Considerations for using predictive models that include race as an input variable: The case study of lung cancer screening.

Indiscriminate use of predictive models incorporating race can reinforce biases present in source data and lead to an exacerbation of health disparities. In some countries, such as the United States, there is therefore a push to remove race from prediction models; however, there are still many prediction models that use race as an input. Biomedical informaticists who are given the responsibility of using these predictive models in healthcare environments are likely to be faced with questions like how to deal with race covariates in these models. Thus, there is a need for a pragmatic framework to help model users think through how to include race in their chosen model so as to avoid inadvertently exacerbating disparities. In this paper, we use the case study of lung cancer screening to propose a simple framework to guide how model users can approach the use (or non-use) of race inputs in the predictive models they are tasked with leveraging in electronic health records and clinical workflows.

Association of Disparities in Family History and Family Cancer History in the Electronic Health Record With Sex, Race, Hispanic or Latino Ethnicity, and Language Preference in 2 Large US Health Care Systems.

Importance: Clinical decision support (CDS) algorithms are increasingly being implemented in health care systems to identify patients for specialty care. However, systematic differences in missingness of electronic health record (EHR) data may lead to disparities in identification by CDS algorithms. Objective: To examine the availability and comprehensiveness of cancer family history information (FHI) in patients' EHRs by sex, race, Hispanic or Latino ethnicity, and language preference in 2 large health care systems in 2021. Design, Setting, and Participants: This retrospective EHR quality improvement study used EHR data from 2 health care systems: University of Utah Health (UHealth) and NYU Langone Health (NYULH). Participants included patients aged 25 to 60 years who had a primary care appointment in the previous 3 years. Data were collected or abstracted from the EHR from December 10, 2020, to October 31, 2021, and analyzed from June 15 to October 31, 2021. Exposures: Prior collection of cancer FHI in primary care settings. Main Outcomes and Measures: Availability was defined as having any FHI and any cancer FHI in the EHR and was examined at the patient level. Comprehensiveness was defined as whether a cancer family history observation in the EHR specified the type of cancer diagnosed in a family member, the relationship of the family member to the patient, and the age at onset for the family member and was examined at the observation level. Results: Among 144 484 patients in the UHealth system, 53.6% were women; 74.4% were non-Hispanic or non-Latino and 67.6% were White; and 83.0% had an English language preference. Among 377 621 patients in the NYULH system, 55.3% were women; 63.2% were non-Hispanic or non-Latino, and 55.3% were White; and 89.9% had an English language preference. Patients from historically medically undeserved groups-specifically, Black vs White patients (UHealth: 17.3% [95% CI, 16.1%-18.6%] vs 42.8% [95% CI, 42.5%-43.1%]; NYULH: 24.4% [95% CI, 24.0%-24.8%] vs 33.8% [95% CI, 33.6%-34.0%]), Hispanic or Latino vs non-Hispanic or non-Latino patients (UHealth: 27.2% [95% CI, 26.5%-27.8%] vs 40.2% [95% CI, 39.9%-40.5%]; NYULH: 24.4% [95% CI, 24.1%-24.7%] vs 31.6% [95% CI, 31.4%-31.8%]), Spanish-speaking vs English-speaking patients (UHealth: 18.4% [95% CI, 17.2%-19.1%] vs 40.0% [95% CI, 39.7%-40.3%]; NYULH: 15.1% [95% CI, 14.6%-15.6%] vs 31.1% [95% CI, 30.9%-31.2%), and men vs women (UHealth: 30.8% [95% CI, 30.4%-31.2%] vs 43.0% [95% CI, 42.6%-43.3%]; NYULH: 23.1% [95% CI, 22.9%-23.3%] vs 34.9% [95% CI, 34.7%-35.1%])-had significantly lower availability and comprehensiveness of cancer FHI (P < .001). Conclusions and Relevance: These findings suggest that systematic differences in the availability and comprehensiveness of FHI in the EHR may introduce informative presence bias as inputs to CDS algorithms. The observed differences may also exacerbate disparities for medically underserved groups. System-, clinician-, and patient-level efforts are needed to improve the collection of FHI.

GARDE: a standards-based clinical decision support platform for identifying population health management cohorts.

