Aims. The aim of this consensus was to develop a definition of post-operative fibrosis of the knee. Patients and Methods. An international panel of experts took part in a formal consensus process composed of a discussion phase and three Delphi rounds. Results. Post-operative fibrosis of the knee was defined as a limited range of movement (ROM) in flexion and/or extension, that is not attributable to an osseous or prosthetic block to movement from malaligned, malpositioned or incorrectly sized components, metal hardware, ligament reconstruction, infection (septic arthritis), pain, chronic regional pain syndrome (CRPS) or other specific causes, but due to soft-tissue fibrosis that was not present pre-operatively. Limitation of movement was graded as mild, moderate or severe according to the range of flexion (90° to 100°, 70° to 89°, < 70°) or extension deficit (5° to 10°, 11° to 20°, > 20°). Recommended investigations to support the diagnosis and a strategy for its management were also agreed. Conclusion. The development of standardised, accepted criteria for the diagnosis, classification and grading of the severity of post-operative fibrosis of the knee will facilitate the identification of patients for inclusion in clinical trials, the development of clinical guidelines, and eventually help to inform the management of this difficult condition. Cite this article: Bone Joint J 2016;98-B:1479–88

Aims. Meniscal allograft transplantation (MAT) for patients with symptomatic meniscal loss has demonstrated good clinical results and survivorship. Factors that affect both functional outcome and survivorship have been reported in the literature. These are typically single-centre case series with relatively small numbers and conflicting results. Our aim was to describe an international, two-centre case series, and identify factors that affect both functional outcome and survival. Methods. We report factors that affect outcome on 526 patients undergoing MAT across two sites (one in the UK and one in Italy). Outcomes of interest were the Knee injury and Osteoarthritis Outcome Score four (KOOS4) at two years and failure rates. We performed multiple regression analysis to examine for factors affecting KOOS, and Cox proportional hazards models for survivorship. Results. Our results indicate that baseline KOOS4 score affects functional outcome at two years, but no other included factors were significantly related to functional outcome. The only factor that affected failure rate was the presence of cartilage lesions down to bone on both the femur and tibia, decreasing the five-year survivorship from 95% (95% confidence interval (CI) 91 to 99) to 84% (95% CI 74 to 94). Conclusion. To our knowledge, this is the largest international cohort reporting on MAT. Our results indicate that factors such as age, BMI, and cartilage lesions down to bone on both the femur and tibia of the affected compartment should not present barriers to offering MAT. Baseline KOOS4 score and the presence of bone-on-bone arthritis can be used to help counsel patients regarding the expected risks and rewards of surgery. Cite this article: Bone Joint J 2022;104-B(6):657–662

Aims. Implantation of ultra-purified alginate (UPAL) gel is safe and effective in animal osteochondral defect models. This study aimed to examine the applicability of UPAL gel implantation to acellular therapy in humans with cartilage injury. Methods. A total of 12 patients (12 knees) with symptomatic, post-traumatic, full-thickness cartilage lesions (1.0 to 4.0 cm. 2. ) were included in this study. UPAL gel was implanted into chondral defects after performing bone marrow stimulation technique, and assessed for up to three years postoperatively. The primary outcomes were the feasibility and safety of the procedure. The secondary outcomes were self-assessed clinical scores, arthroscopic scores, tissue biopsies, and MRI-based estimations. Results. No obvious adverse events related to UPAL gel implantation were observed. Self-assessed clinical scores, including pain, symptoms, activities of daily living, sports activity, and quality of life, were improved significantly at three years after surgery. Defect filling was confirmed using second-look arthroscopy at 72 weeks. Significantly improved MRI scores were observed from 12 to 144 weeks postoperatively. Histological examination of biopsy specimens obtained at 72 weeks after implantation revealed an extracellular matrix rich in glycosaminoglycan and type II collagen in the reparative tissue. Histological assessment yielded a mean overall International Cartilage Regeneration & Joint Preservation Society II score of 69.1 points (SD 10.4; 50 to 80). Conclusion. This study provides evidence supporting the safety of acellular UPAL gel implantation in facilitating cartilage repair. Despite being a single-arm study, it demonstrated the efficacy of UPAL gel implantation, suggesting it is an easy-to-use, one-step method of cartilage tissue repair circumventing the need to harvest donor cells. Cite this article: Bone Joint J 2023;105-B(8):880–887

