Search

The concepts of bounded paracompactness and bounded metacompactness were introduced and studied in [3]. In this paper we define bounded full normality and show that this concept is equivalent to bounded paracompactness.It is known that countable paracompactness and countable metacompactness are equivalent properties in a normal space. We show that bounded countable metacompactness is equivalent to bounded countable paracompactness in a normal space and that bounded countable paracompactness is equivalent to bounded paracompactness in a hereditarily paracompact space. [ABSTRACT FROM PUBLISHER]

Background: While major pathways of human PFAS exposure are thought to be drinking water and diet, other pathways and sources have also been shown to contribute to a person's cumulative exposure. However, the degree of contribution of these other sources to PFAS body burdens is still not well understood and occurrence data for PFAS in conssumer products and household materials are sparse. Questionnaire data concordant with biomonitoring may improve understanding of associations between other PFAS exposure pathways and exposure in human populations., Objective: This study aims to better understand maternal and early-life exposures to PFAS from various potential sources and pathways in the context of household and community level characteristics., Methods: PFAS data from the National Children's Study (NCS) Vanguard Data and Sample Archive Access System were analyzed from serum of 427 pregnant women residing in 7 counties throughout the United States. Location and self-reported questionnaire responses were used to analyze variability in serum concentrations based on demographics, housing characteristics, behaviors, and geography. Spatial mapping analyses incorporated publicly available data to further hypothesize potential sources of exposure in two NCS counties., Results: Location was associated with serum concentrations for all PFAS chemicals measured. Questionnaire responses for race/ethnicity, income, education level, number of household members, drinking water source, home age, and fast-food consumption were associated with PFAS levels. Statistical differences were observed between participants with the same questionnaire responses but in different locations. Spatial mapping analyses suggested that participants' proximity to local point sources can overshadow expected trends with demographic information., Significance: By increasing understanding of maternal and early-life PFAS exposures from various potential sources and pathways, as well as highlighting the importance of proximity to potential sources in identifying vulnerable populations and locations, this work reveals environmental justice considerations and contributes to risk management strategies that maximize public health protection., Impact: This work increases understanding of maternal and early-life PFAS exposures, reveals environmental justice considerations, and contributes to study design and risk management strategies., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Human exposure to per- and polyfluoroalkyl substances has been modeled to estimate serum concentrations. Given that the production and use of these compounds have decreased in recent years, especially PFOA and PFOS, and that additional concentration data have become available from the US and other industrialized countries over the past decade, aggregate median intakes of these two compounds were estimated using more recent data., Methods: Summary statistics from secondary sources were collected, averaged, and mapped for indoor and outdoor air, water, dust, and soil for PFOA and PFOS to estimate exposures for adults and children. European dietary intake estimates were used to estimate daily intake from food., Results: In accordance with decreased concentrations in media, daily intake estimates among adults, i.e., 40 ng/day PFOA and 40 ng/day PFOS, are substantially lower than those reported previously, as are children's estimates of 14 ng/day PFOA and 17 ng/day PFOS. Using a first-order pharmacokinetic model, these results compare favorably to the National Health and Nutrition Examination Survey serum concentration measurements., Conclusion: Concomitant blood concentrations support this enhanced estimation approach that captures the decline of PFOA/PFOS serum concentration over a decade., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Background: Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting., Methods: In this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed., Results: A total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, -0.5 percentage points; 95% confidence interval [CI], -0.6 to -0.3; P<0.001). The percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter did not differ significantly between the two groups (13-week adjusted difference, 0.0 percentage points; 95% CI, -0.1 to 0.04; P<0.001 for noninferiority). The rate of severe hypoglycemia was 17.7 events per 100 participant-years in the bionic-pancreas group and 10.8 events per 100 participant-years in the standard-care group (P = 0.39). No episodes of diabetic ketoacidosis occurred in either group., Conclusions: In this 13-week, randomized trial involving adults and children with type 1 diabetes, use of a bionic pancreas was associated with a greater reduction than standard care in the glycated hemoglobin level. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT04200313.)., (Copyright © 2022 Massachusetts Medical Society.)

Objective: Very young children with type 1 diabetes often struggle to achieve glycemic targets, putting them at risk for long-term complications and creating an immense management burden for caregivers. We conducted the first evaluation of the Omnipod 5 Automated Insulin Delivery System in this population., Research Design and Methods: A total of 80 children aged 2.0-5.9 years used the investigational system in a single-arm study for 13 weeks following 14 days of baseline data collection with their usual therapy., Results: There were no episodes of severe hypoglycemia or diabetic ketoacidosis. By study end, HbA1c decreased by 0.55% (6.0 mmol/mol) (P < 0.0001). Time with sensor glucose levels in target range 70-180 mg/dL increased by 10.9%, or 2.6 h/day (P < 0.0001), while time with levels <70 mg/dL declined by median 0.27% (P = 0.0204)., Conclusions: Use of the automated insulin delivery system was safe, and participants experienced improved glycemic measures and reduced hypoglycemia during the study phase compared with baseline., (© 2022 by the American Diabetes Association.)

