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1دورية أكاديمية
المؤلفون: Edd, Shannon N, Castañeda, Javier, Choudhary, Pratik, Kolassa, Ralf, Keuthage, Winfried, Kroeger, Jens, Thivolet, Charles, Evans, Mark, Ré, Roseline, Cellot, Jessica, de Portu, Simona, Vorrink, Linda, Shin, John, van den Heuvel, Tim, Cohen, Ohad, ADAPT study Group
مصطلحات موضوعية: insulin pump therapy, patient reported outcomes, randomized trial, subcutaneous injection, type 1 diabetes, Humans, Adult, Diabetes Mellitus, Type 1, Hypoglycemic Agents, Insulin, Glycated Hemoglobin, Prospective Studies, Blood Glucose Self-Monitoring, Reproducibility of Results, Blood Glucose, Insulin Infusion Systems
الوصف: Funder: Medtronic International Trading Sàrl ; AIMS: To reassess the 6-month efficacy and to assess the 12-month sustained efficacy of the MiniMed™ 780G advanced hybrid closed-loop automated insulin delivery (AID) system compared to multiple daily injections plus intermittently scanned glucose monitoring (MDI+isCGM) in people with type 1 diabetes not meeting glucose targets. METHODS: The ADAPT study was a prospective, multicentre, open-label, randomized control trial in people with type 1 diabetes, with a glycated haemoglobin (HbA1c) concentration of at least 8.0% (64 mmol/mol), on MDI+isCGM therapy. After a 6-month study phase, participants randomized at baseline to MDI+isCGM switched to AID (SWITCH) while the others continued AID therapy (SUSTAIN) for an additional 6 months. The primary endpoint of this continuation phase was the within-group change in mean HbA1c between 6 and 12 months, with superiority in the SWITCH group and noninferiority in the SUSTAIN group (ClinicalTrials.gov: NCT04235504). RESULTS: A total of 39 SWITCH and 36 SUSTAIN participants entered the continuation phase. In the SWITCH group, HbA1c was significantly decreased by -1.4% (95% confidence interval [CI] -1.7% to -1.1%; P < 0.001) from a mean ± SD of 8.9% ± 0.8% (73.9 ± 8.6 mmol/mol) at 6 months to 7.5% ± 0.6% (58.5 ± 6.9 mmol/mol) at 12 months. Mean HbA1c increased by 0.1% (95% CI -0.05% to +0.25%), from 7.3% ± 0.6% (56.5 ± 6.7 mmol/mol) to 7.4% ± 0.8% (57.7 ± 9.1 mmol/mol) in the SUSTAIN group, meeting noninferiority criteria. Three severe hypoglycaemia events occurred in two SWITCH participants during the continuation phase. CONCLUSION: ADAPT study phase glycaemic improvements were reproduced and sustained in the continuation phase, supporting the early adoption of AID therapy in people with type 1 diabetes not meeting glucose targets on MDI therapy. ; The study was funded by Medtronic International Trading
وصف الملف: application/pdf; text/xml
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2دورية أكاديمية
المؤلفون: Leelarathna, Lalantha, Sutton, Christopher J, Evans, Mark L, Neupane, Sankalpa, Rayman, Gerry, Lumley, Sarah, Cranston, Iain, Narendran, Parth, Krishan, Ashma, Taxiarchi, Vicky P, Barnard-Kelly, Katharine, Elliott, Rachel A, Burns, Matthew, Camm, Maisie, Thabit, Hood, Wilmot, Emma G, FLASH-UK Trial Study Group
مصطلحات موضوعية: continuous blood glucose monitoring, deprivation, insulin, type 1 diabetes, Adult, Female, Humans, Aged, Diabetes Mellitus, Type 1, Blood Glucose, Glycated Hemoglobin, Blood Glucose Self-Monitoring, Continuous Glucose Monitoring, United Kingdom, Hypoglycemic Agents
الوصف: Publication status: Published ; Funder: Diabetes UK; doi: http://dx.doi.org/10.13039/501100000361Test ; AIMS: The FLASH-UK trial showed lower HbA1c with intermittently scanned continuous glucose monitoring (isCGM), as compared with self monitoring of blood glucose (SMBG), in adults with type 1 diabetes and HbA1c ≥58 mmol/mol (≥7.5%). Here, we present results from the pre-specified subgroup analysis for the 24-week HbA1c (primary outcome) and selected sensor-based secondary outcomes. METHODS: This was a multi-centre, parallel-design, randomised controlled trial. The difference in treatment effect between subgroups (baseline HbA1c [≤75 vs. >75 mmol/mol] [≤9.0 vs >9.0%], treatment modality [pump vs injections], prior participation in structured