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With the increasing success of islet transplantation, beta-cell replacement therapy has had renewed interest. To make such a therapy available to more than a few of the thousands of patients with diabetes, new sources of insulin-producing cells must become readily available. The most promising sources are stem cells, whether embryonic or adult stem cells. Clearly identifiable adult pancreatic stem cells have yet to be characterized. Although considerable evidence suggests their possibility, recent lineage-tracing experiments challenge their existence. Even in light of these lineage-tracing experiments, we suggest that evidence for neogenesis or new islet formation after birth remains strong. Our work has suggested that the pancreatic duct epithelium itself serves as a pool for progenitors for both islet and acinar tissues after birth and into adulthood and, thus, that the duct epithelium can be considered 'facultative stem cells'. We will develop our case for this hypothesis in this perspective. [ABSTRACT FROM AUTHOR]

Gluconeogenesis (GNG) is enhanced in type 2 diabetes. In experimental animals, insulin at high doses decreases the incorporation of labeled GNG precursors into plasma glucose. Whether physiological hyperinsulinemia has any effect on total GNG in humans has not been determined. We combined the insulin clamp with the (2)H(2)O technique to measure total GNG in 33 subjects with type 2 diabetes (BMI 29.0 +/- 0.6 kg/m(2), fasting plasma glucose 8.1 +/- 0.3 mmol/l) and in 9 nondiabetic BMI-matched subjects after 16 h of fasting and after euglycemic hyperinsulinemia. A primed-constant infusion of 6,6-(2)H-glucose was used to monitor endogenous glucose output (EGO); insulin (40 mU. min(-1). m(-2)) was then infused while clamping plasma glucose for 2 h (at 5.8 +/- 0.1 and 4.9 +/- 0.2 mmol/l for diabetic and control subjects, respectively). In the fasting state, EGO averaged 15.2 +/- 0.4 micromol. min(-1). kg(-1)(ffm) (62% from GNG) in diabetic subjects and 12.2 +/- 0.7 micromol. min(-1). kg(-1)(ffm) (55% from GNG) in control subjects (P < 0.05 or less for both fluxes). Glycogenolysis (EGO - GNG) was similar in the two groups (P = NS). During the last 40 min of the clamp, both EGO and GNG were significantly (P < 0.01 or less, compared with fasting) inhibited (EGO 7.1 +/- 0.9 and 3.6 +/- 0.5 and GNG 7.9 +/- 0.5 and 4.5 +/- 1.0 respectively) but remained significantly (P < 0.05) higher in diabetic subjects, whereas glycogenolysis was suppressed completely and equally in both groups. During hyperinsulinemia, GNG micromol. min(-1). kg(-1)(ffm) in diabetic and control subjects, was reciprocally related to plasma glucose clearance. In conclusion, physiological hyperinsulinemia suppresses GNG by approximately 20%, while completely blocking glycogenolysis. Resistance of GNG (to insulin suppression) and resistance of glucose uptake (to insulin stimulation) are coupled phenomena. In type 2 diabetes, the excess GNG of the fasting state is carried over to the insulinized state, thereby contributing to glucose overproduction under both conditions. [ABSTRACT FROM AUTHOR]

The aim of this work was to develop a mathematical model describing the functional dependence of insulin secretion on plasma glucose concentrations during 24 h of free living. We obtained hourly central venous blood samples from a group of healthy volunteers who spent 24 h in a calorimetric chamber, where they consumed standardized meals. Insulin secretory rates were reconstructed from plasma C-peptide concentrations by deconvolution. The relationship between insulin release and plasma glucose concentrations was modeled as the sum of three components: a static component (describing the dependence on plasma glucose concentration itself, with an embedded circadian oscillation), a dynamic component (modeling the dependence on glucose rate of change), and a residual component (including the fraction of insulin secretion not explained by glucose levels). The model fit of the individual 24-h secretion profiles was satisfactory (within the assigned experimental error of glucose and C-peptide concentrations). The static component yielded a dose-response function in which insulin release increased quasi-linearly (from 40 to 400 pmol/min on average) over the range of 4-9 mmol/l glucose. The dynamic component was significantly different from zero in coincidence with meal-related glucose excursions. The circadian oscillation and the residual component accounted for the day/night difference in the ability of glucose to stimulate insulin release. Over 24 h, total insulin release averaged 257+/-58 nmol (or 43+/-10 U). The static and dynamic component together accounted for approximately 80% of total insulin release. The model proposed here provides a detailed robust description of glucose-related insulin release during free-living conditions. In nondiabetic subjects, non-glucose-dependent insulin release is a small fraction of total insulin secretion. [ABSTRACT FROM AUTHOR]

The contribution of gluconeogenesis (GNG) to endogenous glucose output (EGO) in type 2 diabetes is controversial. Little information is available on the separate influence of obesity on GNG. We measured percent GNG (by the 2H2O technique) and EGO (by 6,6-[2H]glucose) in 37 type 2 diabetic subjects (9 lean and 28 obese, mean fasting plasma glucose [FPG] 8.3 +/- 0.3 mmol/l) and 18 control subjects (6 lean and 12 obese) after a 15-h fast. Percent GNG averaged 47 +/- 5% in lean control subjects and was significantly increased in association with both obesity (P < 0.01) and diabetes (P = 0.004). By multivariate analysis, percent GNG was independently associated with BMI (partial r = 0.27, P < 0.05, with a predicted increase of 0.9% per BMI unit) and FPG (partial r = 0.44, P = 0.0009, with a predicted increase of 2.7% per mmol/l of FPG). In contrast, EGO was increased in both lean and obese diabetic subjects (15.6 +/- 0.5 micromol x min(-1) x kg(-1) of fat-free mass, n = 37, P = 0.002) but not in obese nondiabetic control subjects (13.1 0.7, NS) as compared with lean control subjects (12.4 +/- 1.4). Consequently, gluconeogenic flux (percent GNG x EGO) was increased in obesity (P = 0.01) and markedly elevated in diabetic subjects (P = 0.0004), whereas glycogenolytic flux was reduced only in association with obesity (P = 0.05). Fasting plasma glucagon levels were significantly increased in diabetic subjects (P < 0.05) and positively related to EGO, whereas plasma insulin was higher in obese control subjects than lean control subjects (P = 0.05) and unrelated to measured glucose fluxes. We conclude that the percent contribution of GNG to glucose release after a 15-h fast is independently and quantitatively related to the degree of overweight and the severity of fasting hyperglycemia. In obese individuals, reduced glycogenolysis ensures a normal rate of glucose output. In diabetic individuals, hyperglucagonemia contributes to inappropriately elevated rates of glucose output from both GNG and glycogenolysis. [ABSTRACT FROM AUTHOR]

