Prediction of cardiovascular and renal risk among patients with apparent treatment-resistant hypertension in the United States using machine learning methods.

Apparent treatment-resistant hypertension (aTRH), defined as blood pressure (BP) that remains uncontrolled despite unconfirmed concurrent treatment with three antihypertensives, is associated with an increased risk of developing cardiovascular and renal complications compared with controlled hypertension. We aimed to identify the characteristics of aTRH patients with an elevated risk of major adverse cardiovascular events plus (MACE+; defined as stroke, myocardial infarction, or heart failure hospitalization) and end stage renal disease (ESRD). This retrospective cohort study included aTRH patients (BP ≥140/90 mmHg and taking ≥3 antihypertensives) from the United States-based Optum® de-identified Electronic Health Record dataset and used machine learning models to identify risk factors of MACE+ or ESRD. Patients had claims for ≥3 antihypertensive classes within 30 days between January 1, 2015 and June 30, 2021, and two office BP measures recorded 1-90 days apart within 30 days to 11 months after the index regimen date. Of a total 18 797 070 patients identified with any hypertension, 71 100 patients had aTRH. During the study period (mean 25.5 months), 4944 (7.0%) patients had a MACE+ and 2403 (3.4%) developed ESRD. In total, 22 risk factors were included in the MACE+ model and 16 in the ESRD model, and most were significantly associated with study outcomes. The risk factors with the largest impact on MACE+ risk were congestive heart failure, stages 4 and 5 chronic kidney disease (CKD), age ≥80 years, and living in the Southern region of the United States. The risk factors with the largest impact on ESRD risk, other than pre-existing CKD, were anemia, congestive heart failure, and type 2 diabetes. The overall study cohort had a 5-year predicted MACE+ risk of 13.4%; this risk was increased in those in the top 50% and 25% high-risk groups (21.2% and 29.5%, respectively). The overall study cohort had a predicted 5-year risk of ESRD of 6.8%, which was increased in the top 50% and 25% high-risk groups (10.9% and 17.1%, respectively). We conclude that risk models developed in our study can reliably identify patients with aTRH at risk of MACE+ and ESRD based on information available in electronic health records; such models may be used to identify aTRH patients at high risk of adverse outcomes who may benefit from novel treatment interventions.

Real-World Impact of Blood Pressure Control in Patients With Apparent Treatment-Resistant or Difficult-to-Control Hypertension and Stages 3 and 4 Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is a common comorbidity in patients with apparent treatment-resistant hypertension (aTRH). We assessed clinical outcomes, healthcare resource utilization events, and costs in patients with aTRH or difficult-to-control hypertension and stage 3-4 CKD with uncontrolled vs. controlled BP. METHODS: This retrospective cohort study used linked IQVIA Ambulatory EMR-US and IQVIA PharMetrics Plus claims databases. Adult patients had claims for ≥3 antihypertensive medication classes within 30 days between 01/01/2015 and 06/30/2021, 2 office BP measures recorded 1-90 days apart, ≥1 claim with ICD-9/10-CM diagnosis codes for CKD 3/4, and ≥1 year of continuous enrollment. Baseline BP was defined as uncontrolled (≥130/80 mm Hg) or controlled (<130/80 mm Hg) BP. Outcomes included risk of major adverse cardiovascular events plus (MACE+; stroke, myocardial infarction, heart failure hospitalization), end-stage renal disease (ESRD), healthcare resource utilization events, and costs during follow-up. RESULTS: Of 3,966 patients with stage 3-4 CKD using ≥3 antihypertensive medications, 2,479 had uncontrolled BP and 1,487 had controlled BP. After adjusting for baseline differences, patients with uncontrolled vs. controlled BP had a higher risk of MACE+ (HR [95% CI]: 1.18 [1.03-1.36]), ESRD (1.85 [1.44-2.39]), inpatient hospitalization (rate ratio [95% CI]: 1.35 [1.28-1.43]), and outpatient visits (1.12 [1.11-1.12]) and incurred higher total medical and pharmacy costs (mean difference [95% CI]: $10,055 [$6,741-$13,646] per patient per year). CONCLUSIONS: Patients with aTRH and stage 3-4 CKD and uncontrolled BP despite treatment with ≥3 antihypertensive classes had an increased risk of MACE+ and ESRD and incurred greater healthcare resource utilization and medical expenditures compared with patients taking ≥3 antihypertensive classes with controlled BP.

