Distribution-based Methods Research Articles

Minimum clinical important difference for resilience scale specific to cancer: a prospective analysis

BackgroundThe minimum clinical important differences (MCIDs) of resilience instruments in patients with cancer have not been comprehensively described.This study was designed to evaluate MCIDs of 10-item and 25-item resilience scales specific to cancer (RS-SC-10 and RS-SC-25).MethodsFrom June 2015 to December 2018, RS-SCs were longitudinally measured in 765 patients with different cancer diagnoses at baseline (T0) and 3 months later (T1). The EORTC QLQ-C30, Connor-Davidson Resilience Scale, Hospital Anxiety and Depression Scale, and Allostatic Load Index were measured concurrently as anchors. Anchor-based methods (linear regression, within-group), distribution-based methods(within-group), and receiver operating characteristic curves (ROCs, within-subject) were performed to evaluate the MCIDs.Results623 of 765 (84.1%) patients had paired RS-SCs scores. Moderate correlations were identified between the change in RS-SCs and change in anchors (r = 0.38–0.44, all p < 0.001). Linear regression estimated + 8.9 and − 6.7 as the MCIDs of RS-SC-25, and + 3.4 and − 2.5 for RS-SC-10. Distribution-based methods estimated + 9.9 and − 9.9 as the MCIDs of RS-SC-25, and + 4.0 and − 4.0 for RS-SC-10. ROC estimated + 5.5 and − 4.5 as the MCIDs of RS-SC-25, and + 2.0 and − 1.5 for RS-SC-10.ConclusionsThe most reliable MCID is around 5 points for RS-SC-25 and 2 points for RS-SC-10. RS-SCs are more responsive to the worsening status of resilience in patients with cancer and these estimates could be useful in future resilience-based intervention trials.

PNS238 Is There a Need for a Consensus on How to Synthesize a Single Meaningful within-Patient Change Threshold from Different Sources?

Determining a meaningful within-patient change (”responder”) threshold is key to interpret patient-reported outcome (PRO) data. There are numerous methods to estimate responder thresholds, including distribution-based methods (e.g., 0.5 standard deviation), anchor-based methods (using patient-reported and clinical biomarker anchors), and qualitative methods. Most authors use a combination of methods, which often results in several responder thresholds that may be similar but not numerically identical. We were interested in examining how authors synthesized thresholds derived using different sources into a single one. A targeted literature review of methods used to derive a single responder threshold derived from multiple methods was conducted using PubMed, Embase, and the websites of several congresses, and of regulatory and payer bodies. Searches were limited to the last 15 years with no geographic restrictions. The searches identified 596 unique publications; 22 were included in the review. There is no consensus on the optimal method or rationale to be applied to derive a single responder threshold. Three methods were proposed in the reviewed studies: (1) hierarchical integration of anchor-based and distribution-based approaches (with the former and ROC-derived thresholds given more weight and distribution-based thresholds used only to confirm the others), (2) graphical display of threshold estimates with the highest value often being selected for primary analysis and (3) triangulation methodology without weighting. The latter shares the same approach as the first method but is also applicable to qualitative-derived thresholds. A commonality across these three methods is their subjectivity and the need for critical review of the adequacy of the different threshold sources and of impact of false positives and false negatives before a threshold is selected. There is no established best practice to derive a single threshold. It would facilitate the field of PRO research greatly if a preferred method could be agreed.

Do Self-Reported Drug Allergies Influence Clinically Significant Outcome Improvement Following Osteochondral Allograft Transplantation? A Nested Cohort Study.

