BACKGROUND: Prolonging effects of adjuncts to local anaesthetics in peripheral nerve blocks have been demonstrated in randomised clinical trials. The chosen primary outcome and anticipated effect size have major impact on the clinical relevance of results in these trials. This scoping review aims to provide an overview of frequently used outcomes and anticipated effect sizes in randomised trials on peripheral nerve block adjuncts.
METHODS: For our scoping review, we searched MEDLINE, Embase and CENTRAL for trials assessing effects of adjuncts for peripheral nerve blocks published in 10 major anaesthesia journals. We included randomised clinical trials assessing adjuncts for single-shot ultrasound-guided peripheral nerve blocks, regardless of the type of interventional adjunct and control group, local anaesthetic used and anatomical localization. Our primary outcome was the choice of primary outcomes and corresponding anticipated effect size used for sample size estimation. Secondary outcomes were assessor of primary outcomes, the reporting of sample size calculations and statistically significant and non-significant results related to the anticipated effect sizes.
RESULTS: Of 11,854 screened trials, we included 59. The most frequent primary outcome was duration of analgesia (35/59 trials, 59%) with absolute and relative median (interquartile range) anticipated effect sizes for adjunct versus placebo/no adjunct: 240 min (180-318) and 30% (25-40) and for adjunct versus active comparator: 210 min (180-308) and 17% (15-28). Adequate sample size calculations were reported in 78% of trials. Statistically significant results were reported for primary outcomes in 45/59 trials (76%), of which 22% did not reach the anticipated effect size.
CONCLUSIONS: The reported outcomes and associated anticipated effect sizes can be used in future trials on adjuncts for peripheral nerve blocks to increase methodological homogeneity.

The Extended Glasgow Outcome Scale (GOSE) is accepted as the primary outcome measure in registrational studies for traumatic brain injury (TBI). The Disability Rating Scale (DRS) is used to assess functional progress from initial acute injury, through rehabilitation and reintegration into the community and life. For these reasons, the DRS is an alternative measure for assessing meaningful global outcomes in chronic TBI. The objective of this study was to determine the minimally clinically important difference (MCID) for the DRS in chronic TBI, by determining the magnitude of DRS change associated with the MCID for the GOSE of 1 point. This study is a retrospective analysis of the multi-center, prospective, longitudinal, Traumatic Brain Injury Model Systems National Database of persons with outcomes at 1, 2, and 5 years and every 5 years thereafter post-injury. Spearman\'s correlations for dynamic and static relationships between the DRS and GOSE were significant. For the 1-point MCID for the GOSE, the dynamic MCID estimate for the DRS of a -0.68-point change was calculated as the mean DRS change associated with the difference of the GOSE score between year 1 and year 2 (score range, 3-8), using all persons in the study (n = 11,102), whereas the exploratory static MCID estimate for the DRS of -1.28 points was calculated from the slope of the best-fit line between the DRS and GOSE at year 1 follow-up (score range, 3-8; n = 13,415). The final MCID for the DRS was calculated by using the triangulation method (i.e., the arithmetic mean of the dynamic and exploratory static MCID estimates), which resulted in a -1.0-point change. The significant correlation between the DRS and GOSE has allowed for the establishment of a -1.0-point MCID for the DRS, which supports the use of the DRS as an alternative primary outcome measure for chronic TBI research studies, including clinical trials.