N-carboxybutyl chitosan and fibrin glue were studied in wound healing. Open wounds were performed on the back of 12 New Zealand rabbits by removing cutaneous and subcutaneous tissue down to superficial muscle's fascia. The rabbits were divided in two groups: the first one was treated weekly with N-carboxybutyl chitosan and the second one with fibrin glue. No signifi cant differences in healing time and no suppurative complications were observed. On the 15th day, the fibrin glue group histology showed initial heal ing with a multilayered epithelial tissue more evident than in the other group. The vascular structures were present in both groups but the histoarchitectural order of the stromal matrix was better in the N-carboxybutyl chitosan group. On the 30th day, complete reepithelialization was observed for the N-car boxybutyl chitosan group with all the epithelial cellular layers represented. Underlying connective tissue was mature but looser than for the fibrin glue group. Results show that with regard to biological functions, both fibrin glue and N-carboxybutyl chitosan provided positive results in tissue healing processes. Furthermore, N-carboxybutyl chitosan produced a more regular histoarchitectural restoration, with very limited inflammatory processes. N-carboxybutyl chitosan presents interesting features that can open new per spectives in tissue reconstruction. [ABSTRACT FROM PUBLISHER]

Abstract Background Signs of serious clinical events overlap with those of sepsis. We hypothesised that any education on severe sepsis/septic shock may affect the outcome of all hospital patients. We designed this study to assess the trend of the mortality rate of adults admitted to hospital for at least one night in relationship with a hospital staff educational program dedicated to severe sepsis/septic shock. Methods This study was performed in six Italian hospitals in the same region. Multidisciplinary Sepsis Teams members were selected by each hospital management among senior staff. The education included the following steps: i) the Teams were taught about adult learning, problem based learning, and Surviving Sepsis guidelines, and provided with educational material (literature, electronic presentations, scenarios of clinical cases for training and booklets); ii) they started delivering courses and seminars each to their own hospital staff in the last quarter of 2007. To analyse mortality, we selected adult patients, admitted for at least one night to the wards or units present in all the study hospitals and responsible for 80% of hospital deaths. We fitted a Poisson model with monthly hospital mortality rates from December 2003 to August 2009 as dependent variable. The effect of the educational program on hospital mortality was measured as two dummy variables identifying a first (November 2007 to December 2008) and a second (January to August 2009) education period. The analysis was adjusted for a linear time trend, seasonality and monthly average values of age, Charlson score, length of stay in hospital and urgent/non-urgent admission. Results The hospital staff educated reached 30.6% at the end of June 2009. In comparison with the pre-education period, the Relative Risk of death of the patient population considered was 0.93 (95% confidence interval [CI] 0.87-0.99; p 0.025) for in-patients in the first, and 0.89 (95% CI 0.81-0.98; p 0.012) for those in the second period after education. Conclusion Our hypothesis that a program educating hospital staff to early detection and treatment of severe sepsis/septic shock may affect the outcome of all hospital patients is original, but it has to be corroborated by other experiences.

Objective: A subgroup analysis of the Hypoglycemia Awareness Restoration Programme for people with type 1 diabetes and problematic hypoglycemia persisting despite optimized care (HARPdoc) trial was conducted to explore the impact of Blood Glucose Awareness Training (BGAT, a hypoglycemia awareness training program) and the HARPdoc (a psychoeducation addressing unhelpful hypoglycemia beliefs) in reducing severe hypoglycemia (SH) in individuals using advanced diabetes technologies (ADTs). Methods: Data from trial participants who utilized ADTs, including continuous glucose monitors or automated insulin delivery systems, were extracted. Generalized linear mixed-effects models with Poisson distribution or linear mixed-effects models were used to evaluate SH incidence, and Gold questionnaire, Attitudes to Awareness of Hypoglycemia (A2A), Problem Areas in Diabetes (PAID), Hospital Anxiety and Depress Scale (HADS)-anxiety, and HADS-depression scores as measures of hypoglycemia awareness, unhelpful hypoglycemia beliefs, diabetes distress, and anxiety and depression symptoms, respectively. Results: In the 45 participants using ADTs, the BGAT and HARPdoc interventions both reduced SH incidence by more than 50% ( P < 0.0001) and yielded improvements in hypoglycemia awareness ( P < 0.05). HARPdoc outperformed BGAT in reducing SH at month 24 ( P = 0.01). HARPdoc also mitigated unhelpful hypoglycemia beliefs ( P < 0.0001), diabetes distress ( P < 0.05), and anxiety symptoms ( P < 0.05); BGAT demonstrated no significant impacts in these respects. Neither HARPdoc nor BGAT had significant effects on depression symptoms. Conclusion: Psychoeducation (BGAT and HARPdoc) was effective in reducing SH in people using ADTs. HARPdoc may also provide greater long-term SH reduction and improves psychological well-being in this patient group.

Objective: Continuous glucose monitoring (CGM) use in older adults with type 1 diabetes (T1D) has shown benefits. However, the impact of CGM use, coupled with simplified treatment regimens and personalized glycemic goals that are better suited for older patients with multiple comorbidities and hypoglycemia, is not known., Research Design and Methods: Older adults (≥65 years) with T1D with hypoglycemia (two or more episodes of hypoglycemia [blood glucose <70 mg/dL for ≥20 min over 2 weeks]) who were CGM naïve or CGM users were randomized to intervention and control groups. The intervention consisted of the combined use of CGM with geriatric principles (i.e., adjusting goals based on overall health, and simplification of regimens based on CGM patterns and clinical characteristics) over 6 months. The control group received usual care by their endocrinologist. The primary end point was change in time when blood glucose was <70 mg/dL from baseline to 6 months. Cost-effectiveness was calculated using a health care sector perspective., Results: We randomized 131 participants (aged 71 ± 5 years; 21% ≥75 years old) to the intervention (n = 68; CGM users = 33) or the control (n = 63; CGM users = 40) group. The median change in hypoglycemia from baseline to 6 months was -2·6% in the intervention group and -0.3% in the control group (median difference, -2.3% [95% CI -3.7%, -1.3%]; P < 0.001). This improvement was seen in both CGM naïve (-2.8%; 95% CI -5.6%, -0.8%) and CGM users (-1.2%; 95% CI -2.7%, -0.1%). The HbA1c did not differ between the groups (7.5% vs 7.3%). The intervention was cost-effective (incremental cost-effectiveness ratio $71,623 per quality adjusted life-year)., Conclusions: In older adults with T1D and high risk of hypoglycemia, CGM use enhanced by geriatric principles can lower hypoglycemia without worsening glycemic control in a cost-effective fashion., (© 2024 by the American Diabetes Association.)

