Data entry errors and design for model-based tight glycemic control in critical care

Introduction

Tight glycemic control (TGC) has shown benefits but has been difficult to achieve consistently. Model-based methods and computerized protocols offer the opportunity to improve TGC quality but require human data entry, particularly of blood glucose (BG) values, which can be significantly prone to error. This study presents the design and optimization of data entry methods to minimize error for a computerized and model-based TGC method prior to pilot clinical trials.

Method

To minimize data entry error, two tests were carried out to optimize a method with errors less than the 5%-plus reported in other studies. Four initial methods were tested on 40 subjects in random order, and the best two were tested more rigorously on 34 subjects. The tests measured entry speed and accuracy. Errors were reported as corrected and uncorrected errors, with the sum comprising a total error rate. The first set of tests used randomly selected values, while the second set used the same values for all subjects to allow comparisons across users and direct assessment of the magnitude of errors. These research tests were approved by the University of Canterbury Ethics Committee.

Results

The final data entry method tested reduced errors to less than 1–2%, a 60–80% reduction from reported values. The magnitude of errors was clinically significant and was typically by 10.0 mmol/liter or an order of magnitude but only for extreme values of BG < 2.0 mmol/liter or BG > 15.0–20.0 mmol/liter, both of which could be easily corrected with automated checking of extreme values for safety.

Conclusions

The data entry method selected significantly reduced data entry errors in the limited design tests presented, and is in use on a clinical pilot TGC study. The overall approach and testing methods are easily performed and generalizable to other applications and protocols.     

Interface design and human factors considerations for model-based tight glycemic control in critical care

Introduction

Tight glycemic control (TGC) has shown benefits but has been difficult to implement. Model-based methods and computerized protocols offer the opportunity to improve TGC quality and compliance. This research presents an interface design to maximize compliance, minimize real and perceived clinical effort, and minimize error based on simple human factors and end user input.

Method

The graphical user interface (GUI) design is presented by construction based on a series of simple, short design criteria based on fundamental human factors engineering and includes the use of user feedback and focus groups comprising nursing staff at Christchurch Hospital. The overall design maximizes ease of use and minimizes (unnecessary) interaction and use. It is coupled to a protocol that allows nurse staff to select measurement intervals and thus self-manage workload.

Results

The overall GUI design is presented and requires only one data entry point per intervention cycle. The design and main interface are heavily focused on the nurse end users who are the predominant users, while additional detailed and longitudinal data, which are of interest to doctors guiding overall patient care, are available via tabs. This dichotomy of needs and interests based on the end user''s immediate focus and goals shows how interfaces must adapt to offer different information to multiple types of users.

Conclusions

The interface is designed to minimize real and perceived clinical effort, and ongoing pilot trials have reported high levels of acceptance. The overall design principles, approach, and testing methods are based on fundamental human factors principles designed to reduce user effort and error and are readily generalizable.     

Monitoring the Impact of Aggressive Glycemic Intervention during Critical Care after Cardiac Surgery with a Glycemic Expert System for Nurse-Implemented Euglycemia: The MAGIC GENIE Project

A novel, multi-dimensional protocol named GENIE has been in use for intensive insulin therapy (IIT, target glucose <140 mg/dL) in the surgical intensive care unit (SICU) after open heart surgery (OHS) at VA Pittsburgh since 2005. Despite concerns over increased mortality from IIT after the publication of the NICE-SUGAR Trial, it remains in use, with ongoing monitoring under the MAGIC GENIE Project showing that GENIE performance over 12 years (2005-2016) aligns with the current consensus that IIT with target blood glucose (BG) <140 mg/dL is advisable only if it does not provoke severe hypoglycemia (SH). Two studies have been conducted to monitor glucometrics and outcomes during GENIE use in the SICU. One compares GENIE (n = 382) with a traditional IIT protocol (FORMULA, n = 289) during four years of contemporaneous use (2005-2008). The other compares GENIE’s impact overall (n = 1404) with a cohort of patients who maintained euglycemia after OHS (euglycemic no-insulin [ENo-I], n = 111) extending across 12 years (2005-2016). GENIE performed significantly better than FORMULA during contemporaneous use, maintaining lower time-averaged glucose, provoking less frequent, severe, prolonged, or repetitive hypoglycemia, and achieving 50% lower one-year mortality, with no deaths from mediastinitis (0 of 8 cases vs 4 of 9 on FORMULA). Those benefits were sustained over the subsequent eight years of exclusive use in OHS patients, with an overall one-year mortality rate (4.2%) equivalent to the ENo-I cohort (4.5%). The results of the MAGIC GENIE Project show that GENIE can maintain tight glycemic control without provoking SH in patients undergoing OHS, and may be associated with a durable survival benefit. The results, however, await confirmation in a randomized control trial.     