UNASSIGNED: Clinical outcomes following primary total hip arthroplasty (THA) are commonly assessed through patient-reported outcome measures (PROM). The purpose of this study was to use progressively more stringent definitions of success to evaluate clinical outcomes of primary THA at 1-year postoperatively and to determine if demographic variables were associated with achievement of clinical success.
UNASSIGNED: The American Joint Replacement Registry (AJRR) was queried from 2012-2020 for primary THA. Patients that completed the following PROMs preoperatively and 1-year postoperatively were included: Western Ontario and McMaster Universities Arthritis Index (WOMAC), Hip Injury and Osteoarthritis Outcome Score (HOOS) and HOOS for Joint Replacement (HOOS, JR). Mean PROM scores were determined for each visit and between-visit changes were evaluated using paired t-tests. Rates of achievement of minimal clinically important difference (MCID) by distribution-based and anchor-based criteria, patient acceptable symptom state (PASS), and substantial clinical benefit (SCB) were calculated. Logistic regression was used to evaluate associations between demographic variables and odds of success.
UNASSIGNED: 7,001 THAs were included. Mean improvement in PROM scores were: HOOS, JR, 37; WOMAC-Pain, 39; WOMAC-Function, 41 (p<0.0001 for all). Rates of achievement of each metric were: distribution-based MCID, 88-93%; anchor-based MCID, 68-90%; PASS, 47-84%; SCB, 68-84%. Age and sex were the most influential demographic factors on achievement of clinical success.
UNASSIGNED: There is significant variability in clinical outcomes at 1 year after primary THA when using a tiered approach to define success from the patient\'s perspective. Tiered approaches to interpretation of PROMs should be considered for future research and clinical assessment. Level of Evidence: III.

OBJECTIVE: Patient-reported outcome measures (PROMs) are evaluated in randomized controlled trials (RCTs) in patients with systemic lupus erythematosus (SLE), but not widely used in clinical practice. However, interest in incorporating PROMs into the management of SLE is increasing as PROMs provide a unique insight into the patient\'s perception of lupus disease activity. The objective was to assess agreement in PROMs answered using a web app versus an outpatient touchscreen among patients with SLE.
METHODS: In a crossover RCT, SLE patients answered the following PROMs in a random order using the web app and the outpatient touchscreen: Systemic Lupus Erythematosus Activity Questionnaire (SLAQ) Global Health, SLAQ Symptom, SLAQ Total, SLAQ Worsening, Pain Visual Analog Scale (VAS), Fatigue VAS, Patient Global Health VAS, Health Assessment Questionnaire Disability Index (HAQ-DI), Patient Acceptable Symptom State (PASS), and an Anchoring Question. Equivalence between the two device types was demonstrated if the 95% confidence interval (95% CI) of the difference in PROM scores was within the prespecified equivalence margin. Agreement between the two device types was assessed using mixed linear models.
RESULTS: Thirty-four patients with SLE were included. Equivalence was demonstrated between the two device types for SLAQ Global Health with a difference of -0.21 (95% CI: -0.65 to 0.23). Moreover, equivalence was also found for HAQ-DI, Pain VAS, and Fatigue VAS whereas only comparability within the limits of the Minimal Clinically Important Difference (MCID) was demonstrated for VAS Patient Global Health. Statistical comparability was demonstrated for SLAQ Total, SLAQ Worsening, PASS, and Anchoring Question (no predefined MCID/equivalence margins available). However, a statistically significant difference between device types was observed for the SLAQ Symptom of -0.56 (95% CI: -1.10 to -0.01). The difference was, however, very small when considering the scale range of 0-24; thus, it was not judged to be of clinical relevance. Preference for the web app was very high (91.2%).
CONCLUSIONS: For the first time ever, equivalence and comparability between two electronic device types for various PROMs were demonstrated among patients with SLE. Implementation of the device is expected to improve the management of SLE.

