bluuebunny/crossref_metadata_2025 huggingface dataset:
GlucoMen Day Continuous Glucose Monitoring System: A Screening for Enzymatic and Electrochemical Interferents
Authors: Lucarelli Fausto , Ricci Francesco , Caprio Felice , Valgimigli Francesco , Scuffi Cosimo , Moscone Danila , Palleschi Giuseppe
Published: January 2014

Background:

While most of the common drugs with the potential to interfere with continuous glucose monitoring (CGM) systems are accessible over the counter and can be assumed by CGM patients without medical supervision, many other chemicals are frequently used to treat critically ill patients. Continuous glucose monitoring reading accuracy may also be compromised in patients characterized by abnormally high concentrations of physiological interferents. In this article, 22 species selected from endogenous and exogenous chemicals were screened as possible interferents of GlucoMen®Day (GMD), the new microdialysis-based CGM system from A. Menarini Diagnostics.

Method:

Interference testing was performed according to the EP7-A2 guideline (Clinical and Laboratory Standards Institute 2005). Interference was evaluated at two levels of glucose, with each interferent additionally tested at two concentrations. Furthermore, two configurations of the GMD disposable sensor kit—one designed for subcutaneous application, the other for direct intravascular CGM—were challenged with interferent-spiked serum and blood samples, respectively.

Results:

With the exception of dopamine (however, at very high, nonphysiological concentrations), no interference was observed for all the tested substances. Interestingly, none of the common electrochemical interferents (including ascorbic acid, acetaminophen, and salicylic acid, which represent the major specificity issue for the competing CGM systems) significantly affected the system's output.

Conclusions:

These results provide clear insights into the advantages offered by the use of a microdialysis-based CGM system that additionally relies on the detection of hydrogen peroxide at low operating potential. GlucoMen Day may become the CGM system of choice for those patients who require either regular administration of drugs or their glycemia to be tightly controlled in the intensive care unit or similar environments.
Mobile Health Applications to Assist Patients with Diabetes: Lessons Learned and Design Implications
Authors: Årsand Eirik , Frøisland Dag Helge , Skrøvseth Stein Olav , Chomutare Taridzo , Tatara Naoe , Hartvigsen Gunnar , Tufano James T.
Published: January 2014

Self-management is critical to achieving diabetes treatment goals. Mobile phones and Bluetooth® can support self-management and lifestyle changes for chronic diseases such as diabetes. A mobile health (mHealth) research platform—the Few Touch Application (FTA)—is a tool designed to support the self-management of diabetes. The FTA consists of a mobile phone-based diabetes diary, which can be updated both manually from user input and automatically by wireless data transfer, and which provides personalized decision support for the achievement of personal health goals. Studies and applications (apps) based on FTAs have included: (1) automatic transfer of blood glucose (BG) data; (2) short message service (SMS)-based education for type 1 diabetes (T1DM); (3) a diabetes diary for type 2 diabetes (T2DM); (4) integrating a patient diabetes diary with health care (HC) providers; (5) a diabetes diary for T1DM; (6) a food picture diary for T1DM; (7) physical activity monitoring for T2DM; (8) nutrition information for T2DM; (9) context sensitivity in mobile self-help tools; and (10) modeling of BG using mobile phones.

We have analyzed the performance of these 10 FTA-based apps to identify lessons for designing the most effective mHealth apps. From each of the 10 apps of FTA, respectively, we conclude: (1) automatic BG data transfer is easy to use and provides reassurance; (2) SMS-based education facilitates parent-child communication in T1DM; (3) the T2DM mobile phone diary encourages reflection; (4) the mobile phone diary enhances discussion between patients and HC professionals; (5) the T1DM mobile phone diary is useful and motivational; (6) the T1DM mobile phone picture diary is useful in identifying treatment obstacles; (7) the step counter with automatic data transfer promotes motivation and increases physical activity in T2DM; (8) food information on a phone for T2DM should not be at a detailed level; (9) context sensitivity has good prospects and is possible to implement on today's phones; and (10) BG modeling on mobile phones is promising for motivated T1DM users. We expect that the following elements will be important in future FTA designs: (A) automatic data transfer when possible; (B) motivational and visual user interfaces; (C) apps with considerable health benefits in relation to the effort required; (D) dynamic usage, e.g., both personal and together with HC personnel, long-/short-term perspective; and (E) inclusion of context sensitivity in apps. We conclude that mHealth apps will empower patients to take a more active role in managing their own health.
Treatment of Diabetes Prior to and after Bariatric Surgery
Authors: Thorell Anders , Hagström-Toft Eva
Published: January 2014

The number of patients undergoing bariatric surgery for morbid obesity is increasing. Type 2 diabetes is common among patients undergoing bariatric surgery. The effect of bariatric surgery on glycemia is profound in patients with diabetes and might vary between different bariatric surgical procedures. Therefore, almost invariably, there is a need to adjust antidiabetic drug dosages in the postoperative period in order to prevent hypoglycemia.

