Enhancing equity in access to automated insulin delivery systems in an ethnically and socioeconomically diverse group of children with type 1 diabetes.

INTRODUCTION: Manufacturer-supported didactic teaching programmes offer effective automated insulin delivery (AID) systems onboarding in children and young people (CYP) with type 1 diabetes (T1D). However, this approach has limited flexibility to accommodate the needs of families requiring additional support. RESEARCH DESIGN AND METHODS: Evaluate the efficacy of an inperson manufacturer-supported didactic teaching programme (Group A), in comparison to a flexible flipped learning approach delivered virtually or inperson (Group B). Retrospective analysis of CYP with T1D using continuous glucose monitoring (CGM), who were initiated on AID systems between 2021 and 2023. Compare CGM metrics from baseline to 90 days for both groups A and B. Additionally, compare the two groups for change in CGM metrics over the 90-day period (∆), patient demographics and onboarding time. RESULTS: Group A consisted of 74 CYP (53% male) with median age of 13.9 years and Group B 91 CYP (54% male) with median age of 12.7 years. From baseline to 90 days, Group A lowered mean (±SD) time above range (TAR, >10.0 mmol/L) from 47.6% (±15.0) to 33.2% (±15.0) (p<0.001), increased time in range (TIR, 3.9-10.0 mmol/L) from 50.4% (±14.0) to 64.7% (±10.2) (p<0.001). From baseline to 90 days, Group B lowered TAR from 51.3% (±15.1) to 34.5% (±11.3) (p<0.001) and increased TIR from 46.5% (±14.5) to 63.7% (±11.0) (p<0.001). There was no difference from baseline to 90 days for time below range (TBR, <3.9 mmol/L) for Group A and Group B. ∆ TAR, TIR and TBR for both groups were comparable. Group B consisted of CYP with higher socioeconomic deprivation, greater ethnic diversity and lower carer education achievement (p<0.05). The majority of Group B (n=79, 87%) chose virtual flipped learning, halving diabetes educator time and increasing onboarding cadence by fivefold. CONCLUSIONS: A flexible virtual flipped learning programme increases onboarding cadence and capacity to offer equitable AID system onboarding.

Assessment of the effect of the COVID-19 pandemic on UK HbA1c testing: implications for diabetes management and diagnosis.

AIMS: The COVID-19 pandemic, and the focus on mitigating its effects, has disrupted diabetes healthcare services worldwide. We aimed to quantify the effect of the pandemic on diabetes diagnosis/management, using glycated haemoglobin (HbA1c) as surrogate, across six UK centres. METHODS: Using routinely collected laboratory data, we estimated the number of missed HbA1c tests for 'diagnostic'/'screening'/'management' purposes during the COVID-19 impact period (CIP; 23 March 2020 to 30 September 2020). We examined potential impact in terms of: (1) diabetes control in people with diabetes and (2) detection of new diabetes and prediabetes cases. RESULTS: In April 2020, HbA1c test numbers fell by ~80%. Overall, across six centres, 369 871 tests were missed during the 6.28 months of the CIP, equivalent to >6.6 million tests nationwide. We identified 79 131 missed 'monitoring' tests in people with diabetes. In those 28 564 people with suboptimal control, this delayed monitoring was associated with a 2-3 mmol/mol HbA1c increase. Overall, 149 455 'screening' and 141 285 'diagnostic' tests were also missed. Across the UK, our findings equate to 1.41 million missed/delayed diabetes monitoring tests (including 0.51 million in people with suboptimal control), 2.67 million screening tests in high-risk groups (0.48 million within the prediabetes range) and 2.52 million tests for diagnosis (0.21 million in the pre-diabetes range; ~70 000 in the diabetes range). CONCLUSIONS: Our findings illustrate the widespread collateral impact of implementing measures to mitigate the impact of COVID-19 in people with, or being investigated for, diabetes. For people with diabetes, missed tests will result in further deterioration in diabetes control, especially in those whose HbA1c levels are already high.

An effective and cost-saving structured education program teaching dynamic glucose management strategies to a socio-economically deprived cohort with type 1 diabetes in a VIRTUAL setting.

