Distribution-based Approach Research Articles

Mycosis fungoides - differentiation from inflammation and detection of circulating tumor cells with the EuroClonality-NGS assay.

Mycosis fungoides (MF) is a rare malignancy characterized by the presence of circulating tumor cells (CTCs) in a subgroup of patients. Reliably distinguishing MF from inflammatory skin conditions (IF) is a challenging task. This study aimed to evaluate the potential benefits of next-generation sequencing (NGS)-based T-cell receptor (TR) rearrangement repertoire analysis for detecting clonal rearrangements in MF and IF. Skin biopsies and blood samples from 33 MF patients (diagnosed according to WHO-EORTC criteria) and 10 IF patients were analyzed using TRB- and TRG-NGS. 27/33 MF patients were early-stage IA (n=19), IB (n=8), and six had advanced stages (IIB, n=5; IIIA, n=1). Analysis applying the standard abundance thresholds identified at least one clonal rearrangement in the skin DNA of 32/33 MF (97%) and 9/10 IF cases (90%). To enhance specificity, an abundance- and distribution-based approach was applied, considering only rearrangements that significantly stood out from the physiological background as clonal (MF 29/33, IF 1/10), allowing for a highly sensitive (88%) and specific (90%) discrimination between MF and IF. CTCs were detected in 11/24 (46%) early-stage and 3/5 (60%) late-stage MF patients. NGS-based TR repertoire analysis is a highly sensitive and specific method for the differential diagnosis of early-stage MF compared to IF, and for the sensitive molecular detection of CTCs.

Establishing the minimum clinically important difference of the Quality of Life in Childhood Epilepsy Questionnaire.

To estimate the minimum clinically important difference (MCID) for the parent-reported 55-item Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) and its shortened 16-item version, QOLCE-16. Data came from 74 children with epilepsy (CWE) (ages 4-10, mean age = 8 [SD = 1.8]) enrolled in the Making Mindfulness Matter in Epilepsy (M3-E) trial, a pilot, parallel randomized-controlled trial of a mindfulness-based intervention. Both anchor-based and distribution-based methods were used to estimate MCID values for the QOLCE-55 and QOLCE-16. For the anchor-based approach, the Patient Centered Global Ratings of Change (PCGRC) scale and linear regression analysis were used to estimate the MCID. For the distribution-based approach, .5 SD of the health-related quality of life (HRQOL) change score distribution was used to estimate the MCID. For the QOLCE-55, the MCID obtained using an anchor-based approach was 10 points and using a distribution-based method was 6 points. For the QOLCE-16, the MCID obtained using an anchor-based method was 13 points and using a distribution-based method was 7 points. This is the first study to estimate MCID values for the QOLCE-55 and the QOLCE-16. It has been well documented that CWE are at risk of experiencing psychological, behavioral, and cognitive impairments, which can negatively impact their HRQOL. Reporting MCID values for the QOLCE-55 and QOLCE-16 is important in determining whether changes in HRQOL observed are meaningful to CWE themselves, as a key factor in shaping the nature of epilepsy care delivered.

Precision in Progress: Unraveling the Clinimetric Properties of Beery-Buktenica Developmental Test of Visual-Motor Integration in Children With Cerebral Palsy Across Diverse Motor Severities

BackgroundIn the realm of pediatric cerebral palsy (CP), visual motor challenges often overshadow a child's developmental journey. This study delves into the responsiveness and crucial benchmarks, specifically the minimal clinically important difference (MCID), of the Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery VMI) among children with varying motor severities. MethodEighty-eight children with CP (50 males, 38 females; aged three to 12 years) with Gross Motor Function Classification System (GMFCS) levels I to III were recruited from the rehabilitation department of Chang Gung Memorial Hospital in Taiwan. Each participant received the Beery VMI tests at baseline and at one-year follow-up. The standardized response mean (SRM) was calculated to determine the responsiveness of Beery VMI, and a distribution-based approach was used to estimate MCID. ResultsThe Beery VMI exhibited remarkable responsiveness across GMFCS levels I to III (SRM = 0.98-2.36). MCIDs for Beery VMI varied across severities, with ranges of 2.93 to 4.41 (0.2 S.D.), 7.31 to 11.49 (0.5 S.D.), and 11.70 to 18.38 (0.8 S.D.). Notably, in the visual perception subset, MCIDs were 3.93 to 4.03 (0.2 S.D.), 9.83 to 10.07 (0.5 S.D.), and 15.73 to 16.11 (0.8 S.D.). In the supplemental motor coordination subtest, MCIDs spanned 1.67 to 4.87 (0.2 S.D.), 4.18 to 12.17 (0.5 S.D.), and 6.68 to 19.47 (0.8 S.D.). ConclusionsBeery VMI demonstrates robust responsiveness in children with CP. Motor-severity-tailored MCIDs offer a guide for clinicians and researchers, hinting at treatment efficacy. Particularly, lower change scores in VMI and motor coordination subtests may signal effective interventions for moderate motor disability over mild cases.

