Publications
156 results found
Afentakis I, Unsworth R, Herrero P, et al., 2023, Development and Validation of Binary Classifiers to Predict Nocturnal Hypoglycemia in Adults With Type 1 Diabetes., J Diabetes Sci Technol
BACKGROUND: One of the biggest challenges for people with type 1 diabetes (T1D) using multiple daily injections (MDIs) is nocturnal hypoglycemia (NH). Recurrent NH can lead to serious complications; hence, prevention is of high importance. In this work, we develop and externally validate, device-agnostic Machine Learning (ML) models to provide bedtime decision support to people with T1D and minimize the risk of NH. METHODS: We present the design and development of binary classifiers to predict NH (blood glucose levels occurring below 70 mg/dL). Using data collected from a 6-month study of 37 adult participants with T1D under free-living conditions, we extract daytime features from continuous glucose monitor (CGM) sensors, administered insulin, meal, and physical activity information. We use these features to train and test the performance of two ML algorithms: Random Forests (RF) and Support Vector Machines (SVMs). We further evaluate our model in an external population of 20 adults with T1D using MDI insulin therapy and wearing CGM and flash glucose monitoring sensors for two periods of eight weeks each. RESULTS: At population-level, SVM outperforms RF algorithm with a receiver operating characteristic-area under curve (ROC-AUC) of 79.36% (95% CI: 76.86%, 81.86%). The proposed SVM model generalizes well in an unseen population (ROC-AUC = 77.06%), as well as between the two different glucose sensors (ROC-AUC = 77.74%). CONCLUSIONS: Our model shows state-of-the-art performance, generalizability, and robustness in sensor devices from different manufacturers. We believe it is a potential viable approach to inform people with T1D about their risk of NH before it occurs.
Zhu T, Li K, Herrero P, et al., 2023, GluGAN: Generating Personalized Glucose Time Series Using Generative Adversarial Networks., IEEE J Biomed Health Inform, Vol: PP
Time series data generated by continuous glucose monitoring sensors offer unparalleled opportunities for developing data-driven approaches, especially deep learning-based models, in diabetes management. Although these approaches have achieved state-of-the-art performance in various fields such as glucose prediction in type 1 diabetes (T1D), challenges remain in the acquisition of large-scale individual data for personalized modeling due to the elevated cost of clinical trials and data privacy regulations. In this work, we introduce GluGAN, a framework specifically designed for generating personalized glucose time series based on generative adversarial networks (GANs). Employing recurrent neural network (RNN) modules, the proposed framework uses a combination of unsupervised and supervised training to learn temporal dynamics in latent spaces. Aiming to assess the quality of synthetic data, we apply clinical metrics, distance scores, and discriminative and predictive scores computed by post-hoc RNNs in evaluation. Across three clinical datasets with 47 T1D subjects (including one publicly available and two proprietary datasets), GluGAN achieved better performance for all the considered metrics when compared with four baseline GAN models. The performance of data augmentation is evaluated by three machine learning-based glucose predictors. Using the training sets augmented by GluGAN significantly reduced the root mean square error for the predictors over 30 and 60-minute horizons. The results suggest that GluGAN is an effective method in generating high-quality synthetic glucose time series and has the potential to be used for evaluating the effectiveness of automated insulin delivery algorithms and as a digital twin to substitute for pre-clinical trials.
