It is good to feel better, but better to feel good: whether a patient finds treatment ‘successful’ or not depends on the questions researchers ask

IntroductionIn sports physiotherapy, medicine and orthopaedic randomised controlled trials (RCT), the investigators (and readers) focus on the difference between groups in change scores from baseline to follow-up. Mean score changes are difficult to interpret (‘is an improvement of 20 units good?’), and follow-up scores may be more meaningful. We investigated how applying three different responder criteria to change and follow-up scores would affect the ‘outcome’ of RCTs. Responder criteria refers to participants’ perceptions of how the intervention affected them.MethodsWe applied three different criteria—minimal important change (MIC), patient acceptable symptom state (PASS) and treatment failure (TF)—to the aggregate Knee injury and Osteoarthritis Outcome Score (KOOS4) and the five KOOS subscales, the primary and secondary outcomes of the KANON trial (ISRCTN84752559). This trial included young active adults with an acute ACL injury and compared two treatment strategies: exercise therapy plus early reconstructive surgery, and exercise therapy plus delayed reconstructive surgery, if needed.ResultsMIC: At 2 years, more than 90% in the two treatment arms reported themselves to be minimally but importantly improved for the primary outcome KOOS4. PASS: About 50% of participants in both treatment arms reported their KOOS4 follow-up scores to be satisfactory. TF: Almost 10% of participants in both treatment arms found their outcomes so unsatisfactory that they thought their treatment had failed. There were no statistically significant or meaningful differences between treatment arms using these criteria.ConclusionWe applied change criteria as well as cross-sectional follow-up criteria to interpret trial outcomes with more clinical focus. We suggest researchers apply MIC, PASS and TF thresholds to enhance interpretation of KOOS and other patient-reported scores. The findings from this study can improve shared decision-making processes for people with an acute ACL injury.

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Responsiveness and Minimal Important Change of the IKDC of Middle-Aged and Older Patients With a Meniscal Tear

The American Journal of Sports Medicine ◽

10.1177/0363546518812880 ◽

2019 ◽

Vol 47 (2) ◽

pp. 364-371 ◽

Cited By ~ 3

Author(s):

Julia C.A. Noorduyn ◽

Victor A. van de Graaf ◽

Lidwine B. Mokkink ◽

Nienke W. Willigenburg ◽

Rudolf W. Poolman ◽

...

Keyword(s):

Physical Therapy ◽

Older Patients ◽

Meniscal Tear ◽

Important Change ◽

Minimal Important Change ◽

Meniscal Tears ◽

Arthroscopic Partial Meniscectomy ◽

Patient Reported ◽

Ikdc Score

Background: Responsiveness and the minimal important change (MIC) are important measurement properties to evaluate treatment effects and to interpret clinical trial results. The International Knee Documentation Committee (IKDC) Subjective Knee Form is a reliable and valid instrument for measuring patient-reported knee-specific symptoms, functioning, and sports activities in a population with meniscal tears. However, evidence on responsiveness is of limited methodological quality, and the MIC has not yet been established for patients with symptomatic meniscal tears. Purpose: To evaluate the responsiveness and determine the MIC of the IKDC for patients with meniscal tears. Study Design: Cohort study (design); Level of evidence 2. Methods: This study was part of the ESCAPE trial: a noninferiority multicenter randomized controlled trial comparing arthroscopic partial meniscectomy with physical therapy. Patients aged 45 to 70 years who were treated for a meniscal tear by arthroscopic partial meniscectomy or physical therapy completed the IKDC and 3 other questionnaires (RAND 36-Item Health Survey, EuroQol-5D-5L, and visual analog scales for pain) at baseline and 6-month follow-up. Responsiveness was evaluated by testing predefined hypotheses about the relation of the change in IKDC with regard to the change in the other self-reported outcomes. An external anchor question was used to distinguish patients reporting improvement versus no change in daily functioning. The MIC was determined by the optimal cutoff point in the receiver operating characteristic curve, which quantifies the IKDC score that best discriminated between patients with and without improvement in daily function. Results: Data from all 298 patients who completed baseline and 6-month follow-up questionnaires were analyzed. Responsiveness of the IKDC was confirmed in 7 of 10 predefined hypotheses about the change in IKDC score with regard to other patient-reported outcome measures. One hypothesis differed in the expected direction, while 2 hypotheses failed to meet the expected magnitude by 0.02 and 0.01 points. An MIC of 10.9 points was calculated for the IKDC of middle-aged and older patients with meniscal tears. Conclusion: This study showed that the IKDC is responsive to change among patients aged 45 to 70 years with meniscal tears, with an MIC of 10.9 points. This strengthens the value of the IKDC in quantifying treatment effects in this population.

