Spectrophotometric Evaluation of Translucency of Various Commercially Available Zirconium Oxide Ceramic Systems: An In Vitro Study.

AIM: To evaluate and compare the translucency of various commercially available zirconium oxide ceramic systems, i.e., Ceramill® Zolid Classic, Ceramill® Zi, and DD Bio ZX²71 by using a dual beam UV-visible spectrophotometer. MATERIALS AND METHODS: The present study comprised of 21 disk-shaped samples of zirconia for every group, i.e., group I-Ceramill® Zolid Classic, group II-Ceramill Zi®, and group III-DD Bio ZX²71. Furthermore, each group was split into three subgroups and every subgroup had seven samples each one of 0.7, 0.8, and 0.9 mm thickness. The samples were prepared by computer-aided design/computer-aided manufacturing (CAD/CAM) system devised by Amann Girrbach AG in accord with the steps provided by the manufacturer. The entire sample was designed having 10 mm in diameter with 0.7, 0.8, and 0.9 mm thickness for every group. The UV-visible dual beam spectrophotometer equipped with D2 lamp and W lamp was used for the measurement of absorbance and transmittance in order to assess the translucency of the fabricated zirconia samples. RESULTS: The mean value of transmittance % for Ceramill® Zi at 0.8 mm came out to be 0.849 ± 0.024, i.e., the least among all, whereas the mean value of Ceramill® Zolid Classic was 1.408 ± 0.033, being the highest for the same thickness. DD Bio ZX²71 had an intermediate value of 1.274 ± 0.012. The mean value of absorbance for Ceramill® Zi at 0.8 mm came out to be 2.086 ± 0.013, i.e., the maximum among all, whereas the mean value of Ceramill® Zolid Classic was, being the lowest for the same thickness. DD Bio ZX²71 had an intermediate value of 1.902 ± 0.004. CONCLUSION: The present study data suggest that all the materials subjected to evaluation exhibited a substantial translucency. We attempted to study few of the desirable properties, these materials should possess when used for prosthetic rehabilitation with esthetic contentment a clinical setup. There has been an ambiguous distinction that Ceramill® Zi Zirconia supersedes the Ceramill® Zolid Classic and DD Bio ZX²71. Furthermore, 0.8 mm thickness substantiates to be the most ideal among 0.7, 0.8, and 0.9 mm. CLINICAL SIGNIFICANCE: The desired outcome of the procedure becomes dependent solely on the clinician's judgment to opt for the material whose properties are most fitting as per the demands of the esthetics. While a clinician should always be ambitious, but a good clinician should also bear in mind that the success of any treatment procedure not only depends on the assortment of properties of these materials but also the host response and satisfaction evoked by these materials.

Comparison of the Antimicrobial Activity of Aloevera Mouthwash with Chlorhexidine Mouthwash in Fixed Orthodontic Patients.

AIM: Aim of the present research was to compare the antimicrobial activity of Aloevera mouthwash with chlorhexidine mouthwash in fixed orthodontic patients. MATERIALS AND METHODS: A sample of 90 fixed Orthodontic patients participated in this study. Full-mouth oral prophylaxis was performed for every patient at the start of the study. Patients were advised to brush twice a day with the modified bass technique and rinse with respective mouthwashes for 20 days. Once the patients with fixed orthodontic appliances were accepted to participate in the study, they received dental prophylaxis which includes the removal of plaque, calculus, and stains from the teeth by scaling and polishing. Then they were randomly divided into the following three groups: chlorhexidine (group I), Aloevera (group II), and control (group III). A washout period of 8-10 days (baseline) was awaited post-oral prophylaxis and then the following clinical parameters were recorded: Plaque index (PI) and gingival index (GI). The data included clinical examination, inspection, and microscopic observation techniques. RESULTS: The mean reduction of the PI score on the 20th day of group II was 0.03 ± 0.18, group I was 0.43 ± 0.49, and the control group was 1.65 ± 0.88. The mean reduction of GI score on the 20th day of group II was 0.83 ± 0.40, group I was 0.93 ± 0.55, and group III was 1.85 ± 0.77. Student's t-test had been used to evaluate within each group between day 1 and day 20, group I and group II had shown higher differences compared to control. CONCLUSION: In conclusion, both chlorhexidine mouthwash and Aloevera mouthwash are important chemical adjuncts in controlling gingival inflammation, gingival bleeding, and plaque accumulation in orthodontic patients. Aloevera could be an alternative to chlorhexidine in patients who are seeking a chemical-free, indigenous, and patient-friendly oral hygiene aid. CLINICAL SIGNIFICANCE: Chlorhexidine is known to produce temporary tooth discoloration, allergic responses, dry mouth, burning in the mouth, and transient bad taste, which deter patients from using this mouthwash. The hunt for plant extract-based antimicrobial medicines has been prompted by the emergence of medication resistance and the unfavorable side effects of several antibiotics. These natural remedies can be a valuable substitute for creating a comparable effect.

Enhanced Li-ion diffusion and electrochemical performance in strained-manganese-iron oxide core-shell nanoparticles.

