Publications (8)32.5 Total impact
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Article: Exenatide BID Observational Study (ExOS): results for primary and secondary endpoints of a prospective research study to evaluate the clinical effectiveness of exenatide BID use in patients with type 2 diabetes in a real-world setting.
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ABSTRACT: The Exenatide BID Observational Study (ExOS) was designed to evaluate the clinical effectiveness of exenatide BID use in patients with type 2 diabetes (T2D) in a real-world clinical practice setting in the United States. Patients were enrolled from 74 practice sites from 9/2007 through 1/2009 and followed for 12 months. The primary effectiveness endpoint was achieving or maintaining hemoglobin A1C of ≤7.0%, or an absolute drop of 0.5% from baseline. Secondary measures included absolute and percentage change from baseline for a variety of clinical measures (lipid markers, weight, BMI, etc.), and quality of life (QOL) was assessed using the Impact of Weight on Quality of Life (IWQOL)-Lite. A total of 452 patients were included in the primary study population. At baseline, patients (60% female) had mean (SD) age of 55 (11), T2D duration of 9 (8) years, HbA1c of 8.0 (1.7) %, and body mass index (BMI) of 38.2 (7.4) kg/m(2). Family history of T2D was reported in 73.9% of patients. Hypertension was reported in 61.5% of patients, and 47.1% had hyperlipidemia. The HbA1c goal was achieved in 76.3% of the 118 patients with A1C measurements available at 12 months (P < 0.0001). Patients with available clinical measurements achieved significant improvements in HbA1c, weight, BMI, and QOL measurements at 12 months. A mean improvement of 4.56 was seen in the total IWQOL-Lite score at 12 months (P = 0.001). The single-arm design of this study is a limitation; however, the overall objective of the study was to observe patients on exenatide BID therapy over time, comparing their status at endpoint to baseline, rather than to make comparisons among different drug therapies. The Exenatide BID Observational Study supports the clinical effectiveness of exenatide BID observed in previous clinical trials and retrospective database studies.Current Medical Research and Opinion 11/2011; 27(12):2335-42. · 2.38 Impact Factor -
Article: Exenatide bid observational study (ExOS): baseline population characteristics of a prospective research study to evaluate the clinical effectiveness of exenatide bid use in patients with type 2 diabetes in a real-world setting.
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ABSTRACT: To describe the Exenatide Observational Study (ExOS) and patients initiating exenatide therapy in a real-world clinical practice setting. ExOS is a prospective, single-arm, multicenter, observational study to assess the effectiveness of up to 24 months of exenatide therapy in patients with type 2 diabetes (T2D). Patients with T2D ≥18 years of age, who initiated exenatide therapy, were eligible. The primary effectiveness endpoint is achieving or maintaining hemoglobin A1C of ≤7.0%, or an absolute drop of 0.5% from baseline. Secondary objective measures evaluate the absolute and percentage changes from baseline for a variety of clinical measures (lipid markers, weight, BMI, etc.) and quality of life (QOL) is assessed using the Impact of Weight on Quality of Life (IWQOL)-Lite. On average, the baseline population (n = 531) was aged 55 years, predominantly female (62%), white (79%), educated, obese (mean BMI 39 kg/m(2)), with mean HbA(1c), blood pressure, total cholesterol, and triglyceride values of 8.0%, 129/76 mmHg, 174 mg/dL, and 197 mg/dL, respectively. A total of 28% entered the study with HbA(1c) ≤7.0% and 67% were being treated with oral antihyperglycemic drug(s) (OAD) only [1 (28.4%), 2 (28.4%), >2 (10.2%)], or some form of insulin ±OADs (19%), and ≥50% were on a cholesterol-lowering drug(s) ± antihypertensive medication(s). The single-arm design of this study is a limitation; however, the overall objective of the ongoing study is to observe patients on exenatide therapy over time, comparing their status at endpoint to baseline, rather than to make comparisons among different drug therapies. Patients treated with exenatide tended to be obese, middle-aged women on various combinations of OADs and/or insulin who often had hypertension and/or dyslipidemia. Further planned analyses will provide the largest sample of prospective data on outcomes of exenatide therapy for up to 24 months in this usual-care population.Current Medical Research and Opinion 03/2011; 27(3):531-40. · 2.38 Impact Factor -
Article: Healthcare resource utilization and costs assessment of type 2 diabetes patients initiating exenatide BID or glargine: a retrospective database analysis.