Background: Human exposure to per- and polyfluoroalkyl substances (PFAS) has been primarily attributed to contaminated food and drinking water. There is information indicating other sources and pathways of exposure in residential environments, but few studies report relationships between these indoor media and human biomonitoring measurements., Methods: This study adapts existing systematic review tools and methodologies to synthesize evidence for PFAS exposure pathways from indoor environment media including consumer products, household articles, cleaning products, personal care products, and indoor air and dust. Studies were identified using innovative machine learning approaches and pathway-specific search strings to reduce time needed for literature search and screening. The included studies and systematic review were evaluated using tools modified specifically for exposure studies. The systematic review was conducted following a previously published protocol (DeLuca et al., 2021) that describes the systematic review methodology used in detail., Results: Only 7 studies were identified that measured the targeted subset of 8 PFAS chemicals in concordant household media (primarily house dust) and participant serum. Data extracted from the included studies were used to calculate exposure intake rates and estimate a percentage of occupant serum concentrations that could be attributed to the indoor exposure pathways. These calculations showed that exposure to PFOA, PFOS, PFNA, and PFHxS from contaminated house dust could account for 13%, 3%, 7%, and 25% of serum concentrations, respectively. Inhalation of PFAS in indoor air could account for less than 4% of serum PFOA concentrations and less than 2% of serum PFOS and PFNA concentrations. A risk of bias was identified due to participant profiles in most of the studies being skewed towards white, female, and higher socioeconomic status., Conclusions: Along with synthesizing evidence for estimated contributions to serum PFAS levels from indoor exposure media, this systematic review also identifies a consistent risk of bias across exposure study populations that should be considered in future studies. It highlights a major research gap and need for studies that measure concordant data from both indoor exposure media and participant serum and the need for continued research on exposure modeling parameters for many PFAS chemicals., (Published by Elsevier Ltd.)

Background: The use of systems science methodologies to understand complex environmental and human health relationships is increasing. Requirements for advanced datasets, models, and expertise limit current application of these approaches by many environmental and public health practitioners., Methods: A conceptual system-of-systems model was applied for children in North Carolina counties that includes example indicators of children's physical environment (home age, Brownfield sites, Superfund sites), social environment (caregiver's income, education, insurance), and health (low birthweight, asthma, blood lead levels). The web-based Toxicological Prioritization Index (ToxPi) tool was used to normalize the data, rank the resulting vulnerability index, and visualize impacts from each indicator in a county. Hierarchical clustering was used to sort the 100 North Carolina counties into groups based on similar ToxPi model results. The ToxPi charts for each county were also superimposed over a map of percentage county population under age 5 to visualize spatial distribution of vulnerability clusters across the state., Results: Data driven clustering for this systems model suggests 5 groups of counties. One group includes 6 counties with the highest vulnerability scores showing strong influences from all three categories of indicators (social environment, physical environment, and health). A second group contains 15 counties with high vulnerability scores driven by strong influences from home age in the physical environment and poverty in the social environment. A third group is driven by data on Superfund sites in the physical environment., Conclusions: This analysis demonstrated how systems science principles can be used to synthesize holistic insights for decision making using publicly available data and computational tools, focusing on a children's environmental health example. Where more traditional reductionist approaches can elucidate individual relationships between environmental variables and health, the study of collective, system-wide interactions can enable insights into the factors that contribute to regional vulnerabilities and interventions that better address complex real-world conditions., (© 2022. The Author(s).)

Background: Clinic-to-clinic telemedicine can increase visit frequency in pediatric patients with type 1 diabetes (T1D) living far from a diabetes specialty clinic, but the impact on adoption of diabetes technology is unclear. Materials and Methods: Pediatric patients with T1D in Colorado and surrounding states who received diabetes care using clinic-to-clinic telemedicine were enrolled. Medical records and surveys were reviewed to ascertain technology use, and data were compared to patients from the main clinic population. Results: Patients ( N  = 128, baseline mean age 12.4 ± 4.2 years, median T1D duration 3.3 years [IQR 1.4-7.7], mean A1c 8.9% ± 1.8%, 60% male, 75% non-Hispanic white, 77% private insurance) who utilized telemedicine were included. Technology use among telemedicine patients was not associated with gender, T1D duration, insurance, distance from the main clinic or rural designation but was associated with ethnicity and A1c. Compared to the main clinic cohort ( N  = 3636), continuous glucose monitor (CGM) use and pump/CGM combination use was lower among patients participating in clinic-to-clinic telemedicine (CGM: 29.7% vs. 56.0%, P  < 0.001; CGM/pump combination: 27.3% vs. 40.3%, P  = 0.004). Technology use was associated with lower A1c regardless of cohort. Conclusions: Compared to patients attending in-person clinic, pediatric T1D patients who use clinic-to-clinic telemedicine due to their distance from the main clinic, have lower CGM and combination CGM/pump use. For both telemedicine and main clinic patients, CGM and CGM/pump combination was associated with lower A1c. Additional research is needed to explore reasons for this discrepancy and find methods to improve CGM use in this population.

