bluuebunny/crossref_metadata_2025 huggingface dataset:
Accuracy and Precision of the Axis-Shield Afinion Hemoglobin A1c Measurement Device
Authors: Wood Jamie R. , Kaminski Brett M. , Kollman Craig , Beck Roy W. , Hall Callyn A. , Yun Jason P. , Cengiz Eda , Haller Michael J. , Hassan Krishna , Klingensmith Georgeanna J. , Tamborlane William V.
Published: January 2014

Background:

The Afinion HbA1c (Axis-Shield) is a newer point-of-care device for measurement of hemoglobin A1c (A1C) using a boronate affinity method unlike the more commonly used DCA immunoassay method (Siemens Medical Solutions Diagnostics). The Afinion's accuracy and precision, when compared with high-performance liquid chromatography (HPLC) and DCA methods, have not been established in pediatric practice settings.

Methods:

Capillary blood was collected from 700 subjects with diabetes mellitus at seven Pediatric Diabetes Consortium sites. Each subject's A1C was measured locally using Afinion and DCA devices, and by a central laboratory (University of Minnesota) using a Tosoh HPLC method. In addition, repeated measurements on six whole blood samples provided by the National Glycohemoglobin Standardization Program (NGSP) were taken at three clinical centers using the Afinion and DCA methods and centrally using the Tosoh HPLC method to assess the precision of each device.

Results:

The coefficient of variation for measurements of whole blood samples for precision analysis was 2% for Afinion, 3% for DCA, and 1% for HPLC. In the patient samples measured at the seven clinic sites, the Afinion generated higher A1C results than the HPLC (mean difference = +0.15; p < 0.001), while the DCA produced lower values (mean difference = −0.19; p < 0.001). The absolute differences with HPLC were similar for the Afinion and DCA (median 0.2%) with a slight advantage for the Afinion when compared with DCA ( p < 0.001 by rank test). The DCA tended to read lower than HPLC, particularly at high A1C levels ( p < 0.001), while the Afinion's accuracy did not vary by A1C.

Conclusions:

When compared to the central laboratory HPLC method, the differences between the results of the Afinion and DCA devices are clinically insignificant, and the Afinion and DCA have similar accuracy and precision when used in pediatric practice settings.
The Accuracy of Point-of-Care Glucose Measurements
Authors: Rebel Annette , Rice Mark A. , Fahy Brenda G.
Published: January 2014

Control of blood glucose (BG) in an acceptable range is a major therapy target for diabetes patients in both the hospital and outpatient environments. This review focuses on the state of point-of-care (POC) glucose monitoring and the accuracy of the measurement devices. The accuracy of the POC glucose monitor depends on device methodology and other factors, including sample source and collection and patient characteristics. Patient parameters capable of influencing measurements include variations in pH, blood oxygen, hematocrit, changes in microcirculation, and vasopressor therapy. These elements alone or when combined can significantly impact BG measurement accuracy with POC glucose monitoring devices (POCGMDs). In general, currently available POCGMDs exhibit the greatest accuracy within the range of physiological glucose levels but become less reliable at the lower and higher ranges of BG levels. This issue raises serious safety concerns and the importance of understanding the limitations of POCGMDs. This review will discuss potential interferences and shortcomings of the current POCGMDs and stress when these may impact the reliability of POCGMDs for clinical decision-making.
Tighter Accuracy Standards within Point-of-Care Blood Glucose Monitoring: How Six Commonly Used Systems Compare
Authors: Robinson Charlotte S. , Sharp Patrick
Published: January 2014

Introduction:

Blood glucose monitoring systems (BGMS) are used in the hospital environment to manage blood glucose levels in patients at the bedside. The International Organization for Standardization (ISO) 15197:2003 standard is currently used by regulatory bodies as a minimum requirement for the performance of BGMS, specific to self-testing. There are calls for the tightening of accuracy requirements and implementation of a standard specifically for point-of-care (POC) BGMS.

Methods:

The accuracy of six commonly used BGMS was assessed in a clinical setting, with 108 patients' finger stick capillary samples. Using the accuracy criteria from the existing standard and a range of tightened accuracy criteria, system performance was compared. Other contributors to system performance have been measured, including hematocrit sensitivity and meter error rates encountered in the clinical setting.

Results and Discussion:

Five of the six BGMS evaluated met current accuracy criteria within the ISO 15197 standard. Only the Optium Xceed system had >95% of all readings within a tightened criteria of ±12.5% from the reference at glucose levels ≥72 mg/dl (4 mmol/liter) and ±9 mg/dl (0.5 mmol/liter) at glucose levels <72 mg/dl (4 mmol/liter). The Nova StatStrip Xpress had the greatest number of error messages observed; Optium Xceed the least. OneTouch Ultra2, Nova StatStrip Xpress, Accu-Chek Performa, and Contour TS products were all significantly influenced by blood hematocrit levels.

Conclusions:

From evidence obtained during this clinical evaluation, the Optium Xceed system is most likely to meet future anticipated accuracy standards for POC BGMS. In this clinical study, the results demonstrated the Optium Xceed product to have the highest level of accuracy, to have the lowest occurrence of error messages, and to be least influenced by blood hematocrit levels.
Safety and Efficacy of Mild Compression (18–25 mm Hg) Therapy in Patients with Diabetes and Lower Extremity Edema
Authors: Wu Stephanie C. , Crews Ryan T. , Najafi Bijan , Slone-Rivera Nancy , Minder Jessica L. , Andersen Charles A.
Published: January 2014

Background:

Patients with diabetes often present with lower extremity (LE) edema; however, because of concomitant peripheral arterial disease, compression therapy is generally avoided by providers in fear of compromising arterial circulation. This pilot study sought to assess whether diabetic socks with mild compression (18–25 mm Hg) can reduce LE edema in patients with diabetes without negatively impacting vascularity.

