Impact of pre-existing type 2 diabetes with and without cardiovascular disease on patients with COVID-19.

AIM: To compare adverse outcomes among COVID-19 patients with pre-existing type 2 diabetes (T2D) only, T2D and cardiovascular disease (CVD), or neither. METHODS: This retrospective cohort study used administrative claims, laboratory and mortality data from the HealthCore Integrated Research Database. Patients with COVID-19 were identified from 3 January 2020 to 31 May 2021 and stratified by the presence of T2D and CVD. Outcomes included hospitalization, intensive care unit (ICU) admission, mortality and complications following COVID-19 infection. Propensity score matching and multivariable analyses were performed. RESULTS: A total of 321 232 COVID-19 patients were identified (21 651 T2D + CVD, 28 184 T2D only, and 271 397 neither) with a mean (SD) follow-up of 5.4 (3.0) months. After matching, 6 967 patients were identified for each group, and residual baseline differences remained. Adjusted analyses showed that COVID-19 patients with T2D + CVD were 59% more probable to be hospitalized, 74% more probable to be admitted to the ICU, and had a 26% higher mortality risk than those with neither. COVID-19 patients with T2D only were 28% and 32% more probable to be admitted to the hospital and ICU than those with neither, respectively. Among all T2D + CVD patients, acute respiratory distress syndrome (31%) and acute kidney disease (24%) were observed. CONCLUSION: Our study highlights the incrementally poorer outcomes associated with pre-existing T2D + CVD in COVID-19 patients compared with those without T2D/CVD and suggests consideration of a more optimal management approach in these patients.

Antibiotic prescribing by telephone in primary care.

OBJECTIVES: Little is known about the contribution of telephone-based prescribing on overall antibiotic utilization. The objective of this study was to determine the extent and characteristics of telephone-based antibiotic prescribing in teaching and non-teaching primary care practices. METHODS: This retrospective cohort study included all patients (n = 114 610) cared for by teaching and non-teaching internal medicine, pediatrics, family practice, and obstetrics/gynecology practices (n = 19) affiliated with a large US healthcare system during 2006-2010 and using a common electronic medical record. Rates and types of antibiotics prescribed by teaching and non-teaching practices via telephone contact and office visit were compared among the overall cohort. All telephone-related prescriptions during 2008 underwent chart review to determine indications for antibiotic prescribing. RESULTS: Overall, 28.9 antibiotic prescriptions were issued per 100 patient-years, with 63 418 total antibiotic prescriptions and 7876 (12.4%) generated after telephone contact. Telephone-based prescribing increased steadily from 2.2 to 4.2 per 100 patient-years during the study period. Both telephone-based and office-based antibiotic prescribing were higher in non-teaching practices. Of 1790 antibiotics prescribed by telephone during 2008, the majority were for urinary tract infection (28.3%), sinusitis (20.1%), and unspecified upper respiratory infection (URI, 15.0%). CONCLUSIONS: Overall, one in every eight antibiotics was prescribed via telephone encounter. These data highlight the need to include the impact of this practice in analysis of outcomes associated with outpatient antibiotic prescribing and to incorporate telephonic prescribing into guidelines facilitating appropriate antibiotic use.

Impact of Pre-existing Type 2 Diabetes Mellitus and Cardiovascular Disease on Healthcare Resource Utilization and Costs in Patients With COVID-19.

Background: The economic burden associated with type 2 diabetes mellitus (T2DM) and concurrent cardiovascular disease (CVD) among patients with COVID-19 is unclear. Objective: We compared healthcare resource utilization (HCRU) and costs in patients with COVID-19 and T2DM and CVD (T2DM + CVD), T2DM only, or neither T2DM nor CVD (T2DM/CVD). Methods: A retrospective observational study in COVID-19 patients using data from the Healthcare Integrated Research Database (HIRD®) was conducted. Patients with COVID-19 were identified between March 1, 2020, and May 31, 2021, and followed from first diagnosis or positive lab test to the end of health plan enrollment, end of study period, or death. Patients were assigned one of 3 cohorts: pre-existing T2DM+CVD, T2DM only, or neither T2DM/CVD. Propensity score matching and multivariable analyses were performed to control for differences in baseline characteristics. Study outcomes included all-cause and COVID-19-related HCRU and costs. Results: In all, 321 232 COVID-19 patients were identified (21 651 with T2DM + CVD, 28 184 with T2DM only, and 271 397 with neither T2DM/CVD). After matching, 6967 patients were in each group. Before matching, 46.0% of patients in the T2DM + CVD cohort were hospitalized for any cause, compared with 18.0% in the T2DM-only cohort and 6.3% in the neither T2DM/CVD cohort; the corresponding values after matching were 34.2%, 26.0%, and 21.2%. The proportion of patients with emergency department visits, telehealth visits, or use of skilled nursing facilities was higher in patients with COVID-19 and T2DM + CVD compared with the other cohorts. Average all-cause costs during follow-up were 12 324,7882, and $7277 per-patient-per-month after matching for patients with T2DM + CVD, T2DM-only, and neither T2DM/CVD, respectively. COVID-19-related costs contributed to 78%, 75%, and 64% of the overall costs, respectively. The multivariable model showed that per-patient-per-month all-cause costs for T2DM + CVD and T2DM-only were 54% and 21% higher, respectively, than those with neither T2DM/CVD after adjusting for residual confounding. Conclusion: HCRU and costs in patients were incrementally higher with COVID-19 and pre-existing T2DM + CVD compared with those with T2DM-only and neither T2DM/CVD, even after accounting for baseline differences between groups, confirming that pre-existing T2DM + CVD is associated with increased HCRU and costs in COVID-19 patients, highlighting the importance of proactive management.