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Vitamin D and Hospital Admission in Older Adults: A Prospective Association

Nutrients ◽

10.3390/nu13020616 ◽

2021 ◽

Vol 13 (2) ◽

pp. 616

Author(s):

Avril Beirne ◽

Kevin McCarroll ◽

James Bernard Walsh ◽

Miriam Casey ◽

Eamon Laird ◽

...

Keyword(s):

Older Adults ◽

Vitamin D ◽

Hospital Admission ◽

Cross Sectional Study ◽

Vitamin D Supplementation ◽

Inverse Association ◽

Cross Sectional ◽

Prospective Association ◽

Randomised Controlled

The health effects of vitamin D are well documented, with increasing evidence of its roles beyond bone. There is, however, little evidence of the effects of vitamin D on hospitalisation among older adults. This study aimed to prospectively determine the relationship of vitamin D status in older adults with hospital admission and emergency department (ED) attendance. Trinity University of Ulster Department of Agriculture (TUDA) is a large cross-sectional study of older adults with a community population from three disease-defined cohorts (cognitive dysfunction, hypertension, and osteoporosis). Participants included in this analysis were recruited between 2008 and 2012. ED and hospital admission data were gathered from the date of TUDA participation until June 2013, with a mean follow up of 3.6 years. Of the 3093 participants, 1577 (50.9%) attended the ED during the period of follow-up. Attendees had lower mean serum 25(OH)D concentrations than non-attendees (59.1 vs. 70.6 nmol/L). Fully adjusted models showed an inverse association between vitamin D and ED attendance (Hazard Ratio (HR) 0.996; 95% Confidence Interval (CI) 0.995–0.998; p < 0.001). A total of 1269 participants (41%) were admitted to hospital during the follow-up. Those admitted had lower mean vitamin D concentrations (58.4 vs. 69.3 nmol/L, p < 0.001). In fully adjusted models, higher vitamin D was inversely associated with hospital admission (HR 0.996; 95% CI 0.994–0.998; p < 0.001) and length of stay (LOS) (β = −0.95, p = 0.006). This study showed independent prospective associations between vitamin D deficiency and increased hospitalisation by older adults. The need for further evaluation of current recommendations in relation to vitamin D supplementation, with consideration beyond bone health, is warranted and should focus on randomised controlled trials.

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Assessing baseline dependency of anchor-based minimal important change (MIC): don’t stratify on the baseline score!

Quality of Life Research ◽

10.1007/s11136-021-02886-2 ◽

2021 ◽

Author(s):

Berend Terluin ◽

Ewa M. Roos ◽

Caroline B. Terwee ◽

Jonas B. Thorlund ◽

Lina H. Ingelsrud

Keyword(s):

Real Data ◽

Patient Reported Outcome ◽

Health Condition ◽

Important Change ◽

Alternative Methods ◽

Minimal Important Change ◽

Baseline Score ◽

Patient Reported ◽

Before And After ◽

Parallel Tests

Abstract Purpose The minimal important change (MIC) of a patient-reported outcome measure (PROM) is often suspected to be baseline dependent, typically in the sense that patients who are in a poorer baseline health condition need greater improvement to qualify as minimally important. Testing MIC baseline dependency is commonly performed by creating two or more subgroups, stratified on the baseline PROM score. This study’s purpose was to show that this practice produces biased subgroup MIC estimates resulting in spurious MIC baseline dependency, and to develop alternative methods to evaluate MIC baseline dependency. Methods Datasets with PROM baseline and follow-up scores and transition ratings were simulated with and without MIC baseline dependency. Mean change MICs, ROC-based MICs, predictive MICs, and adjusted MICs were estimated before and after stratification on the baseline score. Three alternative methods were developed and evaluated. The methods were applied in a real data example for illustration. Results Baseline stratification resulted in biased subgroup MIC estimates and the false impression of MIC baseline dependency, due to redistribution of measurement error. Two of the alternative methods require a second baseline measurement with the same PROM or another correlated PROM. The third method involves the construction of two parallel tests based on splitting the PROM’s item set. Two methods could be applied to the real data. Conclusion MIC baseline dependency should not be tested in subgroups based on stratification on the baseline PROM score. Instead, one or more of the suggested alternative methods should be used.