468. CALCULATING THE MINIMAL CLINICALLY IMPORTANT DIFFERENCE FOR THE FACT-E FROM ESOPHAGECTOMY TO RECOVERY USING DISTRIBUTION-BASED METHODS

Abstract Background The Functional Assessment of Cancer Therapy-Esophageal (FACT-E) is a validated patient-reported outcome instrument that measures four subscales of general cancer health and one subscale specific to esophageal cancer. To make the instrument more clinically useful, therapeutic thresholds known as minimal clinically important differences (MCID) are needed. The purpose of this study was to calculate the MCID for the FACT-E and its subscales for patients undergoing an esophagectomy. Methods The study was based on a retrospective analysis of a registry maintained by a high volume North American tertiary care referral centre, which includes the FACT-E collected between August 2004 and September 2023. The FACT-E was administered at nine time points over the course of a patient’s care, ranging from the time of first presentation to 5 years post-esophagectomy. This study used two distribution-based approaches – the standard error (SE) and the standard deviation (SD) – to calculate the MCID for the FACT-E’s total score and its five subscales. Nonparametric bootstrapping was used to generate 95% confidence intervals for each MCID. Results There were 731 participants included in this study but not all of those completed each subscale at each time point. The MCID for physical well-being ranged from 2.2-3.1 using SE and 2.3-3.4 using SD, from 2.1-3.6 using SE and 2.2-3.6 using SD for social well-being, 1.2-1.7 using SE and from 1.4-2.0 using SD for emotional well-being, 2.1-2.4 using SE and 3.2-3.6 using SD for functional well-being, and from 3.2-4.3 using SE and from 4.3-6.4 using SD for the esophagus cancer subscale. The MCID for the total score ranged from 6.7-8.3 using SE and from 8.9-11.2 using SD. Conclusion The MCID thresholds for the FACT-E subscales vary depending on when they are collected and how they are measured. In general, smaller thresholds of change are needed in the social and emotional well-being subscales, while larger ones are needed for the esophagus cancer subscale. Overall, the MCID for the FACT-E total score ranged from 6 to 11. Clinicians should consider these MCID if using the FACT-E to assess changes in patients’ symptom severity before and after esophagectomy.

Minimal important difference of Berg Balance Scale, performance-oriented mobility assessment and dynamic gait index in chronic stroke survivors

ObjectiveThe Berg Balance Scale (BBS), Performance-Oriented Mobility Assessment (POMA), and Dynamic Gait Index (DGI) are crucial standard tools used to evaluate functional balance. However, their minimal important difference (MID) threshold is yet to be established. The objective of this research was to explore the MID for BBS, POMA, and DGI in people suffering from chronic stroke. MethodsA total of 130 chronic stroke patients were assessed using BBS, POMA and DGI before and after undergoing interventions. The treatment procedures included a series of task-oriented exercises focusing on motor re-learning. In anchor-based approach, the Clinical Global Impression of Improvement scale served as the anchor. The Receiver Operating Characteristic (ROC) curve was employed to identify the best MID cut-off point for BBS, POMA, and DGI. In the distribution-based approach, one-third standard deviation (SD), half SD, one standard error of measurement (SEM), and the total score of BBS, POMA and DGI were used to determine the MID. ResultsThe MID from the ROC curve was greater than 2 points for BBS, greater than 1 point for POMA and DGI. For the distribution-based approach, the MIDs corresponding to one-third of the SD, half of the SD, and one SEM for BBS were 1.92, 3.20, and 0.90; for POMA were 1.47, 2.45, and 1.96; for DGI were 1.48, 2.47, and 1.16 points, respectively. ConclusionBBS, POMA and DGI are suitable instruments for assessing functional balance in individuals with chronic stroke, with demonstrable MID. Additionally, the results indicated that DGI has higher sensitivity and specificity than the other examined scales for distinguishing between groups without change and those with minimal balance improvement after receiving interventions.

