Restructuring of Pancreatic Islets and Insulin Secretion in a Postnatal Critical Window

Function and structure of adult pancreatic islets are determined by early postnatal development, which in rats corresponds to the first month of life. We analyzed changes in blood glucose and hormones during this stage and their association with morphological and functional changes of alpha and beta cell populations during this period. At day 20 (d20), insulin and glucose plasma levels were two- and six-fold higher, respectively, as compared to d6. Interestingly, this period is characterized by physiological hyperglycemia and hyperinsulinemia, where peripheral insulin resistance and a high plasmatic concentration of glucagon are also observed. These functional changes were paralleled by reorganization of islet structure, cell mass and aggregate size of alpha and beta cells. Cultured beta cells from d20 secreted the same amount of insulin in 15.6 mM than in 5.6 mM glucose (basal conditions), and were characterized by a high basal insulin secretion. However, beta cells from d28 were already glucose sensitive. Understanding and establishing morphophysiological relationships in the developing endocrine pancreas may explain how events in early life are important in determining adult islet physiology and metabolism

Development of a core outcome set for clinical trials in squamous cell carcinoma: study protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey

Abstract Background Squamous cell carcinoma (SCC) is a common skin cancer that poses a risk of metastasis. Clinical investigations into SCC treatment are common, but the outcomes reported are highly variable, omitted, or clinically irrelevant. The outcome heterogeneity and reporting bias of these studies leave clinicians unable to accurately compare studies. Core outcome sets (COSs) are an agreed minimum set of outcomes recommended to be measured and reported in all clinical trials of a given condition or disease. Although COSs are under development for several dermatologic conditions, work has yet to be done to identify core outcomes specific for SCC. Methods/design Outcome extraction for COS generation will occur via four methods: (1) systematic literature review; (2) patient interviews; (3) other published sources; and (4) input from stakeholders in medicine, pharmacy, and other relevant industries. The list of outcomes will be revaluated by the Measuring PRiority Outcome Variables via Excellence in Dermatologic surgery (IMPROVED) Steering Committee. Delphi processes will be performed separately by expert clinicians and patients to condense the list of outcomes generated. A consensus meeting with relevant stakeholders will be conducted after the Delphi exercise to further select outcomes, taking into account participant scores. At the end of the meeting, members will vote and decide on a final recommended set of core outcomes. The Core Outcome Measures in Effectiveness Trials (COMET) organization and the Cochrane Skin Group - Core Outcome Set Initiative (CSG-COUSIN) will serve as advisers throughout the COS generation process. Discussion Comparison of clinical trials via systematic reviews and meta-analyses is facilitated when investigators study outcomes that are relevant and similar. The aim of this project is to develop a COS to guide use for future clinical trials

Development of a core outcome set for clinical trials in basal cell carcinoma: study protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey

Abstract Background Basal cell carcinoma is the most common skin cancer worldwide. Treatment options include both surgical and topical modalities. Although risk of metastasis is low, basal cell carcinoma can be invasive and infiltrate important underlying structures such as bone or cartilage. While many clinical trials examining therapies for basal cell carcinoma exist, the lack of consensus in outcome reporting across all trials poses a concern. Proper evaluation and comparison of treatment modalities is challenging. In order to address the inconsistencies present, this project aims to determine a core set of outcomes which should be evaluated in all clinical trials of basal cell carcinoma. Methods/design Outcomes will be extracted over four phases: (1) a systematic literature review, (2) patient interviews, (3) other published sources, and (4) stakeholder involvement. Potential outcomes will then be examined by the Steering Committee, who may add or remove outcomes. The Delphi process will then be performed to condense the list of outcomes generated. Two rounds of Delphi surveys will be performed with two groups of participants – physicians and patients. A consensus meeting with relevant stakeholders will be conducted after the Delphi exercise to further select outcomes, taking into account participant scores. By the end of the meeting, members will vote and decide on a final recommended set of core outcomes. For the duration of the study, we will be in collaboration with both the Core Outcome Measures in Effectiveness Trials (COMET) initiative and the Cochrane Skin Group – Core Outcome Set Initiative (CSG-COUSIN). Discussion This study aims to develop a core outcome set to guide assessment in clinical trials on basal cell carcinoma. The end-goal is to improve the consistency of outcome reporting and allow proper evaluation of treatment effectiveness

Development of a core outcome set for cutaneous squamous cell carcinoma trials: identification of core domains and outcomes

