Geoffrey Chase

Glucose control positively influences patient outcome: A retrospective study

OBJECTIVE The goal of this research is to demonstrate that well-regulated glycemia is beneficial to patient outcome, regardless of how it is achieved. METHODS This analysis used data from 1701 patients from 2, independent studies. Glycemic outcome was measured using cumulative time in band (cTIB), calculated for 3 glycemic bands and for threshold values of t = 0.5, 0.6, 0.7, and 0.8. For each day of intensive care unit stay, patients were classified by cTIB, threshold, and hospital mortality, and odds of living (OL) and odds ratio were calculated. RESULTS The OL given cTIB ≥ t is higher than the OL given cTIB <t for all values of t, every day, for all 3 glycemic bands studied. The difference between the odds clearly increased over intensive care unit stay for t>0.6. Higher cTIB thresholds resulted in larger increases to odds ratio over time and were particularly significant for the 4.0 to 7.0 mmol/L glycemic band. CONCLUSION Increased cTIB was associated with higher OL. These results suggest that effective glycemic control positively influences patient outcome, regardless of how the glycemic regulation is achieved. Blood glucose < 7.0 mmol/L is associated with a measurable increase in the odds of survival, if hypoglycemia is avoided.

Does the achievement of an intermediate glycemic target reduce organ failure and mortality? A post hoc analysis of the Glucontrol trial.

OBJECTIVE This research evaluates the impact of the achievement of an intermediate target glycemic band on the severity of organ failure and mortality. METHODS Daily Sequential Organ Failure Assessment (SOFA) score and the cumulative time in a 4.0 to 7.0 mmol/L band (cTIB) were evaluated daily up to 14 days in 704 participants of the multicentre Glucontrol trial (16 centers) that randomized patients to intensive group A (blood glucose [BG] target: 4.4-6.1 mmol/L) or conventional group B (BG target: 7.8-10.0 mmol/L). Sequential Organ Failure Assessment evolution was measured by percentage of patients with SOFA less than or equal to 5 on each day, percentage of individual organ failures, and percentage of organ failure-free days. Conditional and joint probability analysis of SOFA and cTIB 0.5 or more assessed the impact of achieving 4.0 to 7.0 mmol/L target glycemic range on organ failure. Odds ratios (OR) compare the odds risk of death for cTIB 0.5 or more vs cTIB less than 0.5, where a ratio greater than 1.0 indicates an improvement for achieving cTIB 0.5 or more independent of SOFA or glycemic target. RESULTS Groups A and B were matched for demographic and severity of illness data. Blood glucose differed between groups A and B (P<.05), as expected. There was no difference in the percentage of patients with SOFA less than or equal to 5, individual organ failures, and organ failure-free days between groups A and B over days 1 to 14. However, 20% to 30% of group A patients failed to achieve cTIB 0.5 or more for all days, and significant crossover confounds interpretation. Mortality OR was greater than 1.0 for patients with cTIB 0.5 or more in both groups but much higher for group A on all days. CONCLUSIONS There was no difference in organ failure in the Glucontrol study based on intention to treat to different glycemic targets. Actual outcomes and significant crossover indicate that this result may not be due to the difference in target or treatment. Odds ratios-associated achieving an intermediate 4.0 to 7.0 mmol/L range improved outcome.

Asymptotic output tracking in blood glucose control. A case study

Glucose is the primary source of energy for the human body. Keeping the blood glucose level between certain thresholds is essential for the proper energy transport. Insulin plays a key role in maintaining the glucose homeostasis. Because of its great importance, many models were published on either to describe the glucose-insulin interaction in case of patients under Intensive Care Unit (ICU), or to model Type 1 Diabetes Mellitus (T1DM). Currently for most of the models linear control concepts are used in order to design an appropriate controller. The aim of the current paper is to investigate applicability of nonlinear control theory providing exact mathematical background in the control problem of glucose-insulin interaction. Both ICU and T1DM cases are analyzed on well-known models with different complexity. Our aim is to hide the nonlinearity of the models by transforming the input signal so that the response of the model would mimic the behavior of a linear system; hence extending the validity of linear controllers. The asymptotic tracking problem needs the value of the state variables; therefore extended Kalman-filter is applied. The capabilities of this approach are examined through classical control algorithms and input data recorded in clinical environment.