Spirometry: tool for pharmacy practitioners to expand direct patient care services.

OBJECTIVES: To introduce pharmacy practitioners to spirometry testing and provide strategies for integrating this "value-added" tool with other direct patient care pharmacy services. DATA SOURCES: Spirometry literature and resources obtained through search strategies including Ovid, PubMed, and Google Scholar. SUMMARY: Pharmacists are distinctive members of the multidisciplinary patient care team and can contribute by performing spirometry services for pulmonary patients. Pharmacists have been largely absent from performing this much needed service, perhaps as a result of lack of training or because this testing may be perceived as irrelevant to the pharmacist scope of practice. However, pharmacists are actively integrated with many aspects of pulmonary patient care, including recommending and adjusting inhaled pharmacological agents, monitoring for potential drug-drug and drug-disease interactions, recommending smoking cessation, assessing patient prescription insurance coverage, and educating patients, caregivers, and health care providers on use of prescribed respiratory delivery devices. Adding quality spirometry services, based on American Thoracic Society guidelines for accuracy, would increase the breadth and depth of services for pharmacy practitioners. CONCLUSION: Spirometry testing is an added tool for expanding direct patient care pharmacy services. Physician support, appropriate pharmacist training, and understanding of reimbursement of spirometry services are essential in providing quality spirometry testing. Future studies are needed to assess the role of pharmacists in performing spirometry and measuring the performance outcomes of pulmonary patients.

Patient Perspectives on the Burden of Heart Failure with Preserved Ejection Fraction in a US Commercially Insured and Medicare Advantage Population: A Survey Study.

Background: Patient-reported health related quality of life (HRQOL) is not routinely assessed in clinical practice. Little is known about health status outcomes reported by patients with heart failure with preserved ejection fraction (HFpEF) in non-clinical trial settings. Purpose: To better understand patient burden of HFpEF in terms of HF-specific functional and symptom status, HRQOL, healthcare resource utilization (HCRU) and costs in a US-based commercial and Medicare Advantage insured population. Patients and methods: We conducted a cross-sectional survey of patients with HFpEF and linked their survey and administrative claims data. Consenting, eligible patients completed a survey that included the 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ-23) and the PROMIS Global Health-10 (GH-10) questionnaire, as well as clinical and demographic questions. HF medication use, HCRU and costs during the 12-month baseline period before the survey were determined from claims data. Generalized linear regression was used to assess the associations between baseline characteristics and the KCCQ-23 overall summary score. Results: Of 598 survey respondents with survey and claims data, 54.7% were female with mean age 74.0 years. The KCCQ-23 overall summary and clinical summary scores were 64.8 and 63.0, respectively, and the GH-10 physical and mental health summary scores were 39.9 and 45.5. Factors related to lower KCCQ-23 overall summary scores were HF treatment and symptom changes during the past 4-weeks before the survey, hospital admission during the past year, low household income, high comorbidity index, and morbid obesity (BMI>40). Total all-cause healthcare costs were $38,243 during the year prior to the survey, of which 42% were HF-related. Conclusion: Patient-reported outcome measure scores indicated impairment due to HF symptoms and physical limitations in this real-world sample of patients with HFpEF, highlighting a need to assess patient-reported outcomes as well as the clinical and economic outcomes traditionally assessed by clinicians, health systems and payers.

Descriptive study of the economic burden among patients with type 2 diabetes mellitus, chronic kidney disease, and chronic kidney disease and type 2 diabetes mellitus in a large US commercially insured population.

BACKGROUND: Chronic kidney disease (CKD) is a major public health concern that affects 37 million adults in the United States. It is well known that CKD presents a large economic burden, especially in the Medicare population. However, studies of the economic burden of CKD in younger populations are scarce. In particular, there is a gap in understanding how the presence of type 2 diabetes mellitus (T2DM) affects the burden of CKD in commercially insured populations. OBJECTIVE: To describe the economic and health care resource utilization (HCRU) burden of CKD within 3 patient groups (T2DM only, CKD only, and CKD and T2DM) aged 45-64 years overall and by Kidney Disease Improving Global Outcomes (KDIGO) CKD estimated glomerular filtration rate-based stage categories. METHODS: A descriptive, observational retrospective cohort study was conducted using administrative medical and pharmacy claims integrated with laboratory results data available in the HealthCore Integrated Research Database from January 1, 2017, to December 31, 2019. Three mutually exclusive groups of commercially insured patients aged 45-64 years were identified: T2DM only, CKD only, and CKD and T2DM. All-cause and disease-specific HCRU and costs in total, by medical and pharmacy benefits and across all places of service, were described for each of these groups 12 months after index date. For the CKD only and CKD and T2DM groups, costs were also described by KDIGO CKD stage. RESULTS: The CKD and T2DM group (n = 13,052) had numerically higher 12-month post-index all-cause and CKD/T2DM-related HCRU across all places of service. Mean 12-month all-cause costs for this group were $35,649, whereas costs for the CKD only group (n = 7,876) were $25,010 and costs for the T2DM only group (n = 120,364) were $16,121. Costs also tended to increase as CKD stage increased, with the greatest increases beginning at KDIGO stage 3b and higher. Mean 12-month all-cause costs for the CKD and T2DM group ranged from $29,993 to $41,222 for stages 1 to 3a and from $46,796 to $119,944 for stages 3b to 5. CONCLUSIONS: Commercially insured patients aged 45-64 years with CKD, especially those who also have T2DM, present a substantial burden in terms of elevated HCRU and costs. Costs tend to increase across KDIGO CKD stages and increase most rapidly at stage 3b and later. Therefore, there is an opportunity to reduce the burden of CKD in this population by investing in interventions to prevent or delay CKD disease progression. DISCLOSURES: HealthCore, Inc, received funding to perform this research, as well as funding from multiple pharmaceutical companies to perform various research studies outside of the submitted work. Mr Crowe and Dr Willey are employees of HealthCore, Inc., a wholly owned subsidiary of Elevance Health, Inc. Ms Chung was an employee of HealthCore, Inc., a wholly owned subsidiary of Elevance Health, Inc, at the time of study performance. Ms Chung and Dr Willey are shareholders of Elevance Health, Inc. Dr Kong, Dr Singh, Mr Farej, Dr Elliot, and Dr Williamson are employees of Bayer US, LLC. Dr Singh is a shareholder of Bayer US, LLC.

