Minimal Clinically Important Change Research Articles

Minimal Clinically Important Change of Movement Pain in Musculoskeletal Pain Conditions

Movement pain, which is distinct from resting pain, is frequently reported by individuals with musculoskeletal pain. There is growing interest in measuring movement pain as a primary outcome in clinical trials, but no minimally clinically important change (MCIC) has been established, limiting interpretations. We analyzed data from 315 participants who participated in previous clinical trials (65 with chronic Achilles tendinopathy; 250 with fibromyalgia) to establish an MCIC for movement pain. A composite movement pain score was defined as the average pain (Numeric Rating Scale: 0–10) during 2 clinically relevant activities. The change in movement pain was calculated as the change in movement pain from pre-intervention to post-intervention. A Global Scale (GS: 1–7) was completed after the intervention on perceived change in health status. Participants were dichotomized into non-responders (GS ≥4) and responders (GS <3). Receiver operating characteristic curves were calculated to determine threshold values and corresponding sensitivity and specificity. We used the Euclidean method to determine the optimal threshold point of the Receiver operating characteristic curve to determine the MCIC. The MCIC for raw change in movement pain was 1.1 (95% confidence interval [CI]: .9–1.6) with a sensitivity of .83 (95% CI: .75–.92) and specificity of .79 (95% CI: .72–.86). For percent change in movement pain the MCIC was 27% (95% CI: 10–44%) with a sensitivity of .79 (95% CI: .70–.88) and a specificity of .82 (95% CI: .72–.90). Establishing an MCIC for movement pain will improve interpretations in clinical practice and research. PerspectiveA minimal clinically important change (MCIC) of 1.1- points (95% CI: .9–1.6) for movement pain discriminates between responders and non-responders to rehabilitation. This MCIC provides context for interpreting the meaningfulness of improvement in pain specific to movement tasks.

Measurement Properties of the Oxford Shoulder Score and Minimal Clinically Important Changes After Primary Total Shoulder Replacement Surgery.

We evaluated the measurement properties of the Oxford Shoulder Score (OSS) and estimated the minimal clinically important change (MCIC) in patients undergoing primary total shoulder replacement in Australia. Deidentified data from the Australian Orthopaedic Association National Joint Replacement Registry were used for this analysis. Pre- and 6-month postoperative OSS scores were used, with the 5-level EuroQoL quality of life instrument and shoulder pain scores used as comparators. Floor and ceiling effects, internal consistency reliability, construct validity, and responsiveness to change were evaluated using standard psychometric methods. Mean change and predictive modeling approaches (with and without adjustment for the proportion of improved patients) were used to calculate MCIC thresholds, with patient-perceived improvement after surgery as the anchor. Preoperative OSS data were available for 1,117 patients (59% female; 90% aged ≥60 years) undergoing primary total shoulder replacement. No floor or ceiling effects were observed pre- or postoperatively. The OSS showed high internal consistency reliability (Cronbach alpha >0.89), good construct validity, and high responsiveness to change (effect size 1.88). The MCIC derived from the mean change method was 6.50 points (95% confidence interval [95% CI] 4.41-8.61). The predictive modeling approach produced an MCIC estimate of 8.42 points (95% CI 5.68-12.23) after adjustment. The OSS has good measurement properties to capture pain and function outcomes after shoulder replacement procedures and is highly responsive to change. Based on robust methods, an increase in OSS scores of at least eight points can be considered as meaningful improvement after surgery from the patient's perspective.

Multiple Sclerosis vision questionnaire (MSVQ-7): Reliability, validity, precision and discrimination

