Extraction With Sweat-Sebum Emulsion as a New Test Method for Leachables in Patch-Based Medical Devices, Illustrated by Assessment of Isobornylacrylate (IBOA) in Diabetes Products.

BACKGROUND: The increasing offering of patch-based medical devices is accompanied by growing numbers of reported adverse skin reactions. Procedures for testing leachables according to ISO 10993 may not be optimal for lipophilic substances that can be mobilized on skin by sweat and sebum. We propose an improved extraction method for targeted analysis of leachables using low volumes of a sweat-sebum emulsion. The approach is illustrated by the analysis of isobornylacrylate (IBOA), a compound found in some devices and suspected for allergenic potential. METHOD: Three patch-based products were tested: an implantable device for continuous glucose monitoring (CGM), an intermittently scanned CGM (isCGM) device, and a micro-insulin pump. Quantification of IBOA was performed by gas chromatography and allergenic potential of IBOA levels was assessed by the KeratinoSens cell assay. Different combinations were used for extraction solvent (isopropanol, 5% ethanol-water solution, and sweat-sebum emulsion), extraction volumes (complete immersion vs partial immersion in 2 mm of solvent), and extraction time (3, 5, and 14 days). RESULTS: Isobornylacrylate was only found in the isCGM device. About 20 mg/L IBOA were eluted after 3 days in isopropanol but only about 1 mg/L in ethanol-water. Sweat-sebum emulsion dissolves IBOA better and gives a more stable solution than ethanol-water. Decomposition of IBOA solutions requires adjusted extraction timing or correction of results. In the sweat-sebum extract, IBOA levels were about 20 mg/L after 3 days and about 30 mg/L after 5 days, clearly above the threshold found in the KerationSens assay for keratinocyte activation (10 mg/L). CONCLUSION: Extraction by low volumes of sweat-sebum emulsion can be a superior alternative for the targeted simulating-use assessment of leachables in patch-based medical devices.

Evaluation of a New Digital Automated Glycemic Pattern Detection Tool.

BACKGROUND: Blood glucose meters are reliable devices for data collection, providing electronic logs of historical data easier to interpret than handwritten logbooks. Automated tools to analyze these data are necessary to facilitate glucose pattern detection and support treatment adjustment. These tools emerge in a broad variety in a more or less nonevaluated manner. The aim of this study was to compare eDetecta, a new automated pattern detection tool, to nonautomated pattern analysis in terms of time investment, data interpretation, and clinical utility, with the overarching goal to identify early in development and implementation of tool areas of improvement and potential safety risks. METHODS: Multicenter web-based evaluation in which 37 endocrinologists were asked to assess glycemic patterns of 4 real reports (2 continuous subcutaneous insulin infusion [CSII] and 2 multiple daily injection [MDI]). Endocrinologist and eDetecta analyses were compared on time spent to analyze each report and agreement on the presence or absence of defined patterns. RESULTS: eDetecta module markedly reduced the time taken to analyze each case on the basis of the emminens eConecta reports (CSII: 18 min; MDI: 12.5), compared to the automatic eDetecta analysis. Agreement between endocrinologists and eDetecta varied depending on the patterns, with high level of agreement in patterns of glycemic variability. Further analysis of low level of agreement led to identifying areas where algorithms used could be improved to optimize trend pattern identification. CONCLUSION: eDetecta was a useful tool for glycemic pattern detection, helping clinicians to reduce time required to review emminens eConecta glycemic reports. No safety risks were identified during the study.

Development of a New Tool to Assess Bolus Calculation and Carbohydrate Estimation.

BACKGROUND: Carbohydrate estimation and bolus calculation are two important skills for handling intensive insulin therapy and effectively using bolus calculators. Structured assessment of both skills is lacking. A new tool for the assessment of skills in carbohydrate estimation and bolus calculation was developed and evaluated. MATERIALS AND METHODS: A new assessment tool (SMART) was developed that included 10 items for bolus calculation and 12 items for carbohydrate estimation. In total, 411 patients on intensive insulin treatment were recruited. Different parameters of glycemic control were used as validity criteria. RESULTS: The SMART tool achieved good reliability for the assessment of bolus calculation (Cronbach's α = 0.78) and sufficient reliability for the assessment of carbohydrate estimation (Cronbach's α = 0.67). A good bolus calculation skill was significantly associated with lower glycated hemoglobin values (r = -0.27), lower mean blood glucose levels (r = -0.29), and higher fluctuation of blood glucose control (r = -0.43). A good carbohydrate estimation skill was significantly associated with a lower frequency of severe hyperglycemia (r = -0.27) and a higher frequency of euglycemia (r = 0.26). CONCLUSIONS: SMART is a reliable and valid tool for the assessment of both skills. Bolus calculation as well as carbohydrate estimation was associated with glycemic control. With the help of SMART, important skills for the management of intensive insulin therapy can be assessed separately. Thus, in clinical practice patients in need of assistance from a bolus calculator can be identified.

Glycemic Variability Is Associated with Frequency of Blood Glucose Testing and Bolus: Post Hoc Analysis Results from the ProAct Study.