Efforts to improve energy storage depend greatly on the development of efficient electrode materials. Recently, strain has been employed as an alternate approach to improve ion mobility. While lattice strain has been well-researched in catalytic applications, its effects on electrochemical energy storage are largely limited to computational studies due to complexities associated with strain control in nanomaterials as well as loss of strain due to the phase change of the active material during charging-discharging. In this work, we overcome these challenges and investigate the effects of strain on supercapacitor performance in Li-ion-based energy devices. We synthesize epitaxial Fe3O4@MnFe2O4 (core@shell) nanoparticles with varying shell thickness to control the lattice strain. A narrow voltage window for electrochemical testing is used to limit the storage mechanism to lithiation-delithiation, preventing a phase change and maintaining structural strain. Cyclic voltammetry reveals a pseudocapacitive behavior and similar levels of surface charge storage in both strained- and unstrained-MnFe2O4 samples; however, diffusive charge storage in the strained sample is twice as high as the unstrained sample. The strained-MnFe2O4 electrode exceeds the performance of the unstrained-MnFe2O4 electrode in energy density by ∼33%, power density by ∼28%, and specific capacitance by ∼48%. Density functional theory shows lower formation energies for Li-intercalation and lower activation barrier for Li-diffusion in strained-MnFe2O4, corresponding to a threefold increase in the diffusion coefficient. The enhanced Li-ion diffusion rate in the strained-electrodes is further confirmed using the galvanostatic intermittent titration technique. This work provides a starting point to using strain engineering as a novel approach for designing high performance energy storage devices.

Effect of Continuous Glucose Monitoring on Glycemic Control in Patients With Type 2 Diabetes Treated With Basal Insulin: A Randomized Clinical Trial.

Importance: Continuous glucose monitoring (CGM) has been shown to be beneficial for adults with type 2 diabetes using intensive insulin therapy, but its use in type 2 diabetes treated with basal insulin without prandial insulin has not been well studied. Objective: To determine the effectiveness of CGM in adults with type 2 diabetes treated with basal insulin without prandial insulin in primary care practices. Design, Setting, and Participants: This randomized clinical trial was conducted at 15 centers in the US (enrollment from July 30, 2018, to October 30, 2019; follow-up completed July 7, 2020) and included adults with type 2 diabetes receiving their diabetes care from a primary care clinician and treated with 1 or 2 daily injections of long- or intermediate-acting basal insulin without prandial insulin, with or without noninsulin glucose-lowering medications. Interventions: Random assignment 2:1 to CGM (n = 116) or traditional blood glucose meter (BGM) monitoring (n = 59). Main Outcomes and Measures: The primary outcome was hemoglobin A1c (HbA1c) level at 8 months. Key secondary outcomes were CGM-measured time in target glucose range of 70 to 180 mg/dL, time with glucose level at greater than 250 mg/dL, and mean glucose level at 8 months. Results: Among 175 randomized participants (mean [SD] age, 57 [9] years; 88 women [50%]; 92 racial/ethnic minority individuals [53%]; mean [SD] baseline HbA1c level, 9.1% [0.9%]), 165 (94%) completed the trial. Mean HbA1c level decreased from 9.1% at baseline to 8.0% at 8 months in the CGM group and from 9.0% to 8.4% in the BGM group (adjusted difference, -0.4% [95% CI, -0.8% to -0.1%]; P = .02). In the CGM group, compared with the BGM group, the mean percentage of CGM-measured time in the target glucose range of 70 to 180 mg/dL was 59% vs 43% (adjusted difference, 15% [95% CI, 8% to 23%]; P < .001), the mean percentage of time at greater than 250 mg/dL was 11% vs 27% (adjusted difference, -16% [95% CI, -21% to -11%]; P < .001), and the means of the mean glucose values were 179 mg/dL vs 206 mg/dL (adjusted difference, -26 mg/dL [95% CI, -41 to -12]; P < .001). Severe hypoglycemic events occurred in 1 participant (1%) in the CGM group and in 1 (2%) in the BGM group. Conclusions and Relevance: Among adults with poorly controlled type 2 diabetes treated with basal insulin without prandial insulin, continuous glucose monitoring, as compared with blood glucose meter monitoring, resulted in significantly lower HbA1c levels at 8 months. Trial Registration: ClinicalTrials.gov Identifier: NCT03566693.

Tertiary Hierarchical Complexity in Assemblies of Sulfur-Bridged Metal Chiral Clusters.

