Background:
As the use of continuous glucose monitoring (CGM) increases, there is a need to better understand key metrics of time in range 70-180 mg/dL (TIR70-180) and hyperglycemia and how they ...relate to hemoglobin A1c (A1C).
Methods:
Analyses were conducted utilizing datasets from four randomized trials encompassing 545 adults with type 1 diabetes (T1D) who had central-laboratory measurements of A1C. CGM metrics were calculated and compared with each other and A1C cross-sectionally and longitudinally.
Results:
Correlations among CGM metrics (TIR70-180, time >180 mg/dL, time >250 mg/dL, mean glucose, area under the curve above 180 mg/dL, high blood glucose index, and time in range 70-140 mg/dL) were typically 0.90 or greater. Correlations of each metric with A1C were lower (absolute values 0.66-0.71 at baseline and 0.73-0.78 at month 6). For a given TIR70-180 percentage, there was a wide range of possible A1C levels that could be associated with that TIR70-180 level. On average, a TIR70-180 of 70% and 50% corresponded with an A1C of approximately 7% and 8%, respectively. There also was considerable spread of change in A1C for a given change in TIR70-180, and vice versa. An increase in TIR70-180 of 10% (2.4 hours per day) corresponded to a decrease in A1C of 0.6%, on average.
Conclusions:
In T1D, CGM measures reflecting hyperglycemia (including TIR and mean glucose) are highly correlated with each other but only moderately correlated with A1C. For a given TIR or change in TIR there is a wide range of possible corresponding A1C values.
This book is a first person narrative from a parent/community advocate. Examining my personal experiences as a parent of color in a Higher Learning Institute, I highlight some of the frustrations ...experienced by urban working class parents of color as they attempt to engage teachers in their community's schools. I underscore the importance of one community organization in Los Angeles, called Parent U-Turn that works to equip novice teachers for the challenges they will face. Parent-U-Turn offers outreach strategies focused not only on improving "parenting skills" to parents but also on providing teachers with the tools and skills they need to effectively advocate and outreach to urban families and their children. I conclude by presenting seven strategies for novice teachers who want to improve and be successful in urban schools. The majority of these strategies are grounded in my own personal experiences, thus are action research based. In addition to my experiences with my own children, I draw upon my experiences working with Teacher Of America, UCLA Center X Teacher ED Program and parents in LAUSD and Lynwood USD to promote activism by parents so that their voices are heard for the benefit of low-income children. The seven stages of teacher strategies seek to create a new model and perspectives for teacher preparation programs that include all teachers in our ethnically and linguistically diverse schools/communities for the 21st Century.
Anterior cruciate ligament (ACL) injury leads to a sustained increase in synovial fluid concentrations of inflammatory cytokines and biomarkers of cartilage breakdown. While this has been documented ...post‐injury, it remains unclear whether ACL reconstruction surgery contributes to the inflammatory process and/or cartilage breakdown. This study is a secondary analysis of 14 patients (nine males/five females, mean age = 9, mean BMI = 28) enrolled in an IRB‐approved randomized clinical trial. Arthrocentesis was performed at initial presentation (mean = 6 days post‐injury), immediately prior to surgery (mean = 23 days post‐injury), 1‐week post‐surgery, and 1‐month post‐surgery. Enzyme‐linked immunosorbant assay kits were used to determine concentrations of carboxy‐terminal telopeptides of type II collagen (CTXII), interleukin‐6 (IL‐6), and IL‐1β in the synovial fluid. The log‐transformed IL‐1β was not normally distributed; therefore, changes between time points were evaluated using a non‐parametric Kruskal‐Wallis one‐way ANOVA. IL‐1β concentrations significantly increased from the day of surgery to the first postoperative time point (P ≤ .001) and significantly decreased at the 4‐week postoperative visit (P = .03). IL‐1β concentrations at the 4‐week postoperative visit remained significantly greater than both preoperative time points (P > .05). IL‐6 concentrations at 1‐week post‐surgery were significantly higher than at initial presentation (P = .013), the day of surgery (P < .001), and 4 weeks after surgery (P = .002). CTX‐II concentrations did not differ between the first three‐time points (P > .99) but significantly increased at 4 weeks post‐surgery (P < .01). ACL reconstruction appears to reinitiate an inflammatory response followed by an increase in markers for cartilage degradation. ACL reconstruction appears to initiate a second “inflammatory hit” resulting in increased chondral breakdown suggesting that post‐operative chondroprotection may be needed.
Management of type 1 diabetes is challenging. We compared outcomes using a commercially available hybrid closed-loop system versus a new investigational system with features potentially useful for ...adolescents and young adults with type 1 diabetes.
