Consensus Recommendations for the Use of Automated Insulin Delivery (AID) Technologies in Clinical Practice

International audienceThe significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers and payers. While maintaining near-normal glucose levels has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past six years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems have recently become an integral part of diabetes management. However, recommendations for using AID systems in clinical settings have been lacking. Such guided recommendations are critical for AID success and acceptance. All clinicians working with PwD need to become familiar with the available systems in order to eliminate disparities in diabetes quality of care. This report provides much-needed guidance for clinicians who are interested in utilizing AIDs and presents a comprehensive listing of the evidence payers should consider when determining eligibility criteria for AID insurance coverage

SARS-CoV-2 lineage B.1.1.7 is associated with greater disease severity among hospitalised women but not men: multicentre cohort study.

BACKGROUND: SARS-CoV-2 lineage B.1.1.7 has been associated with an increased rate of transmission and disease severity among subjects testing positive in the community. Its impact on hospitalised patients is less well documented. METHODS: We collected viral sequences and clinical data of patients admitted with SARS-CoV-2 and hospital-onset COVID-19 infections (HOCIs), sampled 16 November 2020 to 10 January 2021, from eight hospitals participating in the COG-UK-HOCI study. Associations between the variant and the outcomes of all-cause mortality and intensive therapy unit (ITU) admission were evaluated using mixed effects Cox models adjusted by age, sex, comorbidities, care home residence, pregnancy and ethnicity. FINDINGS: Sequences were obtained from 2341 inpatients (HOCI cases=786) and analysis of clinical outcomes was carried out in 2147 inpatients with all data available. The HR for mortality of B.1.1.7 compared with other lineages was 1.01 (95% CI 0.79 to 1.28, p=0.94) and for ITU admission was 1.01 (95% CI 0.75 to 1.37, p=0.96). Analysis of sex-specific effects of B.1.1.7 identified increased risk of mortality (HR 1.30, 95% CI 0.95 to 1.78, p=0.096) and ITU admission (HR 1.82, 95% CI 1.15 to 2.90, p=0.011) in females infected with the variant but not males (mortality HR 0.82, 95% CI 0.61 to 1.10, p=0.177; ITU HR 0.74, 95% CI 0.52 to 1.04, p=0.086). INTERPRETATION: In common with smaller studies of patients hospitalised with SARS-CoV-2, we did not find an overall increase in mortality or ITU admission associated with B.1.1.7 compared with other lineages. However, women with B.1.1.7 may be at an increased risk of admission to intensive care and at modestly increased risk of mortality.This report was produced by members of the COG-UK-HOCI Variant substudy consortium. COG-UK-HOCI is part of COG-UK. COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute

Consensus recommendations for the use of automated insulin delivery technologies in clinical practice

The significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers, and payers. While maintaining near-normal glucose levels has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past 6 years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems have recently become an integral part of diabetes management. However, recommendations for using AID systems in clinical settings have been lacking. Such guided recommendations are critical for AID success and acceptance. All clinicians working with PwD need to become familiar with the available systems in order to eliminate disparities in diabetes quality of care. This report provides much-needed guidance for clinicians who are interested in utilizing AIDs and presents a comprehensive listing of the evidence payers should consider when determining eligibility criteria for AID insurance coverage

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Maternal adverse childhood experiences (ACEs) and DNA methylation of newborns in cord blood

BackgroundAdverse childhood experiences (ACEs) increase the risk of poor health outcomes later in life. Psychosocial stressors may also have intergenerational health effects by which parental ACEs are associated with mental and physical health of children. Epigenetic programming may be one mechanism linking parental ACEs to child health. This study aimed to investigate epigenome-wide associations of maternal preconception ACEs with DNA methylation patterns of children. In the Center for the Health Assessment of Mothers and Children of Salinas study, cord blood DNA methylation was measured using the Illumina HumanMethylation450 BeadChip. Preconception ACEs, which occurred during the mothers' childhoods, were collected using a standard ACE questionnaire including 10 ACE indicators. Maternal ACE exposures were defined in this study as (1) the total number of ACEs; (2) the total number of ACEs categorized as 0, 1-3, and > 4; and (3) individual ACEs. Associations of ACE exposures with differential methylated positions, regions, and CpG modules determined using weighted gene co-expression network analysis were evaluated adjusting for covariates.ResultsData on maternal ACEs and cord blood DNA methylation were available for 196 mother/newborn pairs. One differential methylated position was associated with maternal experience of emotional abuse (cg05486260/FAM135B gene; q value < 0.05). Five differential methylated regions were significantly associated with the total number of ACEs, and 36 unique differential methylated regions were associated with individual ACEs (Šidák p value < 0.05). Fifteen CpG modules were significantly correlated with the total number of ACEs or individual ACEs, of which 8 remained significant in fully adjusted models (p value < 0.05). Significant modules were enriched for pathways related to neurological and immune development and function.ConclusionsMaternal ACEs prior to conception were associated with cord blood DNA methylation of offspring at birth. Although there was limited overlap between differential methylated regions and CpGs in modules associated with ACE exposures, statistically significant regions and networks were related to genes involved in neurological and immune function. Findings may provide insights to pathways linking psychosocial stressors to health. Further research is needed to understand the relationship between changes in DNA methylation and child health

Maternal adverse childhood experiences (ACEs) and DNA methylation of newborns in cord blood

Abstract Background Adverse childhood experiences (ACEs) increase the risk of poor health outcomes later in life. Psychosocial stressors may also have intergenerational health effects by which parental ACEs are associated with mental and physical health of children. Epigenetic programming may be one mechanism linking parental ACEs to child health. This study aimed to investigate epigenome-wide associations of maternal preconception ACEs with DNA methylation patterns of children. In the Center for the Health Assessment of Mothers and Children of Salinas study, cord blood DNA methylation was measured using the Illumina HumanMethylation450 BeadChip. Preconception ACEs, which occurred during the mothers’ childhoods, were collected using a standard ACE questionnaire including 10 ACE indicators. Maternal ACE exposures were defined in this study as (1) the total number of ACEs; (2) the total number of ACEs categorized as 0, 1–3, and > 4; and (3) individual ACEs. Associations of ACE exposures with differential methylated positions, regions, and CpG modules determined using weighted gene co-expression network analysis were evaluated adjusting for covariates. Results Data on maternal ACEs and cord blood DNA methylation were available for 196 mother/newborn pairs. One differential methylated position was associated with maternal experience of emotional abuse (cg05486260/FAM135B gene; q value < 0.05). Five differential methylated regions were significantly associated with the total number of ACEs, and 36 unique differential methylated regions were associated with individual ACEs (Šidák p value < 0.05). Fifteen CpG modules were significantly correlated with the total number of ACEs or individual ACEs, of which 8 remained significant in fully adjusted models (p value < 0.05). Significant modules were enriched for pathways related to neurological and immune development and function. Conclusions Maternal ACEs prior to conception were associated with cord blood DNA methylation of offspring at birth. Although there was limited overlap between differential methylated regions and CpGs in modules associated with ACE exposures, statistically significant regions and networks were related to genes involved in neurological and immune function. Findings may provide insights to pathways linking psychosocial stressors to health. Further research is needed to understand the relationship between changes in DNA methylation and child health