Unsworth R, Armiger R, Jugnee N, et al., 2023, Safety and efficacy of an adaptive bolus calculator for Type 1 diabetes: a randomised control cross over study, Diabetes Technology and Therapeutics, Vol: 25, Pages: 414-425, ISSN: 1520-9156
Background The Advanced Bolus Calculator for Type 1 Diabetes (ABC4D) is a decision support system employing the artificial intelligence technique of case-based reasoning to adapt and personalise insulin bolus doses. The integrated system comprises a smartphone application and clinical web portal. We aimed to assess safety and efficacy of the ABC4D (intervention) compared to a non-adaptive bolus calculator (control). Methods This was a prospective randomised controlled crossover study. Following a 2-week run-in period, participants were randomised to ABC4D or control for 12 weeks. After a 6-week washout period, participants crossed over for 12 weeks. The primary outcome was difference in percentage (%) time in range (TIR) (3.9-10.0 mmol/L (70-180mg/dL)) change during the daytime (07:00-22:00) between groups. Results 37 adults with type 1 diabetes on multiple daily injections of insulin were randomised, median (IQR) age 44.7 (28.2-55.2) years, diabetes duration 15.0 (9.5-29.0) years, HbA1C 61.0 (58.0-67.0) mmol/mol (7.7 (7.5-8.3)%). Data from 33 participants were analysed. There was no significant difference in daytime %TIR change with ABC4D compared to control (median (IQR) +0.1 (-2.6 to + 4.0)% versus +1.9 (-3.8 to + 10.1)%; p = 0.53). Participants accepted fewer meal dose recommendations in the intervention compared to control (78.7 (55.8-97.6)% versus 93.5 (73.8-100)%; p = 0.009) with a greater reduction in insulin dosage from that recommended. Conclusion The ABC4D is safe for adapting insulin bolus doses and provided the same level of glycaemic control as the non-adaptive bolus calculator. Results suggest that participants did not follow ABC4D recommendations as frequently as control, impacting its effectiveness.
Zhu T, Kuang L, Daniels J, et al., 2023, IoMT-Enabled Real-Time Blood Glucose Prediction With Deep Learning and Edge Computing, IEEE INTERNET OF THINGS JOURNAL, Vol: 10, Pages: 3706-3719, ISSN: 2327-4662
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- Citations: 10
Zhu T, Li K, Herrero P, et al., 2023, Personalized blood glucose prediction for Type 1 diabetes using evidential deep learning and meta-learning., IEEE Transactions on Biomedical Engineering, Vol: 70, Pages: 193-204, ISSN: 0018-9294
The availability of large amounts of data from continuous glucose monitoring (CGM), together with the latest advances in deep learning techniques, have opened the door to a new paradigm of algorithm design for personalized blood glucose (BG) prediction in type 1 diabetes (T1D) with superior performance. However, there are several challenges that prevent the widespread implementation of deep learning algorithms in actual clinical settings, including unclear prediction confidence and limited training data for new T1D subjects. To this end, we propose a novel deep learning framework, Fast-adaptive and Confident Neural Network (FCNN), to meet these clinical challenges. In particular, an attention-based recurrent neural network is used to learn representations from CGM input and forward a weighted sum of hidden states to an evidential output layer, aiming to compute personalized BG predictions with theoretically supported model confidence. The model-agnostic meta-learning is employed to enable fast adaptation for a new T1D subject with limited training data. The proposed framework has been validated on three clinical datasets. In particular, for a dataset including 12 subjects with T1D, FCNN achieved a root mean square error of 18.64±2.60 mg/dL and 31.07±3.62 mg/dL for 30 and 60-minute prediction horizons, respectively, which outperformed all the considered baseline methods with significant improvements. These results indicate that FCNN is a viable and effective approach for predicting BG levels in T1D. The well-trained models can be implemented in smartphone apps to improve glycemic control by enabling proactive actions through real-time glucose alerts.
Herrero Vinas P, Wilson R, Armiger R, et al., 2022, Closed-loop control of continuous piperacillin delivery: an in silico study, Frontiers in Bioengineering and Biotechnology, Vol: 10, ISSN: 2296-4185
Background and objective: Sub-therapeutic dosing of piperacillin-tazobactam in critically-ill patients is associated with poor clinical outcomes and may promote the emergence of drug-resistant infections. In this paper, an in silico investigation of whether closed-loop control can improve pharmacokinetic-pharmacodynamic (PK-PD) target attainment is described.Method: An in silico platform was developed using PK data from 20 critically-ill patients receiving piperacillin-tazobactam where serum and tissue interstitial fluid (ISF) PK were defined. Intra-day variability on renal clearance, ISF sensor error, and infusion constraints were taken into account. Proportional-integral-derivative (PID) control was selected for drug delivery modulation. Dose adjustment was made based on ISF sensor data with a 30-minute sampling period, targeting a serum piperacillin concentration between 32-64 mg/L. A single tuning parameter set was employed across the virtual population. The PID controller was compared to standard therapy, including bolus and continuous infusion of piperacillin-tazobactam.Results: Despite significant inter-subject and simulated intra-day PK variability and sensor error, PID demonstrated a significant improvement in target attainment compared to traditional bolus and continuous infusion approaches. Conclusion: A PID controller driven by ISF drug concentration measurements has the potential to precisely deliver piperacillin-tazobactam in critically-ill patients undergoing treatment for sepsis.