BackgroundVisual dysfunction is common in people with Multiple Sclerosis (pwMS), associated with a variety of visual symptoms. Capturing the patient experience of these complex patterns of visual pathology is challenging. A valid and reliable patient reported measure, capable of detecting clinically significant change, would have considerable research and clinical benefits. We examined the properties of the MS Vision Questionnaire (MSVQ-7) in a large MS population. MethodsData were collected from participants in the UK-wide Trajectories of Outcome in Neurological Conditions-MS (TONiC-MS) study: MS subtype and Expanded Disability Status Scale (EDSS) band from the clinical team, as well as serial packs including the MSVQ-7 and questionnaires on depression, anxiety and stigma. A calibration sample of 1000 pwMS contributing several years of follow-up were split into training and validation samples for a Confirmatory Factor Analysis and Rasch analysis. The Minimal Detectable Change (MDC) was computed as well as the Minimal Clinically Important Change (MIC), by an anchor-based method, for different MS subtypes. ResultsThe MSVQ-7 is unidimensional and can be fit to the Rasch model with a solution discarding 3% of variance. Providing all 7 items are answered, the total can be converted to an interval-level metric for calculation of change scores and other parametric analyses. The % of missing values did not exceed 1.7%. Among 5478 pwMS, 80% reported visual problems. MSVQ-7 scores were categorised as mild for 36.1%, moderate for 33.6% and severe for 10.3%, and varied by MS subtype. In the follow-up sample of 2227 pwMS, 42.5% changed MSVQ-7 category between baseline and first follow-up (mean 22.6 months). The MIC exceeded the MDC so clinically significant change exceeds measurement error. While MDC was identical for relapsing and progressive MS, MIC varied by MS subtype, with smaller MIC in relapsing MS. Over one-quarter of the follow-up sample reported a clinically significant change in MSVQ-7: 12.2% improved and 13.5% deteriorated. For pwMS recruited within 2 years of diagnosis, 17.3% reported significant change on follow-up, all improving. MSVQ-7 scores showed strong associations with anxiety, depression and stigma (effect sizes>0.8). Duration, EDSS band and MS subtype all had effect sizes 0.2–0.49. A multinomial logistic regression exploring vision disturbance and depression, adjusted for age, gender, MS subtype, duration and disability, showed vision is the strongest significant predictor of depression. Each unit increase in interval MSVQ-7 increases risk by 10% of ‘possible’ and by 17% of ‘probable’ depression. ConclusionsThe MSVQ-7 is a brief self-report measure of visual problems for pwMS. It can easily be converted to interval-level measurement for change scores or power calculations and has good precision and discrimination. Visual problems were reported by 80% of pwMS and changed over time, evidencing the need for regular monitoring. MIC varied by MS subtype, indicating that perception of impact changes over the disease course. Visual dysfunction significantly affects depression risk and perceived stigma, highlighting the importance of routine assessment of visual problems in comprehensive care. The MSVQ-7 has strong psychometric properties for adoption as a measure for vision in clinical and research settings.

Responsiveness of the Persian Version of Forgotten Joint Score-12 Questionnaire After Lower Limb Surgery

Background and Objectives: The Persian version of the forgotten joint score-12 (FJS-12) questionnaire with acceptable reliability and validity is used to measure the extent of awareness of the joint and the ability of the patient in forgetting the involved joint. This study aims to evaluate the responsiveness of the Persian version of FJS-12 among Persian-speaking subjects following anterior cruciate ligament (ACL) surgery, total knee arthroplasty (TKA), and total hip arthroplasty (THA). Methods: Twenty-five candidates for ACL surgery, 54 subjects with TKA, and 33 subjects with THA participated in this study. They filled the FJS-12 and Western Ontario and McMaster Universities osteoarthritis index (WOMAC) questionnaires before the surgery and 7 weeks after surgery as well as after physiotherapy. For analysis, receiving operator characteristic (ROC) method and gamma correlation coefficient were used. Results: The receiving ROC area under the curve (AUC) for FJS-12 and WOMAC index was 0.77 for both, this meant acceptable value, and minimal clinically important change (MCIC) was 32.45 for FJS-12. Finally, the gamma correlation coefficient of the questionnaire was estimated at an average of 0.5. Conclusion: The FJS-12 questionnaire has acceptable responsiveness that can be used to evaluate the therapeutic effects in clinical settings.

From once-weekly to semi-weekly whole prostate gland stereotactic radiotherapy with focal boosting: Primary endpoint analysis of the multicenter phase II hypo-FLAME 2.0 trial

Background and purposeThe hypo-FLAME trial showed that once-weekly (QW) focal boosted prostate stereotactic body radiotherapy (SBRT) is associated with acceptable acute genitourinary (GU) and gastrointestinal (GI) toxicity. Currently, we investigated the safety of reducing the overall treatment time (OTT) of focal boosted prostate SBRT from 29 to 15 days. Material and methodsPatients with intermediate- and high-risk prostate cancer were treated with SBRT delivering 35 Gy in 5 fractions to the whole prostate gland with an iso-toxic boost up to 50 Gy to the intraprostatic lesion(s) in a semi-weekly (BIW) schedule. The primary endpoint was radiation-induced acute toxicity (CTCAE v5.0). Changes in quality of life (QoL) were examined in terms of proportions achieving a minimal clinically important change (MCIC). Finally, acute toxicity and QoL scores of the BIW schedule were compared with the results of the prior QW hypo-FLAME schedule (n = 100). ResultsBetween August 2020 and February 2022, 124 patients were enrolled and treated BIW. No grade ≥3 GU or GI toxicity was observed. The 90-days cumulative incidence of grade 2 GU and GI toxicity rates were 47.5% and 7.4%, respectively. Patients treated QW scored significant less grade 2 GU toxicity (34.0%, p = 0.01). No significant differences in acute GI toxicity were observed. Furthermore, patients treated QW had a superior acute bowel and urinary QoL. ConclusionSemi-weekly prostate SBRT with iso-toxic focal boosting is associated with acceptable acute GU and GI toxicity. Based on the comparison between the QW and BIW schedule, patients should be counselled regarding the short-term advantages of a more protracted schedule.Registration number ClinicalTrials.gov: NCT04045717.

Two-fraction stereotactic MRI-guided ablative radiotherapy with simultaneous boost to dominant intraprostatic lesion: Results from the 2SMART phase 2 trial.

