Percentage Time In Target Range Research Articles

Retrospective, observational study to see the effect of evogliptin on continuous glucose monitoring (CGM) in T2DM Indian patients: A real-world experience

This study aimed to assess effectiveness of Evogliptin 5 mg through continues glucose monitoring (CGM) in patients with T2DM in retrospective observational real world settings. Overall 6 patients who received Evogliptin as routine clinical practice in management of T2DM were analyzed retrospectively from single center. Data collected from past medical records. FreeStyle Librepro 1.0.6 was used for CGM. CGM was done 15 days prior to adding Evogliptin and repeated immediately after that for next 15 days. Mean BG level, Percentage time in target range (80-140mg/dl), Percentage time above target and Percentage time below target were assessed prior and after adding Evogliptin in existing treatment regimen. Significant reduction in Mean blood glucose level seen after adding Evogliptin in existing treatment regimen from 215 mg/dl to 138 mg/dl (-77 mg/dl P=0.006). Significant improvement seen in Percentage time in target range (80-140mg/dl) from 17% to 44% (27% P value 0.007) and in Percentage time above target from 81% to 43% (- 38%, P valve 0.003). 13.5 % of the patients seen below target. Evogliptin was found to be effective when added to the patients who were uncontrolled on other oral anti-diabetic medications. It effectively showed improvement in continues glucose monitoring (CGM) parameters like Mean blood glucose, more number of patients were in Time in Target range i.e (80-140mg/dl) after adding Evogliptin to existing anti-diabetic medications & well tolerated. Small sample size and retrospective study

Real-World, Patient-Reported and Clinic Data from Individuals with Type 1 Diabetes Using the MiniMed 670G Hybrid Closed-Loop System.

Background: The purpose of this study was to collect 1 year of real-world data from individuals with type 1 diabetes (T1D) initiating the Medtronic 670G hybrid closed-loop insulin delivery system as part of usual care. We sought to expand current knowledge to understand how use of the system impacts patient-reported outcomes, in addition to clinical outcomes, for children and adults with T1D. Methods: Questionnaires were completed by the participant (and/or parent) before initiation of the 670G system (baseline) and at 6 weeks, 6 months, and 12 months from enrollment. Clinical data were obtained at routine clinical visits. Results: Of 132 participants who initiated Auto Mode, 80 completed the 12-month questionnaires while persisting with the system. Nearly all reported receiving adequate training on the 670G. Participant and parent-reported fear of hypoglycemia decreased by 6 and 11 points, respectively, from baseline to 12 months. More than half reported issues with sleep interruption at night due to alarms and 40% did not like frequent exits from Auto Mode. For the subset who had complete continuous glucose monitor data (n = 27), mean percent time in target range (70-180 mg/dL) was 66% at baseline, and 74% and 68% at 6 and 12 months, respectively. Conclusions: With this study, we have captured real-time feedback from patients with T1D who initiated the 670G system and continued to use it over 12 months regarding their experience with the system. This has helped to illuminate both benefits and burdens associated with the first commercially available hybrid closed-loop system.

Safety Evaluation of the Omnipod® 5 Automated Insulin Delivery System Over Three Months of Use in Children With Type 1 Diabetes (T1D)

