The achievement of glycaemic control remains challenging for patients with type 1 diabetes. We assessed the effectiveness of day-and-night hybrid closed-loop insulin delivery compared with ...sensor-augmented pump therapy in people with suboptimally controlled type 1 diabetes aged 6 years and older.
In this open-label, multicentre, multinational, single-period, parallel randomised controlled trial, participants were recruited from diabetes outpatient clinics at four hospitals in the UK and two centres in the USA. We randomly assigned participants with type 1 diabetes aged 6 years and older treated with insulin pump and with suboptimal glycaemic control (glycated haemoglobin HbA1c 7·5–10·0%) to receive either hybrid closed-loop therapy or sensor-augmented pump therapy over 12 weeks of free living. Training on study insulin pump and continuous glucose monitoring took place over a 4-week run-in period. Eligible subjects were randomly assigned using central randomisation software. Allocation to the two study groups was unblinded, and randomisation was stratified within centre by low (<8·5%) or high (≥8·5%) HbA1c. The primary endpoint was the proportion of time that glucose concentration was within the target range of 3·9–10·0 mmol/L at 12 weeks post randomisation. Analyses of primary outcome and safety measures were done in all randomised patients. The trial is registered with ClinicalTrials.gov, number NCT02523131, and is closed to accrual.
From May 12, 2016, to Nov 17, 2017, 114 individuals were screened, and 86 eligible patients were randomly assigned to receive hybrid closed-loop therapy (n=46) or sensor-augmented pump therapy (n=40; control group). The proportion of time that glucose concentration was within the target range was significantly higher in the closed-loop group (65%, SD 8) compared with the control group (54%, SD 9; mean difference in change 10·8 percentage points, 95% CI 8·2 to 13·5; p<0·0001). In the closed-loop group, HbA1c was reduced from a screening value of 8·3% (SD 0·6) to 8·0% (SD 0·6) after the 4-week run-in, and to 7·4% (SD 0·6) after the 12-week intervention period. In the control group, the HbA1c values were 8·2% (SD 0·5) at screening, 7·8% (SD 0·6) after run-in, and 7·7% (SD 0·5) after intervention; reductions in HbA1c percentages were significantly greater in the closed-loop group compared with the control group (mean difference in change 0·36%, 95% CI 0·19 to 0·53; p<0·0001). The time spent with glucose concentrations below 3·9 mmol/L (mean difference in change −0·83 percentage points, −1·40 to −0·16; p=0·0013) and above 10·0 mmol/L (mean difference in change −10·3 percentage points, −13·2 to −7·5; p<0·0001) was shorter in the closed-loop group than the control group. The coefficient of variation of sensor-measured glucose was not different between interventions (mean difference in change −0·4%, 95% CI −1·4% to 0·7%; p=0·50). Similarly, total daily insulin dose was not different (mean difference in change 0·031 U/kg per day, 95% CI −0·005 to 0·067; p=0·09) and bodyweight did not differ (mean difference in change 0·68 kg, 95% CI −0·34 to 1·69; p=0·19). No severe hypoglycaemia occurred. One diabetic ketoacidosis occurred in the closed-loop group due to infusion set failure. Two participants in each study group had significant hyperglycaemia, and there were 13 other adverse events in the closed-loop group and three in the control group.
Hybrid closed-loop insulin delivery improves glucose control while reducing the risk of hypoglycaemia across a wide age range in patients with suboptimally controlled type 1 diabetes.
JDRF, NIHR, and Wellcome Trust.
