Safety and effectiveness of a novel home-use therapeutic ultrasound device for the treatment of vaginal dryness in postmenopausal women: a pilot study.

To evaluate safety and effectiveness of therapeutic ultrasound for treatment of postmenopausal vaginal dryness. In a pilot study, postmenopausal women with self-reported vaginal dryness were randomized (1:1) to double-blind ultrasound treatment (n = 21) or sham (n = 21) for 12 weeks. Primary effectiveness endpoint was change from baseline to week 12 in Vaginal Assessment Scale symptoms (dryness, soreness, irritation, dyspareunia). Secondary effectiveness endpoint was scoring of clinician-reported Vaginal Health Index (elasticity, fluid, pH, mucosa, moisture). After 12 weeks, participants received open-label ultrasound treatment to 1 year. Safety endpoint was treatment-emergent adverse events. In the modified intent-to-treat population, women showed (mean ± standard error) reduction in Vaginal Assessment Scale with ultrasound treatment versus sham (n = 15, −0.5 ± 0.2 vs n = 15, −0.4 ± 0.3; P = 0.9) and improved Vaginal Health Index (n = 9, 2.7 ± 0.9 vs n = 9, 0.6 ± 1.4; P = 0.3). In the per-protocol analysis population, ultrasound treatment (n = 9) versus sham (n = 8) significantly reduced symptoms score (−0.6 ± 0.3 vs −0.0 ± 0.4; P = 0.05) and significantly improved Vaginal Health Index (2.7 ± 0.9 vs −0.4 ± 1.2; P = 0.03). Improvement in effectiveness endpoints were seen at 1 year compared with baseline. There were no differences in treatment-emergent adverse events between ultrasound treatment versus sham and no serious adverse events. Home-use ultrasound was safe and effective for treating vaginal dryness after 12 weeks. Effectiveness was maintained to 1 year. Therapeutic ultrasound could offer a new, nonhormonal treatment option for postmenopausal women with vulvovaginal atrophy.

Comparing Patch vs Pen Bolus Insulin Delivery in Type 2 Diabetes Using Continuous Glucose Monitoring Metrics and Profiles.

OBJECTIVE: CeQur Simplicity™ (CeQur, Marlborough, MA) is a 3-day insulin delivery patch designed to meet mealtime insulin requirements. A recently reported 48-week, randomized, multicenter, interventional trial compared efficacy, safety and self-reported outcomes in 278 adults with type 2 diabetes (T2D) on basal insulin therapy who initiated and managed mealtime insulin therapy with a patch pump versus insulin pen. We assessed changes in key glycemic metrics among a subset of patients who wore a continuous glucose monitoring (CGM) device. METHODS: Study participants (patch, n = 49; pen, n = 48) wore a CGM device in masked setting during the baseline period and prior to week 24. Glycemic control was assessed using international consensus guidelines for percentage of Time In Range (%TIR: >70% at 70-180 mg/dL), Time Below Range (%TBR: <4% at <70 mg/dL; <1% at <54 mg/dL), and Time Above Range (%TAR: <25% at >180 mg/dL; <5% at >250 mg/dL). RESULTS: Both the patch and pen groups achieved recommended targets in %TIR (74.1% ± 18.7%, 75.2 ± 16.1%, respectively) and marked reductions in %TAR >180 mg/dL (21.1% ± 19.9%, 19.7% ± 17.5%, respectively) but with increased %TBR <70 mg/dL (4.7% ± 5.2%, 5.1 ± 5.8, respectively), all P < .0001. No significant between-group differences in glycemic improvements or adverse events were observed. CONCLUSIONS: CGM confirmed that the patch or pen can be used to safely initiate and optimize basal-bolus therapy using a simple insulin adjustment algorithm with SMBG. Preference data suggest that use of the patch vs pen may enhance treatment adherence.

Implementation of Basal-Bolus Therapy in Type 2 Diabetes: A Randomized Controlled Trial Comparing Bolus Insulin Delivery Using an Insulin Patch with an Insulin Pen.

Background: Barriers to mealtime insulin include complexity, fear of injections, and lifestyle interference. This multicenter, randomized controlled trial evaluated efficacy, safety, and self-reported outcomes in adults with type 2 diabetes, inadequately controlled on basal insulin, initiating and managing mealtime insulin with a wearable patch versus an insulin pen. Methods: Adults with type 2 diabetes (n = 278, age: 59.2 ± 8.9 years), were randomized to patch (n = 139) versus pen (n = 139) for 48 weeks, with crossover at week 44. Baseline insulin was divided 1:1 basal: bolus. Using a pattern-control logbook, subjects adjusted basal and bolus insulin weekly using fasting and premeal glucose targets. Results: Glycated hemoglobin (HbA1c) change (least squares mean ± standard error) from baseline to week 24 (primary endpoint) improved (P < 0.0001) in both arms, -1.7% ± 0.1% and -1.6% ± 0.1% for patch and pen (-18.6 ± 1.1 and -17.5 ± 1.1 mmol/mol), and was maintained at 44 weeks. The coefficient of variation of 7-point self-monitoring blood glucose decreased more (P = 0.02) from baseline to week 44 for patch versus pen. There were no differences in adverse events, including hypoglycemia (three severe episodes per arm), and changes in weight and insulin doses. Subject-reported treatment satisfaction, quality of life, experience ratings at week 24, and device preferences at week 48 significantly favored the patch. Most health care providers preferred patch for mealtime insulin. Conclusions: Bolus insulin delivered by patch and pen using an algorithm-based weekly insulin dose titration significantly improved HbA1c in adults with type 2 diabetes, with improved subject and health care provider experience and preference for the patch.