Advances in diabetes technology have transformed the treatment paradigm for T1D, yet the burden of the disease remains significant. The pediatric population poses unique challenges to glucose management with unpredictable exercise and food consumption. The Omnipod 5 System is a novel hybrid closed-loop (HCL) system with fully on-body operation. A tubeless insulin pump (pod) containing a personalized Model Predictive Control algorithm communicates directly with a Dexcom G6 continuous glucose monitor (CGM, or sensor) to automate insulin delivery. Therapy customization is enabled through glucose targets from 110–150 mg/dL, adjustable by time of day, which is a critical component to individualize glucose management in children. We report on the first, pivotal outpatient safety evaluation of the Omnipod 5 System in a large cohort of children with T1D.Participants aged 6–13.9y with T1D≥6 months and A1C<10% used the HCL system for 3 months at home after a 14-day run-in phase of their standard therapy (ST, included both pump therapy and multiple daily injections). The primary safety and effectiveness endpoints, respectively, were occurrence of severe hypoglycemia (SH) and diabetic ketoacidosis (DKA), and change in A1C and sensor glucose percent time in target range (TIR) (70–180 mg/dL) during HCL compared with ST.Participants (N=112) were aged (mean±SD) 10.3±2.2y with T1D duration 4.7±2.6y and baseline A1C 7.7±0.9% (range 5.8–10.3%). TIR increased significantly from ST to HCL, from 52.5±15.6% to 68.0±8.1% (p<0.0001), corresponding to an additional 3.7 hours/day in target range. A1C at end of study was reduced by 0.7% to 7.0±0.6% (p<0.0001). Percentages of time in hyperglycemia were reduced: >180 mg/dL from 45.3±16.7% to 30.2±8.7% and ≥250 mg/dL from 19.1±13.1% to 9.6±5.4% (both p<0.0001). Percentages of time in hypoglycemia remained low from ST to HCL: <54 mg/dL from 0.4±0.8% to 0.3±0.3% and <70 mg/dL from 2.2±2.7% to 1.8±1.4% (both p>0.05). Mean glucose decreased from 183±32 to 160±15 mg/dL (p<0.0001). During the HCL phase there was 1 episode of SH (delayed eating after pre-meal bolus) and 1 episode of DKA (suspected infusion site failure) reported. Virtually all participants completing the pivotal study (99%) continued system use during an extension phase.In this multi-center pivotal study in a large cohort of children with T1D, the Omnipod 5 System was safe and effective when used for 3 months at home. There were significant improvements in both TIR and A1C, while time below range (<70 mg/dL) remained low. The beneficial glycemic outcomes are critical for children, given that neurologic outcomes can be negatively impacted by hyperglycemia. The current results and commitment to the extension phase emphasize the safe and effective use of the HCL system, as well as the preference for the Omnipod 5 System over participants’ previous therapy.

Safety Evaluation of the Omnipod® 5 Automated Insulin Delivery System Over Three Months of Use in Adults and Adolescents With Type 1 Diabetes (T1D)

Abstract Advances in diabetes technology have transformed the treatment paradigm for type 1 diabetes (T1D), yet the burden of disease remains significant. The Omnipod 5 Automated Insulin Delivery System is a novel hybrid closed-loop (HCL) system with fully on-body operation. The system consists of a tubeless insulin pump (pod) containing a personalized Model Predictive Control algorithm which communicates directly with a Dexcom G6 continuous glucose monitor (CGM, or sensor) to automate insulin delivery. Therapy customization is enabled through glucose targets from 110-150 mg/dL, adjustable by time of day. The system adapts to changing insulin needs with each pod change. We report on the first, pivotal outpatient safety evaluation of the system in a large cohort of adults and adolescents with T1D. Participants aged 14-70y with T1D≥6 months and A1C&amp;lt;10% used the HCL system for 3 months at home after a 14-day run-in phase of their standard therapy (ST). Prior therapy included both pump therapy and multiple daily injections. The primary safety and effectiveness endpoints, respectively, were occurrence of severe hypoglycemia (SH) and diabetic ketoacidosis (DKA), and change in A1C and sensor glucose percent time in target range (TIR) (70-180 mg/dL) during HCL compared with ST. Participants (N=128) were aged (mean±SD) 37±14y with T1D duration 18±12y and baseline A1C 7.2±0.9% (range 5.2-9.8%). There was a significant increase in TIR from ST to HCL, from 64.7±16.6% to 73.9±11.0% (p&amp;lt;0.0001), corresponding to an additional 2.2 hours/day in target range. A1C at end of study was reduced by 0.4%, from 7.2±0.9% to 6.8±0.7% (p&amp;lt;0.0001). Glycemic outcomes for percent of time with CGM readings below and above target range were all reduced (p&amp;lt;0.0001): &amp;lt;54 mg/dL from 0.6±1.2% to 0.2±0.3% (a decrease of 6 minutes/day), &amp;lt;70 mg/dL from 2.9±3.1% to 1.3±1.1% (a decrease of 23 minutes/day), &amp;gt;180 mg/dL from 32.4±17.3% to 24.7±11.2% (a decrease of 1.8 hours/day), and ≥250 mg/dL from 10.1±10.5% to 5.8±5.5% (a decrease of 1.0 hours/day). The mean glucose also decreased from 161±28 to 154±17 mg/dL (p=0.0002). During the 3-month HCL phase there were 2 episodes of SH (both following user-initiated boluses) and no episodes of DKA reported. Most participants completing the pivotal study (92%) opted to continue using the system during an extension phase. In this outpatient, multi-center pivotal study in a large cohort of adults and adolescents with T1D, the Omnipod 5 System was safe and effective when used for 3 months at home. There were significant improvements in both TIR and A1C with use of the system, while time in hypoglycemic ranges was also reduced. The current results and commitment to the extension phase highlight the safe and effective use of the HCL system, as well as the preference for the Omnipod 5 System over participants’ previous therapy.