Self-assembly of three-dimensional structures with order across multiple length scales-hierarchical assembly-is of great importance for biomolecules for the functions of life. Creation of similar complex architectures from inorganic building blocks has been pursued toward artificial biomaterials and advanced functional materials. Current research, however, primarily employs only large, nonreactive building blocks such as Au colloids. By contrast, sulfur-bridged transition metal clusters (<2 nm) are able to offer more functionality in catalytic and biochemical reactions. Hierarchical assembly of these systems has not been well researched because of the difficulty in obtaining single-phase clusters and the lack of suitable ligands to direct structure construction. To overcome these challenges, we employ a rigid planar ligand with an aromatic ring and bifunctional bond sites. We demonstrate the synthesis and assembly of 1.2 nm sulfur-bridged copper (SB-Cu) clusters with tertiary hierarchical complexity. The primary structure is clockwise/counterclockwise chiral cap and core molecules. They combine to form clusters, and due to the cap-core interaction (C-H···π), only two enantiomeric isomers are formed (secondary structure). A tertiary hierarchical architecture is achieved through the self-assembly of alternating enantiomers with hydrogen bonds as the intermolecular driving force. The SB-Cu clusters are air stable and have a distribution of oxidation states ranging from Cu(0) to Cu(I), making them interesting for redox and catalytic activities. This study shows that structural complexity at different length scales, mimicking biomolecules, can occur in active-metal clusters and provides a new platform for investigation of those systems and for the design of advanced functional materials.

Automated insulin dosing guidance to optimise insulin management in patients with type 2 diabetes: a multicentre, randomised controlled trial.

BACKGROUND: Insulin therapy is most effective if dosage titrations are done regularly and frequently, which is seldom practical for most clinicians, resulting in an insulin titration gap. The d-Nav Insulin Guidance System (Hygieia, Livonia, MI, USA) is a handheld device that is used to measure glucose, determine glucose patterns, and automatically determine the appropriate next insulin dose. We aimed to determine whether the combination of the d-Nav device and health-care professional support is superior to health-care professional support alone. METHODS: In this multicentre, randomised, controlled study, we recruited patients from three diabetes centres in the USA (in Detroit MI; Minneapolis, MN; and Des Moines IA). Patients were eligible if they were aged 21-70 years, diagnosed with type 2 diabetes with a glycated haemoglobin (HbA1c) concentration of 7·5% or higher (≥58 mmol/mol) and 11% or lower (≤97 mmol/mol), and had been using the same insulin regimen for the previous 3 months. Exclusion criteria included body-mass index of 45 kg/m2 or higher; severe cardiac, hepatic, or renal impairment; and more than two severe hypoglycaemic events in the past year. Eligible participants were randomly assigned (1:1), with randomisation blocked within each site, to either d-Nav and health-care professional support (intervention group) or health-care professional support alone (control group). Both groups were contacted seven times (three face-to-face and four phone visits) during 6 months of follow-up. The primary objective was to compare average change in HbA1c from baseline to 6 months. Safety was assessed by the frequency of hypoglycaemic events. The primary objective and safety were assessed in the intention-to-treat population. We used Student's t test to assess the primary outcome for statistical significance. This study was registered with ClinicalTrials.gov, number NCT02424500. FINDINGS: Between Feb 2, 2015, and March 17, 2017, 236 patients were screened for eligibility, of whom 181 (77%) were enrolled and randomly assigned to the intervention (n=93) and control (n=88) groups. At baseline, mean HbA1c was 8·7% (SD 0·8; 72 mmol/mol [SD 8·8]) in the intervention group and 8·5% (SD 0·8; 69 mmol/mol [SD 8·8]) in the control group. The mean decrease in HbA1c from baseline to 6 months was 1·0% (SD 1·0; 11 mmol/mol [SD 11]) in the intervention group, and 0·3% (SD 0·9; 3·3 mmol/mol [9·9]) in the control group (p<0·0001). The frequency of hypoglycaemic events per month was similar between the groups (0·29 events per month [SD 0·48] in the intervention group vs 0·29 [SD 1·12] in the control group; p=0·96). INTERPRETATION: The combination of automated insulin titration guidance with support from health-care professionals offers superior glycaemic control compared with support from health-care professionals alone. Such a solution facilitated safe and effective insulin titration in a large group of patients with type 2 diabetes, and now needs to be evaluated across large health-care systems to confirm these findings and study cost-effectiveness. FUNDING: US National Institutes of Health, National Institute of Digestive and Kidney Diseases.

Human regular U-500 insulin via continuous subcutaneous insulin infusion versus multiple daily injections in adults with type 2 diabetes: The VIVID study.

AIM: To compare the safety and efficacy of U500-R delivered by a novel, specifically designed U500-R insulin pump with U-500R delivered by multiple daily injections (MDI). METHODS: The phase 3 VIVID study randomized people with type 2 diabetes to U-500R by continuous subcutaneous insulin infusion (CSII) or MDI. Participants (aged 18-85 years) had HbA1c ≥7.5% and ≤12.0% and a total daily dose of insulin >200 and ≤600 U/day. After a 2-week transition to three times daily injections of U-500R, participants were treated for 24 weeks with U-500R by CSII or MDI. Treatment arms were compared using mixed model repeated measures analysis. RESULTS: The study randomized 420 participants (CSII: 209, MDI: 211) with 365 completers. Mean changes from baseline were: HbA1c, -1.27% (-13.9 mmol/mol) with CSII and -0.85% (-9.3 mmol/mol) with MDI (difference - 0.42% [-4.6 mmol/mol], P <0.001); fasting plasma glucose, -33.9 mg/dL (-1.9 mmol/L) with CSII and 1.7 mg/dL (0.09 mmol/L) with MDI (difference - 35.6 mg/dL [-2.0 mmol/L], P <0.001); total daily dose, 2.8 U with CSII and 51.3 U with MDI (P < 0.001). Weight changes and rates of documented symptomatic and severe hypoglycaemia were similar between groups; the CSII group had a higher rate of nocturnal hypoglycaemia. CONCLUSIONS: In type 2 diabetes requiring high doses of insulin, both methods of U-500R delivery lowered HbA1c. However, the CSII group attained greater HbA1c reduction with significantly less insulin. Individualized dose titration will be important to balance glycaemic control with hypoglycaemia risk.