Association of uncontrolled blood pressure in apparent treatment-resistant hypertension with increased risk of major adverse cardiovascular events plus.

Patients with apparent treatment-resistant hypertension (aTRH) are at increased risk of end-organ damage and cardiovascular events. Little is known about the effects of blood pressure (BP) control in this population. Using a national claims database integrated with electronic medical records, the authors evaluated the relationships between uncontrolled BP (UBP; ≥130/80 mmHg) or controlled BP (CBP; <130/80 mmHg) and risk of major adverse cardiovascular events plus (MACE+; stroke, myocardial infarction, heart failure requiring hospitalization) and end-stage renal disease (ESRD) in adult patients with aTRH (taking ≥3 antihypertensive medication classes concurrently within 30 days between January 1, 2015 and June 30, 2021). MACE+ components were also evaluated separately. Multivariable regression models were used to adjust for baseline differences in demographic and clinical characteristics, and sensitivity analyses using CBP <140/90 mmHg were conducted. Patients with UBP (n = 22 333) were younger and had fewer comorbidities at baseline than those with CBP (n = 11 427). In the primary analysis, which adjusted for these baseline differences, UBP versus CBP patients were at an 8% increased risk of MACE+ (driven by a 31% increased risk of stroke) and a 53% increased risk of ESRD after 2.7 years of follow-up. Greater MACE+ (22%) and ESRD (98%) risk increases with UBP versus CBP were seen in the sensitivity analysis. These real-world data showed an association between suboptimal BP control in patients with aTRH and higher incidence of MACE+ and ESRD linked with UBP despite the use of multidrug regimens. Thus, there remains a need for improved aTRH management.

Effect of phosphodiesterase type 5 inhibitors on major adverse cardiovascular events and overall mortality in a large nationwide cohort of men with erectile dysfunction and cardiovascular risk factors: A retrospective, observational study based on healthcare claims and national death index data.

BACKGROUND: Treatment with phosphodiesterase type 5 inhibitors (PDE-5is) is effective in treating erectile dysfunction (ED). AIM: The objective of this study was to determine the effect of PDE-5is on the incidence of major adverse cardiovascular (CV) events (MACE; composite outcome of CV death, hospitalization for myocardial infarction, coronary revascularization, stroke, heart failure, and unstable angina pectoris) and overall mortality. METHODS: A retrospective observational cohort study was conducted in a large US claims database in men with ≥1 diagnosis of ED without prior MACE within 1 year, from January 1, 2006, to October 31, 2020. The exposed group had ≥1 claim for PDE-5i and the unexposed group had no claims for PDE-5i, and the groups were matched up to 1:4 on baseline risk variables. OUTCOME: The primary outcome was MACE and the secondary outcomes were overall mortality and individual components of MACE, determined by multivariable Cox proportional hazard modeling. RESULTS: Matched plus multivariable analyses showed that MACE was lower by 13% in men exposed (n = 23 816) to PDE-5is (hazard ratio [HR] 0.87; 95% CI 0.79-0.95; P = .001) vs nonexposure (n = 48 682) over mean follow-up periods of 37 and 29 months, respectively, with lower incidence of coronary revascularization (HR 0.85; 95% CI 0.73-0.98; P = .029), heart failure (HR 0.83; 95% CI 0.72-0.97; P = .016), unstable angina (HR 0.78; 95% CI 0.64-0.96; P = .021), and CV death (HR 0.61; 95% CI 0.41-0.90; P = .014) with PDE-5i exposure. Phosphodiesterase type 5 inhibitor-exposed men had a 25% lower incidence of overall mortality (HR 0.75; 95% CI 0.65-0.87; P < .001). Men without coronary artery disease (CAD) but with CV risk factors at baseline showed a similar pattern. In the main study cohort, men in the highest quartile of PDE-5i exposure had the lowest incidence of MACE (HR 0.45; 95% CI 0.37-0.54; P < .001) and overall mortality (HR 0.51; 95% CI 0.37-0.71; P < .001) vs the lowest exposure quartile. In a subgroup with baseline type 2 diabetes (n = 6503), PDE-5i exposure was associated with a lower MACE risk (HR 0.79; 95% CI 0.64-0.97; P = .022). CLINICAL IMPLICATIONS: PDE-5is may have cardioprotective effects. STRENGTHS AND LIMITATIONS: Strengths are the large numbers of participants and consistency of the data; limitations include the retrospective nature of the study and unknown confounders. CONCLUSIONS: In a large population of US men with ED, PDE-5i exposure was associated with lower incidence of MACE, CV death, and overall mortality risk compared to non-exposure. Risk reduction correlated with PDE-5i exposure level.

