bluuebunny/crossref_metadata_2025_split huggingface dataset:
EyePACS: An Adaptable Telemedicine System for Diabetic Retinopathy Screening
Authors: Cuadros Jorge , Bresnick George 
Published: January 2014

Background: Annual retinal screening of patients with diabetes is the standard clinical practice to prevent visual impairment and blindness from diabetic retinopathy. Telemedicine-based diabetic retinopathy screening (DRS) in primary care settings can effectively detect sight-threatening retinopathy and significantly increase compliance with annual retinal exams. EyePACS is a license-free Web-based DRS system designed to simplify the process of image capture, transmission, and review. The system provides a flexible platform for collaboration among clinicians about diabetic retinopathy. Methods: Primary clinic personnel (i.e., nursing, technical, or administrative staff) are trained and certified by the EyePACS program to acquire retinal images from standard digital retinal cameras. Relevant clinical data and eight high-resolution images per patient (two external and six retinal images) are encrypted and transmitted to a secure Internet server, using a standard computer and Web browser. Images are then interpreted by certified EyePACS reviewers or local eye care providers who are certified through the EyePACS Retinopathy Grading System. Reports indicating retinopathy level and referral recommendations are transmitted back to primary care providers through the EyePACS Web site or through interfaces between EyePACS and Health Level 7-compliant electronic medical records or chronic disease registries. Results: The pilot phase of the EyePACS DRS program in California (2005–2006) recorded 3562 encounters. Since 2006, EyePACS has been expanded to over 120 primary care sites throughout California and elsewhere recording over 34,000 DRSs. The overall rate of referral is 8.21% for sight-threatening retinopathy and 7.83% for other conditions (e.g., cataract and glaucoma). Conclusion: The use of license-free Web-based software, standard interfaces, and flexible protocols has allowed primary care providers to adopt retinopathy screening with minimal effort and resources.
Technosphere® Insulin: Defining the Role of Technosphere Particles at the Cellular Level
Authors: Angelo Robert , Rousseau Kathleen , Grant Marshall , Leone-Bay Andrea , Richardson Peter 
Published: January 2014

Background: Technosphere® Insulin (TI) is a novel inhalation powder for the treatment of diabetes mellitus. Technosphere Insulin delivers insulin with an ultra rapid pharmacokinetic profile that is distinctly different from all other insulin products but similar to natural insulin release. Such rapid absorption is often associated with penetration enhancers that disrupt cellular integrity. Methods: Technosphere Insulin was compared to a panel of known penetration enhancers in vitro using the Calu-3 lung cell line to investigate the effects of TI on insulin transport. Results: Measures of tight junction integrity such as transepithelial electrical resistance, Lucifer yellow permeability, and F-actin staining patterns were all unaffected by TI. Cell viability and plasma membrane integrity were also not affected by TI. In contrast, cells treated with comparable (or lower) concentrations of penetration enhancers showed elevated Lucifer yellow permeability, disruption of the F-actin network, reduced cell viability, and compromised plasma membranes. Conclusions: These results demonstrate that TI is not cytotoxic in an in vitro human lung cell model and does not function as a penetration enhancer. Furthermore, TI does not appear to affect the transport of insulin across cellular barriers.
Are Current Insulin Pumps Accessible to Blind and Visually Impaired People?
Authors: Burton Darren M. , Uslan Mark M. , Blubaugh Morgan V. , Clements Charles W. 
Published: January 2014

Background: In 2004, Uslan and colleagues determined that insulin pumps (IPs) on the market were largely inaccessible to blind and visually impaired persons. The objective of this study is to determine if accessibility status changed in the ensuing 4 years. Methods: Five IPs on the market in 2008 were acquired and analyzed for key accessibility traits such as speech and other audio output, tactual nature of control buttons, and the quality of visual displays. It was also determined whether or not a blind or visually impaired person could independently complete tasks such as programming the IP for insulin delivery, replacing batteries, and reading manuals and other documentation. Results: It was found that IPs have not improved in accessibility since 2004. None have speech output, and with the exception of the Animas IR 2020, no significantly improved visual display characteristics were found. Documentation is still not completely accessible. Conclusion: Insulin pumps are relatively complex devices, with serious health consequences resulting from improper use. For IPs to be used safely and independently by blind and visually impaired patients, they must include voice output to communicate all the information presented on their display screens. Enhancing display contrast and the size of the displayed information would also improve accessibility for visually impaired users. The IPs must also come with accessible user documentation in alternate formats.
Noninvasive Optical Screening for Diabetes
Authors: Ediger Marwood N. , Olson Byron P. , Maynard John D. 
Published: January 2014