Aim: Young women with type 1 diabetes are a high-risk population for eating disorders (ED). Prevention programs are lacking. In young women without diabetes, the Body Project has produced reductions in ED risk factors, ED symptoms and future ED onset. Therefore, the Body Project was adapted to type 1 diabetes, the Diabetes Body Project (DBP). In this protocol, we describe the multi-site randomized controlled trial (RCT) to evaluate efficacy of the DBP., Methods: This is an ongoing RCT with four sites (Europe and US). In total 280, 14-35 year-old, women with type 1 diabetes ≥1 year and some level of body image concerns will be recruited in 2023. Participants are randomized to either virtual DBP groups or an educational control. The study constitutes 5 measurement points distributed over 2 years. The primary aim is to test if DBP will produce significantly greater reductions in ED behaviours, ED symptoms and future ED onset. The secondary aim is to test if DBP has significantly greater improvements in diabetes distress, quality of life and glycaemic outcomes., Results: We expect that DBP will be more efficacious in reducing ED behaviours, ED symptoms and ED onset compared to the control condition. Additionally, we hope to gain new knowledge on how DBP may affect diabetes-related outcomes., Conclusions: If DBP proves efficacious, it has potential for immediate, clinical implementation at low-cost and may contribute to broad prevention of future ED onset among young women with type 1 diabetes., Gov Identifier: NCT05399446., (© 2024 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Optimizing postprandial glucose control in persons with type 1 diabetes (T1D) is challenging. We hypothesized that in free-living individuals, meal composition (high and low glycemic index [HGI and LGI], high and low fat [HF and LF]) may impact insulin requirements. Adults ( N = 25) with T1D using open-loop insulin and continuous glucose monitoring were provided a meal-tagging app and prepackaged meals with defined macronutrient content. Data from 463 meals were analyzed. LGI meals required significantly more insulin than HGI meals ( P = 0.01). Furthermore, the mean (±standard deviation) carbohydrate-to-insulin ratio (CIR) was significantly different overall among the LGI-LF (5.5 ± 3.4), LGI-HF (4.5 ± 3.8), HGI-LF (7.6 ± 5.1), and HGI-HF (8.7 ± 5.8) meals ( P = 0.001). The risk of nocturnal hypoglycemia is associated with daytime hypoglycemia and amount of insulin administered prior to the evening and exercise. This exploratory study designed to examine the impact of different meal types on insulin dosing requirements in free-living adults with T1D emphasizes the need for individualized adjustment of the CIR depending on meal composition.

Avian botulism is a paralytic disease due to the ingestion of botulinum neurotoxins (BoNT) produced by anaerobic, sporigenic bacteria (notably, Clostridium botulinum ). Wild waterbirds worldwide are affected with variable recurrence and severity, and organic material decaying in wetland habitats may constitute a suitable substrate for the replication of clostridia strains producing BoNT in conditions of high temperatures and the absence of oxygen. Here, we describe a large outbreak of avian botulism that occurred in the Valle Mandriole protected area of northeastern Italy (VM). After the recovery in late summer of a few duck carcasses that molecularly tested positive for BoNT-producing clostridia, in October 2019, the avian botulism escalation led to a total of 2367 birds being recovered (2158 carcasses and 209 sick birds). Among these, 2365/2367 were waterbirds, with ducks accounting for 91.8% of the total (2173/2367) and green-winged teals representing 93.5% of the ducks. After the quick collection of dead and sick birds (from 4 to 11 October 2019) and the flooding of the VM wetland (from 5 to 12 October 2019), the 2019 botulism emergency apparently ended. Following two water inputs in May and July 2020, only one pooled sample obtained from 16 bird carcasses found that year in VM tested positive for clostridia type C by real-time PCR, whereas, after to the implementation of measures deterring the bird's presence, new avian botulism cases-due to clostridia type C and C/D, according to molecular and animal-model tests of confirmation-led to the collection of 176 waterbirds (82 carcasses and 94 sick ducks) and 16 waterbirds (9 carcasses and 7 sick ducks) in the summers 2021 and 2022, respectively. In conclusion, the prevention, management, and control of the disease rely on habitat management, the quick and careful collection/removal of animal carcasses, and the regular monitoring and surveillance of live and dead birds.

The older population is increasing worldwide and up to 30% of older adults have diabetes. Older adults with diabetes are at risk of glucose-related acute and chronic complications. Recently, mostly in type 1 diabetes (T1D), continuous glucose monitoring (CGM) devices have proven beneficial in improving time in range (TIR glucose, 70-180 mg/dL or glucose 3.9-10 mmol/L), glycated hemoglobin (HbA1c), and in lowering hypoglycemia (time below range [TBR] glucose <70 mg/dL or glucose <3.9 mmol/L). The international consensus group formulated CGM glycemic targets relating to older adults with diabetes based on very limited data. Their recommendations, based on expert opinion, were aimed at mitigating hypoglycemia in all older adults. However, older adults with diabetes are a heterogeneous group, ranging from healthy to very complex frail individuals based on chronological, biological, and functional aging. Recent clinical trial and real-world data, mostly from healthy older adults with T1D, demonstrated that older adults often achieve CGM targets, including TIR recommended for non-vulnerable groups, but less often meet the recommended TBR <1%. Existing data also support that hypoglycemia avoidance may be more strongly related to minimization of glucose variability (coefficient of variation [CV]) rather than lower TIR. Very limited data are available for glucose goals in older adults adjusted for the complexity of their health status. Herein, we review the bidirectional associations between glucose and health status in older adults with diabetes; use of diabetes technologies, and their impact on glucose control; discuss current guidelines; and propose a new set of CGM targets for older adults with insulin-treated diabetes that are individualized for health and living status., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: ET is a consultant for Vertex/Sequel. DON has received research support from Medtronic, Insulet, Dexcom, Roche, GlySens, BioCapillary, and Endogenex. He is on the advisory boards for Medtronic, Insulet, Abbott, Ypsomed, Novo Nordisk, and Sanofi. He has also received honoraria for lectures from Medtronic, Insulet, Abbott, Novo Nordisk, and Sanofi. MM is a consultant for Sanofi. AJ has no conflicts of interest.