Methods:

Eighteen subjects (9 males, 9 females) aged 61 ± 11 years with diabetes, LE edema, and a mean ankle-brachial index (ABI) of 1.10 ± 0.21 successfully completed this uncontrolled study. At baseline, subjects were fitted and instructed to wear the socks during all waking hours. Follow-up visits occurred weekly for four consecutive weeks. Edema was quantified through midfoot, ankle, and calf circumferences and cutaneous fluid measurements. Vascular status was tracked via ABI.

Results:

Repeated measures analysis of variance and least significant difference post hoc analyses were used for data analyses. Calf circumferences showed a statistically significant ( p < .05) decrease of 1.3 ± 0.28 cm after just one week and remained significantly smaller than baseline throughout the study. Foot circumferences were significantly reduced at week 2 (-0.98 ± 0.35 cm) and remained significantly below baseline for the remainder of the study. The ankle also demonstrated a trend of circumference reduction but was not statistically significant. Cutaneous edema significantly reduced by week 3 (-3.1 ± 1.3 U) and remained so at week 4. Ankle-brachial index significantly increased (0.14 ± 0.049) at week 2 but was not significantly higher at weeks 3 or 4. No adverse events occurred during the study.

Conclusions:

Mild compression therapy (18–25 mm Hg) decreased swelling in diabetes patients with LE edema without compromising vascularity.
Usage and Perceptions of Pen Injectors for Diabetes Management: A Survey of Type 2 Diabetes Patients in the United States
Authors: Toscano Deborah , Brice Jennifer , Alfaro Christina
Published: January 2014

Background:

This study was conducted to investigate type 2 diabetes mellitus (T2DM) patient perceptions of their pen injectors and determine which features were deemed most important to overall satisfaction.

Methods:

Frost & Sullivan conducted a Web-based survey of T2DM patients in the United States in November 2010. Survey participants were initially screened prior to full participation. A total of 1002 adult T2DM patients who were using a pen injector on a regular basis to administer their diabetes medication(s) were surveyed. The survey consisted of 24 questions focused on awareness and current usage of pen injectors by type and brand, specific features of pen injectors, and patients' preferences for and satisfaction with pen injectors.

Results:

The majority of surveyed patients were using prefilled pen injectors as compared with durable pens. The LANTUS SoloSTAR (sanofi-aventis) was reported to be the most commonly used pen. The LANTUS SoloSTAR was also ranked highly for overall satisfaction and likelihood of continued usage. Regardless of brand, most surveyed patients reported that they were likely to continue using their current pen. In general, the single most important feature for user satisfaction was an easy push-button injection.

Conclusions:

Ease of self-administration is of highest priority to users of pen injectors. Important features facilitating ease of use, such as an easily depressed push-button injection, are likely to minimize the burden on T2DM patients, thereby improving compliance and clinical outcomes.
The Challenges of Measuring Glycemic Variability
Authors: Rodbard David
Published: January 2014

This commentary reviews several of the challenges encountered when attempting to quantify glycemic variability and correlate it with risk of diabetes complications. These challenges include (1) immaturity of the field, including problems of data accuracy, precision, reliability, cost, and availability; (2) larger relative error in the estimates of glycemic variability than in the estimates of the mean glucose; (3) high correlation between glycemic variability and mean glucose level; (4) multiplicity of measures; (5) correlation of the multiple measures; (6) duplication or reinvention of methods; (7) confusion of measures of glycemic variability with measures of quality of glycemic control; (8) the problem of multiple comparisons when assessing relationships among multiple measures of variability and multiple clinical end points; and (9) differing needs for routine clinical practice and clinical research applications.
Pharmacokinetics and Postprandial Glycemic Excursions following Insulin Lispro Delivered by Intradermal Microneedle or Subcutaneous Infusion
Authors: McVey Elaine , Hirsch Laurence , Sutter Diane E. , Kapitza Christoph , Dellweg Sibylle , Clair Janina , Rebrin Kerstin , Judge Kevin , Pettis Ronald J.
Published: January 2014

Background:

Intradermal (ID) delivery has been shown to accelerate insulin pharmacokinetics (PK). We compared the PK and pharmacodynamic (PD) effects of insulin lispro administered before two daily standardized solid mixed meals (breakfast and lunch), using microneedle-based ID or traditional subcutaneous (SC) delivery.

Method:

The study included 22 subjects with type 1 diabetes in an eight-arm full crossover block design. One arm established each subject's optimal meal dose. In six additional arms, the optimal, higher, and lower doses (+30%, −30%) were each given ID and SC delivery, in random order. The final arm assessed earlier timing for the ID optimal dose (−12 versus −2 min). The PK/PD data were collected for 6 h following meals. Intravenous basal regular insulin was given throughout, and premeal blood glucose (BG) adjusted to 115 mg/dl.