education, age, educational level, impaired awareness of hypoglycaemia, deprivation index quintile sex, ethnic group and Patient Health Questionnaire-9 [PHQ-9] detected depression category) were evaluated. RESULTS: One hundred fifty-six participants (females 44%, mean [SD] baseline HbA1c 71 [9] mmol/mol 8.6 [0.8%], age 44 [15]) were randomly assigned, in a 1:1 ratio to isCGM (n = 78) or SMBG (n = 78). The mean (SD) baseline HbA1c (%) was 8.7 (0.9) in the isCGM group and 8.5 (0.8) in the SMBG group, lowering to 7.9 (0.8) versus 8.3 (0.9), respectively, at 24 weeks (adjusted mean difference -0.5, 95% confidence interval [CI] -0.7 to -0.3; p < 0.001]. For HbA1c, there was no impact of treatment modality, prior participation in structured education, deprivation index quintile, sex or baseline depression category. The between-group difference in HbA1c was larger for younger people (a reduction of 2.7 [95% CI 0.3-5.0; p = 0.028] mmol/mol for every additional 15 years of age). Those with HbA1c 76-97 mmol/mol (>9.0%-11.0%) had a marginally non-significant higher reduction in HbA1c of 8.4 mmol/mol (3.3-13.5) compared to 3.1 (0.3-6.0) in those with HbA1c 58-75 mmol/mol (p = 0.08). For 'Time in range' (% 3.9-10 mmol/L), the difference was larger for those with at least a ...
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3دورية أكاديمية
المؤلفون: Elliott, Rachel A, Rogers, Gabriel, Evans, Mark L, Neupane, Sankalpa, Rayman, Gerry, Lumley, Sarah, Cranston, Iain, Narendran, Parth, Sutton, Christopher J, Taxiarchi, Vicky P, Burns, Matthew, Thabit, Hood, Wilmot, Emma G, Leelarathna, Lalantha, FLASH-UK Trial Study Group
مصطلحات موضوعية: Cost-effectiveness analysis, glucose monitoring, intermittently scanned continuous glucose monitoring, randomised controlled trial, type one diabetes, Adult, Humans, Diabetes Mellitus, Type 1, Blood Glucose, Cost-Benefit Analysis, Blood Glucose Self-Monitoring, Glycated Hemoglobin, Continuous Glucose Monitoring, State Medicine, England, Hypoglycemic Agents
الوصف: Funder: Diabetes UK; doi: http://dx.doi.org/10.13039/501100000361Test ; OBJECTIVE: We previously showed that intermittently scanned continuous glucose monitoring (isCGM) reduces HbA1c at 24 weeks compared with self-monitoring of blood glucose with finger pricking (SMBG) in adults with type 1 diabetes and high HbA1c levels (58-97 mmol/mol [7.5%-11%]). We aim to assess the economic impact of isCGM compared with SMBG. METHODS: Participant-level baseline and follow-up health status (EQ-5D-5L) and within-trial healthcare resource-use data were collected. Quality-adjusted life-years (QALYs) were derived at 24 weeks, adjusting for baseline EQ-5D-5L. Participant-level costs were generated. Using the IQVIA CORE Diabetes Model, economic analysis was performed from the National Health Service perspective over a lifetime horizon, discounted at 3.5%. RESULTS: Within-trial EQ-5D-5L showed non-significant adjusted incremental QALY gain of 0.006 (95% CI: -0.007 to 0.019) for isCGM compared with SMBG and an adjusted cost increase of £548 (95% CI: 381-714) per participant. The lifetime projected incremental cost (95% CI) of isCGM was £1954 (-5108 to 8904) with an incremental QALY (95% CI) gain of 0.436 (0.195-0.652) resulting in an incremental cost-per-QALY of £4477. In all subgroups, isCGM had an incremental cost-per-QALY better than £20,000 compared with SMBG; for people with baseline HbA1c >75 mmol/mol (9.0%), it was cost-saving. Sensitivity analysis suggested that isCGM remains cost-effective if its effectiveness lasts for at least 7 years. CONCLUSION: While isCGM is associated with increased short-term costs, compared with SMBG, its benefits in lowering HbA1c will lead to sufficient long-term health-gains and cost-savings to justify costs, so long as the effect lasts into the medium term. ; This work was supported by Diabetes UK grant number 18/0005836. The device manufacturer played no part in design, conduct or any other aspects of the study. The study devices were paid by the National Health Service (NHS) UK. Work was ...