Aims: To assess the cost-effectiveness of HARPdoc (Hypoglycaemia Awareness Restoration Programme for adults with type 1 diabetes and problematic hypoglycaemia despite optimised care), focussed upon cognitions and motivation, versus BGAT (Blood Glucose Awareness Training), focussed on behaviours and education, as adjunctive treatments for treatment-resistant problematic hypoglycaemia in type 1 diabetes, in a randomised controlled trial., Methods: Eligible adults were randomised to either intervention. Quality of life (QoL, measured using EQ-5D-5L); cost of utilisation of health services (using the adult services utilization schedule, AD-SUS) and of programme implementation and curriculum delivery were measured. A cost-utility analysis was undertaken using quality-adjusted life years (QALYs) as a measure of trial participant outcome and cost-effectiveness was evaluated with reference to the incremental net benefit (INB) of HARPdoc compared to BGAT., Results: Over 24 months mean total cost per participant was £194 lower for HARPdoc compared to BGAT (95% CI: -£2498 to £1942). HARPdoc was associated with a mean incremental gain of 0.067 QALYs/participant over 24 months post-randomisation: an equivalent gain of 24 days in full health. The mean INB of HARPdoc compared to BGAT over 24 months was positive: £1521/participant, indicating comparative cost-effectiveness, with an 85% probability of correctly inferring an INB > 0., Conclusions: Addressing health cognitions in people with treatment-resistant hypoglycaemia achieved cost-effectiveness compared to an alternative approach through improved QoL and reduced need for medical services, including hospital admissions. Compared to BGAT, HARPdoc offers a cost-effective adjunct to educational and technological solutions for problematic hypoglycaemia., (© 2024 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Background: In 2016, the Food and Drug Administration approved the first hybrid closed-loop (HCL) insulin delivery system for adults with type 1 diabetes (T1D). There is limited information on the impact of using HCL systems on patient-reported outcomes (PROs) in patients with T1D in real-world clinical practice. In this independent study, we evaluated glycemic parameters and PROs over one year of continuous use of Medtronic's 670G HCL in real-world clinical practice., Aim: To assess the effects of hybrid closed loop system on glycemic control and quality of life in adults with T1D., Methods: We evaluated 71 patients with T1D (mean age: 45.5 ± 12.1 years; 59% females; body weight: 83.8 ± 18.7 kg, body mass index: 28.7 ± 5.6 kg/m 2 , A1C: 7.6% ± 0.8%) who were treated with HCL at Joslin Clinic from 2017 to 2019. We measured A1C and percent of glucose time-in-range (%TIR) at baseline and 12 months. We measured percent time in auto mode (%TiAM) for the last two weeks preceding the final visit and assessed PROs through several validated quality-of-life surveys related to general health and diabetes management., Results: At 12 mo, A1C decreased by 0.3% ± 0.1% ( P = 0.001) and %TIR increased by 8.1% ± 2.5% ( P = 0.002). The average %TiAM was only 64.3% ± 32.8% and was not associated with A1C, %TIR or PROs. PROs, provided at baseline and at the end of the study, showed that the physical functioning submodule of 36Item Short-Form Health Survey increased significantly by 22.9% ( P < 0.001). Hypoglycemia fear survey/worry scale decreased significantly by 24.9% ( P < 0.000); Problem Areas In Diabetes reduced significantly by -17.2% ( P = 0.002). The emotional burden submodules of dietary diversity score reduced significantly by -44.7% ( P = 0.001). Furthermore, analysis of Clarke questionnaire showed no increase in awareness of hypoglycemic episodes. WHO-5 showed no improvements in subject's wellbeing among participants after starting the 670G HCL system. Finally, analysis of Pittsburgh Sleep Quality Index showed no difference in sleep quality, sleep latency, or duration of sleep from baseline to 12 mo., Conclusion: The use of HCL in real-world clinical practice for one year was associated with significant improvements in A1C, %TIR, physical functioning, hypoglycemia fear, emotional distress, and emotional burden related to diabetes management. However, these changes were not associated with time in auto mode., Competing Interests: Conflict-of-interest statement: Eldib A, Dhaver S, Kibaa K, Atakov-Castillo A, Salah T, Al-Badri M, Khater A, McCarragher R, Elenani O, Toschi E: Nothing to disclose. Hamdy O: Consultant to Abbott Nutrition, Sanofi Aventis; his employer Joslin Diabetes Center receives research grants from Novo-Nordisk, Eli-Lilly, Gilead Sciences, and National Dairy Council; on SAB of Twin Health; and is a shareholder of Healthimation Inc., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: The LIFT-YA (leveraging intensive follow-up treatment in young adults) quality improvement program was developed to address clinical and social barriers in young adults (YA) with type 1 diabetes (T1D), using telehealth visits to promote clinic attendance and improve diabetes care., Methods: LIFT-YA enrolled YA aged 18-30 with T1D and HbA1c >8% (64 mmol/mol) who had established adult care in our diabetes clinic. The 6-month, 7-visit hybrid program was facilitated by a case manager serving as the liaison between participants and the care team. The primary end-points were within-group and between-group changes from the baseline in HbA1c at the last visit and adoption of continuous glucose monitoring (CGM)., Results: Of the 57 eligible YA, 24 were enrolled and 33 were unable to participate (UTP). Thirteen of the enrolled participants attended at least 4/7 visits ("completers", C), whereas 11 were noncompleters (NC). HbA1c at the end of the program was significantly lower in the C versus UTP group [median -1.0; IQR (-0.6, -2.5) vs -0.25 (0.2, -1.0) in UTP; P < .05]. The percentage of CGM users significantly increased by 70% in the C group (P < .05), but did not change in the NC and UTP groups. Limited access to telehealth and the high cost of frequent visits were the main hurdles preventing enrollment into or completion of the program., Conclusions: The LIFT-YA pathway was associated with a significant HbA1c reduction and an increase in the adoption of CGM. Policy changes are necessary to expand access to LIFT-YA and other programs for high-risk YA with T1D in underserved communities and across all backgrounds., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2023 AACE. Published by Elsevier Inc. All rights reserved.)

Objective: Older adults are generally less proficient in technology use compared with younger adults. Data on telemedicine use during the COVID-19 pandemic in older persons with type 1 diabetes (T1D) and the association of telemedicine with the use of diabetes-related technology are limited. We evaluated care delivery to older adults compared with younger adults with T1D in a prepandemic and pandemic period. Methods: Data from electronic health records were evaluated for visit types (in-person, phone, and video) from two sequential 12-month intervals: prepandemic (April 2019-March 2020) and pandemic (April 2020-March 2021). Results: Data from 2,832 unique adults with T1D were evaluated in two age cohorts: younger (40-64 years) and older (≥65 years). Half of each group used continuous glucose monitoring (CGM), whereas 54% of the younger and 37% of the older cohort used pump therapy ( p < 0.001). During the pandemic compared with the prepandemic period, visit frequency increased in both the younger (0.65 vs. 0.76 visits/patient/quarter; p < 0.01) and older (0.72 vs. 0.80 visits/patient/quarter; p < 0.01) cohorts. During the pandemic, older adults used more phone visits compared with younger adults (48% vs. 32%; p  = 0.001). Patients using either pump therapy or CGM were more likely to use video visits compared with phone visits in both younger (41% vs. 24%; p < 0.001) and older cohorts (53% vs. 42%; p < 0.001). Conclusions: Adults using diabetes-related technologies, independent of age, accessed more video visits than those not using devices. Telemedicine visits appeared to maintain continuity of care for younger and older adults with T1D, supporting the future of a hybrid-care model.

The integration of technologies such as continuous glucose monitors, insulin pumps, and smart pens into diabetes management has the potential to support the transformation of health care services that provide a higher quality of diabetes care, lower costs and administrative burdens, and greater empowerment for people with diabetes and their caregivers. Among people with diabetes, older adults are a distinct subpopulation in terms of their clinical heterogeneity, care priorities, and technology integration. The scientific evidence and clinical experience with these technologies among older adults are growing but are still modest. In this review, we describe the current knowledge regarding the impact of technology in older adults with diabetes, identify major barriers to the use of existing and emerging technologies, describe areas of care that could be optimized by technology, and identify areas for future research to fulfill the potential promise of evidence-based technology integrated into care for this important population., (© 2023 by the American Diabetes Association.)

