7-point Change Research Articles

Qualitative Exploration in Exit Interviews of Changes Observed in Clinical Trials for Individuals with Autism Spectrum Disorder Without Intellectual Disability.

To explore, from the perspective of Study Partners (SPs; eg, caregivers) of clinical trial participants with autism spectrum disorder (ASD), any changes experienced in socialization and communication over the clinical trial, how these changes manifested, and the impact these changes had on the autistic individual, the SP, and family. This helps interpret whether changes in trial outcomes were meaningful. Interviews were conducted with the SPs of individuals with ASD, without intellectual disability, from 2 clinical trials: 86 children (aged 5-12 years) or adolescents (aged 13-17 years) who took part in the aV1ation trial (83.7% male), and 41 adults (aged 18+ years) who took part in the V1aduct trial (80.5% male). The primary endpoint for both trials was change from baseline in the VinelandTM-II two-domain composite, consisting of the mean of the Socialization and Communication domains. In these interviews the participants verbally indicated level of change for each of these key domains on 7-point change scales. Improvements in the Socialization domain enabled greater awareness of the feelings of others and allowed for stronger empathy and kindness. Improvements in the Communication domain allowed for the autistic individual to be better at listening and better at self-expression. Together, changes in these two domains, which were considered most important, allowed for richer, deeper relationships. Study Partners noted that improvements in these domains allowed for better integration within the family unit, decreased stress, and increased optimism about the autistic individual's future. The impacts of changes in either domain were synergistic, combining together to create positive experiences which in turn led to further positive impacts in other skills. These qualitative insights provide context to the changes that were observed during the clinical trial and captured using the VinelandTM-II, illustrating the meaning of these changes to the individuals with ASD without intellectual disability and their families, and the impact that they have on people's everyday lives and overall health-related quality of life.

Associations in health-related quality of life between patients and family caregivers 1 year after oesophageal cancer surgery.

Whether patients' health-related quality of life (HRQL) influences the HRQL of their family caregivers remains to be clarified. Therefore, the aim of this study was to investigate the association in HRQL between patients and family caregivers one year after oesophageal cancer surgery. The study was based on a prospective, nationwide, and population-based cohort including patients treated by surgery for oesophageal cancer in Sweden from 2013 to 2021 and their family caregivers. Data were collected one year after surgery, using the summary score of the EORTC QLQ-C30 and the RAND-36 questionnaire. Univariate and multivariate linear regression models providing regression coefficients with confidence intervals (CI) were used to estimate the association between the HRQL among patients and family caregivers. The analyses were adjusted for potential covariates. In total, 275 patients and paired family caregivers were included in the study. Patients reported a mean HRQL summary score of 81.4, indicating reductions in functions as well as many burdensome symptoms. Among family caregivers, lowest HRQL scores were reported for pain (69.2±26.0) and energy/fatigue (65.1±20.4). A 10-point change in the patients' summary score corresponded to a 7-point change for family caregivers' emotional role function (β=7.0; 95% CI: 3.6-10.3). For other HRQL dimensions among the family caregivers, no clinically relevant associations with patients HRQL were found. The current study indicates that family caregivers' emotional role function is influenced by patients' overall HRQL one year after surgery. The finding suggests that follow-up interventions should include not only patients but also their family caregivers.

Using standard celeration makes COVID-19 data more meaningful.

The fourth sudden acute respiratory syndrome (SARS) virus, COVID-19, emerged in late 2019, leading to the most devastating pandemic since the Spanish influenza (H1N1) of 1918, which seized 50 million lives worldwide (https://www.cdc.gov/flu/pandemic-resources/1918-pandemic-h1n1.html). Elected officials must make critical system-level decisions for stymieing the spread of the virus. Businesspersons must make personnel, financial, and operational decisions to minimize transmission while preserving their business's vitality. Members of the public must make personal decisions about personal protective equipment and changing social, recreational, occupational, and spiritual behavior to protect themselves and others. The scientific community can shift how they illustrate the virus's behavior to the public in an appropriate and understandable way so that the public can make informed decisions. This article suggests the use of a single-case design and logarithmic analyses to improve the current methodologies for COVID-19 analysis and illustration. The Standard Celeration Chart was used with Theil's incomplete regression and a 7-point change analysis; the authors demonstrate a suitable virus-tracking and mitigation methodology. Analysis and data visualization are standardized, providing an accurate depiction of the virus's growth for public dissemination and decision-making. An analytic strategy is demonstrated for retrospectively detecting meaningful changes in viral growth or prospectively measuring such changes that coincide with known mitigation strategies. The authors suggest improvements in bridging science to application by making COVID-19 informatics more meaningful and actionable by lawmakers, businesspersons, and the public. Limitations and future directions for COVID-19 informatics are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Abstract PD13-04: Impact of tucatinib on health-related quality of life in patients with HER2+ metastatic breast cancer with stable and active brain metastases