Aims. To determine the relationship between articular cartilage status and clinical outcomes after medial opening-wedge high tibial osteotomy (MOHTO) for medial compartmental knee osteoarthritis at intermediate follow-up. Methods. We reviewed 155 patients (155 knees) who underwent MOHTO from January 2008 to December 2016 followed by second-look arthroscopy with a mean 5.3-year follow-up (2.0 to 11.7). Arthroscopic findings were assessed according to the International Cartilage Repair Society (ICRS) Cartilage Repair Assessment (CRA) grading system. Patients were divided into two groups based on the presence of normal or nearly normal quality cartilage in the medial femoral condyle: good (second-look arthroscopic) status (ICRS grade I or II; n = 70), and poor (second-look arthroscopic) status (ICRS grade III or IV; n = 85) groups at the time of second-look arthroscopy. Clinical outcomes were assessed using the International Knee Documentation Committee (IKDC) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 36-Item Short Form survey. Results. Significant improvements in all clinical outcome categories were found between the preoperative and second-look arthroscopic assessments in both groups (p < 0.001). At the latest follow-up, the mean IKDC and WOMAC scores in the good status group further improved compared with those at the time of second-look arthroscopic surgery (p < 0.001), which was not shown in the poor status group. The mean IKDC (good status, 72.8 (SD 12.5); poor status, 64.7 (SD 12.1); p = 0.002) and mean WOMAC scores (good status, 15.7 (SD 10.8); poor status, 21.8 (SD 13.6); p = 0.004) significantly differed between both groups at the latest follow-up. Moreover, significant correlations were observed between ICRS CRA grades and IKDC scores (negative correlation; p < 0.001) and WOMAC scores (positive correlation; p < 0.001) at the latest follow-up. Good cartilage status was found more frequently in knees with the desired range of 2° to 6° valgus correction than in those with corrections outside this range (p = 0.019). Conclusion. Second-look arthroscopic cartilage status correlated with clinical outcomes after MOHTO at intermediate-term follow-up, despite the relatively small clinical differences between groups. Cite this article: Bone Joint J 2021;103-B(11):1686–1694

Aims. The aim of this study was to compare patient-reported outcomes (PROMs) following isolated anterior cruciate ligament reconstruction (ACLR), with those following ACLR and concomitant meniscal resection or repair. Methods. We reviewed prospectively collected data from the UK National Ligament Registry for patients who underwent primary ACLR between January 2013 and December 2022. Patients were categorized into five groups: isolated ACLR, ACLR with medial meniscus (MM) repair, ACLR with MM resection, ACLR with lateral meniscus (LM) repair, and ACLR with LM resection. Linear regression analysis, with isolated ACLR as the reference, was performed after adjusting for confounders. Results. From 14,895 ACLR patients, 4,400 had two- or five-year Knee injury and Osteoarthritis Outcome Scores (KOOS) available. At two years postoperatively, the MM repair group demonstrated inferior scores in KOOS pain (β = −3.63, p < 0.001), symptoms (β = − 4.88, p < 0.001), ADL (β = − 2.43, p = 0.002), sport and recreation (β = − 5.23, p < 0.001), quality of life (QoL) (β = − 5.73, p < 0.001), and International Knee Documentation Committee (β = − 4.1, p < 0.001) compared with the isolated ACLR group. The LM repair group was associated with worse KOOS sports and recreation scores at two years (β = − 4.264, p < 0.001). At five years, PROMs were comparable between the groups. At five years, PROMs were comparable between the groups. Participants undergoing ACLR surgery within 12 weeks from index injury demonstrated superior PROMs at two and five years. Conclusion. Our study showed that MM repair, and to a lesser extent LM repairs in combination with ACLR, were associated with inferior patient-reported outcome measures (PROMs) compared to isolated ACLR at two years postoperatively, while meniscal resection groups exhibited comparable outcomes. However, by five years postoperation, no significant differences in PROMs were evident. Further longer-term, cross-sectional studies are warranted to investigate the outcomes of ACLR and concomitant meniscal surgery