Increasing numbers of chemicals are on the market and present in consumer products. Emerging evidence on the relationship between environmental contributions and prevalent diseases suggests associations between early-life exposure to manufactured chemicals and a wide range of children's health outcomes. Using current assessment methodologies, public health and chemical management decisionmakers face challenges in evaluating and anticipating the potential impacts of exposure to chemicals on children's health in the broader context of their physical (built and natural) and social environments. Here, we consider a systems approach to address the complexity of children's environmental health and the role of exposure to chemicals during early life, in the context of nonchemical stressors, on health outcomes. By advancing the tools for integrating this more complex information, the scope of considerations that support chemical management decisions can be extended to include holistic impacts on children's health.

Background: Revision THA represents approximately 5% to 10% of all THAs. Despite the complexity of these procedures, revision arthroplasty service lines are generally absent even at high-volume orthopaedic centers. We wanted to evaluate whether financial compensation is a barrier for the development of revision THA service lines as assessed by RVUs., Questions/purposes: Therefore, we asked: (1) Are physicians fairly compensated for revision THA on a per-minute basis compared with primary THA? (2) Are physicians fairly compensated for revision THA on a per-day basis compared with primary THA?, Methods: Our deterministic financial model was derived from retrospective data of all patients undergoing primary or revision THA between January 2016 and June 2018 at an academic healthcare organization. Patients were divided into five cohorts based on their surgical procedure: primary THA, head and liner exchange, acetabular component revision THA, femoral component revision THA, and combined femoral and acetabular component revision THA. Mean surgical times were calculated for each cohort, and each cohort was assigned a relative value unit (RVU) derived from the 2018 Center for Medicaid and Medicare assigned RVU fee schedule. Using a combination of mean surgical time and RVUs rewarded for each procedure, three models were developed to assess the financial incentive to perform THA services for each cohort. These models included: (1) RVUs earned per the mean surgical time, (2) RVUs earned for a single operating room for a full day of THAs, and (3) RVUs earned for two operating rooms for a full day of primary THAs versus a single rooms for a full day of revision THAs. A sixth cohort was added in the latter two models to more accurately reflect the variety in a typical surgical day. This consisted of a blend of revision THAs: one acetabular, one femoral, and one full revision. The RVUs generated in each model were compared across the cohorts., Results: Compared with primary THA by RVU per minute, in revision THA, head and liner exchange demonstrated a 4% per minute deficit, acetabular component revision demonstrated a 29% deficit, femoral component revision demonstrated a 32% deficit, and full revision demonstrated a 27% deficit. Compared with primary service lines with one room, revision surgeons with a variety of revision THA surgeries lost 26% potential relative value units per day. Compared with a two-room primary THA service, revision surgeons lost 55% potential relative value units per day., Conclusions: In a comparison of relative value units of a typical two-room primary THA service line versus those of a dedicated revision THA service line, we found that revision specialists may lose between 28% and 55% of their RVU earnings. The current Centers for Medicare and Medicaid Services reimbursement model is not viable for the arthroplasty surgeon and limits patient access to revision THA specialists., Level of Evidence: Level III, economic and decision analysis.

Context: Our pediatric diabetes center initiated insulin pump therapy for more than 250 patients with type 1 diabetes in 2014, but onboarding was inefficient., Objective: To decrease time from the decision to initiate pump therapy to the ambulatory encounter after pump start (lead time) for new pump users from 132.5 days to less than 110 days within 5 months., Design: Define, Measure, Analyze, Improve, Control method. We identified key problems: Long wait for training classes, unclear metrics, complicated scheduling, and nonstandardized processes. We then implemented 17 changes, including shortened classes, increased class offerings and space, clarified metrics, built a reporting dashboard, designated and cross-trained staff, created appeals letter templates, and educated clinicians. At project conclusion, we established a reaction plan if the processes were not performing as designed., Main Outcome Measures: Outcomes of pump orders placed before and after improvements were implemented., Results: During this project, 229 patients initiated the pump start process. Median lead time decreased from 132.5 to 98.5 days (p = 0.007). Patients with lead time under 110 days increased from 37% to 60% (p = 0.001). There were 31 pump nonstarters, with no significant association between group and whether the patient was a starter or nonstarter (p = 0.58). Nonstarters had a longer diabetes duration (median = 3.43 vs 2.05 years, p = 0.001)., Conclusion: Project goals were met. A high proportion of patients not starting pump therapy was discovered, but this was not affected by the project. We implemented further changes and a process-monitoring system.