Abstract Background Patients (pts) with human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer (MBC) who have brain metastases (BM) have limited treatment options and lower health-related quality of life (HRQoL) compared with pts without BM (Hurvitz 2019). HER2CLIMB is a randomized trial (2:1) of tucatinib vs. placebo in combination with trastuzumab and capecitabine in pts with HER2+ MBC that included pts with stable and active brain metastases (NCT02614794). In HER2CLIMB, the addition of tucatinib to trastuzumab + capecitabine demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) in pts with HER2+ MBC and in those with stable and active BM, with importantly, a tolerable and manageable safety profile (Murthy 2020). An evaluation of the impact of tucatinib on HRQoL in pts with stable and active BM is presented here. Methods HRQoL data were available from 330 of 612 pts, including 163 pts with BMs. HRQoL was assessed using the EQ-5D-5L tool which includes a visual analog scale (EQ-VAS) and a descriptive system (EQ-5D) comprising 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Data were collected at Cycle 1 Day 1, Cycles 3-9 (every 2 cycles; 21-day cycles), Cycle 12 and beyond (every 3 cycles), and at the 30-day follow-up. The EQ-5D-5L scores were summarized by cycle for each treatment arm. Time to deterioration, defined as a >7-point change from baseline on the EQ-VAS, was estimated by the Kaplan-Meier approach. The median time to deterioration (and 95% CIs) were computed for each arm. Results In total, 163 pts with stable and active BM were included in this HRQoL analysis, 107 pts on the tucatinib arm and 56 pts on the placebo arm. Compared to the placebo arm, pts on the tucatinib arm had an approximately 49% reduction in the risk of deterioration (hazard ratio: 0.51; 95% CI: 0.28, 0.93); the median time to deterioration has not been reached in the tucatinib arm with available follow-up and was 5.5 months (95% CI; 4.2, -) in the placebo arm. Decline in all domains of the EQ-5D-5L and the EQ-VAS scores were seen once pts discontinued therapy, particularly on the ‘usual activities’ domain. Additional available QoL data will be presented. Conclusions Pts with MBC and BM treated with tucatinib in combination with trastuzumab + capecitabine demonstrated significantly longer and clinically meaningful time to deterioration of HRQoL. HRQoL was maintained throughout the treatment course, allowing them to receive full benefit of the therapeutic approach and resulting in statistically significant and clinically meaningful improvement in OS. References Hurvitz SA, O’Shaugnessy J, Mason G, et al. Central Nervous System Metastasis in Patients with HER2-Positive Metastatic Breast Cancer: Patient Characteristics, Treatment, and Survival from SystHERs. Clin Cancer Res. 2019;25(8):2433-2441.Murthy RK, Loi S, Okines A, et al. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2020;382(7):597-609. Citation Format: Andrew Wardley, Volkmar Mueller, Elisavet Paplomata, Laurence Crouzet, Nayyer Iqbal, Sramila Aithal, Margaret Block, Søren Cold, Marie-Agnes By, Olwen Hahn, Teja Poosarla, Erica Stringer-Reasor, Marco Colleoni, David Cameron, Giuseppe Curigliano, Kendra DeBusk, Muriel Siadak, Jorge Ramos, Xuebei An, Karen Gelmon. Impact of tucatinib on health-related quality of life in patients with HER2+ metastatic breast cancer with stable and active brain metastases [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD13-04.