Population health management (PHM) is an important approach to promote wellness and deliver health care to targeted individuals who meet criteria for preventive measures or treatment. A critical component for any PHM program is a data analytics platform that can target those eligible individuals. OBJECTIVE: The aim of this study was to design and implement a scalable standards-based clinical decision support (CDS) approach to identify patient cohorts for PHM and maximize opportunities for multi-site dissemination. MATERIALS AND METHODS: An architecture was established to support bidirectional data exchanges between heterogeneous electronic health record (EHR) data sources, PHM systems, and CDS components. HL7 Fast Healthcare Interoperability Resources and CDS Hooks were used to facilitate interoperability and dissemination. The approach was validated by deploying the platform at multiple sites to identify patients who meet the criteria for genetic evaluation of familial cancer. RESULTS: The Genetic Cancer Risk Detector (GARDE) platform was created and is comprised of four components: (1) an open-source CDS Hooks server for computing patient eligibility for PHM cohorts, (2) an open-source Population Coordinator that processes GARDE requests and communicates results to a PHM system, (3) an EHR Patient Data Repository, and (4) EHR PHM Tools to manage patients and perform outreach functions. Site-specific deployments were performed on onsite virtual machines and cloud-based Amazon Web Services. DISCUSSION: GARDE's component architecture establishes generalizable standards-based methods for computing PHM cohorts. Replicating deployments using one of the established deployment methods requires minimal local customization. Most of the deployment effort was related to obtaining site-specific information technology governance approvals.

Patient Interactions With an Automated Conversational Agent Delivering Pretest Genetics Education: Descriptive Study.

BACKGROUND: Cancer genetic testing to assess an individual's cancer risk and to enable genomics-informed cancer treatment has grown exponentially in the past decade. Because of this continued growth and a shortage of health care workers, there is a need for automated strategies that provide high-quality genetics services to patients to reduce the clinical demand for genetics providers. Conversational agents have shown promise in managing mental health, pain, and other chronic conditions and are increasingly being used in cancer genetic services. However, research on how patients interact with these agents to satisfy their information needs is limited. OBJECTIVE: Our primary aim is to assess user interactions with a conversational agent for pretest genetics education. METHODS: We conducted a feasibility study of user interactions with a conversational agent who delivers pretest genetics education to primary care patients without cancer who are eligible for cancer genetic evaluation. The conversational agent provided scripted content similar to that delivered in a pretest genetic counseling visit for cancer genetic testing. Outside of a core set of information delivered to all patients, users were able to navigate within the chat to request additional content in their areas of interest. An artificial intelligence-based preprogrammed library was also established to allow users to ask open-ended questions to the conversational agent. Transcripts of the interactions were recorded. Here, we describe the information selected, time spent to complete the chat, and use of the open-ended question feature. Descriptive statistics were used for quantitative measures, and thematic analyses were used for qualitative responses. RESULTS: We invited 103 patients to participate, of which 88.3% (91/103) were offered access to the conversational agent, 39% (36/91) started the chat, and 32% (30/91) completed the chat. Most users who completed the chat indicated that they wanted to continue with genetic testing (21/30, 70%), few were unsure (9/30, 30%), and no patient declined to move forward with testing. Those who decided to test spent an average of 10 (SD 2.57) minutes on the chat, selected an average of 1.87 (SD 1.2) additional pieces of information, and generally did not ask open-ended questions. Those who were unsure spent 4 more minutes on average (mean 14.1, SD 7.41; P=.03) on the chat, selected an average of 3.67 (SD 2.9) additional pieces of information, and asked at least one open-ended question. CONCLUSIONS: The pretest chat provided enough information for most patients to decide on cancer genetic testing, as indicated by the small number of open-ended questions. A subset of participants were still unsure about receiving genetic testing and may require additional education or interpersonal support before making a testing decision. Conversational agents have the potential to become a scalable alternative for pretest genetics education, reducing the clinical demand on genetics providers.

Comparing models of delivery for cancer genetics services among patients receiving primary care who meet criteria for genetic evaluation in two healthcare systems: BRIDGE randomized controlled trial.