A Study of Adrenal Insufficiency in Hemodynamically Stable Patients with Cirrhosis.

Adrenal insufficiency (AI) is well entrenched in medical constraints like septic shock, critically ill and multi-morbid hemodynamically unstable patients but its exact prevalence or differences in the cases of chronic liver disease (CLD) at variable grades of severity has recently gained momentum. The eventuality of AI propounding in stable compensated and decompensated cirrhosis without sepsis or in early and late stages of liver desecration are the existing lacunae in popular literature that this study aims to address. MATERIAL: A prospective, analytical study was conducted from March 2021 to December 2021 encompassing 100 hemodynamically stable patients with cirrhosis without infection, admitted at SMS Medical College, Jaipur, who were assessed clinically, biochemically and for adrenal functions. Adrenal insufficiency was defined on multivariable approach including basal 8am cortisol levels, followed by giving 250mcg synthetic adrenocorticotrophic hormone IM injection and retaking serum cortisol levels post-hourly interval to delineate peak and delta cortisol variables. All samples were processed by chemoluminiscence based method on fully automatic immunoassay analyser. OBSERVATION: The study comprised 81 males and 19 females with the mean age being 45.4±12.92 years, with CLD etiology concentrating substantially around alcohol consumption (71%). Viral comorbidities viz. HBV, HCV, both viral and alcohol related and miscellaneous causes were documented in 23, 10, 14 and 12 patients respectively. AI surfaced in 38% patients with CLD being statistically significant with p< 0.001. Inclusively, 10.5% patients with Child-Turcotte-Pugh (CTP) class A, 57.89% with CTP class B and 31.57% cases with CTP class C developed adrenal insufficiency. No statistical differences were found in age, sex; mean arterial pressure, heart rate, HDL, cirrhosis etiology, degree of alcohol consumption and manifestations of portal hypertension between patients with or without AI. For prudence, serum albumin levels were lower (p<0.5) with INR raised (p<0.33) in patients with AI than their counterparts. However, multivariate analysis revealed no direct independent adrenal insufficiency predictor. ROC curve showed that the CTP score may be a good predictor for AI in liver cirrhosis patients as supplemented by significant negative correlations found between CTP score and peak cortisol levels (p=0.001). CONCLUSION: Adrenal insufficiency found frequent even in stable cirrhotic patients form an integral division of the CLD spectra and worsening glucocorticoid levels should be periodically assessed in such patients for preventing parallel comorbidities.

A Study of Left Ventricular Dysfunction in Normotensive Non Diabetic Patients with Non Alcoholic Fatty Liver Disease.