Aims. The aim of this study was to evaluate the association between chondral injury and interval from anterior cruciate ligament (ACL) tear to surgical reconstruction (ACLr). Methods. Between January 2012 and January 2022, 1,840 consecutive ACLrs were performed and included in a single-centre retrospective cohort. Exclusion criteria were partial tears, multiligament knee injuries, prior ipsilateral knee surgery, concomitant unicompartmental knee arthroplasty or high tibial osteotomy, ACL agenesis, and unknown date of tear. A total of 1,317 patients were included in the final analysis, with a median age of 29 years (interquartile range (IQR) 23 to 38). The median preoperative Tegner Activity Score (TAS) was 6 (IQR 6 to 7). Patients were categorized into four groups according to the delay to ACLr: < three months (427; 32%), three to six months (388; 29%), > six to 12 months (248; 19%), and > 12 months (254; 19%). Chondral injury was assessed during arthroscopy using the International Cartilage Regeneration and Joint Preservation Society classification, and its association with delay to ACLr was analyzed using multivariable analysis. Results. In the medial compartment, delaying ACLr for more than 12 months was associated with an increased rate (odds ratio (OR) 1.93 (95% confidence interval (CI) 1.27 to 2.95); p = 0.002) and severity (OR 1.23 (95% CI 1.08 to 1.40); p = 0.002) of chondral injuries, compared with < three months, with no association in patients aged > 50 years old. No association was found for shorter delays, but the overall dose-effect analysis was significant for the rate (p = 0.015) and severity (p = 0.026) of medial chondral injuries. Increased TAS was associated with a significantly reduced rate (OR 0.88 (95% CI 0.78 to 0.99); p = 0.036) and severity (OR 0.96 (95% CI 0.92 to 0.99); p = 0.017) of medial chondral injuries. In the lateral compartment, no association was found between delay and chondral injuries. Conclusion. Delay was associated with an increased rate and severity of medial chondral injuries in a dose-effect fashion, in particular for delays > 12 months. Younger patients seem to be at higher risk of chondral injury when delaying surgery. The timing of ACLr should be optimally reduced in this population. Cite this article: Bone Joint J 2023;105-B(9):953–960

Aims. The diagnosis of periprosthetic joint infection (PJI) continues to present a significant clinical challenge. New biomarkers have been proposed to support clinical decision-making; among them, synovial fluid alpha-defensin has gained interest. Current research methodology suggests reference methods are needed to establish solid evidence for use of the test. This prospective study aims to evaluate the diagnostic accuracy of high-performance liquid chromatography coupled with the mass spectrometry (LC-MS) method to detect alpha-defensin in synovial fluid. Methods. Between October 2017 and September 2019, we collected synovial fluid samples from patients scheduled to undergo revision surgery for painful total knee arthroplasty (TKA). The International Consensus Meeting criteria were used to classify 33 PJIs and 92 aseptic joints. LC-MS assay was performed to measure alpha-defensin in synovial fluid of all included patients. Sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic curve (AUC) were calculated to define the test diagnostic accuracy. Results. The AUC was 0.99 (95% confidence interval (CI) 0.98 to 1.00). Receiver operating characteristic (ROC) analysis showed that the optimal cut-off value of synovial fluid alpha-defensin was 1.0 μg/l. The sensitivity of alpha-defensin was 100% (95% CI 96 to 100), the specificity was 97% (95% CI 90 to 98), the positive predictive value was 89.2% (95% CI 82 to 94), and negative predictive value was 100% (95% CI 96 to 100). ROC analysis demonstrated an AUC of 0.99 (95% CI 0.98 to 1.0). Conclusion. The present study confirms the utility of alpha-defensin in the synovial fluid in patients with painful TKA to select cases of PJI. Since LC-MS is still a time-consuming technology and is available in highly specialized laboratories, further translational research studies are needed to take this evidence into routine procedures and promote a new diagnostic approach. Cite this article: Bone Joint J 2022;104-B(9):1047–1051