Zhu T, Uduku C, Li K, et al., 2022, Enhancing self-management in type 1 diabetes with wearables and deep learning, npj Digital Medicine, Vol: 5, ISSN: 2398-6352
People living with type 1 diabetes (T1D) require lifelong selfmanagement to maintain glucose levels in a safe range. Failure to do socan lead to adverse glycemic events with short and long-term complications. Continuous glucose monitoring (CGM) is widely used in T1Dself-management for real-time glucose measurements, while smartphoneapps are adopted as basic electronic diaries, data visualization tools, andsimple decision support tools for insulin dosing. Applying a mixed effectslogistic regression analysis to the outcomes of a six-week longitudinalstudy in 12 T1D adults using CGM and a clinically validated wearablesensor wristband (NCT ID: NCT03643692), we identified several significant associations between physiological measurements and hypo- andhyperglycemic events measured an hour later. We proceeded to developa new smartphone-based platform, ARISES (Adaptive, Real-time, and Intelligent System to Enhance Self-care), with an embedded deep learning algorithm utilizing multi-modal data from CGM, daily entries of mealand bolus insulin, and the sensor wristband to predict glucose levels andhypo- and hyperglycemia. For a 60-minute prediction horizon, the proposed algorithm achieved the average root mean square error (RMSE)of 35.28±5.77 mg/dL with the Matthews correlation coefficients fordetecting hypoglycemia and hyperglycemia of 0.56±0.07 and 0.70±0.05,respectively. The use of wristband data significantly reduced the RMSEby 2.25 mg/dL (p < 0.01). The well-trained model is implemented onthe ARISES app to provide real-time decision support. These resultsindicate that the ARISES has great potential to mitigate the risk ofsevere complications and enhance self-management for people with T1D.
Akturk HK, Herrero P, Oliver N, et al., 2022, Impact of Different Types of Data Loss on Optimal Continuous Glucose Monitoring Sampling Duration, DIABETES TECHNOLOGY & THERAPEUTICS, Vol: 24, Pages: 749-753, ISSN: 1520-9156
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- Citations: 4
Herrero P, Reddy M, Georgiou P, et al., 2022, Identifying Continuous Glucose Monitoring Data Using Machine Learning, DIABETES TECHNOLOGY & THERAPEUTICS, Vol: 24, Pages: 403-408, ISSN: 1520-9156
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- Citations: 3
Daniels J, Herrero P, Georgiou P, 2022, A Deep Learning Framework for Automatic Meal Detection and Estimation in Artificial Pancreas Systems, SENSORS, Vol: 22
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- Citations: 3
Armiger R, Reddy M, Oliver NS, et al., 2022, An In Silico Head-to-Head Comparison of the Do-It-Yourself Artificial Pancreas Loop and Bio-Inspired Artificial Pancreas Control Algorithms, JOURNAL OF DIABETES SCIENCE AND TECHNOLOGY, Vol: 16, Pages: 29-39, ISSN: 1932-2968
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- Citations: 1
Daniels J, Herrero P, Georgiou P, 2022, A Multitask Learning Approach to Personalized Blood Glucose Prediction, IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS, Vol: 26, Pages: 436-445, ISSN: 2168-2194
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- Citations: 4
Hernandez B, Herrero-Viñas P, Rawson TM, et al., 2021, Resistance trend estimation using regression analysis to enhance antimicrobial surveillance: a multi-centre study in London 2009-2016, Antibiotics, Vol: 10, Pages: 1-16, ISSN: 2079-6382