The number of older adults with type 1 diabetes (T1D) is increasing due to an overall increase in life expectancy and improvement in diabetes management and treatment of complications. They are a heterogeneous cohort due to the dynamic process of aging and the presence of comorbidities and diabetes-related complications. A high risk for hypoglycemia unawareness and severe hypoglycemia has been described. Periodic assessment of health status and adjustment of glycemic goals to mitigate hypoglycemia is imperative. Continuous glucose monitoring, insulin pump, and hybrid closed-loop systems are promising tools to improve glycemic control and mitigate hypoglycemia in this age group., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Older adults with type 1 diabetes (T1D) have unique challenges and needs. In this mixed-methods study, we explored the impact of isolation during a pandemic on diabetes management and overall quality of life in this population. Older adults (age ≥ 65 years) with T1D receiving care at a tertiary care diabetes center participated in semi-structured interviews during COVID-19 pandemic isolation between June and August 2020. A multi-disciplinary team coded transcripts and conducted thematic analysis. Thirty-four older adults (age 71 ± 5 years, 97% non-Hispanic white, diabetes duration of 38 ± 7 years, A1C of 7.4 ± 0.9% (57.3 ± 10.1 mmol/mol) were recruited. Three themes related to diabetes self-care emerged regarding impact of isolation on: (1) diabetes management and self-care behaviors (how isolation prompted changes in physical activity and dietary habits); (2) emotional stress and anxiety (related to isolation and lack of support system, economic concerns); and (3) concerns regarding the COVID-19 pandemic (impact on timely medical care and access to information). Our findings identify modifiable barriers and challenges faced by older adults with T1D during isolation. As this population has a higher risk of decline in physical and psychosocial support even during non-pandemic times, clinicians will benefit from understanding these issues to improve care of this population., (© 2023. The Author(s).)

Background: The COVID-19 lockdown imposed a sudden change in lifestyle with self-isolation and a rapid shift to the use of technology to maintain clinical care and social connections., Objective: In this mixed methods study, we explored the impact of isolation during the lockdown on the use of technology in older adults with type 1 diabetes (T1D)., Methods: Older adults (aged ≥65 years) with T1D using continuous glucose monitoring (CGM) participated in semistructured interviews during the COVID-19 lockdown. A multidisciplinary team coded the interviews. In addition, CGM metrics from a subgroup of participants were collected before and during the lockdown., Results: We evaluated 34 participants (mean age 71, SD 5 years). Three themes related to technology use emerged from the thematic analysis regarding the impact of isolation on (1) insulin pump and CGM use to manage diabetes, including timely access to supplies, and changing Medicare eligibility regulations; (2) technology use for social interaction; and (3) telehealth use to maintain medical care. The CGM data from a subgroup (19/34, 56%; mean age 74, SD 5 years) showed an increase in time in range (mean 57%, SD 17% vs mean 63%, SD 15%; P=.001), a decrease in hyperglycemia (>180 mg/dL; mean 41%, SD 19% vs mean 35%, SD 17%; P<.001), and no change in hypoglycemia (<70 mg/dL; median 0.7%, IQR 0%-2% vs median 1.1%, IQR 0%-4%; P=.40) during the lockdown compared to before the lockdown., Conclusions: These findings show that our cohort of older adults successfully used technology during isolation. Participants provided the positive and negative perceptions of technology use. Clinicians can benefit from our findings by identifying barriers to technology use during times of isolation and developing strategies to overcome these barriers., (©Elena Toschi, Christine Slyne, Katie Weinger, Sarah Sy, Kayla Sifre, Amy Michals, DaiQuann Davis, Rachel Dewar, Astrid Atakov-Castillo, Saira Haque, Stirling Cummings, Stephen Brown, Medha Munshi. Originally published in JMIR Diabetes (https://diabetes.jmir.org), 18.11.2022.)

In Silico Trials methodologies will play a growing and fundamental role in the development and de-risking of new medical devices in the future. While the regulatory pathway for Digital Patient and Personal Health Forecasting solutions is clear, it is more complex for In Silico Trials solutions, and therefore deserves a deeper analysis. In this position paper, we investigate the current state of the art towards the regulatory system for in silico trials applied to medical devices while exploring the European regulatory system toward this topic. We suggest that the European regulatory system should start a process of innovation: in principle to limit distorted quality by different internal processes within notified bodies, hence avoiding that the more innovative and competitive companies focus their attention on the needs of other large markets, like the USA, where the use of such radical innovations is already rapidly developing.

Background: The 2019 novel coronavirus disease (COVID-19) pandemic has highlighted the importance of health research and fostered clinical research as never before. A huge number of clinical trials for potential COVID-19 interventions have been launched worldwide. Therefore, the effort of monitoring and characterizing the ongoing research portfolio of COVID-19 clinical trials has become crucial in order to fill evidence gaps that can arise, define research priorities and methodological issues, and eventually, formulate valuable recommendations for investigators and sponsors. The main purpose of the present work was to analyze the landscape of COVID-19 clinical research in Italy, by mapping and describing the characteristics of planned clinical trials investigating the role of drugs and convalescent plasma for treatment or prevention of COVID-19 disease., Methods: During an 11-month period between May 2020 and April 2021, we performed a survey of the Italian COVID-19 clinical trials on therapeutic and prophylactic drugs and convalescent plasma. Clinical trials registered in the Italian Medicines Agency (AIFA) and ClinicalTrials.gov websites were regularly monitored. In the present paper, we report an analysis of study design characteristics and other trial features at 6 April 2021., Results: Ninety-four clinical trials planned to be carried out in Italy were identified. Almost all of them (91%) had a therapeutic purpose; as for the study design, the majority of them adopted a parallel group (74%) and randomized (76%) design. Few of them were blinded (33%). Eight multiarm studies were identified, and two of them were multinational platform trials. Many therapeutic strategies were investigated, mostly following a drug repositioning therapeutic approach., Conclusions: Our study describes the characteristics of COVID-19 clinical trials planned to be carried out in Italy over about 1 year of pandemic emergency. High level quality clinical trials were identified, although some weaknesses in study design and replications of experimental interventions were observed, particularly in the early phase of the pandemic. Our findings provide a critical view of the clinical research strategies adopted for COVID-19 in Italy during the early phase of the pandemic. Further actions could include monitoring and follow-up of trial results and publications and focus on non-pharmacological research areas., (© 2022. The Author(s).)