BackgroundThe lack of uniformity in the outcomes reported in clinical studies of the treatment of cutaneous squamous cell carcinoma (cSCC) complicates efforts to compare treatment effectiveness across trials.ObjectivesTo develop a core outcome set (COS), a minimum set of agreed-upon outcomes to be measured in all clinical trials of a given disease or outcome, for the treatment of cSCC.MethodsOne hundred and nine outcomes were identified via a systematic literature review and interviews with 28 stakeholders. After consolidation of this long list, 55 candidate outcomes were rated by 19 physician and 10 patient stakeholders, in two rounds of Delphi exercises. Outcomes scored 'critically important' (score of 7, 8 or 9) by ≥ 70% of patients and ≥ 70% of physicians were provisionally included. At the consensus meeting, after discussion and voting of 44 international experts and patients, the provisional list was reduced to a final core set, for which consensus was achieved among all meeting participants.ResultsA core set of seven outcomes was finalized at the consensus meeting: (i) serious or persistent adverse events, (ii) patient-reported quality of life, (iii) complete response, (iv) partial response, (v) recurrence-free survival, (vi) progression-free survival and (vii) disease-specific survival.ConclusionsIn order to increase the comparability of results across trials and to reduce selective reporting bias, cSCC researchers should consider reporting these core outcomes. Further work needs to be performed to identify the measures that should be reported for each of these outcomes

Development of a core outcome set for cutaneous squamous cell carcinoma trials: identification of core domains and outcomes

Background: The lack of uniformity in the outcomes reported in clinical studies of the treatment of cutaneous squamous cell carcinoma (cSCC) complicates efforts to compare treatment effectiveness across trials. Objectives: To develop a core outcome set (COS), a minimum set of agreed-upon outcomes to be measured in all clinical trials of a given disease or outcome, for the treatment of cSCC. Methods: One hundred and nine outcomes were identified via a systematic literature review and interviews with 28 stakeholders. After consolidation of this long list, 55 candidate outcomes were rated by 19 physician and 10 patient stakeholders, in two rounds of Delphi exercises. Outcomes scored ‘critically important’ (score of 7, 8 or 9) by ≥ 70% of patients and ≥ 70% of physicians were provisionally included. At the consensus meeting, after discussion and voting of 44 international experts and patients, the provisional list was reduced to a final core set, for which consensus was achieved among all meeting participants. Results: A core set of seven outcomes was finalized at the consensus meeting: (i) serious or persistent adverse events, (ii) patient-reported quality of life, (iii) complete response, (iv) partial response, (v) recurrence-free survival, (vi) progression-free survival and (vii) disease-specific survival. Conclusions: In order to increase the comparability of results across trials and to reduce selective reporting bias, cSCC researchers should consider reporting these core outcomes. Further work needs to be performed to identify the measures that should be reported for each of these outcomes

Development of a Core Outcome Set for Cutaneous Squamous Cell Carcinoma Trials: Identification of Core Domains and Outcomes

BACKGROUND: The lack of uniformity in the outcomes reported in clinical studies of the treatment of cutaneous squamous cell carcinoma (cSCC) complicates efforts to compare treatment effectiveness across trials.OBJECTIVE: To develop a core outcome set (COS), a minimum set of agreed-upon outcomes to be measured in all clinical trials of a given disease or outcome, for the treatment of cSCC.METHODS: One hundred nine outcomes were identified via a systematic literature review and interviews with 28 stakeholders. After consolidation of this long list, 55 candidate outcomes were rated by 19 physician and 10 patient stakeholders, respectively, in two rounds of Delphi exercises. Outcomes scored 'critically important' (scored 7,8, or 9) by 70% of patients and 70% of physicians were provisionally included. At the consensus meeting, after discussion and voting of 44 international experts and patients, the provisional list was reduced to a final core set, for which consensus was achieved among all meeting participants.RESULTS: A core set of seven outcomes was finalized at the consensus meeting: serious or persistent adverse events, patient-reported quality of life, complete response, partial response, recurrence-free survival, progression-free survival, and disease-specific survival.CONCLUSIONS: In order to increase the comparability of results across trials and to reduce selective reporting bias, cSCC researchers should consider reporting these core outcomes. Further work needs to be performed to identify the measures that should be reported for each of these outcomes

Development of a core outcome set for cutaneous squamous cell carcinoma trials: identification of core domains and outcomes

International audienceBackground: The lack of uniformity in the outcomes reported in clinical studies of the treatment of cutaneous squamous cell carcinoma (cSCC) complicates efforts to compare treatment effectiveness across trials. Objectives: To develop a core outcome set (COS), a minimum set of agreed-upon outcomes to be measured in all clinical trials of a given disease or outcome, for the treatment of cSCC. Methods: One hundred and nine outcomes were identified via a systematic literature review and interviews with 28 stakeholders. After consolidation of this long list, 55 candidate outcomes were rated by 19 physician and 10 patient stakeholders, in two rounds of Delphi exercises. Outcomes scored ‘critically important’ (score of 7, 8 or 9) by ≥ 70% of patients and ≥ 70% of physicians were provisionally included. At the consensus meeting, after discussion and voting of 44 international experts and patients, the provisional list was reduced to a final core set, for which consensus was achieved among all meeting participants. Results: A core set of seven outcomes was finalized at the consensus meeting: (i) serious or persistent adverse events, (ii) patient-reported quality of life, (iii) complete response, (iv) partial response, (v) recurrence-free survival, (vi) progression-free survival and (vii) disease-specific survival. Conclusions: In order to increase the comparability of results across trials and to reduce selective reporting bias, cSCC researchers should consider reporting these core outcomes. Further work needs to be performed to identify the measures that should be reported for each of these outcomes