Innovating Therapies for Down Syndrome: An International Virtual Conference of the T21 Research Society.

Research focused on Down syndrome continued to gain momentum in the last several years and is advancing our understanding of how trisomy 21 (T21) modifies molecular and cellular processes. The Trisomy 21 Research Society (T21RS) is the premier scientific organization for researchers and clinicians studying Down syndrome. During the COVID pandemic, T21RS held its first virtual conference program, sponsored by the University of California at Irvine, on June 8-10, 2021 and brought together 342 scientists, families, and industry representatives from over 25 countries to share the latest discoveries on underlying cellular and molecular mechanisms of T21, cognitive and behavioral changes, and comorbidities associated with Down syndrome, including Alzheimer's disease and Regression Disorder. Presentations of 91 cutting-edge abstracts reflecting neuroscience, neurology, model systems, psychology, biomarkers, and molecular and pharmacological therapeutic approaches demonstrate the compelling interest and continuing advancement toward innovating biomarkers and therapies aimed at ameliorating health conditions associated with T21.

Development of a core outcome set for basal cell carcinoma.

BACKGROUND: There is variation in the outcomes reported in clinical studies of basal cell carcinoma. This can prevent effective meta-analyses from answering important clinical questions. OBJECTIVE: To identify a recommended minimum set of core outcomes for basal cell carcinoma clinical trials. METHODS: Patient and professional Delphi process to cull a long list, culminating in a consensus meeting. To be provisionally accepted, outcomes needed to be deemed important (score, 7-9, with 9 being the maximum) by 70% of each stakeholder group. RESULTS: Two hundred thirty-five candidate outcomes identified via a systematic literature review and survey of key stakeholders were reduced to 74 that were rated by 100 health care professionals and patients in 2 Delphi rounds. Twenty-seven outcomes were provisionally accepted. The final core set of 5 agreed-upon outcomes after the consensus meeting included complete response; persistent or serious adverse events; recurrence-free survival; quality of life; and patient satisfaction, including cosmetic outcome. LIMITATIONS: English-speaking patients and professionals rated outcomes extracted from English language studies. CONCLUSION: A core outcome set for basal cell carcinoma has been developed. The use of relevant measures may improve the utility of clinical research and the quality of therapeutic guidance available to clinicians.

Interpolation Flaps in the Outpatient Mohs Surgery Setting: A Prospective Cohort Study of Patient Pain, Anxiety, and Satisfaction.

BACKGROUND: Staged interpolation flaps (SIFs) have historically been performed under general anesthesia by specialties outside of dermatologic surgery. However, SIFs performed under local anesthesia by dermatologic surgeons have shown lower or equal complication rates. OBJECTIVE: To date, no studies have evaluated pain, anxiety, satisfaction, and use of perioperative analgesics in patients undergoing SIFs in an outpatient setting under local anesthesia. METHODS/MATERIALS: This is a prospective cohort study of 39 patients who received Mohs micrographic surgery and subsequent SIF repair in an outpatient setting under local anesthesia. Pain, anxiety, and satisfaction scores were recorded using 100-point validated visual analog scales. Perioperative analgesic use was quantified. RESULTS: The defect size was ≥4 cm2 in 72% of patients; 41% had full-thickness (skin/cartilage/mucosa) defects. All pain and anxiety measures were minimal to mild. Pain scores ranged from highest (mean = 39 ± 4.1) on postoperative Day (POD) 1 to lowest (mean = 12.3 ± 2.0) on POD 7. Anxiety scores ranged from highest (mean = 42 ± 4.5) on POD 1 to lowest (mean = 18.5 ± 3.7) on POD 7. Perioperative patient satisfaction was high (mean = 95 ± 1.7). Postoperative narcotic analgesics were prescribed in 15% of patients. CONCLUSION: Staged interpolation flaps performed under local anesthesia in the outpatient setting are well tolerated with low pain and anxiety, high patient satisfaction, and minimal analgesic use.

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.

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.

Is Early Palliative Care Feasible in Patients With Multiple Myeloma?

CONTEXT: Evidence for the benefits of early palliative care (EPC) in patients with solid tumors is strong, but EPC has received scant attention in hematologic malignancies. OBJECTIVE: To assess the benefits of outpatient-based EPC for symptom control in patients with multiple myeloma. METHODS: Retrospective study of patients attending the Multiple Myeloma Palliative Care Clinic at our hospital in the year 2013 (February 1-December 31). The following symptoms were assessed at baseline and at three follow-up consultations using a Numerical Visual Scale (0 = no symptoms; 10 = worst possible): pain, anorexia, constipation, insomnia, nausea/vomiting, dyspnea, anxiety, and sadness. Physical and emotional symptom burden scores were calculated. Pain interference with general activity, sleep, and mood was also evaluated. RESULTS: About 67 patients were included. The proportion of patients reporting moderate-to-severe pain (Numerical Visual Scale ≥5) decreased significantly from baseline to the final follow-up: worst pain decreased from 57% to 18% (P < 0.0001), whereas average pain fell from 24% to 2% (P < 0.0001). The percentage of patients reporting no pain interference increased significantly from baseline: general activity (52% vs. 82%; P = 0.0001), sleep (73% vs. 91%; P = 0.01), and mood (52% vs. 87.5%; P = 0.0001). Physical and emotional symptom burden also improved, with significantly fewer patients reporting depression (13% vs. 5%; P = 0.001). Most patients (86.6%) were alive and still attending the Multiple Myeloma Palliative Care Clinic at study end. CONCLUSIONS: These findings indicate that EPC is feasible in patients with multiple myeloma. Pain and other symptoms were well controlled.

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.

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.

Pediatric nephrogenic systemic fibrosis is rarely reported: a RADAR report.

BACKGROUND: Nephrogenic systemic fibrosis is a fibrosing disorder associated with exposure to gadolinium-based contrast agents in people with severely compromised renal function. OBJECTIVE: The purpose of this study was to determine the reported number of cases of nephrogenic systemic fibrosis in children using three distinct publicly available data sources. MATERIALS AND METHODS: We conducted systematic searches of the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), the International Center for Nephrogenic Systemic Fibrosis Research (ICNSFR) registry and published literature from January 1997 through September 2012. We contacted authors of individual published cases to obtain follow-up data. Data sets were cross-referenced to eliminate duplicate reporting. RESULTS: We identified 23 children with nephrogenic systemic fibrosis. Seventeen had documented exposure to gadolinium-based contrast agents. Six children had been reported in both the FAERS and the literature, four in the FAERS and the ICNSFR registry and five in all three data sources. CONCLUSION: Nephrogenic systemic fibrosis has been rarely reported in children. Although rules related to confidentiality limit the ability to reconcile reports, active pharmaco-vigilance using RADAR (Research on Adverse Drug events And Reports) methodology helped in establishing the number of individual pediatric cases within the three major data sources.

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.