In this multinational, randomised, crossover trial (Fuzzy Logic Automated Insulin Regulation FLAIR), individuals aged 14–29 years old, with a clinical diagnosis of type 1 diabetes with a duration of at least 1 year, using either an insulin pump or multiple daily insulin injections, and glycated haemoglobin (HbA1c) levels of 7·0–11·0% (53–97 mmol/mol) were recruited from seven academic-based endocrinology practices, four in the USA, and one each in Germany, Israel, and Slovenia. After a run-in period to teach participants how to use the study pump and continuous glucose monitor, participants were randomly assigned (1:1) using a computer-generated sequence, with a permuted block design (block sizes of two and four), stratified by baseline HbA1c and use of a personal MiniMed 670G system (Medtronic) at enrolment, to either use of a MiniMed 670G hybrid closed-loop system (670G) or the investigational advanced hybrid closed-loop system (Medtronic) for the first 12-week period, and then participants were crossed over with no washout period, to the other group for use for another 12 weeks. Masking was not possible due to the nature of the systems used. The coprimary outcomes, measured with continuous glucose monitoring, were proportion of time that glucose levels were above 180 mg/dL (>10·0 mmol/L) during 0600 h to 2359 h (ie, daytime), tested for superiority, and proportion of time that glucose levels were below 54 mg/dL (<3·0 mmol/L) calculated over a full 24-h period, tested for non-inferiority (non-inferiority margin 2%). Analysis was by intention to treat. Safety was assessed in all participants randomly assigned to treatment. This trial is registered with ClinicalTrials.gov, NCT03040414, and is now complete.
Between June 3 and Aug 22, 2019, 113 individuals were enrolled into the trial. Mean age was 19 years (SD 4) and 70 (62%) of 113 participants were female. Mean proportion of time with daytime glucose levels above 180 mg/dL (>10·0 mmol/L) was 42% (SD 13) at baseline, 37% (9) during use of the 670G system, and 34% (9) during use of the advanced hybrid closed-loop system (mean difference advanced hybrid closed-loop system minus 670G system −3·00% 95% CI −3·97 to −2·04; p<0·0001). Mean 24-h proportion of time with glucose levels below 54 mg/dL (<3·0 mmol/L) was 0·46% (SD 0·42) at baseline, 0·50% (0·35) during use of the 670G system, and 0·46% (0·33) during use of the advanced hybrid closed-loop system (mean difference advanced hybrid closed-loop system minus 670G system −0·06% 95% CI −0·11 to −0·02; p<0·0001 for non-inferiority). One severe hypoglycaemic event occurred in the advanced hybrid closed-loop system group, determined to be unrelated to study treatment, and none occurred in the 670G group.
Hyperglycaemia was reduced without increasing hypoglycaemia in adolescents and young adults with type 1 diabetes using the investigational advanced hybrid closed-loop system compared with the commercially available MiniMed 670G system. Testing an advanced hybrid closed-loop system in populations that are underserved due to socioeconomic factors and testing during pregnancy and in individuals with impaired awareness of hypoglycaemia would advance the effective use of this technology
National Institute of Diabetes and Digestive and Kidney Diseases.
Use of continuous glucose monitoring (CGM) is recognized as a valuable component of diabetes self-management and is increasingly considered a standard of care for individuals with diabetes who are ...treated with intensive insulin therapy. As the clinical use of CGM technology expands, consistent and standardized glycemic metrics and glucose profile visualization have become increasingly important. A common set of CGM metrics has been proposed by an international expert panel in 2017, including standard definitions of time in ranges, glucose variability, and adequacy of data collection. We describe the core CGM metrics, as well as the standardized glucose profile format consolidating 2 weeks of CGM measurements, referred to as the ambulatory glucose profile (AGP), which was also recommended by the CGM expert panel. We present an updated AGP report featuring the core CGM metrics and a visualization of glucose patterns that need clinical attention. New tools for use by clinicians and patients to interpret AGP data are reviewed. Strategies based on the authors' experience in implementing CGM technology across the clinical care spectrum are highlighted.
A guideline that both evaluates current practice and provides recommendations to address sedation, pain, and delirium management with regard for neuromuscular blockade and withdrawal is not currently ...available.
To develop comprehensive clinical practice guidelines for critically ill infants and children, with specific attention to seven domains of care including pain, sedation/agitation, iatrogenic withdrawal, neuromuscular blockade, delirium, PICU environment, and early mobility.