349 Background: Prostate stereotactic ablative radiotherapy (SABR) for localised prostate cancer is commonly delivered over 5 fractions. Focal boost to the dominant intraprostatic lesion (DIL) seen on multiparametric magnetic resonance imaging (mpMRI) is an approach for dose-escalation in prostate SABR. This is the first report of the outcomes of the 2SMART trial, a phase 2 single-arm study using 2-fraction prostate SABR with DIL boost. Methods: Men with low to intermediate risk prostate cancer were enrolled in the study. Three gold fiducial markers were inserted for image guidance. The clinical target volume (CTV) included the prostate gland, and the planning target volume (PTV) was a 2mm expansion antero-posterior and laterally, and 2.5mm supero-inferiorly. The DIL was contoured on fused mpMRI. The prescribed dose was 26Gy in 2 fractions (EQD2 110Gy, α/β of 1.4) to the CTV, and up to 32Gy in 2 fractions (EQD2 164Gy) to the DIL as long as the dose constraints for the organs at risks were not exceeded. Each fraction was delivered 1 week apart. Daily image guidance with cone-beam computed tomography was used pre- and post-treatment. The primary endpoint was acute (≤3 months) changes in quality of life (QOL), assessed using the EPIC questionnaire. Minimal clinically important change (MCIC) in QOL was defined as an EPIC score decrease of &gt;0.5 standard deviation of the baseline EPIC score for each domain. Secondary endpoints were acute and late toxicities (assessed using CTCAEv4), and biochemical failure (based on Phoenix criteria). Results: 30 men were enrolled in the study, of which 2 (7%) had low risk and 28 (93%) had intermediate risk prostate cancer. The median follow-up was 44 months (range: 39-49 months). The median PSA nadir was 0.2ng/mL, with median time to nadir of 37 months. One patient (3%) had biochemical failure at 44 months post-treatment. 1 (3%) and 17 (57%) had acute Grade 2 GU and GI toxicities, while 3 (10%) and 15 (50%) had late (&gt;6 months) Grade 2 GU and GI toxicities. No acute or late Grade ≥3 GU or GI was reported. 10 (33%), 6 (20%), and 3 (10%) men had acute MCIC in urinary, bowel and sexual domains respectively. 15 (50%), 9 (30%) and 13 (43%) had late MCIC in urinary, bowel and sexual domain respectively. Conclusions: Two-fraction prostate SABR with DIL boost is a safe approach for dose-escalation for localised prostate cancer, with minimal impact on acute QOL, and no grade 3-4 toxicities. Clinical trial information: NCT03588819 .

Two-fraction stereotactic ablative radiotherapy with simultaneous boost to MRI-defined dominant intra-prostatic lesion – Results from the 2SMART phase 2 trial

PurposeThis is the first report of the 2SMART Phase II trial evaluating the safety of two-fraction stereotactic ablative radiotherapy (SABR) with focal boost to magnetic resonance imaging (MRI) defined dominant intra-prostatic lesion (DIL) for localised prostate cancer. Materials and methodsMen with low or intermediate risk prostate cancer were eligible for the study. The gross tumour volume (GTV) was MRI-defined DIL, and the clinical target volume (CTV) was entire prostate gland. The planning target volume (PTV) was a 2 mm expansion anteroposterior and lateral, and 2.5 mm superoinferior. The prescribed dose was 32 Gy to GTV, and 26 Gy to CTV. Primary endpoint was minimal clinically important change (MCIC) in quality of life (QOL) within 3-months of SABR, assessed using the EPIC-26 questionnaire. Secondary endpoints were acute and late toxicities (assessed using CTCAEv4), PSA nadir, and biochemical failure (based on Phoenix criteria). ResultsThirty men were enrolled in the study – 2 (7%) had low-risk and 28 (93%) had intermediate risk prostate cancer. The median follow-up was 44 months (range:39–49 months). The median PSA nadir was 0.25 ng/mL, with median time to nadir of 37 months. One patient (3%) had biochemical failure at 44 months post-treatment. Ten (33%), six (20%), and three (10%) men had acute MCIC in urinary, bowel, and sexual QOL domains respectively. No acute or late grade ≥ 3 urinary or bowel toxicities were observed. ConclusionThis novel protocol of two-fraction prostate SABR with MRI-defined DIL boost is a safe approach for dose-escalation, with minimal impact on acute QOL and no grade ≥ 3 toxicities.

Cross-cultural adaptation and validation of the Traditional Chinese version of the Core Outcome Measures Index in patients with low back pain.