UNASSIGNED: To determine minimally clinically important differences (MCIDs) for Disability Rating Scale (DRS), Fugl-Meyer Upper Extremity Subscale (FM-UE), Fugl-Meyer Lower Extremity Subscale (FM-LE), and Fugl-Meyer Motor Scale (FMMS) in patients with chronic motor deficits secondary to traumatic brain injury (TBI).
UNASSIGNED: Retrospective analysis from the 1-year, double-blind, randomized, surgical sham-controlled, Phase 2 STEMTRA trial (NCT02416492), in which patients with chronic motor deficits secondary to TBI (N = 61) underwent intracerebral stereotactic implantation of modified bone marrow-derived mesenchymal stromal (SB623) cells. MCIDs for DRS, FM-UE, FM-LE, and FMMS were triangulated with distribution-based, anchor-based, and Delphi panel estimates.
UNASSIGNED: Triangulated MCIDs were: 1) -1.5 points for the Disability Rating Scale; 2) 6.2 points for the Fugl-Meyer Upper Extremity Subscale; 3) 3.2 points for the Fugl-Meyer Lower Extremity Subscale; and 4) 8.4 points for the Fugl-Meyer Motor Scale.
UNASSIGNED: For the first time in the setting of patients with chronic motor deficits secondary to TBI, this study reports triangulated MCIDs for: 1) DRS, a measure of global outcome; and 2) Fugl-Meyer Scales, measures of motor impairment. These findings guide the use of DRS and Fugl-Meyer Scales in the assessment of global disability outcome and motor impairment in future TBI clinical trials.

OBJECTIVE: This study was conducted to determine the minimal clinically important difference (MCID) of the Patient-Reported Outcomes Information System (PROMIS) Physical Function computer adaptive test (CAT) after distal radius fracture.
METHODS: This study retrospectively analyzed data from 187 adults receiving nonsurgical care for a unilateral distal radius fracture at a single institution between February 2016 and November 2017. All patients completed the PROMIS Physical Function v1.2/2.0 CAT at each visit. At follow-up, patients also completed 2 multiple-choice clinical anchor questions querying their overall response to treatment. The MCID estimate was then calculated with an anchor-based method as the mean PROMIS Physical Function score change for the group reporting mild improvement and with a distribution-based method considering effect sizes of change and the minimum detectable change (MDC). The MCID estimate was examined for the influence of patient age, follow-up interval, and initial PROMIS score.
RESULTS: Change in PROMIS Physical Function scores between visits was significantly different between patients reporting no change, mild improvement, and much improvement on the anchor questions. The anchor-based MCID estimate for PROMIS Physical Function was 3.6 points (SD, 8.4). Among patients reporting mild improvement, individual changes in PROMIS Physical Function were not correlated with patient age or time between visits but were moderately negatively correlated with the initial absolute PROMIS Physical Function score. Applying the effect size parameters to our data when patients indicated minimal change, the distribution-based MCID estimate was 4.6 (SD, 1.8). Both the anchor-based and the distribution-based MCID estimates were judged sufficient because they exceeded the MDC value of 2.3.
CONCLUSIONS: The MCID value for PROMIS Physical Function is estimated between 3.6 and 4.6 in patients treated nonsurgically for distal radius fractures. Clinical improvement is associated with smaller magnitudes of change on PROMIS Physical Function when patients present with better reported function.
CONCLUSIONS: The MCID estimations are needed to determine the clinical relevance of changes in PROMIS scores and to more accurately calculate sample sizes needed for research incorporating PROMIS.

Comorbidities are common in respiratory disease patients and have been well-known to impact their quality of life. The objective of this study is to estimate the minimal clinically important difference (MCID) of the health-related quality of life (HRQOL) among respiratory disease patients with different comorbidities in a Vietnamese tertiary hospital. We performed a cross-sectional study from October to November 2016 at the Respiratory Center of Bach Mai Hospital, Hanoi, with a total of 508 participants. Information about socio-economic characteristics, HRQOL and comorbidities of participants was collected. ANOVA was used to identify MCID between patients with and without specific comorbid conditions. Tobit regression was used to explore the associations between comorbidities and the HRQOL. Results showed that the prevalence of cardiovascular comorbidities was 23.8%, followed by musculoskeletal diseases (12.0%), digestive diseases (11.8%), endocrine diseases (10.0%), kidney diseases (5.1%) and ear, nose, and throat diseases (4.5%). Regarding HRQOL, having a problem in pain/discomfort was observed in 61.0% of participants, followed by anxiety/depression (48.2%). Mean EQ-5D index was 0.66 (SD (Standard Deviation) = 0.31). The significant MCID (p < 0.05) was found between patients with and without cardiovascular diseases, musculoskeletal diseases, kidney diseases, and endocrine diseases. The multivariate regression model showed that only musculoskeletal diseases were found to be related with the marked decrement of EQ-5D index score (Coef. = -0.13; 95% CI (Confident Interval) = -0.23; -0.02). Suffering at least one chronic illness was correlated to the marked decrease of EQ-5D index score (Coef. = -0.09; 95%CI = -0.17; -0.01). These results underline the importance of appropriate pain management as well as the provision of an interprofessional care approach to patients in order to alleviate the burden of comorbidities to their treatment outcomes and HRQOL.