In the last years, there has been an increase of antimicrobial resistance rates around the world with the misuse and overuse of antimicrobials as one of the main leading drivers. In response to this threat, a variety of initiatives have arisen to promote the efficient use of antimicrobials. These initiatives rely on antimicrobial surveillance systems to promote appropriate prescription practices and are provided by national or global health care institutions with limited consideration of the variations within hospitals. As a consequence, physicians’ adherence to these generic guidelines is still limited. To fill this gap, this work presents an automated approach to performing local antimicrobial surveillance from microbiology data. Moreover, in addition to the commonly reported resistance rates, this work estimates secular resistance trends through regression analysis to provide a single value that effectively communicates the resistance trend to a wider audience. The methods considered for trend estimation were ordinary least squares regression, weighted least squares regression with weights inversely proportional to the number of microbiology records available and autoregressive integrated moving average. Among these, weighted least squares regression was found to be the most robust against changes in the granularity of the time series and presented the best performance. To validate the results, three case studies have been thoroughly compared with the existing literature: (i) Escherichia coli in urine cultures; (ii) Escherichia coli in blood cultures; and (iii) Staphylococcus aureus in wound cultures. The benefits of providing local rather than general antimicrobial surveillance data of a higher quality is two fold. Firstly, it has the potential to stimulate engagement among physicians to strengthen their knowledge and awareness on antimicrobial resistance which might encourage prescribers to change their prescription habits more willingly. Moreover, it pro
Zhu T, Li K, Herrero P, et al., 2021, Deep Learning for Diabetes: A Systematic Review, IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS, Vol: 25, Pages: 2744-2757, ISSN: 2168-2194
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- Citations: 24
Rawson TM, Wilson RC, O'Hare D, et al., 2021, Optimizing antimicrobial use: challenges, advances and opportunities, NATURE REVIEWS MICROBIOLOGY, Vol: 19, Pages: 747-758, ISSN: 1740-1526
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- Citations: 28
Rawson TM, Hernandez B, Moore L, et al., 2021, A real-world evaluation of a case-based reasoning algorithm to support antimicrobial prescribing decisions in acute care, Clinical Infectious Diseases, Vol: 72, Pages: 2103-2111, ISSN: 1058-4838
BackgroundA locally developed Case-Based Reasoning (CBR) algorithm, designed to augment antimicrobial prescribing in secondary care was evaluated.MethodsPrescribing recommendations made by a CBR algorithm were compared to decisions made by physicians in clinical practice. Comparisons were examined in two patient populations. Firstly, in patients with confirmed Escherichia coli blood stream infections (‘E.coli patients’), and secondly in ward-based patients presenting with a range of potential infections (‘ward patients’). Prescribing recommendations were compared against the Antimicrobial Spectrum Index (ASI) and the WHO Essential Medicine List Access, Watch, Reserve (AWaRe) classification system. Appropriateness of a prescription was defined as the spectrum of the prescription covering the known, or most-likely organism antimicrobial sensitivity profile.ResultsIn total, 224 patients (145 E.coli patients and 79 ward patients) were included. Mean (SD) age was 66 (18) years with 108/224 (48%) female gender. The CBR recommendations were appropriate in 202/224 (90%) compared to 186/224 (83%) in practice (OR: 1.24 95%CI:0.392-3.936;p=0.71). CBR recommendations had a smaller ASI compared to practice with a median (range) of 6 (0-13) compared to 8 (0-12) (p<0.01). CBR recommendations were more likely to be classified as Access class antimicrobials compared to physicians’ prescriptions at 110/224 (49%) vs. 79/224 (35%) (OR: 1.77 95%CI:1.212-2.588 p<0.01). Results were similar for E.coli and ward patients on subgroup analysis.ConclusionsA CBR-driven decision support system provided appropriate recommendations within a narrower spectrum compared to current clinical practice. Future work must investigate the impact of this intervention on prescribing behaviours more broadly and patient outcomes.