Effect of Continuous Glucose Monitoring on Hypoglycemia in Older Adults With Type 1 Diabetes: A Randomized Clinical Trial.

Importance: Continuous glucose monitoring (CGM) provides real-time assessment of glucose levels and may be beneficial in reducing hypoglycemia in older adults with type 1 diabetes. Objective: To determine whether CGM is effective in reducing hypoglycemia compared with standard blood glucose monitoring (BGM) in older adults with type 1 diabetes. Design, Setting, and Participants: Randomized clinical trial conducted at 22 endocrinology practices in the United States among 203 adults at least 60 years of age with type 1 diabetes. Interventions: Participants were randomly assigned in a 1:1 ratio to use CGM (n = 103) or standard BGM (n = 100). Main Outcomes and Measures: The primary outcome was CGM-measured percentage of time that sensor glucose values were less than 70 mg/dL during 6 months of follow-up. There were 31 prespecified secondary outcomes, including additional CGM metrics for hypoglycemia, hyperglycemia, and glucose control; hemoglobin A1c (HbA1c); and cognition and patient-reported outcomes, with adjustment for multiple comparisons to control for false-discovery rate. Results: Of the 203 participants (median age, 68 [interquartile range {IQR}, 65-71] years; median type 1 diabetes duration, 36 [IQR, 25-48] years; 52% female; 53% insulin pump use; mean HbA1c, 7.5% [SD, 0.9%]), 83% used CGM at least 6 days per week during month 6. Median time with glucose levels less than 70 mg/dL was 5.1% (73 minutes per day) at baseline and 2.7% (39 minutes per day) during follow-up in the CGM group vs 4.7% (68 minutes per day) and 4.9% (70 minutes per day), respectively, in the standard BGM group (adjusted treatment difference, -1.9% (-27 minutes per day); 95% CI, -2.8% to -1.1% [-40 to -16 minutes per day]; P <.001). Of the 31 prespecified secondary end points, there were statistically significant differences for all 9 CGM metrics, 6 of 7 HbA1c outcomes, and none of the 15 cognitive and patient-reported outcomes. Mean HbA1c decreased in the CGM group compared with the standard BGM group (adjusted group difference, -0.3%; 95% CI, -0.4% to -0.1%; P <.001). The most commonly reported adverse events using CGM and standard BGM, respectively, were severe hypoglycemia (1 and 10), fractures (5 and 1), falls (4 and 3), and emergency department visits (6 and 8). Conclusions and Relevance: Among adults aged 60 years or older with type 1 diabetes, continuous glucose monitoring compared with standard blood glucose monitoring resulted in a small but statistically significant improvement in hypoglycemia over 6 months. Further research is needed to understand the long-term clinical benefit. Trial Registration: ClinicalTrials.gov Identifier: NCT03240432.

Day-to-day fasting self-monitored blood glucose variability is associated with risk of hypoglycaemia in insulin-treated patients with type 1 and type 2 diabetes: A post hoc analysis of the SWITCH Trials.

AIMS: To investigate the association between day-to-day fasting self-monitored blood glucose (SMBG) variability and risk of hypoglycaemia in type 1 (T1D) and type 2 diabetes (T2D), and to compare day-to-day fasting SMBG variability between treatments with insulin degludec (degludec) and insulin glargine 100 units/mL (glargine U100). MATERIALS AND METHODS: Data were retrieved from two double-blind, randomized, treat-to-target, two-period (32 weeks each) crossover trials of degludec vs glargine U100 in T1D (SWITCH 1, n = 501) and T2D (SWITCH 2, n = 720). Available fasting SMBGs were used to determine the standard deviation (SD) of day-to-day fasting SMBG variability for each patient and the treatment combination. The association between day-to-day fasting SMBG variability and overall symptomatic, nocturnal symptomatic and severe hypoglycaemia was analysed for the pooled population using linear regression, with fasting SMBG variability included as a three-level factor defined by population tertiles. Finally, day-to-day fasting SMBG variability was compared between treatments. RESULTS: Linear regression showed that day-to-day fasting SMBG variability was significantly associated with overall symptomatic, nocturnal symptomatic and severe hypoglycaemia risk in T1D and T2D (P < 0.05). Day-to-day fasting SMBG variability was significantly associated (P < 0.01) with all categories of hypoglycaemia risk, with the exception of severe hypoglycaemia in T2D when analysed within tertiles. Degludec was associated with 4% lower day-to-day fasting SMBG variability than glargine U100 in T1D (P = 0.0082) and with 10% lower day-to-day fasting SMBG variability in T2D (P < 0.0001). CONCLUSIONS: Higher day-to-day fasting SMBG variability is associated with an increased risk of overall symptomatic, nocturnal symptomatic and severe hypoglycaemia. Degludec has significantly lower day-to-day fasting SMBG variability vs glargine U100.