Aims. This study used an artificial neural network (ANN) model to determine the most important pre- and perioperative variables to predict same-day discharge in patients undergoing total knee arthroplasty (TKA). Methods. Data for this study were collected from the National Surgery Quality Improvement Program (NSQIP) database from the year 2018. Patients who received a primary, elective, unilateral TKA with a diagnosis of primary osteoarthritis were included. Demographic, preoperative, and intraoperative variables were analyzed. The ANN model was compared to a logistic regression model, which is a conventional machine-learning algorithm. Variables collected from 28,742 patients were analyzed based on their contribution to hospital length of stay. Results. The predictability of the ANN model, area under the curve (AUC) = 0.801, was similar to the logistic regression model (AUC = 0.796) and identified certain variables as important factors to predict same-day discharge. The ten most important factors favouring same-day discharge in the ANN model include preoperative sodium, preoperative international normalized ratio, BMI, age, anaesthesia type, operating time, dyspnoea status, functional status, race, anaemia status, and chronic obstructive pulmonary disease (COPD). Six of these variables were also found to be significant on logistic regression analysis. Conclusion. Both ANN modelling and logistic regression analysis revealed clinically important factors in predicting patients who can undergo safely undergo same-day discharge from an outpatient TKA. The ANN model provides a beneficial approach to help determine which perioperative factors can predict same-day discharge as of 2018 perioperative recovery protocols. Cite this article: Bone Joint J 2021;103-B(8):1358–1366

Aims. The Oswestry-Bristol Classification (OBC) is an MRI-specific assessment tool to grade trochlear dysplasia. The aim of this study is to validate clinically the OBC by demonstrating its use in selecting treatments that are safe and effective. Methods. The OBC and the patellotrochlear index were used as part of the Oswestry Patellotrochlear Algorithm (OPTA) to guide the surgical treatment of patients with patellar instability. Patients were assigned to one of four treatment groups: medial patellofemoral ligament reconstruction (MPFLr); MPFLr + tibial tubercle distalization (TTD); trochleoplasty; or trochleoplasty + TTD. A prospective analysis of a longitudinal patellofemoral database was performed. Between 2012 and 2018, 202 patients (233 knees) with a mean age of 24.2 years (SD 8.1), with recurrent patellar instability were treated by two fellowship-trained consultant sports/knee surgeons at The Robert Jones and Agnes Hunt Orthopaedic Hospital. Clinical efficacy of each treatment group was assessed by Kujala, International Knee Documentation Committee (IKDC), and EuroQol five-dimension questionnaire (EQ-5D) scores at baseline, and up to 60 months postoperatively. Their safety was assessed by complication rate and requirement for further surgery. The pattern of clinical outcome over time was analyzed using mixed regression modelling. Results. In all, 135 knees (mean age 24.9 years (SD 9.4)) were treated using a MPFLr. Ten knees (7.4%) required additional surgery. A total of 50 knees (mean age 24.4 years (SD 6.3)) were treated using MPFLr + TTD. Ten (20%) required additional surgery. A total of 20 knees (mean age 19.5 years (SD 3.0)) were treated using trochleoplasty + TTD. Three patients (15%) required additional surgery. In each treatment group, there was a significant improvement in Kujala, IKDC, and EQ-5D at one year postoperatively (p < 0.001) with a recognized level of overall complication rate. Conclusion. The OBC is a valid assessment tool to grade patients with trochlear dysplasia and, when used as part of the OPTA, helps to determine treatments that are safe and effective. This fulfils the requirements for its application in mainstream clinical practice. Cite this article: Bone Joint J 2021;103-B(10):1586–1594

Aims. Anterior cruciate ligament (ACL) rupture commonly leads to post-traumatic osteoarthritis, regardless of surgical reconstruction. This study uses standing MRI to investigate changes in contact area, contact centroid location, and tibiofemoral alignment between ACL-injured knees and healthy controls, to examine the effect of ACL reconstruction on these parameters. Methods. An upright, open MRI was used to directly measure tibiofemoral contact area, centroid location, and alignment in 18 individuals with unilateral ACL rupture within the last five years. Eight participants had been treated nonoperatively and ten had ACL reconstruction performed within one year of injury. All participants were high-functioning and had returned to sport or recreational activities. Healthy contralateral knees served as controls. Participants were imaged in a standing posture with knees fully extended. Results. Participants’ mean age was 28.4 years (SD 7.3), the mean time since injury was 2.7 years (SD 1.6), and the mean International Knee Documentation Subjective Knee Form score was 84.4 (SD 13.5). ACL injury was associated with a 10% increase (p = 0.001) in contact area, controlling for compartment, sex, posture, age, body mass, and time since injury. ACL injury was associated with a 5.2% more posteriorly translated medial centroid (p = 0.001), equivalent to a 2.6 mm posterior translation on a representative tibia with mean posteroanterior width of 49.4 mm. Relative to the femur, the tibiae of ACL ruptured knees were 2.3 mm more anteriorly translated (p = 0.003) and 2.6° less externally rotated (p = 0.010) than healthy controls. ACL reconstruction was not associated with an improvement in any measure. Conclusion. ACL rupture was associated with an increased contact area, posteriorly translated medial centroid, anterior tibial translation, and reduced tibial external rotation in full extension. These changes were present 2.7 years post-injury regardless of ACL reconstruction status. Cite this article: Bone Joint J 2021;103-B(9):1505–1513