Study design and baseline profile for adults with type 2 diabetes in the once-weekly subcutaneous SEmaglutide randomized PRAgmatic (SEPRA) trial.

INTRODUCTION: Once-weekly subcutaneous semaglutide, a glucagon-like peptide-1 analog, is approved in the USA as an adjunct to diet and exercise for adults with inadequately controlled type 2 diabetes (T2D) to improve glycemic control and reduce the risk of major adverse cardiovascular events in people with T2D and established cardiovascular disease. The Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) phase III clinical trial program demonstrated the efficacy and safety of once-weekly subcutaneous semaglutide; however, determining its effectiveness in a real-world setting could support decision-making by clinicians, payers and policy makers in routine clinical practice. RESEARCH DESIGN AND METHODS: SEmaglutide PRAgmatic (SEPRA) is an ongoing open-label, randomized, pragmatic clinical trial designed to compare the effects of once-weekly subcutaneous semaglutide versus standard of care in US health-insured adults with T2D and physician-determined inadequate glycemic control. The primary end point is the proportion of participants achieving glycated hemoglobin (HbA1c) <7.0% at year 1; other key outcomes include glycemic control, weight loss, healthcare utilization, and patient-reported outcomes. Individual-level data will be collected from routine clinical practice and health insurance claims. The last patient last visit is expected by June 2023. RESULTS: Between July 2018 and March 2021, 1278 participants were enrolled from 138 study sites across the USA. At baseline, 54% were male with mean±SD age 57.4±11.1 years and body mass index 35.7±8.0 kg/m2. Mean diabetes duration was 7.4±6.0 years and mean HbA1c was 8.5±1.6%. At baseline, concomitant antidiabetes medications included metformin, sulfonylureas, sodium-glucose co-transporter-2 inhibitors, and dipeptidyl peptidase-4 inhibitors. The majority of participants had hypertension and dyslipidemia. The trial design was self-assessed using the PRagmatic Explanatory Continuum Indicator Summary-2 tool by the study steering group and was scored 4-5 in all domains suggesting a highly pragmatic study. CONCLUSIONS: SEPRA, a highly pragmatic ongoing study, will provide data on the effects of once-weekly subcutaneous semaglutide in a real-world setting when used during routine management of T2D. TRIAL REGISTRATION NUMBER: NCT03596450.

Rigorous and rapid evidence assessment in digital health with the evidence DEFINED framework.

Dozens of frameworks have been proposed to assess evidence for digital health interventions (DHIs), but existing frameworks may not facilitate DHI evidence reviews that meet the needs of stakeholder organizations including payers, health systems, trade organizations, and others. These organizations may benefit from a DHI assessment framework that is both rigorous and rapid. Here we propose a framework to assess Evidence in Digital health for EFfectiveness of INterventions with Evaluative Depth (Evidence DEFINED). Designed for real-world use, the Evidence DEFINED Quick Start Guide may help streamline DHI assessment. A checklist is provided summarizing high-priority evidence considerations in digital health. Evidence-to-recommendation guidelines are proposed, specifying degrees of adoption that may be appropriate for a range of evidence quality levels. Evidence DEFINED differs from prior frameworks in its inclusion of unique elements designed for rigor and speed. Rigor is increased by addressing three gaps in prior frameworks. First, prior frameworks are not adapted adequately to address evidence considerations that are unique to digital health. Second, prior frameworks do not specify evidence quality criteria requiring increased vigilance for DHIs in the current regulatory context. Third, extant frameworks rarely leverage established, robust methodologies that were developed for non-digital interventions. Speed is achieved in the Evidence DEFINED Framework through screening optimization and deprioritization of steps that may have limited value. The primary goals of Evidence DEFINED are to a) facilitate standardized, rapid, rigorous DHI evidence assessment in organizations and b) guide digital health solutions providers who wish to generate evidence that drives DHI adoption.

A digital approach to asthma self-management in adults: Protocol for a pragmatic randomized controlled trial.