Estimating minimal clinically important difference (MCID) for gastrointestinal symptoms in cystic fibrosis

BackgroundMinimal clinically important difference (MCID) is important to establish as a meaningful outcome in research when using patient reported outcome measures (PROMs). We determined the MCID using the distribution-based approach for three measurements used as part of the GALAXY study, which is an observational prospective study on gastrointestinal (GI) symptoms in cystic fibrosis (CF). MethodsFour hundred and two persons with cystic fibrosis (PwCF) participated in the GALAXY study, all with baseline values available for all questionnaires. Mean age was 20.9 years (2.1- 61.1) with 75 females and 94 males under the age of 18 (42.04 %) and 118 females and 115 males aged 18 or older (57.99 %). MCID was measured for Patient Assessment of Constipation Symptoms (PAC-SYM), Patient Assessment of Upper Gastrointestinal Symptoms (PAGI-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL) and their subscales. Two distribution-based approaches, defined as multiplications of the standard deviation (SD) or standard error of the mean (SEM), were used to approximate the MCID. ResultsThe two distribution-based approaches for determining the MCID estimates produced comparable results in trends in MCIDs across the subscales and total scores. In general, MCID estimates of subscales for all three measurements were higher than their total score MCIDs. The one-half SD- and SEM-based MCID estimates for total scores of each questionnaire are as follows: PAC-SYM: 0.26 and 0.14; PAGI-SYM: 0.32 and 0.15; PAC-QOL: 0.27 and 0.18, respectively. ConclusionThis paper establishes initial MCIDs estimated by the distribution-based approach for the PAC-SYM, PAGI-SYM and PAC-QOL that can now be used to evaluate interventional studies that may impact gastrointestinal symptoms in PwCF.

Finding continuers in Swedish Sign Language

Abstract In this paper, I use methods from corpus linguistics and computer vision to find candidates for continuers – that is, conversational markers that signal comprehension and encouragement to the primary speaker/signer to continue – in a corpus of Swedish Sign Language (STS). Using different methods based on distributional patterns in conversational turns, I identify a small set of manual signs – particularly the sign JA@ub ‘yes’ – that exhibit the characteristics associated with continuers, such as occurring frequently in repeated sequences of overlapping but noncompetitive turns. The identified signs correspond to those found in previous research on manual backchannels in STS, demonstrating that quantitative, distribution-based approaches are successful in identifying continuers. In a second step, I employ methods from computer vision to analyze a subset of the corpus videos, and find that the continuer candidates show interesting form characteristics: they are small in visible articulation and thus conversationally unobtrusive by often being articulated low and with little movement in signing space. The results show that distribution-based approaches can be used successfully with sign language corpus data, and that the nature of continuers exhibits similarities across modalities of human language.

Establishing minimal clinically important differences and patient acceptable symptom state thresholds following birmingham hip resurfacing

IntroductionBirmingham Hip Resurfacing (BHR) has emerged as a compelling and innovative alternative to total hip arthroplasty (THA), especially among young, active patients. However, the Minimal Clinically Important Difference (MCID) and the Patient Acceptable Symptom State (PASS) thresholds have not yet been determined for patients undergoing BHR. Therefore, the current study aimed to (1) determine the MCID and PASS thresholds for both the Hip disability and Osteoarthritis Outcome Score (HOOS)-Pain and HOOS physical function shortform (PS), for patients who underwent BHR; and (2) identify factors influencing the achievement of MCID and PASS for HOOS-Pain and HOOS-PS.MethodsProspectively collected data from patients undergoing BHR was analyzed. Patients with osteoarthritis and completed preoperative and 1-year postoperative PROMs were included. Distribution-based and anchored-based approaches were used to estimate MCID and PASS, respectively. The optimal cut-off point for PASS thresholds was calculated using the Youden index.ResultsMCID for HOOS-Pain and PS were calculated to be 9.2 and 9.3, respectively. The PASS threshold for HOOS-Pain and PS were ≥ 77.7 and ≥ 87.3, respectively. The current study identified several factors affecting postoperative achievement of thresholds. Baseline Mental Component Summary (MCS) scores were a predictor for achieving MCID for postoperative HOOS-Pain, achieving MCID for postoperative HOOS-PS, achieving PASS for postoperative HOOS-Pain, and achieving PASS for postoperative HOOS-PS. Furthermore, baseline HOOS-Pain was a significant predictor for achieving MCID for postoperative HOOS-PS, achieving PASS for postoperative HOOS-Pain, and achieving PASS for postoperative HOOS-PS.ConclusionsMCID and PASS thresholds were established for HOOS-Pain and PS domains following BHR with most patients achieving these clinically meaningful benchmarks. Additionally, several factors affecting achievement of MCID and PASS were identified, including modifiable risk factors that may allow clinicians to implement optimization strategies and further improve outcomes.