P125 A mixed methods feasibility study of a gait rehabilitation programme for people with early rheumatoid arthritis and foot pain

Abstract Background Foot pain, a hallmark feature of rheumatoid arthritis (RA), is associated with slow and unsteady gait patterns, and persistent walking disability is common. Great Strides is a new gait rehabilitation programme designed to improve/preserve lower limb function in early RA. It is delivered by physiotherapists or podiatrists over 12-weeks and is supplemented with a home programme and support materials (DVD and illustrated booklet). It consists of a 6-task gait circuit and is underpinned by behaviour change techniques driven by motivational interviewing. The aims of this feasibility study were to 1) evaluate patient acceptability, adherence to, and safety of Great Strides, and 2) identify a suitable primary outcome measure for the main trial. Methods This study was a multi-centre (n = 3), single arm, repeated measures (pre- and post-intervention) design, with interviews exploring participants’ intervention perceptions. People with early (<2 years) RA who had foot pain were invited to participate. Intervention acceptability was evaluated using a 3-item intervention acceptability questionnaire. Adherence was evaluated using the Exercise Adherence Rating Scale (EARS). Safety was monitored using case report forms. Complementary mixed methods integrated descriptive quantitative acceptability, adherence, safety and thematic analyses to corroborate findings. Measurement properties of candidate primary outcomes (10-metre walking time, Foot Function Index disability subscale [FFI-DS], Recent Onset Arthritis Disability lower extremity subscale, and Patient-Reported Outcomes Measurement Information System physical function short-form) were evaluated against a 7-point Change in Walking Ability scale (CWA). Results 35 participants (68.6% female) with median age (inter-quartile range [IQR]) 60 [49-68] years and disease duration 9 [4-16] months), were recruited over 9 months and 23 (67%) completed 12-week follow-up. 12 participants completed interviews after the 12-week intervention period. Intervention acceptability was excellent; 21/23 were confident that it could help the problem; 21/23 reported that they would recommend it to a friend; 22/23 indicated it made sense to them. Intervention adherence was moderate, with a median [IQR] EARS score of 12/24 [7-19]. 1 participant reported transient post-exercise soreness. No serious adverse events were reported that were related to the intervention. From interviews, 10/12 participants reported they had continued with the intervention after 12-weeks. Participants revealed that the intervention provided structure and control to their day/week. Additional perceptions of benefit reported included improvements to lower limb joint health, and feelings of increased confidence to return to, or progress to further exercise in the community. The main challenge identified by some participants was lack of space to do the intervention at home. Correlations with the CWA were better for FFI-DS change-scores. Conclusion Great Strides has excellent acceptability and appears safe for people with early RA. Levels of adherence may be improved by intervention refinement. FFI-DS scores were theoretically consistent for selection as primary outcome for the main trial. Disclosures G.J. Hendry None. L. Bearne None. N. Foster None. E. Godfrey None. S. Hider None. M. van der Leeden None. H. Mason None. A. McConnachie None. I. McInnes None. A. Patience None. C. Sackley None. M. Sekhon None. A. Williams None. J. Woodburn None. M. Steultjens None.

Physical activity and prenatal depression: going beyond statistical significance by assessing the impact of reliable and clinical significant change.

Previous literature supports exercise as a preventative agent for prenatal depression; however, treatment effects for women at risk for prenatal depression remain unexplored. The purpose of the study was to examine whether exercise can lower depressive symptoms among women who began pregnancy at risk for depression using both a statistical significance and reliable and clinically significant change criteria. This study is a secondary analysis of two randomized controlled trials that followed the same exercise protocol. Pregnant women were allocated to an exercise intervention group (IG) or control group (CG). All participants completed the Center for Epidemiological Depression (CES-D) scale at gestational week 9-16 and 36-38. Women with a baseline score ⩾16 were included. A clinically reliable cut-off was calculated as a 7-point change in scores from pre- to post-intervention. Thirty-six women in the IG and 25 women in the CG scored ⩾16 on the CES-D at baseline. At week 36-38 the IG had a statistically significant lower CES-D score (14.4 ± 8.6) than the CG (19.4 ± 11.1; p < 0.05). Twenty-two women in the IG (61%) had a clinically reliable decrease in their post-intervention score compared to eight women in the CG (32%; p < 0.05). Among the women who met the reliable change criteria, 18 (81%) in the IG and 7 (88%) in the CG had a score <16 post-intervention, with no difference between groups (p > 0.05). A structured exercise program might be a useful treatment option for women at risk for prenatal depression.

