Non-Invasive Transcutaneous Afferent Patterned Stimulation Therapy Offers Action Tremor Relief in Parkinson's Disease.

Background: Many patients with Parkinson's disease (PD) experience action tremor (including postural and kinetic tremors) that impair activities of daily living. Transcutaneous afferent patterned stimulation (TAPS) is a non-invasive neuromodulation therapy that modulates tremorgenic activity at the ventral intermediate nucleus (VIM). Most TAPS evidence evaluated relief of action tremor associated with essential tremor (ET). This study evaluated whether TAPS results in similar relief of action tremor associated with PD. Methods: Forty PD patients with action tremors were enrolled in a prospective, single-arm, open-label study with four weeks of unsupervised at-home TAPS sessions in the dominant hand twice daily in between supervised TAPS sessions at two telemedicine appointments. The primary endpoint was change in tremor power as measured by the on-board accelerometer before and immediately after a stimulation session. Additional study endpoints included change in Movement Disorder Society-Sponsored Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS), change in Bain and Findley Activities of Daily Living (BF-ADL) scale, and clinician and patient global impressions of improvement (CGI-I and PGI-I). Results: TAPS reduced tremor power by 64% (54%-79%) (median (interquartile range), p < 0.001), with 79% of patients experiencing at least 50% reduction. When comparing pre-stimulation scores at visit 1 to post-stimulation scores at visit 2, TAPS improved per-task MDS-UPDRS III ratings of postural and kinetic tremors (0.6 ± 0.5, t(34) = 7.05, p < 0.001) and per-task patient-ratings of BF-ADL ADL upper limb motion ratings (0.5 ± 0.5, t(34) = 5.69, p < 0.001). Clinicians reported improvement in 78-83% of patients and 75-80% of patients reported improvement. Adverse events, most commonly skin reaction at the stimulation site, occurred in 18% of patients. Conclusion: Objective, clinician-rated, and patient-rated assessments demonstrated that TAPS provided clinically meaningful relief of action tremor in patients with PD.

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.

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.

Differential effects of alendronate treatment on bone from growing osteogenesis imperfecta and wild-type mouse.

Bisphosphonates have been reported to decrease the number of fractures in children with osteogenesis imperfecta (OI). The current study sought to further explore bisphosphonate-associated bone changes in OI by investigating the effects of alendronate (ALN) treatment on bone mechanical and material properties in osteogenesis imperfecta (oim/oim) and wild-type (+/+) mice treated with 26-73 microg kg(-1) day(-1) of ALN for 8 weeks via subcutaneously implanted pumps. Femoral three-point bend tests to evaluate cortical bone were combined with geometric and material density analysis. Cortical and trabecular architecture of metaphyseal bone were histomorphometrically evaluated and material density assessed by quantitative backscattered electron imaging (qBEI). For the cortical oim/oim bone, which revealed principally inferior biomechanical properties compared to +/+ bone, ALN neither improved cortical strength or any other mechanical property, nor affected cortical width (Ct.Wi.) or material density. In contrast, for the +/+ mice, bone strength was enhanced (+22%, P < 0.05) though coupled with increased brittleness (+28%, P < 0.05). This mechanical improvement was associated with an increase in Ct.Wi. (+17.3%, P = 0.02) and a reduction in heterogeneity of cortical mineralization (Ca(Width), -4%, P = 0.04). In the metaphysis, ALN raised cancellous bone volume (BV/TV) significantly in oim/oim as well as in +/+ mice (+97%, P = 0.008 and +200%, P < 0.0001, respectively). This occurred without any change in either material density or trabecular thickness (Tb.Th.) in the oim/oim mice, while in the +/+ mice, material density increased slightly but significantly (+3%, P = 0.004), and Tb.Th. increased by 77% (P < 0.0001). Taken together, these results illustrate the differential effects of ALN on oim/oim vs. +/+ bone, as well as on specific skeletal sites, i.e., cortical vs. trabecular bone. ALN augmented the mechanical, geometrical, and material properties of +/+ cortical and trabecular bone, while the only observable improvement to the oim/oim bone was increased cancellous bone volume. This suggests that in this mouse model of OI, the previously demonstrated bisphosphonate-associated reduction in fractures is primarily attributable to increased metaphyseal bone mass.