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ABSTRACT: To examine resource utilization and healthcare costs associated with the use of exenatide versus glargine in type 2 diabetes (T2D) patients. A retrospective analysis comprised of patients with T2D initiating exenatide (n = 7,255) or glargine (n = 2,819) between 04/01/2005 and 06/30/2007. Propensity score matching was used (2,506 matched pairs) to control for baseline demographic, clinical, resource use, and cost variables to balance treatment groups. Mean medical costs and other cost components were estimated using nonparametric bootstrapping. Exenatide-treated patients had 19% lower likelihood of all-cause hospitalizations (odds ratio [OR]: 0.81, p = 0.009) compared to glargine-treated patients. Exenatide-treated patients had significantly lower total medical costs of $2,597 (p = 0.008). Exenatide-treated patients had significantly lower inpatient costs of $1,968 (p = 0.004) and outpatient costs of $1,324 (p = 0.011), but higher prescription costs of $706 (p < 0.001). Exenatide-treated patients further incurred lower hospitalization costs of $1,910 (p = 0.005) and physician office visit costs of $608 (p = 0.008). Key limitations: Lack of availability of clinical measures including duration of diabetes, severity of T2D and lack of control for unmeasured confounding. Patients initiating exenatide treatment had significantly lower healthcare resource utilization and total medical costs. Cost offsets were observed in inpatient and outpatient costs despite higher prescription costs.Journal of Medical Economics 01/2011; 14(1):16-27. -
Article: The type I error and power of non-parametric logrank and Wilcoxon tests with adjustment for covariates--a simulation study.
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ABSTRACT: Time-to-event outcomes are common for oncology clinical trials. Conventional methods of analysis for these endpoints include logrank or Wilcoxon tests for treatment group comparisons, Kaplan-Meier survival estimates, and Cox proportional hazards models to estimate the treatment group hazard ratio (both unadjusted and adjusted for relevant covariates). Adjusting for covariates reduces bias and may increase precision and power (Statist. Med. 2002; 21:2899-2908). However, the appropriateness of the Cox proportional hazards model depends on parametric assumptions. One way to address these issues is to use non-parametric analysis of covariance (J. Biopharm. Statist. 1999; 9:307-338). Here, we carry out simulations to investigate the type I error and power of the unadjusted and covariate-adjusted non-parametric logrank test and Wilcoxon test, and the Cox proportion hazards model. A comparison between the covariate-adjusted and unadjusted methods is also illustrated with an oncology clinical trial example.Statistics in Medicine 10/2008; 27(28):5850-60. · 1.88 Impact Factor -
Article: Growth hormone replacement therapy in adults with growth hormone deficiency improves maximal oxygen consumption independently of dosing regimen or physical activity.
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ABSTRACT: Several studies have demonstrated an improvement in aerobic exercise capacity with 6 months of GH replacement in adults with GH deficiency (GHD). The objective of the study was to determine whether improvements in aerobic exercise capacity with GH treatment in adults with GHD are related to changes in physical activity or affected by the GH dosing regimen. This was a randomized, two-arm, parallel, open-label study. The study was conducted at five academic medical centers with exercise physiology laboratories. Study subjects were adults (n = 29) with GHD due to hypothalamic-pituitary disease. The intervention was GH replacement therapy, administered either as a fixed body weight-based dosing regimen as an individualized dose titration regimen for 32 wk. Maximal oxygen consumption (VO2 max) and oxygen consumption (VO2) at the lactate threshold, ventilatory threshold using a cycle ergometry protocol, and weekly energy expenditure (physical activity questionnaire), assessed at baseline and end point, were measured. In the group as a whole, VO2 max increased significantly (by 9%) from baseline (19.1+/- 0.89 ml/kg.min) to end point (21.6 +/- 1.23 ml/kg.min, P = 0.010). Compared with baseline, VO2 max also changed significantly within the individualized dose titration regimen group (+2.5 +/- 0.98 ml/kg.min, P =0.034) but not within the fixed body weight-based dosing regimen group (+1.2 +/- 0.78 ml/kg.min, P = 0.15), although these changes from baseline were not significantly different between the two groups. VO2 at lactate threshold, VO2 at ventilatory threshold, and weekly energy expenditure also did not change. GH replacement therapy in GH-deficient adults improved VO2 max similarly with both dosing regimens, without any influence of physical activity. There was no effect on submaximal exercise performance.Journal of Clinical Endocrinology & Metabolism 02/2008; 93(1):125-30. · 6.50 Impact Factor -
Article: Effect of growth hormone replacement on BMD in adult-onset growth hormone deficiency.
