Sudhir Unni

The effect of pharmacogenetic profiling with a clinical decision support tool on healthcare resource utilization and estimated costs in the elderly exposed to polypharmacy

Abstract Objective: To compare healthcare resource utilization (HRU) and clinical decision-making for elderly patients based on cytochrome P450 (CYP) pharmacogenetic testing and the use of a comprehensive medication management clinical decision support tool (CDST), to a cohort of similar non-tested patients. Methods: An observational study compared a prospective cohort of patients ≥65 years subjected to pharmacogenetic testing to a propensity score (PS) matched historical cohort of untested patients in a claims database. Patients had a prescribed medication or dose change of at least one of 61 oral drugs or combinations of ≥3 drugs at enrollment. Four-month HRU outcomes examined included hospitalizations, emergency department (ED) and outpatient visits and provider acceptance of test recommendations. Costs were estimated using national data sources. Results: There were 205 tested patients PS matched to 820 untested patients. Hospitalization rate was 9.8% in the tested group vs 16.1% in the untested group (RR = 0.61, 95% CI = 0.39–0.95, p = 0.027), ED visit rate was 4.4% in the tested group vs 15.4% in the untested group (RR = 0.29, 95% CI = 0.15–0.55, p = 0.0002) and outpatient visit rate was 71.7% in the tested group vs 36.5% in the untested group (RR = 1.97, 95% CI = 1.74–2.23, p < 0.0001). The rate of overall HRU was 72.2% in the tested group vs 49.0% in the untested group (RR = 1.47, 95% CI = 1.32–1.64, p < 0.0001). Potential cost savings were estimated at

Evaluation of the relationship between weight change and glycemic control after initiation of antidiabetic therapy in patients with type 2 diabetes using electronic medical record data

218 (mean) in the tested group. The provider majority (95%) considered the test helpful and 46% followed CDST provided recommendations. Conclusion: Patients CYP DNA tested and treated according to the personalized prescribing system had a significant decrease in hospitalizations and emergency department visits, resulting in potential cost savings. Providers had a high satisfaction rate with the clinical utility of the system and followed recommendations when appropriate.

Effect of Medicare reimbursement reduction for imaging services on osteoporosis screening rates.

AIMS This study evaluates the relationship between HbA1c and weight change outcomes by anti-diabetic weight-effect properties in patients newly treated for type 2 diabetes; a relationship not previously characterized. METHODS Electronic medical records of patients with type 2 diabetes newly prescribed anti-diabetic monotherapy were assessed to identify HbA1c goal attainment [(<53 mmol/mol)] and weight change at 1-year. Anti-diabetics were categorized by weight-effect properties: weight-gain (sulfonylureas, thiazolidinediones) and weight-loss/neutral (metformin, DPP-4 inhibitors, GLP-1 agonists). Logistic regression analyses identified likelihood of attaining HbA1c goal or ≥3% weight loss by anti-diabetic category controlling for baseline characteristics. MANOVA was used to identify correlation between changes in weight and HbA1c. RESULTS The study included 28,290 patients. Mean age ± sd was 61 years ±11.8. Baseline HbA1c was 7.4% ± 1.6 (57 mmol/mol ± 17); 67.3% were prescribed a weight-loss/neutral anti-diabetic. At 1-year, more patients in the weight-loss/neutral anti-diabetic category lost weight (≥3%) than in the weight-gain anti-diabetic category (40.4% vs. 24.2%, p<0.001) or had an HbA1c<7.0% (<53 mmol/mol) (71.1% vs. 63.8%, p<0.001). Those prescribed a weight-gain anti-diabetic were 53% less likely to lose weight and 29% less likely to be at HbA1c goal than those prescribed a weight-loss/neutral anti-diabetic (p<0.001). Weight loss and HbA1c outcomes were significantly correlated (p<0.001). CONCLUSIONS Weight loss of ≥3% was associated with better glycemic control in patients newly treated for type 2 diabetes. Anti-diabetics associated with weight-loss/neutrality were associated with greater weight loss and HbA1c goal attainment and may facilitate efforts to co-manage weight and glycemia in the ambulatory-care setting.