This study aimed to carry out a cross-cultural adaptation of the Core Outcome Measures Index (COMI) for use in Traditional Chinese-speaking patients with low back pain (LBP) and to investigate its psychometric properties. A total of 224 patients with LBP > 6weeks who visited our spine center from May 2018 to May 2019 were included in the study. Patients completed a booklet of questionnaires including the following: (1) pain Numeric Rating Scale, (2) Oswestry Disability Index, (3) Roland-Morris Disability Questionnaire, (4) EuroQol-five dimension (EQ-5D), and (5) COMI. Patients were sent a second booklet (also containing a transition question to indicate any change in condition) to be completed again within one month after the first. Fifty-two patients did not receive any intervening treatment (group 1), while the other 172 patients received medical treatment (group 2) between the two questionnaires. The intraclass correlation coefficient (ICC) for the COMI summary score was 0.94 (95% CI 0.89-0.97); the standard error of measurement (SEM) was 0.41 and the minimum detectable change (MDC) score was 1.14. The COMI summary scores showed a low floor effect (1.8%) and ceiling effect (0.4%). All COMI item scores demonstrated the hypothesized correlations with their corresponding full-length questionnaires except for the pain item (correlation stronger than hypothesized). Standardized response means (SRM) for the COMI items in the treated group were between 0.58 and 1.30. Regarding the ability of the COMI change score to differentiate between good and poor outcomes, the area under the receiver operating characteristic (AUROC) curve was 0.77 [standard error (SE) 0.07, 95% confidence interval (CI) 0.68-0.84] and the minimal clinically important change (MCIC) score was ≥ 1.85 points. The Traditional Chinese COMI represents a practical and reliable tool for the assessment of Traditional Chinese-speaking patients with back problems.

Impact on productivity impairment of a digital care program for chronic low back pain: A prospective longitudinal cohort study

BackgroundLow back pain (LBP) is the leading cause of disability in the United States and the main reason for absenteeism. Successful management of chronic LBP (CLBP) is dependent on multimodal evidence-based interventions. Digital interventions (DI) may ease accessibility to such treatments, increasing adherence, while reducing healthcare-related costs. ObjectivesAssess the impact of a completely remote multimodal DI on productivity impairment in a real-work context cohort of patients with CLBP. DesignLongitudinal study. MethodsAd-hoc analysis of an interventional, single-arm study of individuals with CLBP undergoing a DI for 12 weeks. Outcomes included the mean change in work productivity and activity impairment (including overall and non-work related activities), pain, depression, anxiety, fear-avoidance beliefs, analgesic usage, and engagement. Minimal clinically important change (MCIC) was calculated for productivity using anchor- and distribution-based methods. ResultsFrom 560 patients at program start, 78.4% completed the DI. A significant improvement in overall productivity (20.21, 95%CI: 16.48–23.94) and in non-work related activities (21.36, 95%CI: 17.49–25.22) was observed, corresponding to a responder rate of 57.1–83.3% and 60.5–79.8%, respectively, and depending on the MCIC method. Significant improvements were reported for pain (2.32 points, 95%CI: 2.02–2.61), anxiety (5.24, 95%CI: 4.18–6.29), depression (6.38, 95%CI: 4.78–7.98) and fear-avoidance beliefs (8.11, 95%CI: 6.20–10.02). Both engagement (sessions per week) and patient satisfaction scores were high, 2.9 (SD 1.0) and 8.8/10 (SD 1.6), respectively. ConclusionsThis study demonstrated the utility of a multimodal DI to address productivity impairment. DIs have great potential to ease the burden of CLBP, providing an accessible and cost-effective modality of care. Trial registrationThe study was approved by the New England IRB (protocol number 120190313) and prospectively registered in ClinicalTrials.gov, NCT04092946, on September 17th, 2019.

Development of a mapping function ("crosswalk") for the conversion of scores between the Oswestry Disability Index (ODI) and the Core Outcome Measures Index (COMI).

The Oswestry Disability Index (ODI) and the Core Outcome Measures Index (COMI) are two commonly used self-rating outcome instruments in patients with lumbar spinal disorders. No formal crosswalk between them exists that would otherwise allow the scores of one to be interpreted in terms of the other. We aimed to create such a mapping function. We performed a secondary analysis of ODI and COMI data previously collected from 3324 patients (57 ± 17y; 60.3% female) at baseline and 1y after surgical or conservative treatment. Correlations between scores and Cohen's kappa for agreement (κ) regarding achievement of the minimal clinically important change (MCIC) score on each instrument (ODI, 12.8 points; COMI, 2.2 points) were calculated, and regression models were built. The latter were tested for accuracy in an independent set of registry data from 634 patients (60 ± 15y; 56.8% female). All pairs of measures were significantly positively correlated (baseline, 0.73; 1y follow-up (FU), 0.84; change-scores, 0.73). MCIC for COMI was achieved in 53.9% patients and for ODI, in 52.4%, with 78% agreement on an individual basis (κ = 0.56). Standard errors for the regression slopes and intercepts were low, indicating excellent prediction at the group level, but root mean square residuals (reflecting individual error) were relatively high. ODI was predicted as COMI × 7.13-4.20 (at baseline), COMI × 6.34 + 2.67 (at FU) and COMI × 5.18 + 1.92 (for change-score); COMI was predicted as ODI × 0.075 + 3.64 (baseline), ODI × 0.113 + 0.96 (FU), and ODI × 0.102 + 1.10 (change-score). ICCs were 0.63-0.87 for derived versus actual scores. Predictions at the group level were very good and met standards justifying the pooling of data. However, we caution against using individual values for treatment decisions, e.g. attempting to monitor patients over time, first with one instrument and then with the other, due to the lower statistical precision at the individual level. The ability to convert scores via the developed mapping function should open up more centres/registries for collaboration and facilitate the combining of data in meta-analyses.

