The Effect of Prestudy Insulin Therapy on Safety and Efficacy of Human Regular U-500 Insulin by Pump or Injection: A Posthoc Analysis

ObjectiveWe conducted a posthoc analysis of the VIVID study (Safety and Efficacy of Human Regular U-500 Insulin Administered by Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Injections in Subjects With Type 2 Diabetes Mellitus: A Randomized, Open-Label, Parallel Clinical Trial), comparing 2 delivery methods of human regular U-500 insulin (U-500R), continuous subcutaneous insulin infusion (CSII) versus multiple daily injection (MDI), in type 2 diabetes requiring high insulin, to determine influence of prestudy insulin on glycemic outcomes.MethodsWe compared A1C, total daily insulin dose (TDD), weight, and hypoglycemia by subgroups of prestudy insulin (prestudy U-500R vs non-U-500R) and treatment (CSII vs MDI).ResultsAt baseline, prestudy U-500R had higher TDD, higher body mass index, lower A1C and fasting plasma glucose, and higher rate of hypoglycemia compared to non-U-500R. Active titration of U-500R reduced A1C in both subgroups, with maximum benefit at 8 weeks. At 26 weeks, CSII provided the greatest reduction in A1C in both subgroups, with a greater reduction in non-U-500R. MDI provided an A1C reduction in both subgroups, with the greater reduction in non-U-500R. At 8 weeks, prestudy U-500R reached its lowest A1C; thereafter, A1C rebounded with MDI and remained stable with CSII. In non-U-500R, A1C continued to decrease to study end. In non-U-500R, hypoglycemia increased during active titration, but then decreased in the posttitration maintenance period. In both subgroups, TDD increased from baseline with MDI but not with CSII. Body weight increased in both subgroups but was greater in prestudy U-500R with CSII compared to MDI.ConclusionRegardless of previous insulin, people on high-dose insulin could lower A1C with U-500R, with additional benefit from CSII. These results may provide guidance for use of U-500R in clinical practice.     

丙泊酚镇静对颅脑损伤患者脑氧供需平衡的影响

目的:探讨丙泊酚实施不同程度镇静对颅脑损伤患者脑氧供需平衡的影响。方法:选择急性闭合性颅脑损伤需行机械通气患者46例,随机分为轻度镇静组(A组),设定目标脑电双频谱指数(BIS)值75%;中度镇静组(B组),设定目标BIS值65%。主要观察达设定目标BIS值时丙泊酚靶控输注(TCI)浓度、Ramsay镇静评分、脑氧供需平衡指标颈内静脉血氧饱和度(SjvO_2)和脑氧摄取率(CERO_2)以及心率(HR)、平均动脉压(MAP)。结果:两组设定镇静目标需丙泊酚TCI浓度有明显差异(P0.05),但Ramsay评分比较差异无统计学意义;中度镇静组SjvO_2较基础值增加约12%(P0.05),CERO_2较基础值下降约15%(P0.05);而轻度镇静组对SjvO_2和CERO_2基础值没有影响。两组HR均较基础值减慢(P0.05),但对MAP均没有影响。结论:颅脑损伤患者维持目标镇静BIS值65%,调控丙泊酚靶浓度1.5-1.6μg/mL,更有利于改善脑氧供需平衡。     

Factors Associated With Insulin Pump Discontinuation in Adults With Diabetes: A Time-to-Invent Analysis and Prediction Model

ObjectiveInsulin pump discontinuation has mostly been studied in children and adolescents living with diabetes. We aimed to assess the rate of insulin pump continuation in a population of adult patients with diabetes, at 18 months after initiation; determine the factors associated with pump discontinuation; and develop a simple prediction model.MethodsThis single-center, retrospective study included all adult patients with type 1 diabetes or type 2 diabetes who started insulin pump treatment between January 2015 and June 2018. The exclusion criteria were pregnancy, short-term pregnancy plans, and insulin pump discontinuation within the previous 6 months. The probability of insulin pump continuation after 18 months was estimated using the Kaplan-Meier method. Factors associated with insulin pump discontinuation were studied using a Cox regression model, and an exponential model was built for prediction purposes.ResultsThe study included 315 patients. The mean age was 41 years, the mean duration of diabetes was 16 years, 50% were men, 74% had type 1 diabetes, and the mean hemoglobin A1c level was 9.1% (76 mmol/mol). After 18 months, the rate of insulin pump continuation was 0.80 (95% Confidence Interval (CI), 0.76-0.85). By multivariate analysis, the occurrence of severe hypoglycemia in the previous year was associated with insulin pump discontinuation (hazard ratio, 2.42; 95% CI, 1.30-4.51), while other factors did not reach statistical significance.ConclusionInsulin pump discontinuation occurred in 20% of patients at 18 months after initiation and was mainly associated with a recent history of severe hypoglycemia. The type of diabetes and glycemic control at baseline were not associated with treatment discontinuation.     

Urine levels of aluminum after drinking tea

A microwave-assisted acid digestion procedure coupled with a graphite furnace atomic absorption method has been applied in the determination of aluminum (Al) in urine to verify the correlation of free forms of Al in tea infusions and urinary excretion of Al. Significant urinary Al excretion has been found in 24-h urine of four volunteers after tea drinking. However, the difference in amount of Al excretion in urine between the consumption of Oolong (black tea) and Long-Jin (green tea), each of them with unique Al contents and species, was not significant. These findings indicated that the high levels of free Al species in tea infusions did not result in significant change in urinary excretion of the metal, possibly owing to the transformation by ligands present in food and the gastrointestinal tract (GIT). However, it could not be assumed that there was no big difference in absorption of the metal in the human body if fractions of consumed Al retained in the body or excreted by bile or feces were considered.     