Computerized Algorithms: Multicenter Validation of a Computer-Based Clinical Decision Support Tool for Glucose Control in Adult and Pediatric Intensive Care Units

Introduction

Hyperglycemia during critical illness is common, and intravenous insulin therapy (IIT) to normalize blood glucose improves outcomes in selected populations. Methods differ widely in complexity, insulin dosing approaches, efficacy, and rates of hypoglycemia. We developed a simple bedside-computerized decision support protocol (eProtocol-insulin) that yields promising results in the development center. We examined the effectiveness and safety of this tool in six adult and five pediatric intensive care units (ICUs) in other centers.

Methods

We required attending physicians of eligible patients to independently intend to use intravenous insulin to normalize blood glucose. We used eProtocol-insulin for glucose control for a duration determined by the clinical caregivers. Adults had an anticipated length of stay of 3 or more days. In pediatric ICUs, we also required support or intended support with mechanical ventilation for greater than 24 hours or with a vasoactive infusion. We recorded all instances in which eProtocol-insulin instructions were not accepted and all blood glucose values. An independent data safety and monitoring board monitored study results and subject safety. Bedside nurses were selected randomly to complete a paper survey describing their perceptions of quality of care and workload related to eProtocol-insulin use.

Results

Clinicians accepted 93% of eProtocol-insulin instructions (11,773/12,645) in 100 adult and 48 pediatric subjects. Forty-eight percent of glucose values were in the target range. Both of these results met a priori-defined efficacy thresholds. Only 0.18% of glucose values were ≤40 mg/dl. This is lower than values reported in prior IIT studies. Although nurses reported eProtocol-insulin required as much work as managing a mechanical ventilator, most nurses felt eProtocol-insulin had a low impact on their ability to complete non-IIT nursing activities.

Conclusions

A multicenter validation demonstrated that eProtocol-insulin is a valid, exportable tool that can assist clinicians in achieving control of glucose in critically ill adults and children.     

Numerical and Clinical Accuracy of a Continuous Glucose Monitoring System during Intravenous Insulin Therapy in the Surgical and Burn Intensive Care Units

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^TM 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.     

Technical Challenges and Clinical Outcomes of Using a Closed-Loop Glycemic Control System in the Hospital

According to large randomized trials, results suggest that maintaining normoglycemia postoperatively through tight glycemic control (TGC) and intensive insulin therapy (IIT) can improve surgical outcomes as well as reduce mortality and morbidity in critically ill patients. However, trials examining the effects of TGC have had conflicting results. Systematic reviews and meta-analyses have also led to differing conclusions. The main reason these clinical trials and meta-analyses show negative results for TGC is the high incidence of hypoglycemia induced by IIT. This could not be prevented because there is no reliable technique that can avoid this condition during IIT. The development of accurate, continuous blood glucose monitoring devices and closed-loop systems for computer-assisted blood glucose control in the intensive care unit (ICU) will probably help avoid hypoglycemia in these situations.The STG closed-loop glycemic control system was introduced to our department to be used and evaluated for strict serum glucose control with no hypoglycemic episodes during IIT in the surgical ICU, to reduce the workload of ICU nurses, and to decrease incidents related to the management of blood glucose levels according to manual conventional venous infusion insulin therapy. The goal of our team was to use the STG closed-loop glycemic control system for perioperative TGC in surgical patients to solve the complications of IIT and reduce risk of hypoglycemia. The challenge at our hospital demonstrated that the STG closed-loop glycemic control system can be expected to achieve TGC with no occurrence of hypoglycemia induced by IIT after surgery.     