Clinically important change on the Unified Dyskinesia Rating Scale among patients with Parkinson's disease experiencing dyskinesia.

The Unified Dyskinesia Rating Scale (UDysRS) evaluates dyskinesia in patients with Parkinson's disease (PD). A minimal clinically important change (MCIC)-the smallest change in a treatment outcome that a patient considers important-remains undefined for the UDysRS. To utilize pivotal amantadine delayed-release/extended-release (DR/ER) trial data to derive MCICs for the UDysRS total score in patients with PD experiencing dyskinesia. Pivotal trials included PD patients with ≥1 h daily ON time with troublesome dyskinesia and baseline scores ≥2 on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV, item 4.2. Patients randomized to amantadine DR/ER or placebo completed two consecutive 24-h diaries before each clinic visit and were evaluated during ON time with dyskinesia using the UDysRS, MDS-UPDRS, and Clinician Global Impression of Change (CGI-C). The UDysRS changes from baseline to week 12 were anchored to corresponding changes in MDS-UPDRS item 4.2 scores. A minimal clinically important improvement in the CGI-C and diary-reported ON time with troublesome dyskinesia (≥0.5 h) were supportive anchors. Receiver operating characteristic curves determined the UDysRS change values optimizing sensitivity and specificity to at least minimal improvement on each anchor. The analyses included 196 patients. Week 12 UDysRS total score reduction of ≥8 points corresponded to at least minimal MDS-UPDRS item 4.2 improvement. UDysRS reduction of ≥9 points corresponded to decreased ON time with troublesome dyskinesia of ≥0.5 h per patient diaries, and UDysRS reduction of ≥10 points corresponded to at least minimal improvement on the CGI-C. Anchored to the MDS-UPDRS Part IV, item 4.2, an 8-point reduction in the UDysRS total score can be considered an MCIC for PD patients with dyskinesia.

Digitally Delivered Exercise and Education Treatment Program for Low Back Pain: Longitudinal Observational Cohort Study.

BackgroundExercise and education is recommended as first-line treatment by evidence-based, international guidelines for low back pain (LBP). Despite consensus regarding the treatment, there is a gap between guidelines and what is offered to patients. Digital LBP treatments are an emerging way of delivering first-line treatment.ObjectiveThe aim of this study is to evaluate outcomes after participation in a 3-month digitally delivered treatment program for individuals with subacute or chronic LBP.MethodsWe analyzed data from 2593 consecutively recruited participants in a digitally delivered treatment program, available via the national health care system in Sweden. The program consists of video-instructed and progressive adaptable exercises, education through text lessons, and a chat and video function connecting participants with a personal physiotherapist. The primary outcome was mean change and proportion reaching a minimal clinically important change (MCIC) for LBP (2 points or 30% decrease) assessed with the numerical rating scale (average pain during the past week, discrete boxes, 0-10, best to worst). Secondary outcomes were mean change and proportion reaching MCIC (10 points or 30%) in disability, assessed with the Oswestry Disability Index (ODI; 0-100, best to worst) and a question on patient acceptable symptom state (PASS).ResultsThe mean participant age was 63 years, 73.85% (1915/2593) were female, 54.72% (1419/2593) had higher education, 50.56% (1311/2593) were retired, and the mean BMI was 26.5 kg/m2. Participants completed on average 84% of the prescribed exercises and lessons, with an adherence of ≥80% in 69.26% (1796/2593) and ≥90% in 50.13% (1300/2593) of the participants. Mean reduction in pain from baseline to 3 months was 1.7 (95% CI –1.8 to –1.6), corresponding to a 35% relative change. MCIC was reached by 58.50% (1517/2593) of participants. ODI decreased 4 points (95% CI –4.5 to –3.7), and 36.48% (946/2593) reached an MCIC. A change from no to yes in PASS was seen in 30.35% (787/2593) of participants. Multivariable analysis showed positive associations between reaching an MCIC in pain and high baseline pain (odds ratio [OR] 1.9, 95% CI 1.6-2.1), adherence (OR 1.5, 95% CI 1.3-1.8), and motivation (OR 1.2, 95% CI 1.0-1.5), while we found negative associations for wish for surgery (OR 0.6, 95% CI 0.5-0.9) and pain in other joints (OR 0.9, 95% CI 0.7-0.9). We found no associations between sociodemographic characteristics and pain reduction.ConclusionsParticipants in this digitally delivered treatment for LBP had reduced pain at 3-month follow-up, and 58.50% (1517/2593) reported an MCIC in pain. Our findings suggest that digital treatment programs can reduce pain at clinically important levels for people with high adherence to treatment but that those with such severe LBP problems that they wish to undergo surgery may benefit from additional support.Trial RegistrationClinicalTrials.gov NCT05226156; https://clinicaltrials.gov/ct2/show/NCT05226156

