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Introduction: The Integrated Alzheimer's Disease Rating Scale (iADRS) has been used to detect differences in disease progression in early Alzheimer's disease (AD). The objectives of this study were to enhance understanding of iADRS point changes within the context of clinical trials, and to establish a minimal clinically important difference (MCID) on the iADRS. Methods: Data from AMARANTH and EXPEDITION3 were analyzed using various approaches, including anchor-based, distribution-based, regression analyses, and cumulative distribution function (CDF) plots. Three potential anchors were examined, including the Clinical Dementia Rating-Sum of Boxes, Mini-Mental State Examination, and Functional Activities Questionnaire. Triangulation of all results was used to determine the MCID for participants with mild cognitive impairment (MCI) due to AD and AD with mild dementia. Results: All three anchors met criteria for "sufficiently associated" (|r| = 0.4-0.7). Cumulatively, results from anchor-based and distribution-based results converged to suggest an iADRS MCID of 5 points for MCI due to AD and 9 points for AD with mild dementia. Regression analyses and CDF plots supported these values. Discussion: These findings suggest the iADRS can be used in clinical trials to detect a clinically meaningful outcome of AD progression.
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BACKGROUND: This analysis assessed improvements in patients with radiographic axial spondyloarthritis (r-axSpA) treated with ixekizumab in the Assessment of Spondyloarthritis International Society (ASAS) treatment response domains and additional patient-reported outcomes at 1 year of treatment. METHODS: COAST-V and COAST-W were 52-week, phase 3, randomized controlled trials evaluating the efficacy and safety of ixekizumab in biologic disease-modifying antirheumatic drug (bDMARD)-naïve and tumor necrosis factor inhibitor (TNFi)-experienced patients with radiographic spondyloarthritis, respectively. Patients were treated with 80-mg ixekizumab either every 2 weeks or every 4 weeks. Patient-reported outcomes included Patient Global Disease Activity, Spinal Pain, stiffness as measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Questions 5 and 6, function as measured by the Bath Ankylosing Spondylitis Functional Index, fatigue as measured by the Fatigue Numeric Rating Scale and BASDAI question 1, Spinal Pain at Night, and sleep quality as measured by the Jenkins Sleep Evaluation Questionnaire. Mixed-effects models for repeated measures were used to analyze changes from baseline in patient-reported outcomes from weeks 1 to 16, and descriptive statistics were reported from weeks 20 to 52. Analysis of covariance with Scheffé's method was used for the ASAS response association analyses. RESULTS: This study assessed 341 bDMARD-naïve and 316 TNFi-experienced patients in the placebo-controlled blinded treatment dosing period (weeks 1-16) as well as 329 bDMARD-naïve and 281 TNFi-experienced patients in the dose double-blind extended treatment period (weeks 20-52). bDMARD-naïve or TNFi-experienced patients treated with ixekizumab every 2 weeks and every 4 weeks reported improvements in patient global disease activity, spinal pain, function, stiffness, fatigue, spinal pain at night, and sleep quality through week 52. Greater correlations with improvements in all response domains were seen when comparing ASAS40 responders to ASAS20 non-responders (p < 0.001), with up to 10.5-fold greater improvements observed in ASAS40 responses compared with ASAS20 non-responders. Function and fatigue demonstrated the highest values. CONCLUSIONS: Ixekizumab-treated bDMARD-naïve and TNFi-experienced patients with radiographic axial spondyloarthritis achieving ASAS40 reported sustained and consistent improvement in all ASAS response domains and other patient-reported outcomes though week 52, with spinal pain, function, and stiffness as major drivers of the response. TRIAL REGISTRATION: NCT02696785 and NCT02696798 , March 2, 2016.
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INTRODUCTION: Frailty can be quantified using an index score to effectively predict surgical outcomes and complications. The modified frailty index (mFI) score includes 5 patient-specific medical history comorbidities including diabetes mellitus, congestive heart failure, hypertension, chronic obstructive pulmonary disease/pneumonia, and nonindependent functional status. The purpose of our study was to apply the 5-item mFI score to predict and minimize complications in patients undergoing breast reconstruction. METHODS: The National Surgical Quality Improvement Program was queried for all patients undergoing primary breast reconstruction from 2016 to 2018. Patients were divided based on timing of reconstruction and type of reconstruction: immediate or delayed, and implant based or autologous based. A validated modified fragility score was applied to all patients. Patients were stratified by mFI scores of 0 (no comorbidities), 1 (1 comorbidity), and 2+ (2 or more comorbidities). Patient demographics and 30-day complications rates were recorded. RESULTS: A total of 22,700 patients were identified. There were 10,673 patients who underwent immediate breast reconstruction, and 12,027 patients who underwent delayed breast reconstruction. A total of 14,159 patients underwent implant-based, and 8541 underwent autologous-based reconstruction. A total of 16,627 patients had an mFI score of 0, 4923 had a mFI score of 1, and 1150 had a mFI score of 2+. Compared with patients with an mFI score of 0, patients with an mFI score of 2 or greater were more likely to develop a postoperative complication (7.2 vs 12.3; P < 0.0001). Patients undergoing immediate reconstruction were more likely to develop a postoperative complications for every mFI category. The most common complications were wound and hematologic related. CONCLUSION: Patients with higher mFI scores are likely to have an increase in postoperative complications after breast reconstruction. Increasing body mass index increases postoperative complications independent of frailty index scores. Patients with increasing frailty index scores undergoing immediate breast reconstruction have a significantly higher risk of postoperative complications compared with delayed reconstruction.Patients with increasing frailty index scores undergoing autologous breast reconstruction have a significantly higher risk of postoperative complications compared with implant-based reconstruction. High frailty index scores are associated with a higher risk of postoperative complications, reoperation rates, and readmission rates. Patients with higher mFI scores may benefit from a delayed implant-based reconstruction.
