MDI Group Research Articles

Continuous subcutaneous insulin infusion versus multiple daily injection therapy in pregnant women with type 1 diabetes.

The study aimed to compare glycemic control and pregnancy outcomes in women with type 1 diabetes mellitus (T1DM) using multiple daily injection therapy (MDI) and continuous subcutaneous insulin infusion (CSII) and to compare outcomes of women treated with long-acting insulin or neutral protamine Hagedorn (NPH). This multicenter prospective cohort study involved women with pregestational T1DM treated with MDI and CSII. Primary outcome was glycated hemoglobin (HbA1c) before and during pregnancy. Secondary outcomes included maternal and neonatal outcomes and quality of life. Of the 121 studied women, the average age was 28.48 years, and the average body mass index was 21.29 kg/m2 at conception and 26.32 kg/m2 at delivery. Of the studied women, 78.51% had planned pregnancy. Women treated with MDI and CSII had comparable HbA1c before pregnancy or in the first and second trimesters. In the third trimester, women on CSII therapy had significantly lower HbA1c (6.07 ± 0.62 vs 6.20 ± 0.88%, p = .017), higher HbA1c on-target rate (71.43% vs 64.62%, p = .030), and greater decline of HbA1c from preconception to the third trimester (-0.65 vs -0.30%, p = .047). Fewer daily insulin requirements were observed in those used CSII compared with MDI-treated women (0.60 ± 0.22 vs 0.73 ± 0.25 U/kg/day, p = .004). Newborns born of mothers treated with the CSII method were more likely to have neonatal jaundice (adjusted odds ratio [OR] 2.76, 95% confidence interval [CI] 1.16-6.57) and neonatal intensive care unit (adjusted OR 3.73, 95%CI 1.24-11.16), and women on CSII had lower scores in patient-reported quality of life (p = .045). In the MDI group, those receiving long-acting insulin had nonsignificant lower HbA1c and higher HbA1c on-target rate in the second and third trimesters, compared with those treated with NPH. Insulin pump users may achieve better glycemic control than multiple daily insulin injections, which did not substantially improve pregnancy outcome.

Real-world glycaemic outcomes in patients with type 1 diabetes using glucose sensors-Experience from a single centre in Dublin.

To evaluate changes in glycated haemoglobin (HbA1 c) and sensor-based glycaemic metrics after glucose sensor commencement in adults with T1D. We performed a retrospective observational single-centre study on HbA1 c, and sensor-based glycaemic data following the initiation of continuous glucose monitoring (CGM) in adults with T1D (n = 209). We observed an overall improvement in HbA1 c from 66 (59-78) mmol/mol [8.2 (7.5-9.3)%] pre-sensor to 60 (53-71) mmol/mol [7.6 (7.0-8.6)%] on-sensor (p < .001). The pre-sensor HbA1 c improved from 66 (57-74) mmol/mol [8.2 (7.4-8.9)%] to 62 (54-71) mmol/mol [7.8 (7.1-8.7)%] within the first year of usage to 60 (53-69) mmol/mol [7.6 (7.0-8.4)%] in the following year (n = 121, p < .001). RT-CGM-user had a significant improvement in HbA1 c (Dexcom G6; p < .001, r = 0.33 and Guardian 3; p < .001, r = 0.59) while a non-significant reduction was seen in FGM-user (Libre 1; p = .279). Both MDI (p < .001, r = 0.33) and CSII group (p < .001, r = 0.41) also demonstrated significant HbA1 c improvement. Patients with pre-sensor HbA1 c of ≥64 mmol/mol [8.0%] (n = 125), had attenuation of pre-sensor HbA1 c from 75 (68-83) mmol/mol [9.0 (8.4-9.7)%] to 67 (59-75) mmol/mol [8.2 (7.6-9.0)%] (p < .001, r = 0.44). Altogether, 25.8% of patients achieved the recommended HbA1 c goal of ≤53 mmol/mol and 16.7% attained the recommended ≥70% time in range (3.9-10.0 mmol/L). Our study demonstrated that minimally invasive glucose sensor technology in adults with T1D is associated with improvement in glycaemic outcomes. However, despite significant improvements in HbA1 c, achieving the recommended goals for all glycaemic metrics remained challenging.

Rotator cuff muscle imbalance associates with shoulder instability direction.

