Use of human predictive patch test (HPPT) data for the classification of skin sensitization hazard and potency.

Since the 1940s, patch tests in healthy volunteers (Human Predictive Patch Tests, HPPTs) have been used to identify chemicals that cause skin sensitization in humans. Recently, we reported the results of a major curation effort to support the development of OECD Guideline 497 on Defined Approaches (DAs) for skin sensitization (OECD in Guideline No. 497: Defined Approaches on Skin Sensitisation, 2021a. https://doi.org/10.1787/b92879a4-en ). In the course of this work, we compiled and published a database of 2277 HPPT results for 1366 unique test substances (Strickland et al. in Arch Toxicol 97:2825-2837, 2023. https://doi.org/10.1007/s00204-023-03530-3 ). Here we report a detailed analysis of the value of HPPT data for classification of chemicals as skin sensitizers under the United Nations' Globally Harmonized System of Classification and Labelling of Chemicals (GHS). As a result, we propose the dose per skin area (DSA) used for classification by the GHS to be replaced by or complemented with a dose descriptor that may better reflect sensitization incidence [e.g., the DSA causing induction of sensitization in one individual (DSA1+) or the DSA leading to an incidence of induction in 5% of the tested individuals (DSA05)]. We also propose standardized concepts and workflows for assessing individual HPPT results, for integrating multiple HPPT results and for using them in concert with Local Lymph Node Assay (LLNA) data in a weight of evidence (WoE) assessment. Overall, our findings show that HPPT results are often not sufficient for deriving unambiguous classifications on their own. However, where they are, the resulting classifications are reliable and reproducible and can be integrated well with those from other skin sensitization data, such as the LLNA.

Computational application of internationally harmonized defined approaches to skin sensitization: DASS App.

BACKGROUND: Chemically induced skin sensitization, or allergic contact dermatitis, is a common occupational and public health issue. Regulatory authorities require an assessment of potential to cause skin sensitization for many chemical products. Defined approaches for skin sensitization (DASS) identify potential chemical skin sensitizers by integrating data from multiple non-animal tests based on human cells, molecular targets, and computational model predictions using standardized data interpretation procedures. While several DASS are internationally accepted by regulatory agencies, the data interpretation procedures vary in logical complexity, and manual application can be time-consuming or prone to error. RESULTS: We developed the DASS App, an open-source web application, to facilitate user application of three regulatory testing strategies for skin sensitization assessment: the Two-out-of-Three (2o3), the Integrated Testing Strategy (ITS), and the Key Event 3/1 Sequential Testing Strategy (KE 3/1 STS) without the need for software downloads or computational expertise. The application supports upload and analysis of user-provided data, includes steps to identify inconsistencies and formatting issues, and provides predictions in a downloadable format. CONCLUSION: This open-access web-based implementation of internationally harmonized regulatory guidelines for an important public health endpoint is designed to support broad user uptake and consistent, reproducible application. The DASS App is freely accessible via https://ntp.niehs.nih.gov/go/952311 and all scripts are available on GitHub ( https://github.com/NIEHS/DASS ).

Comparative Toxicity of Seven Aqueous Film-Forming Foam to In Vitro Systems and Mus.

The comparative toxicity of six per- and polyfluoroalkyl substance (PFAS)-free and one PFAS-containing aqueous film-forming foam (AFFF) was evaluated in an outbred mouse species as well as several in vitro assays. The in vivo toxicological profile of PFAS-free AFFFs in short-term, high-concentration exposures is different than that of a PFAS-containing AFFF. The PFAS-containing reference product induced increased liver weights, while the PFAS-free AFFFs were linked to either decreased or unaffected relative liver weights. The in vitro toxicological profile across PFAS-free AFFFs was uniform except in the Microtox® assay, where thresholds were variable and spanned several orders of magnitude. This direct comparison of products through short-term toxicity tests and in vitro screenings represents early data to support evaluation of potential regrettable substitutions when selecting alternative PFAS-free AFFFs. Further work in diverse taxa (e.g., aquatic organisms, terrestrial invertebrates, birds) and mammalian studies capturing sensitive life stages will refine and expand this data set across a range of risk-relevant toxicological endpoints. Environ Toxicol Chem 2023;42:2364-2374. Published 2023. This article is a U.S. Government work and is in the public domain in the USA.

Early Initiation of Vestibular Therapy Following Sports-Related Concussions: A Retrospective Cohort Study.

BACKGROUND: Vestibular dysfunction is common following sports-related concussions (SRC). Within the current practice, it is theorized that patients with vestibular dysfunction as sequelae of sports-related concussion have a prolonged recovery time compared to those without vestibular dysfunction. STUDY METHOD:  A retrospective, cohort investigation of 282 subjects with sports-related concussions with vestibular dysfunction was conducted at The Sports Medicine Concussion Clinic, Duke University. The primary endpoint was the return-to-play (RTP) date. RESULTS: For every one-day increase in time from injury to initial vestibular therapy, the geometric mean time from injury to RTP increases by 1.02 days (exp{ß}=1.02 days; 95% CI: 1.01, 1.02 days; p<0.001). CONCLUSION:  Our data suggest an association between the timing of vestibular therapy in SRC and a direct relationship to earlier recovery and return to sport.

