Patient-Centered Home Care Using Digital Medicine and Telemetric Data for Hypertension: Feasibility and Acceptability of Objective Ambulatory Assessment.

Objective information that can be passively obtained in an ambulatory setting could be potentially useful for determining appropriate care in blood pressure (BP) management. This study utilized digital medicine (DM) prototypes and telemetric data acquisition to directly confirm medication use and to assess habits of daily living in a hypertensive population. Thirty-seven patients (23 men age 62±9 years) used the system for 6 weeks. DM prototypes consisted of valsartan 80 mg or 160 mg placed in a gelatin hemicapsule with an excipient tablet as a "stopper," with a poppy seed-sized ingestible sensor (IS) made of foodstuff on its external surface and capable of creating a biogalvanic current on ingestion to alert a wearable sensor (WS) that was worn on the torso. Passive data collection included IS ingestion dates and times, daily step count, BP, and weight. Automatic short message service (SMS) reminders were sent whenever BP or weight values were not received. Passive detection of DM ingestion was 98% when compared with directly observed dosing. Mean taking and timing adherence rates were 90% and 83%, respectively, and the average step count at a pace of ≥60 steps per minute was 2.0±1.5 h/d. An automatic SMS was sent and 100% confirmed for 251 BP and 14 weight values that were not received. Mild and transient WS-related skin irritation was the most common device-related adverse event. There were no serious or unanticipated adverse events. Ninety percent of patients did not mind swallowing a DM capsule, and 75% had a positive overall experience with the system. Ambulatory evaluation of medication adherence and habits of daily living appear to be feasible and acceptable using DM and passive acquisition of telemetric data.

Impact of mifepristone, a glucocorticoid/progesterone antagonist, on HDL cholesterol, HDL particle concentration, and HDL function.

CONTEXT: Mifepristone is a glucocorticoid and progestin antagonist under investigation for the treatment of Cushing's syndrome. Mifepristone decreases high-density lipoprotein (HDL) cholesterol (HDL-C) levels in treated patients, but the clinical significance of this is unclear because recent studies suggest that functional properties of HDL predict cardiovascular disease status better than does HDL-C concentration. OBJECTIVE: The aim of the study was to characterize the impact of mifepristone administration on HDL particle concentration and function. DESIGN AND SETTING: We conducted a double-blind, randomized, placebo-controlled trial at a single-site, clinical research center. PARTICIPANTS: Thirty healthy postmenopausal female volunteers participated in the study. INTERVENTION: Individuals were randomized to receive daily oral mifepristone (600 mg) or placebo for 6 wk. MAIN OUTCOME MEASURES: We measured HDL-C, serum HDL particle concentration, and HDL-mediated cholesterol efflux by treatment group. RESULTS: As expected, ACTH, cortisol, estradiol, and testosterone levels increased in the mifepristone group. Mifepristone treatment decreased HDL-C and HDL particle concentration by 26 and 25%, respectively, but did not alter pre-ß HDL concentration. In contrast, the serum HDL-mediated cholesterol efflux decreased with mifepristone treatment by only 12%, resulting in an effective increase of the efflux capacity per HDL particle. No changes were observed in cholesterol ester transfer protein or lecithin:cholesterol acyltransferase activity. CONCLUSIONS: Treatment with mifepristone reduced HDL-C, HDL particle concentration, and serum HDL cholesterol efflux in postmenopausal women. However, on a per particle basis, the efflux capacity of serum HDL increased. These observations support the concept that a decrease in HDL-C may not represent proportional impairment of HDL function.

Effect of denosumab on bone mineral density and biochemical markers of bone turnover: six-year results of a phase 2 clinical trial.