Although muscle weakness and/or imbalance of the rotator cuff are thought to contribute to the development of shoulder instability, the association between muscular dysfunction and shoulder instability is not completely understood. The purpose of this study was to evaluate rotator cuff and deltoid muscle cross-sectional areas in different types of shoulder instability (anterior, posterior, and multidirectional instability (MDI)) and to determine the associations between muscular imbalance and shoulder instability direction. Preoperative magnetic resonance images of patients with shoulder instability who subsequently underwent arthroscopic glenohumeral labral repair or capsular plication were evaluated. Shoulder instability was classified into three categories by direction: (1) anterior, (2) posterior, and (3) MDI. The rotator cuff (supraspinatus, subscapularis, and infraspinatus+teres minor) and deltoid (anterior and posterior portions, and total) muscle areas were measured on T1 sagittal and axial slices, respectively. The ratios of the subscapularis to infraspinatus+teres minor area (SSC/ISP-Tm ratio) and the anterior deltoid to posterior deltoid area (AD/PD ratio) were calculated to quantify the transverse force couple imbalance. A total of 189 patients were included, where each group consisted of 63 patients. The infraspinatus+teres minor muscle area was smaller than the subscapularis muscle area in the anterior instability group (P=0.007). The subscapularis muscle area was smaller than the infraspinatus+teres minor muscle area in the posterior instability and MDI groups (P≤0.003). The anterior deltoid muscle area was smaller than the posterior deltoid muscle area in all groups (P≤0.001). The SSC/ISP-Tm ratio in the anterior instability group (1.18±0.40) was higher than that in the posterior instability and MDI groups (0.79±0.31 and 0.93±0.33, respectively; P<0.001). There was no difference in the AD/PD ratio among the 3 groups. Patients with anterior instability have smaller muscle area of the posterior rotator cuff as compared with the anterior rotator cuff. In contrast, patients with posterior instability and MDI have smaller muscle area of the anterior rotator cuff as compared with the posterior rotator cuff. Thus, the direction of shoulder instability is associated with rotator cuff muscle area.

Adaptation to New Dentures and 5 Years of Clinical Use: A Comparison between Complete Denture and Mini-implant Mandibular Overdenture Patients based on Oral Health-Related Quality of Life (OHRQoL) and Orofacial Esthetics.

Objective of workIt is unclear how long patients need to adapt to new dentures. This study assessed adaptation and five years of clinical use, comparing complete denture wearers (CDs) and mini-implant mandibular overdenture wearers opposing a maxillary CD (MDI-OD), based on oral health reported quality of life (OHRQoL) and orofacial esthetics (OES).Material and MethodsA total of 36 subjects in the CD group (25 females) and 30 subjects in the MDI group (20 females) completed the 5-year study. All patients received new CDs, but in the MDI-OD group, four mini-implants were inserted interforaminally in the mandible before denture manufacture. Participants filled in the OHIP-EDENT and OES questionnaires one day after dentures’ delivery, on the 3rd, 8th, 15th, 30th day, and at the 1-, 3- and 5-year follow-up examinations. Statistical analysis comprised descriptive methods, X2 test, independent t-test, Friedman, and Mann-Whitney test.Results and ConclusionsBoth groups' adaptation to new dentures was completed within a month. The MDI-OD group had significantly better OHRQoL in all follow-ups except for the 3rd and 8th day, probably due to soreness and pain, the reason why the MDI-OD group had limitation in functioning in the first days after new dentures’ delivery. Already after the third year and at the fifth year, OHRQoL worsened (p<0.01) in both groups. However it was significantly more pronounced in the conventional CD wearers (p<0.01) than in the MDI-OD group. Orofacial esthetics was highly scored in both groups. The scores dropped down only after three years, equally in both groups.KeywordsOHRQoL, OES, prospective study, complete dentures, mini-implants, adaptationMeSH TermsComplete Dentures; Dental Implants; Quality of Life; Dental Esthetics

607-P: Glycemic Metrics in Japanese Flash Glucose Monitoring Users by Diabetes Type and Therapy

Our aim was to assess differences in glycemic metrics according to diabetes type and therapy in Japan. An optional survey was conducted for users of FreeStyle LibreTM readers in Japan (Jun2020 - Oct2020). Survey responses were linked to glucose data from Jan2017 - Oct2020. Four groups (adults) were used: type 1 diabetes (T1), type 2 on intensive insulin (T2 MDI), T2 on basal or pre-mixed insulin (T2 non-MDI), and T2 not on insulin (T2 non-insulin). A total of 2,434 users in Japan were analyzed: 1,237 T1, 429 T2 MDI, 256 T2 non-MDI, and 512 T2 non-insulin. Glucose control for T2 MDI and T2 non-MDI groups was similar. Mean avg glucose for T1 was similar to T2 insulin users, but TIR was lower and TB70 was higher for T1. The non-insulin group had high engagement (mean 21 scans/day), but tested BG less than once/day prior to the sensor. These patients also largely pay for the device without reimbursement and have more recent diabetes diagnoses than other groups. These data show the variety of users of the FreeStyle Libre system in Japan. The non-insulin group's engagement through high average scan rates despite lack of consistent BG testing before using the sensor demonstrates that patients find value in easier monitoring. High scan rates in all groups indicate that scanning is not a barrier to glucose monitoring. The data selects those users who responded to the optional survey but is comparable to the overall glucose control of all users in Japan.View largeDownload slideView largeDownload slide DisclosureW. Ogawa: Advisory Panel; Self; Abbott Diabetes, Novo Nordisk Pharma Ltd., Research Support; Self; Eli Lilly Japan K. K., Nippon Boehringer Ingelheim Co. Ltd., Takeda Pharmaceutical Co., Speaker's Bureau; Self; Dainippon Sumitomo Pharm, Kowa Company, Ltd., MSD K. K., Novartis Pharma K. K., Ono Pharmaceutical Co., Ltd. T. Urakami: None. T. Kadowaki: Other Relationship; Self; Asahi Mutual Life Insurance Company, MSD Corporation, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Pharma Ltd., Takeda Pharmaceutical Company Limited, Research Support; Self; Daiichi Sankyo Company, Limited, Eli Lilly Japan K. K., Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD Corporation, Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K. K., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Co., Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo Company, Limited, Eli Lilly Japan K. K., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD Corporation, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K. K., Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd. K. Kao: Employee; Self; Abbott Diabetes. L. Brandner: Employee; Self; Abbott Diabetes. K. Shimizu: Employee; Self; Abbott Japan Co., Ltd. T. Dunn: Employee; Self; Abbott Diabetes.