Aims/hypothesis: Problematic hypoglycaemia still complicates insulin therapy for some with type 1 diabetes. This study describes baseline emotional, cognitive and behavioural characteristics in participants in the HARPdoc trial, which evaluates a novel intervention for treatment-resistant problematic hypoglycaemia., Methods: We documented a cross-sectional baseline description of 99 adults with type 1 diabetes and problematic hypoglycaemia despite structured education in flexible insulin therapy. The following measures were included: Hypoglycaemia Fear Survey II (HFS-II); Attitudes to Awareness of Hypoglycaemia questionnaire (A2A); Hospital Anxiety and Depression Index; and Problem Areas In Diabetes. k-mean cluster analysis was applied to HFS-II and A2A factors. Data were compared with a peer group without problematic hypoglycaemia, propensity-matched for age, sex and diabetes duration (n = 81)., Results: The HARPdoc cohort had long-duration diabetes (mean ± SD 35.8 ± 15.4 years), mean ± SD Gold score 5.3 ± 1.2 and a median (IQR) of 5.0 (2.0-12.0) severe hypoglycaemia episodes in the previous year. Most individuals had been offered technology and 49.5% screened positive for anxiety (35.0% for depression and 31.3% for high diabetes distress). The cohort segregated into two clusters: in one (n = 68), people endorsed A2A cognitive barriers to hypoglycaemia avoidance, with low fear on HFS-II factors; in the other (n = 29), A2A factor scores were low and HFS-II high. Anxiety and depression scores were significantly lower in the comparator group., Conclusions/interpretation: The HARPdoc protocol successfully recruited people with treatment-resistant problematic hypoglycaemia. The participants had high anxiety and depression. Most of the cohort endorsed unhelpful health beliefs around hypoglycaemia, with low fear of hypoglycaemia, a combination that may contribute to persistence of problematic hypoglycaemia and may be a target for adjunctive psychological therapies., (© 2022. The Author(s).)

Smart pen technology has evolved over the past decade with new features such as Bluetooth connectivity, bolus dose calculators, and integration with mobile apps and continuous glucose monitors. While similar in appearance to a traditional insulin pen, smart pens have the ability to record and store data of insulin injections. These devices have the potential to transform diabetes management for clinicians, and patients with type 1 and type 2 diabetes on insulin therapy by improving adherence, glycemic control, and addressing barriers to diabetes management. Smart pens can also highlight the relationship between insulin, food, and physical activity, and provide insight into optimizing insulin regimens. Education of clinicians and patients, and more clinical studies showing the benefits of smart pens and cost-effectiveness, are needed.

Impaired awareness of hypoglycaemia (IAH) is a major risk for severe hypoglycaemia in insulin treatment of type 1 diabetes (T1D). To explore the hypothesis that unhelpful health beliefs create barriers to regaining awareness, we conducted a multi-centre, randomised, parallel, two-arm trial (ClinicalTrials.gov NCT02940873) in adults with T1D and treatment-resistant IAH and severe hypoglycaemia, with blinded analysis of 12-month recall of severe hypoglycaemia at 12 and/or 24 months the primary outcome. Secondary outcomes included cognitive and emotional measures. Adults with T1D, IAH and severe hypoglycaemia despite structured education in insulin adjustment, +/- diabetes technologies, were randomised to the "Hypoglycaemia Awareness Restoration Programme despite optimised self-care" (HARPdoc, n = 49), a psychoeducation programme uniquely focussing on changing cognitive barriers to avoiding hypoglycaemia, or the evidence-based "Blood Glucose Awareness Training" (BGAT, n = 50), both delivered over six weeks. Median [IQR] severe hypoglycaemia at baseline was 5[2-12] per patient/year, 1[0-5] at 12 months and 0[0-2] at 24 months, with no superiority for HARPdoc (HARPdoc vs BGAT incident rate ratios [95% CI] 1.25[0.51, 3.09], p = 0.62 and 1.26[0.48, 3.35], p = 0.64 respectively), nor for changes in hypoglycaemia awareness scores or fear. Compared to BGAT, HARPdoc significantly reduced endorsement of unhelpful cognitions (Estimated Mean Difference for Attitudes to Awareness scores at 24 months, -2.07 [-3.37,-0.560], p = 0.01) and reduced scores for diabetes distress (-6.70[-12.50,-0.89], p = 0.02); depression (-1.86[-3.30, -0.43], p = 0.01) and anxiety (-1.89[-3.32, -0.47], p = 0.01). Despite positive impact on cognitive barriers around hypoglycaemia avoidance and on diabetes-related and general emotional distress scores, HARPdoc was not more effective than BGAT at reducing severe hypoglycaemia., (© 2022. The Author(s).)

Aims: A multidisciplinary team of clinicians and researchers, patients and family members, and representative from national advocacy groups and research organization met to review the literature, highlight gaps, and identify best practices to improve adult care delivery for young adults (YA) with diabetes., Methods: The participants prepared presentations in advance, rotated through sessions, and contributed to group discussions in three areas: physical health, mental health, and quality of life (QoL). Session moderators and scribes used thematic analysis to summarize discussions for each topic., Results: Thematic analysis revealed four foci for addressing physical health, mental health and QoL: 1) best practices to facilitate the process of transfer; 2) age-specific curricula and guidelines for prevention and management of comorbidities and complications; 3) collaboration with behavioral health clinicians to address diabetes distress and mental health disorders; and 4) research on the impact of diabetes on QoL in YA., Conclusion: There was substantial interest and need among adult clinicians to work in concert with pediatric and mental health professionals to identify best practices and future directions to improve healthcare process and diabetes-related outcome measures in YA with diabetes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Toschi, Leblanc, Hafida, Mehta, Ritholz, Gabbay and Laffel.)

Objective: Adults with type 1 diabetes (T1D) are aging successfully. The impact of diabetes duration on clinical and functional status as people age with T1D is not well known., Research Design and Methods: We performed a cross-sectional study of older adults (age ≥65 years) with T1D., Results: We evaluated 165 older adults, mean age 70 ± 10 years. After adjustment for age, sex, and A1C, longer duration of T1D, ≥50 years, was associated with a higher likelihood of depression (odds ratio [OR] 2.8; P = 0.008), hypoglycemia unawareness (OR 2.6; P = 0.01), lower scores on 6-Minute Walk Test (OR 0.99; P = 0.01) and the Physical Component Summary (PCS) of Short Form-36 (SF-36) (OR 0.96; P = 0.02), and greater daily medication use (OR 1.1; P = 0.004) compared with those with duration <50 years., Conclusions: In older adults with T1D, duration of diabetes impacts clinical and functional status, independent of age and glycemic control, and should be considered in development of management strategies for safety and success., (© 2022 by the American Diabetes Association.)