وصف الملف: application/pdf; text/xml
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4دورية أكاديمية
المؤلفون: Tatovic, D, Jones, AG, Evans, C, Long, AE, Gillespie, K, Besser, REJ, Leslie, RD, Dayan, CM, Type 1 diabetes UK Immunotherapy Consortium
مصطلحات موضوعية: Adult, Diabetes Mellitus, Type 1, Type 2, Genetic Predisposition to Disease, Humans, Immunotherapy, United Kingdom
الوصف: This is the final version. Available from Wiley via the DOI in this record. ; National Institute for Health Research (NIHR)
العلاقة: https://www.ncbi.nlm.nih.gov/pubmed/35488476Test; Diabet Med, 39(7); orcid:0000-0002-0883-7599 (Jones, Angus G); Vol. 39, No. 7, article e14862; https://doi.org/10.1111/dme.14862Test; http://hdl.handle.net/10871/132538Test; Diabetic Medicine
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5دورية أكاديمية
المؤلفون: Jones, RL, Chawla, SP, Attia, S, Schöffski, P, Gelderblom, H, Chmielowski, B, Le Cesne, A, Van Tine, BA, Trent, JC, Patel, S, Wagner, AJ, Chugh, R, Heyburn, JW, Weil, SC, Wang, W, Viele, K, Maki, RG
المساهمون: Jones, Robin
مصطلحات موضوعية: MORAb-004, endosialin, ontuxizumab, sarcomas, tumor endothelial marker 1 (TEM-1), Adult, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antigens, CD, Neoplasm, Antimetabolites, Antineoplastic, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Cohort Studies, Deoxycytidine, Docetaxel, Double-Blind Method, Female, Humans, Male, Middle Aged, Progression-Free Survival, Sarcoma, Young Adult
جغرافية الموضوع: United States
الوصف: BACKGROUND: Ontuxizumab, a humanized monoclonal antibody, targets endosialin (tumor endothelial marker 1 [TEM-1] or CD248), which is expressed on sarcoma cells and is believed to be involved in tumor angiogenesis. This is the first trial to evaluate ontuxizumab in patients with sarcoma. METHODS: Part 1 was an open-label, dose-finding, safety lead-in: 4, 6, or 8 mg/kg with gemcitabine and docetaxel (G/D; 900 mg/m2 gemcitabine on days 1 and 8 and 75 mg/m2 docetaxel on day 8). In part 2, patients were randomized in a double-blind fashion in 2:1 ratio to ontuxizumab (8 mg/kg) or a placebo with G/D. Randomization was stratified by 4 histological cohorts. RESULTS: In part 2 with 209 patients, no significant difference in progression-free survival between ontuxizumab plus G/D (4.3 months; 95% confidence interval [CI], 2.7-6.3 months) and the placebo plus G/D (5.6 months; 95% CI, 2.6-8.3 months) was observed (P = .67; hazard ratio [HR], 1.07; 95% CI, 0.77-1.49). Similarly, there was no significant difference in median overall survival between the 2 groups: 18.3 months for the ontuxizumab plus G/D group (95% CI, 16.2-21.1 months) and 21.1 months for the placebo plus G/D group (95% CI, 14.2 months to not reached; P = .32; HR, 1.23; 95% CI, 0.82-1.82). No significant differences between the treatment groups occurred for any efficacy parameter by sarcoma cohort. The combination of ontuxizumab plus G/D was generally well tolerated. CONCLUSIONS: Ontuxizumab plus G/D showed no enhanced activity over chemotherapy alone in soft-tissue sarcomas, whereas the safety profile of the combination was consistent with G/D alone.