Development of Azeliragon, an Oral Small Molecule Antagonist of the Receptor for Advanced Glycation Endproducts, for the Potential Slowing of Loss of Cognition in Mild Alzheimer's Disease.

Increasing evidence supports the role of the Receptor for Advanced Glycation Endproducts (RAGE) in the pathology of Alzheimer's disease. Azeliragon (TTP488) is an orally bioavailable small molecule inhibitor of RAGE in Phase 3 development as a potential treatment to slow disease progression in patients mild AD. Preclinical studies in animal models of AD (tgAPPSwedish/London) have shown azeliragon to decrease Aβ plaque deposition; reduce total Aβ brain concentration while increasing plasma Aβ levels; decreases sAPPβ while increasing sAPPα; reduce levels of inflammatory cytokines; and slow cognitive decline and improve cerebral blood flow. In the Phase 2b study, 18-months treatment in patients with mild-to-moderate AD indicated a baseline to endpoint change in ADAS-cog of 3.1 points in favor of drug. A greater magnitude of effect was evident in the sub-group of patients with mild AD (MMSE 21-26) with a baseline to endpoint change of 4 points on the ADAS-cog in favor of azeliragon and a 1 point change in CDR-sb in favor of drug. Azeliragon 5 mg/day delayed time to cognitive deterioration (7-point change in ADAS-cog from baseline, logrank p=0.0149). Based on promising results from the Phase 2b study, a Phase 3 registration program (STEADFAST) is being conducted under a Special Protocol Assessment from FDA. The ongoing Phase 3 program, if successful may demonstrate azeliragon can slow cognitive decline in mild AD patients.

Defining surgical criteria for empty nose syndrome: Validation of the office‐based cotton test and clinical interpretability of the validated Empty Nose Syndrome 6‐Item Questionnaire

The validated Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) identifies empty nose syndrome (ENS) patients. The unvalidated cotton test assesses improvement in ENS-related symptoms. By first validating the cotton test using the ENS6Q, we define the minimal clinically important difference (MCID) score for the ENS6Q. Individual case-control study. Fifteen patients diagnosed with ENS and 18 controls with non-ENS sinonasal conditions underwent office cotton placement. Both groups completed ENS6Q testing in three conditions-precotton, cotton in situ, and postcotton-to measure the reproducibility of ENS6Q scoring. Participants also completed a five-item transition scale ranging from "much better" to "much worse" to rate subjective changes in nasal breathing with and without cotton placement. Mean changes for each transition point, and the ENS6Q MCID, were then calculated. In the precotton condition, significant differences (P < .001) in all ENS6Q questions between ENS and controls were noted. With cotton in situ, nearly all prior ENS6Q differences normalized between ENS and control patients. For ENS patients, the changes in the mean differences between the precotton and cotton in situ conditions compared to postcotton versus cotton in situ conditions were insignificant among individuals. Including all 33 participants, the mean change in the ENS6Q between the parameters "a little better" and "about the same" was 4.25 (standard deviation [SD] = 5.79) and -2.00 (SD = 3.70), giving an MCID of 6.25. Cotton testing is a validated office test to assess for ENS patients. Cotton testing also helped to determine the MCID of the ENS6Q, which is a 7-point change from the baseline ENS6Q score. 3b. Laryngoscope, 127:1746-1752, 2017.

Short-Term Effects of Tolvaptan in Patients With Acute Heart Failure and Volume Overload

