenous TCM, compared with those who did not, were similar in age and sex and had fewer cardiovascular risk factors. In multivariable hierarchical models, admission to a secondary (versus tertiary) hospital was most strongly associated with early intravenous TCM use (odds ratio: 2.85; 95% confidence interval: 1.98-4.11). Hospital-level factors accounted for 55% of the variance (adjusted median odds ratio: 2.84). In exploratory analyses, there were no significant associations between early intravenous TCM and in-hospital bleeding or mortality. CONCLUSIONS: Early intravenous TCM use for AMI in China is increasing despite the lack of evidence of their benefit or harm. There is an urgent need to define the effects of these medications because they have become a staple of treatment in the world's most populous country. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01624883.

Sex Differences in Omega-3 and -6 Fatty Acids and Health Status Among Young Adults With Acute Myocardial Infarction: Results From the VIRGO Study.

BACKGROUND: Young women (aged ≤55 years) with acute myocardial infarction (AMI) have poorer health status outcomes than similarly aged men. Low omega-3 fatty acids (FAs) have been implicated as risk factors for cardiovascular outcomes in AMI patients, but it is not clear whether young women have similar or different post-AMI omega-3 FA profiles compared with young men. METHODS AND RESULTS: We assessed the sex differences in post-AMI omega-3 FAs and the associations of these biomarkers with patient-reported outcomes (symptom, functioning status, and quality of life) at 12-month follow-up, using data from 2985 US adults with AMI aged 18 to 55 years enrolled in the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young Acute Myocardial Infarction Patients) study. Biomarkers including eicosapentaenoic acid, docosahexaenoic acid, arachidonic acid (AA), eicosapentaenoic acid/AA ratio, omega-3/omega-6 ratio, and omega-3 index were measured 1 month after AMI. Overall, the omega-3 FAs and AA were similar in young men and women with AMI. In both unadjusted and adjusted analysis (controlling for age, sex, race, smoking, hypertension, diabetes mellitus, body mass index, and health status score at 1 month), omega-3 FAs and AA were not significantly associated with 12-month health status scores using the Bonferroni corrected statistical threshold. CONCLUSIONS: We found no evidence of sex differences in omega-3 FAs and AA in young men and women 1 month after AMI. Omega-3 FAs and AA at 1-month after AMI were generally not associated with 12-month patient-reported health status after adjusting for patient demographic, clinical characteristics, and the corresponding 1-month health status score.

Identifying county characteristics associated with resident well-being: A population based study.

BACKGROUND: Well-being is a positively-framed, holistic assessment of health and quality of life that is associated with longevity and better health outcomes. We aimed to identify county attributes that are independently associated with a comprehensive, multi-dimensional assessment of individual well-being. METHODS: We performed a cross-sectional study examining associations between 77 pre-specified county attributes and a multi-dimensional assessment of individual US residents' well-being, captured by the Gallup-Sharecare Well-Being Index. Our cohort included 338,846 survey participants, randomly sampled from 3,118 US counties or county equivalents. FINDINGS: We identified twelve county-level factors that were independently associated with individual well-being scores. Together, these twelve factors explained 91% of the variance in individual well-being scores, and they represent four conceptually distinct categories: demographic (% black); social and economic (child poverty, education level [

Association of the Overall Well-being of a Population With Health Care Spending for People 65 Years of Age or Older.