وصف الملف: Print-Electronic; 2454; application/pdf
العلاقة: Cancer, 2019, 125 (14), pp. 2445 - 2454; https://repository.icr.ac.uk/handle/internal/5394Test
الإتاحة: https://doi.org/10.1002/cncr.32084Test
https://repository.icr.ac.uk/handle/internal/5394Test -
6دورية أكاديمية
المصدر: 942 ; 941
مصطلحات موضوعية: Science & Technology, Life Sciences & Biomedicine, Hematology, CELL LEUKEMIA-LYMPHOMA, ADULT, MOGAMULIZUMAB, CHEMOTHERAPY, SURVIVAL, Human T-lymphotropic virus 1, Humans, Leukemia-Lymphoma, Adult T-Cell, 1102 Cardiorespiratory Medicine and Haematology, Immunology
العلاقة: British Journal of Haematology; http://hdl.handle.net/10044Test/1/98327
الإتاحة: https://doi.org/10.1111/bjh.18363Test
http://hdl.handle.net/10044Test/1/98327 -
7دورية أكاديمية
المؤلفون: Alejandro Ruiz‐Patiño, Oscar Arrieta, Andrés F. Cardona, Claudio Martín, Luis E. Raez, Zyanya L. Zatarain‐Barrón, Feliciano Barrón, Luisa Ricaurte, María A. Bravo‐Garzón, Luis Mas, Luis Corrales, Leonardo Rojas, Lorena Lupinacci, Florencia Perazzo, Carlos Bas, Omar Carranza, Carmen Puparelli, Manglio Rizzo, Rossana Ruiz, Christian Rolfo, Pilar Archila, July Rodríguez, Carolina Sotelo, Carlos Vargas, Hernán Carranza, Jorge Otero, Luis E. Pino, Carlos Ortíz, Paola Laguado, Rafael Rosell, on behalf of the CLICaP
المصدر: Thoracic Cancer, Vol 11, Iss 2, Pp 353-361 (2020)
مصطلحات موضوعية: Adult, immunotherapy, lung neoplasms, neoplasms/drug therapy, programmed cell death 1 receptor/antagonists & inhibitors, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Background To compare survival outcomes of patients with advanced or metastatic non‐small cell lung cancer (NSCLC) who received immunotherapy as first‐, second‐ or beyond line, versus matched patients receiving standard chemotherapy with special characterization of hyperprogressors. Methods A retrospective cohort study of 296 patients with unresectable/metastatic NSCLC treated with either, first‐, second‐, third‐ or fourth‐line of immunotherapy was conducted. A matched comparison with a historical cohort of first‐line chemotherapy and a random forest tree analysis to characterize hyperprogressors was conducted. Results Median age was 64 years (range 34–90), 40.2% of patients were female. A total of 91.2% of patients had an Eastern Cooperative Oncology Group (ECOG) performance score ≤ 1. Immunotherapy as first‐line was given to 39 patients (13.7%), second‐line to 140 (48.8%), and as third‐line and beyond to 108 (37.6%). Median overall survival was 12.7 months (95% CI 9.67–14 months) and progression‐free survival (PFS) of 4.27 months (95% CI 3.97–5.0). Factors associated with increased survival included treatment with immunotherapy as first‐line (P
وصف الملف: electronic resource
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المؤلفون: Shoshana S. Tell, Michal Schafer, Timothy Vigers, Amy D. Baumgartner, Ellen Lyon, Susan Gross, Sarit Polsky, Janet K. Snell‐Bergeon, Irene E. Schauer, Kristen J. Nadeau
المصدر: Diabetes, Obesity and Metabolism. 24:2148-2158
مصطلحات موضوعية: Adult, Blood Glucose, Cross-Over Studies, Adolescent, Blood Glucose Self-Monitoring, Endocrinology, Diabetes and Metabolism, Middle Aged, Lipids, Young Adult, Diabetes Mellitus, Type 1, Endocrinology, Double-Blind Method, Glucagon-Like Peptide 1, Creatinine, Hyperglycemia, Internal Medicine, Humans, Insulin, Insulin Resistance, Child, Bromocriptine