Objective: Pediatric patients in Colorado with new onset type 1 diabetes (T1D) presenting with diabetic ketoacidosis (DKA) increased from 29.9% to 46.2% from 1998 to 2012. The purpose of this study was to compare differences between patients with newly diagnosed T1D who presented in DKA with those who did not across three domains: sociodemographic factors, access to medical care, and medical provider factors, aiming to identify potential targets for intervention., Methods: Sixty-one patients <17 years of age with T1D duration <6 months completed the questionnaire. Groups were compared using Fisher's exact test or the Kruskal-Wallis test., Results: Parents of 28% of patients researched their child's symptoms on the Internet prior to diagnosis. At the first healthcare visit for symptoms of T1D, 23% were not diagnosed. There were no significant differences between groups (DKA vs non-DKA) in demographics, first healthcare setting for T1D symptoms, provider type at first visit or at diagnosis, insurance status, or specific barriers to care. DKA patients had a longer interval between previous well visit to diagnosis (median 172 vs 263 days, P = 0.01). Non-DKA patients were more likely to have blood glucose measured at P = 0.02, and had fewer symptoms prior to (P = 0.01) the first visit for diabetes symptoms. Parents of non-DKA patients were more likely to be familiar with symptoms of diabetes (P < 0.001) and to suspect diabetes (P = 0.01)., Conclusion: Targets for campaigns to prevent DKA include increasing provider glucose and ketone testing, increasing public knowledge about diabetes, and understanding how socio-demographic factors may delay T1D diagnosis., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Prior studies examining beta-cell preservation in type 1 diabetes have predominantly assessed stimulated C-peptide concentrations approximately 10 wk after diagnosis. We examined whether earlier assessments might aid in prediction of beta cell function over time., Methods: Using data from a multi-center randomized trial assessing the effect of intensive diabetes management initiated within 1 wk of diagnosis, we assessed which clinical factors predicted 90-min mixed-meal tolerance test (MMTT) stimulated C-peptide values obtained 2 and 6 wk after diagnosis. We also studied associations of these factors with C-peptide values at 1- and 2-year post-diagnosis. Data from intervention and control groups were pooled., Results: Among 67 study participants (mean age 13.3 ± 5.7 yr, range 7.8-45.7 yr) in multivariable analyses, C-peptide increased from baseline to 2 wks and then 6 wk. C-peptide levels at these times were significantly correlated with 1- and 2-yr C-peptide concentrations (all p < 0.001), with the strongest observed associations between 6-wk C-peptide and the 1- and 2-yr values (r = 0.66 and r = 0.61, respectively). In multivariable analyses, greater baseline and 6-wk C-peptide, and older age independently predicted greater 1- and 2-yr C-peptide concentrations., Conclusions: C-peptide assessments close to diagnosis were predictive of subsequent C-peptide production. Our data demonstrate a clear increase in C-peptide over the initial 6 wk after diabetes diagnosis followed by a plateau. Our data do not suggest that MMTT assessments performed closer to diagnosis than 6 wk would improve prediction of subsequent residual beta cell function., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The American Diabetes Association (ADA) recommends that children with type 1 diabetes (T1D) see a multidisciplinary team and have hemoglobin A1c (A1C) levels measured every 3 months. Patients in rural areas may not follow guidelines because of limited specialty care access. We hypothesized that videoconferencing would result in equivalent A1C compared with in-person visits and increased compliance with ADA recommendations., Materials and Methods: The Barbara Davis Center (BDC) (Aurora, CO) telemedicine program provides diabetes care to pediatric patients in Casper and Cheyenne, WY, via remote consultation with annual in-person visits. Over 27 months, 70 patients were consented, and 54 patients completed 1 year in the study., Results: Patients were 70% male, with a mean age of 12.1 ± 4.1 years and T1D duration of 5.4 ± 4.1 years. There was no significant change between baseline and 1-year A1C levels for patients with data at both time points. Patients saw diabetes specialists an average of 2.0 ± 1.3 times per year in the year prior to starting telemedicine and 2.9 ± 1.3 times (P < 0.0001) in the year after starting telemedicine. Patients and families missed significantly less school and work time to attend appointments., Conclusions: Our study suggests telemedicine is equivalent to in-person visits to maintain A1C, whereas families increase the number of visits in line with ADA recommendations. Patients and families miss less school and work. Decreased financial burden and increased access may improve overall diabetes care and compliance for rural patients. Further study is needed to detect long-term differences in complications screenings and the financial impact of telemedicine on pediatric diabetes care.

Pediatric headaches are common, and many may never require intervention by a health care provider. However, migraines can become more difficult to treat, especially if they become chronic daily headaches. Pediatric headache is a subjective and unique experience that requires attention to both psychological and physiologic components in diagnosis and treatment. A biopsychosocial, multidisciplinary approach, including both medication management and psychological treatment, is considered essential for effective management.