BACKGROUND: Outcomes reporting in rotator cuff repair (RCR) literature has been variable. The minimal clinical important difference (MCID), substantial clinical benefit (SCB), and patient acceptable symptomatic state (PASS) bridge the gap between statistical significance and clinical relevance.
METHODS: The American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), Single Assessment Numeric Evaluation (SANE), and Constant-Murley (Constant) scores were collected preoperatively and 1 year postoperatively for patients undergoing RCR between 2014 and 2017. An anchor-based approach was used to calculate the MCID, SCB change, and PASS for the ASES questionnaire.
RESULTS: The study included 288 patients who underwent RCR. The MCID, SCB, and PASS were, respectively, 11.1, 17.5, and 86.7 for ASES, 4.6, 5.5, and 23.3 for the Constant score, and 16.9, 29.8, and 82.5 for the SANE score. Factors associated with reduced odds of achieving MCID were current smoking for ASES (odds ratio, 0.056) and single-row repair for the Constant score (odds ratio, 0.310). Workers\' compensation patients had reduced odds of achieving ASES SCB (odds ratio, 0.267) and were associated with reduced odds of achieving PASS by ASES (odds ratio, 0.244), SANE (OR, 0.452), and Constant (odds ratio, 0.313). Lower preoperative scores were associated with achieving MCID and SCB and higher preoperative Constant scores associated with PASS (P < .001).
CONCLUSIONS: This study establishes MCID, SCB, and PASS for ASES, Constant, and SANE scores in patients undergoing RCR. Factors associated with failing to achieve clinically significant values included current smoking, single-row repairs, high body mass index, and workers\' compensation status.

BACKGROUND: Clinical significance in a randomized controlled trial (RCT) can be determined using the minimal clinically important difference (MCID), which should inform the delta value used to determine sample size. The primary objective was to assess clinical significance in the pediatric oncology randomized controlled trial (RCT) treatment literature by evaluating: (1) the relationship between the treatment effect and the delta value as reported in the sample size calculation, and (2) the concordance between statistical and clinical significance. The secondary objective was to evaluate the reporting of methodological attributes related to clinical significance.
METHODS: RCTs of pediatric cancer treatments, where a sample size calculation with a delta value was reported or could be calculated, were systematically reviewed. MEDLINE, EMBASE, and the Cochrane Childhood Cancer Group Specialized Register through CENTRAL were searched from inception to July 2016.
RESULTS: RCTs (77 overall; 11 and 66), representing 95 (13 and 82) randomized questions were included for non-inferiority and superiority RCTs (herein, respectively). The minority (22.1% overall; 76.9 and 13.4%) of randomized questions reported conclusions based on clinical significance, and only 4.2% (15.4 and 2.4%) explicitly based the delta value on the MCID. Over half (67.4% overall; 92.3 and 63.4%) reported a confidence interval or standard error for the primary outcome experimental and control values and 12.6% (46.2 and 7.3%) reported the treatment effect, respectively. Of the 47 randomized questions in superiority trials that reported statistically non-significant findings, 25.5% were possibly clinically significant. Of the 24 randomized questions in superiority trials that were statistically significant, only 8.3% were definitely clinically significant.
CONCLUSIONS: A minority of RCTs in the pediatric oncology literature reported methodological attributes related to clinical significance and a notable portion of statistically insignificant studies were possibly clinically significance.