Moving Towards Patient-Centered Care in the Emergency Department: Importance of Improvement in Pain-Related Outcomes

Musculoskeletal pain is a common emergency department (ED) presentation. Patient-centered care for patients with musculoskeletal pain may improve quality-of-life, satisfaction with care, and clinical outcomes. Providing patient-centered care in the ED requires understanding patients’ goals and priorities. We conducted a cross-sectional survey of the demographic, clinical, and biopsychosocial characteristics of adult ED patients (n=215) with musculoskeletal pain. Patients completed the Patient Centered Outcomes Questionnaire (PCOQ) to quantify importance of improvements in pain, interference with daily activities, fatigue, and emotion. Improvement ratings were from 0 (unimportant) to 100 (most important) and cluster analysis identified patient subgroups by these ratings. Comparisons used Kruskal-Wallis tests for continuous measures and Chi-Square tests for categorical measures. Patients with completed PCOQ were analyzed (n=176). All domains were rated as highly important (median/mean (sd) pain, interference, fatigue, and emotion ratings 100/91 (18), 96/79 (32), 93/72 (35), and 93/69 (39)). Cluster analysis identified three subgroups: 1) Multiple domains important (MDI, n=120) characterized by high importance for all domains 2) pain and function important (PFI, n=34) with high importance in pain and interference domains, and 3) only pain domain important (PI, n=22). The MDI group reported higher psychological symptoms, (p<0.0001 for both depression and anxiety symptoms) and was more likely female (p=0.019). The PI group had the least severe clinical characteristics including lowest weekly pain intensity (p=0.029), shortest time experiencing pain (p=0.003), and fewest symptoms from other body systems (p=0.034). ED patients with musculoskeletal pain seek improvements in outcomes beyond pain relief. Furthermore, the identification of three subgroups with differing priorities for their pain care may inform delivery of patient-centered care. These findings build on previous studies of the PCOQ and mirror subgroups from outpatient physical therapy settings. Additional research is needed to better validate these PCOQ subgroups and to longitudinally investigate their clinical utility. Musculoskeletal pain is a common emergency department (ED) presentation. Patient-centered care for patients with musculoskeletal pain may improve quality-of-life, satisfaction with care, and clinical outcomes. Providing patient-centered care in the ED requires understanding patients’ goals and priorities. We conducted a cross-sectional survey of the demographic, clinical, and biopsychosocial characteristics of adult ED patients (n=215) with musculoskeletal pain. Patients completed the Patient Centered Outcomes Questionnaire (PCOQ) to quantify importance of improvements in pain, interference with daily activities, fatigue, and emotion. Improvement ratings were from 0 (unimportant) to 100 (most important) and cluster analysis identified patient subgroups by these ratings. Comparisons used Kruskal-Wallis tests for continuous measures and Chi-Square tests for categorical measures. Patients with completed PCOQ were analyzed (n=176). All domains were rated as highly important (median/mean (sd) pain, interference, fatigue, and emotion ratings 100/91 (18), 96/79 (32), 93/72 (35), and 93/69 (39)). Cluster analysis identified three subgroups: 1) Multiple domains important (MDI, n=120) characterized by high importance for all domains 2) pain and function important (PFI, n=34) with high importance in pain and interference domains, and 3) only pain domain important (PI, n=22). The MDI group reported higher psychological symptoms, (p<0.0001 for both depression and anxiety symptoms) and was more likely female (p=0.019). The PI group had the least severe clinical characteristics including lowest weekly pain intensity (p=0.029), shortest time experiencing pain (p=0.003), and fewest symptoms from other body systems (p=0.034). ED patients with musculoskeletal pain seek improvements in outcomes beyond pain relief. Furthermore, the identification of three subgroups with differing priorities for their pain care may inform delivery of patient-centered care. These findings build on previous studies of the PCOQ and mirror subgroups from outpatient physical therapy settings. Additional research is needed to better validate these PCOQ subgroups and to longitudinally investigate their clinical utility.