Asthma self-management can improve symptom control, but adherence to established self-management behaviors is often poor. With adult asthma uncontrolled in over 60% of U.S. cases, there is a need for scalable, cost-effective tools to improve asthma outcomes. Here we describe a protocol for the Asthma Digital Study, a 24-month, decentralized, pragmatic, open-label, randomized controlled trial investigating the impact of a digital asthma self-management (DASM) program on asthma outcomes in adults. The program leverages consumer-grade devices with a smartphone app to provide "smart nudges," symptom logging, trigger tracking, and other features. Participants are recruited (target N = 900) from throughout the U.S., and randomized to a DASM or control arm (1:1). Co-primary outcomes at one year are a) asthma-associated costs for acute care and b) change from baseline in Asthma Control Test™ scores. Findings may inform decisions around adoption of digital tools for asthma self-management. Trial registration:clinicaltrials.gov identifier: NCT04609644. Registered: Oct 30, 2020.

Effect of compliance with GOLD treatment recommendations on COPD health care resource utilization, cost, and exacerbations among patients with COPD on maintenance therapy.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) report for the management of chronic obstructive pulmonary disease (COPD) focuses on reducing existing symptoms, decreasing the risk of future exacerbations, and improving health status by recommending specific drug therapy based on exacerbation risk and symptoms. However, disparities exist between evidence-based recommendations and clinical practice. Research that quantifies the real-world effect of COPD regimen alignment with the GOLD recommendations on clinical and economic outcomes is needed. OBJECTIVE: To compare COPD-related health care resource utilization (HRU) and costs, as well as exacerbation rates, among patients with COPD on maintenance therapy based on 2017 GOLD treatment recommendation compliance status per GOLD ABCD risk group classification in a U.S. commercially insured/Medicare Advantage population. METHODS: This retrospective cohort study utilized administrative claims data in the HealthCore Integrated Research Database. The COPD population was identified using a previously validated claims-based predictive model. Among this population, patients with ≥ 1 claim for a COPD maintenance medication (earliest maintenance fill-date = index date) between January 1, 2014, and March 31, 2017, were identified. Patients were required to be aged ≥ 40 years, have ≥ 12 months of pre-index and ≥ 30 days of post-index health plan enrollment, with no diagnosis for asthma, cystic fibrosis, and/or lung cancer at any time from January 1, 2013, to March 31, 2018. Patients were categorized into exacerbation risk/symptomatology groups according to the 2017 GOLD ABCD assessment recommendations and were then classified into treatment-compliance status based on their maintenance therapy. Multivariable analyses were conducted to examine post-index COPD-related HRU, costs, and exacerbations by compliance status. RESULTS: The primary analytical study sample included 38,382 patients in the GOLD A/B group and 6,525 in the GOLD C/D group. Patients were further categorized into GOLD A (n = 19,345), B (n = 19,037), C (n = 1,865), and D (n = 4,670). GOLD-compliant regimens were observed in 32.9% of patients in the GOLD A/B group and in 58.9% of patients in the GOLD C/D group. Inhaled corticosteroid-containing regimens were the most commonly observed noncompliant regimen. Patients on compliant regimens had significantly fewer COPD-related inpatient and emergency department visits and therefore had significantly lower COPD-related medical costs in both the GOLD A/B and C/D cohorts. Similar results were observed for individual GOLD cohorts B, C, and D. These savings were offset by increased pharmacy expenditures. Being on GOLD guideline-compliant regimens significantly reduced the risk of exacerbation by 8% (hazard ratio [HR] = 0.92; P < 0.0001) in the GOLD A/B cohort and by 12% (HR = 0.88; P = 0.0005) in the GOLD C/D cohort, and was also associated with a significantly reduced exacerbation rate in the GOLD A/B (rate ratio [RR] = 0.93; P < 0.0001) and GOLD C/D (RR = 0.93; P = 0.0129) groups. CONCLUSIONS: This study suggests a continuing trend of high prevalence of suboptimal prescriber compliance to GOLD treatment recommendations. Treatment regimens compliant with GOLD recommendations were associated with improvement in exacerbations, reduced COPD-related HRU, and COPD-related medical cost offsets. DISCLOSURES: This study was funded by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI). BIPI was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations. Palli and Shaikh are employees of BIPI. Willey is an employee of HealthCore, which was contracted by BIPI to conduct this study. Zhou was an employee of HealthCore at the time of study execution. Data were presented in part during an AMCP webinar (recording not made public) held in lieu of the Spring 2020 AMCP conference, which was canceled due to the COVID-19 pandemic.

Real-World Effectiveness of Once-Weekly Semaglutide From a US Commercially Insured and Medicare Advantage Population.

