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Few studies have been conducted among Asian children and adolescents with type 1 diabetes mellitus (T1DM) using do-it-yourself artificial pancreas system (DIY-APS). We evaluated real-world data of pediatric T1DM patients using DIY-APS. Data were obtained for 10 patients using a DIY-APS with algorithms. We collected sensor glucose and insulin delivery data from each participant for a period of 4 weeks. Average glycosylated hemoglobin was 6.2%±0.3%. The mean percentage of time that glucose level remained in the target range of 70 to 180 mg/dL was 82.4%±7.8%. Other parameters including time above range, time below range and mean glucose were also within the recommended level, similar to previous commercial and DIY-APS studies. However, despite meeting the target range, unadjusted gaps were still observed between the median basal setting and temporary basal insulin, which should be handled by healthcare providers.

Background: User-developed automated insulin delivery systems, also referred to as do-it-yourself artificial pancreas systems (DIY APS), are in use by people living with type 1 diabetes. In this work, we evaluate, in silico, the DIY APS Loop control algorithm and compare it head-to-head with the bio-inspired artificial pancreas (BiAP) controller for which clinical data are available. Methods: The Python version of the Loop control algorithm called PyLoopKit was employed for evaluation purposes. A Python-MATLAB interface was created to integrate PyLoopKit with the UVa-Padova simulator. Two configurations of BiAP (non-adaptive and adaptive) were evaluated. In addition, the Tandem Basal-IQ predictive low-glucose suspend was used as a baseline algorithm. Two scenarios with different levels of variability were used to challenge the algorithms on the adult (n = 10) and adolescent (n = 10) virtual cohorts of the simulator. Results: Both BiAP and Loop improve, or maintain, glycemic control when compared with Basal-IQ. Under the scenario with lower variability, BiAP and Loop perform relatively similarly. However, BiAP, and in particular its adaptive configuration, outperformed Loop in the scenario with higher variability by increasing the percentage time in glucose target range 70-180 mg/dL (BiAP-Adaptive vs Loop vs Basal-IQ) (adults: 89.9% ± 3.2%* vs 79.5% ± 5.3%* vs 67.9% ± 8.3%; adolescents: 74.6 ± 9.5%* vs 53.0% ± 7.7% vs 55.4% ± 12.0%, where * indicates the significance of P < .05 calculated in sequential order) while maintaining the percentage time below range (adults: 0.89% ± 0.37% vs 1.72% ± 1.26% vs 3.41 ± 1.92%; adolescents: 2.87% ± 2.77% vs 4.90% ± 1.92% vs 4.17% ± 2.74%). Conclusions: Both Loop and BiAP algorithms are safe and improve glycemic control when compared, in silico, with Basal-IQ. However, BiAP appears significantly more robust to real-world challenges by outperforming Loop and Basal-IQ in the more challenging scenario.

Background: Automated insulin delivery systems are associated with improved glycemic outcomes for patients with diabetes. Ultra rapid lispro (URLi), which has an accelerated pharmacokinetic profile...

Our study objective was to identify a subcutaneous enoxaparin dosage that provided a consistent anticoagulant intensity in dogs. Our hypotheses were that a dose of 0.8 mg/kg would provide inconsistent anticoagulation, a higher dose would provide consistent anticoagulation over a greater duration of time, and viscoelastometry would effectively monitor the anticoagulant status. Six healthy dogs received two subcutaneous enoxaparin doses (0.8 and 2 mg/kg) for anti-Xa activity determinations and pharmacokinetic modeling. Based on calculations derived from these results, 1.3 mg/kg, SC, q8 h was administered for seven doses. Target ranges for anticoagulant intensity were defined as anti-Xa activity of 0.5-1 U/ml, and change from baseline of two viscoelastometric parameters: activated clotting time (ΔACT; ≥40 s), and clot rate (CRpost; ≤20 U/min). Following an initial injection at 1.3 mg/kg, anti-Xa activity of 5/6 dogs reached or exceeded the target range. Following the final dose, anti-Xa activity reached or exceeded the target range in all dogs, and ΔACT and CRpost values exceeded target for 2-6 and 4-12 h, respectively. At an enoxaparin dosage of 1.3 mg/kg, SC, q8 h, anti-Xa activity was consistently above the minimum threshold of the target range; however, the safety of this dosage remains to be determined.