To compare clinical outcomes for patients who underwent osteochondral allograft transplantation (OCA) based on the presence or absence of one or more self-reported drug allergies. Prospective data were collected from 245 consecutive patients after OCA of the knee from one large academic institution. Patient-reported allergies were obtained via chart review. Patient-reported outcome measures, including activities of daily living of the Knee Outcome Survey (KOS-ADL), Marx Activity Scale, International Knee Documentation Committee (IKDC), and visual analogue scale (VAS) pain were all collected. The minimal clinically important difference (MCID) for each outcome was quantified using a distribution-based method. Independent t tests were used to compare patient-reported outcome measures between those with and without self-reported allergies, while chi-square analysis of association was used to compare rates of MCID achievement. Of 245 patients included, 83 (33.9%) reported having at least one drug allergy at the time of OCA. There were no statistically significant differences with regard to patient demographics, including age, body mass index, gender, or sports participation between those with and without a reported allergy. Similarly, there were no significant differences found between baseline preoperative patient-reported outcomes. Overall, both cohorts demonstrated a significant improvement from baseline scores at 2 years postoperatively. There were no differences found between any patient-reported outcome at 2 years postoperatively. The presence of at least one self-reported drug allergy was not a significant risk factor for failing to achieve the MCID in any specific outcome measure. The presence of one or more drug allergy was not associated with worse patient-reported outcomes or lower rates of clinically significant outcome improvement after OCA.

On the class overlap problem in imbalanced data classification

Class imbalance is an active research area in the machine learning community. However, existing and recent literature showed that class overlap had a higher negative impact on the performance of learning algorithms. This paper provides detailed critical discussion and objective evaluation of class overlap in the context of imbalanced data and its impact on classification accuracy. First, we present a thorough experimental comparison of class overlap and class imbalance. Unlike previous work, our experiment was carried out on the full scale of class overlap and an extreme range of class imbalance degrees. Second, we provide an in-depth critical technical review of existing approaches to handle imbalanced datasets. Existing solutions from selective literature are critically reviewed and categorised as class distribution-based and class overlap-based methods. Emerging techniques and the latest development in this area are also discussed in detail. Experimental results in this paper are consistent with existing literature and show clearly that the performance of the learning algorithm deteriorates across varying degrees of class overlap whereas class imbalance does not always have an effect. The review emphasises the need for further research towards handling class overlap in imbalanced datasets to effectively improve learning algorithms’ performance.

The Effect of Travel Distance on Outcomes for Hip Resurfacing Arthroplasty at a High-Volume Center

BackgroundPatients are increasingly traveling greater distances to receive care at high-volume centers. The effect of travel distance on patient-reported outcomes after hip resurfacing arthroplasty has not been described. MethodsPatients undergoing HRA by a single surgeon from January 2007 to April 2018 with minimum 2-year follow-up were reviewed retrospectively. Five hundred ninety-nine patients were identified and divided into 2 cohorts: home-to-hospital distance >100 miles and ≤100 miles from our institution. Preoperative and 2-year postoperative patient-reported outcome measures (PROMs) were assessed, including the modified Harris Hip Score and Hip disability and Osteoarthritis Outcome Score. The minimal clinically important difference (MCID) for each PROM was calculated using the distribution-based method. Chi-square tests were used for univariate comparison. Poisson regressions controlling for demographic variables were performed to determine the effect of travel distance on whether patients achieved the MCID. Multivariate linear regressions were used to determine association between distance and improvement in PROMs. ResultsA total of 599 patients met criteria for inclusion. There were 113 (18.9%) with a home-to-hospital distance >100 miles and 486 (81.1%) with distance ≤100 miles. Age was the only demographic factor different between these groups (mean: 1.1-year difference, P < .001). There were no significant differences in reaching the MCID on any PROM between these groups. Multivariate linear regressions revealed no associations between travel distance and improvement in PROMs. ConclusionsTravel distance to a high-volume center did not affect 2-year patient-reported outcomes or rate of achieving the MCID in patients undergoing hip resurfacing arthroplasty.

Determining the Minimal Clinical Important Difference for Medication Quantification Scale III and Morphine Milligram Equivalents in Patients with Failed Back Surgery Syndrome.