Results:

The primary end point, postprandial time in range (70–180 mg/dl), showed no route-based differences with a high level of overall BG control for both SC and ID delivery. Secondary insulin PK end points showed more rapid ID availability versus SC across doses and meals (ΔTmax −16 min, ΔT50rising −7 min, ΔT50falling −30 min, all p < .05). Both intrasubject and intersubject variability for ID Tmax were significantly lower. Intradermal delivery showed modest, statistically significant secondary PD differences across doses and meals, generally within 90–120 min postprandially (Δ12 mg/dl BG at 90 min, Δ7 mg/dl BGmax, Δ7 mg/dl mean BG 0–2 h, all p < .05).

Conclusions:

This study indicates that ID insulin delivery is superior to SC delivery in speed of systemic availability and PK consistency and may improve postprandial glucose control.
A Review of a Family of Ultra-Rapid-Acting Insulins: Formulation Development
Authors: Krasner Alan , Pohl Roderike , Simms Patrick , Pichotta Philip , Hauser Robert , De Souza Errol
Published: January 2014

This review summarizes the clinical development of a family of ultra-rapid-acting recombinant human insulin formulations. These formulations use ethylenediaminetetraacetic acid (EDTA) to chelate zinc and thereby destabilize insulin hexamers. In addition, insulin monomer surface charges are chemically masked with citrate to prevent reaggregation. The first phase 1 trials were performed using BIOD-090, an acidic 25 unit U/ml insulin formulation, which contained disodium-EDTA (NaEDTA). When compared with regular human insulin (RHI) and/or insulin lispro in multiple phase 1 studies, BIOD-090 consistently showed more rapid absorption and/or onset of action. A standard meal challenge study also demonstrated improved postprandial glucose profiles associated with BIOD-090. However, increased patient exposure in larger phase 3 trials showed that this formulation was associated with an increased incidence of local injection site reactions, most commonly pain. A next generation formulation, BIOD-100, contained the same excipients as a standard insulin concentration of 100 U/ml. BIOD-100 maintained an ultra-rapid action profile and was associated with modest but significantly improved toleration when compared with BIOD-090. In order to further improve toleration, the hypothesis that NaEDTA contributed to discomfort by chelating endogenous calcium was tested by either substituting calcium-EDTA for NaEDTA or by adding calcium chloride to the NaEDTA formulation. These calcium formulations essentially eliminated the excess discomfort associated with BIOD-090 but were associated with less optimal pharmacokinetic profiles in humans. Recent efforts have succeeded in developing ultra-rapid-acting human insulin formulations with acceptable injection site toleration by optimizing concentrations of calcium (BIOD-125) and with the use of magnesium sulfate to mitigate discomfort (BIOD-123). Similar formulation technology has also been shown to accelerate absorption of insulin analogs in animal models.
Feasibility of Overnight Closed-Loop Control Based on Hourly Blood Glucose Measurements
Authors: Patte Caroline , Pleus Stefan , Galley Paul , Weinert Stefan , Haug Cornelia , Freckmann Guido
Published: January 2014

Introduction:

Safe and effective closed-loop control (artificial pancreas) is the ultimate goal of insulin delivery. In this study, we examined the performance of a closed-loop control algorithm used for the overnight time period to safely achieve a narrow target range of blood glucose (BG) concentrations prior to breakfast. The primary goal was to compare the quality of algorithm control during repeated overnight experiments.

Materials and Methods:

Twenty-three subjects with type 1 diabetes performed 2 overnight experiments on each of three visits at the study site, resulting in 138 overnight experiments. On the first evening, the subject's insulin therapy was applied; on the second, the insulin was delivered by an algorithm based on subcutaneous continuous glucose measurements (including meal control) until midnight. Overnight closed-loop control was applied between midnight and 6 a.m. based on hourly venous BG measurements during the first and second nights.

Results:

The number of BG values within the target range (90–150 mg/dl) increased from 52.9% (219 out of 414 measurements) during the first nights to 72.2% (299 out of 414 measurements) during the second nights ( p < .001, X2-test). The occurrence of hypoglycemia interventions was reduced from 14 oral glucose interventions, the latest occurring at 2:36 a.m. during the first nights, to 1 intervention occurring at 1:02 a.m. during the second nights ( p < .001, X2-test).

Conclusions:

Overnight controller performance improved when optimized initial control was given; this was suggested by the better metabolic control during the second night. Adequate controller run-in time seems to be important for achieving good overnight control. In addition, the findings demonstrate that hourly BG data are sufficient for the closed-loop control algorithm tested to achieve appropriate glycemic control.
Comparison of Patient Preference for Two Insulin Injection Pen Devices in Relation to Patient Dexterity Skills
Authors: Pfützner Andreas , Schipper Christina , Niemeyer Marcus , Qvist Marianne , Löffler Andrea , Forst Thomas , Musholt Petra B.
Published: January 2014

Background:

Impaired dexterity has been reported to be prevalent in diabetes patients independent from the existence of diabetic neuropathy. This study was performed to investigate the impact of dexterity impairment on patient preference for two insulin pen injection devices (InnoLet and FlexTouch).