PURPOSE: Patients managing type 2 diabetes mellitus (T2DM) often require combination therapy to meet their blood glucose control targets. With limited real-world evidence focused on the use of glucagon-like peptide 1 receptor agonist (GLP-1RA) therapies, the objective of this study was to describe the association between semaglutide once weekly (OW) initiation and changes in hemoglobin A1c (A1c) levels. METHODS: This retrospective, descriptive cohort study used the HealthCore Integrated Research Environment (HIRE) to examine commercially insured and Medicare Advantage patients who had T2DM while taking semaglutide OW from December 1, 2017, to April 30, 2019. The first semaglutide OW prescription fill was defined as the study index date. Changes in mean A1c levels and A1c target attainment were evaluated among an intention-to-treat (ITT) population (overall group). Furthermore, a persistent population (PP) analysis on the same outcomes was performed that was limited to ITT patients who were observed to continue to use semaglutide OW at the time of the postindex A1c measurement. In addition, these outcomes were explored in patients stratified based on prior use of GLP-1RA therapy (experienced vs naive) and baseline A1c values >9% (75 mmol/mol). FINDINGS: A total of 1888 patients were identified in the overall ITT group. The mean change in the overall ITT group between preindex and postindex A1c values was -0.9% percentage points (-9.8 mmol/mol) (mean preindex A1c, 8.2% [66.1 mmol/mol]) and -1.1 percentage points (-12.0 mmol/mol) (mean preindex A1c, 8.2% [66.1 mmol/mol]) in the PP subgroup (all P < 0.001). Among the subgroup of patients with a baseline A1c value >9% (75 mmol/mol), percentage point changes in A1c were -2.2 (-24.0 mmol/mol) and -2.4 (-26.2 mmol/mol) (all P < 0.001). When accounting for prior GLP-1RA use, the GLP-1RA-naive stratum had double the mean reduction in A1c compared with the GLP-1RA-experienced stratum (-1.2 [-13.1 mmol/mol] vs -0.6 [-6.6 mmol/mol] percentage points). IMPLICATIONS: Semaglutide OW is associated with clinically and statistically significant A1C reduction and increases in reaching A1 targets using real-world data, even in GLP-1RA-experienced patients, despite more frequent use of insulin or sodium glucose transport protein 2 inhibitors in this group. Target A1c attainment significantly increased overall and within all subgroups and strata, with approximately half of all patients attaining an A1c value <7% (53 mmol/mol) and three-quarters attaining an A1c value <8% (64 mmol/mol).

Epidemiologic study of aripiprazole use and the incidence of suicide events.

PURPOSE: Because second generation antipsychotics (SGA) might affect the risk of suicide, systematic assessment of suicide risk associated with SGA in the postmarketing setting is important and of interest to regulatory authorities. To fulfill a postmarketing request, our objective was to determine suicide event (attempted or completed) incidence in patients with schizophrenia or bipolar disorder, prescribed aripiprazole. METHODS: Using administrative data from three US sources, we assessed study endpoints of suicide attempts and death by suicide in patients aged ≥18 enrolled continuously for ≥3 months in their health plans before receiving their first ever antipsychotic (November 2002-December 2005). RESULTS: Among 20 489 antipsychotic users (8985 patient-years), unadjusted suicide event rates (per 1000 patient-years) were: 20.69 (aripiprazole); 23.99 (olanzapine); 32.33 (quetiapine); 19.69 (risperidone); 48.52 (ziprasidone). Compared with current users of other SGA combined, aripiprazole users did not have an increased risk of suicide events (crude hazard ratio (HR) = 0.79, 95%CI: 0.48-1.30; adjusted HR = 0.69, 95%CI: 0.42-1.14-(controlling for study site, age, sex, index prescription year, antipsychotic use history, other pharmacotherapy exposure, comorbidity presence, schizophrenia/bipolar disorder, suicide attempts, number inpatient/outpatient encounters). CONCLUSIONS: In this large, multi-site study, compared with other SGA combined, aripiprazole is not associated with an increased risk of suicide events in an inception cohort of patients with ICD-9/ICD-10 codes indicative of schizophrenia or bipolar disorder.

Assessing risk of future cardiovascular events, healthcare resource utilization and costs in patients with type 2 diabetes, prior cardiovascular disease and both.

BACKGROUND: Description of risk of cardiovascular (CV) events associated with diabetes is evolving. This US-based real-world study estimated risk of future CV events and heart failure (HF) from type 2 diabetes (T2DM) only, prior CV events only or T2DM plus prior CV events, versus controls, and evaluated healthcare resource utilization (HCRU) and costs. METHODS AND MATERIALS: This retrospective cohort study queried claims and mortality data for 638,301 patients: T2DM only (377,205); prior CV events only (130,964); both T2DM and prior CV events (130,132); and matched (1:1) controls, during 1 January 2012-31 December 2012. Cardiovascular diagnoses/events and death were assessed individually, and as composite endpoint (myocardial infarction [MI], stroke, transient ischemic attack [TIA], peripheral artery disease [PAD]), during follow-up, ending 31 July 2018. RESULTS: Adjusting for age and gender, patients with T2DM only were 1.6, prior CV events only 2.5 and T2DM plus prior CV events 3.8 times likelier to have primary composite CV events relative to controls, p < .001. HF development was elevated across all three cohorts. Adjusted results showed inpatient admissions for T2DM only, CV events only and T2DM plus prior CV events were 1.37, 2.76 and 3.63 times greater than controls, respectively. All-cause healthcare costs were highest in the T2DM plus prior CV events cohort ($2783 per patient per month [PPPM]) followed by the prior CV events only ($1910 PPPM) and T2DM only cohorts ($1343 PPPM), and controls ($825 PPPM). Adjusted all-cause total costs were 1.48 for T2DM only, 1.49 for prior CV events only and 1.93 for T2DM plus prior CV events times higher compared to controls. CONCLUSION: In this large and geographically broad US based cohort, CV risk for T2DM patients was elevated, as was the risk for patients with prior CV events, while patients with T2DM plus prior CV events had the highest risk of future CV events. The substantial clinical and economic burden of CV events and HF in patients with both T2DM and prior CV events suggest a need for an integrated treatment and targeted intervention across both conditions.