Background: Advanced glycation end products (AGEs) are implicated in the complications of diabetes. Advanced glycation end products also accumulate in the skin and are sensitive biomarkers for the risk of developing diabetes and related complications. Some AGEs fluoresce and can be measured noninvasively by optical spectroscopy. Methods: Noninvasive screening for diabetes has been evaluated in an 18-site study involving a cohort of 2793 subjects meeting American Diabetes Association-based screening criteria. Subjects were measured with a specialized skin fluorimeter and also received traditional blood glucose and glycated hemoglobin tests. Results: Retrospective results indicated that the noninvasive technology measuring dermal fluorescence is more sensitive at detecting abnormal glucose tolerance than either fasting plasma glucose or glycated hemoglobin A1C. Conclusions: These results suggest that noninvasive measurement of dermal fluorescence may be an effective tool to identify individuals at risk for diabetes and its complications. The noninvasive technology yields immediate results, and since measuring dermal fluorescence requires no blood draws or patient fasting, the instrument may be well suited for opportunistic screening.
A Feasibility Study of Bihormonal Closed-Loop Blood Glucose Control Using Dual Subcutaneous Infusion of Insulin and Glucagon in Ambulatory Diabetic Swine
Authors: El-Khatib Firas H. , Jiang John , Damiano Edward R. 
Published: January 2014

Background: We sought to test the feasibility and efficacy of bihormonal closed-loop blood glucose (BG) control that utilizes subcutaneous (SC) infusion of insulin and glucagon, a model-predictive control algorithm for determining insulin dosing, and a proportional-derivative control algorithm for determining glucagon dosing. Methods: Thirteen closed-loop experiments (∼7–27 h in length) were conducted in six ambulatory diabetic pigs weighing 26–50 kg. In all experiments, venous BG was sampled through a central line in the vena cava. Efficacy was evaluated in terms of the controller's ability to regulate BG in response to large meal disturbances (∼5 g of carbohydrate per kilogram of body mass per meal) based only on regular frequent venous BG sampling and requiring only the subject's weight for initialization. Results: Closed-loop results demonstrated successful BG regulation to normoglycemic range, with average insulin-to-carbohydrate ratios between ∼1:20 and 1:40 U/g. The total insulin bolus doses averaged ∼6 U for a meal containing ∼6 g per kilogram body mass. Mean BG values in two 24 h experiments were ∼142 and ∼155 mg/dl, with the total daily dose (TDD) of insulin being ∼0.8–1.0 U per kilogram of body mass and the TDD of glucagon being ∼0.02–0.05 mg. Results also affirmed the efficacy of SC doses of glucagon in staving off episodic hypoglycemia. Conclusions: We demonstrate the feasibility of bihormonal closed-loop BG regulation using a control system that employs SC infusion of insulin and glucagon as governed by an algorithm that reacts only to BG without any feedforward information regarding carbohydrate consumption or physical activity. As such, this study can reasonably be regarded as the first practical implementation of an artificial endocrine pancreas that has a hormonally derived counterregulatory capability.
Screening for Diabetic Retinopathy Using Computer Vision and Physiological Markers
Authors: Hann Christopher E. , Revie James A. , Hewett Darren , Chase J. Geoffrey , Shaw Geoffrey M. 
Published: January 2014