Assessment of HER2 testing patterns, HER2+ disease, and the utilization of HER2-directed therapy in early breast cancer

To determine bone mineral density (BMD) testing rates and the proportion of women diagnosed after BMD screening vs an osteoporosis‐related fracture before and after reductions in Medicare reimbursement for office‐based imaging services in 2007, which was projected to save

Glycemic Control and Weight Outcomes for Exenatide Once Weekly Versus Liraglutide in Patients with Type 2 Diabetes: A 1-Year Retrospective Cohort Analysis.

2.8B over 5 years.

Real-World Glycemic Control from GLP-1RA Therapy with and Without Concurrent Insulin in Patients with Type 2 Diabetes

Context Determining human epidermal growth factor receptor 2 (HER2) status is critical for the management of early-stage breast cancer (ESBC). An understanding of HER2 testing practices can provide insight into how test results influence the use of HER2-directed therapy. Objective To assess HER2 testing, HER2+ disease, and HER2-directed therapy in ESBC at the Huntsman Cancer Institute before and after the 2007 American Society of Clinical Oncology and College of American Pathologist (ASCO/CAP) guidelines on HER2 testing were published. Methods Patients were identified from an institutional tumor registry. HER2 testing patterns and results were examined using a chart review of pathology and clinical notes. Patient characteristics, HER2+ rate, and trastuzumab use were evaluated descriptively. Discordance rate with reflex testing (immunohistochemistry [IHC]2+ retested by fluorescence in situ hybridization [FISH]) was also evaluated. Results A total of 1,459 women were included (mean age: 57 years). The rate of HER2+ disease was 17% (number [N] =245). The discordance rate between IHC2+ and FISH was 10%. After the 2007 ASCO/CAP guidelines, fewer tumors were classified as IHC3+ (16% post- versus 21.9% pre-2007), more tumors were characterized as IHC2+ (26.4% post- versus 20.7% pre-2007), and the overall HER2+ rate was decreased (18.7% versus 21.9%), but this was not statistically significant (P=0.519). Most patients with HER2+ ESBC received HER2-targeted therapy (N=185). Conclusion The HER2+ rate was 17% and within the range of the reported rates in the literature. Reflex testing identified additional HER2+ tumors by approximately 10%, and should be considered a potential quality indicator. ASCO/CAP HER2 testing guidelines in 2007 appeared to impact the interpretation and classification of HER2+ tumors.

Characterization of Patients Undergoing Total Hip Arthroplasty in a Real-World Setting and Pain-Related Medication Prescriptions for Management of Postoperative Pain

PURPOSE Data comparing real-world effectiveness of the glucagon-like peptide-1 receptor agonists (GLP-1RAs) exenatide once weekly (QW) and liraglutide in the treatment of type 2 diabetes (T2D) are limited. Furthermore, there is limited information on exenatide QW or liraglutide response by glycemic control and insulin use status. This study identifies 1-year glycosylated hemoglobin (HbA1c) and weight outcomes with exenatide QW and liraglutide in the real-world setting overall and in insulin-naive patients with uncontrolled T2D. METHODS This retrospective cohort study using national electronic medical record data compared 1-year HbA1c and weight outcomes in patients with T2D prescribed exenatide QW or liraglutide. Included patients were adults (≥18 years old) with T2D who were GLP-1RA naive when newly prescribed exenatide QW or liraglutide between January 1, 2012, and March 31, 2013 (index date). Outcomes were reported descriptively overall and in subsets of insulin-naive patients with baseline HbA1c ≥7.0% or ≥9.0%. Multivariable linear regression analyses were performed to estimate adjusted change in HbA1c and weight. FINDINGS The study included 808 exenatide QW and 4333 liraglutide patients. Mean (SD) age was 57 (11) years in both groups. Mean baseline HbA1c was 8.3% (1.5%) in exenatide QW patients and 8.4% (1.6%) in liraglutide patients (P = 0.66); 16 (2%) of the exenatide QW and 1099 (25.4%) of the liraglutide patients were newly prescribed insulin on the index date (P < 0.001). Adjusted mean HbA1c change at 1 year was -0.37% (95% CI, -0.53% to -0.21%) for exenatide QW and -0.37% (95% CI, -0.55% to -0.18%) for liraglutide. Adjusted HbA1c reduction was more pronounced in insulin-naive patients with baseline HbA1c ≥7.0% (-0.71% and -0.80% for the exenatide QW and liraglutide patients, respectively, P > 0.05) and ≥9.0% (-1.73% and -1.57% for exenatide QW and liraglutide patients, respectively, P > 0.05). Mean (adjusted) weight loss was -2.22 kg (95% CI, -3.06 to -1.37 kg) with exenatide QW and -2.21 kg (95% CI, -3.18 to -1.23 kg) with liraglutide. IMPLICATIONS Exenatide QW and liraglutide lead to similar HbA1c and weight reductions at 1 year in the real-world setting. Greater HbA1c reductions occurred in insulin-naive patients with baseline HbA1c ≥7.0%. Both agents are appropriate options for patients needing antidiabetes therapy to lower HbA1c while promoting weight loss.