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Robot-assisted training after proximal humeral fracture: A randomised controlled multicentre intervention trial

Clinical Rehabilitation ◽

10.1177/0269215520961654 ◽

2020 ◽

pp. 026921552096165

Author(s):

Inga Kröger ◽

Corinna Nerz ◽

Lars Schwickert ◽

Sabine Schölch ◽

Janina Anna Müßig ◽

...

Keyword(s):

Prospective Trial ◽

Intervention Group ◽

Humeral Fracture ◽

Patient Reported Outcome ◽

Control Group ◽

Robot Assisted ◽

Patient Reported ◽

Usual Therapy ◽

Randomised Controlled

Objective: To examine whether robotic-assisted training as a supplement to usual therapy is safe, acceptable and improves function and patient reported outcome after proximal humeral fractures (PHF). Design: Multicentre, assessor-blinded, randomised controlled prospective trial. Setting: Three different rehabilitation hospitals in Germany. Subjects: In total 928 PHF patients between 35 and 70 years were screened. Forty-eight participants were included in the study (intervention group n = 23; control group n = 25). Intervention: The control group received usual occupational and physiotherapy over three weeks, and the intervention group received additional 12 robot-assisted training sessions at the ARMEO®-Spring. Main measures: Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH), the Wolf Motor Function Test-Orthopaedic, active range of motion and grip strength were determined before and after intervention period. The DASH was additionally obtained postal 6 and 13 months following surgery. Results: The mean age of participants was 55 ± 10 years and was similar in both groups ( p > 0.05). The change in DASH as the primary endpoint in the intervention group after intervention was −15 (CI = 8–22), at follow-up six month −7 (CI = −2 to 16) at follow up 13 month −9 (CI = 1–16); in control group −14 (CI = 11–18), at follow-up six month −13 (CI = 7–19) at follow up 13 month −6 (CI = −3 to 14). No difference in the change was found between groups ( p > 0.05). None of the follow-up time points demonstrated an additional benefit of the robotic therapy. Conclusion: The additional robot-assisted therapy was safe, acceptable but showed no improvement in functional shoulder outcome compared to usual therapy only.

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Efficacy and toxicity according to hormone therapy used in the CHHiP trial.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.316 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 316-316 ◽

Cited By ~ 1

Author(s):

Alison Tree ◽

Clare Griffin ◽

Emma Hall ◽

David P. Dearnaley ◽

Keyword(s):

Erectile Function ◽

Cox Regression ◽

Controlled Trial ◽

Similar Efficacy ◽

Trend Test ◽

Chi Square ◽

Patient Reported ◽

Toxicity Analysis ◽

Randomised Controlled

316 Background: CHHiP (CRUK/06/016) is a multicentre randomised controlled trial which investigated the use of moderately hypofractionated radiotherapy (RT) dose schedules for treatment of localised prostate cancer. 97% of participants (pts) had concurrent androgen deprivation therapy (ADT). Luteinising Hormone Releasing Hormone analogues (LHRHa) and bicalutamide 150mg (BIC) daily were permitted. This exploratory analysis investigates whether both ADT regimens show similar efficacy and whether BIC has the propensity to preserve erectile function. Methods: In CHHiP, 2700 pts received LHRH and 403 BIC, median duration 5.6 months. The primary endpoint was biochemical or clinical failure (BCF). ADT groups were compared with Cox regression adjusted forage, NCCN risk group, Gleason score,T-stage and stratified by RT dose. A key secondary endpoint was erectile function assessed by clinicians (LENTSOM subjective erectile function for vaginal penetration score) and pts (single items within UCLA-PCI and EPIC-50 questionnaires) at 2 years. 195/875 (22%) pts were excluded from this toxicity analysis as they had erectile dysfunction pre-ADT (grade (G) 3/4 LENTSOM). A chi square trend test compared ADT regimens. Results: Baseline demographics were similar except BIC pts were significantly younger (median 67 years BIC, 69 years LHRHa). With a median follow-up of 9.2 years, there was no evidence of a difference in BCF with an adjusted hazard ratio 0.95 (95% CI 0.75-1.20), p = 0.657. Eight year BCF rates were 80.7% (95%CI 79.0-82.2) and 80.3% (95%CI 75.8-84.0) for LHRHa and BIC pts respectively. At two years, LENTSOM erectile function was significantly worse (p < 0.0001) for LHRHa pts with 93/585 (16%), 95/585 (16%) and 125/585 (21%) G2, G3 and G4, compared to 3/68 (4%), 5/68 (7%) and 9/68 (13%) in BIC. At 2 years, the ability to have an erection, as reported by pts, was graded poor and very poor in 73/278 (26%) and 57/278 (21%) LHRHa pts and 5/23 (22%) and 4/23 (17%) in BIC pts (p = 0.584). Conclusions: There was no evidence of a difference in efficacy according to ADT received. BIC preserved clinician assessed (LENTSOM) erectile function at 2 years but patient reported outcomes did not show statistically significant differences with type of ADT. Clinical trial information: 97182923.