Background: Hyperglycemia and diabetes result in vascular complications, most notably diabetic retinopathy (DR). The prevalence of DR is growing and is a leading cause of blindness and/or visual impairment in developed countries. Current methods of detecting, screening, and monitoring DR are based on subjective human evaluation, which is also slow and time-consuming. As a result, initiation and progress monitoring of DR is clinically hard. Methods: Computer vision methods are developed to isolate and detect two of the most common DR dysfunctions—dot hemorrhages (DH) and exudates. The algorithms use specific color channels and segmentation methods to separate these DR manifestations from physiological features in digital fundus images. The algorithms are tested on the first 100 images from a published database. The diagnostic outcome and the resulting positive and negative prediction values (PPV and NPV) are reported. The first 50 images are marked with specialist determined ground truth for each individual exudate and/or DH, which are also compared to algorithm identification. Results: Exudate identification had 96.7% sensitivity and 94.9% specificity for diagnosis (PPV = 97%, NPV = 95%). Dot hemorrhage identification had 98.7% sensitivity and 100% specificity (PPV = 100%, NPV = 96%). Greater than 95% of ground truth identified exudates, and DHs were found by the algorithm in the marked first 50 images, with less than 0.5% false positives. Conclusions: A direct computer vision approach enabled high-quality identification of exudates and DHs in an independent data set of fundus images. The methods are readily generalizable to other clinical manifestations of DR. The results justify a blinded clinical trial of the system to prove its capability to detect, diagnose, and, over the long term, monitor the state of DR in individuals with diabetes.
An Evaluation of “I, Pancreas” Algorithm Performance In Silico
Authors: Wilinska Malgorzata E. , Nodale Marianna 
Published: January 2014

Background: The objective of this study was to investigate the performance of a newly proposed insulin titrating algorithm to achieve tight glycemic control in the critically ill. Methods: A simulation environment with 10 critically ill virtual subjects was employed to evaluate the “I, Pancreas” algorithm proposed by Braithwaite et al. and described in an article in this issue of Journal of Diabetes Science and Technology. The algorithm was coded in MATLAB® and was “plugged in” to a simulation environment to provide glucose control in a 48-hour-long simulated study. Results: Mean blood glucose was 6.5 ± 0.4 mmol/liter (118 ± 7.8 mg/dl), percentage of time spent in the target glucose range was 38% (32–44%), and the hyperglycemic index was 0.6 (0.4 −1.0) mmol/liter [11.1 (7.7–18.1) mg/dl]. A single episode of mild hypoglycemia at 3.8 mmol/liter (69 mg/dl) was observed during 480 hours of glucose control. Conclusion: In this initial in silico evaluation, the “I, Pancreas” algorithm provided a safe control of glucose in the simulated study and achieved tight glycemic control 38% of the time.
Enhanced Glucose Sensor Linearity Using Poly(Vinyl Alcohol) Hydrogels
Authors: Vaddiraju SanthiSagar , Singh Hardeep , Burgess Diane J. , Jain Faquir C. , Papadimitrakopoulos Fotios 
Published: January 2014

Background: High linearities, sensitivities, and low oxygen dependence constitute prime requisites for electrochemical glucose sensors. However, for implantable sensors the need to control tissue inflammation requires the use of outer membranes that permit inward analyte diffusion while continuously releasing anti-inflammatory drugs and other tissue response-modifying (TRM) agents. We have shown previously that while outer membranes based on layer-by-layer (LBL) assembly enhance linearity, poly(vinyl alcohol)(PVA) hydrogels loaded with TRM-containing microspheres enable a significant reduction in tissue inflammation. This article discusses the amperometric performance of glucose sensors coated with stacked LBL/PVA hydrogel outer membranes. Methods: Sensors were fabricated by immobilizing glucose oxidase enzyme on a 50-μm platinum wire followed by deposition of stacked LBL/PVA hydrogel outer membranes. The sensor response to various glucose concentrations was determined by applying 0.7 V vs an Ag/AgCl reference electrode in phosphate-buffered saline (37°C). Michaelis—Menten analysis was performed to quantify sensor performance in terms of linearity ( Kappm,glu) and oxygen dependence ( Kappm,O2/[Glucose]). Results: When overlaid onto LBL-assembled outer membranes, PVA hydrogels improved sensor linearity by 60% from 10 to 16 m M of glucose and resulted in a twofold decrease in oxygen dependence. Conclusions: Enhancement in the performance of a PVA-coated sensor is attributed to the oxygen-storing capability of PVA hydrogel due to the formation of hydrophobic domains during its freezing and thawing employed to physical cross-link the PVA. Such membranes with the capability to release TRMs continuously while storing oxygen constitute a major improvement over current outer membrane technologies.
A Minimal C-Peptide Sampling Method to Capture Peak and Total Prehepatic Insulin Secretion in Model-Based Experimental Insulin Sensitivity Studies
Authors: Lotz Thomas , Göltenbott Uli , Chase J. Geoffrey , Docherty Paul , Hann Christopher E. 
Published: January 2014