Incorporating vertical movement of fishes in habitat use models.

Fish telemetry studies now routinely collect positional and depth data, yet analytical approaches that integrate three-dimensional data are limited. Here we apply the potential path volume (PPV) model, a method previously developed to estimate habitat volume based on rates of avian movement, to free-swimming fish. Using a telemetry dataset of white sucker (Catastomus commersonii) from Turkey Lake (Ontario, Canada), we evaluated the effects of the number of spatial positions and different methods of selecting swim speed (vswim), a key parameter for PPV models, on habitat volume estimates. We subsequently compared habitat volume estimates and habitat overlap among white sucker pairs from the PPV models to those calculated using kernel utilization distribution-based approaches. The number of spatial positions in the PPV model had a significant effect on habitat volume estimates, whereas the magnitude of the vswim parameter or its specificity (constant value vs. fish-season specific parameter values) did not affect habitat volume estimates. The PPV method resulted in larger habitat volume estimates and greater habitat overlap estimates among fish pairs relative to those obtained from a three-dimensional kernel utilization distribution method. The PPV model is a useful analytical tool that, by incorporating potential animal movement into habitat use evaluations, can help answer key ecological questions and provide insight into fish space use in a wide range of conservation and management applications.

Poster 306: Establishing the Minimum Clinically Important Difference Two Years Following Medial Patellofemoral Ligament Reconstruction

Objectives: Medial patellofemoral ligament (MPFL) reconstruction is used to address cases of recurrent patellar instability. Minimal clinically important difference (MCID) is an important marker that relays the smallest clinical improvement in which patients feel a significant change after surgery. MCID has been previously established for MPFL reconstruction after 6 months and 1 year. To date, no study has established MCID for patient reported outcomes 2 years after MPFL reconstruction. The purpose of this study is to define the MCID for the Kujala, International Knee Documentation Committee (IKDC), and Knee Injury and Osteoarthritis Outcome Score for Joint Reconstruction (KOOS JR) at minimum two-year follow-ups after isolated MPFL reconstruction. Methods: All patients undergoing isolated MPFL reconstruction for recurrent patellar instability at a single institution between December 2015-June 2021 were included. Patients with concomitant osseous procedures beyond chondroplasty and any ligamentous procedure were excluded. A distribution-based approach was used to calculate the MCID. This was performed by determining the standard deviation (SD) of the delta two-year patient reported outcome scores (PROS) and then multiplying the SD by 0.5. The number of patients achieving MCID were then presented as a percentage. Results: Eighty-six of 117 patients who underwent isolated MPFL reconstruction completed preoperative and a two-year follow-up PRO survey (59 female, 27 male; age 21.1 ± 8.7 years). For Kujala, the preoperative mean was 59.3 ± 17.1, two-year follow-up mean was 87.6 ± 13.6, and MCID was 9.2 with 88% of the cohort achieving MCID. For IKDC, preoperative mean was 50.2 ± 17.2, two-year mean was 80.5 ± 18.6, and MCID was 12.4 with 80% of patients achieving MCID. KOOS JR had a preoperative man of 66.0 ± 14.6, two-year follow-up mean of 88.8 ± 11.9, and MCID of 8.5 with 72% of patients meeting this MCID (Figure 1). Conclusions: At two years following MPFL reconstruction, the MCID’s for clinically relevant subjective PROS were 9.2 (Kujala), 12.5 (IKDC), and 8.5 (KOOS JR). MCID’s for MPFL reconstruction are already established for 6-month and 1-year time points, and this was the first presentation of two-year MCID values. Establishing the 2-year MCID for MPFL reconstruction gives surgeons another tool to use in the diagnoses of patellar instability patients who may be struggling post-operatively.