Non-Alcoholic Fatty Liver Disease is an emerging epidemic in the face of the new generation. It is considered the hepatic manifestation of the metabolic syndrome. With the increasing prevalence of obesity and metabolic syndrome, it has become a common sight in our outpatient department. We have investigated the echocardiographic parameters for systolic and diastolic dysfunction in the patients with NAFLD to evaluate its effects on the heart and hope our study could shine a light and provide us with a perspective into the various effects the metabolic syndrome has on our body. MATERIAL: We recruited 35 Normotensive, Non-Diabetic Non-Alcoholic Fatty Liver Disease Patients (NAFLD) of age ranging from 18 to 60 years of age diagnosed on the basis of ultrasound Abdomen and 35 Controls from both inpatient and outpatient department of Sawai Man Singh Medical College and Allied Hospitals from the month of August 2021 to October 2021 for the study. Every Patient underwent conventional transthoracic and Tissue Doppler Echocardiography along with their physical and metabolic parameters. All the patients of NAFLD were graded ultrasongraphically based on Hamaguchi et al criteria. OBSERVATION: NAFLD patients had higher Body Mass Indices, Abdominal circumferences, Systolic Blood pressures, Total Cholesterol levels and Low-Density Lipoprotein levels in comparison to their normal counterparts. On the Echocardiographic front, the patient underwent transthoracic 2D ECHO and we observed an increased interventricular septum thickness (0.99 ± 0.04 vs 0.78 ± 0.05, p <0.0001), posterior wall thickness (0.96±0.05 vs 0.75±0.04 p < 0.0001) and left ventricular Mass (173±22.6 vs 116±8.24 p < 0.0001). On Tissue Doppler Imaging (TDI) we observed a decreased E/A ratio (1.25 ± 0.17 vs 1.44 ± 0.22 p < 0.0001) which was suggestive of an increased Left ventricular Dysfunction. On correlational analysis, we had made an observation that there was a positive correlation of the grading of fatty liver with that of interventricular septum thickness (r= 0.5305 p = 0.001), posterior wall thickness (r = 0.4362 p= 0.088) and left ventricular mass (r = 0.6292, p = 0.0001) with the grade of fatty liver. CONCLUSION: From our study, it was imperative that NAFLD even in the absence of Hypertension or Diabetes has a role in the impairment of Systolic and Diastolic function of the left ventricle and its role in cardiovascular morbidity and mortality cannot be ignored.

Ruxolitinib Re-Treatment in Patients with Myelofibrosis: Real-World Evidence on Patient Characteristics and Outcomes.

Ruxolitinib is an FDA-approved treatment of intermediate- and high-risk myelofibrosis. In the phase 3 COMFORT studies, ruxolitinib reduced spleen volume in patients with myelofibrosis, with a median time to response of 3 months. However, nearly 20% of patients discontinued by month 4 with few treatment options available following discontinuation of ruxolitinib treatment. In this study, 2 independent patient care data sources were queried (Cardinal Health Oncology Provider Extended Network [OPEN] and HealthCore Integrated Research Environment [HIRE®]), and a retrospective review of medical charts was conducted. Patients aged ≥18 years with a diagnosis of myelofibrosis (primary or secondary), use of ruxolitinib for myelofibrosis, and documented physician-directed ruxolitinib interruption were included. Among 26 included patients, pre-interruption median (interquartile range [IQR]) ruxolitinib treatment duration was 123 (57-391, OPEN) and 110 (37-148, HIRE) days. Half the patients interrupted treatment within 3 months, commonly for adverse events (42% and 71%, respectively). After restarting ruxolitinib, median (IQR) re-treatment duration was 196 (54-553) and 166 (108-262) days, respectively. Consistent with previous reports, symptoms and spleen size improved in (OPEN/HIRE) 45%/43% and 40%/33% of evaluable patients, respectively. Further studies investigating the management of dose modifications and interruptions are needed to optimize benefit from ruxolitinib therapy.

Treatment Experiences with CDK4&6 Inhibitors Among Women with Metastatic Breast Cancer: A Qualitative Study.