Aims and Background: Model-based insulin sensitivity testing via the intravenous glucose tolerance test (IVGTT) or similar is clinically very intensive due to the need for frequent sampling to accurately capture the dynamics of insulin secretion and clearance. The goal of this study was to significantly reduce the number of samples required in intravenous glucose tolerance test protocols to accurately identify C-peptide and insulin secretion characteristics. Methods: Frequently sampled IVGTT data from 12 subjects [5 normal glucose-tolerant (NGT) and 7 type 2 diabetes mellitus (T2DM)] were analyzed to calculate insulin and C-peptide secretion using a well-accepted C-peptide model. Samples were reduced in a series of steps based on the critical IVGTT profile points required for the accurate estimation of C-peptide secretion. The full data set of 23 measurements was reduced to sets with six or four measurements. The peak secretion rate and total secreted C-peptide during 10 and 20 minutes postglucose input and during the total test time were calculated. Results were compared to those from the full data set using the Wilcoxon rank sum to assess any differences. Results: In each case, the calculated secretion metrics were largely unchanged, within expected assay variation, and not significantly different from results obtained using the full 23 measurement data set ( P < 0.05). Conclusions: Peak and total C-peptide and insulin secretory characteristics can be estimated accurately in an IVGTT from as few as four systematically chosen samples, providing an opportunity to minimize sampling, cost, and burden.
Numerical and Clinical Accuracy of a Continuous Glucose Monitoring System during Intravenous Insulin Therapy in the Surgical and Burn Intensive Care Units
Authors: Rabiee Atoosa , Andreasik Virginia , Abu-Hamdah Rania , Galiatsatos Panagis , Khouri Zeina , Gibson B. Robert , Andersen Dana K. , Elahi Dariush 
Published: January 2014

Background: Intensive insulin therapy (IIT) for glycemic control in critically ill patients has been shown to be beneficial. Continuous glucose monitoring systems (CGMSs) have been approved as an adjunct to complement standard glucose monitoring in type 2 diabetes mellitus. This study was designed to evaluate the accuracy of a real-time CGMS (DexCom™ STS) in the intensive care unit (ICU). We also evaluated its reliability and accuracy using a hyperinsulinemic-euglycemic and a hyperglycemic clamp study. Methods: Nineteen patients were enrolled in this 7-day study [13 = surgical intensive care unit (SICU), 6 = burn intensive care unit (BICU)]. The patients were on IIT for at least 2 h prior the subcutaneous sensor insertion. Mean age and body mass index for SICU and BICU patients were 60.3 ± 3.7 and 64.5 ± 6.2 years and 36.6 ± 5.0 and 33.85 ± 3.4 kg/m2, respectively. DexCom accuracy was analyzed separately for the Johnson & Johnson (J&J) calibration finger sticks, Roche Accucheck finger sticks, and the Hitachi 917 analyzer measurements on serum using Clarke error grid analysis and Bland—Altman analysis. In the clamp studies, 20 patients were enrolled, and the data were analyzed similarly. Results: There were 1065 pairs of DexCom—Accucheck, 232 pairs of DexCom—J&J, and 84 pairs of DexCom—Hitachi in ICU patients. For DexCom—Accucheck, 68.26% of the pairs fell into zone A, 31.83% into zone B, and 0.75% into zone C. There were no values in zones D or E. From the 1102 matching DexCom—Beckman pairs in clamp studies, 42.29% were in zone A, 55.90% were in zone B, and 4.08% were in zone C. Conclusions: Despite the high percentage of measurements in zones A and B, underestimation of hypoglycemia by DexCom measurements makes it an unreliable device in the ICU setting.
Sources of Glycemic Variability—What Type of Technology is Needed?
Authors: Kildegaard Jonas , Christensen Toke Folke , Hejlesen Ole Kristian 
Published: January 2014

