Search

OBJECTIVE Advances in diabetes technology have transformed the treatment paradigm for type 1 diabetes, yet the burden of disease is significant. We report on a pivotal safety study of the first tubeless, on-body automated insulin delivery system with customizable glycemic targets. RESEARCH DESIGN AND METHODS This single-arm, multicenter, prospective study enrolled 112 children (age 6–13.9 years) and 129 adults (age 14–70 years). A 2-week standard therapy phase (usual insulin regimen) was followed by 3 months of automated insulin delivery. Primary safety outcomes were incidence of severe hypoglycemia and diabetic ketoacidosis. Primary effectiveness outcomes were change in HbA1c and percent time in sensor glucose range 70–180 mg/dL (“time in range”). RESULTS A total of 235 participants (98% of enrolled, including 111 children and 124 adults) completed the study. HbA1c was significantly reduced in children by 0.71% (7.8 mmol/mol) (mean ± SD: 7.67 ± 0.95% to 6.99 ± 0.63% [60 ± 10.4 mmol/mol to 53 ± 6.9 mmol/mol], P < 0.0001) and in adults by 0.38% (4.2 mmol/mol) (7.16 ± 0.86% to 6.78 ± 0.68% [55 ± 9.4 mmol/mol to 51 ± 7.4 mmol/mol], P < 0.0001). Time in range was improved from standard therapy by 15.6 ± 11.5% or 3.7 h/day in children and 9.3 ± 11.8% or 2.2 h/day in adults (both P < 0.0001). This was accomplished with a reduction in time in hypoglycemia CONCLUSIONS This tubeless automated insulin delivery system was safe and allowed participants to significantly improve HbA1c levels and time in target glucose range with a very low occurrence of hypoglycemia.

Objective: Very young children with type 1 diabetes often struggle to achieve glycemic targets, putting them at risk of long-term complications and creating an immense management burden for caregivers. We conducted the first evaluation of the Omnipod® 5 Automated Insulin Delivery (AID) System in this population. Research Design and Methods: Eighty children aged 2-5.9 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 (SH) or diabetic ketoacidosis (DKA). By study end, HbA1c decreased by 0.55% (6.0mmol/mol) (p Conclusions: Use of the AID system was safe, and participants experienced improved glycemic measures and reduced hypoglycemia during the study phase compared with baseline.

The Omnipod 5 System is a novel hybrid closed-loop (HCL) system with full on-body operation. A tubeless insulin pump containing a personalized MPC algorithm communicates directly with a Dexcom G6 CGM to automate insulin delivery. Following demonstration of positive safety and efficacy in older children (≥6y) and adults, we evaluated the system in very young children (2-5.9y) with T1D. Preschoolers with T1D often have erratic eating behaviors and may dislike being tethered to devices, and parental concern may lead to permissive hyperglycemia. This HCL system may be ideal for young children, given its customizable glucose targets from 110-150mg/dL, wireless system interaction through a mobile application, and bolus calculator that incorporates CGM trend information. Also, the system has no minimum weight or total daily dose (TDD) requirement. Participants with T1D and A1C180mg/dL was 39.4±16.5%, and ≥250mg/dL was 14.7±12.0%. The same efficacy analysis is planned for the 3-month HCL phase upon its completion in January 2021. This multi-center pivotal study has, to date, demonstrated safety of the Omnipod 5 System in very young children with T1D. At completion, this will be the largest study of HCL in this age group reported to date. Disclosure J. Sherr: Advisory Panel; Self; Cecelia Health, Insulet Corporation, Medtronic, Consultant; Self; Insulet Corporation, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Research Support; Self; Dexcom, Inc., Insulet Corporation, Medtronic, Speaker’s Bureau; Self; Lilly Diabetes. D. W. Hansen: None. T. T. Ly: Employee; Self; Insulet Corporation. Omnipod 5 in preschoolers study group: n/a. B. W. Bode: Advisory Panel; Self; Eli Lilly and Company, Consultant; Self; Bigfoot Biomedical, Inc., Companion Medical, Lexicon Pharmaceuticals, Inc., Medtronic, Novo Nordisk Inc., Zealand Pharma A/S, Research Support; Self; Abvance Therapeutics, Dexcom, Inc., Diasome Pharmaceuticals, Inc., Dompe, Eli Lilly and Company, Eyenuk, Inc., Insulet Corporation, Jaeb Center for Health Research, Medtronic, Nova Biomedical, Novo Nordisk, Provention Bio, Inc., REMD Biotherapeutics, Sanofi, Senseonics, Viacyte, Inc., vTv Therapeutics, Xeris Pharmaceuticals, Inc., Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MannKind Corporation, Medtronic, Novo Nordisk, Sanofi, Stock/Shareholder; Self; AgaMatrix, Aseko, Inc., Glytec, LLC. G. P. Forlenza: Advisory Panel; Self; Medtronic, Consultant; Self; Beta Bionics, Inc., Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Research Support; Self; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. L. M. Laffel: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompe, Insulogic LLC, Janssen Pharmaceuticals, Inc., Laxmi Therapeutic Devices, LifeScan, Lilly Diabetes, Medtronic, Provention Bio, Inc. S. A. Brown: Research Support; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care, Tandem Diabetes Care, Tolerion, Inc. B. A. Buckingham: Advisory Panel; Self; Medtronic, Tolerion, Inc., Research Support; Self; Beta Bionics, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. A. B. Criego: Consultant; Self; Bigfoot Biomedical, Inc., Other Relationship; Self; Sanofi, Research Support; Self; Abbott Diabetes, Eli Lilly and Company, Insulet Corporation, Medtronic. D. Desalvo: Consultant; Self; Insulet Corporation, Research Support; Self; Insulet Corporation, Speaker’s Bureau; Self; Dexcom, Inc. S. A. Macleish: Advisory Panel; Self; Insulet Corporation. Funding Insulet Corporation