The Medication Quantification Scale III (MQS) is a tool to represent the negative impact of medication. A reduction in medication can serve as an indicator to evaluate treatment success. However, no cut-off value has yet been determined to evaluate whether a decrease in medication is clinically relevant. Therefore, the objective is to estimate the thresholds for the MQS and morphine milligram equivalents (MMEs) that best identify a clinically relevant important improvement for patients. Data from the Discover registry, in which patients with failed back surgery syndrome were treated with high-dose spinal cord stimulation, were used. Patient satisfaction was utilized to evaluate a clinically important outcome 12 months after stimulation. Anchor-based and distribution-based methods were applied to determine the minimal clinical important difference (MCID). Distribution-based methods revealed a value of 4.28 for the MQS and 33.61 for the MME as MCID. Anchor-based methods indicated a percentage change score of 41.2% for the MQS and 28.2% for the MME or an absolute change score of 4.72 for the MQS and 22.65 for the MME. For assessing a treatment outcome, we recommend using the percentage change score, which better reflects a clinically important outcome and is not severely influenced by high medication intake at baseline.

Peripheral Neuropathy Symptoms, Pain and Functioning in Relapsed or Refractory Multiple Myeloma Patients Treated with Selinexor, Bortezomib, and Dexamethasone

Peripheral Neuropathy Symptoms, Pain and Functioning in Relapsed or Refractory Multiple Myeloma Patients Treated with Selinexor, Bortezomib, and Dexamethasone

Health-Related Quality of Life in Patients with AL Amyloidosis Treated with Daratumumab, Bortezomib, Cyclophosphamide, and Dexamethasone: Results from the Phase 3 Andromeda Study

Health-Related Quality of Life in Patients with AL Amyloidosis Treated with Daratumumab, Bortezomib, Cyclophosphamide, and Dexamethasone: Results from the Phase 3 Andromeda Study

DREAMM-2: Single-Agent Belantamab Mafodotin (Belamaf) Effects on Patient-Reported Outcome (PRO) Measures in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)

DREAMM-2: Single-Agent Belantamab Mafodotin (Belamaf) Effects on Patient-Reported Outcome (PRO) Measures in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)

Development of prediction models for clinically meaningful improvement in PROMIS scores after lumbar decompression

The ability to preoperatively predict which patients will achieve a minimal clinically important difference (MCID) after lumbar spine decompression surgery can help determine the appropriateness and timing of surgery. Patient-Reported Outcome Measurement Information System (PROMIS) scores are an increasingly popular outcome instrument. The purpose of this study was to develop algorithms predictive of achieving MCID after primary lumbar decompression surgery. This was a retrospective study at two academic medical centers and three community medical centers including adult patients 18 years or older undergoing one or two level posterior decompression for lumbar disc herniation or lumbar spinal stenosis between January 1, 2016 and April 1, 2019. The primary outcome, MCID, was defined using distribution-based methods as one half the standard deviation of postoperative patient-reported outcomes (PROMIS physical function, pain interference, pain intensity). Five machine learning algorithms were developed to predict MCID on these surveys and assessed by discrimination, calibration, Brier score, and decision curve analysis. The final model was incorporated into an open access digital application. Overall, 906 patients completed at least one PROMs survey in the 90 days before surgery and at least one PROMs survey in the year after surgery. Attainment of MCID during the study period by PROMIS instrument was 74.3% for physical function, 75.8% for pain interference, and 79.2% for pain intensity. Factors identified for preoperative prediction of MCID attainment on these outcomes included preoperative PROs, percent unemployment in neighborhood of residence, comorbidities, body mass index, private insurance, preoperative opioid use, surgery for disc herniation, and federal poverty level in neighborhood of residence. The discrimination (c-statistic) of the final algorithms for these outcomes was 0.79 for physical function, 0.74 for pain interference, and 0.69 for pain intensity with good calibration. The open access digital application for these algorithms can be found here: https://sorg-apps.shinyapps.io/promis_pld_mcid/ CONCLUSION: Lower preoperative PROMIS scores, fewer comorbidities, and certain sociodemographic factors increase the likelihood of achieving MCID for PROMIS after lumbar spine decompression.