Aims. MRI has been suggested as an objective method of assessing anterior crucate ligament (ACL) graft “ligamentization” after reconstruction. It has been proposed that the MRI appearances could be used as an indicator of graft maturity and used as part of a return-to-sport assessment. The aim of this study was to evaluate the correlation between MRI graft signal and postoperative functional scores, anterior knee laxity, and patient age at operation. Methods. A consecutive cohort of 149 patients who had undergone semitendinosus autograft ACL reconstruction, using femoral and tibial adjustable loop fixations, were evaluated retrospectively postoperatively at two years. All underwent MRI analysis of the ACL graft, performed using signal-to-noise quotient (SNQ) and the Howell score. Functional outcome scores (Lysholm, Tegner, International Knee Documentation Committee (IKDC) subjective, and IKDC objective) were obtained and all patients underwent instrumented side-to-side anterior laxity differential laxity testing. Results. Two-year postoperative mean outcome scores were: Tegner 6.5 (2 to 10); Lysholm 89.8 (SD 10.4; 52 to 100); and IKDC subjective 86.8 (SD 11.8; 51 to 100). The objective IKDC score was 86% A (128 patients), 13% B (19 patients), and 1% C (two patients). Mean side-to-side anterior laxity difference (134 N force) was 0.6 mm (SD 1.8; -4.1 to 5.6). Mean graft SNQ was 2.0 (SD 3.5; -14 to 17). Graft Howell scores were I (61%, 91 patients), II (25%, 37 patients), III (13%, 19 patients), and IV (1%, two patients). There was no correlation between either Howell score or SNQ with instrumented anterior or Lysholm, Tegner, and IKDC scores, nor was any correlation found between patient age and ACL graft SNQ or Howell score. Conclusion. The two-year postoperative MRI appearances of four-strand, semitendinosus ACL autografts (as measured by SNQ and Howell score) do not appear to have a relationship with postoperative functional scores, instrumented anterior laxity, or patient age at surgery. Other tools for analysis of graft maturity should be developed. Cite this article: Bone Jt Open 2021;2(8):569–575

Aims. Although knee osteoarthritis (OA) is diagnosed and monitored radiologically, actual full-thickness cartilage loss (FTCL) has rarely been correlated with radiological classification. This study aims to analyze which classification system correlates best with FTCL and to assess their reliability. Methods. A prospective study of 300 consecutive patients undergoing unilateral total knee arthroplasty (TKA) for OA (mean age 69 years (44 to 91; standard deviation (SD) 9.5), 178 (59%) female). Two blinded examiners independently graded preoperative radiographs using five common systems: Kellgren-Lawrence (KL); International Knee Documentation Committee (IKDC); Fairbank; Brandt; and Ahlbäck. Interobserver agreement was assessed using the intraclass correlation coefficient (ICC). Intraoperatively, anterior cruciate ligament (ACL) status and the presence of FTCL in 16 regions of interest were recorded. Radiological classification and FTCL were correlated using the Spearman correlation coefficient. Results. Knees had a mean of 6.8 regions of FTCL (SD 3.1), most common medially. The commonest patterns of FTCL were medial ± patellofemoral (143/300, 48%) and tricompartmental (89/300, 30%). ACL status was associated with pattern of FTCL (p = 0.023). All radiological classification systems demonstrated moderate ICC, but this was highest for the IKDC: whole knee 0.68 (95% confidence interval (CI) 0.60 to 0.74); medial compartment 0.84 (95% CI 0.80 to 0.87); and lateral compartment 0.79 (95% CI 0.73 to 0.83). Correlation with actual FTCL was strongest for Ahlbäck (Spearman rho 0.27 to 0.39) and KL (0.30 to 0.33) systems, although all systems demonstrated medium correlation. The Ahlbäck score was the most discriminating in severe knee OA. Osteophyte presence in the medial compartment had high positive predictive value (PPV) for FTCL, but not in the lateral compartment. Conclusion. The Ahlbäck and KL systems had the highest correlation with confirmed cartilage loss at TKA. However, the IKDC system displayed the best interobserver reliability, with favourable correlation with FTCL in medial and lateral compartments, although it was less discriminating in more severe disease. Cite this article: Bone Joint J 2020;102-B(3):301–309