Real-World Treatment Patterns, Healthcare Resource Utilization, and Costs for Patients with Newly Diagnosed Systolic versus Diastolic Heart Failure.

BACKGROUND: Although the significant burden of heart failure (HF) is well recognized, the relative contributions of systolic HF versus diastolic HF are less defined. OBJECTIVE: To explore the differential burden between patients with systolic and diastolic HF in terms of treatment patterns, healthcare resource utilization (HCRU), costs, and mortality risk. METHODS: This retrospective cohort study used administrative claims data from a large US commercial health insurer integrated with mortality data. Patients newly diagnosed with HF between January 1, 2010, and June 30, 2016, were identified and grouped according to systolic HF or diastolic HF diagnosis and were followed up to 4 years after diagnosis. Treatment patterns, HCRU, costs, and mortality were compared between the 2 groups of patients. RESULTS: Overall, 46,885 patients with systolic HF and 21,854 with diastolic HF were identified and included in the study. Patients with systolic HF had less HCRU than those with diastolic HF during the first year after HF diagnosis, including hospital admissions (70.2% vs 82.4%, respectively; P <.001) and emergency department visits (30.5% vs 39.1%, respectively; P <.001). The average per-patient costs for patients with systolic HF during the 1-year follow-up were higher than for those with diastolic HF ($64,154 vs $59,652, respectively; P <.001), but lower during years 2 through 4 (approximately $23,000-$25,000 annually vs approximately $28,000-$29,000 annually; P <.001). Patients with diastolic HF had a higher adjusted hospitalization risk (odds ratio, 1.62; 95% confidence interval [CI], 1.55-1.69), but comparable adjusted costs (exponentiated estimate, 1.01; 95% CI, 0.99-1.02) and slightly lower mortality risk (hazard ratio, 0.96; 95% CI, 0.93-0.99) versus patients with systolic HF. The number of HF-related medication classes received for other diagnoses during the year preceding an HF diagnosis was associated with lower risks for hospitalization, mortality, and lower costs, with a trend in benefits toward patients with systolic HF. Of note, 21.9% of patients with systolic HF and 25% of patients with diastolic HF filled no HF-related prescriptions in the year after diagnosis. CONCLUSION: This real-world analysis confirms a high disease burden associated with HF and provides insight across the systolic HF and diastolic HF phenotypes. HF-related medication use after diagnosis was suboptimal and underscores a gap in patient care.

Healthcare Costs of Diabetes and Microvascular and Macrovascular Disease in Individuals with Incident Type 2 Diabetes Mellitus: A Ten-Year Longitudinal Study.

OBJECTIVE: The objective of this study was to estimate the incremental long-term costs associated with T2DM attributable to vascular diseases. RESEARCH DESIGN AND METHODS: This retrospective cohort study identified newly diagnosed (incident) T2DM patients in 2007 (baseline to 01/01/2006) using the HealthCore Integrated Research Database, a repository of nationally representative claims data. Incident T2DM patients were 1:1 exact matched on age, gender and other factors of interest to non-DM patients, and followed until the earlier of 8 follow-up years or death. Patients with documented vascular disease diagnosis were identified during the study period. All-cause and T2DM/vascular disease-related annual healthcare costs were examined for each follow-up year. RESULTS: The study included 13,883 individuals with T2DM and matched non-DM controls. Among individuals with T2DM, 11,792 (85%) had vascular disease versus 9251 (66.6%) non-T2DM between 01/01/2006 and 12/31/2015. Among T2DM patients, mean all-cause annual costs were greater than in non-T2DM patients ($13,806 vs $7,243, baseline, $21,745 vs $8,524, post-index year 1, $12,756-$14,793 vs $8,349-$9,940 years 2-8, p< 0.001), respectively. A similar trend was observed for T2DM/vascular disease-related costs (p< 0. 001). T2DM/vascular disease-related costs were largest during post-index year 1, accounting for the majority of all-cause cost difference between T2DM patients and matched non-DM controls. Incident T2DM individuals without vascular disease at any time had significantly lower costs compared to non-DM controls (p< 0. 001) between years 2-8 of follow-up. CONCLUSION: Vascular disease increased the cost burden for individuals with T2DM. The cost impact of diabetes and vascular disease was highest in the year after diagnosis, and persisted for at least seven additional years, while the cost of T2DM patients without vascular disease trended lower than for matched non-DM patients. These data highlight potential costs that could be offset by earlier and more effective detection and management of T2DM aimed at reducing vascular disease burden.

The incidence of diabetes in atypical antipsychotic users differs according to agent--results from a multisite epidemiologic study.