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Incidence and prognostic factors of knee extension deficits following anterior cruciate ligament reconstruction: A systematic review and meta-analysis of randomised controlled trials

10.1101/2020.11.26.20239046 ◽

2020 ◽

Author(s):

Nalan Ektas ◽

Corey Scholes ◽

Meredith Harrison-Brown ◽

Maha Jegatheesan ◽

Ashwin Rajesh ◽

...

Keyword(s):

Prognostic Factors ◽

Randomised Controlled Trials ◽

Acl Injury ◽

Knee Extension ◽

Cochrane Library ◽

Controlled Trials ◽

Extension Deficit ◽

Eligibility Criteria ◽

Randomised Controlled

ABSTRACTBackground and aimsKnee extension deficits complicate recovery from ACL injury and reconstruction, however the incidence of knee extension loss is not well defined. The aim of this review was to identify the incidence of loss of extension (LOE) following ACL rupture and reconstruction, explore the definitions of knee extension deficits reported and identify prognostic factors affecting LOE incidence.Methods and analysisA systematic search was conducted in Medline, Cochrane Library and PEDro for studies in publication up to September 2019, with no restrictions on publication year. References were screened and assessed for inclusion using predetermined eligibility criteria. Randomised controlled trials (RCTs) that quantified knee angle, loss of extension or incidence of extension deficit were included for quality assessment and data extraction. Statistical summaries were generated and meta-analyses performed in two parts to examine: (i) the probability of a datapoint being zero incidence compared to a non-zero incidence, and (ii) the relationship between the predictors and non-zero LOE incidence.ResultsA sample of 8594 papers were retrieved using the search criteria, with 48 studies meeting eligibility criteria. Pooled results from 4065 participants were included for analysis, with 3965 participants who had undergone ACLR. The proportion of included studies judged at an overall low risk of bias was small (6%). The analysis revealed median LOE incidence of 15.9% (IQR 1.4 - 46.5) at a median follow up from treatment of 4.9 months (IQR 1.9 - 24). Median LOE incidence was 23 % (IQR 8.4 - 50.0) for the subset of studies reporting up to 12 months of follow up. The observed group and study were the most important predictors for whether a datapoint reported an incidence of extension deficit. Time to follow up (P < 0.001) and graft type (P = 0.02) were found to have a significant influence on non-zero LOE incidence (%).ConclusionsThis review examined the definitions for the measurement and interpretation of postoperative knee extension, and established the trajectory of knee extension deficit after ACL injury and reconstruction. While factors associated with loss of extension were identified, the trajectory of knee extension deficits were difficult to infer due to discrepancies in measurement techniques and patient variation. Clinicians should expect up to 1 in 3 patients to present postoperatively with loss of extension of at least 3 degrees, which may partially resolve over time. Future work should focus on the development of a standardised framework for postoperative measurement and reporting of LOE.

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Assessing baseline dependency of anchor-based minimal important change (MIC): don’t stratify on the baseline score!