Methods:

Ninety patients [54 male/36 female; age (mean ± standard deviation), 62 ± 8 years; disease duration, 18 ± 11 years; hemoglobin A1c, 7.2 ± 1.0%] were included in this investigation and were stratified into four different groups based on the results of a dexterity test (Jebsen—Taylor Hand Function Test) and assessment of visual impairment: 15 type 1 (group A) and 30 type 2 (group B) patients with impaired dexterity, 30 type 1/type 2 patients with visual impairment (group C), and 15 type 1/type 2 patients without any impairment (group D). The patients performed a cognitive function test (number connection test), were introduced to the devices in random order, and were asked to perform some mock injections before completing a six-item standardized preference questionnaire.

Results:

There was a strong preference for FlexTouch in all groups. All unimpaired patients (100%, group D) preferred FlexTouch, as did the vast majority in all other groups. Only 11% of the patients with impaired cognitive function preferred InnoLet, as did a few patients with more severely impaired dexterity or with visual impairment (group A, 13%; group B, 3%; group C, 14%).

Conclusions:

Patient dexterity skills may have an influence on device preference, especially if the impairment is more pronounced.
Performance of a New Speech Translation Device in Translating Verbal Recommendations of Medication Action Plans for Patients with Diabetes
Authors: Soller R. William , Chan Philip , Higa Amy
Published: January 2014

Background:

Language barriers are significant hurdles for chronic disease patients in achieving self-management goals of therapy, particularly in settings where practitioners have limited nonprimary language skills, and in-person translators may not always be available. S-MINDS© (Speaking Multilingual Interactive Natural Dialog System), a concept-based speech translation approach developed by Fluential Inc., can be applied to bridge the technologic gaps that limit the complexity and length of utterances that can be recognized and translated by devices and has the potential to broaden access to translation services in the clinical settings.

Methods:

The prototype translation system was evaluated prospectively for accuracy and patient satisfaction in underserved Spanish-speaking patients with diabetes and limited English proficiency and was compared with other commercial systems for robustness against degradation of translation due to ambient noise and speech patterns.

Results:

Accuracy related to translating the English-Spanish-English communication string from practitioner to device to patient to device to practitioner was high (97–100%). Patient satisfaction was high (means of 4.7–4.9 over four domains on a 5-point Likert scale). The device outperformed three other commercial speech translation systems in terms of accuracy during fast speech utterances, under quiet and noisy fluent speech conditions, and when challenged with various speech disfluencies (i.e., fillers, false starts, stutters, repairs, and long pauses).

Conclusions:

A concept-based English-Spanish speech translation system has been successfully developed in prototype form that can accept long utterances (up to 20 words) with limited to no degradation in accuracy. The functionality of the system is superior to leading commercial speech translation systems.
Self-Monitoring of Blood Glucose: One STeP Forward?
Authors: Schramm Wendelin
Published: January 2014

Introduction:

In times of short health care budgets, reimbursement for self-monitoring of blood glucose (SMBG) in diabetes patients without insulin treatment is subject to debate. The Structured Testing Program (STeP) trial found a positive correlation of test frequency and improved hemoglobin A1c (HbA1c) levels in poorly controlled type 2 diabetes patients not treated with insulin.

Methods:

A structured literature search for other clinical studies reporting on SMBG frequency was performed.

Results:

There is scarce evidence: Three trials, including STeP, noted a significant and relevant correlation between testing frequency and improved HbA1c levels (FA effect), whereas two studies did not. The comparability between the identified studies is problematic.

Conclusion:

Future research should consider correlations between testing frequency and level of glycemic control. More emphasis should be placed on a structured approach to use SMBG and to address adherence to testing and therapy.
Continuous Glucose Monitoring Accuracy Results Vary between Assessment at Home and Assessment at the Clinical Research Center
Authors: Luijf Yoeri M. , Avogaro Angelo , Benesch Carsten , Bruttomesso Daniela , Cobelli Claudio , Ellmerer Martin , Heinemann Lutz , Mader Julia K. , DeVries J. Hans
Published: January 2014

Background:

Continuous glucose monitoring system (CGMS) accuracy is of critical importance both in delivering therapeutic value and as a component of a closed-loop system. This study aims at assessing the differences between accuracy assessments of CGMS at home and at the clinical research center (CRC).

Methods:

Twelve patients with type 1 diabetes used the Dexcom® SEVEN® PLUS (DexCom, Inc.) CGMS for 7 days. Patients performed ≥6 finger pricks [self-measurement of blood glucose (SMBG)] per day while at home. Reference blood glucose measurements were taken during a 24 h CRC admission (YSI 2300 STAT Plus™). Continuous glucose monitoring system data were compared with YSI and SMBG values. Outcome measures included mean absolute relative difference (MARD) and Clarke error grid analysis (CEGA).

Results:

During CRC admission, the MARD of CGMS vs YSI glucose values was 19.2% ( n = 509)—significantly higher than 16.8% at home ( n = 611) ( p = .004). In the hypoglycemic range, MARD was 23.9% at CRC ( n = 26)—not significantly different from 41.6% at home ( n = 39) ( p = .269). In the hyperglycemic range, CRC MARD at 20.3% ( n = 115) was significantly higher than home MARD at 11.2% ( n = 118) ( p = .001). Clarke error grid analysis showed no significant difference in distribution of data pairs (overall p = .317).