PURPOSE: The purpose of this study was to examine the association between atypical antipsychotics, including the newer agents, aripiprazole and ziprasidone, and newly treated diabetes, using the largest post-marketing cohort of patients exposed to these newer treatments that has been studied to date. METHODS: Identified two overlapping cohorts-a simple cohort (all antipsychotic users) and an inception cohort (new users of antipsychotics)-using automated data from three United States sites (60.4 million covered lives). Patients exposed to antipsychotics > or = 45 days were identified and followed for incident diagnoses of treated diabetes. Data analysis accounted for drug switching and non-consistent drug use. RESULTS: In the 55 287-member inception cohort, 357 cases of newly treated diabetes were identified. Compared with current use of typical antipsychotics, current users of aripiprazole (adjusted hazard ratio (aHR) 0.93, 95% confidence interval (CI) 0.50-1.76), quetiapine (aHR 1.04, 95%CI, 0.67-1.62), risperidone (aHR 0.85, 95%CI, 0.54-1.36) and ziprasidone (aHR 1.05, 95%CI, 0.54-2.08) had similar low risk of diabetes. Patients exposed to olanzapine had an increased risk of diabetes (aHR 1.71, 95%CI, 1.12-2.61), and although the effect estimate is imprecise, clozapine-exposed patients had a trend towards an elevated hazard ratio (aHR 2.58, 95%CI, 0.76-8.80). Results for the simple cohort were similar. CONCLUSIONS: Relative to typical antipsychotics, aripiprazole, ziprasidone, risperidone and quetiapine were not associated with an increased risk of diabetes; olanzapine and clozapine were associated with an increased risk. This analysis constitutes the largest post-marketing pharmacoepidemiologic study to date that includes the newer agents.

Health Plan Enrollment and Disenrollment of Individuals With and Without Established Chronic Disease in a U.S. Commercially Insured and Medicare Advantage Population.

BACKGROUND: Chronic disease is associated with increased health care resource utilization and costs. Effective development and implementation of health care management and clinical intervention programs require an understanding of health plan member enrollment and disenrollment behavior. OBJECTIVE: To examine the health plan enrollment and disenrollment behavior of commercially insured and Medicare Advantage members with established chronic disease compared with matched members without the disease of interest, using data from a large national health insurer in the United States. METHODS: This retrospective matched cohort study used administrative claims data from the HealthCore Integrated Research Database from January 1, 2006, to November 30, 2015, to identify adults with chronic disease (type 2 diabetes mellitus [T2DM], cardiovascular disease [CVD], chronic obstructive pulmonary disease [COPD], rheumatoid arthritis [RA], and breast cancer [BC]). Members with no established chronic disease (controls) were directly matched to members with established chronic disease (cases) on demographic characteristics. The earliest date on which members met the criteria for a given disease was defined as the index date. Controls had the same index date as the matched cases. All members had ≥ 12 months of continuous health plan enrollment before the index date. Outcomes included health plan member disenrollment and enrollment duration. Incidence rates per 1,000 member-years for member disenrollment were evaluated along with incidence rate ratios (relative risk) using a Poisson model. Time to disenrollment was analyzed by Cox proportional hazard models and Kaplan-Meier survival curves. Sensitivity analyses were conducted where death was included as a disenrollment event. RESULTS: 70,907 health plan members with BC (99.7% female, mean age 60.5 years); 28,883 members with COPD (52.3% female, mean age 66.7); 835,358 members with CVD (50.5% female, mean age 62.7 years); 210,936 members with T2DM (45.2% female, mean age 53.6 years); and 31,954 members with RA (72.0% female, mean age 55.5 years) were matched to controls and met the study criteria. The incidence rates of health plan disenrollment ranged from 155 to 192 members per 1,000 members per year. Compared with controls, members with chronic disease were 30%-40% less likely to disenroll from a health plan (P < 0.001 for all comparisons). Among those who disenrolled, enrollment duration ranged from 2.3 to 2.7 years among cases and 1.5 to 1.8 years among matched controls (P ≤ 0.001 for all comparisons). CONCLUSIONS: This real-world study demonstrated that members with chronic disease had a significantly lower rate of disenrollment and a longer duration of enrollment compared with matched controls and were continuously enrolled for almost a year longer than members without a diagnosed chronic disease. Understanding health plan enrollment and disenrollment behavior may provide a valuable context for determining the time frame for the effect of health care programs and initiatives. DISCLOSURES: Funding for this study was provided by HealthCore, a wholly owned subsidiary of Anthem. Chung, Deshpande, Zolotarjova, Quimbo, and Willey are employees of HealthCore. Kern and Cochetti are former employees of HealthCore. Quimbo, Cochetti, and Willey are shareholders of Anthem. HealthCore receives funding from multiple pharmaceutical companies to perform various research studies outside of the submitted work. The preliminary results of this study were presented at AMCP Nexus 2015; March 26-29, 2015; Orlando, FL, and the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2017 Conference; May 20-24, 2017; Boston, MA.