MEDi-SOL: Multi Ensemble Distribution Model for Estimating Sleep Onset Latency.

Sleep onset latency (SOL) is an important factor relating to the sleep quality of a subject. Therefore, accurate prediction of SOL is useful to identify individuals at risk of sleep disorders and to improve sleep quality. In this study, we estimate SOL distribution and falling asleep function using an electroencephalogram (EEG), which can measure the electric field of brain activity. We proposed a Multi Ensemble Distribution model for estimating Sleep Onset Latency (MEDi-SOL), consisting of a temporal encoder and a time distribution decoder. We evaluated the performance of the proposed model using a public dataset from the Sleep Heart Health Study. We considered four distributions, Normal, log-Normal, Weibull, and log-Logistic, and compared them with a survival model and a regression model. The temporal encoder with the ensemble log-Logistic and log-Normal distribution showed the best and second-best scores in the concordance index (C-index) and mean absolute error (MAE). Our MEDi-SOL, multi ensemble distribution with combining log-Logistic and log-Normal distribution, shows the best score in C-index and MAE, with a fast training time. Furthermore, our model can visualize the process of falling asleep for individual subjects. As a result, a distribution-based ensemble approach with appropriate distribution is more useful than point estimation.

Responsiveness and Minimal Clinically Important Difference of the Canadian Occupational Performance Measure Among Patients With Frozen Shoulder.

Patient-reported outcome measures provide insights into intervention effects on patients. The Canadian Occupational Performance Measure (COPM) emphasizes identifying priorities in daily activity engagement and evaluating an individual's perception of changes over time. To assess the responsiveness of the COPM and the minimal clinically important difference (MCID) among patients with frozen shoulders. Prospective, single-blind, randomized controlled trial. Two physical medicine and rehabilitation clinics. Ninety-four patients with frozen shoulders enrolled in a previous study. Baseline and 3-mo evaluations of the COPM and other measures. Responsiveness was assessed using effect size (ES) and standardized response mean (SRM). The MCID values were determined through a distribution-based approach, which used the 0.5 standard deviation and ES methods, and an anchor-based approach, which used the receiver operating characteristic curve method. The ES and SRM results indicated that the COPM had high responsiveness. The distribution-based MCID values for COPM Performance and COPM Satisfaction were 1.17 and 1.44, respectively. The anchor-based MCID values were 2.5 (area under the curve [AUC] = 0.78, 95% confidence interval [CI] [0.64-0.91]) and 2.1 (AUC = 0.76, 95% CI [0.60-0.91]), respectively. The findings suggest that the COPM is a responsive outcome measure for patients with frozen shoulder. The established MCID values for the COPM can be valuable for interpreting changes in patient performance and satisfaction, thus aiding clinical interventions and research planning. Plain-Language Summary: This is the first study to review the effectiveness of the Canadian Occupational Performance Measure (COPM) to determine the success of occupational therapy interventions for people with a frozen shoulder. The findings suggest that the COPM is an effective and valuable tool for clients with a frozen shoulder to understand their experiences and treatment priorities and to detect meaningful changes in their performance and satisfaction after an occupational therapy intervention.