Glycemic control and safety in Chinese patients with type 2 diabetes mellitus who switched from premixed insulin to insulin glargine plus oral antidiabetics: a large,prospective, observational study

In some circumstances, the premixed insulin should be switched to alternative therapy. The effectiveness and the safety of switching from premixed insulin to insulin glargine plus oral antidiabetic drugs (OADs) in Chinese patients with type 2 diabetes mellitus (T2DM) have not been clarified and, hence, will be assessed in this study. Chinese patients with T2DM (2013 men and women aged 18–75 years) who had received premixed insulin ± OADs for ≥3 months with glycated hemoglobin (HbA1c) ≤ 10% were enrolled in a prospective, observational study conducted at 53 hospitals across China. At baseline and at the discretion of the physician, patients switched from premixed insulin to insulin glargine plus OADs. Changes in HbA1c, fasting plasma glucose (FPG), 2‐hour postprandial glucose (PPG), treatment satisfaction, and the incidence of hypoglycemia were assessed for 16 weeks. In total, 1850 patients completed the study. Mean HbA1c level for the group decreased significantly (from 7.8% ± 1.2% at week 1 to 7.0% ± 1.0% at week 16; P  < .0001), and 55.2% of patients achieved HbA1c < 7% at week 16. Mean FPG and 2‐hour PPG decreased significantly (−1.4 ± 2.2 and −2.1 ± 3.9 mmol/L, respectively; both P  < .0001), whereas patient satisfaction improved significantly. Adverse events were reported in 18.7% of patients. Chinese patients with T2DM who switched from premixed insulin to insulin glargine plus OADs achieved significantly improved glycemic control and treatment satisfaction with a low incidence of hypoglycemia. Patients who are most likely to achieve the HbA1c target less than 7% are younger, have shorter disease duration, and have lower baseline HbA1c and FPG levels.     

Association between intensive glycemic control and mortality in elderly diabetic patients in the primary care: A retrospective cohort study

ObjectiveTo examine the association between the most recent HbA1c values and the mortality of elderly Type 2 Diabetic (T2DM) patients managed in the public primary care setting and to explore the associating risk factors.DesignRetrospective cohort study.SubjectsAll T2DM patients aged 65 or above, who attended a public primary care clinic for regular follow up from 01/01/2012 to 31/12/2012 were included. Their follow up status till 31/12/2017 was reviewed. Those who were deceased on or before 31/12/2017 were matched randomly with controls that were alive in the same cohort for comparison.Main Outcome MeasuresPatients’ demographics, smoking status, duration of T2DM, biochemical parameters including the most recent HbA1c, lipid profile, renal function test, drug profile, co-morbidities and all-cause mortality were retrieved from Hospital Authority’s CDARS and CMS systems.ResultsBoth high (>8.0%) and low (<6.5%) HbA1c values were associated with increased odd ratio of all-cause mortality among T2DM elderly patients treated in the primary care. There was a 3-fold increase in odd ratio when the HbA1c reading was very low (<6.0%). Associated risk factors for all-cause mortality in elderly T2DM patients included smoker status, lower BMIs, and higher LDL levels and use of sulphonylureas.ConclusionsGlycemic target for elderly T2DM patients should be approached cautiously. Over-aggressive treatment may lead to increased mortality among elderly T2DM patients.     

Efficacy and safety of empagliflozin in combination with insulin in Chinese patients with type 2 diabetes and insufficient glycaemic control: A phase III,randomized, double-blind,placebo-controlled,parallel study

Aim

To evaluate the efficacy and safety of empagliflozin in combination with insulin ± oral antidiabetic drugs (OADs) over 24 weeks, in Chinese patients with type 2 diabetes (T2D) who had insufficient glycaemic control.

Materials and Methods

This was a randomized, double-blind, placebo-controlled, parallel group, multicentre phase III study. Adult patients with T2D and insufficient glycaemic control who received insulin ± up to two OADs were randomized (1:1:1) to receive empagliflozin 10 or 25 mg, or placebo for 24 weeks. The primary endpoint was change from baseline in HbA1c at week 24.

Results

Of 219 randomized patients, 73 patients were in each treatment group; baseline characteristics were comparable among the groups. There was a significantly larger decrease from baseline in HbA1c (adjusted mean treatment difference −0.99 and −0.98 for in the empagliflozin 10 and 25 mg groups, respectively; P < .0001) with both doses of empagliflozin than with placebo. There were also significantly larger decreases from baseline in fasting plasma glucose, 2-hour postprandial glucose and body weight with both empagliflozin doses than with placebo. Among patients in the empagliflozin 10 mg, 25 mg and placebo groups, 17.8%, 9.6% and 11.0% reported confirmed hypoglycaemic events, respectively (nominal P = .2422 and .7661 in the empagliflozin 10 and 25 mg groups, respectively), and no Clinical Events Committee-confirmed diabetic ketoacidosis events were reported.