BACKGROUND: Advances in genetics and sequencing technologies are enabling the identification of more individuals with inherited cancer susceptibility who could benefit from tailored screening and prevention recommendations. While cancer family history information is used in primary care settings to identify unaffected patients who could benefit from a cancer genetics evaluation, this information is underutilized. System-level population health management strategies are needed to assist health care systems in identifying patients who may benefit from genetic services. In addition, because of the limited number of trained genetics specialists and increasing patient volume, the development of innovative and sustainable approaches to delivering cancer genetic services is essential. METHODS: We are conducting a randomized controlled trial, entitled Broadening the Reach, Impact, and Delivery of Genetic Services (BRIDGE), to address these needs. The trial is comparing uptake of genetic counseling, uptake of genetic testing, and patient adherence to management recommendations for automated, patient-directed versus enhanced standard of care cancer genetics services delivery models. An algorithm-based system that utilizes structured cancer family history data available in the electronic health record (EHR) is used to identify unaffected patients who receive primary care at the study sites and meet current guidelines for cancer genetic testing. We are enrolling eligible patients at two healthcare systems (University of Utah Health and New York University Langone Health) through outreach to a randomly selected sample of 2780 eligible patients in the two sites, with 1:1 randomization to the genetic services delivery arms within sites. Study outcomes are assessed through genetics clinic records, EHR, and two follow-up questionnaires at 4 weeks and 12 months after last genetic counseling contactpre-test genetic counseling. DISCUSSION: BRIDGE is being conducted in two healthcare systems with different clinical structures and patient populations. Innovative aspects of the trial include a randomized comparison of a chatbot-based genetic services delivery model to standard of care, as well as identification of at-risk individuals through a sustainable EHR-based system. The findings from the BRIDGE trial will advance the state of the science in identification of unaffected patients with inherited cancer susceptibility and delivery of genetic services to those patients. TRIAL REGISTRATION: BRIDGE is registered as NCT03985852 . The trial was registered on June 6, 2019 at clinicaltrials.gov .

Applying A/B Testing to Clinical Decision Support: Rapid Randomized Controlled Trials.

BACKGROUND: Clinical decision support (CDS) is a valuable feature of electronic health records (EHRs) designed to improve quality and safety. However, due to the complexities of system design and inconsistent results, CDS tools may inadvertently increase alert fatigue and contribute to physician burnout. A/B testing, or rapid-cycle randomized tests, is a useful method that can be applied to the EHR in order to rapidly understand and iteratively improve design choices embedded within CDS tools. OBJECTIVE: This paper describes how rapid randomized controlled trials (RCTs) embedded within EHRs can be used to quickly ascertain the superiority of potential CDS design changes to improve their usability, reduce alert fatigue, and promote quality of care. METHODS: A multistep process combining tools from user-centered design, A/B testing, and implementation science was used to understand, ideate, prototype, test, analyze, and improve each candidate CDS. CDS engagement metrics (alert views, acceptance rates) were used to evaluate which CDS version is superior. RESULTS: To demonstrate the impact of the process, 2 experiments are highlighted. First, after multiple rounds of usability testing, a revised CDS influenza alert was tested against usual care CDS in a rapid (~6 weeks) RCT. The new alert text resulted in minimal impact on reducing firings per patients per day, but this failure triggered another round of review that identified key technical improvements (ie, removal of dismissal button and firings in procedural areas) that led to a dramatic decrease in firings per patient per day (23.1 to 7.3). In the second experiment, the process was used to test 3 versions (financial, quality, regulatory) of text supporting tobacco cessation alerts as well as 3 supporting images. Based on 3 rounds of RCTs, there was no significant difference in acceptance rates based on the framing of the messages or addition of images. CONCLUSIONS: These experiments support the potential for this new process to rapidly develop, deploy, and rigorously evaluate CDS within an EHR. We also identified important considerations in applying these methods. This approach may be an important tool for improving the impact of and experience with CDS. TRIAL REGISTRATION: Flu alert trial: ClinicalTrials.gov NCT03415425; https://clinicaltrials.gov/ct2/show/NCT03415425. Tobacco alert trial: ClinicalTrials.gov NCT03714191; https://clinicaltrials.gov/ct2/show/NCT03714191.

Design and implementation of a clinical decision support tool for primary palliative Care for Emergency Medicine (PRIM-ER).