Worst Itch Numeric Rating Scale for Prurigo Nodularis

Prurigo nodularis (PN) is a debilitating skin disease characterized by the hallmark symptom of chronic itch; the intensity of itch in PN was assessed using the Worst Itch Numeric Rating Scale (WI-NRS) to evaluate the primary efficacy end point of 2 recent phase 3 studies of dupilumab treatment for PN. To validate the psychometric properties and to determine the clinically meaningful improvement threshold for WI-NRS in patients with moderate to severe PN. In this secondary analysis of the PRIME and PRIME2 trials, content validity of WI-NRS was assessed through in-depth patient interviews. Psychometric assessments used pooled data from masked, intention-to-treat (ITT) patients with PN from randomized, double-masked, and placebo-controlled studies. Psychometric assessments included test-retest reliability, construct validity, known-groups validity, and sensitivity to change in adult patients with moderate-to-severe PN. Thresholds for meaningful within-patient improvement in the WI-NRS score were determined using anchor and distribution-based approaches. Data were analyzed after completion of each study, December 2019 to November 2021 for PRIME and January 2020 to August 2021 for PRIME2. Dupilumab (300 mg) or placebo subcutaneously every 2 weeks for 24 weeks. WI-NRS score at specified time points up to 24 weeks after randomization. A total of 20 patients were included across the 2 studies (mean [SD] age, 49.3 [17.2] years; 11 female [55%]); 311 patients were included in the pooled intention-to-treat analysis (mean [SD] age, 49.5 [16.1] years; 203 female [65.3%]). The WI-NRS questions (20 of 20 patients), recall period (19 of 20 patients), and response scale (20 of 20 patients) were easy to understand and relevant for patients with PN. Adequate test-retest reliability was observed between screening and baseline (intraclass correlation coefficient = 0.72, using Patient Global Impression of Severity [PGIS] to define stable patients). Convergent and discriminant validity was supported by moderate to strong correlations (absolute r range = 0.34-0.73) with other conceptually related measures and weaker correlations (absolute r range = 0.06-0.32) with less-related measures, respectively. WI-NRS was sensitive to change, as demonstrated by differences in change from baseline among groups (per PGIS change and PGI of Change [PGIC]). Using anchor-based approach with PGIS and PGIC, the clinically meaningful improvement threshold was 4 points (range, 3.0-4.5), which was also supported by distribution-based methods. This study found that WI-NRS may be a fit-for-purpose instrument to support efficacy end points measuring the intensity of itching in adults with PN. NCT04183335 (PRIME) and NCT04202679 (PRIME2).

TENDINopathy Severity assessment–Achilles (TENDINS-A): evaluation of reliability and validity in accordance with COSMIN recommendations

ObjectiveTo evaluate the construct validity (structural validity and hypothesis testing), reliability (test–retest reliability, measurement error and internal consistency) and minimal important change (MIC) of the 13-item TENDINopathy Severity assessment–Achilles (TENDINS-A).MethodsParticipants...

Transcriptomic point of departure determination: a comparison of distribution-based and gene set-based approaches.

A key step in assessing the potential human and environmental health risks of industrial and agricultural chemicals is to determine the toxicity point of departure (POD), which is the highest dose level that causes no adverse effect. Transcriptomic POD (tPOD) values have been suggested to accurately estimate toxicity POD values. One step in the most common approach for tPOD determination involves mapping genes to annotated gene sets, a process that might lead to substantial information loss particularly in species with poor gene annotation. Alternatively, methods that calculate tPOD values directly from the distribution of individual gene POD values omit this mapping step. Using rat transcriptome data for 79 molecules obtained from Open TG-GATEs (Toxicogenomics Project Genomics Assisted Toxicity Evaluation System), the hypothesis was tested that methods based on the distribution of all individual gene POD values will give a similar tPOD value to that obtained via the gene set-based method. Gene set-based tPOD values using four different gene set structures were compared to tPOD values from five different individual gene distribution methods. Results revealed a high tPOD concordance for all methods tested, especially for molecules with at least 300 dose-responsive probesets: for 90% of those molecules, the tPOD values from all methods were within 4-fold of each other. In addition, random gene sets based upon the structure of biological knowledge-derived gene sets produced tPOD values with a median absolute fold change of 1.3-1.4 when compared to the original biological knowledge-derived gene set counterparts, suggesting that little biological information is used in the gene set-based tPOD generation approach. These findings indicate using individual gene distributions to calculate a tPOD is a viable and parsimonious alternative to using gene sets. Importantly, individual gene distribution-based tPOD methods do not require knowledge of biological organization and can be applied to any species including those with poorly annotated gene sets.

Establishing the minimal clinically important difference of the Brief Fatigue Inventory for brain or CNS cancer patients undergoing radiotherapy.