Objective: Nocturnal hypoglycemia can cause seizures and is a major impediment to tight glycemic control, especially in young children with type 1 diabetes. We conducted an in-home randomized trial to assess the efficacy and safety of a continuous glucose monitor-based overnight predictive low-glucose suspend (PLGS) system., Research Design and Methods: In two age-groups of children with type 1 diabetes (11-14 and 4-10 years of age), a 42-night trial for each child was conducted wherein each night was assigned randomly to either having the PLGS system active (intervention night) or inactive (control night). The primary outcome was percent time <70 mg/dL overnight., Results: Median time at <70 mg/dL was reduced by 54% from 10.1% on control nights to 4.6% on intervention nights (P < 0.001) in 11-14-year-olds (n = 45) and by 50% from 6.2% to 3.1% (P < 0.001) in 4-10-year-olds (n = 36). Mean overnight glucose was lower on control versus intervention nights in both age-groups (144 ± 18 vs. 152 ± 19 mg/dL [P < 0.001] and 153 ± 14 vs. 160 ± 16 mg/dL [P = 0.004], respectively). Mean morning blood glucose was 159 ± 29 vs. 176 ± 28 mg/dL (P < 0.001) in the 11-14-year-olds and 154 ± 25 vs. 158 ± 22 mg/dL (P = 0.11) in the 4-10-year-olds, respectively. No differences were found between intervention and control in either age-group in morning blood ketosis., Conclusions: In 4-14-year-olds, use of a nocturnal PLGS system can substantially reduce overnight hypoglycemia without an increase in morning ketosis, although overnight mean glucose is slightly higher., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Aims/hypothesis: The aim of this work was to assess the association between continuous glucose monitoring (CGM) data, HbA1c, insulin-dose-adjusted HbA1c (IDAA1c) and C-peptide responses during the first 2 years following diagnosis of type 1 diabetes., Methods: A secondary analysis was conducted of data collected from a randomised trial assessing the effect of intensive management initiated within 1 week of diagnosis of type 1 diabetes, in which mixed-meal tolerance tests were performed at baseline and at eight additional time points through 24 months. CGM data were collected at each visit., Results: Among 67 study participants (mean age [± SD] 13.3 ± 5.7 years), HbA1c was inversely correlated with C-peptide at each time point (p < 0.001), as were changes in each measure between time points (p < 0.001). However, C-peptide at one visit did not predict the change in HbA1c at the next visit and vice versa. Higher C-peptide levels correlated with increased proportion of CGM glucose values between 3.9 and 7.8 mmol/l and lower CV (p = 0.001 and p = 0.02, respectively) but not with CGM glucose levels <3.9 mmol/l. Virtually all participants with IDAA1c < 9 retained substantial insulin secretion but when evaluated together with CGM, time in the range of 3.9-7.8 mmol/l and CV did not provide additional value in predicting C-peptide levels., Conclusions/interpretation: In the first 2 years after diagnosis of type 1 diabetes, higher C-peptide levels are associated with increased sensor glucose levels in the target range and with lower glucose variability but not hypoglycaemia. CGM metrics do not provide added value over the IDAA1c in predicting C-peptide levels.

Objective: Overnight hypoglycemia occurs frequently in individuals with type 1 diabetes and can result in loss of consciousness, seizure, or even death. We conducted an in-home randomized trial to determine whether nocturnal hypoglycemia could be safely reduced by temporarily suspending pump insulin delivery when hypoglycemia was predicted by an algorithm based on continuous glucose monitoring (CGM) glucose levels., Research Design and Methods: Following an initial run-in phase, a 42-night trial was conducted in 45 individuals aged 15-45 years with type 1 diabetes in which each night was assigned randomly to either having the predictive low-glucose suspend system active (intervention night) or inactive (control night). The primary outcome was the proportion of nights in which ≥1 CGM glucose values ≤60 mg/dL occurred., Results: Overnight hypoglycemia with at least one CGM value ≤60 mg/dL occurred on 196 of 942 (21%) intervention nights versus 322 of 970 (33%) control nights (odds ratio 0.52 [95% CI 0.43-0.64]; P < 0.001). Median hypoglycemia area under the curve was reduced by 81%, and hypoglycemia lasting >2 h was reduced by 74%. Overnight sensor glucose was >180 mg/dL during 57% of control nights and 59% of intervention nights (P = 0.17), while morning blood glucose was >180 mg/dL following 21% and 27% of nights, respectively (P < 0.001), and >250 mg/dL following 6% and 6%, respectively. Morning ketosis was present <1% of the time in each arm., Conclusions: Use of a nocturnal low-glucose suspend system can substantially reduce overnight hypoglycemia without an increase in morning ketosis., (© 2014 by the American Diabetes Association.)