Moreover, preoperatively, very low calorie diet protocols are applied in many centers to facilitate surgery by reducing liver volume. Because low caloric intake will increase insulin sensitivity, there is also a need for dose adjustments of glucose-lowering drugs during this period as well. Guidelines for adjustments of antidiabetic treatment before and after bariatric surgery are scarce. In this article, an overview of different bariatric surgical procedures as well as their effects on diabetes are presented. Recommendations on the perioperative antidiabetic treatment are proposed.
Use of an Intravascular Fluorescent Continuous Glucose Sensor in Subjects with Type 1 Diabetes Mellitus
Authors: Romey Matthew , Jovanoviĉ Lois , Bevier Wendy , Markova Kateryna , Strasma Paul , Zisser Howard
Published: January 2014

Background:

Stress hyperglycemia in the critically ill is associated with increased morbidity and mortality. Continuous glucose monitoring offers a solution to the difficulties of dosing intravenous insulin properly to maintain glycemic control. The purpose of this study was to evaluate an intravascular continuous glucose monitoring (IV-CGM) system with a sensing element based on the concept of quenched fluorescence.

Method:

A second-generation intravascular continuous glucose sensor was evaluated in 13 volunteer subjects with type 1 diabetes mellitus. There were 21 study sessions of up to 24 h in duration. Sensors were inserted into peripheral veins of the upper extremity, up to two sensors per subject per study session. Sensor output was compared with temporally correlated reference measurements obtained from venous samples on a laboratory glucose analyzer.

Results:

Data were obtained from 23 sensors in 13 study sessions with 942 paired reference values. Fourteen out of 23 sensors (60.9%) had a mean absolute relative difference ≤ 10%. Eighty-nine percent of paired points were in the clinically accurate A zone of the Clarke error grid and met ISO 15197 performance criteria. Adequate venous blood flow was identified as a necessary condition for accuracy when local sensor readings are compared with venous blood glucose.

Conclusions:

The IV-CGM system was capable of achieving a high level of glucose measurement accuracy. However, superficial peripheral veins may not provide adequate blood flow for reliable indwelling blood glucose monitoring.
Pilot Study of a Prototype Minimally Invasive Intradermal Continuous Glucose Monitor
Authors: Weinstock Ruth S. , Bristol Suzan , Armenia Andrew , Gesswein A. Chris , Bequette B. Wayne , Willis John P.
Published: January 2014

Introduction:

The purpose of this study was to assess point accuracy, rate-of-change accuracy, and safety of a prototype, minimally invasive continuous glucose monitoring (CGM) device over a 12 h in-clinic study. The CGM system consisted of a wireless electronics module with a disposable glucose sensor attached to the bottom. The electronics module was affixed to the abdomen using an adhesive pad on the bottom of the disposable sensor housing.

Methods:

Two CGM sensors were inserted into the abdominal tissue (left and right) of 15 adults aged 26–67 years, 5 with normoglycemia, 5 with type 1 diabetes, and 5 with type 2 diabetes. Over a 12 h period, each participant was fed three meals. Reference venous blood samples were drawn at periodic intervals (12.4 ± 5.3 min), and glucose was measured at the bedside using a laboratory reference method. For each participant, a single plasma equivalent glucose concentration was used for retrospective sensor calibration.

Results:

A total of 1082 paired data points were obtained from 15 subjects and 25 of 30 sensors. Statistical analysis yielded a mean absolute relative difference of 12.6% and a mean absolute difference of 16.0 mg/dl. Continuous glucose error grid analysis showed the combined point and rate-of-change accuracy was 97.4% in zone A and 1.5% in zone B (98.9% A+B), with 1.1% erroneous readings.

Conclusions:

The prototype CGM system provided clinically accurate results 98.9% of the time and was well tolerated by participants, with little or no pain and no adverse events.
Oral Delivery of Glucagon-like Peptide-1 and Analogs: Alternatives for Diabetes Control?
Authors: Araújo Francisca , Fonte Pedro , Santos Hélder A. , Sarmento Bruno
Published: January 2014

Type 2 diabetes mellitus (T2DM) is one of the most prevalent diseases worldwide. Current treatments are often associated with off-target effects and do not significantly impact disease progression. New therapies are therefore urgently needed to overcome this social burden. Glucagon-like peptide-1 (GLP-1), an incretin hormone, has been used to control T2DM symptomatology. However, the administration of peptide or proteins drugs is still a huge challenge in the pharmaceutical field, requiring administration by parenteral routes. This article reviews the main hurdles in oral administration of GLP-1 and focuses on the strategies utilized to overcome them.
Acute In Vivo Performance Evaluation of the Fluorescence Affinity Sensor in the Intravascular and Interstitial Space in Swine
Authors: Dutt-Ballerstadt Ralph , Evans Colton , Pillai Arun P. , Gowda Ashok , McNichols Roger , Rios Jesse , Cohn William
Published: January 2014

Objective:

We assessed and compared the performance levels of a fiber-coupled fluorescence affinity sensor (FAS) for glucose detection in the intradermal tissue and intravascular bed during glucose clamping and insulin administration in a large animal model.

Research Design and Methods:

The FAS (BioTex Inc., Houston, TX) was implanted in interstitial tissue and in the intravenous space in nondiabetic, anesthetized pigs over 6–7 h. For intradermal assessment, a needle-type FAS was implanted in the upper back using a hypodermic needle. For intravenous assessment, the FAS was inserted through a catheter into the femoral artery and vein. Blood glucose changes were induced by infusion of dextrose and insulin through a catheterized ear or jugular vein.

Results:

Based on retrospective analysis, the mean absolute relative error (MARE) of the sensor in blood and interstitial tissue was 11.9% [standard deviation (SD) = ±9.6%] and 23.8% (SD = ±19.4%), respectively. When excluding data sets from sensors that were affected by exogenous insulin, the MARE for those sensors tested in interstitial tissue was reduced to 16.3% (SD = ±12.5%).