Minimal clinically important change in Abnormal Involuntary Movement Scale score in tardive dyskinesia as assessed in pivotal trials of deutetrabenazine

IntroductionDeutetrabenazine is approved by the US Food and Drug Administration to treat tardive dyskinesia (TD) based on 2 pivotal, 12-week, placebo-controlled studies (ARM-TD and AIM-TD) evaluating safety and efficacy in patients with baseline total motor Abnormal Involuntary Movement Scale (AIMS) score ≥6. This analysis estimated the minimal clinically important change (MCIC) in total motor AIMS score in TD patients treated with deutetrabenazine. MethodsThe pooled analysis population included all patients in ARM-TD and AIM-TD who received study drug and had ≥1 postbaseline AIMS assessment. MCIC analyses were performed using Patient Global Impression of Change (PGIC) and Clinical Global Impression of Change (CGIC) as anchors. MCIC was defined as the mean change from baseline in total motor AIMS score in patients treated with deutetrabenazine who were rated minimally improved on PGIC or CGIC at Week 12. ResultsThis analysis included 295 patients (deutetrabenazine, n = 197; placebo, n = 98). At Week 12, the MCIC in deutetrabenazine-treated patients was −2.4 based on the PGIC and −2.1 based on the CGIC. Mean change from baseline in total motor AIMS score for placebo-treated patients rated minimally improved was −1.4 based on the PGIC and −1.5 based on the CGIC. The proportion of deutetrabenazine-treated patients who achieved improvement in total motor AIMS score by ≥2 and ≥3 points was 66% and 55%, respectively. ConclusionUsing anchor-based methodology, the MCIC on the AIMS for deutetrabenazine in patients with TD was approximately −2, suggesting that a reduction in total motor AIMS score of ∼2 is associated with clinically meaningful improvement in TD symptoms.

Validation of the work ability index\u2014single item and the pain disability index\u2014work item in patients with chronic low back pain

PurposeA cross-sectional and longitudinal study was conducted to analyse construct validity, responsiveness, and Minimal Clinically Important Change (MCIC) in the Work Ability Score (WAS) and Pain Disability Index Work item (PDI-W) in patients with Chronic Low Back Pain (CLBP).MethodConstruct validity was assessed by testing predefined hypotheses. Responsiveness and MCIC were measured with an anchor-based method. The area under the receiver Operating Characteristic Curve (AUC) and the optimal cut-off point were calculated. Smallest Detectable Change (SDC) was calculated to determine measurement error.ResultsIn total, 1502 patients (age 18–65 years) with CLBP were included. For validity of the WAS and PDI-W, respectively, seven and six out of 10 hypotheses were not rejected. The WAS (n = 355) was responsive to change with an AUC of 0.70. MCIC was 1.5 point, SDCindividual 4.9, and SDCgroup 0.3. MCICs were 4.5, 1.5, and − 0.5 points for, respectively, low, middle, and high scoring baseline groups. The PDI-W (n = 297) was responsive to change with an AUC of 0.80. MCIC was − 2.5 points, SDCindividual 5.2, and SDCgroup 0.3. MCICs were − 0.5, − 2.5, and − 4.5 points for, respectively, low, middle, and high scoring baseline groups.ConclusionConstruct validity of the WAS and PDI-W was insufficient in this patient sample. The WAS and PDI-W are responsive to change. On average, improvements of 1.5 point (WAS) and − 2.5 points (PDI-W) were interpreted as clinically important. However, MCICs are also baseline dependent. Due to a risk of measurement error, at the individual level change scores should be interpreted with caution.

Responsiveness of Nepali version of Oswestry Disability Index (ODI) on individuals with non-specific low back pain

BackgroundLow back pain (LBP) is a common musculoskeletal problem, associated with disability and high societal costs. The Oswestry Disability Index (ODI) is among the most commonly used patient reported outcome measures to measure disability due to LBP. Evidence supporting the reliability and validity of the Nepali Version of Oswestry Disability Index (NODI) exists, but its responsiveness is yet to be assessed.ObjectiveWe aimed to assess the responsiveness of NODI in participants with non-specific low back pain.MethodsThe study included 102 (Male 41, Female 61) participants with non-specific low back pain, attending the physiotherapy outpatient department of a tertiary care hospital and nearby community. The NODI was administered to the patients at baseline and again 2 weeks later along with a 7-item Nepali Version of Global Rating of Change (GROC-NP). Responsiveness of NODI was assessed by plotting Receivers Operating Characteristics (ROC) curve.ResultsThe area under curve (AUC) of NODI was 0.88. The best cut-off point on the NODI for improvement on the GROC-NP or the minimal clinical important change (MIC) was 4.22 and ranged from 3.11 to 6.34. The sensitivity and specificity was 77.4% and 84.2% respectively.ConclusionNODI is a responsive scale which can discriminate between participants whose level of disability due to LBP is stable or improving. The result for minimal clinically important change, sensitivity and specificity are consistent with other cross culturally adopted versions.