Conclusions:

This study illustrates the importance of the setting used when assessing CGMS accuracy. Continuous glucose monitoring system accuracy at home appeared better than at the CRC. This is probably due to the higher sampling rate of reference measurements, feasible only in the CRC. Testing CGMS accuracy in the CRC provides valuable information over and above home testing.
Inpatient Studies of a Kalman-Filter-Based Predictive Pump Shutoff Algorithm
Authors: Cameron Fraser , Wilson Darrell M. , Buckingham Bruce A. , Arzumanyan Hasmik , Clinton Paula , Chase H. Peter , Lum John , Maahs David M. , Calhoun Peter M. , Bequette B. Wayne
Published: January 2014

Background:

An insulin pump shutoff system can prevent nocturnal hypoglycemia and is a first step on the pathway toward a closed-loop artificial pancreas. In previous pump shutoff studies using a voting algorithm and a 1 min continuous glucose monitor (CGM), 80% of induced hypoglycemic events were prevented.

Methods:

The pump shutoff algorithm used in previous studies was revised to a single Kalman filter to reduce complexity, incorporate CGMs with different sample times, handle sensor signal dropouts, and enforce safety constraints on the allowable pump shutoff time.

Results:

Retrospective testing of the new algorithm on previous clinical data sets indicated that, for the four cases where the previous algorithm failed (minimum reference glucose less than 60 mg/dl), the mean suspension start time was 30 min earlier than the previous algorithm. Inpatient studies of the new algorithm have been conducted on 16 subjects. The algorithm prevented hypoglycemia in 73% of subjects. Suspension-induced hyperglycemia is not assessed, because this study forced excessive basal insulin infusion rates.

Conclusions:

The new algorithm functioned well and is flexible enough to handle variable sensor sample times and sensor dropouts. It also provides a framework for handling sensor signal attenuations, which can be challenging, particularly when they occur overnight.
Autonomic Markers of Impaired Glucose Metabolism: Effects of Sleep-Disordered Breathing
Authors: Wang Wenli , Redline Susan , Khoo Michael C. K.
Published: January 2014

Background:

The association between diabetes and abnormalities in autonomic function is well-known, but it is not clear if this association can be extended to subjects with prediabetic impaired glucose metabolism (IGM). Sleep-disordered breathing (SDB), which commonly occurs in this population, is often overlooked. We sought to determine how autonomic function, monitored in an overnight sleep study setting, may be impaired in subjects with IGM and/or SDB.

Methods:

Polysomnograms (PSGs) selected from the Cleveland Family Study database were categorized into four groups: normal, SDB (respiratory disturbance index > 5/h), IGM, and both SDB and IGM. Impaired glucose metabolism was defined as an oral glucose tolerance test (OGTT) level > 140 mg/dl. Time-domain and frequency-domain indices of heart rate variability were used to quantify autonomic impairment. Baroreflex sensitivity determined using pulse transit time (BRSPTT), an indirect measure of baroreflex sensitivity based on spontaneous pulse transit time fluctuations, was used as a surrogate measure of baroreflex sensitivity.

Results:

Based on 31 PSGs from subjects (16 males, 15 females) ages 20.8–61.2 years, both SDNN and BRSPTT were found to be 20–25% lower in SDB and ∼40% lower in IGM and SDB + IGM as compared to subjects without either condition. In analyses of continuous measures, mean standard deviation of 5 min R-R intervals (SDNN) and BRSPTT were found to be negatively correlated with OGTT following adjustment for age and body mass index. Oral glucose tolerance test and age were the two most significant factors for predicting SDNN and BRSPTT.

Conclusions:

Our analyses suggest that cardiac autonomic control is impaired in IGM, regardless of whether SDB is present. The abnormal autonomic function involves degradation of baroreflex regulation.
Pilot Study of the SPRINT Glycemic Control Protocol in a Hungarian Medical Intensive Care Unit
Authors: Benyo Balazs , Illyés Attila , Némedi Noémi Szabó , Le Compte Aaron J. , Havas Attila , Kovacs Levente , Fisk Liam , Shaw Geoffrey M. , Chase J. Geoffrey
Published: January 2014

Introduction:

Stress-induced hyperglycemia increases morbidity and mortality. Tight control can reduce mortality but has proven difficult to achieve. The SPRINT (Specialized Relative Insulin and Nutrition Tables) protocol is the only protocol that reduced both mortality and hypoglycemia by modulating both insulin and nutrition, but it has not been tested in independent hospitals.

Methods:

SPRINT was used for 12 adult intensive care unit patients (949 h) at Kálmán Pándy Hospital (Gyula, Hungary) as a clinical practice assessment. Insulin recommendations (0–6 U/h) were administered via constant infusion rather than bolus delivery. Nutrition was administered per local standard protocol, weaning parenteral to enteral nutrition, but was modulated per SPRINT recommendations. Measurement was every 1 to 2 h, per protocol. Glycemic performance is assessed by percentage of blood glucose (BG) measurements in glycemic bands for the cohort and per patient. Safety from hypoglycemia is assessed by numbers of patients with BG <2.2 (severe) and %BG <3.0 and <4.0 mmol/liter (moderate and light). Clinical effort is assessed by measurements per day. Results are median (interquartile range).