Basal Glucose Control in Type 1 Diabetes Using Deep Reinforcement Learning: An In Silico Validation.

People with Type 1 diabetes (T1D) require regular exogenous infusion of insulin to maintain their blood glucose concentration in a therapeutically adequate target range. Although the artificial pancreas and continuous glucose monitoring have been proven to be effective in achieving closed-loop control, significant challenges still remain due to the high complexity of glucose dynamics and limitations in the technology. In this work, we propose a novel deep reinforcement learning model for single-hormone (insulin) and dual-hormone (insulin and glucagon) delivery. In particular, the delivery strategies are developed by double Q-learning with dilated recurrent neural networks. For designing and testing purposes, the FDA-accepted UVA/Padova Type 1 simulator was employed. First, we performed long-term generalized training to obtain a population model. Then, this model was personalized with a small data-set of subject-specific data. In silico results show that the single and dual-hormone delivery strategies achieve good glucose control when compared to a standard basal-bolus therapy with low-glucose insulin suspension. Specifically, in the adult cohort (n = 10), percentage time in target range 70, 180 mg/dL improved from 77.6% to 80.9% with single-hormone control, and to 85.6% with dual-hormone control. In the adolescent cohort (n = 10), percentage time in target range improved from 55.5% to [Formula: see text] with single-hormone control, and to 78.8% with dual-hormone control. In all scenarios, a significant decrease in hypoglycemia was observed. These results show that the use of deep reinforcement learning is a viable approach for closed-loop glucose control in T1D.

An Insulin Bolus Advisor for Type 1 Diabetes Using Deep Reinforcement Learning.

(1) Background: People living with type 1 diabetes (T1D) require self-management to maintain blood glucose (BG) levels in a therapeutic range through the delivery of exogenous insulin. However, due to the various variability, uncertainty and complex glucose dynamics, optimizing the doses of insulin delivery to minimize the risk of hyperglycemia and hypoglycemia is still an open problem. (2) Methods: In this work, we propose a novel insulin bolus advisor which uses deep reinforcement learning (DRL) and continuous glucose monitoring to optimize insulin dosing at mealtime. In particular, an actor-critic model based on deep deterministic policy gradient is designed to compute mealtime insulin doses. The proposed system architecture uses a two-step learning framework, in which a population model is first obtained and then personalized by subject-specific data. Prioritized memory replay is adopted to accelerate the training process in clinical practice. To validate the algorithm, we employ a customized version of the FDA-accepted UVA/Padova T1D simulator to perform in silico trials on 10 adult subjects and 10 adolescent subjects. (3) Results: Compared to a standard bolus calculator as the baseline, the DRL insulin bolus advisor significantly improved the average percentage time in target range (70–180 mg/dL) from to () and to () in the the adult and adolescent cohorts, respectively, while reducing hypoglycemia. (4) Conclusions: The proposed algorithm has the potential to improve mealtime bolus insulin delivery in people with T1D and is a feasible candidate for future clinical validation.

A statistical virtual patient population for the glucoregulatory system in type 1 diabetes with integrated exercise model.

