Impact of Managing Provider Type on Severe Aortic Stenosis Management and Mortality.

Background Many patients with symptomatic severe aortic stenosis do not undergo aortic valve replacement (AVR) despite clinical guidelines. This study analyzed the association of managing provider type with cardiac specialist follow-up, AVR, and mortality for patients with newly diagnosed severe aortic stenosis (sAS). Methods and Results We identified adults with newly diagnosed sAS per echocardiography performed between January 2017 and March 2019 using Optum electronic health record data. We then selected from those meeting all eligibility criteria patients managed by a primary care provider (n=1707 [25%]) or cardiac specialist (n=5039 [75%]). We evaluated the association of managing provider type with cardiac specialist follow-up, AVR, and mortality, as well as the independent association of cardiac specialist follow-up and AVR with mortality, within 1 year of echocardiography detecting sAS. A subgroup analysis was limited to patients with symptomatic sAS. Patient characteristics and comorbidities at baseline were used for covariate-adjusted cause-specific and multivariable Cox proportional hazard models assessing group differences in outcomes by managing provider type. An adjusted Cox proportional hazard model with additional time-dependent covariates for follow-up and AVR was used to assess these practices' association with mortality. Within 1 year of echocardiography detecting sAS, data revealed that primary care provider management was associated with lower rates of cardiac specialist follow-up (hazard ratio [HR], 0.47 [95% CI, 0.43-0.50], P<0.0001) and AVR (HR, 0.58 [95% CI, 0.53-0.64], P<0.0001) and with higher 1-year mortality (HR, 1.45 [95% CI, 1.26-1.66], P<0.0001). Cardiac specialist follow-up and AVR were independently associated with lower mortality (follow-up: HR, 0.55 [95% CI, 0.48-0.63], P<0.0001; AVR: HR, 0.70 [95% CI, 0.60-0.83], P<0.0001). Results were similar for patients with symptomatic sAS. All analyses were adjusted for baseline patient characteristics and comorbidities. Conclusions For patients newly diagnosed with sAS, we observed differences in rates of cardiac specialist follow-up and AVR and risk of mortality between primary care provider- versus cardiologist-managed patients with sAS. In addition, a lower likelihood of receiving follow-up and AVR was independently associated with higher mortality.

A comparison of costs among patients with type 2 diabetes mellitus who initiated therapy with exenatide or insulin glargine.

BACKGROUND: Exenatide (Byetta) and insulin glargine (Lantus) are antidiabetic agents that are typically used after lack of response to an oral antidiabetic agent(s). Although previous research has examined the impact of these medications on glycaemic control, there is little information about the relative costs associated with the medications. OBJECTIVE: To compare costs among patients with type 2 diabetes mellitus treated with exenatide or insulin glargine from a US third-party payer perspective. METHODS: Data from a large, national administrative claims database were used in this study. The intent-to-treat (ITT) cohort included adults who were diagnosed with type 2 diabetes and initiated therapy with either exenatide (n = 4090) or insulin glargine (n = 1660). In addition, included patients were required to have no diagnoses of type 1 diabetes, to have received at least two prescriptions for an oral antidiabetic agent in the 6 months prior to first use of either exenatide or insulin glargine and to have continuous insurance coverage from 6 months before, to 12 months after, initiation on ITT medication. Annual total medical costs and total diabetes-related medical costs, in $US, year 2007 values, were estimated using stepwise multivariate regressions. Major cost components were also examined using either stepwise multivariate regressions or a two-part model that controlled for the probability of using the service. Smearing estimates were used to transform estimated log costs into costs. The analysis controlled for the potential impact of patient demographics, general health, prior resource use, co-morbidities and complications, and timing of treatment initiation. RESULTS: Compared with insulin glargine, initiation of exenatide was associated with significantly lower total direct medical costs ($US19,293 vs $US23,782; p < 0.0001), inpatient costs ($US4121 vs $US7532; p < 0.0001), outpatient costs ($US9501 vs $US12,885; p < 0.0001), emergency department (ED) costs ($US82 vs $US131; p < 0.0001), total diabetes-related medical costs ($US7833 vs $US8536; p < 0.0001), diabetes-related inpatient costs ($US2172 vs $US3538; p < 0.0001) and diabetes-related outpatient costs ($US2739 vs $US3249; p < 0.0001). Initiation of exenatide was associated with significantly higher total overall drug costs ($US6885 vs $US5936; p < 0.0001) and diabetes-related drug costs ($US3160 vs $US2422; p < 0.0001). CONCLUSIONS: Compared with the use of insulin glargine, use of exenatide was associated with significantly lower annual total direct medical costs and significantly lower total diabetes-related medical costs, despite higher total drug costs and higher diabetes-related drug costs. In addition, exenatide was associated with significantly lower total inpatient, outpatient, ED, and diabetes-related inpatient and outpatient costs.