Novel adhesive for label derived from peanut meal and MDI

Peanut meal (PM) as the raw material was crosslinked modification by different mass fractions of 4,4′-diphenylmethane diisocyanate (MDI), to prepare adhesives for label. The properties of the adhesives, including water resistance, the viscosity and solid content were investigated. The performance of the label adhesive modified using MDI were significantly higher than those of the unmodified adhesive, making it suitable for applications in the labels. The water resistance duration was up form 3 h to 77 h when the modifier was added at 15 wt.% (based on PM). Further, the viscosity of the modified adhesive increased to an appropriate 82.2 Pa·s, and its solid content increased from 16.01% to 18.16%. In addition, Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction analysis (XRD) were used to characterize the chemical interactions in the cured adhesives, and the thermogravimetric analysis (TGA) and scanning electron microscopy (SEM) were used to analyze the reason of adhesive performance improvement. It was found that incorporating MDI into the adhesives resulted in the formation of a dense crosslinking network structure because of chemical reactions between MDI and active groups on the protein molecules and the introduction of hydrophobic groups in the adhesives; these factors effectively prevented water penetration, thus improving the water resistance of the cured adhesives.

Influence of hydrophilic nanosilica premixing method on the property of isocyanate-based polymer modified bitumen

Bitumen/PEG (polyethylene glycol)/MDI (4,4′-diphenylmethane diisocyanate)/SiO2 (nanosilica) composites were prepared by simple mixing, during which polyurethane reaction occurs between MDI and polar groups provided by either hydrophilic SiO2, PEG or asphaltenes in bitumen. To induce different sequence of polyurethane reaction between MDI and other three matters, SiO2 nanoparticles were premixed with PEG, MDI, or base bitumen. The content of SiO2 was kept as 0.08 wt% of base bitumen, and this tiny loading of SiO2 could significantly influence the performance of modified bitumen under different premixing methods. Rutting resistance under high temperature of modified bitumen was studied by dynamic shear rheometer with oscillatory frequency sweep and multiple stress creep recovery (MSCR) tests. Crack resistance under low temperature was explored by bending beam rheometer. When SiO2 premixed with base bitumen, the modified bitumen has the worst rutting and crack resistance, even worse than bitumen/PEG/MDI system without SiO2 addition. However, the rutting resistance could be obviously improved when the SiO2 premixed with PEG or MDI. Microstructure evolution was observed for estimation of phase separation, which also could be an indication of thermal stability.

Treatment and long-term follow-up of patients diagnosed with type 1 diabetes mellitus before age 5.

This study aimed to determine the effects of continuous subcutaneous insulin infusion (CSII) treatment on anthropometric measurements, mean HbA1c, and insulin dosage in patients diagnosed under 5 years of age and compare with multiple-dose injection therapy (MDI). Children with type 1 diabetes mellitus, diagnosed <5 years since 2000 and their 19-year follow-up were evaluated retrospectively. Weight, height, body mass index (BMI), blood pressure, and HbA1c values were recorded for each visit. Hundred and five patients (58.1% female, 41.9% male) were included in the study. Sixty-three (60 %) patients were treated by CSII and 42 (40%) by MDI. Mean age at diagnosis was 2.68±1.42 and 3.29±1.30 years respectively. Mean follow-up was 7.42±4.76 and 6.01±4.41 years respectively. For each group, weight standard deviation score (SDS) increased significantly in the first year after the diagnosis (p<0.001), and with the onset of puberty weight SDS decreased significantly (p<0.001). The trend of weight and BMI SDS changes over the years showed similar characteristics in both groups. During follow-up height SDS was similar in both groups except in Tanner stage 5. When puberty was completed, mean height SDS was 0.51±1.03 in CSII and-0.31±0.75 in the MDI group (p: 0.029). Mean HbA1c was significantly lower in the CSII group (7.62±0.82 and 8.17±1.22 respectively). Systolic and diastolic blood pressure change trends during the follow-up were also similar in both groups. CSII treatment had positive effects on metabolic control and height SDS in patients with early-onset diabetes without increasing BMI.

Nutritional Status of Pediatric Patients with Type 1 Diabetes Mellitus from Northeast Poland: A Case-Control Study.

IntroductionA significant increase in the incidence of overweight and obesity is observed among children and adolescents. This problem began to occur not only in healthy populations, but also among young diabetics. The aim of the study was to assess the nutritional status of children and adolescents with type 1 diabetes mellitus (T1DM) compared to those in a control group of healthy subjects as well as to determine the influence of the type of insulin therapy used.MethodsThe case-control study included 169 people aged 9–15 years. The study group (n = 85) consisted of Polish children with T1DM, and the control group (n = 84) consisted of healthy subjects. The assessment of the nutritional status included anthropometric measurements. Analysis of body composition was carried out by bioelectrical impedance analysis. To assess nutritional behavior a questionnaire was used. Approval was obtained from the ethics committee of the Medical University of Białystok (no. R-I-002/168/2017).ResultsMedian body mass index (BMI) value in the T1DM group was 19.2 kg/m2 and was statistically significantly (P < 0.05) higher than in the control group (17.8 kg/m2). Normal BMI was found in 90% of the individuals in the CSII group, while in the MDI group it was only 61%. The percentage of fat mass was 19.1% in the T1DM group and 17.6% in the healthy group. The percentage of muscle mass was 36.1% and 34.5%, respectively. The abdominal obesity according to waist circumference (above 90th percentile) turned out to be statistically significant (P < 0.01) and occurred more often in adolescents with T1DM (27%), while in the healthy group it was 12%.ConclusionsThe healthy individuals as well as the majority of the children and adolescents with type 1 diabetes mellitus were well nourished. People using personal insulin pumps showed better nutritional status than those using insulin pens.Graphical