Summary Background Inhibition of angiogenesis is a valuable treatment strategy for ovarian cancer. Pazopanib is an anti-angiogenic drug active in ovarian cancer. We assessed the effect of adding ...pazopanib to paclitaxel for patients with platinum-resistant or platinum-refractory advanced ovarian cancer. Methods We did this open-label, randomised phase 2 trial at 11 hospitals in Italy. We included patients with platinum-resistant or platinum-refractory ovarian cancer previously treated with a maximum of two lines of chemotherapy, Eastern Cooperative Oncology Group performance status 0–1, and no residual peripheral neurotoxicity. Patients were randomly assigned (1:1) to receive weekly paclitaxel 80 mg/m2 with or without pazopanib 800 mg daily, and stratified by centre, number of previous lines of chemotherapy, and platinum-free interval status. The primary endpoint was progression-free survival, assessed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov , number NCT01644825 . This report is the final analysis; the trial is completed. Findings Between Dec 15, 2010, and Feb 8, 2013, we enrolled 74 patients: 37 were randomly assigned to receive paclitaxel and pazopanib and 37 were randomly assigned to receive paclitaxel only. One patient, in the paclitaxel only group, withdrew from the study and was excluded from analyses. Median follow-up was 16·1 months (IQR 12·5–20·8). Progression-free survival was significantly longer in the pazopanib plus paclitaxel group than in the paclitaxel only group (median 6·35 months 95% CI 5·36–11·02 vs 3·49 months 2·01–5·66; hazard ratio 0·42 95% CI 0·25–0·69; p=0·0002). We recorded no unexpected toxic effects or deaths from toxic effects. Adverse events were more common in the pazopanib and paclitaxel group than in the paclitaxel only group. The most common grade 3–4 adverse events were neutropenia (11 30% in the pazopanib group vs one 3% in the paclitaxel group), fatigue (four 11% vs two 6%), leucopenia (four 11% vs one 3%), hypertension (three 8% vs none 0%), raised aspartate aminotransferase or alanine aminotransferase (three 8% vs none), and anaemia (two 5% vs five 14%). One patient in the pazopanib group had ileal perforation. Interpretation Our findings suggest that a phase 3 study of the combination of weekly paclitaxel plus pazopanib for patients with platinum-resistant or platinum-refractory advanced ovarian cancer is warranted. Funding National Cancer Institute of Napoli and GlaxoSmithKline.
This paper discusses the wide range of real-time line monitoring devices which can be used to determine the dynamic thermal rating of an overhead transmission line with the power system operating ...normally or during a system contingency. The most common types of real-time monitors are described including those that measure the line clearance, conductor temperature, and weather data in the line right of way. The strengths and weaknesses of the various monitoring methods are evaluated, concluding that some are more effective during system normal and others during system contingency conditions.
Provider: - Institution: - Data provided by Europeana Collections- From 2016 to 2018, archaeological excavations were undertaken in Tower 1 and the foundations of the Northern Crusader Bridge in the ...old city of Caesarea (Permit Nos. A-7867, A-7938, A-8175; map ref. 19008-12/71232-6; Fig. 1: Tower 1), prior to construction of a pedestrian bridge along the probable line of the northern Crusader bridge. The excavation, on behalf of the Israel Antiquities Authority, and funded by the Caesarea Development Corporation, was directed by U. 'Ad, with the assistance of Y. Amrani (administration), Y. Hai (area supervision), R. Mishayev, M. Kahan and R. Liran (surveying and drafting), A. Peretz, Y. Marmelstein and N. Davidov (field photography), D. Zell, M. Peleg, E. Greenfeld and the Griffin Company (aerial photography), A. Rosenthal and Y. Shaltiel (planning), J. Peterson and his team (conservation), G. Solomon and his team (mosaic conservation), P. Gendelman and L. Yehuda (pottery identification), M. Yohananof and S. Krispin (metal detection) and D. Siboni (conservation). Also assisting were K. Sa'id, Y. Porath, Y. Sheffer, Y. Sa'ad and V. Shotten-Hallel and the Caesarea National Parks team. At the end of the excavation, the mosaic floors and marble columns were treated, and the columns were re-erected by workers of the IAA Conservation Department.- בשנים 2016-2018 נערכו חפירות במגדל 1 וביסודות הגשר הצלבני הצפוני שבעיר העתיקה בקיסריה (הרשאות מס' 7867-A-7938 ,A-8175 ,A; נ"צ 19008-12/71232-6; איור 1: מגדל 1), לקראת בניית גשר להולכי רגל בתוואי הגשר המשוער מהתקופה הצלבנית. החפירה, מטעם רשות העתיקות ובמימון החברה לפיתוח קיסריה, נוהלה על ידי ע' עד, בסיוע י' עמרני (מנהלה), י' חי (ניהול שטח), ר' מישייב, מ' קאהן ור' לירן (מדידות ושרטוט), א' פרץ, י' מרמלשטיין ונ' דוידוב (צילום שטח), ד' צל, מ' פלג, א' גרינפלד וחברת גריפין (צילום אוויר), ע' רוזנטל וי' שאלתיאל (תכנון), ג' פטרסון וצוותו (שימור), ג' סולומון וצוותו (שימור פסיפסים), פ' גנדלמן ול' יהודה (זיהוי כלי חרס), מ' יוחננוף וש' קריספין (גילוי מתכות) וד' סיבוני (שימור). כן סייעו כ' סעיד, י' פורת, י' שפר, י' סעד וו' שוטן-הלל וצוות העובדים של גן לאומי קיסריה. בתום החפירה טופלו רצפות הפסיפס ועמודי השיש הוצבו במקומם המקורי על ידי עובדי תחום שימור של רשות העתיקות.- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
The Indonesian Government, led by President Joko Widodo, has heralded its commitment to evidence-based policy making. The public health community welcomes this commitment; however, as researchers, ...scientists, and practitioners, we have grave concerns that the government is missing an opportunity to implement an effective response to illicit drugs informed by evidence.