Laboratory and Benchtop Performance of a Mealtime Insulin-Delivery System.

BACKGROUND: A basal bolus insulin regimen requires multiple daily insulin injections, which might discourage patient adherence. As a potential solution, a mealtime insulin-delivery system-a 3-day wearable bolus-only patch-was designed to manually administer mealtime insulin discreetly by actuating buttons through clothing, without the need for multiple needle sticks. METHOD: Extensive functional testing of the patch included dose accuracy (from initial fill of the device to empty), pressure-vacuum leak testing, last-dose lockout and occlusion detection (safety alert features that lock the dosing buttons when no insulin is delivered), assessments of insulin drug stability, toxicological risk (including chemical testing), and system biocompatibility. RESULTS: Dosing accuracy was 2 units ±10% (with U-100 insulin) over a range of environmental conditions, with ≥95% reliability and confidence. The fluid seal performance and the safety alert features performed with ≥95% reliability and ≥95% confidence. The system met acceptable standards for insulin (U-100 lispro and aspart) stability for its intended 3-day use, in addition to the operational requirements. The toxicological risk assessment and demonstrated biocompatibility suggested that the patch is safe for human use. CONCLUSIONS: Benchtop performance showed that the bolus-only patch is a safe, accurate, and reliable device for mealtime insulin delivery.

Patient Perceptions and Preferences for a Mealtime Insulin Delivery Patch.

INTRODUCTION: A basal-bolus insulin regimen is needed to achieve glycated hemoglobin A1c (HbA1c) below 7.0% in people with type 1 (T1D) or type 2 (T2D) diabetes who have significant loss of beta-cell function. Nonadherence to therapy is common and negatively affects the ability to reach treatment goals. We examined patient assessment of a new, wearable mealtime insulin-delivery system (patch) relative to their current mealtime insulin-delivery system (syringe, pen, or pump). The patch is designed to deliver only boluses of fast-acting insulin (no basal insulin), mechanically controlled by the patient. METHODS: Adults (n = 101) with T1D or T2D assessed their current mealtime insulin-delivery system and then assessed simulated (no active medication) patch use over a 3-day period. Participants evaluated mealtime insulin-delivery systems using eight measures from five domains (convenience, interference with daily activities, diabetes-related worry, psychological well-being, and overall satisfaction/preference) on the self-administered Insulin Delivery System Rating Questionnaire. User ratings of their current insulin-delivery systems (syringe, pen, pump) were compared with those for the patch by repeated measure analysis of variance and one-sample t tests. RESULTS: Participants had significant (p < 0.05) preference for patch over syringe in all eight comparisons, and over pen in five out of eight comparisons, with no significant preference for pen. Although there was a preference for patch over pump in six out of eight comparisons, only one showed a significant preference for patch, and one for pump. Significantly more participants reported that they would like to switch to the patch than continue using a syringe (78% vs 22%) or pen (76% vs 24%) but this difference was not significant for the group using a pump (52% vs 48%). CONCLUSIONS: Participants preferred using the patch over pens and syringes. Its ease of use and discreet method of insulin delivery may contribute to improved patient adherence to mealtime insulin regimens among people currently using injection devices. FUNDING: Calibra Medical.

Comparison of a novel insulin bolus-patch with pen/syringe injection to deliver mealtime insulin for efficacy, preference, and quality of life in adults with diabetes: a randomized, crossover, multicenter study.

OBJECTIVE: This study compared the efficacy, safety, device satisfaction, and quality of life (QOL) in people with diabetes using an insulin bolus-patch versus current devices (pen/syringe) to deliver mealtime insulin. RESEARCH DESIGN AND METHODS: Thirty-eight subjects with diabetes (26 with type 1 and 12 with type 2) were randomized to bolus-patch or current injection device (55% pen and 45% syringe) to deliver mealtime insulin in a multicenter, 6-week crossover study. Efficacy was assessed by equivalence in mean daily seven-point blood glucose (MDBG). Safety assessments included severe hypoglycemia episodes, adverse device effects (ADEs), and adverse events (AEs). Device satisfaction was determined by the validated Insulin Delivery System Rating Questionnaire (IDSRQ) and QOL by the validated Diabetes Specific QOL Scale (DSQOLS). RESULTS: Using bolus-patch, MDBG (mean±SE) was equivalent to that using pen/syringe (8.61±0.28 vs. 9.02±0.26 mmol/L; P=0.098). SD of the seven-point blood glucose measurements was lower using bolus-patch (3.18±0.18 vs. 3.63±0.17 mmol/L; P=0.004), as was the coefficient of variation (CV) (37.2±1.7 vs. 40.3±1.7%; P=0.046). Hemoglobin A1c, 1,5-anhydroglucitol, fructosamine, and insulin use were similar between groups. There were no severe hypoglycemia episodes or serious ADEs. Between-device AEs were comparable. Subjects scored better on six of seven subscales on the DSQOLS and five of six subscales on the IDSRQ while using bolus-patch versus pen/syringe. At study completion, 76% of subjects would choose to switch to bolus-patch (P=0.001). CONCLUSIONS: Delivery of mealtime insulin with bolus-patch compared with pen/syringe resulted in equivalent MDBG, lower SD and CV of seven-point blood glucose measurements, good safety, significant device satisfaction, and improved QOL.

