"Randomized phase II study of azacitidine +/- lenalidomide in higher-risk myelodysplastic syndromes and acute myeloid leukemia with a karyotype including Del(5q)"

Non peer reviewe

Glucose management for exercise using continuous glucose monitoring (CGM) and intermittently scanned CGM (isCGM) systems in type 1 diabetes: position statement of the European Association for the Study of Diabetes (EASD) and of the International Society for Pediatric and Adolescent Diabetes (ISPAD) endorsed by JDRF and supported by the American Diabetes Association (ADA)

Physical exercise is an important component in the management of type 1 diabetes across the lifespan. Yet, acute exercise increases the risk of dysglycaemia, and the direction of glycaemic excursions depends, to some extent, on the intensity and duration of the type of exercise. Understandably, fear of hypoglycaemia is one of the strongest barriers to incorporating exercise into daily life. Risk of hypoglycaemia during and after exercise can be lowered when insulin‐dose adjustments are made and/or additional carbohydrates are consumed. Glycaemic management during exercise has been made easier with continuous glucose monitoring (CGM) and intermittently scanned continuous glucose monitoring (isCGM) systems; however, because of the complexity of CGM and isCGM systems, both individuals with type 1 diabetes and their healthcare professionals may struggle with the interpretation of given information to maximise the technological potential for effective use around exercise (ie, before, during and after). This position statement highlights the recent advancements in CGM and isCGM technology, with a focus on the evidence base for their efficacy to sense glucose around exercise and adaptations in the use of these emerging tools, and updates the guidance for exercise in adults, children and adolescents with type 1 diabetes

Fusion of metabolomics and proteomics data for biomarkers discovery: case study on the experimental autoimmune encephalomyelitis

Contains fulltext : 91843.pdf (publisher's version ) (Open Access)12 p

A one-size-fits-all artificial pancreas for people with type 1 diabetes based on physiological insight and feedback control

We propose a model-free artificial pancreas (AP) for people with type 1 diabetes. The algorithmic parameters are tuned to a virtual population of 1,000,000 individuals, and the AP repeatedly estimates the basal and bolus insulin requirements necessary for maintaining normal blood glucose levels. Therefore, the AP can be used without healthcare personnel or engineers customizing the algorithm to each user. The estimates are based on bodyweight, measurements from a continuous glucose monitor (CGM), and estimates of the meal carbohydrate contents. In a virtual clinical trial with a111,000,000 individuals (i.e., a Monte Carlo closed-loop simulation), the AP achieves a mean time in range of more than 87% and over 88% of the participants satisfy several glycemic targets

Use of fast-acting insulin aspart in insulin pump therapy in clinical practice

Fast-acting insulin aspart (faster aspart) is a novel formulation of insulin aspart (IAsp) containing the additional excipients niacinamide and L-arginine. The improved pharmacological profile and greater early glucose-lowering action of faster aspart compared with IAsp suggests that faster aspart may be advantageous for people with diabetes using continuous subcutaneous insulin infusion (CSII). The recent onset 5 trial was the first to evaluate the efficacy and safety of an ultra-fast-acting insulin in CSII therapy in a large number of participants with type 1 diabetes (T1D). Non-inferiority of faster aspart to IAsp in terms of change from baseline in HbA1c was confirmed, with an estimated treatment difference (ETD) of 0.09% (95% CI, 0.01; 0.17; P < 0.001 for non-inferiority [0.4% margin]). Faster aspart was superior to IAsp in terms of change from baseline in 1-hour post-prandial glucose (PPG) increment after a meal test (ETD [95% CI], -0.91 mmol/L [-1.43; -0.39]; P = 0.001), with statistically significant improvements also at 30 minutes and 2 hours. The overall rate of severe or blood glucose-confirmed hypoglycaemia was not statistically significantly different between treatments, with an estimated rate ratio of 1.00 (95% CI, 0.85; 1.16). A numerical imbalance in severe hypoglycaemic episodes between faster aspart and IAsp was seen in the treatment (21 vs 7) and the 4-week run-in periods (4 vs 0). Experience from clinical practice indicates that all pump settings should be reviewed when initiating faster aspart with CSII, and that the use of continuous glucose monitoring or flash glucose monitoring, along with a good understanding of meal content and bolus type, may also facilitate optimal use. This review summarizes the available clinical evidence for faster aspart administered via CSII and highlights practical considerations based on clinical experience that may help healthcare providers and individuals with T1D successfully initiate and adjust faster aspart with CSII.status: publishe