Leon-Vargas F, Martin C, Garcia-Jaramillo M, et al., 2021, Is a cloud-based platform useful for diabetes management in Colombia? The Tidepool experience, COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE, Vol: 208, ISSN: 0169-2607
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- Citations: 1
Zhu T, Li K, Herrero P, et al., 2021, Basal Glucose Control in Type 1 Diabetes Using Deep Reinforcement Learning: An In Silico Validation, IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS, Vol: 25, Pages: 1223-1232, ISSN: 2168-2194
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- Citations: 19
Avari P, Leal Y, Herrero Vinas P, et al., 2021, Safety and feasibility of the PEPPER adaptive bolus advisor and safety system; a randomized control study, Diabetes Technology and Therapeutics, Vol: 23, Pages: 175-186, ISSN: 1520-9156
Background: The Patient Empowerment through Predictive Personalized Decision Support (PEPPER) system provides personalized bolus advice for people with type 1 diabetes. The system incorporates an adaptive insulin recommender system (based on case-based reasoning, an artificial intelligence methodology), coupled with a safety system, which includes predictive glucose alerts and alarms, predictive low-glucose suspend, personalized carbohydrate recommendations, and dynamic bolus insulin constraint. We evaluated the safety and efficacy of the PEPPER system compared to a standard bolus calculator.Methods: This was an open-labeled multicenter randomized controlled crossover study. Following 4-week run-in, participants were randomized to PEPPER/Control or Control/PEPPER in a 1:1 ratio for 12 weeks. Participants then crossed over after a washout period. The primary end-point was percentage time in range (TIR, 3.9–10.0 mmol/L [70–180 mg/dL]). Secondary outcomes included glycemic variability, quality of life, and outcomes on the safety system and insulin recommender.Results: Fifty-four participants on multiple daily injections (MDI) or insulin pump completed the run-in period, making up the intention-to-treat analysis. Median (interquartile range) age was 41.5 (32.3–49.8) years, diabetes duration 21.0 (11.5–26.0) years, and HbA1c 61.0 (58.0–66.1) mmol/mol. No significant difference was observed for percentage TIR between the PEPPER and Control groups (62.5 [52.1–67.8] % vs. 58.4 [49.6–64.3] %, respectively, P = 0.27). For quality of life, participants reported higher perceived hypoglycemia with the PEPPER system despite no objective difference in time spent in hypoglycemia.Conclusions: The PEPPER system was safe, but did not change glycemic outcomes, compared to control. There is wide scope for integrating PEPPER into routine diabetes management for pump and MDI users. Further studies are required to confir
Contreras I, Calm R, Sainz MA, et al., 2021, Combining Grammatical Evolution with Modal Interval Analysis: An Application to Solve Problems with Uncertainty, MATHEMATICS, Vol: 9
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- Citations: 1
Rawson TM, Hernandez B, Wilson R, et al., 2021, Supervised machine learning to support the diagnosis of bacterial infection in the context of COVID-19, JAC-Antimicrobial Resistance, Vol: 3, Pages: 1-4, ISSN: 2632-1823
Background: Bacterial infection has been challenging to diagnose in patients with COVID-19. We developed and evaluated supervised machine learning algorithms to support the diagnosis of secondary bacterial infection in hospitalized patients during COVID-19.Methods: Inpatient data at three London hospitals for the first COVD-19 wave in March and April 2020 were extracted. Demographic, blood test, and microbiology data for individuals with and without SARS-CoV-2 positive PCR were obtained. A Gaussian-Naïve Bayes (GNB), Support Vector Machine (SVM), and Artificial Neuronal Network (ANN) were trained and compared using the area under the receiver operating characteristic curve (AUCROC). The best performing algorithm (SVM with 21 blood test variables) was prospectively piloted in July 2020. AUCROC was calculated for the prediction of a positive microbiological sample within 48 hours of admission. Results: A total of 15,599 daily blood profiles for 1,186 individual patients were identified to train the algorithms. 771/1186 (65%) individuals were SARS-CoV-2 PCR positive. Clinically significant microbiology results were present for 166/1186 (14%) patients during admission. A SVM algorithm trained with 21 routine blood test variables and over 8000 individual profiles had the best performance. AUCROC was 0.913, sensitivity 0.801, and specificity 0.890. Prospective testing on 54 patients on admission (28/54, 52% SARS-CoV-2 PCR positive) demonstrated an AUCROC of 0.960 (0.90-1.00). Conclusion: A SVM using 21 routine blood test variables had excellent performance at inferring the likelihood of positive microbiology. Further prospective evaluation of the algorithms ability to support decision making for the diagnosis of bacterial infection in COVID-19 cohorts is underway.