Assessment of statin therapy, LDL-C levels, and cardiovascular events among high-risk patients in the United States.

BACKGROUND Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are recommended as add-on therapy in patients with uncontrolled type 2 diabetes (T2D), with no specific guidance as to timing versus insulin. Furthermore, real-world data assessing GLP-1RA outcomes with or without concurrent insulin therapy are lacking. OBJECTIVE To identify glycemic response with GLP-1RAs by insulin use in patients with T2D at 1-year follow-up to inform decisions regarding GLP-1RA use with or without insulin. METHODS This uncontrolled retrospective cohort study included adults with T2D in the Quintiles Electronic Medical Records Database who were newly prescribed GLP-1RA therapy with exenatide once weekly or liraglutide once daily between February 1, 2012, and March 31, 2013 (index period). Primary outcomes were change in hemoglobin A1c (A1c) at 1 year and attainment of A1c < 7%, < 8%, and < 9%. Results were stratified by baseline insulin use, which was defined as no insulin use at baseline, insulin initiated with a GLP-1RA on index date, and insulin prescribed before starting GLP-1RA therapy. Secondary outcomes included 1-year weight, low-density lipoprotein cholesterol (LDL-C), and blood pressure outcomes for the study population. Adjusted mean (marginal) change in A1c at 1 year was estimated using multivariate linear regression, and multivariate logistic regression was used to estimate the likelihood of patients attaining A1c < 7% at follow-up, controlling for potential confounders. RESULTS This study included 5,141 patients with a mean (SD) age of 57.0 (10.9) years, 53.5% of whom were females, and with a mean baseline A1c of 8.4% (1.6). Overall, 35.4% had no baseline insulin use, 42.9% were prescribed insulin before starting GLP-1RA therapy, and 21.7% were started on insulin with a GLP-1RA. The adjusted mean A1c reduction at 1 year was 0.75% (95% CI = -0.86 to -0.63) for patients initiating insulin on index date, 0.61% (95% CI = -0.70 to -0.51) for patients with no baseline insulin use, and 0.23% (95% CI = -0.33 to -0.13) for patients prescribed insulin before GLP-1RA therapy. Patients with no baseline insulin or who coinitiated insulin and a GLP-1RA were more likely to attain A1c < 7% at follow-up versus patients prescribed insulin before initiating GLP-1RA therapy (OR = 1.50, 95% CI = 1.08 to 2.09 and OR = 1.85, 95% CI = 1.30 to 2.62, respectively). At 1-year follow-up, significant improvements in weight, LDL-C, and blood pressures were also observed. CONCLUSIONS GLP-1RA therapy was associated with significant improvements in glycemic control when used with or without insulin, as well as reductions in weight and LDL-C overall. However, greater A1c reductions and a higher likelihood of attaining A1c goal levels were observed when a GLP-1RA was initiated alone or with insulin than when a GLP-1RA was added to a regimen that included insulin. GLP-1RA therapy is an effective treatment option when used with or without insulin and may be considered in patients with uncontrolled glycemia. DISCLOSURES The study was funded by a collaborative research grant from AstraZeneca. Employees of AstraZeneca participated in most aspects of the study and in manuscript preparation. Nguyen and Hurd are employed by, and hold stock in, AstraZeneca. McAdam-Marx reports participation in the AMCP Diabetes Partnership and has stock ownership in GlaxoSmithKline. Study concept and design were contributed by Nguyen, McAdam-Marx, and Singhal, along with Unni and Schauerhamer. Singhal, Unni, Nguyen, and McAdam-Marx collected the data, with assistance from Schauerhamer and Hurd, and data interpretation was performed by Unni, Hurd, McAdam-Marx, Singhal, Nguyen, and Schauerhamer. The manuscript was written by Singhal, Schauerhamer, Unni, and McAdam-Marx, along with Nguyen and Hurd, and revised by McAdam-Marx, Singhal, Unni, and Nguyen, along with Schauerhamer and Hurd.