Conclusions:

The study demonstrated that the performance level of the FAS device implanted in interstitial tissue and blood can be very high. However, under certain circumstances, exogenous insulin caused the glucose concentration in interstitial tissue to be lower than in blood, which resulted in an overall lower level of accuracy of the FAS device. How significant this physiological effect is in insulin-treated persons with diabetes remains to be seen. In contrast, the level of accuracy of the FAS device in blood was very high because of high mass transfer conditions in blood. While the use of the FAS in both body sites will need further validation, its application in critically ill patients looks particularly promising.
Fluorescence Intensity- and Lifetime-Based Glucose Sensing Using Glucose/Galactose-Binding Protein
Authors: Pickup John C. , Khan Faaizah , Zhi Zheng-Liang , Coulter Jonathan , Birch David J. S.
Published: January 2014

We review progress in our laboratories toward developing in vivo glucose sensors for diabetes that are based on fluorescence labeling of glucose/galactose-binding protein. Measurement strategies have included both monitoring glucose-induced changes in fluorescence resonance energy transfer and labeling with the environmentally sensitive fluorophore, badan. Measuring fluorescence lifetime rather than intensity has particular potential advantages for in vivo sensing. A prototype fiber-optic-based glucose sensor using this technology is being tested.
Automated Glycemic Pattern Analysis Can Improve Health Care Professional Efficiency and Accuracy
Authors: Katz Laurence B. , Dirani Riad G. , Li Gang , Randoll Randee A. , Mahoney John J.
Published: January 2014

Background:

Health care professionals (HCPs) routinely review handwritten blood glucose (BG) logbooks during office visits of patients with diabetes.

Method:

In this study, 64 HCPs were asked to assess glycemic patterns and estimate BG averages in six simulated handwritten logbooks. The HCPs then reviewed the pattern logs and averages in six OneTouch® Verio™IQ meters containing corresponding data sets.

Results:

The average time needed for pattern review was 7.3 min for handwritten logbooks versus 0.9 min using the meter. The total error rate for logbook pattern identification was 43.0% compared with the meter. The mean percentage deviation between HCP estimates of 30-day BG averages and actual values was 14.5%.

Conclusions:

The meter is associated with faster and more accurate pattern analysis compared with handwritten logbooks.
Determination of Hematocrit Interference in Blood Samples Derived from Patients with Different Blood Glucose Concentrations
Authors: Pfützner Andreas , Schipper Christina , Ramljak Sanja , Flacke Frank , Sieber Jochen , Forst Thomas , Musholt Petra B.
Published: January 2014

Background:

We performed a blood glucose meter hematocrit (HCT) interference test with lower sample manipulation requirements by using blood samples from patients with different blood glucose (BG) levels.

Methods:

Blood from five patients with different BG levels (2.8, 5.6, 8.3, 13.9, 19.4 mmol/liter) was manipulated to contain five different HCT concentrations (35/40/45/50/55%). Each sample was measured three times in parallel with 14 BG testing devices (reference method: YSI 2300 STAT Plus™ Glucose Analyzer). The largest mean deviations in both directions from the reference method (normalized to 100% at 45% HCT) were added as a measure for hematocrit interference factor (HIF). A HIF >10% was considered to represent clinically relevant HCT interference.

Results:

Few devices showed no clinically relevant HCT interference at high/low BG levels: BGStar® (7.2%, 7.3%), iBGStar® (9.0%, 8.6%), Contour® (10.0%, 4.6%), OneTouch® Verio™ 2 (10.0%, 5.2%), and GlucoMen® LX (7.2%, 5.1%). Other devices showed interference at one or both glucose ranges: ACCU-CHEK® Aviva (12.6%, 10.7%), Aviva Nano (7.2%, 10.5%), Breeze2 (3.6%, 30.2%), GlucoCard G+ (12.6%, 7.0%), OneTouch® Ultra®2 (12.6%, 25.6%), FreeStyle Freedom Lite® (9.0%, 11.0%), Precision Xceed (16.2%, 15.3%), and MediTouch® (19.8%, 28.0%). The deviations in all devices were less pronounced in the HCT range of 35–50%.

Conclusions:

The results of this trial with less sample manipulation (HCT only) confirmed previous examinations with HCT and glucose manipulation. The same devices showed HCT stability as previously observed. Artificial sample manipulation may be less crucial than expected when evaluating HCT interference.
Hematocrit Interference of Blood Glucose Meters for Patient Self-Measurement
Authors: Ramljak Sanja , Lock John Paul , Schipper Christina , Musholt Petra B. , Forst Thomas , Lyon Martha , Pfützner Andreas
Published: January 2014

Background:

Abnormal hematocrit levels may interfere with glucose readings of patient self-assessment blood glucose (BG) meters. The aim of this laboratory investigation was to assess the potential influence of hematocrit variations on a variety of BG meters applying different measurement technologies.

Methods:

Venous heparinized blood was manipulated to contain three different BG concentrations (50–90, 120–180, and 280–350 mg/dl) and five different hematocrit levels (25%, 35%, 45%, 55%, and 65%). After careful oxygenation to normal blood oxygen pressure (65–100 mmHg), each sample was measured (eight times) with the following devices: Accu-Chek® Aviva, Nano, and Active, Breeze®2 and Contour®, FreeStyle Freedom Lite®, GlucoDr. auto™, Glucofix® mio Plus, GlucoLab™, GlucoMen® LX Plus, Nova Max® Link, Nova Max® Plus, OneTouch® Ultra®2 and Verio®, On Call® Plus and Platinum, Optium Xceed®, Precision Xceed®, and TaiDoc Fora TD-4227. A YSI 2300 STAT Plus™ glucose analyzer served as reference method. Stability to hematocrit influence was assumed, with <10% mean glucose result bias between the highest and lowest hematocrit levels.