Background: Achieving accurate and consistent acetabular component orientation remains a major challenge in total hip arthroplasty. Methods: We used a pelvic model to compare freehand techniques vs mechanical and anatomical alignment guides in achieving a target operative inclination (OI) and operative anteversion (OA). Thirty subjects comprising consultant orthopedic surgeons, orthopedic trainees, and nonsurgical staff positioned an acetabular component in a pelvic model using 3 different methods for guiding inclination and another 3 for guiding version. Results: Using either a standard mechanical alignment guide (MAG) or a spirit level MAG technique eliminated outliers from target OI, while the freehand method resulted in 46.7% of measurements outside the OI target range. The spirit level MAG technique significantly outperformed the standard MAG technique in median unsigned deviation from target OI (0.8° vs 2.1°, P < .001). Either method of referencing the transverse acetabular ligament for version yielded lower deviations from target OA than the freehand method and fewer outliers from the ±5° target range. Surgical experience was not a significant factor for accurately achieving target OI and OA. Conclusions: Even in an idealized in vitro model, a wide range of OI and OA is seen with the freehand technique of cup placement by subjects of all levels of surgical experience. Using either a standard MAG or a spirit level MAG reduces deviations in target OI, with the spirit level MAG method yielding the best accuracy. Using the transverse acetabular ligament to guide cup anteversion yields more accurate OA.

Supplemental Digital Content is available in the text., Longer time in target range (TTR) for systolic blood pressure (SBP) is associated with a lower risk of cardiovascular events. Team-based care improves SBP control but its effect on the consistency of SBP control over time is unknown. This post hoc analysis used data from a cluster-randomized trial of a physician/pharmacist collaborative model that randomized medical offices to either a 9- or 24-month pharmacist intervention or control group. TTR for SBP was calculated using linear interpolation and an SBP range of 110 to 130 mm Hg. TTR is reported as median values and group comparisons assessed using the Kruskal-Wallis test. Of the 625 participants enrolled, 524 had 9-month and 366 had 24-month SBP data. Participants were a median 59 years old, 59% female, and 52% minority. After 24 months, the median TTR for SBP was 31.9% and 29.8% for the 9- and 24-month intervention groups, respectively, compared with 19% in the control group (P=0.0068). This observation persisted in the subgroup of participants with diabetes or chronic kidney disease and minorities. A longer TTR was not associated with an increased risk of adverse drug events. Time to first observed SBP in the target range was shorter in the intervention group compared with control (270 versus 365 days; P=0.0047). A physician/pharmacist collaborative care model achieved longer TTR for SBP compared with control (usual care).

Trunk modification is associated with knee abduction moment reduction in both healthy groups and individuals with knee osteoarthritis. Ambulatory-related changes in trunk kinematics have been implicated in increased trunk moment. The purpose of this study was to investigate the effect of dose-specific lateral trunk lean on trunk kinetics during ipsilateral and contralateral stance phases. Nineteen healthy participants completed 10 baseline walking trials, followed by 10 trials employing lateral trunk lean. Trunk modification magnitudes were determined based on the average baseline trunk angle. Five trials of both small and large trunk modification magnitudes were completed. Visual real-time biofeedback was projected as a line graph displaying the trunk angle during stance, and a highlighted bandwidth was designated the target range. A 1-factor repeated-measures analysis of variance or Friedman test was used to assess differences between the conditions (P

BackgroundA knowledge gap exists for dolutegravir (DTG) pharmacokinetics and safety during the first 4 weeks of life, preventing safe and effective DTG use in neonates.SettingPopulation pharmacokinetic modeling and simulation were used to assess newborn DTG dosing requirements during the first few days of life as a function of maternal DTG dosing history before delivery.MethodsDTG PK data were obtained from pregnant women and infants enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1026S study. Maternal and neonate population pharmacokinetic models were separately developed. Monte Carlo simulations were performed to simulate neonatal concentrations after 2 doses of DTG after birth for infants born to mothers either receiving or not receiving DTG before delivery.ResultsIn DTG-naïve infants, a 5-mg DTG dose at birth with a second dose after 48 hours maintained median concentrations above the lower bound of the target range (0.77 μg/mL) and below the upper bound of the target range (7.34 μg/mL representing 2-fold above the adult Cmax value). In DTG-exposed infants, a 5-mg DTG dose at 24 hours after birth with a second dose after 48 hours maintained median concentrations within or nearly within the target range, even if the last maternal DTG dose was taken as soon as 6 hours or as long as 24 hours before delivery.ConclusionsNewborn DTG dosing requirements during the first few days of life depend on maternal DTG dosing history before delivery. These results may help the design of future clinical studies of DTG in the neonatal population.