Determinants of glycaemic control in a practice setting: the role of weight loss and treatment adherence (The DELTA Study).

ABSTRACT Presently, no “gold-standard” exists for the management of pain after total knee arthroplasty (TKA) surgery. Understanding pain management methods used in clinical practice and the associated patient outcomes are necessary to fill gaps in pain management strategies. This study characterizes medication use in the immediate postoperative period among patients undergoing TKA at an academic medical center. Additionally, pre- and postoperative measures of pain (numeric pain rating scale), physical function (Knee Society Scale and Lower Extremity Function [LEFS]), and quality of life (Medical Outcomes Study Short-Form [SF]-36) were evaluated. The patient data were extracted from a clinical database at the University of Utah Orthopedic Clinic between September 1, 2008, and November 30, 2010. A total of 168 patients (mean age 64.0 ± 10.1 years, 63.1% were female, mean body mass index [BMI] 31.7 ± 7.1 kg/m2) were included. The most common comorbidities in these patients were osteoarthritis, hypertension, and major depressive disorders. Bupivacaine and fentanyl were commonly given on the day of surgery with oxycodone, hydrocodone/acetaminophen, and celecoxib prescribed at hospital discharge. Preoperative pain levels were reduced by half at 6 weeks. Physical function and quality of life were similar to established benchmarks and previously reported levels, respectively. Confirmation of results over a longer follow-up period is warranted.

Hypertension Control and Antihypertensive Therapy in Patients With Chronic Kidney Disease

BACKGROUND Statins have demonstrated significant benefit in reducing cardiovascular disease (CVD) risk. OBJECTIVE To evaluate statin treatment patterns by intensity, elevated low-density lipoprotein cholesterol (LDL-C) levels, and cardiovascular (CV) events in high-risk CVD patients. METHODS Patients included were aged ≥ 18 years, with a coronary heart disease (CHD; Jan 1, 2007-Dec 31, 2011, index date) or CHD risk equivalent (CHD RE) diagnosis (Jan 1, 2007-Dec 31, 2010, index date), in the Truven MarketScan claims database, continuously enrolled for 2 years pre- and up to 1 (CHD) or 2 (CHD RE) years post-index. Patients with CHD, CHD RE, rhabdomyolysis, or chronic kidney disease any time pre-index were excluded. Statin therapy was assessed at baseline, 30, 90, and 365 days post-index. LDL-C values were captured in patients with available data at 30-day intervals up to 1 year. CV events were evaluated up to 1 year post-index. Descriptive statistics were used to report results. RESULTS There were 175,103 CHD and 68,290 CHD RE patients; 3333 CHD RE patients had post-index CV events. At 1 year, 38.7% of CHD patients and 44.3% of CHD RE patients with post-index CV events were not prescribed statins. Most patients who were prescribed statins, received a moderate-intensity statin. The percentage of patients with LDL-C ≥ 100 mg/dL reduced over time, but at 1 year, 29.3% of CHD and 30.0% of CHD RE patients with post-index CV events had LDL-C ≥ 100 mg/dL. At 1 year post-index, 9.9% CHD and 7.3% CHD RE patients had at least 1 CV event. CONCLUSION There is room for better LDL-C management among high-risk CVD patients to reduce their overall CV risk.