Zhu T, Kuang L, Li K, et al., 2021, Blood Glucose Prediction in Type 1 Diabetes Using Deep Learning on the Edge, IEEE International Symposium on Circuits and Systems (IEEE ISCAS), Publisher: IEEE, ISSN: 0271-4302
Kuang L, Zhu T, Li K, et al., 2021, Live Demonstration: An IoT Wearable Device for Real-time Blood Glucose Prediction with Edge AI, IEEE Biomedical Circuits and Systems Conference (IEEE BioCAS), Publisher: IEEE
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- Citations: 1
Moscardo V, Herrero P, Reddy M, et al., 2020, Assessment of Glucose Control Metrics by Discriminant Ratio, DIABETES TECHNOLOGY & THERAPEUTICS, Vol: 22, Pages: 719-726, ISSN: 1520-9156
Zhu T, Li K, Chen J, et al., 2020, Dilated Recurrent Neural Networks for Glucose Forecasting in Type 1 Diabetes, JOURNAL OF HEALTHCARE INFORMATICS RESEARCH, Vol: 4, Pages: 308-324, ISSN: 2509-4971
Zhu T, Li K, Kuang L, et al., 2020, An Insulin Bolus Advisor for Type 1 Diabetes Using Deep Reinforcement Learning, SENSORS, Vol: 20
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- Citations: 11
Guemes A, Cappon G, Hernandez B, et al., 2020, Predicting quality of overnight glycaemic control in type 1 diabetes using binary classifiers, IEEE Journal of Biomedical and Health Informatics, Vol: 24, Pages: 1439-1446, ISSN: 2168-2194
In type 1 diabetes management, maintaining nocturnal blood glucose within target range can be challenging. Although semi-automatic systems to modulate insulin pump delivery, such as low-glucose insulin suspension and the artificial pancreas, are starting to become a reality, their elevated cost and performance below user expectations is hindering their adoption. Hence, a decision support system that helps people with type 1 diabetes, on multiple daily injections or insulin pump therapy, to avoid undesirable overnight blood glucose fluctuations (hyper- or hypoglycaemic) is an attractive alternative. In this paper, we introduce a novel data-driven approach to predict the quality of overnight glycaemic control in people with type 1 diabetes by analyzing commonly gathered data during the day-time period (continuous glucose monitoring data, meal intake and insulin boluses). The proposed approach is able to predict whether overnight blood glucose concentrations are going to remain within or outside the target range, and therefore allows the user to take the appropriate preventive action (snack or change in basal insulin). For this purpose, a number of popular established machine learning algorithms for classification were evaluated and compared on a publicly available clinical dataset (i.e. OhioT1DM). Although there is no clearly superior classification algorithm, this study indicates that, by using commonly gathered data in type 1 diabetes management, it is possible to predict the quality of overnight glycaemic control with reasonable accuracy (AUC-ROC= 0.7).
Zhu T, Li K, Uduku C, et al., 2020, PERSONALIZED MEAL INSULIN BOLUS FOR TYPE 1 DIABETES USING DEEP REINFORCEMENT LEARNING, Publisher: MARY ANN LIEBERT, INC, Pages: A115-A116, ISSN: 1520-9156
Daniels J, Zhu T, Li K, et al., 2020, Arises: an advanced clinical decision support platform for the management of type 1 diabetes, The conference name (including place and date(s) of the conference): 13th International Conference on Advanced Technologies & Treatments for Diabetes (ATTD 2020), Publisher: Mary Ann Liebert, Pages: A57-A57, ISSN: 1520-9156
Herrero P, Alalitei A, Reddy M, et al., 2020, Robust determination of the optimal continuous glucose monitoring length of intervention to evaluate long-term glycaemic control, 13th International Conference on Advanced Technologies & Treatments for Diabetes (ATTD 2020), Publisher: Mary Ann Liebert, Pages: A130-A130, ISSN: 1520-9156
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