Effect of annealing method and chemical reaction on the structure and properties of polyethylene/polyethylene glycol modified bitumen

Polyethylene (PE) and polyethylene glycol (PEG) are employed to modify bitumen. The rheological stability is revealed by complex modulus (G*) variation with temperature, and it is found that the starting temperature and stable value of G* plateau can be regulated by different annealing treatments. The sample annealed under the temperature (100 °C) close to the crystallization temperature of PE has the best rheological stability. The reason for this effect is explored on terms of crystallization behavior of PE, whose crystallinity is related to the stiffness of PE-rich network induced by viscoelastic phase separation. When the PEG modifier is partially replaced by the same fraction of 4,4′-diphenylmethane diisocyanate (MDI), the complex modulus, thermal stability and solvent resistance of PE modified bitumen can be significantly improved, while the PE-rich network structure is refined. The main reason for these results is the chemical reaction between MDI and polar groups of PEGs and/or bitumen to form large-scale urethane/urea structure, which is revealed by Fourier transform infrared spectrometer.

Patient-reported outcomes in a study of human regular U-500 insulin delivered by continuous subcutaneous insulin infusion or multiple daily injections in patients with type 2 diabetes.

Human regular U‐500 insulin (U‐500R) provides both basal and prandial coverage to people with diabetes. As part of the VIVID study, we studied patient‐reported outcomes (PRO) of U‐500R delivered by multiple daily injections (MDI, n = 211) and continuous subcutaneous infusion using a novel U‐500R pump (CSII, n = 209). Treatment‐Related Impact Measure for Diabetes (TRIM‐D) for Diabetes Device (TRIM‐DD) questionnaires were administered at weeks 0, 14 and 26. TRIM scores with effect sizes (ES) for within‐group and between‐group change were reported. All TRIM‐D scores significantly improved from baseline for both groups (P < .001). The Diabetes Management domain had the greatest improvement, 16.3 (ES = 0.85) and 10.6 (ES = 0.51) for CSII and MDI, respectively. At the study end, the CSII group had significantly higher TRIM‐D scores than the MDI group (P < .05). Most TRIM‐DD scores had small within‐group improvements and were not different between groups. People with type 2 diabetes on U‐500R by either CSII or MDI reported improvement in PRO, particularly in Diabetes Management, Treatment Burden and Psychological Health domains, with greater improvement in the CSII group. In terms of delivery device and function, the CSII and MDI methods were similarly acceptable.

67-LB: Clinical Cost Offset Analysis Comparing Real-Time CGM (RTCGM) with SMBG Based on the COMISAIR 3-Year Follow-Up Study

This clinical cost offset analysis compared rtCGM vs. SMBG in people with type 1 diabetes (T1D) applying results from a 3-year, nonrandomized, prospective, real-world clinical trial (COMISAIR). Clinical effects for HbA1c reduction using rtCGM vs. SMBG combined with MDI (-0.96%) or CSII (-0.71%) after 3 years were converted directly into an economic benefit and inflated ($U.S. 2020). The MDI group showed reduced 3-year event rates for severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) of 68% and 100%, respectively. The CSII group showed 50% and nearly 0% fewer SH and DKA events, respectively, using rtCGM vs. SMBG. Estimated costs for HbA1c reduction (low/high) along with SH and DKA events were taken from published literature and inflated ($U.S. 2020). Switching from SMBG to rtCGM would result in an estimated 487 and 238 fewer SH and DKA events, respectively, for the MDI group and 208 and 8 fewer SH and DKA events in the CSII group. Table 1 describes the potential economic benefit. Sustained reduction in HbA1c for rtCGM vs. SMBG represents over 95% of the potential economic value and per person savings range from $3,555-$6,747 after 3 years. Our modelling study demonstrates compelling clinical and economic benefits of sustained HbA1c control using rtCGM over SMBG in T1D. Disclosure J. Soupal: Advisory Panel; Self; Abbott. Consultant; Self; Medtronic, Roche Diabetes Care. Speaker’s Bureau; Self; Dexcom, Inc. J.J. Isitt: Employee; Self; Dexcom, Inc. G. Grunberger: Research Support; Self; Medtronic. M. Prazny: Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation, Roche Diabetes Care. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi, Teva Pharmaceutical Industries Ltd. C. Parkin: Consultant; Self; Abbott, CeQur Corporation, Dexcom, Inc., DreaMed Diabetes, Novo Nordisk Inc., Onduo, Roche Diabetes Care, Valeritas, Inc. M.E. Minshall: Consultant; Self; Dexcom, Inc. P.M. Lynch: Employee; Self; Dexcom, Inc. Stock/Shareholder; Self; Dexcom, Inc. Funding Dexcom, Inc.