Conclusions

In Chinese patients with T2D, empagliflozin combined with insulin ± OADs improved glycaemic control and was well tolerated, without an increased risk of hypoglycaemia.     

Influence of preprandial vs. postprandial insulin glulisine on weight and glycaemic control in patients initiating basal-bolus regimen for type 2 diabetes: a multicenter, randomized, parallel, open-label study (NCT00135096)

Aim: Insulin therapy is commonly associated with weight gain. The timing of prandial insulin administration may enhance its efficacy/safety and maintain effective weight control. This study examined the effect of postprandial vs. preprandial insulin glulisine on weight gain and glycaemic control in type 2 diabetes patients taking basal insulin. Methods: This was a multicenter, randomized, open‐label trial conducted in 45 centres in the USA. A total of 716 patients with type 2 diabetes and glycated haemoglobin A_1c (HbA_1c) ≥7.5% and ≤10.0% were screened; 345 were randomized and 322 comprised the intent‐to‐treat group (premeal, 163; postmeal, 159). Insulin glargine once daily, ±metformin and subcutaneous injections of premeal or postmeal insulin glulisine were given for 52 weeks. Main outcome measures included changes in HbA_1c, fasting plasma glucose and weight from study baseline to endpoint (week 52). Results: At study end, insulin glulisine achieved similar glycaemic control whether it was administered before or after meals (HbA_1c: 7.04% premeal vs. 7.16% postmeal, p = NS). Overall hypoglycaemia incidence and severe hypoglycaemia rates were not significantly different between premeal and postmeal groups; however, symptomatic and nocturnal hypoglycaemia rates were higher in the postprandial group. Mean body weight was lower in the postmeal group, with the difference between postmeal and premeal weight change from baseline to week 52 of ?0.87 kg (p = 0.243). Conclusion: Postprandial glulisine administration provided similar glycaemic control and was non‐inferior to preprandial administration on weight gain, without additional risk of severe hypoglycaemia, showing dosing flexibility and the feasibility of such approach when clinically indicated.     

Efficacy and safety of fast‐acting insulin aspart in comparison with insulin aspart in type 1 diabetes (onset 1): A 52‐week,randomized, treat‐to‐target,phase III trial

Aims

To compare the safety and efficacy of fast‐acting insulin aspart (faster aspart) with conventional insulin aspart (IAsp) in adults with type 1 diabetes (T1D).

Materials and methods

onset 1 was a randomized, multicentre, treat‐to‐target, phase III, 52‐week (initial 26 weeks + additional 26 weeks) trial conducted at 165 sites across 9 countries. Adults with T1D were randomly allocated to double‐blind mealtime faster aspart or IAsp, each with once‐ or twice‐daily insulin detemir. The primary endpoint, change in glycated haemoglobin (HbA1c) from baseline after the initial 26 weeks, has been reported previously. In the present paper, we report data from the full 52‐week study period.

Results

Between August 2013 and June 2015, 381 participants were assigned to double‐blind faster aspart and 380 participants to IAsp. After 52 weeks, estimated mean changes from baseline in HbA1c levels were ?0.08% (faster aspart) and +0.01% (IAsp); estimated treatment difference significantly favoured faster aspart (?0.10% [95% confidence interval {CI} ?0.19;?0.00]; P = .0424). Changes from baseline in 1‐hour postprandial plasma glucose (PPG) increment (meal test; faster aspart ?1.05 mmol/L; IAsp ?0.14 mmol/L) also significantly favoured faster aspart (estimated treatment difference ?0.91 mmol/L [95% CI ?1.40;?0.43]; ?16.48 mg/dL [95% CI ?25.17;?7.80]; P = .0002). There was no difference in overall severe or blood glucose‐confirmed hypoglycaemic episodes or treatment‐emergent adverse events between treatments.

Conclusions

At 52 weeks, overall glycaemic control had significantly improved with faster aspart vs IAsp, consistent with the 26‐week study findings. Achieving an insulin profile closer to physiological insulin secretion with faster aspart translates into lower PPG and HbA1c levels compared with those achieved with IAsp in people with T1D.