People on insulin therapy are challenged with evaluation of numerous factors affecting the blood glucose in order to select the optimal dose for reaching their glucose target. Following medical recommendations precisely still results in considerable blood glucose unpredictability, often resulting in frustration in the short term due to hypoglycemia and hyperglycemia, and, in the long term, will likely result in complications. The kinetics of insulin do indeed vary significantly and have become an important focus when developing new insulin analogues and delivery systems; however, numerous of other factors impact glycemic variability. These have different dependences and interactions and are therefore difficult to characterize. Some of the factors are highly dependent and influenced by the type of insulin and devices used in therapy. Development of future therapy products is therefore highly focused on how to minimize glycemic variability.
Glucose Clamp Algorithms and Insulin Time-Action Profiles
Authors: Bequette B. Wayne 
Published: January 2014

Motivation: Most current insulin pumps include an insulin-on-board (IOB) feature to help subjects avoid problems associated with “insulin stacking.” In addition, many control algorithms proposed for a closed-loop artificial pancreas make use of IOB to reduce the probability of hypoglycemic events that often occur due to the integral action of the controller. The IOB curves are generated from the pharmacodynamic (time-activity profiles) actions of subcutaneous insulin, which are obtained from glycemic clamp studies. Methods: Glycemic clamp algorithms are reviewed and in silico studies are performed to analyze the effect of glucose meter bias and noise on glycemic control and the manipulated glucose infusion rates. The glucose infusion rates are used to obtain insulin time-activity profiles, which are then used to generate IOB curves. Results: A model-based, three-step-ahead controller is shown to be equivalent to a proportional-integral control algorithm with time-delay compensation. A systematic glucose meter bias of +6 mg/dl results in a decrease in the glucose area under the curve of 3% but no change in the IOB profiles. Conclusions: Based on these preliminary simulation studies, a substantial amount of glucose meter bias and noise during a glycemic clamp can be tolerated with little net effect on the IOB curves. It is suggested that handheld glucose meters can therefore be used in clamp studies if the measurements are filtered (averaged) before processing by the control algorithm. Clinical studies are needed to confirm these preliminary results.
Closed-Loop Artificial Pancreas Using Subcutaneous Glucose Sensing and Insulin Delivery and a Model Predictive Control Algorithm: Preliminary Studies in Padova and Montpellier
Authors: Bruttomesso Daniela , Farret Anne , Costa Silvana , Marescotti Maria Cristina , Vettore Monica , Avogaro Angelo , Tiengo Antonio , Dalla Man Chiara , Place Jerome , Facchinetti Andrea , Guerra Stefania , Magni Lalo , De Nicolao Giuseppe , Cobelli Claudio , Renard Eric , Maran Alberto 
Published: January 2014

New effort has been made to develop closed-loop glucose control, using subcutaneous (SC) glucose sensing and continuous subcutaneous insulin infusion (CSII) from a pump, and a control algorithm. An approach based on a model predictive control (MPC) algorithm has been utilized during closed-loop control in type 1 diabetes patients. Here we describe the preliminary clinical experience with this approach. In Padova, two out of three subjects showed better performance with the closed-loop system compared to open loop. Altogether, mean overnight plasma glucose (PG) levels were 134 versus 111 mg/dl during open loop versus closed loop, respectively. The percentage of time spent at PG > 140 mg/dl was 45% versus 12%, while postbreakfast mean PG was 165 versus 156 mg/dl during open loop versus closed loop, respectively. Also, in Montpellier, two patients out of three showed a better glucose control during closed-loop trials. Avoidance of nocturnal hypoglycemic excursions was a clear benefit during algorithm-guided insulin delivery in all cases. This preliminary set of studies demonstrates that closed-loop control based entirely on SC glucose sensing and insulin delivery is feasible and can be applied to improve glucose control in patients with type 1 diabetes, although the algorithm needs to be further improved to achieve better glycemic control. Six type 1 diabetes patients (three in each of two clinical investigation centers in Padova and Montpellier), using CSII, aged 36 ± 8 and 48 ± 6 years, duration of diabetes 12 ± 8 and 29 ± 4 years, hemoglobin A1c 7.4% ± 0.1% and 7.3% ± 0.3%, body mass index 23.2 ± 0.3 and 28.4 ± 2.2 kg/m2, respectively, were studied on two occasions during 22 h overnight hospital admissions 2–4 weeks apart. A Freestyle Navigator® continuous glucose monitor and an OmniPod® insulin pump were applied in each trial. Admission 1 used open-loop control, while admission 2 employed closed-loop control using our MPC algorithm.