Safe and effective use of the Omnipod 5 System was demonstrated in adults and children with type 1 diabetes (T1D) during a 3-month pivotal study. Longer studies are needed to evaluate durability of glycemic benefit. Those completing the pivotal study were invited to continue system use for an additional 12 months, with 95% enrolling in the extension. We present results from the first 3-month follow-up. Participants aged 6-70y with T1D≥6 months and A1C Disclosure A. L. Carlson: Board Member; Self; JDRF, Other Relationship; Self; Medtronic, Research Support; Self; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, Omnipod, Sanofi, UnitedHealth Group. J. Sherr: Advisory Panel; Self; Cecelia Health, Insulet Corporation, Medtronic, Consultant; Self; Insulet Corporation, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Research Support; Self; Dexcom, Inc., Insulet Corporation, Medtronic, Speaker’s Bureau; Self; Lilly Diabetes. S. N. Mehta: None. L. M. Laffel: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompe, Insulogic LLC, Janssen Pharmaceuticals, Inc., Laxmi Therapeutic Devices, LifeScan, Lilly Diabetes, Medtronic, Provention Bio, Inc. V. Shah: Advisory Panel; Self; Medscape, Sanofi, Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk, Sanofi, vTv Therapeutics. A. Bhargava: Research Support; Self; Abbott, AbbVie Inc., Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Boston Therapeutics, Inc., Covance Inc., Dexcom, Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Insulet Corporation, Janssen Research & Development, LLC, Kowa Pharmaceuticals America, Inc., Madrigal Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Mylan N. V., Novo Nordisk, Poxel SA, Quintiles, Sanofi, Senseonics, Tolerion, Inc., Viking Therapeutics. R. S. Weinstock: Research Support; Self; Boehringer Ingelheim International GmbH, Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Insulet Corporation, Kowa Research Institute, Inc., Medtronic, Tolerion, Inc. S. A. Macleish: Advisory Panel; Self; Insulet Corporation. D. Desalvo: Consultant; Self; Insulet Corporation, Research Support; Self; Insulet Corporation, Speaker’s Bureau; Self; Dexcom, Inc. T. C. Jones: None. G. Aleppo: Consultant; Self; Dexcom, Inc., Insulet Corporation, Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk. A. B. Criego: Consultant; Self; Bigfoot Biomedical, Inc., Other Relationship; Self; Sanofi, Research Support; Self; Abbott Diabetes, Eli Lilly and Company, Insulet Corporation, Medtronic. B. A. Buckingham: Advisory Panel; Self; Medtronic, Tolerion, Inc., Research Support; Self; Beta Bionics, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. T. T. Ly: Employee; Self; Insulet Corporation. Omnipod 5 research group: n/a. G. P. Forlenza: Advisory Panel; Self; Medtronic, Consultant; Self; Beta Bionics, Inc., Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Research Support; Self; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. B. W. Bode: Advisory Panel; Self; Eli Lilly and Company, Consultant; Self; Bigfoot Biomedical, Inc., Companion Medical, Lexicon Pharmaceuticals, Inc., Medtronic, Novo Nordisk Inc., Zealand Pharma A/S, Research Support; Self; Abvance Therapeutics, Dexcom, Inc., Diasome Pharmaceuticals, Inc., Dompe, Eli Lilly and Company, Eyenuk, Inc., Insulet Corporation, Jaeb Center for Health Research, Medtro Funding Insulet Corporation