Objective: This study determined the association of continuous glucose monitoring glucose (CGM-glucose) levels at different times of the day with improvement in glycated hemoglobin (HbA1c) levels. The potential application of these data is to focus effort to improve glucose control in patients with type 1 diabetes., Research Design and Methods: Data were analyzed from 196 patients with type 1 diabetes who were randomized to receive sensor-augmented pump therapy in the 1-year STAR 3 trial. CGM-glucose values and HbA1c levels from baseline and after 1 year were evaluated to determine associations of improvement in CGM-glucose at different times of the day with longitudinal improvement in HbA1c., Results: Improvement in HbA1c levels after 1 year was related to improvement in mean CGM-glucose levels in daytime (6 a.m.-midnight), overnight (midnight-6 a.m.), and each mealtime period (P<0.0001 for each). In multivariable analysis, only improvement in breakfast meal period was associated with improvement in HbA1c after 1 year, explaining 59% of the HbA1c improvement using the partial R(2) test. Moreover, among those patients who only improved CGM-glucose in the overnight period there was an associated improvement in breakfast meal period CGM-glucose of 26 ± 22 mg/dL (P<0.01)., Conclusions: Breakfast period glucose improvement had the greatest effect on lowering HbA1c levels in patients with type 1 diabetes. Improving glucose control overnight resulted in subsequent improvement in the breakfast period. Although glucose control should be improved at all times, methods to improve overnight and post-breakfast glucose levels may be of primary importance in improving glucose control in patients with type 1 diabetes.

Objective: To assess effectiveness of inpatient hybrid closed-loop control (HCLC) followed by outpatient sensor-augmented pump (SAP) therapy initiated within 7 days of diagnosis of type 1 diabetes on the preservation of β-cell function at 1 year., Research Design and Methods: Sixty-eight individuals (mean age 13.3 ± 5.7 years; 35% female, 92% Caucasian) were randomized to HCLC followed by SAP therapy (intensive group; N = 48) or to the usual-care group treated with multiple daily injections or insulin pump therapy (N = 20). Primary outcome was C-peptide concentrations during mixed-meal tolerance tests at 12 months., Results: Intensive-group participants initiated HCLC a median of 6 days after diagnosis for a median duration of 71.3 h, during which median participant mean glucose concentration was 140 mg/dL (interquartile range 134-153 mg/dL). During outpatient SAP, continuous glucose monitor (CGM) use decreased over time, and at 12 months, only 33% of intensive participants averaged sensor use ≥6 days/week. In the usual-care group, insulin pump and CGM use were initiated prior to 12 months by 15 and 5 participants, respectively. Mean HbA1c levels were similar in both groups throughout the study. At 12 months, the geometric mean (95% CI) of C-peptide area under the curve was 0.43 (0.34-0.52) pmol/mL in the intensive group and 0.52 (0.32-0.75) pmol/mL in the usual-care group (P = 0.49). Thirty-seven (79%) intensive and 16 (80%) usual-care participants had a peak C-peptide concentration ≥0.2 pmol/mL (P = 0.30)., Conclusions: In new-onset type 1 diabetes, HCLC followed by SAP therapy did not provide benefit in preserving β-cell function compared with current standards of care.

Background: This article describes our experience with inpatient hybrid closed-loop control (HCLC) initiated shortly after the diagnosis of type 1 diabetes in a randomized trial designed to assess the effectiveness of inpatient HCLC followed by outpatient sensor-augmented pump (SAP) therapy on the preservation of β-cell function., Subjects and Methods: Forty-eight individuals with newly diagnosed type 1 diabetes and positive pancreatic autoantibodies (7.8-37.7 years old) received inpatient HCLC therapy for up to 93 h, initiated within 7 days of diagnosis., Results: On initiation of HCLC, mean glucose concentration was 240±100 mg/dL. During the first day of HCLC, median of the participant's mean glucose concentrations fell rapidly to 146 mg/dL, a level of control that was sustained on Days 2 and 3 (138 mg/dL and 139 mg/dL, respectively). By Day 3, the median percentage of glucose values >250 and <60 mg/dL was <1%. During the first 2 weeks of SAP treatment at home, the median participant mean glucose level was 126 mg/dL (interquartile range, 117, 137 mg/dL), and the median percentage of values between 71 and 180 mg/dL was 85% (interquartile range, 80%, 90%)., Conclusions: Inpatient HCLC followed by outpatient SAP therapy can provide a safe and effective means to rapidly reverse glucose toxicity and establish near-normal glycemic control in patients with newly diagnosed type 1 diabetes.