BackgroundIn patients with acute heart failure (AHF), dyspnea relief is the most immediate goal. Renal dysfunction, diuretic resistance, and hyponatremia represent treatment impediments. ObjectivesIt was hypothesized that the addition of tolvaptan to a background diuretic improved dyspnea early in patients selected for an enhanced vasopressin antagonism response. MethodsIn a double-blind trial, patients were randomized to tolvaptan 30 mg/day or placebo. Study entry required hospitalization within the previous 36 h, active dyspnea, and any of the following: 1) estimated glomerular filtration rate <60 ml/min/1.73 m2; 2) hyponatremia; or 3) diuretic resistance (urine output ≤125 ml/h following intravenous furosemide ≥40 mg). The primary endpoint was a 7-point change in self-assessed dyspnea at 8 and 16 h, using a novel standardized approach. ResultsWe randomized 250 patients. There was no difference in the primary endpoint of day 1 dyspnea reduction, despite significantly greater weight reduction with tolvaptan (−2.4 ± 2.1 kg vs. −0.9 ± 1.8 kg; p < 0.001). At day 3, dyspnea reduction was greater with tolvaptan (p = 0.01). There were 2 significant treatment-by-subgroup interactions: patients without elevated jugular venous pressure and those without ascites showed directional favorability of tolvaptan over placebo for the primary endpoint compared with patients with these findings. ConclusionsDespite rapid and persistent weight loss with tolvaptan compared with placebo, in patients with AHF who were selected for greater potential benefit from vasopressin receptor inhibition, tolvaptan was not associated with greater early improvement in dyspnea. Apparent subsequent differences in dyspnea warrant further exploration of the temporal relationship between diuresis and dyspnea relief and a possible clinical role for tolvaptan. (Randomized, Double-Blind, Placebo Controlled Study of the Short Term Clinical Effects of Tolvaptan in Patients Hospitalized for Worsening Heart Failure With Challenging Volume Management [SECRET of CHF]; NCT01584557)

Validity of low-contrast letter acuity as a visual performance outcome measure for multiple sclerosis

Low-contrast letter acuity (LCLA) has emerged as the leading outcome measure to assess visual disability in multiple sclerosis (MS) research. As visual dysfunction is one of the most common manifestations of MS, sensitive visual outcome measures are important in examining the effect of treatment. Low-contrast acuity captures visual loss not seen in high-contrast visual acuity (HCVA) measurements. These issues are addressed by the MS Outcome Assessments Consortium (MSOAC), including representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with MS. MSOAC goals are acceptance and qualification by regulators of performance outcomes that are highly reliable and valid, practical, cost-effective, and meaningful to persons with MS. A critical step is elucidation of clinically relevant benchmarks, well-defined degrees of disability, and gradients of change that are clinically meaningful. This review shows that MS and disease-free controls have similar median HCVA, while MS patients have significantly lower LCLA. Deficits in LCLA and vision-specific quality of life are found many years after an episode of acute optic neuritis, even when HCVA has recovered. Studies reveal correlations between LCLA and the Expanded Disability Status Score (EDSS), Multiple Sclerosis Functional Composite (MSFC), retinal nerve fiber layer (RNFL) and ganglion cell layer plus inner plexiform layer (GCL + IPL) thickness on optical coherence tomography (OCT), brain magnetic resonance imaging (MRI), visual evoked potential (VEP), electroretinogram (ERG), pupillary function, and King-Devick testing. This review also concludes that a 7-point change in LCLA is clinically meaningful. The overall goal of this review is to describe and characterize the LCLA metric for research and clinical use among persons with MS.

Specialized Pediatric Palliative Home Care: A Prospective Evaluation

In Germany since 2007 children with advanced life-limiting diseases are eligible for Pediatric Palliative Home Care (PPHC), which is provided by newly established specialized PPHC teams. The objective of this study was to evaluate the acceptance and effectiveness of PPHC as perceived by the parents. Parents of children treated by the PPHC team based at the Munich University Hospital were eligible for this prospective nonrandomized study. The main topics of the two surveys (before and after involvement of the PPHC team) were the assessment of symptom control and quality of life (QoL) in children; and the parents' satisfaction with care, burden of patient care (Häusliche Pflegeskala, home care scale, HPS), anxiety and depression (Hospital Anxiety and Depression Scale, HADS), and QoL (Quality of Life in Life-Threatening Illness-Family Carer Version, QOLLTI-F). Of 43 families newly admitted to PPHC between April 2011 and June 2012, 40 were included in the study. The median interval between the first and second interview was 8.0 weeks. The involvement of the PPHC team led to a significant improvement of children's symptoms and QoL (P<0.001) as perceived by the parents; and the parents' own QoL and burden relief significantly increased (QOLLTI-F, P<0.001; 7-point change on a 10-point scale), while their psychological distress and burden significantly decreased (HADS, P<0.001; HPS, P<0.001). The involvement of specialized PPHC appears to lead to a substantial improvement in QoL of children and their parents, as experienced by the parents, and to lower the burden of home care for the parents of severely ill children.