Effect of MDI on the structure and properties of SBS modified bitumen

The thermal storage stability of styrene–butadiene–styrene (SBS) modified bitumen is not very well since phase separation would happen under high temperature. To solve this problem, 4,4′-diphenylmethane diisocyanate (MDI) is incorporated into bitumen/SBS blend, which could induce the formation of urethane/urea structure with large scale by chemical reaction between MDI and polar groups. For a comparison, Poly (ethylene glycol) (PEG) with hydroxyl group as substitute for partial SBS to study the effect of chemical reactivity on the structure and property of bituminous materials. Optical microscopy, rheological and DMA results indicate that the thermal stability and rutting resistance of bituminous materials are enhanced by MDI addition. This enhancement is more pronounced in the blend with existence of PEG, whose reason relates to the different chemical reactivity of hydroxyl group in different blends.

Protective Effects of Resveratrol Supplementation on Contusion Induced Muscle Injury.

Muscle injuries frequently occur in contact sports events. The current treatment options for soft tissue injuries remain suboptimal and often result in delayed or incomplete recovery of damaged muscles. Resveratrol (RES) is a phenolic phytochemical, well-known for its antioxidant and anti-inflammatory properties. The purpose of this study is to evaluate the potential beneficial effects of RES supplementation on inflammation and regeneration in skeletal muscle after a contusion injury, in comparison to a conventional treatment of nonsteroidal anti-inflammatory drugs (NSAID). After one week of acclimation, forty eight -week-old male ICR mice were randomly divided into the five groups (n=8 per group): 1) normal control (NC), 2) mass-drop injury without any treatment (mass-drop injury, MDI), 3) post-injury NSAID treatment (MDI+ 10mg/kg NSAID), 4) post-injury RES supplementation (MDI+ 25mg/kg/day RES) and 5) post-injury treatment with RES and NSAID (MDI + resveratrol+ NSAID). After muscle contusion injury of the left gastrocnemius muscle, RES or NSAID were orally administered post-injury once a day for 7 days. Results showed that the MDI group had significantly higher serum uric acid (UA), CREA (creatinine), LDH (lactic dehydrogenase) and creatine kinase (CK) than the normal control group. Treatment with resveratrol reduced muscle damage as evidenced by the significantly decreased serum levels of UA, CREA, LDH and CK after contusion-induced muscle injuries in mice. In addition, RES and RES + NSAID groups promoted muscle satellite cell regeneration with increase in desmin protein after injury. Our results suggest that resveratrol combined with NSAID potentially improve muscle recovery and may be a potential candidate for further development as an effective clinical treatment for muscle repair.

A cohort study on short mini-implants for mandibular overdentures compared to those of standard length.

To assess peri-implant bone level, survival and success rates of short (6 or 8mm long) one-piece mini-implants (MDIs) in edentulous patients with extremely resorbed alveolar ridge (interforaminal height <10mm) rehabilitated with mandibular implant overdentures and to compare them with patients having standard length MDIs in 1-year prospective clinical study. The Short MDI group consisted of 28 participants with interforaminal height ≤10mm. Implants being, both, short and slim (short MDIs: 6 or 8mm long, 2 or 2.5mm wide) were inserted. The Standard-MDI group included 35 participants (interforaminal height >13mm) who received standard length MDIs (10-14mm long, 2 or 2.5mm wide). Primary outcomes were assessments of MDI peri-implant bone level, survival and success rates; secondary outcomes were assessments of peri-implant tissue, oral hygiene, and prosthodontic maintenance. The Short MDI group had mean marginal bone loss (MBL) of 0.26±0.35mm, 6.4% of failure, and 92.6% of, both, success and survival rates. The Standard-MDI group had mean MBL of 0.34±0.40mm, 5% of failure, 95% of survival, and 94.3% success. There were no significant differences in MBL (p=.420), survival (p=.414), and success (p=.571) between the groups. The Short MDI group had significantly less plaque (p=.001) and bleeding on probing (p<.001). Within the limitations of this study, short MDIs (6 or 8mm long) in extremely atrophied mandibles (interforaminal height <10mm) showed good clinical results in the first year of function.