Establishing the Minimal Clinically Important Difference, Patient Acceptable Symptomatic State, and Substantial Clinical Benefit of the PROMIS Upper Extremity Questionnaire After Rotator Cuff Repair

Background: The Patient-Reported Outcome Measurement Information System Upper Extremity (PROMIS UE) questionnaire has been validated as an effective and efficient outcome measure after rotator cuff repair (RCR). However, definitions of clinically significant outcomes used in interpreting this outcome measure have yet to be defined. Purpose: To define clinically significant outcomes of the PROMIS UE questionnaire in patients undergoing arthroscopic RCR. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: We reviewed charts of consecutive patients undergoing RCR in our institution between 2017 and 2018 and included patients who were administered the PROMIS UE before surgery and 12 months after surgery. At 12 months postoperatively, patients were asked domain-specific anchor questions regarding their function and satisfaction after surgery, which were then used to determine the minimal clinically important difference (MCID), Patient Acceptable Symptomatic State (PASS), and substantial clinical benefit (SCB) using receiver operating characteristic and area under the curve (AUC) analysis. Univariate and multivariate logistic regression analysis was utilized to identify patient factors associated with clinically significant outcomes. Results: A total of 105 patients with RCR and minimum 12-month postoperative PROMIS UE were included in the analysis. The defined clinically significant outcomes were 4.87 for the MCID using a distribution-based method, 7.95 for the SCB (sensitivity, 0.708; specificity, 0.833; AUC, 0.760), and 39.00 for the PASS (sensitivity, 0.789; specificity, 0.720; AUC, 0.815). Among respondents, 79.0%, 62.9%, and 64.8% achieved the MCID, SCB, and PASS score thresholds, respectively. Workers’ compensation was negatively associated with achievement of the PASS. Lower preoperative PROMIS UE scores were associated with obtaining the MCID (odds ratio [OR], 0.871; P = .001) and the SCB (OR, 0.900; P = .040), whereas higher preoperative scores were predictive of achieving the PASS (OR, 1.111; P = .020). Conclusion: This study defines the clinically significant outcomes for the PROMIS UE after RCR, of which the majority of patients achieved the MCID, PASS, and SCB at 12 months after surgery. These thresholds should be considered in future study design and interpretation of PROMIS UE in patients with RCR.

When is Change Meaningful?: A Comparison of the MCID, MDC, and cMDC

To compare meaningful change of a co-calibrated six item cognition measure, CogMeas, for patients’ post-stroke using three different methods: (1) the minimally clinically important difference (MCID) using the distribution-based method, (2) minimal detectable change with 95% confidence intervals (MDC), and (3) conditional MDC95 (cMDC).

Estimating Minimal Clinically Important Differences for Knee Range of Motion after Stroke

The importance of knee sagittal kinematic parameters, as a predictor of walking performance in post-stroke gait has been emphasised by numerous researchers. However, no studies so far were designed to determine the minimal clinically important differences (MCID), i.e., the smallest difference in the relevant score for the kinematic gait parameters, which are perceived as beneficial for patients with stroke. Studies focusing on clinically important difference are useful because they can identify the clinical relevance of changes in the scores. The purpose of the study was to estimate the MCID for knee range of motion (ROM) in the sagittal plane for the affected and unaffected side at a chronic stage post-stroke. Fifty individuals were identified in a database of a rehabilitation clinic. We estimated MCID values using: an anchor-based method, distribution-based method, linear regression analysis and specification of the receiver operating characteristic (ROC) curve. In the anchor-based study, the mean change in knee flexion/extension ROM for the affected/unaffected side in the MCID group amounted to 8.48°/6.81° (the first MCID estimate). In the distribution-based study, the standard error of measurement for the no-change group was 1.86°/5.63° (the second MCID estimate). Method 3 analyses showed 7.71°/4.66° change in the ROM corresponding to 1.85-point change in the Barthel Index. The best cut-off point, determined with ROC curve, was the value corresponding to 3.9°/3.8° of change in the knee sagittal ROM for the affected/unaffected side (the fourth MCID estimate). We have determined that, in chronic stroke, MCID estimates of knee sagittal ROM for the affected side amount to 8.48° and for the unaffected side to 6.81°. These findings will assist clinicians and researchers in interpreting the significance of changes observed in kinematic sagittal plane parameters of the knee. The data are part of the following clinical trial: Australian New Zealand Clinical Trials Registry: ACTRN12617000436370

Estimation of minimal clinically important difference for quadriceps and inspiratory muscle strength in older outpatients with chronic obstructive pulmonary disease: a prospective cohort study.