Impact of a mobile app on medication adherence and adherence-related beliefs in patients with type 2 diabetes.

OBJECTIVES: To assess the impact of a customizable medication management mobile app (Medsimple) on medication adherence and adherence-related beliefs in patients with type 2 diabetes. The app contains a medication database, list tracking, reminders, cost-saving information, and other features. A second objective was to determine differentiating factors associated with 6 months of use. DESIGN: A prospective, observational, single-cohort study using previously tested scales at 3 time points over 6 months. SETTINGS AND PARTICIPANTS: Participants included a convenience sample of community-dwelling adults with type 2 diabetes in the United States who used at least 2 prescriptions, had Internet access, and used e-mail and a mobile device for operating the study app. OUTCOME MEASURES: Participants who served as their own controls were assessed on psychosocial theory-based concepts of self-efficacy, locus of control, and outcome expectations in addition to self-reported adherence. Instrument reliability, repeated assessments, and differential dropout analyses were conducted. RESULTS: Repeated assessments of 51, 49, and 41 participants occurred at baseline and 90 and 180 days (6 months), respectively. Instrument measurement of concepts showed strong reliability, except in the locus of control subscales. Participants exhibited no significant change on the scales of self-reported adherence behaviors or adherence-related beliefs during the study. Results showed that the mobile app may have influenced specific adherence behaviors or beliefs, but significant differences on overall scales were not found. Differential dropout analyses comparing study finishers to dropouts revealed that 6-month use was associated with being younger, lower self-efficacy beliefs, lower internal locus of control beliefs, and lower adherence behaviors. CONCLUSION: Scales were reliable to measure concepts but the locus of control scale warrants further testing. The mobile app may not affect adherence and adherence-related beliefs in a 6-month period. Further testing is needed to determine benefit for patients with specific adherence behaviors or who hold certain beliefs.

Effect of Insulin Degludec Versus Insulin Glargine U100 on Hypoglycemia in Hispanic Patients With Type 2 Diabetes: Results From the SWITCH 2 Trial.

IN BRIEF Hispanic patients with type 2 diabetes have poorer glycemic control and are at higher risk of severe diabetes complications and mortality than non-Hispanic white patients. This post hoc analysis investigated the safety and efficacy of insulin degludec versus insulin glargine 100 units/mL (glargine U100) in the Hispanic patient subpopulation from the SWITCH 2 trial. In Hispanic patients, hypoglycemia was consistently lower and nocturnal hypoglycemia was significantly lower with degludec versus glargine U100 at similar levels of glycemic control. Overall, results in Hispanic patients in SWITCH 2 were consistent with those in non-Hispanic patients.

X-ray emission spectroscopy: an effective route to extract site occupation of cations.

Cation site occupation is an important determinant of materials properties, especially in a complex system with multiple cations such as in ternary spinels. Many methods for extracting the cation site information have been explored in the past, including analysis of spectra obtained through K-edge X-ray absorption spectroscopy (XAS). In this work, we measure the effectiveness of X-ray emission spectroscopy (XES) for determining the cation site occupation. As a test system we use spinel phase CoxMn3-xO4 nanoparticles contaminated with CoO phases because Co and Mn can occupy all cation sites and the impurity simulates typical products of oxide syntheses. We take advantage of the spin and oxidation state sensitive Kß1,3 peak obtained using XES and demonstrate that XES is a powerful and reliable technique for determining site occupation in ternary spinel systems. Comparison between the extended X-ray absorption fine structure (EXAFS) and XES techniques reveals that XES provides not only the site occupation information as EXAFS, but also additional information on the oxidation states of the cations at each site. We show that the error for EXAFS can be as high as 35% which makes the results obtained ambiguous for certain stoichiometries, whereas for XES, the error determined is consistently smaller than 10%. Thus, we conclude that XES is a superior and a far more accurate method than XAS in extracting cation site occupation in spinel crystal structures.

Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 2 Diabetes: The SWITCH 2 Randomized Clinical Trial.