The Society of Critical Care Medicine Pediatric Pain, Agitation, Neuromuscular Blockade, and Delirium in critically ill pediatric patients with consideration of the PICU Environment and Early Mobility Guideline Taskforce was comprised of 29 national experts who collaborated from 2009 to 2021 via teleconference and/or e-mail at least monthly for planning, literature review, and guideline development, revision, and approval. The full taskforce gathered annually in-person during the Society of Critical Care Medicine Congress for progress reports and further strategizing with the final face-to-face meeting occurring in February 2020. Throughout this process, the Society of Critical Care Medicine standard operating procedures Manual for Guidelines development was adhered to.
Taskforce content experts separated into subgroups addressing pain/analgesia, sedation, tolerance/iatrogenic withdrawal, neuromuscular blockade, delirium, PICU environment (family presence and sleep hygiene), and early mobility. Subgroups created descriptive and actionable Population, Intervention, Comparison, and Outcome questions. An experienced medical information specialist developed search strategies to identify relevant literature between January 1990 and January 2020. Subgroups reviewed literature, determined quality of evidence, and formulated recommendations classified as "strong" with "we recommend" or "conditional" with "we suggest." Good practice statements were used when indirect evidence supported benefit with no or minimal risk. Evidence gaps were noted. Initial recommendations were reviewed by each subgroup and revised as deemed necessary prior to being disseminated for voting by the full taskforce. Individuals who had an overt or potential conflict of interest abstained from relevant votes. Expert opinion alone was not used in substitution for a lack of evidence.
The Pediatric Pain, Agitation, Neuromuscular Blockade, and Delirium in critically ill pediatric patients with consideration of the PICU Environment and Early Mobility taskforce issued 44 recommendations (14 strong and 30 conditional) and five good practice statements.
The current guidelines represent a comprehensive list of practical clinical recommendations for the assessment, prevention, and management of key aspects for the comprehensive critical care of infants and children. Main areas of focus included 1) need for the routine monitoring of pain, agitation, withdrawal, and delirium using validated tools, 2) enhanced use of protocolized sedation and analgesia, and 3) recognition of the importance of nonpharmacologic interventions for enhancing patient comfort and comprehensive care provision.
Mutations in the shelterin protein POT1 are associated with chronic lymphocytic leukemia (CLL), Hodgkin lymphoma, angiosarcoma, melanoma, and other cancers. These cancer‐associated POT1 (caPOT1) ...mutations are generally heterozygous, missense, or nonsense mutations occurring throughout the POT1 reading frame. Cancers with caPOT1 mutations have elongated telomeres and show increased genomic instability, but which of the two phenotypes promotes tumorigenesis is unclear. We tested the effects of CAS9‐engineered caPOT1 mutations in human embryonic and hematopoietic stem cells (hESCs and HSCs, respectively). HSCs with caPOT1 mutations did not show overt telomere damage. In vitro and in vivo competition experiments showed the caPOT1 mutations did not confer a selective disadvantage. Since DNA damage signaling is known to affect the fitness of HSCs, the data argue that caPOT1 mutations do not cause significant telomere damage. Furthermore, hESC lines with caPOT1 mutations showed no detectable telomere damage response while showing consistent telomere elongation. Thus, caPOT1 mutations are likely selected for during cancer progression because of their ability to elongate telomeres and extend the proliferative capacity of the incipient cancer cells.
SYNOPSIS
Whether cancer‐associated mutations in human shelterin protein POT1 (caPOT1) contribute to tumorigenesis via the connected phenomena of telomere elongation or genomic instability has remained controversial. Here, genome editing in human cells demonstrates that caPOT1 mutations lead to telomere elongation without triggering telomeric DNA damage responses.
Engineered caPOT1 mutations do not induce DNA damage responses at telomeres but leads to telomere elongation in hESCs.
caPOT1 mutations do not confer strong proliferative disadvantages in hematopoietic stem cells and differentiated cells in vitro.
caPOT1 mutations are not selected against within the population in a humanized mouse model in vivo.
The familial caPOT1 Y36H mutation leads to telomere elongation in somatic tissues.
Genome‐engineering in human cells demonstrates that mutations in human shelterin subunit POT1 do not confer a selective disadvantage, and may contribute to tumorigenesis via increased telomere length and proliferative capacity.
The intestinal microbiome might affect the development and severity of nonalcoholic fatty liver disease (NAFLD). We analyzed microbiomes of children with and without NAFLD.
We performed a ...prospective, observational, cross-sectional study of 87 children (age range, 8–17 years) with biopsy-proven NAFLD and 37 children with obesity without NAFLD (controls). Fecal samples were collected and microbiome composition and functions were assessed using 16S ribosomal RNA amplicon sequencing and metagenomic shotgun sequencing. Microbial taxa were identified using zero-inflated negative binomial modeling. Genes contributing to bacterial pathways were identified using gene set enrichment analysis.