Background: There are currently few data available on the long-term use of continuous subcutaneous insulin infusion (CSII) (insulin pump) therapy in children., Methods: Charts from 291 youth with type 1 diabetes (T1D) who were treated with CSII therapy for at least 1 year were reviewed. Data analysis included hemoglobin A(1c)(HbA(1c)) values, body mass index (BMI) values, and the occurrence of severe hypoglycemia (SH) or diabetic ketoacidosis (DKA) events., Results: For the 291 patients, the mean age (+/-SD) for beginning CSII therapy was 13.3 +/- 3.7 years. The mean duration of CSII was 3.7 +/- 1.9 years (range 1-9 years). The baseline HbA(1c) value was 8.7 +/- 1.0%, compared to 8.2 +/- 0.9% after 1 year (P < 0.0001). The most recent value for all patients was 8.3 +/- 1.3% (P < 0.0001 compared to the baseline values for the same subjects). There was no advantage in glycemic control in the teen years as a result of initiating CSII in the pre-teen years compared to the teen years. SH events decreased from 9.06 events per 100 patient-years before CSII therapy to 7.96 events per 100 patient-years while on CSII therapy. The incidence of DKA increased from 1.39 events pre-CSII to 3.98 events per 100 patient-years while on CSII therapy. BMI z-scores showed a nonsignificant increase., Conclusions: The long-term use of CSII in pediatric patients is beneficial in lowering mean HbA(1c) levels and the number of SH events. However, there was an increase in the number of DKA episodes.

Objective: The aim of this study was to determine whether the use of meal bolus alarms would result in fewer missed meal boluses per week in youth with type 1 diabetes using continuous subcutaneous insulin infusion (CSII) therapy., Research Design and Methods: This was a randomized trial of 48 youth using CSII, who were in suboptimal glycemic control with HbA(1c) (A1C) values > or =8.0%. Twenty-four subjects were randomized to use a Deltec Cozmo insulin pump with meal bolus alarms (experimental group), while the other 24 subjects continued use of their current insulin pumps (control group) without meal bolus alarms., Results: After 3 months of study, the number of missed meal boluses per week was significantly lower in the experimental group (from 4.9 +/- 3.7 to 2.5 +/- 2.5; P = 0.0005) but not significantly lower in the control group (from 4.3 +/- 2.7 to 4.2 +/- 3.9; P = 0.7610). Also after 3 months, the mean A1C value of the experimental group declined significantly (from 9.32 +/- 1.12 to 8.86 +/- 1.10; P = 0.0430). No significant decline in A1C was present for the control group (from 8.93 +/- 1.04 to 8.67 +/- 1.17; P = 0.1940). After 6 months of study, the significant decline in A1C from baseline in the experimental group was no longer present. Pooling of all available data from the control and experimental groups showed that at baseline and 3 and 6 months, the number of missed meal boluses per week was significantly correlated with A1C values., Conclusions: While meal bolus alarms may have the potential to improve suboptimal glycemic control in youth using CSII, our results demonstrated that these alarms had only a transient, modest effect in doing so.

Objective: The objective of this study was to determine whether earlier diagnosis of diabetes in prospectively followed autoantibody-positive children lowered onset morbidity and improved the clinical course after diagnosis., Research Design and Methods: The Diabetes Autoimmunity Study in the Young (DAISY) follows genetically at-risk children for the development of diabetes. Increased genetic risk is identified by family history of type 1 diabetes or expression of diabetes-associated HLA genotypes. Of the 2,140 prospectively followed children, 112 have developed islet autoantibodies and 30 have progressed to diabetes. Diabetes onset characteristics and early clinical course of these 30 children followed to diabetes were compared with those of 101 age- and sex-matched children concurrently diagnosed with diabetes in the community., Results: Pre-diabetic children followed to diabetes were less often hospitalized than the community cases (3.3 vs. 44%; P < 0.0001). They had a lower mean HbA(1c) at onset (7.2 vs. 10.9%; P < 0.0001) and 1 month after diagnosis (6.9 vs. 8.6%; P < 0.0001) but not after 6 months of diabetes. The mean insulin dose was lower in the DAISY group at 1 (0.30 vs. 0.51 U. kg(-1). day(-1); P = 0.003), 6 (0.37 vs. 0.58; P = 0.001), and 12 months (0.57 vs. 0.72; P = 0.03). There was no difference in growth parameters between the two groups. Comparisons limited to children with a family history of type 1 diabetes in both groups showed a similar pattern., Conclusions: Childhood type 1 diabetes diagnosed through a screening and follow-up program has a less severe onset and a milder clinical course in the first year after diagnosis.