BACKGROUND: The emergency department is a critical juncture in the trajectory of care of patients with serious, life-limiting illness. Implementation of a clinical decision support (CDS) tool automates identification of older adults who may benefit from palliative care instead of relying upon providers to identify such patients, thus improving quality of care by assisting providers with adhering to guidelines. The Primary Palliative Care for Emergency Medicine (PRIM-ER) study aims to optimize the use of the electronic health record by creating a CDS tool to identify high risk patients most likely to benefit from primary palliative care and provide point-of-care clinical recommendations. METHODS: A clinical decision support tool entitled Emergency Department Supportive Care Clinical Decision Support (Support-ED) was developed as part of an institutionally-sponsored value based medicine initiative at the Ronald O. Perelman Department of Emergency Medicine at NYU Langone Health. A multidisciplinary approach was used to develop Support-ED including: a scoping review of ED palliative care screening tools; launch of a workgroup to identify patient screening criteria and appropriate referral services; initial design and usability testing via the standard System Usability Scale questionnaire, education of the ED workforce on the Support-ED background, purpose and use, and; creation of a dashboard for monitoring and feedback. RESULTS: The scoping review identified the Palliative Care and Rapid Emergency Screening (P-CaRES) survey as a validated instrument in which to adapt and apply for the creation of the CDS tool. The multidisciplinary workshops identified two primary objectives of the CDS: to identify patients with indicators of serious life limiting illness, and to assist with referrals to services such as palliative care or social work. Additionally, the iterative design process yielded three specific patient scenarios that trigger a clinical alert to fire, including: 1) when an advance care planning document was present, 2) when a patient had a previous disposition to hospice, and 3) when historical and/or current clinical data points identify a serious life-limiting illness without an advance care planning document present. Monitoring and feedback indicated a need for several modifications to improve CDS functionality. CONCLUSIONS: CDS can be an effective tool in the implementation of primary palliative care quality improvement best practices. Health systems should thoughtfully consider tailoring their CDSs in order to adapt to their unique workflows and environments. The findings of this research can assist health systems in effectively integrating a primary palliative care CDS system seamlessly into their processes of care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03424109. Registered 6 February 2018, Grant Number: AT009844-01.

Primary Palliative Care for Emergency Medicine (PRIM-ER): Protocol for a Pragmatic, Cluster-Randomised, Stepped Wedge Design to Test the Effectiveness of Primary Palliative Care Education, Training and Technical Support for Emergency Medicine.

INTRODUCTION: Emergency departments (ED) care for society's most vulnerable older adults who present with exacerbations of chronic disease at the end of life, yet the clinical paradigm focuses on treatment of acute pathologies. Palliative care interventions in the ED capture high-risk patients at a time of crisis and can dramatically improve patient-centred outcomes. This study aims to implement and evaluate Primary Palliative Care for Emergency Medicine (PRIM-ER) on ED disposition, healthcare utilisation and survival in older adults with serious illness. METHODS AND ANALYSIS: This is the protocol for a pragmatic, cluster-randomised stepped wedge trial to test the effectiveness of PRIM-ER in 35 EDs across the USA. The intervention includes four core components: (1) evidence-based, multidisciplinary primary palliative care education; (2) simulation-based workshops; (3) clinical decision support; and (4) audit and feedback. The study is divided into two phases: a pilot phase, to ensure feasibility in two sites, and an implementation and evaluation phase, where we implement the intervention and test the effectiveness in 33 EDs over 2 years. Using Centers for Medicare and Medicaid Services (CMS) data, we will assess the primary outcomes in approximately 300 000 patients: ED disposition to an acute care setting, healthcare utilisation in the 6 months following the ED visit and survival following the index ED visit. Analysis will also determine the site, provider and patient-level characteristics that are associated with variation in impact of PRIM-ER. ETHICS AND DISSEMINATION: Institutional Review Board approval was obtained at New York University School of Medicine to evaluate the CMS data. Oversight will also be provided by the National Institutes of Health, an Independent Monitoring Committee and a Clinical Informatics Advisory Board. Trial results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT03424109; Pre-results.

Pilot and Feasibility Test of a Mobile Health-Supported Behavioral Counseling Intervention for Weight Management Among Breast Cancer Survivors.