INTRODUCTION: The ProAct study has shown that a pump switch to the Accu-Chek(®) Combo system (Roche Diagnostics Deutschland GmbH, Mannheim, Germany) in type 1 diabetes patients results in stable glycemic control with significant improvements in glycated hemoglobin (HbA1c) in patients with unsatisfactory baseline HbA1c and shorter pump usage time. PATIENTS AND METHODS: In this post hoc analysis of the ProAct database, we investigated the glycemic control and glycemic variability at baseline by determination of several established parameters and scores (HbA1c, hypoglycemia frequency, J-score, Hypoglycemia and Hyperglycemia Indexes, and Index of Glycemic Control) in participants with different daily bolus and blood glucose measurement frequencies (less than four day, four or five per day, and more than five per day, in both cases). The data were derived from up to 299 patients (172 females, 127 males; age [mean±SD], 39.4±15.2 years; pump treatment duration, 7.0±5.2 years). RESULTS: Participants with frequent glucose readings had better glycemic control than those with few readings (more than five readings per day vs. less than four readings per day: HbA1c, 7.2±1.1% vs. 8.0±0.9%; mean daily blood glucose, 151±22 mg/dL vs. 176±30 mg/dL; percentage of readings per month >300 mg/dL, 10±4% vs. 14±5%; percentage of readings in target range [80-180 mg/dL], 59% vs. 48% [P<0.05 in all cases]) and had a lower glycemic variability (J-score, 49±13 vs. 71±25 [P<0.05]; Hyperglycemia Index, 0.9±0.5 vs. 1.9±1.2 [P<0.05]; Index of Glycemic Control, 1.9±0.8 vs. 3.1±1.6 [P<0.05]; Hypoglycemia Index, 0.9±0.8 vs. 1.2±1.3 [not significant]). Frequent self-monitoring of blood glucose was associated with a higher number of bolus applications (6.1±2.2 boluses/day vs. 4.5±2.0 boluses/day [P<0.05]). Therefore, a similar but less pronounced effect on glycemic variability in favor of more daily bolus applications was observed (more than five vs. less than four bolues per day: J-score, 57±17 vs. 63±25 [not significant]; Hypoglycemia Index, 1.0±1.0 vs. 1.5±1.4 [P<0.05]; Hyperglycemia Index, 1.3±0.6 vs. 1.6±1.1 [not significant]; Index of Glycemic Control, 2.3±1.1 vs. 3.1±1.7 [P<0.05]). CONCLUSIONS: Pump users who perform frequent daily glucose readings have a better glycemic control with lower glycemic variability.

ProAct study: new features of insulin pumps improve diabetes management and glycemic control in patients after transition of continuous subcutaneous insulin infusion systems.

BACKGROUND: Continuous subcutaneous insulin infusion (CSII) patients experience switches of pump systems on a regular basis. We investigated the impact of transition from older pumps to the Accu-Chek(®) Combo system (Roche Diagnostics Deutschland GmbH, Mannheim, Germany) on a patient's glycemic control and diabetes management. PATIENTS AND METHODS: In total, 299 patients (172 female, 127 male; mean±SD age, 39.4±15.2 years; CSII duration, 7.0±5.2 years) were enrolled by 61 European sites into this uncontrolled prospective trial. Glycemic control, safety, and diabetes management parameters were measured at baseline and after 3 and 6 months. Changes from baseline were analyzed. RESULTS: After transition to the new insulin pump, mean±SD hemoglobin A1c (HbA1c) values decreased from 7.8±1.1% (baseline) to 7.7±1.1% (end point). The proportion of patients with HbA1c <7.0% was slightly higher at the end of the study (29.6%) than at baseline (25.2%), whereas the proportion of patients with HbA1c >8.0% decreased (baseline, 36.2%; end point, 32.7%; P<0.05). The number of hypoglycemic episodes (blood glucose<70 mg/dL) improved slightly during the study (baseline, 40.4±34.0 events/quarter; end point, 39.2±33.9 events/quarter). Glycemic control improved significantly in the group with an initial HbA1c >8.0% (-0.46%; P<0.001) and remained solidly stable in the group with an initial HbA1c <7% (+0.04%; not significant). Short-term (<3 years) pump users (n=48) had a larger HbA1c decrease (-0.40%) than long-term (≥3 years) users (n=251) (-0.07%; P<0.05). The number of blood glucose measurements increased (3.7±1.9/day vs. 4.4±1.8/day; P<0.05), whereas the number of insulin boluses decreased (5.1±1.9/day vs. 4.6±1.5/day; P<0.05) during the study. CONCLUSIONS: Transition from older pump systems to the Accu-Chek Combo system in a large patient population resulted in stable glycemic control with significant improvements in HbA1c in patients with unsatisfactory baseline HbA1c and shorter pump use. Increased frequency of self-monitoring of blood glucose and decrease of bolus frequency could suggest a more confident diabetes management and a reduced need for correction boluses.

Non-invasive determination of cardiac output: comparison of a novel CW Doppler ultrasonic technique and inert gas rebreathing.

BACKGROUND: Cardiac Output (CO) is an important parameter in the diagnosis and therapy of heart diseases. Inert gas rebreathing (IGR) and continuous wave Doppler ultrasound (CWD) are among the most promising newer techniques aiming at a non-invasive, point of care measurement of CO. A direct comparison of the two methods has not yet been carried out. METHODS: 63 consecutive patients were included in the study. CO was measured twice with both CWD and IGR to assess inter-method agreement and reproducibility. The statistical comparisons were performed as proposed by Bland and Altman. RESULTS: There was a significant correlation between the CO measurements by both methods (r=0.53, p<0.001). Bland-Altman analysis showed a good agreement of measurements with a bias of 0.4+/-1.0 l/min (mean+/-standard deviation). Both methods showed a good reproducibility. CWD measurements were not possible in 14% of patients while IGR measurements were not possible in 5% of patients (p=0.13). CONCLUSION: The determination of CO by IGR and CWD revealed a good agreement and reproducibility with a low rate of impossible measurements, suggesting that IGR and CWD can be used interchangeably in the clinical setting.