IMPORTANCE: Hypoglycemia, a serious risk for insulin-treated patients with type 2 diabetes, negatively affects glycemic control. OBJECTIVE: To test whether treatment with basal insulin degludec is associated with a lower rate of hypoglycemia compared with insulin glargine U100 in patients with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, treat-to-target crossover trial including two 32-week treatment periods, each with a 16-week titration period and a 16-week maintenance period. The trial was conducted at 152 US centers between January 2014 and December 2015 in 721 adults with type 2 diabetes and at least 1 hypoglycemia risk factor who were previously treated with basal insulin with or without oral antidiabetic drugs. INTERVENTIONS: Patients were randomized 1:1 to receive once-daily insulin degludec followed by insulin glargine U100 (n = 361) or to receive insulin glargine U100 followed by insulin degludec (n = 360) and randomized 1:1 to morning or evening dosing within each treatment sequence. MAIN OUTCOMES AND MEASURES: The primary end point was the rate of overall symptomatic hypoglycemic episodes (severe or blood glucose confirmed [<56 mg/dL]) during the maintenance period. Secondary end points were the rate of nocturnal symptomatic hypoglycemic episodes (severe or blood glucose confirmed, occurring between 12:01 am and 5:59 am) and the proportion of patients with severe hypoglycemia during the maintenance period. RESULTS: Of the 721 patients randomized (mean [SD] age, 61.4 [10.5] years; 53.1% male), 580 (80.4%) completed the trial. During the maintenance period, the rates of overall symptomatic hypoglycemia for insulin degludec vs insulin glargine U100 were 185.6 vs 265.4 episodes per 100 patient-years of exposure (PYE) (rate ratio = 0.70 [95% CI, 0.61-0.80]; P < .001; difference, -23.66 episodes/100 PYE [95% CI, -33.98 to -13.33]), and the proportions of patients with hypoglycemic episodes were 22.5% vs 31.6% (difference, -9.1% [95% CI, -13.1% to -5.0%]). The rates of nocturnal symptomatic hypoglycemia with insulin degludec vs insulin glargine U100 were 55.2 vs 93.6 episodes/100 PYE (rate ratio = 0.58 [95% CI, 0.46-0.74]; P < .001; difference, -7.41 episodes/100 PYE [95% CI, -11.98 to -2.85]), and the proportions of patients with hypoglycemic episodes were 9.7% vs 14.7% (difference, -5.1% [95% CI, -8.1% to -2.0%]). The proportions of patients experiencing severe hypoglycemia during the maintenance period were 1.6% (95% CI, 0.6%-2.7%) for insulin degludec vs 2.4% (95% CI, 1.1%-3.7%) for insulin glargine U100 (McNemar P = .35; risk difference, -0.8% [95% CI, -2.2% to 0.5%]). Statistically significant reductions in overall and nocturnal symptomatic hypoglycemia for insulin degludec vs insulin glargine U100 were also seen for the full treatment period. CONCLUSIONS AND RELEVANCE: Among patients with type 2 diabetes treated with insulin and with at least 1 hypoglycemia risk factor, 32 weeks' treatment with insulin degludec vs insulin glargine U100 resulted in a reduced rate of overall symptomatic hypoglycemia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02030600.

Insulin Lispro with Continuous Subcutaneous Insulin Infusion is Safe and Effective in Patients with Type 2 Diabetes: A Randomized Crossover Trial of Insulin Lispro Versus Insulin Aspart.

OBJECTIVE: This study provides clinical information regarding the use of insulin lispro versus insulin aspart in continuous subcutaneous insulin infusion (CSII) in adult patients with type 2 diabetes mellitus (T2D). METHODS: After a 2-week lead-in period, 122 subjects treated with CSII therapy were randomized to 32 weeks of treatment during 2 separate 16-week treatment periods (TPs) with crossover beginning with insulin lispro (n = 60) or insulin aspart (n = 62). Glycated hemoglobin A1c (HbA1c), total daily insulin dose, and weight were recorded at the end of TP1 and TP2. Adverse events (AEs) and hypoglycemic events (overall, documented symptomatic, nocturnal, or severe) were recorded throughout the TPs. Data were analyzed using statistical methods that accounted for repeated measurements. RESULTS: A total of 107 subjects completed the study; 7 discontinued in TP1 and 8 discontinued in TP2. Insulin lispro was noninferior to insulin aspart in endpoint (weeks 16 and 32) HbA1c over TP1 and TP2 combined. Total daily insulin dose, weight change, and incidence and rates of hypoglycemia were not statistically significantly different between treatments. One case of severe hypoglycemia and 1 of diabetic ketoacidosis was observed with insulin aspart. One case of severe infusion site abscess was noted with insulin lispro. Overall, both insulin lispro and insulin aspart were well tolerated with similar AEs reported. CONCLUSION: Insulin lispro and insulin aspart performed similarly after 16 weeks of treatment, with noninferiority for HbA1c and no significant difference in parameters measured. These findings indicate that insulin lispro and insulin aspart can both be used safely and effectively in patients with T2D using CSII.

Two Years with a Tubeless Automated Insulin Delivery System: A Single-Arm Multicenter Trial in Children, Adolescents, and Adults with Type 1 Diabetes.