Objective: The Hypoglycemia Fear Survey-II (HFS-II) is a well-validated measure of fear of hypoglycemia in people with type 1 diabetes. The aim of this study was to explore the relationships between hypoglycemia worries, behaviors, and cognitive barriers to hypoglycemia avoidance and hypoglycemia awareness status, severe hypoglycemia, and HbA1c., Research Design and Methods: Participants with type 1 diabetes (n = 178), with the study population enriched for people at risk for severe hypoglycemia (49%), completed questionnaires for assessing hypoglycemia fear (HFS-II), hyperglycemia avoidance (Hyperglycemia Avoidance Scale [HAS]), diabetes distress (Problem Areas In Diabetes [PAID]), and cognitive barriers to hypoglycemia avoidance (Attitudes to Awareness of Hypoglycemia [A2A]). Exploratory factor analysis was applied to the HFS-II. We sought to establish clusters based on HFS-II, A2A, Gold, HAS, and PAID using k-means clustering., Results: Four HFS-II factors were identified: Sought Safety, Restricted Activity, Ran High, and Worry. While Sought Safety, Restricted Activity, and Worry increased with progressively impaired awareness and recurrent severe hypoglycemia, Ran High did not. With cluster analysis we outlined four clusters: two clusters with preserved hypoglycemia awareness were differentiated by low fear/low cognitive barriers to hypoglycemia avoidance (cluster 1) versus high fear and distress and increased Ran High behaviors (cluster 2). Two clusters with impaired hypoglycemia awareness were differentiated by low fear/high cognitive barriers (cluster 3) as well as high fear/low cognitive barriers (cluster 4)., Conclusions: This is the first study to define clusters of hypoglycemia experience by worry, behaviors, and cognitive barriers to hypoglycemia avoidance. The resulting subtypes may be important in understanding and treating problematic hypoglycemia., (© 2022 by the American Diabetes Association.)

Objective: To assess the impact of initiation of closed-loop control (CLC) on glycemic metrics in older adults with type 1 diabetes (T1D) in the real world. Methods: Retrospective analysis of electronic health records from a single tertiary diabetes center of older adults prescribed CLC between January and December 2020. Results: Forty-eight patients (mean age 70 ± 4 years, T1D duration 42 ± 14 years) were prescribed CLC and 39/48 started on the CLC. Among the CLC starters, 97.5% and 95% were prior pump and continuous glucose monitoring (CGM) users, respectively. CGM metrics showed an increase in time-in-range (62% ± 13% to 76% ± 9%; P  < 0.001), a reduction in both time spent <70 mg/dL [2% (1%-3%) to 1% (1%-2%); P  = 0.03] and >180 mg/dL (30% ± 11% to 20% ± 9%; P  < 0.001) at 3 months. Conclusion: In this real-world data most of the older patients with T1D initiating CLC were prior pump and CGM users. Initiation of CLC improved glycemic control and reduced time spent in hypoglycemia compared with prior therapy.

Background: The use of diabetes-related technology, both for insulin administration and glucose monitoring, has shown benefits in older adults with type 1 diabetes (T1D). However, the characteristics of older adults with T1D and their use of technology in real-world situations are not well documented. Methods: Older adults (age ≥65 years) with T1D, using insulin pump or multiple daily injections (MDI) for insulin administration, and continuous glucose monitoring (CGM) or glucometer (blood glucose monitoring [BGM]) for glucose monitoring were evaluated. Participants wore CGM for 2 weeks, completed surveys, and underwent laboratory evaluation. Results: We evaluated 165 older adults with T1D; mean age 70 ± 10 years, diabetes duration 40 ± 17 years, and A1C 7.4% ± 0.9% (57 ± 10 mmol/mol). For insulin administration, 63 (38%) were using MDI, while 102 (62%) were using pump. Compared to MDI, pump users were less likely to have cognitive dysfunction (49% vs. 65%, P  = 0.04) and had lower scores on the hypoglycemia fear survey ( P  = 0.03). For glucose monitoring, 95 (58%) used CGM, while 70 (42%) used BGM. Compared to BGM, CGM users were more likely to report impaired awareness of hypoglycemia (IAH) ( P  = 0.01), and had lower A1C ( P  = 0.02). Participants who used any technology (pump or CGM) had lower A1C ( P  = 0.04, 0.006), less hypoglycemia ≤54 mg/dL ( P  = 0.0006, <0.0001) and <70 mg/dL ( P  = 0.0002, 0.0001), and fewer glycemic excursions (coefficient of variation %) ( P  = 0.0001, <0.0001), while reporting more IAH ( P  = 0.04, P  = 0.006) and diabetes distress ( P  = 0.02, 0.004). Conclusion: Older adults with T1D who use newer diabetes-related technology had better glycemic control, lower hypoglycemia risk, and fewer glycemic excursions. However, they were more likely to report IAH and diabetes-related distress. Clinical trials.gov NCT03078491.

Objective: To assess the relationship between the glucose management indicator (GMI) and HbA 1c in non-White individuals with diabetes., Research Design and Methods: We performed a retrospective analysis of continuous glucose monitoring metrics in individuals with diabetes divided by race into non-White and White cohorts., Results: We evaluated 316 individuals (non-White n = 68; White n = 248). Although GMI was not different (7.6 vs. 7.7; P = not significant) between the cohorts, HbA 1c was higher in the non-White cohort (8.7% vs. 8.1%; P = 0.004). HbA 1c higher than GMI by ≥0.5% was more frequently observed in the non-White cohort (90% vs. 75%; P = 0.02). In the non-White cohort only, duration of hypoglycemia was longer among those with HbA 1c higher than GMI by ≥0.5% compared with those with HbA 1c and GMI within 0.5%., Conclusions: A differential relationship between HbA 1c and GMI in non-White versus White individuals with diabetes was observed. In non-White individuals, a greater difference between HbA 1c and GMI was associated with higher risk of hypoglycemia., (© 2021 by the American Diabetes Association.)

Objective: As there is significant heterogeneity in the weight loss response to pharmacotherapy, one of the most important clinical questions in obesity medicine is how to predict an individual's response to pharmacotherapy. The present study examines patterns of weight loss among overweight and obese women who demonstrated early robust response to twice daily exenatide treatment compared to those treated with hypocaloric diet and matched placebo injections., Methods: We randomized 182 women (BMI 25-48 kg/m2) to treatment with exenatide alone or matched placebo injections plus hypocaloric diet. In both treatment groups, women who demonstrated ≥ 5% weight loss at 12 weeks were characterized as high responders and those who lost ≥10% of body weight were classified as super responders. Our primary outcome was long-term change in body weight among early high responders to either treatment. An exploratory metabolomic analysis was also performed., Results: We observed individual variability in weight loss with both exenatide and hypocaloric diet plus placebo injections. There was a trend toward a higher percentage of subjects who achieved ≥ 5% weight loss with exenatide compared to diet (56% of those treated with exenatide, 76% of those treated with diet, p = 0.05) but no significant difference in those who achieved ≥ 10% weight loss (23% of individuals treated with exenatide and 36% of those treated with diet, p = 0.55). In both treatment groups, higher weight loss at 3 months of treatment predicted super responder status (diet p=0.0098, exenatide p=0.0080). Both treatment groups also demonstrated similar peak weight loss during the study period. We observed lower cysteine concentrations in the exenatide responder group (0.81 vs 0.48 p < 0.0001) and a trend toward higher levels of serotonin, aminoisobutyric acid, anandamide, and sarcosine in the exenatide super responder group., Conclusion: In a population of early high responders, longer term weight loss with exenatide treatment is similar to that achieved with a hypocaloric diet., Clinical Trial Registration: www.clinicaltrialsgov, identifier NCT01590433., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rodgers, Migdal, Rodríguez, Chen, Nath, Gerszten, Kasid, Toschi, Tripaldi, Heineman, Phan, Ngo, Maratos-Flier and Dushay.)