Role of psychological distress screening in predicting the outcomes of epidural steroid injection in chronic low back pain

BackgroundThere is a paucity of studies investigating relationship between psychological distress and effectiveness of epidural steroid injection in patients with chronic lower back pain (CLBP). AimsThis prospective cohort study assessed whether the outcome can be predicted in CLBP patients undergoing epidural injection by pre-treatment psychological stress stratification using objective screening methods. Methods96 patients with CLBP were recruited to this prospective cohort study. Preoperative level of psychological distress was measured using Modified Zung Index (MZI) and Modified Somatic Perception Questionnaire (MSPQ); pain with Visual Analogue Score (VAS) and McGill Pain Questionnaire (MPQ) and back pain related disability with Oswestry Disability Index (ODI). Fluoroscopic caudal epidural steroid injection comprising 80 mg methylprednisolone and 8 mg of lignocaine was performed. Scores were repeated at 6, 12, and 26 weeks. Successful outcome was Minimal Clinically Important Change (MCIC) in any given measure. ResultsThere were 60 (62.5%) not-distressed patients, 3(3.1%) purely somatising, 15(15.6%) depressed and 18(18.8%) with mixed distress. Preoperative VAS was 82.4, MPQ 18.2 and ODI 51.6. Average VAS and MPQ improved significantly at 6 and 26 weeks. Average magnitude of change of VAS and ODI did not differ between distressed and not-distressed. MPQ improved significantly more in the distressed. MZI was negatively associated with VAS MCIC at 6 weeks and 6 months but it failed to predict the outcome independently. MSPQ was the only individual predictor of MPQ-MCIC at any time; MSPQ≥8 could predict MPQ-MCIC at 6 months with 53%-sensitivity and 78%-specificity. None of psychological measures used showed a significant predictive value of ODI at any follow-up point ConclusionsPsychological distress may predict response only in certain outcome measures in patients suffering from nonspecific CLBP. If the interest lied primarily in pain and functional improvement, the psychological distress failed to discriminate the results at 6 months.

The stereotactic prostate radiotherapy (SPORT) trial: A randomized feasibility study comparing prostate SABR to prostate and pelvic nodal SABR.

248 Background: Stereotactic Ablative Radiotherapy (SABR) is increasingly used to treat low/intermediate risk localised prostate cancer (PCa). However, data on SABR +/- pelvic nodal irradiation (PNI) in high-risk disease is limited to single institution, single-arm studies. The Stereotactic Prostate Radiotherapy (SPORT) trial examined the feasibility of delivering a randomised trial of SABR ± PNI. The composite primary endpoint to determine feasibility comprised: recruitment rate, technical feasibility, acute toxicity (CTCAE v4.0) and quality of life (QoL)(EPIC). Secondary and exploratory endpoints including late toxicity (RTOG) and QoL and potential biomarkers of toxicity (plasma citrulline and DNA damage in circulating lymphocytes) are also presented. Methods: Men with localised PCa demonstrating one of T3a, Gleason score ≥4+3 or PSA&gt;20 were eligible. T3b and T4 disease were excluded. 30 participants were randomised 1:1 to prostate SABR (P-SABR) or prostate and pelvis SABR (PPN-SABR). The prostate and proximal 1-2cm seminal vesicles received 36.25 Gy in 5 fractions over 29 days (prostate CTV 40Gy). The PPN-SABR arm also received 25 Gy in 5 fractions to the pelvic nodes. All patients had fiducial markers and a rectal spacer gel in-situ. As initial toxicity rates were low, the final 10 men received an additional integrated boost to the dominant intraprostatic lesion of up to 50 Gy, irrespective of randomisation. Results: Feasibility was demonstrated. The target recruitment of 30 men was met (83% high risk). Treatment, including an integrated boost plus PNI, was achievable using strict normal tissue constraints. Acute toxicity and QoL were acceptable (Table: Grade≥2 GU 7%, 27% and GI 0%, 7%; minimal clinically important change (MCIC) in EPIC urinary 40%, 60% and bowel score 33%, 47% in P and PPN arms respectively). At median follow up of 30 months (range 18-42 months), late toxicity and QoL were acceptable (Grade≥2 GU 7%, 20% and GI 0%, 13%; MCIC in EPIC urinary 33%, 67% and bowel score 33%, 67% in P and PPN arms respectively). All toxicity was ≤ grade 2 with the exception of one late grade 3 GU toxicity occurring in the PPN arm. Serum citrulline, a marker of small bowel function, trended towards lower levels in the PPN arm, in keeping with a significantly higher dose delivered to the small bowel in this arm. DNA damage foci in circulating lymphocytes increased at 1 hour after radiation. Foci count and repair correlated to toxicity measures will be presented. Conclusions: A randomised clinical trial comparing P-SABR to PPN-SABR is feasible. There was a suggestion of increased toxicity with PPN-SABR, but this remained acceptable. This data will inform a UK multi-centre phase 2 study. Clinical trial information: NCT03253978 . [Table: see text]

Association between the appropriateness of surgery, according to appropriate use criteria, and patient-rated outcomes after surgery for lumbar degenerative spondylolisthesis.