Background: The Omnipod® 5 Automated Insulin Delivery (AID) System was shown to be safe and effective following 3 months of use in people with type 1 diabetes (T1D); however, data on the durability of these results are limited. This study evaluated the long-term safety and effectiveness of Omnipod 5 use in people with T1D during up to 2 years of use. Materials and Methods: After a 3-month single-arm, multicenter, pivotal trial in children (6-13.9 years) and adolescents/adults (14-70 years), participants could continue system use in an extension phase. HbA1c was measured every 3 months for up to 15 months; continuous glucose monitor metrics were collected for up to 2 years. Results: Participants (N = 224) completed median (interquartile range) 22.3 (21.7, 22.7) months of AID. HbA1c was reduced in the pivotal trial from 7.7% ± 0.9% in children and 7.2% ± 0.9% in adolescents/adults to 7.0% ± 0.6% and 6.8% ± 0.7%, respectively, (P < 0.0001), and was maintained at 7.2% ± 0.7% and 6.9% ± 0.6% after 15 months (P < 0.0001 from baseline). Time in target range (70-180 mg/dL) increased from 52.4% ± 15.6% in children and 63.6% ± 16.5% in adolescents/adults at baseline to 67.9% ± 8.0% and 73.8% ± 10.8%, respectively, during the pivotal trial (P < 0.0001) and was maintained at 65.9% ± 8.9% and 72.9% ± 11.3% during the extension (P < 0.0001 from baseline). One episode of diabetic ketoacidosis and seven episodes of severe hypoglycemia occurred during the extension. Children and adolescents/adults spent median 96.1% and 96.3% of time in Automated Mode, respectively. Conclusion: Our study supports that long-term use of the Omnipod 5 AID System can safely maintain improvements in glycemic outcomes for up to 2 years of use in people with T1D. Clinical Trials Registration Number: NCT04196140.

Multicenter Evaluation of Ultra-Rapid Lispro Insulin with Control-IQ Technology in Adults, Adolescents, and Children with Type 1 Diabetes.

Objective: To evaluate the safety and explore the efficacy of use of ultra-rapid lispro (URLi, Lyumjev) insulin in the Tandem t:slim X2 insulin pump with Control-IQ 1.5 technology in children, teenagers, and adults living with type 1 diabetes (T1D). Methods: At 14 U.S. diabetes centers, youth and adults with T1D completed a 16-day lead-in period using lispro in a t:slim X2 insulin pump with Control-IQ 1.5 technology, followed by a 13-week period in which URLi insulin was used in the pump. Results: The trial included 179 individuals with T1D (age 6-75 years). With URLi, 1.7% (3 participants) had a severe hypoglycemia event over 13 weeks attributed to override boluses or a missed meal. No diabetic ketoacidosis events occurred. Two participants stopped URLi use because of infusion-site discomfort, and one stopped after developing a rash. Mean time 70-180 mg/dL increased from 65% ± 15% with lispro to 67% ± 13% with URLi (P = 0.004). Mean insulin treatment satisfaction questionnaire score improved from 75 ± 13 at screening to 80 ± 11 after 13 weeks of URLi use (mean difference = 6; 95% confidence interval 4-8; P < 0.001), with the greatest improvement reported for confidence avoiding symptoms of high blood sugar. Mean treatment-related impact measure-diabetes score improved from 74 ± 12 to 80 ± 12 (P < 0.001), and mean TRIM-Diabetes Device (score improved from 82 ± 11 to 86 ± 12 (P < 0.001). Conclusions: URLi use in the Tandem t:slim X2 insulin pump with Control-IQ 1.5 technology was safe for adult and pediatric participants with T1D, with quality-of-life benefits of URLi use perceived by the study participants. Clinicaltrials.gov registration: NCT05403502.

A Case Series of Prosthetic Rehabilitation of Post-COVID Rhinorbitocerebral Mucormycosis Ocular Defects: A Digital and Analog Experience.

Removal of a part of or the entire orbit results in facial defect, causing psychological trauma to the patient, apart from anatomic loss. This case series presents 6 clinical cases of prosthetic rehabilitation of ocular defects related to post-COVID-19 ROCM by both analog and digital workflow. The basic objective of this case series was to achieve a well retained, user-friendly, maxillofacial ocular prosthesis with esthetic accuracy. Unique size and shape of the ocular defect in each case, variety of skin tones, age range of patients and compromised neuromuscular control made each of the six cases challenging. This clinical series apart from proposing a digital & analog algorithm for rehabilitating ocular defects also illustrates analog workflow for 4 cases and digital workflow for 2 cases for fabrication of ocular prosthesis.

Assessing Time in Range with Postprandial Glucose-Focused Titration of Ultra Rapid Lispro (URLi) in People with Type 1 Diabetes.