Sublingual sugar for infant hypoglycaemia – Authors' reply

1 Harris DL, Weston PJ, Signal M, Chase JG, Harding JE. Dextrose gel for neonatal hypoglycaemia (the Sugar Babies Study): a randomised, double-blind, placebocontrolled trial. Lancet 2013; 382: 2077–83. 2 Barennes H, Valea I, Nagot N, Van de Perre P, Pussard E. Sublingual sugar administration as an alternative to intravenous dextrose administration to correct hypoglycemia among children in the tropics. Pediatrics 2005; 116: e648–53. 3 Graz B, Dicko M, Willcox ML, et al. Sublingual sugar for hypoglycaemia in children with severe malaria: a pilot clinical study. Malar J 2008; 7: 242. 4 Oyama Y, Yamano H, Ohkuma A, Ogawara K, Higaki K, Kimura T. Carrier-mediated transport systems for glucose in mucosal cells of the human oral cavity. J Pharm Sci 1999; 88: 830–34. 5 Ou S, Kwok K, Li Y, Fu L. In vitro study of possible role of dietary fi ber in lowering postprandial serum glucose. J Agric Food Chem 2001; 49: 1026–29. Sublingual sugar for infant hypoglycaemia

O-104 Two Year Outcomes Of Children Treated With Dextrose Gel For Neonatal Hypoglycaemia: Follow Up Of A Randomised Trial

Background Neonatal hypoglycaemia is linked to poor developmental outcome. Dextrose gel reverses hypoglycaemia, but its long term effects are unknown. Aim To determine two year outcomes of children randomised to dextrose or placebo gel for treatment of neonatal hypoglycaemia1. Methods At risk babies who became hypoglycaemic (<2.6 mM) were randomised to 40% dextrose or placebo gel. Children were assessed at two years’ corrected age for neurological function and general health (paediatrician assessed); cognitive, language, behaviour and motor skills (Bayley III); executive function; and vision (clinical examination and global motion perception). Primary outcomes were neurosensory disability (cognitive, language or motor score below -1 SD or cerebral palsy or blind or deaf) and processing problem (executive function or global motion perception worse than 1.5 SD). Data are mean (SD), n (%), or relative risk (RR), 95% confidence interval. Results 184 children were assessed; 90/118 (76%) randomised to dextrose and 94/119 (79%) to placebo gel. Mean birth weight was 3093 (803) g and gestation 37.7 (1.6) wk. 67 children (36%) had neurosensory disability (1 severe, 9 moderate, 57 mild) with similar rates in both groups (dextrose 35 (39%) vs placebo 32 (34%), RR 1.14, 0.78–1.67). Processing difficulty was also similar in both groups (dextrose 8 (10%) vs placebo 16 (18%), RR 0.52, 0.23–1.15). Discussion Neurosensory disability is common amongst children treated for neonatal hypoglycaemia. Treatment with dextrose gel does not change the incidence of disability or processing problems. Reference Harris DL, et al. Dextrose gel for neonatal hypoglycaemia (the Sugar Babies Study). Lancet 2013;382:2077–83

Oral dextrose gel to improve survival in less vigorous newborn triplet lambs: a randomised controlled trial

ABSTRACT Triplet lambs have reduced survival and most deaths occur due to starvation and exposure, but there are a few simple and safe interventions. We hypothesised that buccal dextrose gel would increase blood glucose concentration, vigour, survival and early feeding in less vigorous triplet lambs. Triplet lambs meeting criteria for decreased vigour were randomised to 40% dextrose or placebo gel 1 mL/kg via the buccal mucosa at 1 hour of age. Primary outcome was survival at 3 hours. An additional study exploring the effect of gel on interstitial glucose concentrations was assessed by continuous glucose monitoring in twin lambs. Lambs randomised to dextrose gel did not have higher blood glucose concentrations or better survival than those randomised to placebo. Low temperature at 1 hour after birth, rather than birthweight or blood glucose concentrations, was associated with decreased survival. Interventions to address hypothermia rather than hypoglycaemia may be most effective in improving survival in less vigorous triplet lambs.

Model-based insulin-nutrition administration for glycemic control in Malaysian critical care: First pilot trial

Stress-induced hyperglycemia is prevalent in critical care, even in patients with no history of diabetes. Control of blood glucose level with tight insulin therapy has been shown to reduce incidences of hyperglycemia leading to reduced mortality and improved clinical outcomes. STAR is a tablet-based glucose control protocol with a specialized user interface into which insulin and nutrition information can be entered and predicted. This research describes the first clinical pilot trial of STAR approach in International Islamic University Hospital, Kuantan, Malaysia. The clinically specified target for blood glucose level is between 4.4 and 8.0 mmol/L. Seven episodes (of 359 h) were recruited based on the need for glucose control. Overall, 43.93% of measurement are in the range of 4.4–8.0 mmol/L band. The blood glucose median is 8.30 [6.32–10.00] mmol/L with only 1 patient having below than 2.22 mmol/L which is the guaranteed minimum risk level. This pilot study shows that STAR protocol is a patient specific approach that provides a good glycemic control in critically ill patients. Nevertheless, its implementation in Malaysian intensive care environments requires modifications and improvements in certain areas.