BACKGROUND: Health behavior and weight management interventions for cancer survivors have the potential to prevent future cancer recurrence and improve long-term health; however, their translation can be limited if the intervention is complex and involves high participant burden. Mobile health (mHealth) offers a delivery modality to integrate interventions into daily life routines. OBJECTIVE: The objective of this study was to evaluate the effects of a one-group trial with a pre-post evaluation design on engagement (use and acceptability), physiological (weight), behavioral (diet and physical activity), and other secondary outcomes. METHODS: The 10-week intervention consisted of mHealth components (self-monitoring of selected diet behaviors via daily text messages, wireless devices to automatically track weight and steps) and 4 motivational interviewing-based technology-assisted phone sessions with a nonprofessionally trained counselor. Participants were overweight breast cancer survivors who had completed treatment and owned a smartphone. Weight was measured objectively; diet and physical activity were measured with brief self-reported questionnaires. RESULTS: Ten women participated; they had a mean age of 59 years (SD 6), 50% belonged to a racial or ethnic minority group, 50% had some college or less, and 40% reported using Medicaid health insurance. Engagement was high: out of 70 days in total, the mean number of days recording steps via the wristband pedometer was 64 (SD 7), recording a weight via the scale was 45 (SD 24), and responding to text messages was 60 (SD 13); 100% of participants completed all 4 calls with the counselor. Most (90%) were very likely to participate again and recommend the program to others. Mean weight in pounds decreased (182.5 to 179.1, mean change -3.38 [SD 7.67]), fruit and vegetable daily servings increased (2.89 to 4.42, mean change 1.53 [SD 2.82]), and self-reported moderate physical activity increased in metabolic equivalent of task (MET) minutes per week (2791 to 3336, mean change 545 [SD 1694]). CONCLUSIONS: Findings support the conduct of a fully powered trial to evaluate the efficacy of mHealth as a feasible intervention modality for breast cancer survivors. Future research should employ accelerometer-based physical activity assessment and consider development of an all-in-one app to integrate devices, messaging, and educational content and other mHealth approaches to support behavioral counselors conducting weight management interventions.

Pilot and Feasibility Test of a Mobile Health-Supported Behavioral Counseling Intervention for Weight Management Among Breast Cancer Survivors.

BACKGROUND: Health behavior and weight management interventions for cancer survivors have the potential to prevent future cancer recurrence and improve long-term health; however, their translation can be limited if the intervention is complex and involves high participant burden. Mobile health (mHealth) offers a delivery modality to integrate interventions into daily life routines. OBJECTIVE: The objective of this study was to evaluate the effects of a one-group trial with a pre-post evaluation design on engagement (use and acceptability), physiological (weight), behavioral (diet and physical activity), and other secondary outcomes. METHODS: The 10-week intervention consisted of mHealth components (self-monitoring of selected diet behaviors via daily text messages, wireless devices to automatically track weight and steps) and 4 motivational interviewing-based technology-assisted phone sessions with a nonprofessionally trained counselor. Participants were overweight breast cancer survivors who had completed treatment and owned a smartphone. Weight was measured objectively; diet and physical activity were measured with brief self-reported questionnaires. RESULTS: Ten women participated; they had a mean age of 59 years (SD 6), 50% belonged to a racial or ethnic minority group, 50% had some college or less, and 40% reported using Medicaid health insurance. Engagement was high: out of 70 days in total, the mean number of days recording steps via the wristband pedometer was 64 (SD 7), recording a weight via the scale was 45 (SD 24), and responding to text messages was 60 (SD 13); 100% of participants completed all 4 calls with the counselor. Most (90%) were very likely to participate again and recommend the program to others. Mean weight in pounds decreased (182.5 to 179.1, mean change -3.38 [SD 7.67]), fruit and vegetable daily servings increased (2.89 to 4.42, mean change 1.53 [SD 2.82]), and self-reported moderate physical activity increased in metabolic equivalent of task (MET) minutes per week (2791 to 3336, mean change 545 [SD 1694]). CONCLUSIONS: Findings support the conduct of a fully powered trial to evaluate the efficacy of mHealth as a feasible intervention modality for breast cancer survivors. Future research should employ accelerometer-based physical activity assessment and consider development of an all-in-one app to integrate devices, messaging, and educational content and other mHealth approaches to support behavioral counselors conducting weight management interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT02387671; https://clinicaltrials.gov/ct2/show/NCT02387671 (Archived by WebCite at http://www.webcitation.org/6hGEuttbZ).

Depression severity, diet quality, and physical activity in women with obesity and depression.

Major depressive disorder (MDD) is prevalent in clinical weight-loss settings and predicts poor weight-loss outcomes. It is unknown whether the severity of depressive symptoms among those with MDD is associated with diet quality or physical activity levels. This knowledge is important for improving weight-loss treatment for these patients. It was hypothesized that more severe depression is associated with poorer diet quality and lower physical activity levels among individuals with obesity and MDD. Participants were 161 women with current MDD and obesity enrolled in the baseline phase of a weight-loss trial between 2007 and 2010. Depression severity was measured with the Beck Depression Inventory II. The Alternate Healthy Eating Index was applied to data from three 24-hour diet recalls to capture overall diet quality. Daily metabolic equivalents expended per day were calculated from three 24-hour physical activity recalls. Greater depression severity was associated with poorer overall diet quality (estimate=-0.26, standard error 0.11; P=0.02), but not with physical activity (estimate=0.07, standard error 0.05; P=0.18), in linear regression models controlling for income, education, depression-related appetite change, binge eating disorder, and other potential confounds. Associations with diet quality were primarily driven by greater intake of sugar (r=0.20; P<0.01), saturated fat (r=0.21; P<0.01), and sodium (r=0.22; P<0.01). More severe depression was associated with poorer overall diet quality, but not physical activity, among treatment-seeking women with MDD and obesity. Future studies should identify mechanisms linking depression to diet quality and determine whether diet quality improves with depression treatment.