Results:

There were 742 measurements over 1088 h of control (16.4 measurements/day), which is similar to clinical SPRINT results (16.2/day). Per-patient hours of control were 65 (50–95) h. Initial per-patient BG was 10.5 (7.9–11.2) mmol/liter. All patients (100%) reached 6.1 mmol/liter. Cohort BG was 6.3 (5.5–7.5) mmol/liter, with 42.2%, 65.1% and 77.6% of BG in the 4.0–6.1, 4.0–7.0, and 4.0–8.0 mmol/liter bands. Per-patient, median percentage time in these bands was 40.2 (26.7–51.5)%, 62.5 (46.0–75.7)%, and 74.7 (61.6.8–87.8)%, respectively. No patients had BG <2.2 mmol/liter, and the %BG <4.0 mmol/liter was 1.9%. These results were achieved using 3.0 (3.0–5.0) U/h of insulin with 7.4 (4.4–10.2) g/h of dextrose administration (all sources) for the cohort. Per-patient median insulin administration was 3.0 (3.0–3.0) U/h and 7.1 (3.4–9.6) g/h dextrose. Higher carbohydrate nutrition formulas than were used in SPRINT are offset by slightly higher insulin administration in this study.

Conclusions:

The glycemic performance shows that using the SPRINT protocol to guide insulin infusions and nutrition administration provided very good glycemic control in initial pilot testing, with no severe hypoglycemia. The overall design of the protocol was able to be generalized with good compliance and outcomes across geographically distinct clinical units, patients, and clinical practice.
Minding the Gaps in Continuous Glucose Monitoring: A Method to Repair Gaps to Achieve More Accurate Glucometrics
Authors: Fonda Stephanie J. , Lewis Drew G. , Vigersky Robert A.
Published: January 2014

Estimation of glycemic variability requires frequent measures of glucose and is greatly aided by continuous glucose monitoring (CGM); however, under real-world conditions, missing data or “gaps” of ≥ 10 minutes can occur in CGM data, affecting the reliability of certain estimates. Thus, we determined the magnitude of the gap problem as observed in a cohort of patients with type 2 diabetes and demonstrated an approach to fill the gaps. The approach takes the difference between readings before and after a gap and distributes the difference equally across the number of missing readings, as determined by the sensor's setting for reading frequency. The approach is easy to implement, conservative, and improves estimation of variability measures that reference time, namely, mean of daily differences and continuous overlapping net glycemic action.
Stepwise Self-Titration of Oral Glucose-Lowering Medication Using a Mobile Telephone-Based Telehealth Platform in Type 2 Diabetes: A Feasibility Trial in Primary Care
Authors: Nagrebetsky Alexander , Larsen Mark , Craven Anthea , Turner Jane , McRobert Nicky , Murray Elizabeth , Gibson Oliver , Neil Andrew , Tarassenko Lionel , Farmer Andrew
Published: January 2014

Background:

Telehealth-supported clinical interventions may improve diabetes self-management. We explored the feasibility of stepwise self-titration of oral glucose-lowering medication guided by a mobile telephone-based telehealth platform for improving glycemic control in type 2 diabetes.

Methods:

We recruited 14 type 2 diabetes patients to a one-year feasibility study with 1:1 randomization. Intervention group patients followed a stepwise treatment plan for titration of oral glucose-lowering medication with self-monitoring of glycemia using real-time graphical feedback on a mobile telephone and remote nurse monitoring using a Web-based tool. We carried out an interim analysis at 6 months.

Results:

We screened 3476 type 2 diabetes patients; 94% of the ineligible did not meet the eligibility criteria for hemoglobin A1c (HbA1c) or current treatment. Mean (standard deviation) patient age at baseline was 58 (11) years, HbA1c was 65 (12) mmol/mol (8.1% [1.1%]), body mass index was 32.9 (6.4) kg/m2, median [interquartile range (IQR)] diabetes duration was 2.6 (0.6 to 4.7) years, and 10 (71%) were men. The median (IQR) change in HbA1c from baseline to six months was −10 (−21 to 3) mmol/mol (−0.9% [-1.9% to 0%]) in the intervention group and −5 (−13 to 6) mmol/mol (−0.5% [-1.2% to 0.6%]) in the control group. Six out of seven intervention group patients and four out of seven control group patients changed their oral glucose-lowering medication ( p = .24).

Conclusions:

Self-titration of oral glucose-lowering medication in type 2 diabetes with self-monitoring and remote monitoring of glycemia is feasible, and further studies using adapted recruitment strategies are required to evaluate whether it improves clinical outcomes.
Variability of Blood Glucose Meters for Patient Self-Testing: Analysis of the Article by Brazg and Coauthors
Authors: Pfützner Andreas
Published: January 2014

The article by Brzag and coauthors in this issue of Journal of Diabetes Science and Technology reports a competitive accuracy performance study for a branded meter in comparison with six low-cost meters currently available in the United States. It highlights several important topics: (1) the need for more stringent post-marketing requirements for blood glucose meters after launch and (2) low-cost meters use older technologies and their manufacturers do not usually seriously invest in new technology or constant quality assurance efforts. This may explain the study results, which show superior performance of the branded meter. Finally, the article pinpoints to the “quality versus price” dilemma faced by the prescribing physician and their patients in daily routine, which may be additionally aggravated by budget constraints and prescription rules in reimbursed markets.
Multilevel Model of Type 1 Diabetes Mellitus Patients for Model-Based Glucose Controllers
Authors: Garcia-Gabin Winston , Jacobsen Elling W.
Published: January 2014

Background:

Glucose homeostasis is the result of complex interactions across different biological levels. This multilevel characteristic should be considered when analyzing and designing closed-loop glucose control algorithms. Classic control schemes use only a pharmacokinetic-pharmacodynamic (PKPD) perspective to describe the glucoregulatory system.