Decision Support for Parenteral Nutrition Supplementation in ICU Using Model-Based Glycemic Control Protocol

Nutrition therapy is part of the standard care given to all critically ill patients. In general, nutrition is administered as enteral nutrition (EN) and/or parenteral nutrition (PN). PN is given if the patients have contraindications to EN or as supplement if daily energy requirement cannot be achieved by EN alone. PN can be given as partial (dextrose solution only) or complete (include all macro- and micro-nutrients). The mode of nutrition therapy is influenced by several factors which include the need to maintain normoglycemia. A simulation is done to find the appropriate time to introduce PN while the patients are already on EN. In this context, a virtual study was conducted on 66 retrospectives critically ill patients’ data using clinically validated insulin-nutrition model and Stochastic TARgeted (STAR) protocol. The results suggested that this protocol benefited critically ill patients in two-fold. This approach is not only useful in controlling per-patient normoglycemic level, but also able to recognize the time for PN supplement when patients become hypoglycemic. This serves as a potential decision support in the intensive care environment when healthcare providers faced with the complexity of dynamics between good glycemic control and optimized nutrition therapy.

Simulating and testing a non-contact structural health monitoring system

Structural health monitoring (SHM) is a technique which enables the integrity of a physical structure to be analysed in a non-invasive manner, meaning that no structural disassembly needs to take place. In addition to being non-invasive, information gathered using this technique can be immediately available to engineers. This technique can be applied to a number of different types of structures, ranging from buildings, to bridges, to vehicles. The research discussed in this paper is focused on the development of a novel non-line of sight (NLOS) radio frequency (RF) based technique for performing SHM. RF transceivers will be placed at fixed locations on a structure, and by analysing transmitted and reflected signals around the network, the displacements between the transceivers can be computed. These measurements allow for the calculation of interstorey drift ratios (IDRs), which characterise the significance of the movement of a structure resulting from an external force. These IDRs can be used to understand the stress on the system, from which the structures integrity can be understood. The feasibility of such a technique has been investigated, and the potential signal processing methods to utilise RF in SHM have been evaluated. Frequency-modulated continuous wave (FMCW) radar has been identified as the most suitable method due to its distance resolution and short sampling period. It has also been used in similar applications, demonstrating that the technique is viable in this field. A prototype FMCW system has been developed, and is currently ready for initial testing.

Re: Chung et al.'s Letter to the Editor in response to: Early detection of abnormal left ventricular relaxation in acute myocardial ischemia with a quadratic model. Med Eng Phys 2014;36(September (9)):1101-5 by Morimont et al.

h 1 Dear Dr. Black, We are grateful for the comments to our recent manuscript [1] rovided by Chung et al. and we very much appreciate their effort in urther elucidating left ventricular (LV) relaxation [2]. We are happy o respond to their comments as follows. We fully agree with them that models based on known physologic attributes of isovolumic relaxation (IVR) and their physial/physiologic analogs provide a clearer view and consistent model f IVR. LV relaxation is a complex mechanism that is governed by the ontinuous interplay of the sensitivity of the contractile system to he loading conditions and the dissipating activation [3]. This doule control is modulated by the regional and temporal non-uniform istribution of loading condition and activation front [4]. While mechanical non-uniformity during IVR was documented in everal pathological conditions like acute LV ischemia [5], the clasical method uses a monoexponential fit of IVR. Thereby, this conentional method can fail to accurately detect abnormalities in the elaxation process in some cases. The aim of our study was to proide a clinically applicable, and thus relatively simple, method that ould detect abnormalities in LV relaxation, eventually in real-time t the bedside, by using a non-uniform function, to improve diagnois and/or treatment of acute LV ischemia. Our “quadratic” model is based on a time constant and a degree f “non-uniformity” of LV relaxation. Our model, derived from the loistic model [6], was very sensitive to detect changes in relaxation esulting from ischemia. It was not possible to determine to what xtent physiologic attributes like elastic recoil and/or viscous crossridge relaxation were implied. Chung et al. [2] propose that a best odel should be derived from physical/physiological considerations, hile we believe a best model must first be able to detect changes n relaxation with as much sensitivity as possible. The tension beween these perspectives, and the use of model-based approaches to edicine, includes all the potential difficulties of (real-time) identifiation of model parameters, where their model has significant potenial to be practically unidentifiable when the relationship is linear or early linear, as well as other cases that do not fit the assumed model