Results:

Six of the investigated meters showed a stable performance in this investigation: Accu-Chek Active (7%), Glucofix mio Plus (5%), GlucoMen LX Plus (4%), NovaMax Plus (4%), Nova Max Link (7%), and OneTouch Verio (3%). All other meters failed this hematocrit interference test, with FreeStyle Freedom Lite (11%), and On Call Platinum 12%) being the better devices and On Call Plus (68%), GlucoLab (51%), TaiDoc Fora TD-4227 (39%), and Breeze 2 (38%) showing the worst performance.

Conclusions:

Hematocrit may affect BG meter performance in daily routine. In case of interference, low hematocrit values (<35%) result in too high readings. Our results encourage use of meters that are not affected by hematocrit interference.
Associations of Youth and Parent Weight Status with Reported versus Predicted Daily Energy Intake and Hemoglobin A1c in Youth with Type 1 Diabetes Mellitus
Authors: Sands Amanda L. P. , Higgins Laurie A. , Mehta Sanjeev N. , Nansel Tonja R. , Lipsky Leah M. , Laffel Lori M. B.
Published: January 2014

Background:

The epidemic of overweight/obesity affects youth with type 1 diabetes mellitus (T1DM) and their families. In youth with T1DM and their parents, we examined weight status with reported and expected energy intake and with youth hemoglobin A1c (HbA1c).

Methods:

In 243 youth (48% female, 13 ± 3 years) and their parents (84% female, 45 ± 6 years), we assessed body mass index (BMI), prevalence of overweight/obesity, reported energy intake (REI), and youth glycemic control (HbA1c). The REI was compared with predicted daily energy requirements (DER; based on age, weight, sex, and physical activity).

Results:

Youth had diabetes duration of 6.3 ± 3.4 years and HbA1c of 8.5% ± 1.3%; 69% used insulin pump therapy. Overweight and obesity affected 23% and 11% of youth and 30% and 24% of parents, respectively. Youth and parent BMI ( r = 0.38; p < .001) and weight status (overweight/obese; p < .001) were significantly associated. The ratio of REI:DER was significantly lower in overweight/obese compared with underweight/normal weight parents (1.0 ± 0.4 versus 1.2 ± 0.5; p = .001) but did not differ among youth by weight status. Both youth and parent BMI were positively correlated with youth HbA1c (r = 0.14, p = .02; r = 0.16, p = .01, respectively). Hemoglobin A1c tended to be higher in obese than in overweight and normal weight youth (mean ± standard deviation [SD] 8.4 ± 1.4, 8.4 ± 1.3, and 8.8 ± 1.0, respectively; p = .06) and was significantly higher in youth whose parents were obese versus overweight or underweight/normal weight (mean ± SD 8.2 ± 1.2, 8.5 ± 1.4, and 8.9 ± 1.5, respectively; p < .001).

Conclusions:

Similar to the general population, overweight and obesity are prevalent among families of youth with T1DM. Weight status appears to influence self-REI in parents and glycemic control in youth with T1DM, suggesting the need for family-based dietary interventions.
Model Identification Using Stochastic Differential Equation Grey-Box Models in Diabetes
Authors: Duun-Henriksen Anne Katrine , Schmidt Signe , Røge Rikke Meldgaard , Møller Jonas Bech , Nørgaard Kirsten , Jørgensen John Bagterp , Madsen Henrik
Published: January 2014

Background:

The acceptance of virtual preclinical testing of control algorithms is growing and thus also the need for robust and reliable models. Models based on ordinary differential equations (ODEs) can rarely be validated with standard statistical tools. Stochastic differential equations (SDEs) offer the possibility of building models that can be validated statistically and that are capable of predicting not only a realistic trajectory, but also the uncertainty of the prediction. In an SDE, the prediction error is split into two noise terms. This separation ensures that the errors are uncorrelated and provides the possibility to pinpoint model deficiencies.

Methods:

An identifiable model of the glucoregulatory system in a type 1 diabetes mellitus (T1DM) patient is used as the basis for development of a stochastic-differential-equation-based grey-box model (SDE-GB). The parameters are estimated on clinical data from four T1DM patients. The optimal SDE-GB is determined from likelihood-ratio tests. Finally, parameter tracking is used to track the variation in the “time to peak of meal response” parameter.

Results:

We found that the transformation of the ODE model into an SDE-GB resulted in a significant improvement in the prediction and uncorrelated errors. Tracking of the “peak time of meal absorption” parameter showed that the absorption rate varied according to meal type.

Conclusion:

This study shows the potential of using SDE-GBs in diabetes modeling. Improved model predictions were obtained due to the separation of the prediction error. SDE-GBs offer a solid framework for using statistical tools for model validation and model development.
A Promising Solution to Enhance the Sensocompatibility of Biosensors in Continuous Glucose Monitoring Systems
Authors: van den Bosch Edith E. M. , de Bont Nik H. M. , Qiu Jun , Gelling Onko-Jan
Published: January 2014

Background:

Continuous glucose monitors (CGMs) measure glucose in real time, making it possible to improve glycemic control. A promising technique involves glucose sensors implanted in subcutaneous tissue measuring glucose concentration in interstitial fluid. A major drawback of this technique is sensor bioinstability, which can lead to unpredictable drift and reproducibility. The bioinstability is partly due to sensor design but is also affected by naturally occurring subcutaneous inflammations. Applying a nonbiofouling coating to the sensor membrane could be a means to enhancing sensocompatibility.