Novel antibody assessment method for microbial compositional alteration in the oral cavity

Recently, it has been demonstrated that dysbiosis, an alteration in commensal microflora composition, is intimately involved in the onset of a variety of diseases. It is becoming increasingly evident that the composition of commensal microflora in the oral cavity is closely connected to oral diseases, such as periodontal disease, and systemic diseases, such as inflammatory bowel disease. Next-generation sequencing techniques are used as a method to examine changes in bacterial flora, but additional analytical methods to assess bacterial flora are needed to understand bacterial activity in more detail. In addition, the oral environment is unique because of the role of secretory antibodies contained in saliva in the formation of bacterial flora. The present study aimed to develop a new method for evaluating the compositional change of microbiota using flow cytometry (FCM) with specific antibodies against the bacterial surface antigen, as well as salivary antibodies. Using specific antibodies against Streptococcus mutans, a causative agent of dental caries, and human IgA, bacterial samples from human saliva were analyzed via FCM. The results showed that different profiles could be obtained depending on the oral hygiene status of the subjects. These results suggest that changes in the amount and type of antibodies that bind to oral bacteria may be an indicator for evaluating abnormalities in the oral flora. Therefore, the protocol established in this report could be applied as an evaluation method for alterations in the oral microbiota.     

Combined effects of oleic,linoleic and linolenic acids on lactation performance and the milk fatty acid profile in lactating dairy cows

The potential combined effects of oleic, linoleic and linolenic acids supplementation on lactation performance and the milk fatty acid (FA) profile in dairy cows have not been well investigated. Our objective was to examine the effects of supplementation with a combination of these FA as well as the effects of removing each from the combination on lactation performance and the milk FA profile in dairy cows. Eight Holstein cows (101±11 days in milk) received four intravenously infused treatments in a 4×4 Latin square design, and each period lasted for 12 days which consisted of 5 days of infusion and 7 days of recovery. The control treatment (CTL) contained 58.30, 58.17 and 39.96 g/day of C18: 1 cis-9; C18: 2 cis-9, cis-12; and C18: 3 cis-9, cis-12, cis-15, respectively. The other three treatments were designated −−C18: 1 (20.68, 61.17 and 41.72 g/day of C18: 1 cis-9; C18: 2 cis-9, cis-12; and C18: 3 cis-9, cis-12, cis-15, respectively), −C18: 2 (61.49, 19.55 and 42.13 g/day of C18: 1 cis-9; C18: 2 cis-9, cis-12; and C18: 3 cis-9, cis-12, cis-15, respectively) and −C18: 3 (60.89, 60.16 and 1.53 g/day of C18: 1 cis-9; C18: 2 cis-9, cis-12; and C18: 3 cis-9, cis-12, cis-15, respectively). Dry matter intake and lactose content were not affected by the treatments, but the milk protein content was lower in cows treated with −C18: 2 than that in CTL-treated cows. Milk yield as well as milk fat, protein and lactose yields were higher in cows treated with −C18: 3 than the yields in CTL-treated cows, and these yields increased linearly as the unsaturation degree of the supplemental FA decreased. Compared with the CTL treatment, the −C18: 2 treatment decreased milk C18: 2 cis-9 content (by 2.80%) and yield (by 22.12 g/day), and the −C18: 3 treatment decreased milk C18: 3 cis-9, cis-12, cis-15 content (by 2.72%) and yield (by 22.33 g/day). In contrast, removing C18: 1 cis-9 did not affect the milk content or yield of C18: 1 cis-9. The −C18: 2-treated cows had a higher C18: 1 cis-9 content and tended to have a higher C18: 1 cis-9 yield than CTL-treated cows. The yields of C8: 0, C14: 0 and C16: 0 as well as <C16: 0 tended to increase linearly as the unsaturation degree of the supplemental FA decreased (P=0.06, 0.07, 0.07 and 0.09, respectively). These results indicated that supplementation with C18 unsaturated FA might not independently affect the lactation performance and the milk FA profile of dairy cows.     

Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study model. As the use of mouse models are often a vital step in preclinical drug discovery and drug development^1-8, it is necessary to design a system to introduce drugs into mice in a uniform, reproducible manner. Ideally, the system should permit the collection of blood samples at regular intervals over a set time course. The ability to measure drug concentrations by mass-spectrometry, has allowed investigators to follow the changes in plasma drug levels over time in individual mice^{1, 9, 10}. In this study, paclitaxel was introduced into transgenic mice as a continuous arterial infusion over three hours, while blood samples were simultaneously taken by retro-orbital bleeds at set time points. Carotid artery infusions are a potential alternative to jugular vein infusions, when factors such as mammary tumors or other obstructions make jugular infusions impractical. Using this technique, paclitaxel concentrations in plasma and tissue achieved similar levels as compared to jugular infusion. In this tutorial, we will demonstrate how to successfully catheterize the carotid artery by preparing an optimized catheter for the individual mouse model, then show how to insert and secure the catheter into the mouse carotid artery, thread the end of the catheter out through the back of the mouse’s neck, and hook the mouse to a pump to deliver a controlled rate of drug influx. Multiple low volume retro-orbital bleeds allow for analysis of plasma drug concentrations over time.