Importance: New US health care payment models have increasingly incentivized health care systems to promote health and reduce health care spending at the population level, with Medicare beneficiaries representing one of the largest populations affected by new payment models. Identifying novel strategies to promote health and reduce health care spending is necessary. Objective: To assess whether the overall well-being of a population is associated with health care spending for people 65 years of age or older. Design, Setting, and Participants: This US national, population-based cross-sectional study examined the association between county well-being and Medicare fee-for-service (FFS) spending. Population well-being, a holistic assessment of the overall health of the population comprising interrelated domains, including physical, mental, and social health, as measured by the Gallup-Sharecare Well-Being Index (2010), was linked to the mean spending per Medicare FFS beneficiary (2010) and county characteristics data for all US counties assessed. The data were adjusted for prevalence of 4 low-variation conditions (hip fracture, stroke, colorectal cancer, and acute myocardial infarction) and regional penetration of Medicare Advantage. Data analyses were conducted October 13, 2016, to October 31, 2017. Main Outcomes and Measures: Mean spending per Medicare FFS beneficiary per county. Results: In total, 2998 counties were assessed using county-level mean values, with 4 to 7317 participants (mean [SD] number of participants, 755 [1220]) per county. The mean (SD) values of the demographic characteristics of the participants were 50.8% (1.3%) female, 74.9% (16.5%) white, 12.1% (13.0%) black, 4.0% (5.3%) Asian, and 13.7% (14.8%) Hispanic with a mean (SD) of the median county age of 38.2 (4.4) years. Medicare spent a mean (SE) of $992 ($110) less per Medicare FFS beneficiary in counties in the highest quintile of well-being compared with counties in the lowest well-being quintile. This inverse association persisted after accounting for key population characteristics such as median household income and contextual factors such as urbanicity and health care system capacity. Medicare spent a mean (SE) of $1233 ($104) less per Medicare FFS beneficiary in counties with the greatest access to basic needs than in those with the lowest access. Conclusions and Relevance: In this US national study, the overall well-being of a geographically defined population was inversely associated with its health care spending for people 65 years and older. Identifying this association between well-being and health care spending at the population level may help to lay the foundation for further study to first illuminate the mechanisms underlying the association and to second study interventions aimed at creating greater well-being and lower health care spending at the population level.

National Quality Assessment of Early Clopidogrel Therapy in Chinese Patients With Acute Myocardial Infarction (AMI) in 2006 and 2011: Insights From the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE)-Retrospective AMI Study.

BACKGROUND: Early clopidogrel administration to patients with acute myocardial infarction (AMI) has been demonstrated to improve outcomes in a large Chinese trial. However, patterns of use of clopidogrel for patients with AMI in China are unknown. METHODS AND RESULTS: From a nationally representative sample of AMI patients from 2006 and 2011, we identified 11 944 eligible patients for clopidogrel therapy and measured early clopidogrel use, defined as initiation within 24 hours of hospital admission. Among the patients eligible for clopidogrel, the weighted rate of early clopidogrel therapy increased from 45.7% in 2006 to 79.8% in 2011 (P<0.001). In 2006 and 2011, there was significant variation in early clopidogrel use by region, ranging from 1.5% to 58.0% in 2006 (P<0.001) and 48.7% to 87.7% in 2011 (P<0.001). While early use of clopidogrel was uniformly high in urban hospitals in 2011 (median 89.3%; interquartile range: 80.1% to 94.5%), there was marked heterogeneity among rural hospitals (median 50.0%; interquartile range: 11.5% to 84.4%). Patients without reperfusion therapy and those admitted to rural hospitals were less likely to be treated with clopidogrel. CONCLUSIONS: Although the use of early clopidogrel therapy in patients with AMI has increased substantially in China, there is notable wide variation across hospitals, with much less adoption in rural hospitals. Quality improvement initiatives are needed to increase consistency of early clopidogrel use for patients with AMI. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01624883.

HbA1c and risk of severe hypoglycemia in type 2 diabetes: the Diabetes and Aging Study.