PurposeWe introduce two validated single (SH) and dual hormone (DH) mathematical models that represent an in-silico virtual patient population (VPP) for type 1 diabetes (T1D). The VPP can be used to evaluate automated insulin and glucagon delivery algorithms, so-called artificial pancreas (AP) algorithms that are currently being used to help people with T1D better manage their glucose levels. We present validation results comparing these virtual patients with true clinical patients undergoing AP control and demonstrate that the virtual patients behave similarly to people with T1D.MethodsA single hormone virtual patient population (SH-VPP) was created that is comprised of eight differential equations that describe insulin kinetics, insulin dynamics and carbohydrate absorption. The parameters in this model that represent insulin sensitivity were statistically sampled from a normal distribution to create a population of virtual patients with different levels of insulin sensitivity. A dual hormone virtual patient population (DH-VPP) extended this SH-VPP by incorporating additional equations to represent glucagon kinetics and glucagon dynamics. The DH-VPP is comprised of thirteen differential equations and a parameter representing glucagon sensitivity, which was statistically sampled from a normal distribution to create virtual patients with different levels of glucagon sensitivity. We evaluated the SH-VPP and DH-VPP on a clinical data set of 20 people with T1D who participated in a 3.5-day outpatient AP study. Twenty virtual patients were matched with the 20 clinical patients by total daily insulin requirements and body weight. The identical meals given during the AP study were given to the virtual patients and the identical AP control algorithm that was used to control the glucose of the virtual patients was used on the clinical patients. We compared percent time in target range (70–180 mg/dL), time in hypoglycemia (<70 mg/dL) and time in hyperglycemia (>180 mg/dL) for both the virtual patients and the actual patients.ResultsThe subjects in the SH-VPP performed similarly vs. the actual patients (time in range: 78.1 ± 5.1% vs. 74.3 ± 8.1%, p = 0.11; time in hypoglycemia: 3.4 ± 1.3% vs. 2.8 ± 1.7%, p = 0.23). The subjects in the DH-VPP also performed similarly vs. the actual patients (time in range: 75.6 ± 5.5% vs. 71.9 ± 10.9%, p = 0.13; time in hypoglycemia: 0.9 ± 0.8% vs. 1.3 ± 1%, p = 0.19). While the VPPs tended to over-estimate the time in range relative to actual patients, the difference was not statistically significant.ConclusionsWe have verified that a SH-VPP and a DH-VPP performed comparably with actual patients undergoing AP control using an identical control algorithm. The SH-VPP and DH-VPP may be used as a simulator for pre-evaluation of T1D control algorithms.

1043-P: Glycemic Profiles and Treatment Patterns: Real-World Data from 8,020 Adults with Type 1 Diabetes Using the Omnipod® Insulin Management System with Cloud-Based Data Management

While clinical trials have demonstrated significant benefits of insulin pump therapy for type 1 diabetes, there is increasing recognition of the importance of real-world population data to better understand the impact of diabetes technology on treatment outcomes. This study retrospectively analyzed data from a large cohort of adults with type 1 diabetes using the Omnipod® Insulin Management System (Insulet Corp., Acton, MA) with an integrated BG meter (Abbott Diabetes Care Inc., Alameda, CA) and data management system (Glooko, Mountain View, CA) to characterize glycemic profiles, insulin use and treatment patterns. From January 2015 through September 2018, pump system data were uploaded to the data management system and matched via device serial number to a second database of self-reported demographic data and de-identified. BG and insulin data from ≥3 mo of system use per patient were analyzed. Adults ≥18 y with type 1 diabetes (n=8,020) were age (mean±SD) 40.8±15.3y, 60% female, 61% used a tubeless insulin pump for ≥1 y and 13% used CGM for &amp;gt;50% of overall time of system use. Glycemic profiles included mean glucose 177±39 mg/dL, estimated A1C 7.8%, percent time in target range 70-180 mg/dL, hypoglycemia &amp;lt;70 mg/dL and hyperglycemia &amp;gt;180 mg/dL: 50.2±17.3, 5.9±5.0, and 43.9±18.3, respectively. The total daily insulin was 43.4±18.7 U/d which was delivered as 54% basal and 46% bolus. There were an average of 4.7±2.2 bolus deliveries per day and the average bolus amount was 4.5±2.8 U. These real-world glycemic profiles in adults with type 1 diabetes using the Omnipod® System support the use of diabetes technology in the management of type 1 diabetes. These data indicate that use of a tubeless insulin pump is associated with outcomes that compare favorably to large national registries including the T1D Exchange. Disclosure J.E. Layne: Employee; Self; Insulet Corporation. J. He: Employee; Self; Insulet Corporation. J. Jantz: Employee; Self; Insulet Corporation. Employee; Spouse/Partner; Insulet Corporation. Y. Zheng: Employee; Self; Insulet Corporation. Stock/Shareholder; Self; Insulet Corporation. E. Benjamin: Employee; Self; Insulet Corporation. T.T. Ly: Employee; Self; Insulet Corporation. Funding Insulet Corporation

A Modular Safety System for an Insulin Dose Recommender: A Feasibility Study.