Minimal clinically important differences (MCIDs) quantify the clinical relevance of quality of life results at the individual patient and group level. The aim of this study was to estimate the MCID for the Brief Fatigue Inventory (BFI) and the Worst and Usual Fatigue items in patients with brain or CNS cancer undergoing curative radiotherapy. Data from a multi-site prospective registry was used. The MCID was calculated using distribution-based and anchor-based approaches. For the anchor-based approach, the fatigue item from the PROMIS-10 served as the anchor to determine if a patient improved, deteriorated, or had no change from baseline to end of treatment (EOT). We compared the unadjusted means on the BFI for the 3 groups to calculate the MCID. For the distribution-based approaches, we calculated the MCID as 0.5 SD of the scores and as 1.96 times the standard error of measurement. Three-hundred and fifty nine patients with brain or CNS tumors undergoing curative radiotherapy filled out the 9-item BFI at baseline and EOT. The MCID for the BFI was 1.33 (ranging from 0.99 to 1.70 across the approaches), 1.51 (ranging from 1.16 to 2.02) and 1.76 (ranging from 1.38 to 2.14) for the usual and worst fatigue items, respectively. This study provides the MCID ranges for the BFI and Worst and Usual fatigue items, which will allow clinically meaningful conclusions to be drawn from BFI scores. These results can be used to select optimal treatments for patients with brain or CNS cancer or to interpret BFI scores from clinical trials.

Determining minimal clinically important differences in the Hammersmith Functional Motor Scale Expanded for untreated spinal muscular atrophy patients: An international study.

Spinal muscular atrophy (SMA) is a rare and progressive neuromuscular disorder with varying severity levels. The aim of the study was to calculate minimal clinically important difference (MCID), minimal detectable change (MDC), and values for the Hammersmith Functional Motor Scale Expanded (HFMSE) in an untreated international SMA cohort. The study employed two distinct methods. MDC was calculated using distribution-based approaches to consider standard error of measurement and effect size change in a population of 321 patients (176 SMA II and 145 SMA III), allowing for stratification based on age and function. MCID was assessed using anchor-based methods (receiver operating characteristic [ROC] curve analysis and standard error) on 76 patients (52 SMA II and 24 SMA III) for whom the 12-month HFMSE could be anchored to a caregiver-reported clinical perception questionnaire. With both approaches, SMA type II and type III patients had different profiles. The MCID, using ROC analysis, identified optimal cutoff points of -2 for type II and -4 for type III patients, whereas using the standard error we found the optimal cutoff points to be 1.5 for improvement and -3.2 for deterioration. Furthermore, distribution-based methods uncovered varying values across age and functional status subgroups within each SMA type. These results emphasize that the interpretation of a single MCID or MDC value obtained in large cohorts with different functional status needs to be made with caution, especially when these may be used to assess possible responses to new therapies.

Clinical Significance Thresholds in Primary and Revision Latarjet Procedures With Comparable Outcome Achievements

Background: Given the variability across populations and settings, defining the MCID and the PASS for the Rowe and ASOSS scores and patients undergoing primary and revision Latarjet it is essential to have accurate benchmarks relevant to these groups when interpreting clinical results. Purpose: To determine the minimal clinically important difference (MCID) and Patient Acceptable Symptom State (PASS) thresholds for the visual analog scale (VAS) for pain during sports, Athletic Shoulder Outcome Scoring System (ASOSS), and Rowe scores after primary and revision Latarjet procedures for treatment of shoulder instability. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: Between January 2018 and January 2020, a retrospective review of 149 patients undergoing primary Latarjet (n = 82) and revision Latarjet (n = 67) to treat shoulder instability was performed in a single institution. Patient-reported outcome measures were collected preoperatively and 1 year postoperatively. The delta was defined as the change between the pre- and postoperative scores. Distribution-based and anchored-based approaches were used to estimate the MCID and the PASS, respectively. The optimal cutoff point and the percentage of patients achieving those thresholds were also calculated. Results: The distribution-based MCIDs after primary Latarjet were 1.1, 7.5, and 9.6 for the VAS, Rowe, and ASOSS scores, respectively. The rates of patients who achieved the MCID thresholds were 93.9%, 98.7%, and 100% for the VAS, Rowe, and ASOSS scores, respectively. The PASS thresholds after primary Latarjet were ≤1, ≥90, and ≥85 for the VAS, Rowe, and ASOSS scores, respectively. The percentages of patients who achieved PASS thresholds were 82.9%, 89%, and 86.5% for the VAS, Rowe, and ASOSS scores, respectively. The distribution-based MCIDs after revision Latarjet were 0.6, 6.2, and 3.4 for the VAS, Rowe, and ASOSS scores, respectively. The rates of patients who achieved MCID thresholds were 89.3%, 100%, and 100% for the VAS, Rowe, and ASOSS scores, respectively. The PASS thresholds were ≤3, ≥87, and ≥86 after revision Latarjet for the VAS, Rowe, and ASOSS scores, respectively. The rates of patients who achieved the PASS thresholds were 88%, 88%, and 91% for the VAS, Rowe, and ASOSS, respectively. Conclusion: This study identified useful values for the MCID and PASS thresholds in VAS, Rowe, and ASOSS scores after primary and revision Latarjet procedures for treating shoulder instability. Most patients achieved MCID and PASS benchmarks, indicating successful primary and revision Latarjet procedure outcomes. These metrics can serve as valuable parameters when analyzing parameters in future studies and have the potential to enhance patient care by optimizing treatment strategies and surgical decision making.