OBJECTIVES: Compare the clinical and cost-effectiveness of an established face to face (F2F) structured education program to a new remote (VIRTUAL) program teaching dynamic glucose management (DynamicGM) to children and young people with type 1 diabetes (CYPD) using continuous glucose monitoring (CGM). To ascertain the most effective DynamicGM strategies predicting time in range (TIR) (3.9-10.0 mmol/L) and incorporating these into a user-friendly teaching aid. DESIGN AND METHODS: Effectiveness of the F2F and VIRTUAL programs were ascertained by comparing the mean change (Δ) from baseline to 6 months in HbA1c, TIR and severe hypoglycemia. Delivery cost for the two programs were evaluated. Factors predicting TIR in the combined cohort were determined and incorporated into a user-friendly infographic. RESULTS: First 50 graduates per group were evaluated. The mean difference in Δ HbA1c, Δ TIR and Δ episodes of severe hypoglycemia between VIRTUAL and F2F groups were 1.16 (p = 0.47), 0.76 (p = 0.78) and -0.06 (p = 0.61) respectively. Delivery cost per 50 CYPD for VIRTUAL and F2F were $5752 and $7020, respectively. The strongest predictors of TIR (n = 100) were short bursts of exercise (10-40 min) to lower hyperglycemia (p < 0.001), using trend arrow adjustment tools (p < 0.001) and adjusting pre-meal bolus timing based on trend arrows (p < 0.01). These strategies were translated into a GAME (Stop highs), SET (Stay in target), MATCH (Prevent lows) mnemonic. CONCLUSION: Teaching DynamicGM VIRTUALLY is just as effective as F2F delivery and cost saving. Short bursts of exercise and using CGM trend arrows to adjust insulin dose and timing improves TIR.

On the Relationship between Molecular Hit Rates in High-Throughput Screening and Molecular Descriptors.

High-throughput screening (HTS) is widely used in the pharmaceutical industry to identify novel chemical starting points for drug discovery projects. The current study focuses on the relationship between molecular hit rate in recent in-house HTS and four common molecular descriptors: lipophilicity (ClogP), size (heavy atom count, HEV), fraction of sp(3)-hybridized carbons (Fsp3), and fraction of molecular framework (f(MF)). The molecular hit rate is defined as the fraction of times the molecule has been assigned as active in the HTS campaigns where it has been screened. Beta-binomial statistical models were built to model the molecular hit rate as a function of these descriptors. The advantage of the beta-binomial statistical models is that the correlation between the descriptors is taken into account. Higher degree polynomial terms of the descriptors were also added into the beta-binomial statistic model to improve the model quality. The relative influence of different molecular descriptors on molecular hit rate has been estimated, taking into account that the descriptors are correlated to each other through applying beta-binomial statistical modeling. The results show that ClogP has the largest influence on the molecular hit rate, followed by Fsp3 and HEV. f(MF) has only a minor influence besides its correlation with the other molecular descriptors.

Quantitative histopathological assessment of retardation of islets of langerhans degeneration in rosiglitazone-dosed obese ZDF rats using combined insulin and collagens (I and III) immunohistochemistry with automated image analysis and statistical modeling.

Islets of Langerhans represent a heterogeneous population in insulin resistant and diabetic animals and humans as histological appearances and function vary substantially. Mathematical representation that reflects this morphological diversity will assist in assessment of degeneration and regeneration, enabling comparisons between species, strains, and experimental investigations. Our investigative approach used a model of islet degeneration in diabetic male obese Zucker Diabetic Fatty (ZDF) rats and evaluated its prevention using rosiglitazone treatment. Immunohistochemical staining (insulin and collagens I/III) with automated image analysis reliably measured numbers, area, clustering, and staining intensity of ß-cells and degree of islet fibrosis. Finite mixture mathematical modeling for the joint probability distribution of seven islet parameters to represent islet numerical data variation provided an automatic procedure for islet category allocations as normal or abnormal. Allocations for obese ZDF controls and rosiglitazone-treated animals were significantly different, with no significant difference between the latter and lean ZDF controls, indicative of differences within islet populations of individual animals, between lean and obese rat strains and following drug treatment. Islet morphology showed clear association with mathematical characterization. Information on islet morphology obtained by histopathological assessment of single pancreatic tissue sections was confirmed by this method showing drug-induced retardation of islet of Langerhans degeneration.

New developments in colorectal surgery.