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ABSTRACT: To determine if replacement of GH improves BMD in adult-onset GHD, we administered GH in physiologic amounts to men and women with GHD. GH replacement significantly increased spine BMD in the men by 3.8%. Growth hormone (GH) deficiency (GHD) acquired in adulthood results in diminished BMD; the evidence that replacement of GH improves BMD is not conclusive. We therefore performed a randomized, placebo-controlled trial to determine whether GH replacement would increase lumbar spine BMD in a combined group of men and women with adult-onset GHD. We randomized 67 men and women to receive GH (n=33) or placebo (n=34) for 2 yr. The GH dose was initially 2 microg/kg body weight/d, increased gradually to a maximum of 12 microg/kg/d and adjusted to maintain a normal IGF-I concentration for age and sex. BMD was assessed before treatment and at 6, 12, 18, and 24 mo of treatment. Fifty-four subjects completed the protocol. BMD of the lumbar spine in the entire group increased by 2.9 +/- 3.9% above baseline in the GH-treated subjects, which was significantly (p=0.037) greater than the 1.4 +/- 4.5% increase in the placebo-treated subjects. In a secondary analysis, spine BMD in GH-treated men increased 3.8 +/- 4.3% above baseline, which was significantly (p=0.001) greater than that in placebo-treated men (0.4 +/- 4.7%), but the change in GH-treated women was not significantly different from that in placebo-treated women. Treatment with GH did not increase total hip BMD more than placebo treatment after 2 yr. We conclude that GH replacement in men who have adult-onset GHD improves their spine BMD, but we cannot draw any conclusions about the effect of GH replacement on spine BMD in women with adult-onset GHD.Journal of Bone and Mineral Research 06/2007; 22(5):762-70. · 6.37 Impact Factor -
Article: Efficacy and tolerability of an individualized dosing regimen for adult growth hormone replacement therapy in comparison with fixed body weight-based dosing.
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ABSTRACT: To determine whether an individualized dose titration regimen (ID) for adult GH replacement therapy would have similar efficacy and better tolerability than a fixed body weight-based dosing regimen (FD), 387 adults with GH deficiency were randomized to FD (n = 200) or ID (n = 187) for 32 wk. In FD, subjects received sequentially 4, 8, and 12 microg/kg.d GH. ID was started at 0.2 mg/d and increased by 0.2-mg/d increments, based on clinical and serum IGF-I responses, to a maximum of 0.8 mg/d. Increases (mean +/- sd) in serum IGF-I were similar in both groups (FD, 110.2 +/- 87.8 vs. ID, 99.6 +/- 77.7 microg/liter, P = 0.20) despite higher final GH doses in FD (0.70 +/- 0.32 vs. 0.54 +/- 0.22 mg/d, P < 0.001). Favorable changes in several efficacy measures were observed with no significant differences between the FD and ID groups: lean body mass increased; health-related quality of life improved; and abdominal fat mass, hip circumference, sum of skinfolds, and total and low-density lipoprotein cholesterol decreased. The decrease in fat mass was greater with FD than ID for men (-2.7 +/- 2.7 kg vs. -1.8 +/- 2.5 kg, P = 0.04) but not for women (-2.1 +/- 2.4 vs. -2.0 +/- 3.8 kg). The change in waist circumference was greater with FD than ID for women but not for men. There was a significant reduction of systolic blood pressure in ID but not in FD. The adverse event profile was similar between FD and ID except that ID had a lower occurrence of peripheral edema (9.1% vs. 16.5%, P = 0.03) and rash (1.1% vs. 5.5%, P = 0.02) than FD. In summary, the use of ID resulted in improved tolerability and similar efficacy compared with FD. We conclude that GH replacement therapy should be initiated at a low dose and titrated to a dose producing maximal benefits without adverse side effects and an IGF-I level within the age- and sex-adjusted normal range.Journal of Clinical Endocrinology & Metabolism 08/2004; 89(7):3224-33. · 6.50 Impact Factor -
Article: Sensitivity and specificity of six tests for the diagnosis of adult GH deficiency.