Responsiveness and minimal important change of the Family Reported Outcome Measure (FROM-16)

BackgroundThe FROM-16 is a generic family quality of life (QoL) instrument that measures the QoL impact of patients’ disease on their family members/partners. The study aimed to assess the responsiveness of FROM-16 to change and determine Minimal Important Change (MIC).MethodsResponsiveness and MIC for FROM-16 were assessed prospectively with patients and their family members recruited from outpatient departments of the University Hospital Wales and University Hospital Llandough, Cardiff, United Kingdom. Patients completed the EQ-5D-3L and a global severity question (GSQ) online at baseline and at 3-month follow-up. Family members completed FROM-16 at baseline and a Global Rating of Change (GRC) in addition to FROM-16 at follow-up. Responsiveness was assessed using the distribution-based (effect size-ES, standardized response mean -SRM) and anchor-based (area under the receiver operating characteristics curve ROC-AUC) approaches and by testing hypotheses on expected correlation strength between FROM-16 change score and patient assessment tools (GSQ and EQ-5D). Cohen’s criteria were used for assessing ES. The AUC ≥ 0.7 was considered a good measure of responsiveness. MIC was calculated using anchor-based (ROC analysis and adjusted predictive modelling) and distribution methods based on standard deviation (SD) and standard error of the measurement (SEM).ResultsEighty-three patients with 15 different health conditions and their relatives completed baseline and follow-up questionnaires and were included in the responsiveness analysis. The mean FROM-16 change over 3 months = 1.43 (SD = 4.98). The mean patient EQ-5D change over 3 months = −0.059 (SD = 0.14). The responsiveness analysis showed that the FROM-16 was responsive to change (ES = 0.2, SRM = 0.3; p < 0.01). The ES and SRM of FROM-16 change score ranged from small (ES = 0.2; SRM = 0.3) for the distribution-based method to large (ES = 0.8, SRM = 0.85) for anchor-based methods. The AUC value was above 0.7, indicating good responsiveness. There was a significant positive correlation between the FROM-16 change scores and the patient’s disease severity change scores (p < 0.001). The MIC analysis was based on data from 100 family members of 100 patients. The MIC value of 4 was suggested for FROM-16.ConclusionsThe results of this study confirm the longitudinal validity of FROM-16 which refers to the degree to which an instrument is able to measure change in the construct to be measured. The results yield a MIC value of 4 for FROM-16. These psychometric attributes of the FROM-16 instrument are useful in both clinical research as well as clinical practice.

Estimating the Minimal Clinically Important Difference on the Visual Analogue Scale for Carpometacarpal Thumb Joint Osteoarthritis.

The minimal clinically important difference (MCID) is the smallest perceived treatment effect that patients deem clinically significant. There is currently no agreement on an appropriate MCID for the pain visual analogue scale (VAS) in the context of thumb osteoarthritis (OA). We approximated MCIDs using a distribution-based approach that pooled standard deviations (SDs) associated with baseline mean values of the pain VAS (0-100 mm). We extracted the data from randomized controlled trials (RCTs) included in a systematic review of adults with long-term OA of the thumb. We excluded RCTs that did not report baseline SD values. The MCIDs were derived at 0.4 and 0.5 SDs of the pooled SD and compared with previously published MCIDs for the pain VAS in OA. A total of 403 patients were pooled from 7 RCTs for the analysis. The mean baseline VAS pain score was 5.6 cm. We derived an MCID of 0.72 cm at 0.4 SDs and 0.91 cm at 0.5 SDs using baseline SDs. We found that MCIDs derived from a distribution-based approach approximated published MCIDs for the VAS for pain for OA in the knee and hip. The authors propose that a change of 0.7 to 0.9 cm on the VAS is clinically meaningful in the context of long-term OA of the thumb.