Delivering insulin in type 1 diabetes is a challenging, and potentially risky, activity; hence the importance of including safety measures as part of any insulin dosing or recommender system. This work presents and clinically evaluates a modular safety system that is part of an intelligent insulin dose recommender platform developed within the EU-funded PEPPER project. The proposed safety system is composed of four modules which use a novel glucose forecasting algorithm. These modules are predictive glucose alerts and alarms; a predictive low-glucose basal insulin suspension module; an advanced rescue carbohydrate recommender for resolving hypoglycemia; and a personalized safety constraint applied to insulin recommendations. The technical feasibility of the proposed safety system was evaluated in a pilot study including eight adult subjects with type 1 diabetes on multiple daily injections over a duration of six weeks. Glycemic control and safety system functioning were compared between the two-weeks run-in period and the end point at eight weeks. A standard insulin bolus calculator was employed to recommend insulin doses. Overall, glycemic control improved over the evaluated period. In particular, percentage time in the hypoglycemia range (<3.0 mmol/l) significantly decreased from 0.82% (0.05-4.79) at run-in to 0.33% (0.00-0.93) at endpoint (P = .02). This was associated with a significant increase in percentage time in target range (3.9-10.0 mmol/l) from 52.8% (38.3-61.5) to 61.3% (47.5-71.7) (P = .03). There was also a reduction in number of carbohydrate recommendations. A safety system for an insulin dose recommender has been proven to be a viable solution to reduce the number of adverse events associated to glucose control in type 1 diabetes.

The Effects of a Sleep Extension Intervention on Glucose Control in Youth with Type 1 Diabetes

Although the 2017 Standard of Diabetes Care introduced recommendations to assess sleep patterns in individuals with type 2 diabetes, they do not contain such recommendations for individuals with type 1 diabetes (T1DM). We conducted a randomized clinical trial (RCT) to examine whether increasing sleep duration over a one-week period in youth’s natural environment improved glucose control and neurobehavioral performance. The primary outcomes of glycemic control (percent time in target range and average glucose levels) were assessed via a continuous glucose monitor (CGM) before and after being randomized to a sleep extension condition or a fixed sleep duration condition. Participants between the ages of 10 and 16 were 111 youth with almost half female; 35% were Latino/a, 51% Caucasian, and 14% mixed raced. The majority (80%) increased their sleep by more than 15 minutes; one-third achieved an increase of one hour of additional of sleep. Using actigraphy (wrist-like device that measures movement to estimate sleep) and a sleep diary, the average increase in sleep duration is 43.0 minutes vs. .30 minutes. Comparatively, research has noted that medications are considered to have a benefit to improve sleep if the individual increases sleep by 15 or more minutes. Controlling for baseline, extension participants differed from the fixed sleep duration group by 17mg/dl points, F(1, 102) = 9.55, p = .003, η2 = .39. During the Sleep Modification week, those in the Sleep Extension condition showed a 7.4% improvement in glucose levels, accounting for 11 hours more in the target range than those in the Fixed Sleep condition. These data will contribute to the long-term goal of establishing research evidence that sleep contributes to diabetes clinical care. Disclosure M. Perfect: None. S. Frye: None. G.P. Bluez: None.

Influence of Age on Warfarin Dose, Anticoagulation Control, and Risk of Hemorrhage.

We assessed the influence of age on warfarin dose, percentage time in target range (PTTR), and risk of major hemorrhage. Warfarin users recruited into a large prospective inception cohort study were categorized into three age groups: young (younger than 50yrs), middle aged (50-70yrs), and elderly (older than 70yrs). The influence of age on warfarin dose and PTTR was assessed using regression analysis; risk of major hemorrhage was assessed using proportional hazards analysis. Models were adjusted for demographic, clinical, and genetic factors. Two outpatient anticoagulation clinics. A total of 1498 anticoagulated patients. Warfarin dose (mg/day), PTTR, major hemorrhage. Of the 1498 patients, 22.8% were young, 44.1% were middle aged, and 33.1% were elderly. After accounting for clinical and genetic factors, compared with young warfarin users, warfarin dose requirements were 10.6% lower among the middle aged and an additional 10.6% lower for the elderly. Compared with young patients, middle-aged and elderly patients spent more time in target international normalized ratio (INR) range (p<0.0001), despite having fewer INR assessments (p<0.0001). Compared with young warfarin users, absolute risk of hemorrhage was marginally higher among the middle aged (p=0.08) and significantly higher among the elderly (p=0.016). Compared with young warfarin users, after adjustment, the relative risk of hemorrhage increased by 31% for each age category (p=0.026). In a real-world setting, despite achieving better anticoagulation control, elderly patients had a higher risk of major hemorrhagic events. As the population ages and the candidacy for oral anticoagulation increases, strategies that mitigate the elevated risk of hemorrhage need to be identified.