Aim. Mesenchymal stem cells (MSCs) have several properties that may support their use as an early treatment option for osteoarthritis (OA). This study investigated the role of multiple injections of allogeneic bone marrow-derived stem cells (BMSCs) to alleviate the progression of osteoarthritic changes in the various structures of the mature rabbit knee in an anterior cruciate ligament (ACL)-deficient OA model. Materials and Methods. Two months after bilateral section of the ACL of Japanese white rabbits aged nine months or more, either phosphate buffered saline (PBS) or 1 x 10. 6. MSCs were injected into the knee joint in single or three consecutive doses. After two months, the articular cartilage and meniscus were assessed macroscopically, histologically, and immunohistochemically using collagen I and II. Results. Within the PBS injection (control group), typical progressive degenerative changes were revealed in the various knee structures. In the single MSC injection (single group), osteoarthritic changes were attenuated, but still appeared, especially in the medial compartments involving fibrillation of the articular cartilage, osteophyte formation in the medial plateau, and longitudinal tear of the meniscus. In the multiple-injections group, the smoothness and texture of the articular cartilage and meniscus were improved. Histologically, absence or reduction in matrix staining and cellularity were noticeable in the control and single-injection groups, respectively, in contrast to the multiple-injections group, which showed good intensity of matrix staining and chondrocyte distribution in the various cartilage zones. Osteoarthritis Research Society International (OARSI) scoring showed significantly better results in the multiple-injections group than in the other groups. Immunohistochemically, collagen I existed superficially in the medial femoral condyle in the single group, while collagen II was more evident in the multiple-injections group than the single-injection group. Conclusion. A single injection of MSCs was not enough to restore the condition of osteoarthritic joints. This is in contrast to multiple injections of MSCs, which had the ability to replace lost cells, as well as reducing inflammation. Cite this article: Bone Joint J 2019;101-B:824–831

Aims

The aim of this study was to establish consensus statements on the diagnosis, nonoperative management, and indications, if any, for medial patellofemoral complex (MPFC) repair in patients with patellar instability, using the modified Delphi approach.

Aims

This study aims to determine difference in annual rate of early-onset (≤ 90 days) deep surgical site infection (SSI) following primary total knee arthroplasty (TKA) for osteoarthritis, and to identify risk factors that may be associated with infection.

Aims

To map literature on prognostic factors related to outcomes of revision total knee arthroplasty (rTKA), to identify extensively studied factors and to guide future research into what domains need further exploration.

Aims

Multiligament knee injuries (MLKI) are devastating injuries that can result in significant morbidity and time away from sport. There remains considerable variation in strategies employed for investigation, indications for operative intervention, outcome reporting, and rehabilitation following these injuries. At present no study has yet provided a comprehensive overview evaluating the extent, range, and overall summary of the published literature pertaining to MLKI. Our aim is to perform a methodologically rigorous scoping review, mapping the literature evaluating the diagnosis and management of MLKI.

Aims

Aseptic loosening is the most common cause of failure following cemented total knee arthroplasty (TKA), and has been linked to poor cementation technique. We aimed to develop a consensus on the optimal technique for component cementation in TKA.

Aims

The aim of this study was to describe the prevalence and patterns of neuropathic pain over one year in a cohort of patients with chronic post-surgical pain at three months following total knee arthroplasty (TKA).

Aims

The metabolic equivalent of task (MET) score examines patient performance in relation to energy expenditure before and after knee arthroplasty. This study assesses its use in a knee arthroplasty population in comparison with the widely used Oxford Knee Score (OKS) and EuroQol five-dimension index (EQ-5D), which are reported to be limited by ceiling effects.