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ABSTRACT: Although the use of the insulin tolerance test (ITT) for the diagnosis of adult GH deficiency is well established, diagnostic peak GH cut-points for other commonly used GH stimulation tests are less clearly established. Despite that fact, the majority of patients in the United States who are evaluated for GH deficiency do not undergo insulin tolerance testing. The aim of this study was to evaluate the relative utility of six different methods of testing for adult GH deficiency currently used in practice in the United States and to develop diagnostic cut-points for each of these tests. Thirty-nine patients (26 male, 13 female) with adult-onset hypothalamic-pituitary disease and multiple pituitary hormone deficiencies were studied in comparison with age-, sex-, estrogen status-, and body mass index-matched control subjects (n = 34; 20 male, 14 female). A third group of patients (n = 21) with adult-onset hypothalamic-pituitary disease and no more than one additional pituitary hormone deficiency was also studied. The primary end-point was peak serum GH response to five GH stimulation tests administered in random order at five separate visits: ITT, arginine (ARG), levodopa (L-DOPA), ARG plus L-DOPA, and ARG plus GHRH. Serum IGF-I concentrations were also measured on two occasions. For purposes of analysis, patients with multiple pituitary hormone deficiencies were assumed to be GH deficient. Three diagnostic cut-points were calculated for each test to provide optimal separation of multiple pituitary hormone deficient and control subjects according to three criteria: 1) to minimize misclassification of control subjects and deficient patients (balance between high sensitivity and high specificity); 2) to provide 95% sensitivity for GH deficiency; and 3) to provide 95% specificity for GH deficiency. The greatest diagnostic accuracy occurred with the ITT and the ARG plus GHRH test, although patients preferred the latter (P = 0.001). Using peak serum GH cut-points of 5.1 microg/liter for the ITT and 4.1 microg/liter for the ARG plus GHRH test, high sensitivity (96 and 95%, respectively) and specificity (92 and 91%, respectively) for GH deficiency were achieved. To obtain 95% specificity, the peak serum GH cut-points were lower at 3.3 microg/liter and 1.5 microg/liter for the ITT and ARG plus GHRH test, respectively. There was substantial overlap between patients and control subjects for the ARG plus L-DOPA, ARG, and L-DOPA tests, but test-specific cut-points could be defined for all three tests to provide 95% sensitivity for GH deficiency (peak GH cut-points: 1.5, 1.4 and 0.64 microg/liter, respectively). However, 95% specificity could be achieved with the ARG plus L-DOPA and ARG tests only with very low peak GH cut-points (0.25 and 0.21 microg/liter, respectively) and not at all with the L-DOPA test. Although serum IGF-I levels provided less diagnostic discrimination than all five GH stimulation tests, a value below 77.2 microg/liter was 95% specific for GH deficiency. In conclusion, the diagnosis of adult GH deficiency can be made without performing an ITT, provided that test-specific cut-points are used. The ARG plus GHRH test represents an excellent alternative to the ITT for the diagnosis of GH deficiency in adults.Journal of Clinical Endocrinology & Metabolism 06/2002; 87(5):2067-79. · 6.50 Impact Factor
Top co-authors
Top Journals
Institutions
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2007
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University of Pennsylvania
- Division of Endocrinology, Diabetes and Metabolism
Philadelphia, PA, USA
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2004
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VA Palo Alto Health Care System
Palo Alto, CA, USA
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2002
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Massachusetts General Hospital
Boston, MA, USA
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