Bone and ocular safety of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler in COPD: a 52-week randomized study

BackgroundLong-term use of inhaled corticosteroids (ICSs) has been associated with increased risk of bone and ocular comorbidities. We evaluated the effects of the triple fixed-dose combination budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI), formulated using co-suspension delivery technology, on bone mineral density (BMD) and ocular safety in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD).MethodsIn this extension study, a subset of patients from the 24-week, phase III, randomized, double-blind KRONOS study (NCT02497001) continued treatment (BGF MDI 320/18/9.6 μg, budesonide/formoterol fumarate [BFF] MDI 320/9.6 μg or glycopyrrolate/formoterol fumarate [GFF] MDI 18/9.6 μg, as a non-steroidal comparator) for an additional 28 weeks. Primary endpoints were percentage change from baseline in lumbar spine BMD and change from baseline in lens opacities classification system III posterior subcapsular cataract (P) score, both at Week 52. Adverse events were also assessed.ResultsIn total, 456 patients were included in the safety population (53.1% male, mean age 62.8 years). Changes from baseline in lumbar spine BMD (least squares mean [LSM] range − 0.12 to 0.38%) and P score (LSM range 0.02–0.15) were small for all treatments. Both BGF MDI and BFF MDI were non-inferior to GFF MDI using margins of −2% (BMD) and 0.5 units (P score). The incidence of treatment-emergent adverse events (TEAEs) was generally similar among groups. Rates of confirmed pneumonia were low overall (2.4%) and highest in the GFF MDI group (3.4%), followed by BGF MDI (2.1%) and BFF MDI (1.1%). There were no cumulative adverse effects of treatment over time as the incidence and types of TEAEs, were generally similar in the first 24 weeks of the study and after Week 24.ConclusionsIn patients with COPD, both ICS-containing therapies were non-inferior to GFF MDI for the primary BMD and ophthalmological endpoints. Changes from baseline in all three treatment groups over 52 weeks were small and not clinically meaningful. All treatments were well tolerated with no new or unexpected safety findings.Trial registrationClinicalTrials.gov NCT02536508. Registered 27 August 2015.

Parent-Reported Diabetic-Specific Health Related Quality of Life in Children Treated with Multiple Daily Injection, Continuous Subcutaneous Insulin Infusion and Flexible Multiple Daily Injection: A Comparative Study

Aims: This study aims to identify differences in diabetes specific health related quality of life (HRQoL) in children and adolescents with type 1 diabetes mellitus (T1D) treated with three distinct types of intensive insulin therapy-multiple daily injection (MDI), continuous subcutaneous insulin infusion (CSII) and flexible multiple daily injection (fMDI). Materials and Methods: This survey was conducted in north west Tasmania over a 6-month period, during quarterly clinic visits. A well-known, reliable and validated survey tool -<i>Paediatric Quality of life (PedsQL) Diabetes Module 3.0</i> was used to capture information about the diabetic specific HRQoL in children and adolescents. The parent-proxy version of the forms was completed by the parents electronically using iSurvey application to secure information regarding their children’s diabetes related symptoms (11 items), treatment barriers (4 items), treatment adherence (7 items), worry (3 items) and communication (3 items). All de-identified information was downloaded into an excel spreadsheet and SPSS V24.0 for further analysis. Results: 34 parents completed the electronic data forms on <i>iSurvey</i>. There were no statistically significant differences in HRQoL among the CSII, MDI and fMDI groups as determined by one-way ANOVA in diabetes {<i>F</i> (2, 31) = 0.517, <i>p</i> = 0.601}, treatment {<i>F</i> (2, 31) = 0.385, <i>p</i> = 0.684}, worry {<i>F</i> (2, 31) = 0.076, <i>p</i> = 0.927}, and communication {<i>F</i> (2, 31) = 0.672, <i>p</i> = 0.518}. Conclusion: Although, the impact of T1D on the HRQoL in children and adolescents is higher than the children without T1D, it appears to be independent of the types of three intensive insulin therapy generally used- CSII, MDI and fMDI, suggesting type of insulin therapy may not be the major influencing factor for children’ quality of life as revealed in this first of its kind study. A further study with higher number of participants and the additional impact of various glucose monitoring systems on the HRQoL is highly recommended, which may influence the decision of right therapy suitable for the entire family.

Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, multicentre, phase 3 randomised controlled trial