American Heart Association and American Stroke Association national survey of stroke risk awareness among women.

BACKGROUND: Stroke is the third leading cause of death in the United States and a major cause of morbidity in women. Awareness of risk may be an important first step in stroke prevention. The purpose of this study was to assess knowledge and awareness about stroke in a nationally representative sample of women. METHODS AND RESULTS: An American Heart Association-sponsored telephone survey using random-digit dialing was conducted in June and July of 2003. Respondents were 1024 women > or =25 years of age, including an oversampling of racial/ethnic minorities (68% white, 12% black, 12% Hispanic). Participants were given a standardized questionnaire about heart disease and stroke risk. Only 26% of women > or =65 years of age reported being well informed about stroke, even though this group carries the highest incidence of stroke. Overall, 20% of women stated that they worried a lot about stroke. Among women aged 25 to 34 years, 37% stated that they were not at all informed about stroke, which was significantly higher than for women between 45 and 64 years (13%, P<0.05) and those > or =65 years of age (14%, P<0.05). More Hispanics reported being not at all informed about stroke compared with whites (32% versus 19%, P<0.05) and blacks (32% versus 20%, P<0.05). More white women were aware that at the onset of a stroke, treatment could be given to break up blood clots compared with blacks (92% versus 84%, P<0.05) and Hispanics (92% versus 79%, P<0.05). Correct identification of the warning signs of stroke was low among all racial/ethnic and age groups. More white respondents correctly identified sudden 1-sided weakness or numbness of the face or a limb as a warning sign compared with Hispanics (39% versus 29%, P<0.05). Whites identified difficulty talking or understanding speech as a sign of stroke significantly more often than did Hispanics (29% versus 17%, P<0.05). CONCLUSIONS: Results of this national survey document that awareness and knowledge about stroke is suboptimal among women, especially among racial/ethnic minorities, who are at highest risk. These data support the need for targeted educational programs about stroke risk and symptoms and underscore the importance of public health programs to improve awareness of stroke among women.

Opportunity for intervention to achieve American Heart Association guidelines for optimal lipid levels in high-risk women in a managed care setting.

BACKGROUND: The American Heart Association (AHA) recently established evidence-based recommendations for cardiovascular disease (CVD) prevention in women, including lipid management. This study evaluated optimal lipid-level attainment and treatment patterns on the basis of these guidelines in high-risk women in a managed care setting. METHODS AND RESULTS: We conducted a historical prospective cohort analysis of a 1.1-million-member, integrated, managed-care database. Eligible high-risk women were those with evidence of previous CVD or risk equivalent who had a full lipid panel available between October 1, 1999, and September 30, 2000; were naive to lipid therapy; and had a minimum of 12 months health plan eligibility preindex and postindex lipid panel. Optimal lipid levels were defined as LDL cholesterol (LDL-C) <100 mg/dL, HDL cholesterol (HDL-C) >50 mg/dL, non-HDL-C <130 mg/dL, and triglycerides <150 mg/dL. Laboratory values and lipid pharmacotherapy were assessed longitudinally over the postindex follow-up (up to 36 months). A total of 8353 high-risk women (mean age, 66+/-14 years) with a mean follow-up of 27+/-8 months were included. Only 7% attained optimal combined lipid levels initially, and this increased to 12% after 36 months. Lipid-modifying therapy was initiated in 32% of patients, including 35% of women with LDL-C > or =100 mg/dL and 15% with LDL-C <100 mg/dL. CONCLUSIONS: Among high-risk women, few attained the AHA's standards for all lipid fractions, and only one third received recommended drug therapy, highlighting significant opportunities to apply evidence-based recommendations to manage lipid abnormalities in high-risk women.

National study of physician awareness and adherence to cardiovascular disease prevention guidelines.