PURPOSE OF REVIEW: The field of colorectal surgery continues to move forward as technical innovations emerge and as surgeons ask critical questions. The results of subsequent investigations often lead to changes in practice. This review examines recent publications that describe these practice changes. RECENT FINDINGS: We identified and reviewed recent publications in the areas of rectal cancer controversies, genetic risk profiling, practice improvements, diverticulitis, enhanced recovery protocols, fecal incontinence, and single incision laparoscopic surgery. SUMMARY: New technologies and practice innovations will continue to enhance patient outcomes. Multiinstitutional studies, randomized when able, are necessary to further define the safety and efficacy of new surgical techniques and to further define best practices in colorectal surgery.

Drivers of cost after surgical and medical therapy for chronic ulcerative colitis: a nested case-cohort study in Olmsted County, Minnesota.

BACKGROUND: We previously reported the costs associated with surgery for chronic ulcerative colitis in the Olmsted County population and found that direct medical costs after surgery were significantly reduced compared with before surgery. However, in that study, costs associated with chronic medical therapy for ulcerative colitis were not assessed in nonsurgical patients. OBJECTIVE: To gain insight into the drivers of costs of treatment for chronic ulcerative colitis, we assessed direct costs after surgical and medical therapy in 120 patients in the Rochester Epidemiology Project database. METHODS: A cohort of 60 patients who recovered from surgery for ulcerative colitis from 1988 to 2006 were 1:1 matched by age, sex, and referent year to medically managed patients. Direct health care costs were estimated from an institutional database, and observed cost differences over a 2-year period were calculated. Statistical significance was assessed by paired t tests and bootstrapping; mean costs are adjusted 2009 constant dollars. RESULTS: Two-year direct health care costs in the surgical and medical cohorts were $10,328 vs $6,586 (p = 0.19). In the surgical cohort, Brooke ileostomy patients were observed to have higher costs than patients with ileal pouches ([INCREMENT]$8187, p = 0.04), and after ileal pouch, pouchitis was associated with increased costs ([INCREMENT]$12,763, p < 0.01). In the medical cohort, disease extent ([INCREMENT]$6059, p = 0.04) but not disease severity was associated with increased costs. LIMITATIONS: This study was limited by the relatively small population size and by its performance in a county with a tertiary referral center. CONCLUSIONS: Before the introduction of biologic therapies for ulcerative colitis, patients were observed to have similar health care costs after surgical and medical therapy. In medically treated patients, disease extent was associated with increased costs, whereas in surgically treated patients, permanent ileostomy and pouchitis were observed to be associated with increased costs.

Long-term direct costs before and after proctocolectomy for ulcerative colitis: a population-based study in Olmsted County, Minnesota.

PURPOSE: This study was designed to test the hypothesis that patients undergoing definitive surgery for chronic ulcerative colitis have reduced direct medical costs after, as compared with before, total proctocolectomy. METHODS: A population-based cohort of patients who underwent proctocolectomy for ulcerative colitis from 1988 to 2007 was identified using the Rochester Epidemiology Project. Total direct healthcare costs were estimated from an administrative database. The primary outcome was the observed cost difference between the two-year period before surgery and the two-year period after a surgery/recovery period (surgery + 180 days). Statistical significance was assessed using paired t-tests and bootstrapping methods. Demographic data were presented as median (interquartile range) or frequency (proportion). Mean costs are reported in 2007 constant dollars. RESULTS: Sixty patients were Olmsted County, Minnesota, residents at the time of surgery and for the entire period of observation. Overall 40 patients (66%) were men, median age was 42 (range, 31-52) years, and duration of median colitis was four (range, 1-11) years. Operations included ileal pouch-anal anastomosis (n = 45, mean cost of surgery/recovery period = $50,530) and total proctocolectomy with Brooke ileostomy (n = 15, mean cost of surgery/recovery period = $39,309). In the pouch subgroup, direct medical costs on average were reduced by $9,296 (P < 0.001, bootstrapped 95% confidence interval: $324-$15,628) during the two years after recovery. In the Brooke ileostomy subgroup, direct medical costs on average were reduced by $12,529 (P < 0.001, bootstrapped 95% confidence interval: $6,467-$18,688) in the two years after recovery. CONCLUSION: Surgery for chronic ulcerative colitis resulted in reduced direct costs in the two years after surgical recovery. These observations suggest that surgical intervention for ulcerative colitis is associated with long-term economic benefit.