Methods:

A multilevel model combining a PKPD model with an insulin signaling model is proposed for patients with type 1 diabetes mellitus T1DM (T1DM). The PKPD Dalla Man model for T1DM is expanded to include an intracellular level involving insulin signaling to control glucose uptake through glucose transporter type 4 (GLUT4) translocation. A model-based controller is then designed and used as an example to illustrate the feasibility of the proposal.

Results:

Two significant results were obtained for the controller explicitly utilizing multilevel information. No hypoglycemic events were registered and an excellent performance for interpatient variability was achieved. Controller performance was evaluated using two indexes. The glucose was kept inside the range (70–180) mg/dl more than 99% of the time, and the intrapatient variability measured using control variability grid analysis was solid with 90% of the population inside the target zone.

Conclusions:

Multilevel models open new possibilities for designing glucose control algorithms. They allow controllers to take into account variables that have a strong influence on glucose homeostasis. A model-based controller was used for demonstrating how improved knowledge of the multilevel nature of diabetes increases the robustness and performance of glucose control algorithms. Using the proposed multilevel approach, a reduction of the hypoglycemic risk and robust behaviour for intrapatient variability was demonstrated.
Mobile Applications for Diabetes Self-Management: Status and Potential
Authors: El-Gayar Omar , Timsina Prem , Nawar Nevine , Eid Wael
Published: January 2014

Background:

Advancements in smartphone technology coupled with the proliferation of data connectivity has resulted in increased interest and unprecedented growth in mobile applications for diabetes self-management. The objective of this article is to determine, in a systematic review, whether diabetes applications have been helping patients with type 1 or type 2 diabetes self-manage their condition and to identify issues necessary for large-scale adoption of such interventions.

Methods:

The review covers commercial applications available on the Apple App Store (as a representative of commercially available applications) and articles published in relevant databases covering a period from January 1995 to August 2012. The review included all applications supporting any diabetes self-management task where the patient is the primary actor.

Results:

Available applications support self-management tasks such as physical exercise, insulin dosage or medication, blood glucose testing, and diet. Other support tasks considered include decision support, notification/alert, tagging of input data, and integration with social media. The review points to the potential for mobile applications to have a positive impact on diabetes self-management. Analysis indicates that application usage is associated with improved attitudes favorable to diabetes self-management. Limitations of the applications include lack of personalized feedback; usability issues, particularly the ease of data entry; and integration with patients and electronic health records.

Conclusions:

Research into the adoption and use of user-centered and sociotechnical design principles is needed to improve usability, perceived usefulness, and, ultimately, adoption of the technology. Proliferation and efficacy of interventions involving mobile applications will benefit from a holistic approach that takes into account patients' expectations and providers' needs.
Employment Rights of People with Diabetes: Changing Technology and Changing Law
Authors: Griffin John W.
Published: January 2014

Though the treatment of diabetes has advanced remarkably, the law and many employers have not always kept pace. New insulins, delivery systems, and monitoring systems give people with diabetes exceptional control over their blood sugar and virtually eliminate serious complications such as hypoglycemia and hyperglycemia. Changes in the law, particularly the Americans with Disabilities Act and its 2008 amendments, give people with diabetes greater rights and employment opportunities than ever before. Despite these advances, many employers continue to use blanket bans or ill-considered standards to bar people with diabetes. Efforts to break down these remaining barriers are ongoing through employee litigation and through the American Diabetes Association's collaboration with entities that set occupational standards.
Analysis of a Remote System to Closely Monitor Glycemia and Insulin Pump Delivery—Is This the Beginning of a Wireless Transformation in Diabetes Management?
Authors: Cengiz Eda
Published: January 2014

Episodes of hypoglycemia and hyperglycemia in between blood glucose checks—especially during sleep—can go unrecognized for children and adolescents with type 1 diabetes mellitus (T1DM). Continuous glucose monitoring (CGM) systems have introduced a new tool to monitor glucose levels for people with diabetes in real time and to alert them when glucose levels are above or below target range. However, many of the alarms are not heard at night by the children or adolescents or by their parents who oversee their treatment. The mySentry™ system is a device that is designed to relay real-time insulin pump and CGM data for display elsewhere in the house. In this issue of Journal of Diabetes Science and Technology, Kaiserman and coauthors report on the acceptability, usefulness, and user friendliness of the mySentry for families with children and adolescents with T1DM, which was determined by survey results during a 3-week study period. Based on the results, the mySentry system met all predefined criteria for acceptability without safety issues in this small-scale, short-term study and as an example of wireless systems integration in diabetes management.
Several Steps Forward: A New Meter for Multiple Patient Use
Authors: Le Huong T. , Rice Mark J.
Published: January 2014

Point-of-care (POC) blood glucose testing is becoming ubiquitous in the hospitals because of ease of use, timely results, and cost effectiveness. Historically, these POC devices were designed and regulated for home use by patients with diabetes. Their transition into the hospital multipatient setting has introduced the real risk of cross-contamination and has exposed inadequate accuracy standards. This article highlights some of the current recommendations for these devices and focuses on a new meter that addresses these issues. Although not currently approved for use in the United States, the OneTouch® Verio®Pro blood glucose meter (LifeScan, Inc.), which is the topic of an article by MacRury and coauthors in this issue of the Journal of Diabetes Science and Technology, is a step forward with minimal interferences and good accuracy, and perhaps most importantly, is robust enough to withstand rigorous disinfection.
Oral Insulin Delivery: How Far are We?
Authors: Fonte Pedro , Araújo Francisca , Reis Salette , Sarmento Bruno
Published: January 2014