BACKGROUND: Few data have evaluated physician adherence to cardiovascular disease (CVD) prevention guidelines according to physician specialty or patient characteristics, particularly gender. METHODS AND RESULTS: An online study of 500 randomly selected physicians (300 primary care physicians, 100 obstetricians/gynecologists, and 100 cardiologists) used a standardized questionnaire to assess awareness of, adoption of, and barriers to national CVD prevention guidelines by specialty. An experimental case study design tested physician accuracy and determinants of CVD risk level assignment and application of guidelines among high-, intermediate-, or low-risk patients. Intermediate-risk women, as assessed by the Framingham risk score, were significantly more likely to be assigned to a lower-risk category by primary care physicians than men with identical risk profiles (P<0.0001), and trends were similar for obstetricians/gynecologists and cardiologists. Assignment of risk level significantly predicted recommendations for lifestyle and preventive pharmacotherapy. After adjustment for risk assignment, the impact of patient gender on preventive care was not significant except for less aspirin (P<0.01) and more weight management recommended (P<0.04) for intermediate-risk women. Physicians did not rate themselves as very effective in their ability to help patients prevent CVD. Fewer than 1 in 5 physicians knew that more women than men die each year from CVD. CONCLUSIONS: Perception of risk was the primary factor associated with CVD preventive recommendations. Gender disparities in recommendations for preventive therapy were explained largely by the lower perceived risk despite similar calculated risk for women versus men. Educational interventions for physicians are needed to improve the quality of CVD preventive care and lower morbidity and mortality from CVD for men and women.

Percutaneous coronary intervention and adjunctive pharmacotherapy in women: a statement for healthcare professionals from the American Heart Association.

More than 1.2 million percutaneous coronary interventions are performed annually in the United States, with only an estimated 33% performed in women, despite the established benefits of percutaneous coronary intervention and adjunctive pharmacotherapy in reducing fatal and nonfatal ischemic complications in acute myocardial infarction and high-risk acute coronary syndromes. This statement reviews sex-specific data on the safety and efficacy of contemporary interventional therapies in women.

Tracking women's awareness of heart disease: an American Heart Association national study.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality in men and women in the United States, yet prior research has shown a lack of awareness of risk among women. The purpose of this study was to assess the contemporary awareness, knowledge, and perceptions related to CVD risk among American women and to evaluate trends since 1997, when the American Heart Association initiated a national campaign to improve awareness of CVD among women. METHODS AND RESULTS: A telephone survey of a nationally representative random sample of women was conducted in June and July 2003, with an oversampling of black and Hispanic women; results were compared with those of similar surveys in 2000 and 1997. The present survey included 1024 respondents age > or =25 years; 68% were white, 12% black, 12% Hispanic, and 8% other ethnicities. Awareness, knowledge, and perceptions about heart disease were evaluated by use of a standard interviewer-assisted questionnaire. A shift in awareness of heart disease as the leading killer of women has occurred since 1997. In 2003, 46% of respondents spontaneously identified heart disease as the leading cause of death in women, up from 30% in 1997 (P<0.05) and 34% in 2000 (P<0.05). In contrast, the percentage of women citing cancer as leading cause of death has significantly decreased. Black, Hispanic, and younger women (<45 years old) had lower awareness of heart disease as their leading cause of death than did white and older women. Nearly all women reported comfort in discussing prevention with healthcare providers, but only 38% of women reported that their doctors had ever discussed heart disease with them. CONCLUSIONS: Awareness of CVD has increased, although a significant gap between perceived and actual risk of CVD remains. Educational interventions to improve awareness and knowledge are needed, particularly for minority and younger women.

Modulation of gene expression by RNAi.

RNA interference (RNAi) is a form of posttranscriptional gene silencing in which the presence within the cell of double-stranded RNA (dsRNA) leads to the specific degradation of mRNA with a complimentary sequence. RNAi is a natural phenomenon that can be exploited as a powerful tool to study gene function by generating gene "knockdowns" in various cell types. RNAi is mediated by short interfering RNAs (siRNAs), which are generated within cells from long dsRNAs. To avoid generalized toxic effects, mammalian cells are transfected directly with 21-23-bp-long siRNAs generated either by chemical synthesis or obtained by a series of enzymatic reactions. The present chapter deals with siRNA design, synthesis, transfection, and readout of efficiency in a mammalian cell culture system. The general principle is illustrated by the functional knockdown of p97/VCP (valosin-containing protein) in HeLa cells using five different siRNA sequences.