Melphalan, Prednisone and Lenalidomide Followed by Lenalidomide Maintenance Displays Treatment Characteristics Favourable to Global Quality of Life in Newly Diagnosed Multiple Myeloma (NDMM) Patients ≥ 65 Years,

Abstract 3988 Background:Melphalan, prednisone and lenalidomide followed by lenalidomide maintenance (MPR-R) demonstrated higher response rates (ORR; 77% vs. 50%, p <.001; VGPR or better: 32% vs. 12%, p <.001) and significantly reduced the risk of disease progression (hazard ratio [HR] = 0.423, p <.001) vs. MP alone [Palumbo, 2010]. Alongside efficacy considerations, analyses on health-related quality of life (HRQoL) may help more fully establish a regimen’s overall treatment profile. HRQoL improvements with MPR-R were observed during MPR induction as well as lenalidomide maintenance, documenting a well-balanced profile in terms of efficacy, tolerability and HRQoL [Dimopoulos, 2011]. Alternative findings on novel NDMM treatment have shown efficacy of melphalan, prednisone and bortezomib (VMP) treatment to be associated with an intermittent deterioration in patients’ HRQoL [Dhawan, 2009]. Methods:A mixed effects model was developed based on parameters pre-selected as potentially clinically relevant in impacting HRQoL. Models were run on six domains pre-selected based on clinical relevance: Global QoL, Physical Functioning, Fatigue and Pain (from EORTC QLQ-C30), and Disease Symptoms and Side Effects of Treatment (from EORTC MY20). Cycle 16 was determined as the last observation time point with a statistically meaningful sample size at time of follow-up (May 2010). Following explanatory variables were included: time-dependant covariates at individual HRQoL measurement time points (i.e. cycle 4, 7, 10, 13 and 16), treatment group (MPR-R vs. MP), gender (Female vs. Male), age, baseline QoL, Partial Response (PR) vs. Stable Disease (SD) and Very Good Partial Response or better (≥VGPR) vs. SD, Progressive Disease (PD) and Discontinuation (DC). Neutropenia and anemia, both Grade 3 or 4, were considered the clinically most relevant safety parameters. Main results for Global QoL are reported, with results from other domains found to be comparable. Results:Across all time-dependant covariates, a statistically significant reduction on Global QoL (−4.63; p=.004) was observed at Cycle 4. Being female vs. male significantly reduced Global QoL by -−.07 (p=.026). Each additional life year was found to lower Global QoL b− −0.40 points (p=.034). Baseline Global QoL was also significant, each additional score point leading to +0.30 (p <.001). A response level of ≥VGPR vs. SD increased Global QoL by 9.11 (p=.023); Progressive Disease (PD) reduced Global QoL by -−.34 score points (p <.001). All other pre-defined variables did not significantly impact Global QoL. Clinically meaningful changes for Global QoL in the underlying patient population have been determined to constitute at least a 7-point change [Dimopoulos, 2011]. Progressive disease (reducing Global QoL), respectively ≥VGPR (increasing Global QoL) exerted clinically meaningful changes, as did anemia grade 3–4, which had a clinically meaningful, but not statistically significant negative impact (−9.85; p=.057). Although no significant direct effect of MPR-R over MP on Global QoL was detected in the underlying model, MPR-R displays properties which favor an improved HRQoL profile, including a stronger delay in PD and higher % of VGPR vs. MP patients. Furthermore, certain properties more frequently observed with MPR-R than MP (neutropenia grade 3 or 4 and discontinuation, DC) were shown not to have a significant impact on HRQoL. Anemia grade 3 or 4, exerted a clinically meaningful negative effect but was not significantly more often observed with MPR-R compared to MP (24% vs. 17%, p= 0.091). Conclusions:More patients achieved ≥VGPR when receiving continuous MPR-R treatment than those receiving MP. In the above pooled analysis, ≥VGPR was shown to improve Global QoL in a clinically meaningful and statistically significant way. Furthermore, progression was also shown to negatively impact Global QoL (−8.34; p <.001), with MPR-R significantly reducing the risk of disease progression over MP. Delaying progression with continuous MPR-R therefore helps to maintain a high Global QoL. [Display omitted] Disclosures:Dimopoulos:Celgene: Consultancy, Honoraria. Off Label Use: Lenalidomide in newly diagnosed multiple myeloma. Palumbo:Celgene: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Ortho-Biotech: Honoraria. Hajek:Celgene: Honoraria; Janssen-Cilag: Honoraria; Merck: Honoraria. Petrucci:Celgene: Honoraria. Lewis:Celgene: Employment, Equity Ownership. Millar:Celgene: Consultancy. Zhang:Celgene: Employment, Equity Ownership. Mei:Celgene: Employment, Equity Ownership. Delforge:Celgene: Consultancy, Honoraria, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Speakers Bureau.