Development and validation of a self-assessment tool for albuminuria: results from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

BACKGROUND: The prevalence of albuminuria in the general population is high, but awareness of it is low. Therefore, we sought to develop and validate a self-assessment tool that allows individuals to estimate their probability of having albuminuria. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: The population-based Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study for model development and the National Health and Nutrition Examination Survey (NHANES) 1999-2004 for model validation. US adults 45 years or older in the REGARDS Study (n = 19,697) and NHANES 1999-2004 (n = 7,168). PREDICTOR: Candidate items for the self-assessment tool were collected using a combination of interviewer- and self-administered questionnaires. OUTCOME: Albuminuria was defined as a urinary albumin to urinary creatinine ratio ≥30 mg/g in spot samples. RESULTS: 8 items were included in the self-assessment tool (age, race, sex, current smoking, self-rated health, and self-reported history of diabetes, hypertension, and stroke). These items provided a C statistic of 0.709 (95% CI, 0.699-0.720) and good model fit (Hosmer-Lemeshow χ(2)P = 0.49). In the external validation data set, the C statistic for discriminating individuals with and without albuminuria using the self-assessment tool was 0.714. Using a threshold of ≥10% probability of albuminuria from the self-assessment tool, 36% of US adults 45 years or older in NHANES 1999-2004 would test positive and be recommended for screening. Sensitivity, specificity, and positive and negative predictive values for albuminuria associated with a probability ≥10% were 66%, 68%, 23%, and 93%, respectively. LIMITATIONS: Repeated urine samples were not available to assess the persistency of albuminuria. CONCLUSIONS: 8 self-report items provide good discrimination for the probability of having albuminuria. This tool may encourage individuals with a high probability to request albuminuria screening.

Projected impact of polypill use among US adults: Medication use, cardiovascular risk reduction, and side effects.

BACKGROUND: Polypills, which include multiple medications for reducing cardiovascular disease (CVD) risk in a single pill, have been proposed for population-wide use. The number of US adults eligible for polypills and potential benefits are unknown. METHODS: The National Health and Nutrition Examination Survey 2003-2004 and 2007-2008 were analyzed to estimate treatment rates for medications proposed for inclusion in polypills (aspirin, statin, an angiotensin-converting enzyme [ACE] inhibitor, and a thiazide-type diuretic for those without and a ß-blocker for those with a history of myocardial infarction) among US adults. The number of coronary heart disease (CHD) and stroke events potentially prevented through polypill use was projected by published meta-analyses and 3 large population-based cohort studies. Two polypill eligibility criteria were analyzed: (1) US adults ≥55 years and (2) US adults with a history of CVD. RESULTS: There are 67.6 million US adults ≥55 years and 15.4 million US adults with a history of CVD and, thus, eligible for polypills using the 2 outlined criteria. In 2007 to 2008, 37.3% of US adults ≥55 years and 57.0% of those with a history of CVD were taking statins. Use of other polypill medications was also low. Polypill use by US adults aged ≥55 years is projected to potentially prevent 3.2 million CHD events and 1.7 million strokes over 10 years. Among those with a history of CVD, the potential to prevent of 0.9 million CHD events and 0.5 million strokes is projected. CONCLUSIONS: Polypills have the potential to lower CVD incidence substantially among US adults.

Is measuring C-reactive protein useful for guiding treatment in women > or = 60 years and men > or = 50 years of age?