Residential sunlight exposure is associated with a decreased risk of prostate cancer.

The possibility that exposure to sunlight reduces the risk of clinical prostate cancer has been strongly suggested by ecologic data. However, data on prostate cancer risk in relation to sunlight exposure in individuals are sparse. We analyzed data from the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study in order to test the hypothesis that residential sunlight exposure reduces the risk of prostate cancer. We identified 153 men with incident prostate cancer from a cohort of 3414 white men who completed the baseline interview and dermatologic examination in 1971-1975 and were followed up to 1992. We used Cox proportional hazards modeling to estimate relative risks (RR) and 95% confidence intervals (CI) for measures of residential sunlight exposure, adjusting for age, family history of prostate cancer, and dietary intake of fat and calcium. Residence in the South at baseline (RR = 0.68, CI = 0.41-1.13), state of longest residence in the South (RR = 0.62, CI = 0.40-0.95), and high solar radiation in the state of birth (RR = 0.49, CI = 0.30-0.79) were associated with significant and substantial reductions in prostate cancer risk. These data support the hypothesis that sunlight exposure reduces the risk of prostate cancer and have important implications for prostate cancer prevention.

A dietary supplement attenuates IL-6 and CRP after eccentric exercise in untrained males.

PURPOSE: This study investigated the effects of a dietary supplement on exercise-induced markers of cell damage and the inflammatory mediators C-reactive protein (CRP) and interleukin-6 (IL-6). METHODS: The supplement contained mixed tocopherols, flavonoids, and docosahexaenoate. Forty healthy, nonsmoking, untrained males (aged 18-35 yr) were randomly assigned to receive either the supplement (N = 20) or placebo (N = 20) during the 14-d experimental protocol. Blood samples were collected on day 0 (baseline), day 7 (eccentric exercise-induced injury), day 10, and day 14. OBJECTIVE: Markers of cell damage (creatine kinase (CK) and lactate dehydrogenase (LDH)) and inflammation IL-6 and CRP were assessed at these time points in conjunction with subjective range of motion (ROM) and perceived pain measurements. Statistical analyses were conducted using nonparametric methods (P < 0.05). RESULTS: Eccentric arm curl exercise was used to induce an acute phase injury response as evidenced by significant (P < 0.0001) increases in CK, LDH, and pain, as well as a decreased range of motion 3 d after the exercise. There were no significant differences between groups in CK and LDH responses. In contrast, there were significant group differences for IL-6 (P = 0.008) and CRP (P = 0.003). At day 10, by Mann-Whitney U test of changes, the placebo group had significantly greater increases in IL-6 and CRP than the treatment group (P = 0.05 and P < 0.01), respectively. CONCLUSION: This study suggested that exercise-induced inflammation, evaluated by changes in IL-6 and CRP, was significantly reduced by the dietary supplement.

Oral contraceptive use and increased plasma concentration of C-reactive protein.

We examined, in young adult women, the association between current low dose oral contraceptive (OC) use and plasma levels of C-reactive protein (CRP), an acute phase reactant predictive of cardiovascular disease risk. We conducted a cross-sectional analysis of 30 healthy, non-smoking, non-obese women (18 OC users and 12 nonusers) who were subjects in a randomized diet-controlled trial of the effects of soy intake on sex hormone metabolism. The study was sited at a university outpatient general clinical research center. Fasting plasma CRP levels were measured 4 times during 2 menstrual cycles (2 mid-follicular phase and 2 mid-luteal phase) using a high-sensitivity CRP assay. Differences between OC users and nonusers were examined by 3-way analysis of variance. Multiple regression was used to examine the relationship between OC use and CRP. There were no significant differences in baseline demographic characteristics between OC users and nonusers. Plasma CRP levels (mean +/- SE) were 2 times higher among OC users than among non-users (2.0 +/- 0.2 versus 0.9 +/- 0.3 mg/l, p<0.0001) independent of diet assignment, diet treatment order, and phase of the menstrual cycle. In a multivariate model, OC use predicted 32 percent of the variance in CRP levels (p<0.0001). As all CRP levels were within a previously established normal range, further study is indicated to establish the clinical significance of the observed elevated CRP levels in OC users.