Understanding the effects of antiretroviral treatment (ART) interruption on neurocognition and quality of life (QoL) are important for managing unplanned interruptions and planned interruptions in ...HIV cure research.
Children previously randomized to continuous (continuous ART, n = 41) vs. planned treatment interruption (PTI, n = 47) in the Pediatric European Network for Treatment of AIDS (PENTA) 11 study were enrolled. At study end, PTI children resumed ART. At 1 and 2 years following study end, children were assessed by the coding, symbol search and digit span subtests of Wechsler Intelligence Scale for Children (6-16 years old) or Wechsler Adult Intelligence Scale (≥17 years old) and by Pediatrics QoL questionnaires for physical and psychological QoL. Transformed scaled scores for neurocognition and mean standardized scores for QoL were compared between arms by t-test and Mann-Whitney U test, respectively. Scores indicating clinical concern were compared (<7 for neurocognition and <70 for QoL tests).
Characteristics were similar between arms with a median age of 12.6 years, CD4⁺ of 830 cells/μl and HIV RNA of 1.7 log10copies/ml. The median cumulative ART exposure was 9.6 in continuous ART vs. 7.7 years in PTI (P = 0.02). PTI children had a median of 12 months off ART and had resumed ART for 25.2 months at time of first assessment. Neurocognitive scores were similar between arms for all tests. Physical and psychological QoL scores were no different. About 40% had low neurocognitive and QoL scores indicating clinical concern.
No differences in information processing speed, sustained attention, short-term memory and QoL functioning were observed between children previously randomized to continuous ART vs. PTI in the PENTA 11 trial.
The synovial joint of the knee can be affected by diseases, such as arthritis or osteoarthritis, being a knee replacement the selected clinical solution in irreversible cases. This work is aimed at ...investigating lubricated contact in healthy and pathological knees, with the aim of achieving knowledge that can be used to delay knee replacement. The equivalent geometric model of a rigid ellipsoid on a deformable plane is adopted, where the synovial fluid is considered to be Newtonian and the articular cartilage is a linear elastic material. Studies were carried out varying the modulus of elasticity E of the cartilage, its thickness e and the viscosity of the synovial fluid , adopting values corresponding to healthy and osteoarthritic natural joints, in order to evaluate their influence on the functioning of the joint considering squeeze film lubrication. Compared to what was obtained for a healthy joint, the decrease in the elastic modulus E would not have a significant influence on the minimum lubricant film thickness, while the decrease in cartilage thickness would improve said thickness. The decrease in viscosity decreases the minimum thickness of the lubricating film by 65 %, so viscosupplementation would increase the viscosity, which would also increase said thickness and prevent wear of the articular surfaces. A decrease in cartilage thickness or in cartilage module would produce a decrease of the cartilage tensions. On the other hand, a decrease of viscosity produces an increase of these tensions. In a pathological joint (where the fluid viscosity and the cartilage thickness and elastic module are diminished), and considering a load of 800 N, the minimum film height, the maximum pressure and the maximum Von Mises tension obtained are 66 %, 22 % and 28 % respectively lower than those observed for a healthy articulation.
PDF