Purpose: To describe 11 instances of severe diabetic ketoacidosis (DKA) with secondary intracerebral complications (ICCs), nine of whom were treated early and showed complete recovery., Methods: Three hundred and eighty-one episodes of DKA were treated at Denver Children's Hospital (DCH) from January 1989 to December 1999. Nine instances of DKA with ICC were prospectively identified during this time period. Two additional occurrences were identified via a medical records search (total incidence, 2.9%). The signs, symptoms and laboratory values which led to their diagnosis and treatment are identified., Results: All nine children who received early treatment with i.v. mannitol showed complete recovery. An additional patient had central nervous system involvement upon arrival at our hospital and showed almost complete recovery. Another patient suffered a cardiorespiratory arrest before transfer to our hospital and died without being treated for cerebral edema., Conclusion: Prevention of ICCs by the earlier diagnosis of diabetes and by being aware of possible risk factors for cerebral edema is the eventual goal. Based on our experience, mannitol should be given promptly for the treatment of ICCs indicated by the clinical course even if cerebral edema is not documented by a computed tomography (CT) scan.

Objective: The purpose of this study was to determine the feasibility of continuous subcutaneous insulin infusion (CSII) (insulin pump) therapy in routine pediatric diabetes care by comparing the HbA(1c), body mass index (BMI), and hypoglycemic episodes before and after initiation of CSII therapy., Research Design and Methods: Data from 56 patients (7-23 years old) were collected during regularly scheduled visits at a frequency similar to non-CSII patients., Results: The data were analyzed for the entire cohort and 3 subgroups (decreased, stable, or increased HbA(1c)) stratified according to a >/=0.5% change in HbA(1c). The total cohort demonstrated a decrease in HbA(1c) from 8.5% to 8.3%. The decreased cohort (39.4% of the total cohort) demonstrated a significant decrease in HbA(1c) from 8.6% to 7.6%. The mean HbA(1c) of the stable cohort (41.0%) was 8.7%. The increased cohort (19.6%) had an increase in HbA(1c) from 7.8% to 8.8%. Thirty-six patients (64.3%) maintained or achieved a HbA(1c) <8.0% or achieved a HbA(1c) at least 1% lower than their pre-CSII level. Of concern, 6 patients (10.7%) demonstrated a clinically significant increase in HbA(1c) from 8.3% to 9.6%. For the entire cohort, the rate of severe hypoglycemia before and on CSII therapy was 12.3 and 9.5 events per 100 patient-years, respectively. A statistically significant proportion of patients reported a decrease in seizure frequency versus an increase (17.9% vs 1.8%) as well as a decrease in overall hypoglycemic frequency versus an increase (41.1% vs 17.9%). There was not a clinically significant increase in BMI, even in the decreased HbA(1c) cohort., Conclusions: CSII therapy is an appropriate option for some children in routine pediatric diabetes care. It can effectively decrease the HbA(1c) and reduce hypoglycemic episodes, without producing an abnormal increase in BMI.

Objective: The purpose of this study was to determine whether postprandial administration of the new rapid-acting insulin analog Humalog could effectively reduce glucose excursions in children <5 years old., Design: Human Regular insulin given before a meal was compared with the same dose of Humalog after a meal of equal carbohydrate content in five toddlers with insulin-dependent (type 1) diabetes mellitus. In addition, the use of Humalog before a meal was compared with Humalog given after a meal of equal carbohydrate content in five other toddlers. The dose of long-acting insulin was not changed during the study period. Blood glucose levels were determined at fasting and at 1, 2, and 4 hours postprandially., Results: The 2-hour glucose excursions were significantly lower when postprandial Humalog administration was compared with preprandial Human Regular insulin administration. In contrast, glucose excursions were similar when Humalog was taken before or after the meal., Conclusion: These data show that it is efficacious to give Humalog insulin postprandially in toddlers with type 1 diabetes, allowing increased safety for the young child. The insulin dose can be both matched to the actual food intake and timed to give families increased flexibility and control at mealtime.

Transdermal fentanyl is a new fentanyl delivery system recently approved by the FDA for use in patients with chronic pain. In an open-label clinical trial, 5 patients with cancer pain were switched to transdermal fentanyl patches. Patients were evaluated with visual analogue scales (VAS) for pain, mood, and pain relief. A Functional Living Index--Cancer and a symptom questionnaire were filled out 2 wk and 4 wk after initiation of transdermal fentanyl patches. After 2 wk of treatment all patients had VAS improvements in pain control. Patients experienced a decrease in constipation, improved appetite, and improved mood. One patient had drowsiness, which limited dose. The improvements in pain control allowed these patients to perform tasks that they had previously not felt well enough to do.

To evaluate the effectiveness of clonidine on growth-hormone (GH) release in prepubertal children, and to distinguish between a central alpha-adrenergic effect and a corticotropin-cortisol-mediated response, we measured serum glucose, corticotropin, cortisol, and GH concentrations following levodopa, arginine hydrochloride, and clonidine hydrochloride stimulation in 15 euthyroid children who had short stature. We found that clonidine is an effective and safe stimulator of GH release and provided a clearer distinction between GH-deficient and non-GH-deficient young persons than levodopa or arginine. The action of clonidine is not corticotropin-cortisol mediated.