Health Care Resource Utilization and Exacerbation Rates in Patients with COPD Stratified by Disease Severity in a Commercially Insured Population.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality and is associated with substantial economic burden. There is a lack of data regarding COPD outcomes and costs in a real-world setting, particularly by Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity. OBJECTIVES: To (a) characterize a commercially insured U.S. population with COPD and (b) assess prevalence of exacerbations, health care resource utilization (HCRU), costs, and treatment patterns in a cohort of patients with confirmed COPD, overall and stratified by GOLD stage. METHODS: This retrospective observational cohort study used administrative claims data from the HealthCore Integrated Research Database to identify patients with ≥ 1 inpatient, emergency room (ER), or office visit claim for COPD between January 1, 2012, and November 30, 2013, and continuous enrollment for 1 year before and 2 years after the first COPD diagnosis date. Patients with a spirometry claim within 12 months were eligible for medical record abstraction to confirm COPD diagnosis (forced expiratory volume in 1 second [FEV1]/forced vital capacity ratio < 0.7) and GOLD 1-4 classification (based on postbronchodilator FEV1 percent predicted). HCRU, costs, treatment patterns, and rate of moderate/severe exacerbation were identified from diagnosis up to 24 months. Outcomes were analyzed by univariate analysis stratified by GOLD classification. Multivariable analysis was conducted to assess associations between GOLD classification and outcomes of interest. RESULTS: 53,484 patients newly diagnosed with COPD were identified who met initial inclusion criteria: 14,293 (27%) had a qualifying spirometry claim, and 1,505 had confirmed COPD (GOLD 1, 333 [22%]; GOLD 2, 823 [55%]; GOLD 3, 317 [21%]; GOLD 4, 32 [2%]). Patients with greater disease severity had higher rates of moderate/severe COPD exacerbations (GOLD 1 and 2, 40.4 and 48.9 per 100 person-years, respectively; GOLD 3 and 4, 83.6 and 89.1 per 100 person-years, respectively). All-cause and COPD-related inpatient admissions, COPD-related office visits, and COPD-related ER visits were more prevalent with more severe GOLD classification. Mean annual COPD-related medical costs increased with GOLD classification ($5,945 for GOLD 1 patients, $18,070 for GOLD 4). COPD maintenance medication was filled by 42%, 56%, 73%, and 75% of patients in GOLD 1-4 (57% overall), respectively; combination corticosteroid/long-acting beta2-agonist inhalers were the most commonly used medication, regardless of GOLD classification. Patients with more severe disease had greater adherence (range 44%-68% of days covered for GOLD 1-4) and persistence (range 107-209 days for GOLD 1-4). CONCLUSIONS: Trends toward increases in exacerbations, HCRU, and costs were observed as airflow limitation worsened. Adherence and persistence with COPD maintenance therapy was suboptimal even with severe disease. DISCLOSURES: This study was supported by Boehringer Ingelheim Pharmaceuticals (Ridgefield, CT), which was given the opportunity to review the manuscript for medical and scientific accuracy, as well as intellectual property considerations. Willey and Singer are employees of HealthCore (parent company Anthem), which received funding from Boehringer Ingelheim to complete this study. Wallace and Shinde were employed by HealthCore at the time of this study. Wallace and Singer report stock ownership in Anthem. Napier is an employee of Anthem. Kaila, Bayer, and Shaikh are employees of Boehringer Ingelheim Pharmaceuticsls. Portions of this research were presented at the following conferences: (a) A. Wallace, S. Kaila, V. Zubek, A. Shaikh, M. Shinde, V. Willey, M. Napier, and J. Singer, Healthcare resource utilization, costs, and exacerbation rates in patients with COPD stratified by GOLD airflow limitation classification in a US commercially insured population, presented at AMCP Nexus 2017; October 16-19, 2017; Dallas, TX; and (b) A.E. Wallace, V. Zubek, S. Kaila, A. Shaikh, M. Shinde, V. Willey, M.B. Napier, and J.R. Singer, Real-world treatment patterns among newly diagnosed COPD patients according to GOLD airflow limitation severity classification in a U.S. commercially insured/Medicare Advantage population, presented at CHEST 2017 Annual Meeting; October 28-November 1, 2017; Toronto, Ontario, Canada.

Predictors of Hemoglobin A1c Goal Attainment in Patients Treated With Insulin at a VA Pharmacist-Managed Insulin Clinic.

Showing up to appointments and adherence to treatment recommendations correlated with glycemic goal attainment for patients.

Estimating the Real-World Cost of Diabetes Mellitus in the United States During an 8-Year Period Using 2 Cost Methodologies.

BACKGROUND: Diabetes is associated with substantial clinical and economic burdens on patients and on the US healthcare system. Treatment options for patients with type 1 or type 2 diabetes have increased significantly, from only 3 drug classes in 1995 to more than 12 distinct classes today. Although several of the newer treatments are reported to have improved efficacy and safety profiles, they are often substantially more costly than older medications. Consequently, as drug options increase, the cost of diabetes management continues to grow. OBJECTIVES: To estimate the annual real-world costs of type 1 and 2 diabetes, as well as diabetes prevalence, treatment patterns, care quality, and resource utilization during 8 years. METHODS: In this cross-sectional study, we examined 8 annual cohorts of patients with type 1 or type 2 diabetes, on a biennial basis, using claims data from the HealthCore Integrated Research Database between 2006 and 2014. Patients were matched with controls by age, sex, residency, and health plan type. We assessed the prevalence of diabetes, treatment patterns, care quality measures, and all-cause and diabetes-related healthcare costs using 2 methods. Method 1 calculated the annual costs as the difference in all-cause costs between patients with diabetes and matched controls. Method 2 calculated the costs for healthcare encounters based on specific codes for a diabetes diagnosis or for antidiabetes medications. RESULTS: Between 346,486 and 410,234 patients with type 2 diabetes and between 21,176 and 26,228 patients with type 1 diabetes were included in each study year cohort. Between 2007 and 2014, the prevalence of type 2 diabetes increased from 4.9% to 6.3%. The costs associated with using Method 1 were almost double the cost estimates in Method 2 during most of the study period. For patients with type 1 diabetes, the associated costs were twice greater with Method 1 than with Method 2. Projections to the entire US population in 2014 indicated a total of 19.3 million individuals with diabetes and associated direct costs of $314.8 billion that year. CONCLUSION: Cost estimates can guide the prioritization of healthcare expenditures. The results of this study showed that costs attributable to diabetes differed by approximately 2-fold, depending on the estimation method. The management of the escalating expenses for diabetes management in the United States requires judicious selection of the methods for estimating costs.