الوصف: To evaluate the potential for glycaemic, renal and vascular benefits of bromocriptine quick release (BCQR) in adolescents and adults with type 1 diabetes.Forty adolescents and 40 adults with type 1 diabetes aged 12-60 years old were enrolled in a double-blind, placebo-controlled, random order crossover study of 4 weeks of treatment in the morning with BCQR (titrated weekly from 0.8 mg to 1.6 mg to 3.2 mg, minimum dose 1.6 mg). Study assessments after each phase included blood pressure (BP), lipids, peripheral arterial stiffness and autonomic function, mixed meal tolerance test, continuous glucose monitoring (CGM), creatinine, estimated glomerular filtration rate, estimated insulin sensitivity, insulin dose and indirect calorimetry.Adolescents displayed baseline hyperglycaemia, insulin resistance, metabolic dysfunction and increased renal filtration compared with adults. In both age groups, continuous glucose monitoring measures, estimated insulin sensitivity and insulin dose did not differ with BCQR treatment. In adolescents, BCQR decreased systolic BP, diastolic BP and triangular index and increased serum creatinine. In adults, systolic BP, mean arterial pressure, systemic vascular resistance, and mixed meal tolerance test glucose and glucagon-like peptide 1 areas under the curve were lower, and the orthostatic drop in systolic BP was greater with BCQR.Greater hyperglycaemia, insulin resistance, metabolic dysfunction and renal hyperfiltration in adolescents argues for increased attention during this high-risk age period. Although BCQR had little impact on glycaemia or insulin sensitivity, initial vascular and renal responses suggest potential benefits of BCQR in adolescents and adults with type 1 diabetes requiring further study.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2c1430afbfbce998a2b4eb4ad94c2be2Test
https://doi.org/10.1111/dom.14800Test -
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المؤلفون: Cheryl Steele, Azni L Abdul-Wahab, Sylvia Xu, P. S. Hamblin, Sara Vogrin
المصدر: Internal Medicine Journal. 52:1002-1008
مصطلحات موضوعية: Adult, Pediatrics, medicine.medical_specialty, Type 1 diabetes, endocrine system diseases, Diabetic ketoacidosis, business.industry, nutritional and metabolic diseases, medicine.disease, Mental health, Diabetic Ketoacidosis, Hospitalization, Distress, Diabetes Mellitus, Type 1, Mental Health, Intervention (counseling), Diabetes mellitus, Internal Medicine, medicine, Humans, business, Psychosocial, Depression (differential diagnoses), Retrospective Studies
الوصف: BACKGROUND: Recurrent diabetic ketoacidosis (DKA) has been linked to mental health disorders, but less is known about single DKA episodes. Most studies are retrospective, lacking control groups. AIMS: Prospectively examine psychosocial factors in patients presenting with recurrent or single episode DKA and compare to people who have not had DKA. METHODS: Case-controlled study (consecutive adult DKA admissions April 2015 to December 2016) at Western Health, Melbourne. Data were prospectively collected regarding: diagnosed mental health disorders, likely depression (PHQ-9 questionnaire), diabetes distress (PAID questionnaire) and presence of adverse social factors. A control group without a history of DKA was also recruited. RESULTS: Of 123 patients admitted with DKA (164 consecutive episodes), 70 consented to participate and 73 age matched type 1 diabetes controls were recruited. Eleven of 18 (61%) with recurrent DKA had a diagnosed mental health disorder, versus 8 of 42 (19%) in the single episode group (p=0.016). The prevalence of likely depression using PHQ-9 