Quality of anticoagulation control and hemorrhage risk among African American and European American warfarin users.

We evaluated whether percent time in target range (PTTR), risk of over-anticoagulation [international normalized ratio (INR)>4], and risk of hemorrhage differ by race. As PTTR is a strong predictor of hemorrhage risk, we also determined the influence of PTTR on the risk of hemorrhage by race. Among 1326 warfarin users, PTTR was calculated as the percentage of interpolated INR values within the target range of 2.0-3.0. PTTR was also categorized as poor (PTTR<60%), good (60≤PTTR<70%), or excellent (PTTR≥70%) anticoagulation control. Over-anticoagulation was defined as INR more than 4 and major hemorrhages included serious, life-threatening, and fatal bleeding episodes. Logistic regression and survival analyses were carried out to evaluate the association of race with PTTR (≥60 vs. <60) and major hemorrhages, respectively. Compared with African Americans, European Americans had higher PTTR (57.6 vs. 49.1%; P<0.0001) and were more likely to attain 60≤PTTR<70% (22.9 vs. 13.1%; P<0.001) or PTTR of at least 70% (26.9 vs. 18.2%; P=0.001). Older (>65 years) patients without venous thromboembolism indication and chronic kidney disease were more likely to attain PTTR of at least 60%. After accounting for clinical and genetic factors, and PTTR, African Americans had a higher risk of hemorrhage [hazard ratio (HR)=1.58; 95% confidence interval (CI): 1.04-2.41; P=0.034]. Patients with 60≤PTTR<70% (HR=0.62; 95% CI: 0.38-1.02; P=0.058) and PTTR of at least 70% (HR=0.27; 95% CI: 0.15-0.49; P<0.001) had a lower risk of hemorrhage compared with those with PTTR less than 60%. Despite the provision of warfarin management through anticoagulation clinics, African Americans achieve a lower overall PTTR and have a significantly higher risk of hemorrhage. Personalized medicine interventions tailored to African American warfarin users need to be developed.

Effect of Left Ventricular Systolic Dysfunction on Response to Warfarin

Candidates for chronic warfarin therapy often have co-morbid conditions, such as heart failure, with reduced left ventricular ejection fraction. Previous reports have demonstrated an increased risk of over-anticoagulation due to reduced warfarin dose requirement in patients with decompensated heart failure. However, the influence of left ventricular systolic dysfunction (LVSD), defined as left ventricular ejection fraction <40%, on warfarin response has not been evaluated. Here, we assess the influence of LVSD on warfarin dose, anticoagulation control (percent time in target range), and risk of over-anticoagulation (international normalized ratio >4) and major hemorrhage. Of the 1,354 patients included in this prospective cohort study, 214 patients (16%) had LVSD. Patients with LVSD required 11% lower warfarin dose compared with those without LVSD (p <0.001) using multivariate linear regression analyses. Using multivariate Cox proportional hazards model, patients with LVSD experienced similar levels of anticoagulation control (percent time in target range: 51% vs 53% p= 0.15), risk of over-anticoagulation (international normalized ratio >4; hazard ratio 1.01, 95% confidence interval 0.82 to 1.25; p= 0.91), and risk of major hemorrhage (hazard ratio 1.11; 95% confidence interval 0.70 to 1.74; p= 0.66). Addition of LVSD variable in the model increased the variability explained from 35% to 36% for warfarin dose prediction. In conclusion, our results demonstrate that patients with LVSD require lower doses of warfarin. Whether warfarin dosing algorithms incorporating LVSD in determining initial doses improves outcomes needs to be evaluated.