Methods:

This study evaluates the suitability of a polyethylene-glycol-based coating on sensors in CGMs. Methods used include cross hatch, wet paper rub, paper double rub, bending, hydrophilicity, protein adsorption, biocompatibility, hemocompatibility, and glucose/oxygen permeability testing.

Results:

Results demonstrate that coating homogeneity, adhesion, integrity, and scratch resistance are good. The coating repels lysozyme and bovine serum albumin, and only a low level of fibrin and blood platelet adsorption to the coating was recorded when testing in whole human blood. Cytotoxicity, irritation, sensitization, and hemolysis were assessed, and levels suggested good biocompatibility of the coating in subcutaneous tissue. Finally, it was shown that the coating can be applied to cellulose acetate membranes of different porosity without changing their permeability for glucose and oxygen.

Conclusions:

These results suggest that the mechanical properties of the coating are sufficient for the given application, that the coating is effective in preventing protein adsorption and blood clot formation on the sensor surface, and that the coating can be applied to membranes without hindering their glucose and oxygen transport.
Model-Based Sensor-Augmented Pump Therapy
Authors: Grosman Benyamin , Voskanyan Gayane , Loutseiko Mikhail , Roy Anirban , Mehta Aloke , Kurtz Natalie , Parikh Neha , Kaufman Francine R. , Mastrototaro John J. , Keenan Barry
Published: January 2014

Background:

In insulin pump therapy, optimization of bolus and basal insulin dose settings is a challenge. We introduce a new algorithm that provides individualized basal rates and new carbohydrate ratio and correction factor recommendations. The algorithm utilizes a mathematical model of blood glucose (BG) as a function of carbohydrate intake and delivered insulin, which includes individualized parameters derived from sensor BG and insulin delivery data downloaded from a patient's pump.

Methods:

A mathematical model of BG as a function of carbohydrate intake and delivered insulin was developed. The model includes fixed parameters and several individualized parameters derived from the subject's BG measurements and pump data. Performance of the new algorithm was assessed using n = 4 diabetic canine experiments over a 32 h duration. In addition, 10 in silico adults from the University of Virginia/Padova type 1 diabetes mellitus metabolic simulator were tested.

Results:

The percentage of time in glucose range 80–180 mg/dl was 86%, 85%, 61%, and 30% using model-based therapy and [78%, 100%] (brackets denote multiple experiments conducted under the same therapy and animal model), [75%, 67%], 47%, and 86% for the control experiments for dogs 1 to 4, respectively. The BG measurements obtained in the simulation using our individualized algorithm were in 61–231 mg/dl min-max envelope, whereas use of the simulator's default treatment resulted in BG measurements 90–210 mg/dl min-max envelope.

Conclusions:

The study results demonstrate the potential of this method, which could serve as a platform for improving, facilitating, and standardizing insulin pump therapy based on a single download of data.
Considerations for an Institution for Evaluation of Diabetes Technology Devices to Improve Their Quality in the European Union
Authors: Heinemann Lutz , Freckmann Guido , Koschinsky Theodor
Published: January 2014

All medical devices used for self-monitoring of blood glucose (BG), insulin injection, continuous subcutaneous insulin infusion, and continuous glucose monitoring in the European Union (EU) must have a Communauté Européenne (CE) mark. However, the approval process for obtaining this mark is different from that used by the European Medicines Agency in the EU for drugs or by the Food and Drug Administration in the United States for such medical and in vitro diagnostic devices. The notified bodies involved in the CE mark process perform this evaluation in cooperation with the manufacturers. They have only limited diabetes know-how; they have to handle all kinds of medical devices. There are devices for therapy on the market in the EU (i.e., they have market approval) that do not fulfill quality requirements, as indicated, for example, in the international norm ISO 15197 for BG test systems. Evaluation of the performance of such systems is usually provided by the manufacturers. What is missing in the EU is an independent institution that performs regular and critical evaluation of the quality of devices used for diabetes therapy before and also after their market approval. The work of such an institution would focus on BG test systems (these represent two-thirds of the market of medical devices for diabetes treatment) but would also evaluate the performance of other devices. It has to be clarified what legal framework is required for such an institution and how it can be financed; probably this can be done in a shared manner by the manufacturers of such devices and the health insurance companies. Positive evaluation results should be a prerequisite prior to any reimbursement for such devices.
Development and Feasibility of a Text Messaging and Interactive Voice Response Intervention for Low-Income, Diverse Adults with Type 2 Diabetes Mellitus
Authors: Osborn Chandra Y. , Mulvaney Shelagh A.
Published: January 2014