Using the results of the JUPITER trial, a recent report estimated that up to 11 million older United States (US) adults with C-reactive protein (CRP) levels > or =2 mg/L not currently recommended statins may benefit from treatment. However, the need to measure CRP in making this treatment decision has not been evaluated. Using data from 887 older US men and women (men > or =50 years old, women > or =60 years old) not currently on or recommended statin therapy participating in the National Health and Nutrition Examination Survey 2003 to 2006, we determined the sensitivity, specificity, and positive and negative predictive values of patient characteristics in identifying the presence of CRP > or =2 mg/L. If CRP > or =2 mg/L were included as an indication for statin therapy, then 90% of older US adults would be recommended treatment. Patients with CRP > or =2 mg/L were more likely (p <0.05) to be current smokers, obese, and have chronic kidney disease. However, characteristics (including demographics, cigarette smoking, obesity, chronic kidney disease, and metabolic syndrome) had low positive predictive values (<70%) for identifying patients with CRP > or =2 mg/L and negative predictive values (<60%) for those with CRP <2 mg/L. In conclusion, these findings suggest patient characteristics cannot be easily used to identify patients with CRP > or =2 mg/L. Given the demonstrated benefits of statin therapy, cost of measuring CRP, and large percentage of older US adults with high CRP, universal statin therapy for older US adults warrants investigation.

Relation of high-density lipoprotein cholesterol to mortality after percutaneous coronary interventions in patients with low-density lipoprotein <70 mg/dl.

High-density lipoprotein (HDL) cholesterol level is a strong predictor of morbidity and mortality in the general population. Conflicting data exist on the protective effects of high HDL cholesterol in patients with optimal low-density lipoprotein (LDL) cholesterol levels. To determine the association of high HDL cholesterol with mortality in patients with LDL cholesterol levels <70 mg/dl who undergo percutaneous coronary intervention, 3,616 consecutive patients with LDL cholesterol levels <70 mg/dl who underwent percutaneous coronary intervention from July 1, 1999, to June 1, 2007, were retrospectively analyzed and followed through July 1, 2007. All-cause mortality was identified using the National Death Index. The mortality rates was 34.7, 25.2, 23.7, and 18.8 per 1,000 person-years in patients with HDL cholesterol levels of <40, 40 to 49, 50 to 59, and > or =60 mg/dl, respectively (p for trend <0.001). After multivariate adjustment for demographic characteristics, cigarette smoking, biochemical variables, and co-morbid conditions, the hazard ratios for mortality in patients with HDL cholesterol levels of 40 to 49, 50 to 59, and > or =60 mg/dl, compared with their counterparts with HDL cholesterol levels <40 mg/dl, were 0.68 (95% confidence interval [CI] 0.50 to 0.93), 0.55 (95% CI 0.35 to 0.85), and 0.45 (95% CI 0.27 to 0.74), respectively. For each 1-SD increase in HDL cholesterol level (14 mg/dl), the multivariate-adjusted hazard ratio for all-cause mortality was 0.68 (95% CI 0.58 to 0.79). In conclusion, in patients with LDL cholesterol levels <70 mg/dl who underwent percutaneous coronary intervention, a strong inverse association was present between HDL cholesterol level and all-cause mortality.

Trends in statin use and low-density lipoprotein cholesterol levels among US adults: impact of the 2001 National Cholesterol Education Program guidelines.

BACKGROUND: Few data are available on the use of statins after publication of the National Cholesterol Education Program Third Adult Treatment Panel (ATP-III) guidelines in 2001. OBJECTIVE: To determine changes in statin use and its impact on low-density lipoprotein cholesterol (LDL-C) control among US adults from 1999 to 2004. METHODS: High LDL-C levels and statin use among 1911 participants of the National Health and Nutrition Examination Survey (NHANES) 2003-2004 were determined and compared with 1770 and 2094 participants of NHANES 1999-2000 and NHANES 2001-2002, respectively. Statin use was obtained from review of participants' drug containers. High LDL-C levels and LDL-C control were defined, using risk-specific cut-points from the ATP-III guidelines. RESULTS: Statins were taken by 24 million Americans in 2003-2004, an increase from 12.5 million in 1999-2000. In 1999-2000, 2001-2002, and 2003-2004, statins were being used by 19.6%, 27.3%, and 35.9% of US adults with high LDL-C levels, respectively (p trend <0.001). Age-standardized mean LDL-C declined from 119.9 to 112.0 to 100.7 mg/dL among statin users between 1999-2000, 2001-2002, and 2003-2004. LDL-C control to ATP-III recommended targets was achieved by 49.7%, 67.4%, and 77.6% of statin users in 1999-2000, 2001-2002, and 2003-2004, respectively (p trend <0.001). Among US adults with high LDL-C, after multivariate adjustment, non-Hispanic blacks were 39% less likely (prevalence ratio = 0.61; 95 CI 0.39 to 0.97) than non-Hispanic whites to be taking statins. CONCLUSIONS: Statin use continues to increase among US adults and this has led to substantial improvements in LDL-C control. Nevertheless, suboptimal statin use, especially among racial/ethnic minorities, continues to prevent the maximal public health benefit from this effective drug class.