Abstract 16324: Genetic Predisposition Influences Anticoagulation Control and Major Hemorrhage Among Warfarin Users

Objective: Genetic variants in Cytochrome P450 2C9 ( CYP2C9 ) and Vitamin K epoxide reductase complex 1 ( VKORC1 ) are recognized predictors of warfarin dose. However, their influence on percent time in target range (PTTR; INR range 2-3), overanticoagulation (INR&gt;4) and risk of major hemorrhage have not been extensively evaluated. Herein, categorizing warfarin users possessing CYP2C9 (*2,*3,*5,*6,*11) and/or VKORC1 (-1639 C&gt;T) variants as sensitive responders, we evaluated whether sensitive responders (vs. normal) were more likely to have lower PTTR and a higher risk of overanticoagulation and major hemorrhage. Methods: The analysis included 1262 participants [310 sensitive responders (SR); 952 normal responders (NR)] in a warfarin pharmacogenetics inception cohort. The Rosendaal interpolation method was used to compute the PTTR, percent time above range (PTAR) and percent time below range (PTBR). Major hemorrhages included serious, life threatening and fatal bleeding events. The influence of responder status (SR vs. NR) on PTTR, PTBR, and PBAR was evaluated using linear regression, and overanticoagulation and hemorrhage by Cox proportional hazards analysis adjusting for clinical factors. Results: Participants were followed for an average of 1.4 (± 0.9) years; with 1799 person-years (pyr) accrued. There was no difference in PTTR between SRs (54.4% vs. 53.8%, p=0.66) compared to NRs. However SRs had higher PTAR (20.3% vs. 16.7%, p=0.005) and lower PTBR (25.2% vs. 29.5%, p=0.01) and were more likely to experience over-anticoagulation (HR: 1.38, 95% CI: 1.23-1.56, p&lt;0.001). SRs had higher incidence of hemorrhage compared to NRs ((IRR: 1.48, 95% CI: 1.04-2.08, p=0.03). After adjusting for clinical factors, SRs remained at a higher risk for hemorrhage (HR: 1.81, 95% CI: 1.23-2.68, p=0.003). Conclusion: Warfarin users possessing CYP2C9 and/or VKORC1 variants are sensitive responders, spending higher percent of time above target INR range. These patients are more likely to experience overanticoagulation and major hemorrhagic events. Future research evaluating alterative treatment strategy including candidacy for the non-vitamin K antagonist oral anticoagulants is needed.

Abstract 16445: Anticoagulation Control, Risk of Overanticoagulation and Major Hemorrhage Among Warfarin Users is Influenced by Race

Objective: Racial differences in warfarin response have been of significant interest. Differences in dose requirements have been extensively studied. Herein, we assess whether anticoagulation control [percent time in target range (PTTR; INR range 2-3)], risk of overanticoagulation (INR&gt;4) and major hemorrhage differ by race among warfarin users. Methods: The analysis included 1357 participants [595 African Americans (AA); 762 European Americans (EA)]. The Rosendaal interpolation method was used to compute the PTTR, percent time above range (PTAR) and percent time below range (PTBR). Major hemorrhages included serious, life threatening and fatal bleeding events. The influence of race (AA vs. EA) on PTTR, PTBR, and PBAR was evaluated using linear regression; overanticoagulation and hemorrhage by Cox proportional hazards analysis adjusting for clinical and genetic factors. Results: Over 1912 person-years (pyrs) accrued (average per patient 1.4 (± 0.9) years), after adjusting for covariates, compared to EAs, AAs had lower PTTR (56.3% vs. 50.8% p&lt;0.001), higher PTBR (26.5% vs. 31.2%; p=0.001) and were also more likely to experience overanticoagulation (HR: 1.31, 95% CI 1.10-1.56, p=0.003). A total of 156 major hemorrhagic events were encountered (incidence 8.2/100 pyrs, 95% CI: 7.0 – 9.5/100 pyrs). AAs had higher incidence of hemorrhage compared to EAs (IRR: 1.38, 95% CI 1.00-1.89, p=0.046). After adjusting for clinical and genetic factors, AAs remained at a higher risk for hemorrhage (HR: 1.60, 95% CI: 1.10-2.34, p=0.016). Older age, antiplatelet therapy, renal impairment, and possession of CYP2C9 variants increased the risk of hemorrhage. Higher PTTR was associated with a lower risk of hemorrhage in both race groups. Compared to patients with PTTR&lt;50%; those with PTTR 50-60% had a 37% lower risk (HR=0.63; 95%CI0.4-0.97; p=0.04), those with PTTR 60-70% had a 43% lower risk (HR=0.57; 95%CI 0.35-0.92; p=0.02), and those with PTTR &gt;70 had a 75% lower risk (HR=0.25; 95%CI0.14-0.43; p&lt;0.0001). Conclusion and Relevance: Among warfarin users, African Americans spent less time in target INR range, and had a higher risk of overanticoagulation and hemorrhage. Strategies to improve anticoagulation control among African Americans can lower risk of hemorrhage.