BACKGROUND: Athletes often are cleared to return to activities 6 months after anterior cruciate ligament (ACL) reconstruction; however, knee function measures continue to improve up to 2 years after surgery. Interventions beyond standard care may facilitate successful return to preinjury activities and improve functional outcomes. Perturbation training has been used in nonoperative ACL injury and preoperative ACL reconstruction rehabilitation, but has not been examined in postoperative ACL reconstruction rehabilitation, specifically return to sport rehabilitation.
OBJECTIVE: The purpose of this study was to determine whether there were differences at 1 and 2 years after ACL reconstruction between the male SAP (strengthening, agility, and secondary prevention) and SAP+PERT (SAP protocol with the addition of perturbation training) groups with respect to (1) quadriceps strength and single-legged hop limb symmetry; (2) patient-reported knee outcome scores; (3) the proportion who achieve self-reported normal knee function; and (4) the time from surgery to passing return to sport criteria.
METHODS: Forty men who had completed ACL reconstruction rehabilitation and met enrollment criteria (3-9 months after ACL reconstruction, > 80% quadriceps strength limb symmetry, no pain, full ROM, minimal effusion) were randomized into the SAP or SAP+PERT groups of the Anterior Cruciate Ligament-Specialised Post-Operative Return to Sports trial (ACL-SPORTS), a single-blind randomized clinical study of secondary prevention and return to sport. Quadriceps strength, single-legged hopping, the International Knee Documentation Committee (IKDC) 2000 subjective knee form, Knee Injury and Osteoarthritis Outcome Score (KOOS)-sports and recreation, and KOOS-quality-of-life subscales were collected 1 and 2 years after surgery by investigators blind to group. Athletes were categorized as having normal or abnormal knee function at each time point based on IKDC score, and the time until athletes passed strict return-to-sport criteria was also recorded. T-tests, chi square tests, and analyses of variance were used to identify differences between the treatment groups over time.
RESULTS: There were no differences between groups for quadriceps symmetry (1 year: SAP = 101% ± 14%, SAP+PERT = 101% ± 14%; 2 years: SAP = 103% ± 11%, SAP+PERT = 98% ± 14%; mean differences between groups at 1 year: 0.4 [-9.0 to 9.8], 2 years = 4.5 [-4.3 to 13.1]; mean difference between 1 and 2 years: SAP = -1.0 [-8.6 to 6.6], SAP+PERT = 3.0 [-4.3 to 10.3], p = 0.45) or single-legged hop test limb symmetry. There were no clinically meaningful differences for any patient-reported outcome measures. There was no difference in the proportion of athletes in each group who achieved normal knee function at 1 year (SAP 14 of 19, SAP+PERT 18 of 20, odds ratio 0.31 [0.5-19.0]; p = 0.18); however, the SAP+PERT group had fewer athletes with normal knee function at 2 years (SAP 17 of 17, SAP+PERT 14 of 19, p = 0.03). There were no differences between groups in the time to pass return to sport criteria (SAP = 325 ± 199 days, SAP+PERT = 233 ± 77 days; mean difference 92 [-9 to 192], p = 0.09).
CONCLUSIONS: This randomized trial found few differences between an ACL rehabilitation program consisting of strengthening, agility, and secondary prevention and one consisting of those elements as well as perturbation training. In the absence of clinically meaningful differences between groups in knee function and self-reported outcomes measures, the results indicate that perturbation training may not contribute additional benefit to the strengthening, agility, and secondary prevention base of the ACL-SPORTS training program.
METHODS: Level II, therapeutic study.