Advances in diabetes technology have transformed the treatment paradigm for T1D, yet the burden of the disease remains significant. The pediatric population poses unique challenges to glucose management with unpredictable exercise and food consumption. The Omnipod 5 System is a novel hybrid closed-loop (HCL) system with fully on-body operation. A tubeless insulin pump (pod) containing a personalized Model Predictive Control algorithm communicates directly with a Dexcom G6 continuous glucose monitor (CGM, or sensor) to automate insulin delivery. Therapy customization is enabled through glucose targets from 110–150 mg/dL, adjustable by time of day, which is a critical component to individualize glucose management in children. We report on the first, pivotal outpatient safety evaluation of the Omnipod 5 System in a large cohort of children with T1D. Participants aged 6–13.9y with T1D≥6 months and A1C Participants (N=112) were aged (mean±SD) 10.3±2.2y with T1D duration 4.7±2.6y and baseline A1C 7.7±0.9% (range 5.8–10.3%). TIR increased significantly from ST to HCL, from 52.5±15.6% to 68.0±8.1% (p180 mg/dL from 45.3±16.7% to 30.2±8.7% and ≥250 mg/dL from 19.1±13.1% to 9.6±5.4% (both p0.05). Mean glucose decreased from 183±32 to 160±15 mg/dL (p In this multi-center pivotal study in a large cohort of children with T1D, the Omnipod 5 System was safe and effective when used for 3 months at home. There were significant improvements in both TIR and A1C, while time below range (

Puberty is a pivotal time in an adolescent’s life. Knowing when puberty is precocious or delayed is important to correctly diagnose and treat abnormalities. Being able to appropriately check the progression of puberty is a foundation for reaching the correct diagnosis. Precocious puberty is generally accepted as a testicular volume ≥4 ml prior to 9 years of age, and delayed puberty is the lack of testicular growth by 14 years of age. Causes of precocious puberty include both gonadotropin-dependent (central) and gonadotropin-independent (peripheral) etiologies, and treatment varies according to the etiology. Delayed puberty also has multiple causes, including primary gonadal abnormalities such as testicular injury, and numerous causes of hypogonadotropic hypogonadism, both congenital and acquired. Constitutional delay of growth and puberty is a particularly common etiology of delayed puberty. It is usually benign, but affected boys may benefit from a short course of testosterone. Correctly ascertaining the etiology of delayed puberty will direct the appropriate therapy. While precocious or delayed puberty may be benign, some causes are serious, making the need to understand this topic important for physicians.

The prevalence of nephrocalcinosis in persons with pseudohypoparathyroidism has not been systematically examined. We conducted a retrospective study of renal imaging and biochemical results in 19 patients with pseudohypoparathyroidism with 49 imaging assessments. No cases of nephrocalcinosis were identified. Routine screening for nephrocalcinosis in pseudohypoparathyroidism may not be necessary.