Efficacy, adverse events, and inter-drug comparison of mepolizumab and reslizumab anti-IL-5 treatments of severe asthma – a systematic review and meta-analysis

Background: New, complex, and expensive therapies targeting Interleukin-5 (IL-5) to treat severe eosinophilic asthma are emerging. Objective: To assess efficacy, adverse events, and inter-drug comparison of mepolizumab and reslizumab for treating severe eosinophilic asthma. Design: A systematic review and meta-analysis on randomized, placebo-controlled, clinical trials elucidating two critical (exacerbation rate and oral corticosteroid (OCS) use) and six important clinical outcomes on the efficacy and safety of mepolizumab and reslizumab. Results: Five studies (N = 2197) contributed with data for exacerbation rate, showing a reduction of 53% (95% CI 46; 59) in favour of anti-IL-5, corresponding to –0.94 annual exacerbations (95% CI –1.08;–0.82), thus exceeding the predefined minimal clinical important difference (MCID) of 25% reduction of the estimated ≥2 annual exacerbations. Quality of evidence was considered moderate, with low heterogeneity in study findings (I2 = 0%). One study (N = 135) contributed with data on percentage of patients experiencing ≥50% reduction inoral corticosteroid treatment, showing an effect of 20% (95% CI 2.3;47) in favour of anti-IL-5 treatment (mepolizumab), thus exceeding the predefined MCID of 10%. Quality of evidence was considered low. Compared to placebo, anti-IL-5 showed significant improvements in lung function, asthma control, and asthma-related quality of life, but below the MCIDs. No differences were observed for serious adverse events and number of patients, who dropped out. No studies evaluating sickleave or head-to-head comparisons were identified. By indirect comparison, we found no significant difference between mepolizumab and reslizumab in any ofthe predefined clinical outcomes. OCS treatment reduction could not be compared due to lack of reslizumab studies investigating this outcome. Conclusions: Mepolizumab and reslizumab provide significant and clinically relevant improvements in exacerbation rate and OCS reduction. Indirect, inter-study comparisons revealed no differences between the anti-IL-5 drugs in efficacy or safety measures

Insulin Pump Treatment in Adults with Type 1 Diabetes in the Capital Region of Denmark:Design and Cohort Characteristics of the Steno Tech Survey

INTRODUCTION: Insulin pump therapy can improve quality of life and glycaemic outcomes for many people with type 1 diabetes (T1D). The multidimensional Steno Tech Survey study aims to investigate why some insulin pump users do not achieve treatment goals. In this article, we present the study design and analyse differences in population characteristics between responders and non-responders. METHODS: In June 2020, all 1591 insulin pump users (≥ 18 years) in the Capital Region of Denmark were invited to participate in an online questionnaire that evaluated several dimensions of insulin pump self-management and psychosocial health. Demographic, socioeconomic and clinical characteristics, including age, sex and HbA1c, of the cohort were identified via national registries. Predictors of questionnaire response/non-response were explored with logistic regression analysis. RESULTS: In the full study population, 58% were female, median age was 42 years and median HbA1c was 58 mmol/mol (7.5%); 30% had HbA1c < 53 mmol/mol (7.0%). In total, 770 individuals (48%) responded to the questionnaire. Logistic regression analysis showed that 50+ years of age (odds ratio [OR] = 2.3, 95% confidence interval [CI]: 1.4–3.8), female sex (OR = 1.3, CI: 1.02–1.6), being married (OR = 1.8, CI: 1.3–2.4) and having long higher education (OR = 1.6, CI: 1.004–2.5) were significantly associated with a higher likelihood of responding to the survey; the opposite was found for HbA1c from 64 to < 75 mmol (8.0–9.0%) (OR = 0.6, CI: 0.4–0.8) and HbA1c ≥ 75 mmol/mol (≥ 9.0%) (OR = 0.2, CI: 0.1–0.3). CONCLUSIONS: The established Steno Tech cohort enables future analysis of a range of psychosocial and behavioural aspects of insulin pump self-management. Interpretation and generalization of findings should consider observed differences between responders and non-responders. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13300-021-01181-0