Serum cystatin C and increased coronary heart disease prevalence in US adults without chronic kidney disease.

Previous studies indicated that serum cystatin C, a marker of renal function, was associated with cardiovascular disease (CVD). However, few data about this association are available for persons without chronic kidney disease or albuminuria. Data from 4,991 subjects in the Third National Health and Nutrition Examination Survey with an estimated glomerular filtration rate > or =60 ml/min/1.73 m2 without micro- or macroalbuminuria were analyzed. Subjects were categorized into quartiles of serum cystatin C and compared for prevalence of CVD. CVD was defined as a history of myocardial infarction, angina, or stroke. After age standardization, prevalences of CVD from the lowest to highest quartile of serum cystatin C were 6.0%, 8.8%, 11.8%, and 16.7% (p-trend = 0.006). Also, age-standardized prevalences of myocardial infarction across quartiles of serum cystatin C were 1.9%, 4.4%, 6.6%, and 8.6%; age-standardized prevalences of angina were 2.4%, 4.4%, 4.2%, and 7.1%; and age-standardized prevalences of stroke were 2.5%, 1.6%, 3.5%, and 4.4% (each p-trend <0.05). Each 1-SD higher serum cystatin C level was associated with a multivariate prevalence ratio of CVD of 1.55 (95% confidence interval [CI] 1.13 to 2.13), and multivariate-adjusted prevalence ratios were 1.44 (95% CI 1.01 to 2.07), 1.64 (95% CI 1.02 to 2.64), and 1.65 (95% CI 1.06 to 2.56) for myocardial infarction, angina, and stroke, respectively. In conclusion, a graded association exists between higher serum cystatin C and increased CVD prevalence in patients without established chronic kidney disease.

Overweight, obesity, and elevated serum cystatin C levels in adults in the United States.

BACKGROUND: Although high body mass index (BMI) is a risk factor for hypertension, diabetes, and cardiovascular disease, limited data exist on the association of overweight and obesity with early stages of kidney disease. METHODS: Cross-sectional data for 5083 participants of the nationally representative Third National Health and Nutrition Examination Survey with an estimated glomerular filtration rate > or = 60 mL/min/1.73 m(2) without micro- or macroalbuminuria were analyzed to determine the association between BMI and elevated serum cystatin C. Normal weight, overweight, class I obesity, and class II to III obesity were defined as a BMI of 18.5 to 24.9 kg/m(2), 25.0 to 29.9 kg/m(2), 30.0 to 34.9 kg/m(2), and > or = 35.0 kg/m(2), respectively. Elevated serum cystatin C was defined as > or = 1.09 mg/L (> or = 99th percentile for participants 20-39 years of age without diabetes, hypertension, micro- or macroalbuminuria, or stage 3-5 chronic kidney disease). RESULTS: The age-standardized prevalence of elevated serum cystatin C was 9.6%, 12.9%, 17.4%, and 21.5% among adults of normal weight, overweight, class I obesity, and class II to III obesity, respectively (P trend < .001). After multivariate adjustment for demographics, behaviors, systolic blood pressure, and serum biomarkers, and compared with participants of normal weight, the odds ratio (95% confidence interval) of elevated serum cystatin C was 1.46 (1.02-2.10) for overweight, 2.36 (1.56-3.57) for class I obesity, and 2.82 (1.56-5.11) for class II to III obesity. CONCLUSION: A graded association exists between higher BMI and elevated serum cystatin C. Further research is warranted to assess whether reducing BMI favorably affects elevated serum cystatin C and the development of chronic kidney disease.

Dietary indiscretion and statin use.

To determine whether statin use leads to dietary indiscretion, this longitudinal cohort study examined the impact of statin initiation on saturated fat intake. We interviewed 71 patients who had received a new prescription for statins for primary prevention of cardiovascular disease, first at the time of prescription and then again 3 and 6 months later. Patients were asked about their beliefs regarding diet and medications as well as their diet during the past 24 hours in all interviews and about their adherence to statins in the 3- and 6-month follow-up interviews. At the time of statin prescription, 54 participants (76 percent) wanted to reduce dietary fat, 50 (70 percent) believed statin use could cure their hyperlipidemia, and 31 (44 percent) thought that physicians prescribed statins to them despite their preference to continue to try dietary changes. After 6 months of statin use, no significant change in saturated fat intake was noted.