Treatment failures in spine surgery are often attributable to poor patient selection and the application of inappropriate treatment. We used published appropriate use criteria (AUC) to evaluate the appropriateness of surgery in a large group of patients operated for lumbar degenerative spondylolisthesis (LDS) and to evaluate its association with outcome. This was a retrospective analysis of prospectively collected outcome data from patients operated in our Spine Centre, 2005-2012. Appropriateness of surgery was judged based on the AUC. Patients had completed the multidimensional Core Outcome Measures Index (COMI) before surgery and at 3 months' and 1, 2 and 5years' follow-up (FU). In total, 448 patients (69.8 ± 9.6years; 323 (72%) women) were eligible for inclusion and the AUC could be applied in 393 (88%) of these. Surgery was considered appropriate (A) in 234 (59%) of the patients, uncertain/equivocal (U) in 90 (23%) and inappropriate (I) in 69 (18%). A/U patients had significantly (p < 0.05) greater improvements in COMI than I patients at each FU time point. The minimal clinically important change (MCIC) score for COMI was reached by 82% A, 76% U and 54% I patients at 1-year FU (p < 0.001, I vs A and U); the odds of achieving MCIC were 3-4 times greater in A/U patients than in I patients. The results suggest a relationship between appropriateness of surgery for LDS and the improvements in COMI score after surgery. The findings require confirmation in prospective studies that also include a control group of non-operated patients.

Effectiveness of dry needling in the treatment of neck pain and disability associated with myofascial trigger points

Objective: The aim of this study is to evaluate the effectiveness of dry needling (DN) with fast-in and fast-out technique for myofascial trigger points (MTrPs) in the upper trapezius muscle associated with neck pain. Patients and Methods: Patients aged 18-70 years, who have had neck pain at least one active MTrP in the upper trapezius muscle treated with DN, were included in the study. Pain and disability were assessed with Numeric Rating Scale (NRS) and Neck Disability Index (NDI) before treatment (T0), after first session (T1) and after last session (T2). Number of MTrPs where DN was performed and the number of DN sessions were recorded. Patients were evaluated based on the minimal clinically important change (MCIC) scores for NRS and NDI. Results: A total of 76 patients (Female: 67, Male: 9) were included in the study. Median number of DN sessions was 3 and median of MTrPs that DN performed was 4. Both NRS and NDI showed significant improvement at T1 and T2. More than 90% of patients had MCIC at T1 and T2. Conclusion: Dry needling with fast-in and fast-out technique is effective for pain and disability management in patients with neck pain due to MTrPs.

Measurement properties of the musculoskeletal health questionnaire (MSK-HQ): a between country comparison

BackgroundThe Musculoskeletal Health Questionnaire (MSK-HQ) has been developed to measure musculoskeletal health status across musculoskeletal conditions and settings. However, the MSK-HQ needs to be further evaluated across settings and different languages.ObjectiveThe objective of the study was to evaluate and compare measurement properties of the MSK-HQ across Danish (DK) and English (UK) cohorts of patients from primary care physiotherapy services with musculoskeletal pain.MethodsMSK-HQ was translated into Danish according to international guidelines. Measurement invariance was assessed by differential item functioning (DIF) analyses. Test-retest reliability, measurement error, responsiveness and minimal clinically important change (MCIC) were evaluated and compared between DK (n = 153) and UK (n = 166) cohorts.ResultsThe Danish version demonstrated acceptable face and construct validity. Out of the 14 MSK-HQ items, three items showed DIF for language (pain/stiffness at night, understanding condition and confidence in managing symptoms) and three items showed DIF for pain location (walking, washing/dressing and physical activity levels). Intraclass Correlation Coefficients for test-retest were 0.86 (95% CI 0.81 to 0.91) for DK cohort and 0.77 (95% CI 0.49 to 0.90) for the UK cohort. The systematic measurement error was 1.6 and 3.9 points for the DK and UK cohorts respectively, with random measurement error being 8.6 and 9.9 points. Receiver operating characteristic (ROC) curves of the change scores against patients’ own judgment at 12 weeks exceeded 0.70 in both cohorts. Absolute and relative MCIC estimates were 8–10 points and 26% for the DK cohort and 6–8 points and 29% for the UK cohort.ConclusionsThe measurement properties of MSK-HQ were acceptable across countries, but seem more suited for group than individual level evaluation. Researchers and clinicians should be aware that some discrepancy exits and should take the observed measurement error into account when evaluating change in scores over time.