Low-income, racial/ethnic minorities are often nonadherent to diabetes medications, have uncontrolled glycemia, and have high rates of diabetes-related morbidity. Cell phones provide a viable modality to support medication adherence, but few cell phone-based interventions have been designed for low-income persons, a population with more feature phone penetration than smartphone penetration. In an effort to reach the broadest range of patients, we leveraged the voice and text messaging capabilities shared by all cell phones to design the MEssaging for Diabetes intervention. We specifically advanced and adapted an existing tailored text messaging system to include interactive voice response functionality and support the medication adherence barriers of low-income, diverse adults with type 2 diabetes mellitus. We report on the design process and feasibility testing results (i.e., technical use patterns and subjective user experiences) from patients from the target population who used the intervention in one of three user-centered design iterations. The types of challenges encountered in design were related to providing text message content with valued information and support that engages patients. The design process also highlighted the value of obtaining mixed methods data to provide insight into legitimate versus illegitimate missing data, patterns of use, and subjective user experiences. The iterative testing process and results outlined here provide a potential template for other teams seeking to design technology-based self-care support solutions for comparable patient populations.
An Early Warning System for Hypoglycemic/Hyperglycemic Events Based on Fusion of Adaptive Prediction Models
Authors: Daskalaki Elena , Nørgaard Kirsten , Züger Thomas , Prountzou Aikaterini , Diem Peter , Mougiakakou Stavroula
Published: January 2014

Introduction:

Early warning of future hypoglycemic and hyperglycemic events can improve the safety of type 1 diabetes mellitus (T1DM) patients. The aim of this study is to design and evaluate a hypoglycemia/hyperglycemia early warning system (EWS) for T1DM patients under sensor-augmented pump (SAP) therapy.

Methods:

The EWS is based on the combination of data-driven online adaptive prediction models and a warning algorithm. Three modeling approaches have been investigated: (i) autoregressive (ARX) models, (ii) autoregressive with an output correction module (cARX) models, and (iii) recurrent neural network (RNN) models. The warning algorithm performs postprocessing of the models' outputs and issues alerts if upcoming hypoglycemic/hyperglycemic events are detected. Fusion of the cARX and RNN models, due to their complementary prediction performances, resulted in the hybrid autoregressive with an output correction module/recurrent neural network (cARN)-based EWS.

Results:

The EWS was evaluated on 23 T1DM patients under SAP therapy. The ARX-based system achieved hypoglycemic (hyperglycemic) event prediction with median values of accuracy of 100.0% (100.0%), detection time of 10.0 (8.0) min, and daily false alarms of 0.7 (0.5). The respective values for the cARX-based system were 100.0% (100.0%), 17.5 (14.8) min, and 1.5 (1.3) and, for the RNN-based system, were 100.0% (92.0%), 8.4 (7.0) min, and 0.1 (0.2). The hybrid cARN-based EWS presented outperforming results with 100.0% (100.0%) prediction accuracy, detection 16.7 (14.7) min in advance, and 0.8 (0.8) daily false alarms.

Conclusion:

Combined use of cARX and RNN models for the development of an EWS outperformed the single use of each model, achieving accurate and prompt event prediction with few false alarms, thus providing increased safety and comfort.
A Closed-Loop Artificial Pancreas Using a Proportional Integral Derivative with Double Phase Lead Controller Based on a New Nonlinear Model of Glucose Metabolism
Authors: Abbes Ilham Ben , Richard Pierre-Yves , Lefebvre Marie-Anne , Guilhem Isabelle , Poirier Jean-Yves
Published: January 2014

Background:

Most closed-loop insulin delivery systems rely on model-based controllers to control the blood glucose (BG) level. Simple models of glucose metabolism, which allow easy design of the control law, are limited in their parametric identification from raw data. New control models and controllers issued from them are needed.

Methods:

A proportional integral derivative with double phase lead controller was proposed. Its design was based on a linearization of a new nonlinear control model of the glucose-insulin system in type 1 diabetes mellitus (T1DM) patients validated with the University of Virginia/Padova T1DM metabolic simulator. A 36 h scenario, including six unannounced meals, was tested in nine virtual adults. A previous trial database has been used to compare the performance of our controller with their previous results. The scenario was repeated 25 times for each adult in order to take continuous glucose monitoring noise into account. The primary outcome was the time BG levels were in target (70–180 mg/dl).

Results:

Blood glucose values were in the target range for 77% of the time and below 50 mg/dl and above 250 mg/dl for 0.8% and 0.3% of the time, respectively. The low blood glucose index and high blood glucose index were 1.65 and 3.33, respectively.

Conclusion:

The linear controller presented, based on the linearization of a new easily identifiable nonlinear model, achieves good glucose control with low exposure to hypoglycemia and hyperglycemia.
The Current Status of mHealth for Diabetes: Will it Be the Next Big Thing?
Authors: Klonoff David C.
Published: January 2014

mHealth is an emerging concept in health care and uses mobile communications devices for health services and information. Mobile phones, patient monitoring devices, tablets, personal digital assistants, and other wireless devices can be part of mHealth systems. With mHealth systems, glucose data can now be automatically collected, transmitted, aggregated with other physiologic data, analyzed, stored, and presented as actionable information. mHealth systems use mobile decision support software applications (or apps) to assist or direct health care professionals to make decisions, or they can assist or direct patients to make decisions without waiting for input from a clinician. With real-time decision support for patients, appropriate actions can be taken in real time without waiting to see a clinician. Decisions can be personalized if individual treatment goals and personal preferences for treatment are inputted into an app. Few mHealth apps for diabetes have been rigorously tested. Outcome studies of the use of mHealth for diabetes from the literature have shown the potential for benefits, but higher-quality studies are needed. Regulatory approval of mHealth products will require demonstration of safety and effectiveness, especially where information and trends are not just presented to patients, but used to make treatment recommendations. Three additional hurdles must be overcome to facilitate widespread adoption of this technology, including demonstration of the following: (1) privacy to satisfy regulators, (2) clinical benefit to satisfy clinicians, and (3) economic benefit to satisfy payers. mHealth for diabetes is making rapid strides and is expected to be a transforming technology that will be the next big thing.
“Turn it Off!”: Diabetes Device Alarm Fatigue Considerations for the Present and the Future
Authors: Shivers Joseph P. , Mackowiak Linda , Anhalt Henry , Zisser Howard
Published: January 2014