PURPOSE: To describe patients' perspectives on the use of and potential challenges and barriers with adherence/persistence to cyclin-dependent kinase 4 and 6 inhibitors (CDK4&6i's) to treat metastatic breast cancer (MBC). METHODS: This qualitative study consisted of 60-minute semi-structured telephone interviews with patients with MBC in the US who were either current or recent CDK4&6i users, identified from administrative claims of survey-eligible commercial and Medicare Advantage patients in the HealthCore Integrated Research Database between November 1, 2018 and November 1, 2019. Patients were recruited by email and/or mailed letter. The 60-minute telephone interviews were conducted by a trained facilitator using a study-developed interview discussion guide that included topics impacting treatment choice and adherence/persistence. Interviews were audio-recorded, transcribed, and thematically analyzed. RESULTS: All 462 eligible patients were sent a recruitment email and/or letter to which 36 patients responded, consented to participate, and met study inclusion criteria; 25 patients scheduled interviews, and 24 completed them. Study participants were predominately white, non-Hispanic (96%) with a mean age of 59.5 years. Participants reported a largely positive experience and mentioned very few adherence/persistence issues. They further reported appreciating the ease and convenience of oral oncolytics, coped with side effects, had strong medical and social support, and experienced few cost issues. CONCLUSION: The few adherence/persistence issues reported by participants contrasts with other findings of suboptimal oral oncolytic use. Interview themes indicated several factors that likely contributed to the lack of adherence/persistence issues: trusted relationship with oncologist, belief in importance of medication, positive medication views, strong medical and social support, and minimal personal drug cost. Future research should focus on whether and how much these factors impact adherence/persistence in more diverse populations. If adherence/persistence issues are identified in these populations, then it would be appropriate to study the development of interventions that target factors associated with better adherence/persistence.

Effectiveness, treatment durability, and treatment costs of canagliflozin and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes in the USA.

Introduction: This real-world study compared glycemic effectiveness, treatment durability, and treatment costs with canagliflozin 300 mg versus any dose of glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes mellitus (T2DM) in the USA. Research design and methods: A retrospective cohort study using administrative claims and laboratory data (1 April 2012 to 28 February 2017) from the HealthCore Integrated Research Database were used to assess mean HbA1c at 3-month intervals, achievement of HbA1c thresholds (<7.0%, <8.0%, <9.0%), and treatment durability (ie, adherence, discontinuation, switching, treatment failure (ie, exceeding threshold (7.0%, 8.0%, 9.0%), having a prescription for a new antihyperglycemic agent)) in adults with T2DM who initiated canagliflozin 300 mg or any dose of a GLP-1 receptor agonist. Medication costs were calculated for adherent patients. Results: There were no significant differences in the primary outcome of HbA1c levels at 3-month intervals (≤12 months) in the canagliflozin 300 mg versus any dose GLP-1 receptor agonist cohort. The likelihood of achieving HbA1c<8.0% was not different (p=0.666), the likelihood of achieving HbA1c<7.0% was lower (p=0.016), and the likelihood of achieving HbA1c<9.0% was higher (p=0.020) in the canagliflozin 300 mg versus any dose GLP-1 receptor agonist cohort. The likelihood of treatment failure after reaching any HbA1c target was not different between cohorts. A higher proportion of patients were adherent to treatment (p<0.0001) and a lower proportion discontinued (p<0.0001) or switched medication (p=0.023) in the canagliflozin 300 mg versus any dose GLP-1 receptor agonist cohort. Over 1 year, medication costs were $1421 (p<0.001) lower with canagliflozin 300 mg than any dose of GLP-1 receptor agonists. Conclusions: This real-world, US-based study found that initiation of canagliflozin 300 mg versus any dose of a GLP-1 receptor agonist in patients with T2DM was not associated with significant differences in the primary outcome of HbA1c levels at 3-month intervals for up to 12 months after index, but showed better adherence, less discontinuation, and lower drug acquisition costs compared with initiation of any dose of a GLP-1 receptor agonist.