To estimate the minimal clinically important difference (MCID) of quadriceps and inspiratory muscle strength after a home-based pulmonary rehabilitation program (PRP) in chronic obstructive pulmonary disease (COPD). Eighty-five COPD patients were included. Quadriceps maximal voluntary contraction (QMVC) was measured. We measured maximal inspiratory mouth pressure (PImax), the 6-minute walk distance (6MWD), the chronic respiratory questionnaire (CRQ) and the modified Medical Research Council dyspnoea score (mMRC). All measurements were conducted at baseline and at the end of the PRP. The MCID was calculated using anchor-based (using 6MWD, CRQ, and mMRC as possible anchor variables) and distribution-based (half standard deviation and 1.96 standard error of measurement) approaches. Changes in the five variables were compared in patients with and without changes in QMVC or PImax >MCID for each variable. Sixty-nine COPD patients (age 75±6 years) were analysed. QMVC improved by 2.4 (95%CI 1.1-3.7) kgf, PImax by 5.8 (2.7-8.8) cmH2O, 6MWD by 21 (11-32) meters and CRQ by 3.9 (1.6-6.3) points. The MCID of QMVC and PImax was 3.3-7.5 kgf and 17.2-17.6 cmH2O, respectively. The MCID of QMVC (3.3 kgf) could differentiate individuals with significant improvement in 6MWD and PImax from those without. The MCID of QMVC (3.3 kgf) can identify a meaningful change in quadriceps muscle strength after a PRP. The MCID of PImax (17.2 cmH2O) should be used with careful consideration, because the value is estimated using distributionbased method.

Surgeon-level variance in achieving clinical improvement after lumbar decompression: the importance of adequate risk adjustment

BACKGROUND CONTEXTPatient-Reported Outcome Measurement Information System (PROMIS) scores are increasingly utilized in clinical care. However, it is unclear if PROMIS can discriminate surgeon performance on an individual level. PURPOSEThe purpose of this study was to examine surgeon-level variance in rates of achieving minimal clinically important difference (MCID) after lumbar decompression. PATIENT SAMPLEThis is a prospective, observational cohort study performed across a healthcare enterprise (two academic medical centers and three community centers). Patients 18 years or older undergoing one- to two-level primary decompression for lumbar disc herniation (LDH) or lumbar spinal stenosis (LSS) were included. OUTCOME MEASURESThe primary outcome was achievement of MCID, using a distribution-based method, on paired PROMIS physical function scores. METHODSDescriptive statistics were generated to examine the baseline characteristics of the study cohort. Bivariate analyses were used to examine the impact of surgeon-level variance on rates of MCID. Multivariable analyses were used to examine the risk-adjusted impact of surgeon-level variance on rates of MCID. RESULTSOverall, 636 patients treated by nine surgeons were included. The median patient age was 58 [interquartile range (IQR): 46–70] and 62.3% (n=396) were female. Among all patients, 56.9% (n=362) underwent surgery for LDH. The overall rate of achieving MCID was 75.8% (n=482). Of the surgeons, the median years in practice were 12 (range 4–31) and 55.6% (n=5) were in academic practice settings. On bivariate analysis, patients treated by one of the surgeons had lower rates of achieving MICD (odds ratio=0.37, 95% confidence interval: 0.15–0.91, p=.03). However, on multivariable analysis adjusting for operative indication (LDH vs. LSS), body mass index, number of comorbidities, percent unemployment in patient zip code, and preoperative PROMIS physical function scores, all surgeons were equally likely to obtain MCID. CONCLUSIONSIn this cohort, variance in PROMIS scores after primary lumbar decompression is influenced by patient-related factors and not by individual surgeon. Adequate risk adjustment is needed if ascertaining clinical improvement on an individual surgeon basis. Level of Evidence2

Minimal Clinically Important Difference of the Loewenstein Occupational Therapy Cognitive Assessment-Geriatric (LOTCA-G) in People With Dementia.