Safe and widespread use of diabetes technology is constrained by alarm fatigue: When someone receives so many alarms that he or she becomes less likely to respond appropriately. Alarm fatigue and related usability issues deserve consideration at every stage of alarm system design, especially as new technologies expand the potential number and complexity of alarms. The guiding principle should be patient wellbeing, while taking into consideration the regulatory and liability issues that sometimes contribute to building excessive alarms. With examples from diabetes devices, we illustrate two complementary frameworks for alarm design: A “patient safety first” perspective and a focus on human factors. We also describe opportunities and challenges that will come with new technologies such as remote monitoring, adaptive alarms, and ever-closer integration of glucose sensing with insulin delivery.
Clinical and genetic factors predicting response to therapy in patients with Crohn's disease
Authors: Cravo Marilia , Ferreira Paula , Sousa Patricia , Moura-Santos Paula , Velho Sonia , Tavares Lurdes , Deus João Ramos , Ministro Paula , Silva João Pereira da , Correia Luis , Velosa Jose , Maio Rui , Brito Miguel
Published: January 2014

Aim

To identify clinical and/or genetic predictors of response to several therapies in Crohn's disease (CD) patients.

Methods

We included 242 patients with CD (133 females) aged (mean ± standard deviation) 39 ± 12 years and a disease duration of 12 ± 8 years. The single‐nucleotide polymorphisms (SNPs) studied were ABCB1 C3435T and G2677T/A, IL23R G1142A, C2370A, and G9T, CASP9 C93T, Fas G670A and LgC844T, and ATG16L1 A898G. Genotyping was performed with real‐time PCR with Taqman probes.

Results

Older patients responded better to 5‐aminosalicylic acid (5‐ASA) and to azathioprine (OR 1.07, p  = 0.003 and OR 1.03, p  = 0.01, respectively) while younger ones responded better to biologicals (OR 0.95, p  = 0.06). Previous surgery negatively influenced response to 5‐ASA compounds (OR 0.25, p  = 0.05), but favoured response to azathioprine (OR 2.1, p  = 0.04). In respect to genetic predictors, we observed that heterozygotes for ATGL16L1 SNP had a significantly higher chance of responding to corticosteroids (OR 2.51, p  = 0.04), while homozygotes for Casp9 C93T SNP had a lower chance of responding both to corticosteroids and to azathioprine (OR 0.23, p  = 0.03 and OR 0.08, p  = 0.02,). TT carriers of ABCB1 C3435T SNP had a higher chance of responding to azathioprine (OR 2.38, p  = 0.01), while carriers of ABCB1 G2677T/A SNP, as well as responding better to azathioprine (OR 1.89, p  = 0.07), had a lower chance of responding to biologicals (OR 0.31, p  = 0.07), which became significant after adjusting for gender (OR 0.75, p  = 0.005).

Conclusions

In the present study, we were able to identify a number of clinical and genetic predictors of response to several therapies which may become of potential utility in clinical practice. These are preliminary results that need to be replicated in future pharmacogenomic studies.
TTT-3002 is a novel FLT3 tyrosine kinase inhibitor with activity against FLT3-associated leukemias in vitro and in vivo
Authors: Ma Hayley , Nguyen Bao , Li Li , Greenblatt Sarah , Williams Allen , Zhao Ming , Levis Mark , Rudek Michelle , Duffield Amy , Small Donald
Published: January 2014

Key Points

A novel TKI is discovered with potent and selective activity against FLT3-mutant cell lines and primary patient samples. TTT-3002 is effective in vivo in several mouse tumor models of FLT3/ITD-associated AML with minimal toxicity.
Guiding properties of asymmetric hybrid plasmonic waveguides on dielectric substrates
Authors: Wei Wei , Zhang Xia , Huang Yongqing , Ren Xiaomin
Published: January 2014

We proposed an asymmetric hybrid plasmonic waveguide which is placed on a substrate for practical applications by introducing an asymmetry into a symmetric hybrid plasmonic waveguide. The guiding properties of the asymmetric hybrid plasmonic waveguide are investigated using finite element method. The results show that, with proper waveguide sizes, the proposed waveguide can eliminate the influence of the substrate on its guiding properties and restore its broken symmetric mode. We obtained the maximum propagation length of 2.49 × 103 μm. It is approximately equal to that of the symmetric hybrid plasmonic waveguide embedded in air cladding with comparable nanoscale confinement.
Novel restriction factor RNA-associated early-stage anti-viral factor (REAF) inhibits human and simian immunodeficiency viruses
Authors: Marno Kelly M , Ogunkolade Babatunji W , Pade Corinna , Oliveira Nidia MM , O’Sullivan Eithne , McKnight Áine
Published: January 2014

Background

The discovery of novel anti-viral restriction factors illuminates unknown aspects of innate sensing and immunity. We identified RNA-associated Early-stage Anti-viral Factor (REAF) using a whole genome siRNA screen for restriction factors to human immunodeficiency virus (HIV) that act in the early phase of viral replication.