Oral delivery of insulin may significantly improve the quality of life of diabetes patients who routinely receive insulin by the subcutaneous route. In fact, compared with this administration route, oral delivery of insulin in diabetes treatment offers many advantages: Higher patient compliance, rapid hepatic insulinization, and avoidance of peripheral hyperinsulinemia and other adverse effects such as possible hypoglycemia and weight gain. However, the oral delivery of insulin remains a challenge because its oral absorption is limited. The main barriers faced by insulin in the gastrointestinal tract are degradation by proteolytic enzymes and lack of transport across the intestinal epithelium. Several strategies to deliver insulin orally have been proposed, but without much clinical or commercial success. Protein encapsulation into nanoparticles is regarded as a promising alternative to administer insulin orally because they have the ability to promote insulin paracellular or transcellular transport across the intestinal mucosa. In this review, different delivery systems intended to increase the oral bioavailability of insulin will be discussed, with a special focus on nanoparticulate carrier systems, as well as the efforts that pharmaceutical companies are making to bring to the market the first oral delivery system of insulin. The toxicological and safety data of delivery systems, the clinical value and progress of oral insulin delivery, and the future prospects in this research field will be also scrutinized.
Safety Events during an Automated Telephone Self-Management Support Intervention
Authors: Lyles Courtney R. , Schillinger Dean , Lopez Andrea , Handley Margaret , Ratanawongsa Neda , Sarkar Urmimala
Published: January 2014

Background:

Interactive health information technology (HIT) can support the complex self-management tasks for diabetes. However, less is known about between-visit interactions and patient safety among chronic illness patients treated in the outpatient setting.

Methods:

We classified 13 categories for safety events and potential safety events within a larger trial evaluating a multilingual automated telephone self-management support system for diabetes using interactive voice response. Participants could trigger safety concerns by reporting hyperglycemia or hypoglycemia, inability to obtain medications, medication nonadherence and side effects, and needing appointments and/or supplies. We then examined these triggers across patient demographic and health characteristics to determine which patients were most likely to experience safety events.

Results:

Overall, there were 360 safety triggers that occurred among 155 participants, which represented 53% of individuals and 7.6% of all automated calls over the 27-week intervention. The most common triggers were for pain or medication side effects (22%) and not checking blood sugars (13%). In adjusted models, race/ethnicity and language were related to safety triggers; Spanish-speaking participants were significantly ( p = .02) more likely than English-speaking participants to experience a safety trigger, and black participants were marginally more likely ( p = .09) than white participants to experience a safety trigger.

Conclusion:

About half of patients enrolled in a self-management technology intervention triggered at least one potential safety event over the course of the trial, and this was more frequent among some patients. Systems implementing HIT strategies to improve self-care and remote monitoring should consider specific program design elements to address these potential safety events.
The Impact of Using Mobile-Enabled Devices on Patient Engagement in Remote Monitoring Programs
Authors: Agboola Stephen , Havasy Rob , Myint-U Khinlei , Kvedar Joseph , Jethwani Kamal
Published: January 2014

Background:

Different types of data transmission technologies are used in remote monitoring (RM) programs. This study reports on a retrospective analysis of how participants engage, based on the type of data transfer technology used in a blood pressure (BP) RM program, and its potential impact on RM program design and outcomes.

Methods:

Thirty patients, aged 23–84 years (62 ± 14 years), who had completed at least 2 months in the program and were not participating in any other clinical trial were identified from the Remote Monitoring Data Repository. Half of these patients used wireless-based data transfer devices [wireless-based device (WBD)] while the other half used telephone modem-based data transfer devices [modem-based device (MBD)]. Participants were matched by practice and age. Engagement indices, which include frequency of BP measurements, frequency of data uploads, time to first BP measurement, and time to first data upload, were compared in both groups using the Wilcoxon-Mann-Whitney two-sample rank-sum test. Help desk call data were analyzed by Chi square test.

Results:

The frequency of BP measurements and data uploads was significantly higher in the WBD group versus the MBD group [median = 0.66 versus 0.2 measurements/day ( p = .01) and 0.46 versus 0.01 uploads/day ( p < .001), respectively]. Time to first upload was significantly lower in the WBD group (median = 4 versus 7 days; p = .02), but time to first BP measurement did not differ between the two groups (median = 2 versus 1 day; p = .98).

Conclusion:

Wireless transmission ensures instantaneous transmission of readings, providing clinicians timely data to intervene on. Our findings suggest that mobile-enabled wireless technologies can positively impact patient engagement, outcomes, and operational workflow in RM programs.
Sonographic Detection of a Heterotopic Pregnancy in Natural Conception
Authors: Bildner Amy M.
Published: January 2014

Visualization of a first trimester pregnancy, whether normal or abnormal, is best done using sonography. Heterotopic pregnancies, the combination of an intrauterine and an extrauterine pregnancy, provide a difficult diagnosis as the intrauterine pregnancy gives a sense of false assurance. This case study presents a spontaneous heterotopic pregnancy with one viable intrauterine pregnancy and one ruptured ectopic pregnancy and discusses the role that sonography plays in the detection and management of this problem.