Inhaled corticosteroids have been used in patients with chronic obstructive pulmonary disease (COPD), but the potential benefits of their use in triple therapy are not well known. We aimed to compare the efficacy of a triple therapy with corresponding dual therapies in symptomatic patients with moderate to very severe COPD, without a requirement for a history of exacerbations. In this double-blind, parallel-group, multicentre phase 3 randomised controlled trial, we recruited patients from hospitals and care centres in Canada, China, Japan, and the USA. Eligible patients were 40-80 years of age, were current or former smokers (with a smoking history of ≥10 pack-years), had an established clinical history of COPD, and were symptomatic for COPD, despite receiving two or more inhaled maintenance therapies for at least 6 weeks before screening. We randomly assigned patients (2:2:1:1) using an interactive web response system to receive budesonide/glycopyrrolate/formoterol fumarate metered-dose inhaler 320/18/9·6 μg (BGF MDI), glycopyrrolate/ formoterol fumarate metered-dose inhaler 18/9·6 μg (GFF MDI), budesonide/formoterol fumarate metered-dose inhaler 320/9·6 μg (BFF MDI), or open-label budesonide/formoterol fumarate dry-powder inhaler 400/12 μg (BUD/ FORM DPI). Primary endpoints for the Europe/Canada statistical analysis approach were FEV1 area under the curve from 0-4 h (AUC0-4) for BGF MDI versus BFF MDI and BGF MDI versus BUD/FORM DPI over 24 weeks; and change from baseline in morning pre-dose trough FEV1 for BGF MDI versus GFF MDI and non-inferiority of BFF MDI versus BUD/FORM DPI (margin of -50 mL from lower bound of 95% CI) over 24 weeks. Comparisons with BUD/FORM DPI were made for the Europe/Canada statistical analysis approach only. This study is registered with ClinicalTrials.gov, number NCT02497001. Between Aug 20, 2015, and Jan 5, 2018, 3047 patients were screened from 215 sites, and 1902 were randomly assigned to receive BGF MDI (n=640), GFF MDI (n=627), BFF MDI (n=316), or BUD/FORM DPI (n=319). Over 24 weeks, BGF MDI significantly improved FEV1 AUC0-4 versus BFF MDI (least squares mean difference 104 mL, 95% CI 77 to 131; p<0·0001) and BUD/FORM DPI (91 mL, 64 to 117; p<0·0001). BGF MDI also significantly improved pre-dose trough FEV1 versus GFF MDI (22 mL, 4 to 39; p=0·0139) and was non-inferior to BUD/FORM DPI (-10 mL, -36 to 16; p=0·4390). At week 24, patients in the BGF MDI group had a significantly improved FEV1 AUC0-4 compared with patients receiving BFF MDI (116 mL, 95% CI 80 to 152; p<0·0001); there was a non-significant improvement in the change from baseline in morning pre-dose trough FEV1 at week 24 versus GFF MDI (13 mL, -9 to 36 mL; p=0·2375). The most common treatment-emergent adverse events were nasopharyngitis (n=49 [8%] in the BGF MDI group; n=41 [7%] in the GFF MDI group; n=26 [8%] in the BFF MDI group; and n=30 [9%] in the BUD/FORM DPI group) and upper respiratory tract infection (n=65 [10%]; n=38 [6%]; n=18 [6%]; and n=22 [7%]). Pneumonia incidence was low (<2%) and similar across treatments. There were two treatment-related deaths, both in the GFF MDI group. BGF MDI was efficacious, well tolerated, and could be a more appropriate treatment than the corresponding dual therapies for symptomatic patients with moderate to very severe COPD, irrespective of exacerbation history. Pearl-a member of the AstraZeneca Group.

Characteristics of Patients Newly Prescribed IDegLira in U.S. Real-World Practice

Background: IDegLira, a fixed-ratio combination of a basal insulin (BI), insulin degludec, and liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1), was approved by the FDA in Q4 2016 for the treatment of type 2 diabetes Mellitus (T2DM). This study describes characteristics of adult patients (pts) who initiated IDegLira in a real-world setting. Methods: Demographic and clinical data for pts prescribed IDegLira between May and November 2017 were extracted from the Practice Fusion ambulatory care database. Pt characteristics were described for the 6-months prior to initiation. Pts were grouped by most recent antidiabetic therapy regimen in the prior 6-months. Results: Pts prescribed IDegLira (n=388) received one of five prior therapy regimens: BI as only injectable (BI-INJ, N=88), GLP-1 as only injectable (GLP-INJ, N=47), GLP-1+insulin (GLP-INS, N=65), multiple daily insulin injections (MDI, N=35), and no injectable therapy (N-INJ, N=153). On average, IDegLira pts were 58 years old (SD 11.5); the majority (66%) between 40 and 64 years of age. Pts’ mean BMI was 35 (7.6). Mean A1C was 9.0 (1.82), with 12% below &amp;lt;7%, 19% between 7-7.9%, 25% between 8-8.9%, and 44% &amp;gt;9%. The N-INJ group had the highest mean A1C prior to initiating IDegLira (9.6), BI-INJ and GLP-INJ had intermediate means (both 9.0), and the GLP-INS and MDI groups had the lowest (8.4, 8.3). IDegLira patients previously treated with GLP-INS, MDI, and N-INJ had higher Charlson Comorbidity and Diabetes Complication Severity scores compared to patients previously treated with BI-INJ or GLP-INJ. Most prescriptions were written by PCPs (53%). Conclusion: This analysis shows that initial use of IDegLira has been across a range of practices and clinical profiles. Most IDegLira prescribing occurred among pts on a previous injectable therapy, with those on single injectable therapy having higher A1Cs than those on multiple injectable therapies. Pts prescribed IDegLira with no injectable therapy in the prior 6 months had the highest A1C values. Disclosure M. Mocarski: Employee; Self; Novo Nordisk Inc.. Stock/Shareholder; Self; Novo Nordisk A/S. J. da Rocha Fernandes: Employee; Self; Novo Nordisk A/S, International Diabetes Federation. L. Kallenbach: None. J. Vasey: None. J. Ken: None. A.N. Bogdanov: None. M. Radin: Employee; Self; Novo Nordisk Inc. L.E. Egede: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Advisory Panel; Self; Novo Nordisk Inc..