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

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.

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

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.

The effect of a diabetes collaborative care management program on clinical and economic outcomes in patients with type 2 diabetes.

BACKGROUND: Clinical pharmacy services (CPS) in the primary care setting have been shown to help patients attain treatment goals and improve outcomes. However, the availability of CPS in community-based primary care is not widespread. One reason is that current fee-for-service models offer limited reimbursement opportunities for CPS in the community setting. Furthermore, data demonstrating the value of CPS in this setting are limited, making it difficult for providers to determine the feasibility and sustainability of incorporating CPS into primary care practice. OBJECTIVES: To (a) evaluate the association between a pharmacist-led, diabetes collaborative drug therapy management program and patient outcomes, including glycemic control and health care costs, and (b) assess short-term economic outcomes in a primary care setting. METHODS: A retrospective cohort analysis was conducted using medical record data. This study was conducted using patients with uncontrolled type 2 diabetes (T2DM), defined as HbA1c ≥ 7.0%. Outcomes were compared between patients referred to a diabetes collaborative care management (DCCM) intervention from 2009-2012 and patients who did not participate in the DCCM program. To illustrate the difference in HbA1c between the 2 cohorts over the follow-up period, mean time adjusted HbA1c values were estimated using a panel-type random effects regression model, with results plotted at 90-day intervals from index date through the end of the study period. To help control for confounding by other factors, multivariate regression models were run. A difference-in-difference model was employed to estimate the effect of the program on resource utilization and all-cause charges. RESULTS: A total of 303 DCCM and 394 comparison patients were included. Mean (95% CI) age was 57.4 years (55.963, 58.902) versus 59.9 years (58.613, 61.276; P < 0.001) with 48% and 44% female for DCCM and comparison patients, respectively (P = 0.49). Mean baseline HbA1c was higher for DCCM (10.3%; 10.10, 10.53) than comparison patients (8.4%; 8.26, 8.61; P < 0.001). The greatest reduction in HbA1c was seen for both groups at 9 and 12 months post-index date. At these time points, the mean time adjusted difference in HbA1c between groups was no longer significant. Multivariate modeling identified that the DCCM program was associated with a -0.44% (-0.64, -0.25; P < 0.001) lower HbA1c at follow-up relative to the comparison group controlling for potential confounders, including baseline HbA1c. Change in resource utilization from pre- to post-index date did not differ between groups. However, in the difference-in-difference multivariate analysis the difference in mean all-cause charges from the 12-month pre- to post-index periods DCCM patients experienced a smaller average increase in charges ($250) than comparison patients ($1,341; coefficient = -0.423; 95% CI = -0.779, -0.068). CONCLUSIONS: A pharmacist-led diabetes collaborative care management program in a patient-centered primary care setting was associated with significantly better follow-up glycemic control relative to comparison patients. Further, the data suggest that the DCCM program was associated with a less substantial increase in all-cause total costs in patients with uncontrolled T2DM relative to comparison patients, which could translate into reduced costs and improved outcomes to managed care payers.

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

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.

Real-world evidence in pain research: a review of data sources.

Outcomes research studies use clinical and administrative data generated in the course of patient care or from patient surveys to examine the effectiveness of treatments. Health care providers need to understand the limitations and strengths of the real-world data sources used in outcomes studies to meaningfully use the results. This paper describes five types of databases commonly used in the United States for outcomes research studies, discusses their strengths and limitations, and provides examples of each within the context of pain treatment. The databases specifically discussed are generated from (1) electronic medical records, which are created from patient-provider interactions; (2) administrative claims, which are generated from providers' and patients' transactions with payers; (3) integrated health systems, which are generated by systems that provide both clinical care and insurance benefits and typically represent a combination of electronic medical record and claims data; (4) national surveys, which provide patient-reported responses about their health and behaviors; and (5) patient registries, which are developed to track patients with a given disease or exposure over time for specified purposes, such as population management, safety monitoring, or research.