Results

We observed more than 50 fold rescue of HIV-1 infection, using a focus forming unit (FFU) assay, following knockdown of REAF by specific siRNA. Quantitative PCR was used to show that REAF knockdown results in an increase of early and late reverse transcripts which impacts the level of integration. REAF thus appears to act at an early stage of the viral life cycle during reverse transcription. Conversely when REAF is over-expressed in target cells less infected cells are detectable and fewer reverse transcripts are produced. Human REAF can also inhibit HIV-2 and simian immunodeficiency virus (SIV) infection. REAF associates with viral nucleic acids and may act to prevent reverse transcription.

Conclusions

This report firmly places REAF alongside APOBECs and SAMHD1 as a potent inhibitor of HIV replication acting early in the replication cycle, just after cell entry. We propose that REAF is part of an anti-viral surveillance system destroying incoming retroviruses. This novel mechanism could apply to invasion of cells by any intracellular pathogen.
Bapedi traditional healers in the Limpopo Province, South Africa: Their socio-cultural profile and traditional healing practice
Authors: Semenya Sebua S , Potgieter Martin J
Published: January 2014

Background

Bapedi traditional healers play a vital role in the primary health care of rural inhabitants in the Limpopo Province, South Africa. However, literature profiling their social and demographic variables, as well as their traditional healing practices is lacking.

Methods

Convenience sampling were used to identify and select two traditional healers from 17 municipalities (resulting in 34 healers being used in this pilot survey) of the Limpopo Province in South Africa. Information on the social and demographic variables, and traditional healing practices of these healers was gathered from January 2013 to July 2013, using a semi-structured questionnaire, supplemented by field surveys for plant identification and collection used in the preparation of remedies.

Results

Males constituted nearly two-thirds of the participants. Forty eight percent of them became healers through the mentoring of another healer, while 38% acquired their traditional healing knowledge from parents and 14% from grandparents. In contrast to this, 62% of the females obtained theirs from their parents, 30% from fellow traditional healers, and 8% from grandparents. A total of 154 plant species were indicated as used by healers in the treatment of 52 health-related problems. A vast majority (89%) of these practitioners reported that prepared herbal remedies do expire, which is a temperature-dependent process. Determinations of the efficacy of remedies by most healers (67%) were via consultation with ancestors (90%). This study also found that none of the interviewees had any knowledge of provincial or national environmental legislation.

Conclusions

The current study has shown that Bapedi traditional healers could play a leading role in both the preservation of indigenous knowledge and the primary health care sector. However, of concern is the traditional methods (via consulting ancestors) employed by most of these healers in determining efficacy of remedies, thus indicating a need for a scientific investigations to establish their safety and effectiveness. Equally, there is a need to educate traditional practitioners’ regarding the significance of various conservation legislations in their traditional healing. By addressing these, the national and provincial legislators, medical fraternity as well as environmental agencies will be able to better integrate them in primary health care systems and environmental management.
Unraveling the cytotoxic potential of Temozolomide loaded into PLGA nanoparticles
Authors: Jain Darshana S , Athawale Rajani B , Bajaj Amrita N , Shrikhande Shruti S , Goel Peeyush N , Nikam Yuvraj , Gude Rajiv P
Published: January 2014

Background

Nanotechnology has received great attention since a decade for the treatment of different varieties of cancer. However, there is a limited data available on the cytotoxic potential of Temozolomide (TMZ) formulations. In the current research work, an attempt has been made to understand the anti-metastatic effect of the drug after loading into PLGA nanoparticles against C6 glioma cells.

Nanoparticles were prepared using solvent diffusion method and were characterized for size and morphology. Diffusion of the drug from the nanoparticles was studied by dialysis method. The designed nanoparticles were also assessed for cellular uptake using confocal microscopy and flow cytometry.

Results

PLGA nanoparticles caused a sustained release of the drug and showed a higher cellular uptake. The drug formulations also affected the cellular proliferation and motility.

Conclusion

PLGA coated nanoparticles prolong the activity of the loaded drug while retaining the anti-metastatic activity.
Characterisation of interleukin‐10 expression on different vascular structures in allergic nasal mucosa
Authors: Muller Barbara , van Egmond Danielle , de Groot Esther JJ , Fokkens Wytske J , van Drunen Cornelis M
Published: January 2014

Background

Interleukin‐10 (IL‐10) is a negative regulator of immune responses and was previously shown to be expressed by human nasal endothelial cells, while the adhesion molecule MECA‐79 plays a role in trans‐endothelial migration of immune competent cells. In this study we investigate the relationship between endothelial IL‐10 and MECA‐79 expression to address the question whether immune competent cells could be affected at the mucosal entry site.

Methods

Nasal turbinate biopsies were taken from house dust mite allergic patients, before and after nasal allergen provocation. Subsequent slides of biopsies were stained for IL10, MECA‐79, CD34, and IL10‐Receptor. Capillaries, arteries/veins, and sinusoids were evaluated separately.

Results

90% of sinusoids are IL‐10 positive and all sinusoids are negative for MECA‐79, while 4.8% of capillaries are positive for IL‐10, and 2.2% are positive for MECA‐79. Although about 47% of arteries/veins are positive for IL‐10 and 57.1% are positive for MECA‐79, only about 20% are positive for both markers. Furthermore, we showed that the myo‐fibroblasts surrounding all sinusoids stain positive for IL10R.

Conclusions

IL10 expression on vascular structures is not related to MECA expression for sinusoids and capillaries and only partly related on arteries/veins, however sinusoidal endothelial IL10 expression is always seen in combination with IL‐10R expression of sinusoidal myo‐fibroblasts.