was: recurrent 50%, single 40% and controls 22% (recurrent vs controls, p=0.036, single vs controls, p=0.053). Severe diabetes distress (PAID) was present in 47% of recurrent and 34% of single episode DKA (p=0.387). As a group, DKA patients had significantly more unemployment, illicit drug use and tobacco smoking, a lower level of formal education and less regular medical contact compared to controls. CONCLUSIONS: Mental health disorders and adverse socio-economic factors appear to be common in patients with DKA. The diagnosis of DKA presents an excellent opportunity to screen for depression and offer appropriate intervention. This article is protected by copyright. All rights reserved.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::df7ca1798df3ded6255204d7dae29a97Test
https://doi.org/10.1111/imj.15214Test -
10دورية أكاديمية
المؤلفون: Zhao, K, An, R, Xiang, Q, Li, G, Wang, K, Song, Y, Liao, Z, Li, S, Hua, W, Feng, X, Wu, X, Zhang, Y, Das, A, Yang, C
المصدر: urn:ISSN:0960-7722 ; urn:ISSN:1365-2184 ; Cell Proliferation, 54, 1, e12941
مصطلحات موضوعية: Biotechnology, 1 Underpinning research, 1.1 Normal biological development and functioning, Acid Sensing Ion Channels, Adolescent, Adult, Aged, Cells, Cultured, Child, Female, Humans, Inflammasomes, Inflammation, Intervertebral Disc Degeneration, Male, Middle Aged, NLR Family, Pyrin Domain-Containing 3 Protein, Nucleus Pulposus, Pyroptosis, Young Adult, NLRP3 inflammasome, acid-sensitive ion channel, anzsrc-for: 0601 Biochemistry and Cell Biology
الوصف: Objective: Lactate accumulation is an important factor in the intervertebral disc degeneration (IVDD). Currently, the effect and underlying mechanism of action of lactate on nucleus pulposus (NP) cell inflammation during IVDD are unclear. Previous studies have found that the NLRP3 inflammasome plays an important role in the regulation of NP inflammation. This study focused on the regulation of acid-sensitive ion channels (ASICs) in relation to inflammation and the effect of NLRP3 on pyroptosis levels in NP cells under acidic conditions. Design: For the in vitro experiments, human NP cells were exposed to 6 mM lactate solution; different groups were either treated with NLRP3 inhibitor or transfected with siRNA against NLRP3, siRNA against ASC or a mix of these, and mRNA and protein expression levels were then assessed. For the in vivo experiment, varying concentrations of lactate were injected into rat intervertebral discs and examined via magnetic resonance imaging (MRI) and histological staining. Results: Extracellular lactate promoted NLRP3 inflammasome activation and degeneration of the NP extracellular matrix; furthermore, it increased the levels of inflammation and pyroptosis in the NP. Lactate-induced NLRP3 inflammasome activation was blocked by ASIC inhibitors and NLRP3 siRNA. Conclusions: Extracellular lactate regulates levels of intercellular reactive oxygen species (ROS) through ASIC1 and ASIC3. ROS activate the NF-κB signalling pathway, thus promoting NLRP3 inflammasome activation and IL-1β release, both of which promote NP degeneration.
وصف الملف: application/pdf
العلاقة: http://hdl.handle.net/1959.4/unsworks_74257Test; https://unsworks.unsw.edu.au/bitstreams/69f7b8bc-235f-4f1c-b48e-540c3709950f/downloadTest; https://doi.org/10.1111/cpr.12941Test
الإتاحة: https://doi.org/10.1111/cpr.12941Test
http://hdl.handle.net/1959.4/unsworks_74257Test
https://unsworks.unsw.edu.au/bitstreams/69f7b8bc-235f-4f1c-b48e-540c3709950f/downloadTest
النص الكامل