Comparison of costs among patients with type 2 diabetes treated with exenatide or sitagliptin therapy.

INTRODUCTION: Exenatide (Byetta, Amylin Pharmaceuticals Inc., CA, USA) and sitagliptin (Januvia, Merck & Co, NJ, USA) are two antidiabetic agents recently approved by the US Food and Drug Administration. The purpose of this analysis was to compare costs among patients with type 2 diabetes (T2D) treated with either of these agents. METHODS: Data with dates of service from September 1, 2005 through August 31, 2007, were obtained from a large US retrospective claims database. Intent-to-treat cohorts of adults diagnosed with T2D who began taking either exenatide (n=1885) or sitagliptin (n=2482) and did not use the alternate medication in the 6-month follow-up period were created. Six-month total medical costs were estimated using stepwise multivariate regressions. Six-month total diabetes-related medical costs, a component of total medical costs, were also estimated using stepwise multivariate regressions. In addition, other cost components were examined using either stepwise multivariate regressions or a two-part model that controlled for the probability of using the medical service. Smearing estimates were used to transform estimated log costs into costs. The analysis controlled for the potential impact of patient demographics, general health, prior resource use, comorbidities, and timing of treatment initiation. RESULTS: Exenatide was associated with lower total 6-month direct medical costs ($9340 vs. $9995; P<0.0001), despite some component costs being slightly higher with exenatide: diabetes-related drug costs ($1765 vs. $1743; P=0.0062), diabetes-related medical costs ($4142 vs. $4002; P<0.0001), and emergency room costs ($43 vs. $29; P=0.0388). Exenatide was associated with lower outpatient costs ($4498 vs. $5942; P<0.0001). CONCLUSIONS: Compared with the use of sitagliptin, exenatide was associated with lower total medical costs (difference of $655) despite higher total diabetes-related costs (difference of $140). As a result, there appears to be overall cost savings associated with the use of exenatide relative to sitagliptin.

Patient characteristics, drug adherence patterns, and hypoglycemia costs for patients with type 2 diabetes mellitus newly initiated on exenatide or insulin glargine.

OBJECTIVE: Examine real-world effectiveness and hypoglycemia cost burden in patients with type 2 diabetes newly initiated on exenatide or insulin glargine. DESIGN AND METHODS: Retrospective cohort study describing patient characteristics, drug adherence patterns, and 1-year hypoglycemia rates with associated costs using an administrative claims database. Adult subjects with type 2 diabetes had an initial claim for exenatide or insulin glargine between May 1, 2005 and June 30, 2007, and had continuous eligibility for >or= 6 months pre- and >or= 12 months post-initiation. RESULTS: The exenatide cohort (n = 3262) was 53 +/- 10 years (+/-SD); 54% female. The insulin glargine cohort (n = 3038) was 56 +/- 12 years; 41% female. The mean Deyo-Charlson comorbidity index score was 1.45 for exenatide versus 1.82 for insulin glargine (p < 0.001). Baseline OAD use rates for exenatide and insulin glargine, respectively, were 77% versus 69% metformin; 47% versus 65% sulfonylurea; 50% versus 49% thiazolidinedione; 56% versus 60% multiple OAD. For patients with two or more pharmacy claims for exenatide or insulin glargine, the 12-month medication possession ratio (MPR) was 68 +/- 29% for exenatide and 58 +/- 28% for insulin glargine (p < 0.001). MPR >or= 80% was higher for exenatide (p < 0.001) and fewer patients discontinued therapy (p < 0.001). The probability of a hypoglycemic event was significantly lower for exenatide (p < 0.005), resulting in lower associated annual costs. CONCLUSIONS: This study provides the first real-world observational comparison of type 2 diabetes patients newly initiated on exenatide or insulin glargine. Exenatide patients had a lower comorbidity burden, better drug adherence, and a lower rate of hypoglycemic events with associated costs. Retrospective database analyses examine medical care utilization in large populations using a relatively inexpensive and expedient approach. However, data are only representative of a commercial health-care plan with limited information on multiple variables usually collected during clinical trials.