CONTEXT: This is a study extension to evaluate the efficacy and safety of long-term treatment with denosumab in postmenopausal women with low bone mass. OBJECTIVE: Our objective was to describe changes in bone mineral density (BMD) and bone turnover markers as well as safety with 6 yr of denosumab treatment. DESIGN: We conducted an ongoing 4-yr, open-label, single-arm, extension study of a dose-ranging phase 2 trial. This paper reports a 2-yr interim analysis representing up to 6 yr of continuous denosumab treatment. SETTING: This multicenter study was conducted at 23 U.S. centers. PATIENTS: Of the 262 subjects who completed the parent study, 200 enrolled in the study extension and 178 (89%) completed the first 2 yr. INTERVENTION: All subjects received denosumab 60 mg sc every 6 months. MAIN OUTCOME MEASURES: We evaluated BMD at the lumbar spine, total hip, femoral neck, and one third radius; biochemical markers of bone turnover; and safety, reported as adverse events. RESULTS: Over a period of 6 yr, continuous treatment with denosumab resulted in progressive gains in BMD in postmenopausal women with low bone mass. Reduction in bone resorption was sustained over the course of continuous treatment. Independent of past treatment and discontinuation period, subjects demonstrated responsiveness to denosumab therapy as measured by BMD and bone turnover markers. The safety profile of denosumab did not change over time. CONCLUSIONS: In this study, denosumab was well tolerated and effective through 6 yr of continuous treatment in postmenopausal women with low bone mass.

Accuracy of the 5-day FreeStyle Navigator Continuous Glucose Monitoring System: comparison with frequent laboratory reference measurements.

OBJECTIVE: The purpose of this study was to compare the accuracy of measurements of glucose in interstitial fluid made with the FreeStyle Navigator Continuous Glucose Monitoring System with Yellow Springs Instrument laboratory reference measurements of venous blood glucose. RESEARCH DESIGN AND METHODS: Fifty-eight subjects with type 1 diabetes, aged 18-64 years, were enrolled in a multicenter, prospective, single-arm study. Each subject wore two sensors simultaneously, which were calibrated with capillary fingerstick measurements at 10, 12, 24, and 72 h after insertion. Measurements from the FreeStyle Navigator system were collected at 1-min intervals and compared with venous measurements taken once every 15 min for 50 h over the 5-day period of sensor wear in an in-patient clinical research center. Periods of high rates of change of glucose were induced by insulin and glucose challenges. RESULTS: Comparison of the FreeStyle Navigator measurements with the laboratory reference method (n = 20,362) gave mean and median absolute relative differences (ARDs) of 12.8 and 9.3%, respectively. The percentage in the clinically accurate Clarke error grid A zone was 81.7% and that in the in the benign error B zone was 16.7%. During low rates of change (< +/-1 mg x dl(-1) x min(-1)), the percentage in the A zone was higher (84.9%) and the mean and median ARDs were lower (11.7 and 8.5%, respectively). CONCLUSIONS: Measurements with the FreeStyle Navigator system were found to be consistent and accurate compared with venous measurements made using a laboratory reference method over 5 days of sensor wear (82.5% in the A zone on day 1 and 80.9% on day 5).

Continuous subcutaneous insulin infusion and multiple daily injection therapy are equally effective in type 2 diabetes: a randomized, parallel-group, 24-week study.

OBJECTIVE: Compare the efficacy, safety, and patient satisfaction of continuous subcutaneous insulin infusion (CSII) therapy with multiple daily injection (MDI) therapy for patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 132 CSII-naive type 2 diabetic patients were randomly assigned (1:1) to CSII (using insulin aspart) or MDI therapy (bolus insulin aspart and basal NPH insulin) in a multicenter, open-label, randomized, parallel-group, 24-week study. Efficacy was assessed with HbA(1c) and eight-point blood glucose (BG) profiles. Treatment satisfaction was determined with a self-administered questionnaire. Safety assessments included adverse events, hypoglycemic episodes, laboratory values, and physical examination findings. RESULTS: HbA(1c) values decreased similarly for both groups from baseline (8.2 +/- 1.37% for CSII, 8.0 +/- 1.08% for MDI) to end of study (7.6 +/- 1.22% for CSII, 7.5 +/- 1.22% for MDI). The CSII group showed a trend toward lower eight-point BG values at most time points (only significant 90 min after breakfast; 167 +/- 48 vs. 192 +/- 65 mg/dl for CSII and MDI, respectively; P = 0.019). A total of 93% of CSII-treated subjects preferred the pump to their previous injectable insulin regimen for reasons of convenience, flexibility, ease of use, and overall preference. Safety assessments were comparable for both treatment groups. CONCLUSIONS: Insulin aspart in CSII therapy provided efficacy and safety comparable to MDI therapy for type 2 diabetes. Patients with type 2 diabetes can be trained as outpatients to use CSII and prefer CSII to injections, indicating that pump therapy should be considered when initiating intensive insulin therapy for type 2 diabetes.