OBJECTIVE: We examined the association between HbA1c level and self-reported severe hypoglycemia in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Type 2 diabetic patients in a large, integrated healthcare system, who were 30-77 years of age and treated with glucose-lowering therapy, were asked about severe hypoglycemia requiring assistance in the year prior to the Diabetes Study of Northern California survey conducted in 2005-2006 (62% response rate). The main exposure of interest was the last HbA1c level collected in the year preceding the observation period. Poisson regression models adjusted for selected demographic and clinical variables were specified to evaluate the relative risk (RR) of severe hypoglycemia across HbA1c levels. We also tested whether the HbA1c-hypoglycemia association differed across potential effect modifiers (age, diabetes duration, and category of diabetes medication). RESULTS: Among 9,094 eligible survey respondents (mean age 59.5 ± 9.8 years, mean HbA1c 7.5 ± 1.5%), 985 (10.8%) reported experiencing severe hypoglycemia. Across HbA1c levels, rates of hypoglycemia were 9.3-13.8%. Compared with those with HbA1c of 7-7.9%, the RR of hypoglycemia was 1.25 (95% CI 0.99-1.57), 1.01 (0.87-1.18), 0.99 (0.82-1.20), and 1.16 (0.97-1.38) among those with HbA1c <6, 6-6.9, 8-8.9, and ≥9%, respectively, in a fully adjusted model. Age, diabetes duration, and category of diabetes medication did not significantly modify the HbA1c-hypoglycemia relationship. CONCLUSIONS: Severe hypoglycemia was common among patients with type 2 diabetes across all levels of glycemic control. Risk tended to be higher in patients with either near-normal glycemia or very poor glycemic control.

Beyond insurance coverage: usual source of care in the treatment of hypertension and hypercholesterolemia. Data from the 2003-2006 National Health and Nutrition Examination Survey.

BACKGROUND: Expanding insurance coverage, while necessary, may not be sufficient to ensure high-quality care for adults with cardiovascular disease. We sought to examine the association between having a usual source of care (USOC) and receiving medication treatment of hypertension and hypercholesterolemia. METHODS: Using the 2003-2006 National Health and Nutrition Examination Survey, we categorized USOC (a place to go when sick or need medical advice) and insurance status in adults >or=35 years old with an indication for medication treatment of hypertension (n = 3,142) and hypercholesterolemia (n = 1,134), determined using the Joint National Committee 7 and Adult Treatment Panel III recommendations, respectively. Multivariable logistic regression modeling was used to determine the independent effect of USOC on receiving treatment of hypertension and hypercholesterolemia, controlling for age, sex, race/ethnicity, insurance status, and comorbidities. Separate multivariable models were examined stratified by insurance status. RESULTS: Among subjects with an indication for treatment of hypertension and hypercholesterolemia, 32.4% and 42.0% were untreated, respectively. When compared with adults with a USOC, adults without a USOC were more likely to be untreated for hypertension (adjusted prevalence ratio [aPR] 2.43, 95% CI 1.88-2.85) and hypercholesterolemia (aPR 1.79, 95% CI 1.31-2.13). In stratified analyses among subjects with insurance, no USOC remained associated with being untreated (hypertension, aPR 2.58, 95% CI 1.88-3.08; hypercholesterolemia, aPR 1.65, 95% CI 0.97-2.18). CONCLUSIONS: Absence of a USOC was associated with being untreated for hypertension and hypercholesterolemia, even among individuals with insurance, suggesting that efforts to improve chronic disease management should also facilitate access to a regular source of care.

What are hospitals doing to increase beta-blocker use?

BACKGROUND: Despite the many proposed methods for improving quality, little is known about which methods are being applied in practice across the United States or their perceived effectiveness. METHODS: A descriptive, cross-sectional analysis of data from a telephone survey of quality improvement staff in 234 randomly selected hospitals participating in the National Registry of Myocardial Infarction was conducted to examine the prevalence and perceived effectiveness of various quality improvement interventions directed at increasing beta-blocker use after acute myocardial infarction. RESULTS: The mean and median number of quality improvement interventions directed at beta-blocker use in the past 4 years was 5.0 per hospital. The most commonly reported effort was performance reporting about beta-blocker use (87.9%), although only 26.7% used physician-specific performance reporting. More than half the hospitals implemented clinical pathways (58.1%), standing orders (56.8%), or care coordinators (50.4%). Care coordinators (63.4%) and computer support systems (61.6%) were most frequently rated as "very effective." Clinical pathways (24.2%), counseling physicians who had poor performance (26.9%), and reminder forms (23.0%) were most frequently rated as not effective. CONCLUSIONS: Substantial variation in the types of quality improvement efforts implemented to increase beta-blocker use and perceived effectiveness were evident.