Insulin treatment guided by subcutaneous continuous glucose monitoring compared to frequent point-of-care measurement in critically ill patients: a randomized controlled trial.

IntroductionGlucose measurement in intensive care medicine is performed intermittently with the risk of undetected hypoglycemia. The workload for the ICU nursing staff is substantial. Subcutaneous continuous glucose monitoring (CGM) systems are available and may be able to solve some of these issues in critically ill patients.MethodsIn a randomized controlled design in a mixed ICU in a teaching hospital we compared the use of subcutaneous CGM with frequent point of care (POC) to guide insulin treatment. Adult critically ill patients with an expected stay of more than 24 hours and in need of insulin therapy were included. All patients received subcutaneous CGM. CGM data were blinded in the control group, whereas in the intervention group these data were used to feed a computerized glucose regulation algorithm. The same algorithm was used in the control group fed by intermittent POC glucose measurements. Safety was assessed with the incidence of severe hypoglycemia (<2.2 mmol/L), efficacy with the percentage time in target range (5.0 to 9.0 mmol/L). In addition, we assessed nursing workload and costs.ResultsIn this study, 87 patients were randomized to the intervention and 90 to the control group. CGM device failure resulted in 78 and 78 patients for analysis. The incidence of severe glycemia and percentage of time within target range was similar in both groups. A significant reduction in daily nursing workload for glucose control was found in the intervention group (17 versus 36 minutes; P <0.001). Mean daily costs per patient were significantly reduced with EUR 12 (95% CI −32 to −18, P = 0.02) in the intervention group.ConclusionsSubcutaneous CGM to guide insulin treatment in critically ill patients is as safe and effective as intermittent point-of-care measurements and reduces nursing workload and daily costs. A new algorithm designed for frequent measurements may lead to improved performance and should precede clinical implementation.Trial registrationClinicaltrials.gov, NCT01526044. Registered 1 February 2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-014-0453-9) contains supplementary material, which is available to authorized users.

Insulin treatment guided by subcutaneous continuous glucose monitoring compared to frequent point-of-care measurement in critically ill patients: a randomized controlled trial

Glucose measurement in intensive care medicine is performed intermittently with the risk of undetected hypoglycemia. The workload for the ICU nursing staff is substantial. Subcutaneous continuous glucose monitoring (CGM) systems are available and may be able to solve some of these issues in critically ill patients. In a randomized controlled design in a mixed ICU in a teaching hospital we compared the use of subcutaneous CGM with frequent point of care (POC) to guide insulin treatment. Adult critically ill patients with an expected stay of more than 24 hours and in need of insulin therapy were included. All patients received subcutaneous CGM. CGM data were blinded in the control group, whereas in the intervention group these data were used to feed a computerized glucose regulation algorithm. The same algorithm was used in the control group fed by intermittent POC glucose measurements. Safety was assessed with the incidence of severe hypoglycemia (<2.2 mmol/L), efficacy with the percentage time in target range (5.0 to 9.0 mmol/L). In addition, we assessed nursing workload and costs. In this study, 87 patients were randomized to the intervention and 90 to the control group. CGM device failure resulted in 78 and 78 patients for analysis. The incidence of severe glycemia and percentage of time within target range was similar in both groups. A significant reduction in daily nursing workload for glucose control was found in the intervention group (17 versus 36 minutes; P <0.001). Mean daily costs per patient were significantly reduced with EUR 12 (95% CI −32 to −18, P = 0.02) in the intervention group. Subcutaneous CGM to guide insulin treatment in critically ill patients is as safe and effective as intermittent point-of-care measurements and reduces nursing workload and daily costs. A new algorithm designed for frequent measurements may lead to improved performance and should precede clinical implementation. Clinicaltrials.gov, NCT01526044 . Registered 1 February 2012.