International audience; Bacteria deploy the type VI secretion system (T6SS) to inject effectors into bacterial rivals. Contrary to the prevailing model, a recent study expands the target range of the T6SS by demonstrating that it delivers and potentializes a peptidoglycan-targeting bifunctional toxin into Gram-positive bacteria.

Background Both inadequate and excessive administration of oxygen to acutely unwell patients results in risk of harm. Guidelines recommend titration of oxygen to achieve a target oxygen saturation (SpO2) range. Information regarding whether this is being achieved is limited. Methods In this two-centre non-interventional study we used continuous pulse oximetry in acutely unwell medical patients over a 24-h period to determine the proportion of time spent with SpO2 within the prescribed target range and whether this is influenced by the target range, age, care in a high-dependency area and the number of oxygen adjustments. Results Eighty participants were included in the analysis. The mean (SD) proportion of time spent in target range was 55.6% (23.6), this was lower in those with a reduced hypercapnic target range (88–92% or below) compared to those with a range of 92–96%; difference − 13.1% (95% CI − 3.0 to − 23.2), P = 0.012. The proportion of time spent above range was 16.2% (22.9); this was higher in those with a reduced hypercapnic range; difference 21.6% (31.4 to 12), P P = 0.02. Conclusions Medical patients receiving oxygen in a ward setting spend significant periods of time with SpO2 both above and below the prescribed target range while receiving oxygen therapy.

This study describes LC-ESI-MS/MS method that covers the analysis of various cellular acyl-CoA in a single injection. The method is based on a quick extraction step eliminating LLE/SPE clean up. Method performance characteristics were determined after spiking acyl-CoA standards in different concentrations into a surrogate matrix. The extensive matrix effect for most acyl-CoA except for palmitoyl-CoA was compensated by using isotopically labeled internal standard and matrix-matched calibration. As a result of the high matrix effect, the accuracy for palmitoyl-CoA at the low concentration deviated from the target range of ±20%. The developed method was applied to identify twenty-one cellular acyl-CoA in SK-HEP-1 cells and screening for alterations in acyl-CoA levels post Mito Q antioxidant intervention.

Background The importance of dementia education in improving the care and support that people living with dementia is well established. Previous research has shown ceiling effects in pre and post educational intervention measures of dementia knowledge using Knowledge in Dementia Scale (KIDE) on post-registered health and social care staff in Scotland. The aim was to test the sensitivity of two dementia knowledge instruments, namely the (KIDE) and the Dementia Knowledge Assessment Scale (DKAS). Design A pre and post evaluation comparison of two dementia knowledge scales. Setting The tenth cohort of Scotland's National Dementia Champions Education Programme, September 2019–March 2020. Participants Post-registered Health and Social Care staff (n = 117). Methods Both the DKAS and KIDE scales were administered pre and post programme delivery. Wilcoxon signed-rank tests were performed to examine T1 − T2 differences in dementia knowledge for both validated measures. Results Ceiling effects continued to be present for the KIDE scale at T1 and T2. The DKAS responses showed a different score distribution than that achieved by the KIDE. Ceiling effects noted for KIDE at T1 were not present for the DKAS. Further, at T2, only 6% of respondents scored the maximum on the DKAS. Conclusions The DKAS appears to be a more useful instrument for measuring knowledge in post-registered health and social care staff; however, there was some evidence of ceiling effects post-intervention. There is a need for both scales to be tested in more educationally diverse populations, so educators and researchers can make informed decisions about the instrument's target range. Additionally, further research is needed to develop new sets of dementia knowledge items suitable for use in trained health and social care staff.