Fecal microbiomes of children with NAFLD had lower α-diversity than those of control children (3.32 vs 3.52, P = .016). Fecal microbiomes from children with nonalcoholic steatohepatitis (NASH) had the lowest α-diversity (control, 3.52; NAFLD, 3.36; borderline NASH, 3.37; NASH, 2.97; P = .001). High abundance of Prevotella copri was associated with more severe fibrosis (P = .036). Genes for lipopolysaccharide biosynthesis were enriched in microbiomes from children with NASH (P < .001). Classification and regression tree model with level of alanine aminotransferase and relative abundance of the lipopolysaccharide pathway gene encoding 3-deoxy-d-manno-octulosonate 8-phosphate-phosphatase identified patients with NASH with an area under the receiver operating characteristic curve value of 0.92. Genes involved in flagellar assembly were enriched in the fecal microbiomes of patients with moderate to severe fibrosis (P < .001). Classification and regression tree models based on level of alanine aminotransferase and abundance of genes encoding flagellar biosynthesis protein had good accuracy for identifying case children with moderate to severe fibrosis (area under the receiver operating characteristic curve, 0.87).
In an analysis of fecal microbiomes of children with NAFLD, we associated NAFLD and NASH with intestinal dysbiosis. NAFLD and its severity were associated with greater abundance of genes encoding inflammatory bacterial products. Alterations to the intestinal microbiome might contribute to the pathogenesis of NAFLD and be used as markers of disease or severity.
Evaluate whether structured BGM testing (BGM) or real-time CGM (CGM) lead to improved glucose control (A1c). Determine which approach optimized glucose control more effectively.
trial of three type 2 ...diabetes (T2D) therapies ± metformin: (1) sulfonylurea (SU), (2) incretin (DPP4 inhibitor or GLP-1 agonist), or (3) insulin. After a baseline CGM, 114 adult subjects were randomized to either BGM (4 times daily) or CGM (24/7) for 16 weeks with therapies adjusted every 4 weeks.
A1c means decreased from 8.19 to 7.07 (1.12% difference) with CGM (n = 59) and 7.85 to 7.03 (0.82% difference) with BGM (n = 55) (p < 0.001). BGM and CGM groups showed significant improvements in time in range and glucose variability—with no significant difference between the two groups. Clinically important hypoglycemia (<50 mg/dL) was significantly reduced for the CGM group compared with BGM (p < 0.01), particularly in subjects taking insulin or therapies with higher hypoglycemic risk (SU).
In T2D, structured, consistent use of glucose data regardless of device (structured BGM or CGM) leads to improvements in A1c control. CGM is more effective than BGM in minimizing hypoglycemia particularly for those using higher hypoglycemic risk therapies.
•In T2D, structured, consistent use of glucose data regardless of the device (structured BGM or CGM) lead to improved A1c control.•CGM + AGP report is more effective than BGM in minimizing hypoglycemia particularly when using higher hypoglycemic risk therapies.•Only CGM use led to a reduction in hypoglycemia rates in insulin and SU treatment groups.
OBJECTIVE:To determine the relationship between patient-reported outcomes (PROs) to the single-leg step-down test (SLSD) and the Y-balance anterior reach (YB-A) 6 months after primary anterior ...cruciate ligament reconstruction (ACLR).
DESIGN:Cross-sectional.
SETTING:Laboratory.
PARTICIPANTS:Sixty-six patients 6 months after ACLR participated.
INTERVENTIONS:Patients performed the SLSD, YB-A, and completed PROs after ACLR.
MAIN OUTCOME MEASURES:Patients completed the International Knee Documentation Committee Score (IKDC), the Lysholm Activity Scale, the Tampa Scale of Kinesiophobia (TSK-11), and the Knee Injury and Osteoarthritis Outcome Score (KOOS)–Symptom, –Sport, and –Quality of Life (QOL) subscales. The SLSD requires subjects to complete as many single-leg step-downs as possible in 60 seconds, and the YB-A involves reaching anteriorly on a single limb. Pearson product moment correlations were used to assess relationships between the YB-A and SLSD performance to each PRO.
RESULTS:Single-leg step-down test symmetry was significantly correlated with the TSK-11 (r = −0.70), KOOS-Sport (r = 0.40), -Symptom (r = 0.46), and -QOL (r = 0.42). The YB-A symmetry was significantly correlated with the KOOS-Symptom (r = 0.30) and KOOS-Sport (r = 0.30).
CONCLUSIONS:Single-leg step-down test performance demonstrated stronger relationships to patient-reported knee function than the YB-A. Furthermore, the SLSD symmetry was strongly correlated with fear of movement. The SLSD provides a robust method for clinicians to assess dynamic knee function and may aid in identifying patients who could benefit from intervention to reduce fear of movement or reinjury.
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