For more than twenty years, I have been studying the fascinating relationships between right triangles and their inscribed and escribed circles. An inscribed circle is one that is tangent to all three sides of a triangle and whose center lies inside the triangle. An escribed circle is one that is tangent to one of the sides of the triangle and to the extensions of the other two sides and whose center lies outside the triangle. Every triangle has one inscribed and three escribed circles, as shown in figure 1.

built up from axioms by the use of logical principles. By altering these axioms, dif ferent types of mathematics can be devel oped; for example, Euclidean and non Euclidean geometries differ by only one axiom?the parallel postulate?but this difference is quite sufficient to lead to very different conclusions in each system. This modern concept of mathematics stresses the idea that man invents his mathe matics (and hence controls it to some extent) rather than discovers it (the as sumption here being that mathematics exists apart from and independent of man). Mathematics becomes an intellec tual game. You select your axioms according to taste and work out the corre sponding mathematics, using logical prin ciples. If the results are aesthetically pleasing or elegant, this new system be comes a part of mathematics. Notice here that for the modern mathematician there is no mention of applicability to reality. The system stands alone on its consist ency and beauty. If, for some reason, the system can be used in explaining certain properties of the real world, this is of no import to the mathematician. G. H. Hardy, in his book A Mathematician's Apology, expresses this view quite force fully. It has been said by Huxley that six monkeys pecking unintelligently on typewriters would, after millions of mil lions of years, eventually write all the books in the British Museum (Sir James Jeans quotes Huxley's statement on page 4 of the Mysterious Universe). Similarly, mathematicians randomly selecting vari ous axioms would eventually produce sig nificant mathematical systems, but un doubtedly only after an enormous amount of time had been wasted. Now I do not claim that this is really the way mathematics is produced. In fact, my thesis in this paper is that great mathematics is seldom done by playing these intellectual games; rather, the great mathematicians, in doing their mathe matics, have had an eye out for some thing external to themselves?let us call it the real world?and their hope has been that their mathematics would lead not only to beauty and an internal truth but to external truths as well?namely, sig nificant knowledge oj the real world. Now, the present-day concern with and em phasis on axiomatics (to the exclusion of everything else) has been of fairly recent origin, getting its start in the late nine teenth century or very early twentieth century. Some observers feel that this emphasis has caused a split between mathematics and science. By tracing the development and interests of several mathematicians from the past who have without doubt significantly contributed to the advancement of mathematics, I hope to show that this modern trend of over emphasis on axiomatics should at least be modified to include consideration of the significance of reality in any develop ment of new mathematics. In Men oj Mathematics (1937, p. 218), E. T. Bell says

One article dealing with some of the research on binocular interaction effects being carried out in our laboratory has appeared previously in this Journal (White and Bonelli). In that study, it was found that the amplitude of the visually evoked cortical potential (VER) produced by patterned stimuli viewed with both eyes was directly related to the quality of the retina image. Furthermore, the degree of binocular summation shown by the VERs was also related to image quality, with marked summation occurring when sharply focused patterns were presented but much less evidence of it when the patterns were blurred. In that study the retinal images were reasonably similar, since the degree of blur desired was produced by placing ophthalmic lenses of equal strength before the two eyes. The next situation we decided to test was that in which the images presented to the two eyes were not of the same quality. This paper will deal briefly with some work we have done on that topic, and will also present some other examples of work dealing with binocular interaction and related topics.

From Foreword: "This Monograph is one of a series intended to provide fundamental information required for the estimation and interpretation of atmospheric transmittance at infrared frequencies. Part I of this Monograph presents the fundamental properties of the 2.7m water vapor band in terms of line absorptions and the integrated transmittance at any frequency for infinite resolution. Part II presents examples of the "degraded" transmittance for finite resolution, as a function of the spectral slit width, concentration, and pressure with which direct observations may be compared."

The spectral line positions, strengths, and half-widths of the ν1, 2ν2, and ν3 bands of the 2.7 μ region of absorption for water vapor have been computed and checked against laboratory spectra for the range 2857 to 4444 cm−1. From a knowledge of these lines theoretical transmission spectra at infinite spectral resolution at a given pressure, temperature, and water vapor concentration have been determined. From the theoretical transmission spectra certain degraded spectra for finite slit-width are computed, and a comparison is made with a high-altitude atmospheric absorption spectrum of solar radiation.