INTRODUCTION: To assess time in range (TIR) (70-180 mg/dL) with postprandial glucose (PPG)-focused titration of ultra rapid lispro (URLi; Lyumjev®) in combination with insulin degludec in people with type 1 diabetes (T1D). METHODS: This phase 2, single-group, open-label, exploratory study was conducted in 31 participants with T1D on multiple daily injection therapy. Participants were treated with insulin degludec and Lispro for an 11-day lead-in and then URLi for a 46-day treatment period consisting of 35-day titration and 11-day endpoint maintenance period. Glucose targets for the titration period were PPG < 140 mg/dL or < 20% increase from premeal, fasting glucose 80-110 mg/dL, and overnight excursion ± 30 mg/dL or less. Participants used the InPen™ bolus calculator and Dexcom G6 continuous glucose monitoring (CGM). RESULTS: Primary endpoint mean TIR (70-180 mg/dL) with URLi during the maintenance period was 70.2%. TIR (70-180 mg/dL) and times below/above range were not significantly different with URLi (maintenance) versus lispro (lead-in). HbA1c decreased from 7.1% at screening to 6.8% at endpoint (least squares mean [LSM] change from baseline, - 0.36%; P < 0.001). Fructosamine and 1,5-anhydroglucitol improved (P < 0.001). Mean hourly glucose using CGM was reduced from 8:00 AM to 4:00 PM with URLi. Overall highest PPG excursion across meals was significantly reduced at URLi endpoint compared with lispro lead-in (mean 56.5 vs 72.4 mg/dL; P < 0.001). Insulin-to-carbohydrate ratio (U/X g) was reduced (more insulin given) at breakfast at URLi endpoint vs lead-in (LSM 9.0 vs 9.7 g; P = 0.002) and numerically decreased at other meals. Total daily insulin dose (TDD) was higher at URLi endpoint compared with lispro lead-in (mean 50.2 vs 47.0 U; P = 0.046) with similar prandial/TDD ratio (mean 52.1% vs 51.2%). There were no severe hypoglycemia events during the study. CONCLUSIONS: URLi in a basal-bolus regimen focusing on PPG targets demonstrated improved overall glycemic control and reduced PPG excursions without increased hypoglycemia in participants with T1D. TRIAL REGISTRATION: ClinicalTrial.gov, NCT04585776.

Analog and Digital Protocols for Functional Prosthetic Rehabilitation of Post-COVID-19 Rhino-Orbito Cerebral Mucormycosis Maxillofacial Defects: A Case Series.

The current study aims to present our clinical observations and experience gathered during the diagnosis, clinical presentation, medical/surgical treatment, and functional prosthetic rehabilitation of cases of rhino-orbital/cerebral Mucormycosis patients. Mucormycosis is an aggressive, life-threatening invasive fungal infection that occurs in people who are immune-compromised. The rise of ROCM during the second wave of the COVID-19 pandemic in India suggests a more effective association between Mucormycosis and the SARS-CoV-2 delta variant. The treatment strategy for Mucormycosis is an early diagnosis which is critical for a successful outcome. The initial step is to reduce or remove underlying risk factors followed by surgical excision and debridement of the afflicted tissues supplemented with antifungal medication. The first-line antifungal treatment is Liposomal Amphotericin B. Postsurgical resection defects are rehabilitated by either removable partial prosthesis (obturators) or by fixed zygomatic implant/patient-specific implant supported prosthesis. Management of ROCM requires a multidisciplinary approach. This case series highlights detailed medical, surgical, and functional prosthetic management modalities adopted by our team in managing such a dreaded disease which may be used as a tool for the formulation of standardized prevention and management/treatment/rehabilitation protocols in the future so that disease morbidity and mortality be reduced and an endemic outbreak could be averted.

Evaluation of Extended Infusion Set Performance in Adults with Type 1 Diabetes: Infusion Set Survival Rate and Glycemic Outcomes from a Pivotal Trial.

Background: Standard insulin infusion sets (IISs) are to be replaced every 2 to 3 days to avoid complications and diabetic ketosis due to set failure. This pivotal trial evaluated the safety and performance of a new extended-wear infusion set (EIS) when used for 7 days by adults with type 1 diabetes (T1D). Methods: This single-arm, nonrandomized trial enrolled adults (18-80 years of age) with T1D, who used their own MiniMed™ 670G system with insulin lispro or insulin aspart and the EIS for up to 7 days, across 12 consecutive wears. Safety endpoints included incidence of serious adverse events (SAEs), serious adverse device effects (SADEs), unanticipated adverse device effects (UADEs), severe hypoglycemia (SevHypo), severe hyperglycemia (SevHyper), diabetic ketoacidosis (DKA), and skin infection. The EIS failure rate due to unexplained hyperglycemia (i.e., suspected occlusion), the overall EIS survival rate, glycemic control outcomes (i.e., A1C, mean sensor glucose and time spent in established glucose ranges), total daily insulin delivered, and satisfaction with the EIS were determined. Results: The intention to treat population (n = 259, 48% men, 45.0 ± 14.1 years) wore a total of 3041 EIS devices. No SADE, UADE, or DKA events was reported. Overall rates of SAEs, SevHypo, SevHyper, and skin infection were 3.8, 2.5, 104.1, and 20.1 events per 100 participant-years. The rate of EIS failure due to unexplained hyperglycemia at the end of day 7 was 0.1% (95% confidence interval [CI]: 0.03-0.51) and 0.4% (95% CI: 0.16-1.00) for insulin lispro and aspart use, respectively. Overall EIS survival rate at the end of day 7 was 77.8% (95% CI: 76.2-79.3), glycemic control did not change, and participants reported greater satisfaction with the EIS compared with standard IISs worn before the study (P < 0.001). Conclusions: This investigation demonstrates that the EIS, when worn for up to 7 days, was safe and rated with high satisfaction, without adversely affecting glycemic control in adults with T1D. Clinical Trial Registration number: NCT04113694 (https://clinicaltrials.gov/ct2/show/NCT04113694).