Responsiveness of the foot and ankle ability measure (FAAM) in individuals with diabetes

Background The impact of diabetes on physical function pose a challenge in assessing clinical outcomes. Objective The purpose of this study was to provide evidence of responsiveness for the foot and ankle ability measures (FAAM) in individuals with diabetes mellitus. Methods The two most recent FAAM scores of 155 diabetic patients treated for foot/ankle pathology were analyzed. Based on physical component summary (PCS) scores of the SF-36, subjects were categorized as improved (>7-point positive change), worsened (>7-point negative change), or unchanged (<7-point change). Analyses of the worsened and improved groups were compared to the unchanged group using two-way repeated measures ANOVAs and ROC curve analyses. Results The ANOVAs demonstrated a significant difference between groups ( P = 0.001). ROC curves analysis for detecting an improvement or decline in status were 0.73 (95% CI 0.62–0.84) and 0.70 (95% CI 0.59–0.81), respectively. An increase in FAAM score of 9 points represented the minimal clinically important difference (MCID) with 0.64 sensitivity and 0.78 specificity. A decrease in FAAM score of 2 points represented a MCID with 0.65 sensitivity and 0.61 specificity. Conclusions The FAAM demonstrated responsiveness to change in individuals with orthopedic foot and ankle dysfunction complicated by diabetes and can be used to measure patient outcomes over a 6-month period.

The OnyCOE-t™ questionnaire: responsiveness and clinical meaningfulness of a patient-reported outcomes questionnaire for toenail onychomycosis

BackgroundThis research was conducted to confirm the validity and reliability and to assess the responsiveness and clinical meaningfulness of the OnyCOE-t™, a questionnaire specifically designed to measure patient-reported outcomes (PRO) associated with toenail onychomycosis.Methods504 patients with toenail onychomycosis randomized to receive 12 weeks of terbinafine 250 mg/day with or without target toenail debridement in the IRON-CLAD® trial completed the OnyCOE-t™ at baseline, weeks 6, 12, 24, and 48. The OnyCOE-t™ is composed of 6 multi-item scales and 1 single-item scale. These include a 7-item Toenail Symptom assessment, which comprises both Symptom Frequency and Symptom Bothersomeness scales; an 8-item Appearance Problems scale; a 7-item Physical Activities Problems scale; a 1-item Overall Problem scale; a 7-item Stigma scale; and a 3-item Treatment Satisfaction scale. In total, 33 toenail onychomycosis-specific items are included in the OnyCOE-t™. Clinical data, in particular the percent clearing of mycotic involvement in the target toenail, and OnyCOE-t™ responses were used to evaluate the questionnaire's reliability, validity, responsiveness, and the minimally clinical important difference (MCID). ResultsThe OnyCOE-t™ was shown to be reliable and valid. Construct validity and known groups validity were acceptable. Internal consistency reliability of multi-item scales was demonstrated by Cronbach's alpha > .84. Responsiveness was good, with the Treatment Satisfaction, Symptom Frequency, Overall Problem, and Appearance Problem scales demonstrating the most responsiveness (Guyatt's statistic of 1.72, 1.31, 1.13, and 1.11, respectively). MCID was evaluated for three different clinical measures, and indicated that approximately an 8.5-point change (on a 0 to 100 scale) was clinically meaningful based on a 25% improvement in target nail clearing.ConclusionThe OnyCOE-t™ questionnaire is a unique, toenail-specific PRO questionnaire that can be used with confidence in future studies of toenail onychomycosis. MCID was evaluated for three different clinical measures, and indicated that approximately a 7-point change (on a 0 to 100 scale) was clinically meaningful based on a 12.5% improvement in target nail clearing.