Importance: Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia., Objective: To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia., Design, Setting, and Participants: This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (Pao2/Fio2) ratio between 350 and 200 mm Hg were eligible., Interventions: Patients in the experimental group received intravenous high-titer CP (≥1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations., Main Outcomes and Measures: The primary outcome was a composite of worsening respiratory failure (Pao2/Fio2 ratio <150 mm Hg) or death within 30 days from randomization., Results: Of the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P = .54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P = .04)., Conclusions and Relevance: In patients with moderate to severe COVID-19 pneumonia, high-titer anti-SARS-CoV-2 CP did not reduce the progression to severe respiratory failure or death within 30 days., Trial Registration: ClinicalTrials.gov Identifier: NCT04716556.

The impact of continuous glucose monitoring (CGM) on glycemic control in young adults with type 1 diabetes (T1D) is controversial. Data from 888 young adults with T1D were reviewed (ages 18-30 years, 52% female, glycated hemoglobin [HbA1c] 8.1% ± 1.5%). Prescription of CGM was recorded for 54% of young adults; 66% were pump users, 46% on insulin injections and carbohydrate (carb) counting, and 32% on insulin doses without carb counting ( P  ≤ 0.001). HbA1c was lower in young adults with CGM versus no CGM (7.7% ± 1.3% vs. 8.2% ± 1.7%, P  ≤ 0.001). Difference in HbA1c between CGM versus no CGM was greater in young adults noncarb counting (7.9% ± 1.4% vs. 8.9% ± 2.3%, P  = 0.002) than carb counting (7.7% ± 1.5% vs. 8.2% ± 1.7%, P  = 0.0008), or pump users (7.6 ± 1.2 vs. 7.9 ± 1.1, P  = 0.01). Prescription of CGM was higher with increasing complexity of insulin regimens; however, impact of CGM was greatest with simpler insulin administration methods. Further studies are needed to clarify this association.

The blaNDM-5-producing E. coli Sequence Type (ST)167 high-risk clone is emerging worldwide in human clinical cases, while its presence in companion animals is sporadic and has never been described in Italy. Using a combined Oxford Nanopore (ONT) long-reads and Illumina short-reads sequencing approach, an E. coli ST167 isolated from a hospitalized dog, was in-depth characterized by WGS and the plasmid containing bla NDM-5 was fully reconstructed. The complete sequence of the pMOL008 mosaic plasmid (F36:F31:A4:B1; pMOL008) harbouring bla NDM-5 , was resolved and characterized. Moreover, a (pro)phage and IncFII, containing bla CMY-2 and ermB, and IncI2 plasmid types were also identified. pMOL008 was almost identical to bla NDM-5 -containing plasmids from E. coli ST167 isolated from Italian human clinical cases and from a Swiss dog and colonized humans. bla NDM-5 was located in a class 1 integron together with aadA2, aac(3)-IIa, mph(A), sul1, tet(A) and dfrA12. The risk of spill-over and spill-back transmission of carbapenem-resistance genes, related plasmids and strains between humans and dogs, represents a Public Health threat and highlights the importance of the One Health approach for the AMR surveillance., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Context: Glycemic control in adolescents with type 1 diabetes is poor; yet, it typically improves during early adulthood. Factors related to improvement of glycemic control are unclear., Objective: This work examines how demographic and clinical variables may affect trajectories of glycemic control over time., Methods: This retrospective, observational study comprised 1775 participants ages 18 to 30 years at enrollment in the T1D Exchange clinic registry. Latent class trajectory modeling was used to determine subgroups following a similar glycated hemoglobin A1c (HbA1c) trajectory over time., Results: Five distinct trajectories of HbA1c classes were identified: "low-decline" and "moderate-decline" groups had low or moderate HbA1c with a gradual decline, the "high-stable" group had high HbA1c and remained stable, and the "very high-rapid decline" and "very high-slow decline" groups had very high HbA1c with rapid or gradual decline. Compared with the "high-stable" group, the "low-decline" and "moderate-decline" groups were more likely to be male (P = .009), White non-Hispanic (P = .02), nonsmokers (P < .001), check self-monitoring blood glucose (SMBG) more frequently (P < .001), and have higher education (P < .001), lower body mass index (P = .02), and lower daily insulin dose (P < .001). Compared with the "very high-rapid decline" and "very high-slow decline" groups, the "low-decline" and "moderate-decline" groups were more likely to be male (P = .02), have higher education (P < .001), use insulin pumps (P = .01), be nonsmokers (P < .001), and have a higher number of SMBG checks per day at enrollment (P < .001)., Conclusion: We determined 5 distinct patterns of glycemic control from early adulthood into adulthood. Further evaluation into the modifiable factors associated with a declining HbA1c trajectory would aid in the development of targeted interventions., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Continuous glucose monitoring (CGM) is now commonly used in the management of type 1 diabetes (T1D). The CGM-derived coefficient of variation (CV) measures glucose variability, and the glucose management indicator (GMI) measures mean glycemia (previously called estimated A1C). However, their relationship with laboratory-measured A1C and the risk of hypoglycemia in older adults with T1D is not well studied., Research Design and Methods: In a single-center study, older adults (age ≥65 years) with T1D wore a CGM device for 14 days. The CV (%) and GMI were calculated, and A1C and clinical and demographic information were collected., Results: We evaluated 130 older adults (age 71 ± 5 years), of whom 55% were women, 97% were White, diabetes duration was 39 ± 17 years, and A1C was 7.3 ± 0.6% (56 ± 15 mmol/mol). Participants were stratified by high CV (>36%; n = 77) and low CV (≤36%; n = 53). Although there was no difference in A1C levels between the groups with high and low CV (7.3% [56 mmol/mol] vs. 7.3% [53 mmol/mol], P = 0.4), the high CV group spent more time in hypoglycemia (<70 mg/dL and ≤54 mg/dL) compared with the group with low CV (median 31 vs. 84 min/day, P < 0.0001; 8 vs. 46 min/day, P < 0.001, respectively). An absolute difference between A1C and GMI of ≥0.5% was observed in 46% of the cohort. When the A1C was higher than the GMI by ≥0.5%, a higher duration of hypoglycemia was observed ( P = 0.02)., Conclusions: In older adults with T1D, the use of CGM-derived CV and GMI can better identify individuals at higher risk for hypoglycemia compared with A1C alone. These measures should be combined with A1C for better diabetes management in older adults with T1D., (© 2020 by the American Diabetes Association.)