10.21203/rs.3.rs-317442/v1 ◽

2021 ◽

Author(s):

Berend Terluin ◽

Ewa M Roos ◽

Caroline B Terwee ◽

Jonas B Thorlund ◽

Lina H Ingelsrud

Keyword(s):

Real Data ◽

Patient Reported Outcome ◽

Health Condition ◽

Important Change ◽

Alternative Methods ◽

Minimal Important Change ◽

Baseline Score ◽

Patient Reported ◽

Before And After ◽

Parallel Tests

Abstract Purpose The minimal important change (MIC) of a patient-reported outcome measure (PROM) is often suspected to be baseline dependent, typically in the sense that patients who are in a poorer baseline health condition need greater improvements to qualify as minimally important. Testing MIC baseline dependency is commonly performed by creating two or more subgroups, stratified on the baseline PROM score. This study’s purpose was to show that this practice produces biased subgroup MIC estimates resulting in spurious MIC baseline dependency, and to develop alternative methods to evaluate MIC baseline dependency. Methods Datasets with PROM baseline and follow-up scores and transition ratings were simulated with and without MIC baseline dependency. Mean change MICs, ROC-based MICs, predictive MICs and adjusted MICs were estimated before and after stratification on the baseline score. Three alternative methods were developed and evaluated. The methods were applied in a real data example for illustration. Results Baseline stratification resulted in biased subgroup MIC estimates and the false impression of MIC baseline dependency, due to redistribution of measurement error. Two of the alternative methods require a second baseline measurement with the same PROM or another correlated PROM. The third method involves the construction of two parallel tests based on splitting the PROM’s item set. Two methods could be applied to the real data. Conclusion MIC baseline dependency should not be tested in subgroups based on stratification on the baseline PROM score. Instead, one or more of the suggested alternative methods should be used.

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Correction to: Sample size estimation for randomised controlled trials with repeated assessment of patient-reported outcomes: what correlation between baseline and follow-up outcomes should we assume?

Trials ◽

10.1186/s13063-019-3732-6 ◽

2019 ◽

Vol 20 (1) ◽

Author(s):

Stephen J. Walters ◽

Richard M. Jacques ◽

Inês Bonacho dos Anjos Henriques-Cadby ◽

Jane Candlish ◽

Nikki Totton ◽

...

Keyword(s):

Sample Size ◽

Randomised Controlled Trials ◽

Patient Reported Outcomes ◽

Sample Size Estimation ◽

Controlled Trials ◽

Size Estimation ◽

Patient Reported ◽

Randomised Controlled ◽

Repeated Assessment

Following publication of the original article [1], we have been notified that one of an error in the Conclusions section of the Abstract.

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Children with Hirschsprung's Disease and Syndromes with Cognitive Dysfunction: Manifestations, Treatment, and Outcomes

The Surgery Journal ◽

10.1055/s-0039-1696730 ◽

2019 ◽

Vol 05 (03) ◽

pp. e103-e109

Author(s):

Josefine Hedbys ◽

Johan Hasserius ◽

Christina Granéli ◽

Einar Arnbjörnsson ◽

Kristine Hagelsteen ◽

...

Keyword(s):

Cognitive Dysfunction ◽

Hirschsprung's Disease ◽

Hirschsprung’S Disease ◽

Retrospective Chart Review ◽

Bowel Function ◽

Cross Sectional ◽

Pediatric Surgeon ◽

Initial Symptoms ◽

Patient Reported

Abstract Introduction To assess differences in initial symptoms, treatments, and bowel function between children with Hirschsprung's disease (HD) with or without a cognitive dysfunction (CD). Materials and Methods The study included children with HD who underwent transanal endorectal pull-through. A retrospective chart review was performed to collect data on patient characteristics, diagnosis, and treatment. Data on bowel symptoms in children older than 4 years without a colostomy were compiled during a cross-sectional, patient-reported follow-up. Results Fifty-three children with HD were included; of these, 12 (23%) had CD. The median birth weight was lower, frequency of vomiting as the presenting symptom was lower, and time until the first contact with a pediatric surgeon was higher in children with CD than in those without (3,295 vs. 3,623 g, p = 0.013; 28 vs. 66%, p = 0.02; and 4 days vs. 1 day, p = 0.048, respectively). At follow-up, 5 (15%) of 33 children aged over 4 years had CD. More children without CD had some ability to hold back defecation and sense the urge to defecate than those with CD (p = 0.002 and p = 0.001, respectively). Conclusion HD children who have CD present with different initial symptoms, have a delay in the first consultation with a pediatric surgeon, and experience poorer bowel function outcomes than HD children without CD. Therefore, HD children with CD should receive special attention in both clinical practice and research.

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