The Loewenstein Occupational Therapy Cognitive Assessment-Geriatric (LOTCA-G) can provide multifaceted and comprehensive measures of cognitive function with reduced literacy demands; however, its minimal clinically important difference (MCID) has not been determined for interpreting the change scores. To establish the LOTCA-G MCID for people with dementia. Psychometric field study. Data were collected in communities. Forty-nine participants with mild to moderate dementia who were enrolled in previous research investigating the effects of cognitive stimulation-related interventions with equivalent training hours. The Mini-Mental State Examination and LOTCA-G were used to assess cognitive function before and after the interventions. The anchor-based and distribution-based approaches were used to estimate the LOTCA-G MCID. Using the anchor-based method, we defined 16 participants as the improvement group, with a mean change score of 5.75 points (the first MCID estimate). The second MCID estimate was 6.23 points, which we calculated from the 49 participants by using the distribution-based method with the medium effect size. Current results suggest that a LOTCA-G change score greater than 5.75 points should be considered as meaningful change for people with dementia. It is important to consider the LOTCA-G MCID as one of the indexes for determining the success of interventions in people with dementia. This study is the first to report the LOTCA-G MCID for dementia. Establishing an MCID for standardized cognitive assessment tools for the aging population can be used to support evidence-based practice in rehabilitation clinics.

Responsiveness and minimal clinically important difference of the EQ-5D-5L in cervical intraepithelial neoplasia: a longitudinal study

BackgroundWith the widespread clinical application of the five-level version of the EuroQol five-dimensional questionnaire (EQ-5D-5L), whether the questionnaire scores are responsive to changes in patients’ health and how much changes in questionnaire scores represent patients’ real health changes require consideration. Consequently, we assessed responsiveness and estimated the minimal clinically important difference (MCID) of the EQ-5D-5L in surgically treated patients with cervical intraepithelial neoplasia (CIN) to determine the relationship between MCID and minimal detectable change (MDC).MethodsWe conducted a longitudinal, observational study. Participants were patients with CIN from the gynecology inpatient department of a grade-A tertiary hospital in Shihezi, Xinjiang, China. Participants completed the EQ-5D-5L and the Global Rating of Change Questionnaire (GRCQ) at baseline and one month post-surgery. The Wilcoxon signed-rank test was used to compare EQ-5D-5L scores pre- and post-treatment. We calculated the effect size (ES) and the standardized response mean (SRM) to quantitatively assess responsiveness. Distribution-based, anchor-based, and instrument-defined methods were used to estimate MCID. MCID to MDC ratios at individual- and group-levels were also calculated.ResultsFifty patients with CIN completed the follow-up investigation (mean age 44.76 ± 8.72 years; mean follow-up time 32.28 ± 1.43 days). The index value and EQ visual analogue scale (EQ VAS) of the EQ-5D-5L improved by 0.025 and 6.92 (all p < 0.05) at follow-up as compared to baseline respectively. The ES and the SRM of the index value were 0.47 and 0.42 respectively, indicating small responsiveness; while the ES and the SRM of EQ VAS were 0.50 and 0.49 respectively, indicating small to moderate responsiveness. The average (range) of MCIDs for index value and EQ VAS were 0.039 (0.023–0.064) and 5.35 (3.12–6.99) respectively. These values can only be used to determine whether patients have experienced clinically meaningful health improvements at the group level.ConclusionsThe EQ-5D-5L has only small to moderate responsiveness in post-surgical patients with CIN, and the MCIDs developed in this study can be used for group-level health assessment. However, further study is needed concerning health changes at the individual level.

Establishing the Minimal Clinically Important Difference for the Hernia-Related Quality of Life Survey (HerQLes)

Abstract Background Hernia-Related Quality of Life Survey (HerQLes) assesses quality of life (QoL) after hernia repair, but the minimal clinically important difference (MCID) is unknown. Methods Using 2013–2019 data from the Abdominal Core Health Quality Collaborative, HerQLes summary scores were calculated for VHR patients at baseline and 1-year. MCID was calculated using distribution-based method. Multivariate regression identified factors associated with exceeding MCID at 1 year. Results 1817 patients met criteria. MCID was identified as a change in HerQLes of at least 15.6 points. Mean 1-year post-op score was 74.9 (SD ± 26.2), which exceeded the MCID threshold (p Conclusion Using MCID can help identify patients who may significantly improve QoL after VHR, as well as power clinical trials with QoL as primary outcome.

Establishing Maximal Subjective Outcome Improvement after Total Ankle Arthroplasty

Category:Ankle; Ankle ArthritisIntroduction/Purpose:Total ankle arthroplasty is considered one of the most common treatments for end stage osteoarthritis of the ankle. This procedure results in significant long-term improvements in pain and function while preserving pre-operative range of motion. Patients also demonstrate improvements in patient reported outcome measures (PROMs) - a modality that quantifies patient’s subjective well-being. Understanding the time to maximal subjective medical improvement (MMI) following total ankle arthroplasty can help guide resource allocation and manage patient expectations. The purpose of this investigation is to establish when patients perceive MMI according to PROMs following total ankle arthroplasty.Methods:A systematic review was conducted on the PubMed database to identify studies on total ankle arthroplasty which reported consecutive PROMs for at least two years postoperatively. Pooled analysis was done at 3-months, 6-months, 12-months, and 24-months postoperatively. The minimal clinically important difference (MCID) was established by a distribution-based method, which is one-half of the standard deviation of outcome score change for a given instrument. Clinically significant improvement was determined between pairs of intervals that exceeded the MCID.Results:A total of 12 studies and 1514 patients met the inclusion criteria for this review. Clinically significant improvement was seen up to 6 months postoperatively in both the American Orthopaedic Foot & Ankle Society Ankle-Hindfoot Score (AOFAS) and Visual Analog Scale (VAS) scoring systems but was not demonstrated at later intervals. The Short Musculoskeletal Function Assessment (SMFA) Function and Bother subsections were scored individually and both demonstrated clinically significant improvement until 1 year postoperatively.Conclusion:After total ankle arthroplasty, the maximal subjective medical improvement based on PROMs is seen until one year postoperatively, with clinically insignificant improvement beyond one year. The SMFA scoring system may offer greater sensitivity to subjective improvements compared to the AOFAS or VAS scales. This trajectory may help guide patients in managing their expectations in their functional outcomes during preoperative patient education.

LncLocation: Efficient Subcellular Location Prediction of Long Non-Coding RNA-Based Multi-Source Heterogeneous Feature Fusion.

Recent studies uncover that subcellular location of long non-coding RNAs (lncRNAs) can provide significant information on its function. Due to the lack of experimental data, the number of lncRNAs is very limited, experimentally verified subcellular localization, and the numbers of lncRNAs located in different organelle are wildly imbalanced. The prediction of subcellular location of lncRNAs is actually a multi-classification small sample imbalance problem. The imbalance of data results in the poor recognition effect of machine learning models on small data subsets, which is a puzzling and challenging problem in the existing research. In this study, we integrate multi-source features to construct a sequence-based computational tool, lncLocation, to predict the subcellular location of lncRNAs. Autoencoder is used to enhance part of the features, and the binomial distribution-based filtering method and recursive feature elimination (RFE) are used to filter some of the features. It improves the representation ability of data and reduces the problem of unbalanced multi-classification data. By comprehensive experiments on different feature combinations and machine learning models, we select the optimal features and classifier model scheme to construct a subcellular location prediction tool, lncLocation. LncLocation can obtain an 87.78% accuracy using 5-fold cross validation on the benchmark data, which is higher than the state-of-the-art tools, and the classification performance, especially for small class sets, is improved significantly.