Technical framework for enabling high quality measurements in new approach methodologies (NAMs).

New approach methodologies (NAMs) are in vitro, in chemico, and in silico or computational approaches that can potentially be used to reduce animal testing. For NAMs that require laboratory experiments, it is critical that they provide consistent and reliable results. While guidance has been provided on improving the reproducibility of NAMs that require laboratory experiments, there is not yet an overarching technical framework that details how to add measurement quality features into a protocol. In this manuscript, we discuss such a framework and provide a step-by-step process describing how to refine a protocol using basic quality tools. The steps in this framework include 1) conceptual analysis of sources of technical variability in the assay, 2) within-laboratory evaluation of assay performance, 3) statistical data analysis, and 4) determination of method transferability (if needed). While each of these steps has discrete components, they are all inter-related, and insights from any step can influence the others. Following the steps in this framework can help reveal the advantages and limitations of different choices during the design of an assay such as which in-process control measurements to include and how many replicates to use for each control measurement and for each test substance. Overall, the use of this technical framework can support optimizing NAM reproducibility, thereby supporting meeting research and regulatory needs.

IVIVE: Facilitating the Use of In Vitro Toxicity Data in Risk Assessment and Decision Making.

During the past few decades, the science of toxicology has been undergoing a transformation from observational to predictive science. New approach methodologies (NAMs), including in vitro assays, in silico models, read-across, and in vitro to in vivo extrapolation (IVIVE), are being developed to reduce, refine, or replace whole animal testing, encouraging the judicious use of time and resources. Some of these methods have advanced past the exploratory research stage and are beginning to gain acceptance for the risk assessment of chemicals. A review of the recent literature reveals a burst of IVIVE publications over the past decade. In this review, we propose operational definitions for IVIVE, present literature examples for several common toxicity endpoints, and highlight their implications in decision-making processes across various federal agencies, as well as international organizations, including those in the European Union (EU). The current challenges and future needs are also summarized for IVIVE. In addition to refining and reducing the number of animals in traditional toxicity testing protocols and being used for prioritizing chemical testing, the goal to use IVIVE to facilitate the replacement of animal models can be achieved through their continued evolution and development, including a strategic plan to qualify IVIVE methods for regulatory acceptance.

Venous Thromboembolism Prophylaxis and Hormonal Contraceptive Management Practice Patterns in the Perioperative Period for Anterior Cruciate Ligament Reconstruction.

Purpose: To evaluate the venous thromboembolism (VTE) prophylaxis practices of surgeons performing anterior cruciate ligament reconstruction (ACLR) in female patients using hormonal contraceptives. Methods: Our research team designed an investigational survey using branching logic that was made available to the AANA membership. The survey was designed to identify clinical decision making regarding VTE prophylaxis after ACLR in patients without risk factors for VTE, the counseling of patients about VTE risk associated with hormonal contraceptives, and the use of VTE prophylaxis after ACLR in patients taking hormonal contraceptives. Results: Ninety-four respondents completed the survey. Eighty-nine respondents identified their gender (63% male and 37% female respondents). Respondents reported performing the following number of ACLRs annually: more than 50 (40%), 30 to 50 (29%), 15 to 30 (29%), and fewer than 15 (2%). Of the respondents, 62 (67%) reported that VTE developed after ACLR in their patients (male patients only, 32%; female patients only, 24%; and both male and female patients, 34%). Sixty-seven percent used chemoprophylaxis after ACLR. Surgeons who asked about hormonal contraceptive use were more likely to be women (P = .01; odds ratio [OR], 4.2). Surgeons who changed their VTE prophylaxis plan as a result of asking about hormonal contraceptive use were more likely to be women (P = .02; OR, 2.8). Surgeons who asked about hormonal contraceptive use were more likely to have female patients with VTE after ACLR (P = .03; OR, 2.9). Surgeons who changed their VTE prophylaxis plan as a result of asking about hormonal contraceptive use were more likely to have female patients with VTE after ACLR (P = .001; OR, 4.6). Conclusions: There is no standard of care for VTE prophylaxis after ACLR. A surgeon's own gender and prior clinical experience with VTE after ACLR may influence his or her likelihood to consider a patient's hormonal contraceptive use regarding VTE risk after ACLR. Clinical Relevance: The use of hormonal contraception is a risk factor for VTE in female patients undergoing ACLR. It is important to identify current practice patterns and the need for a standard of care.

Meniscal Treatment as a Predictor of Worse Articular Cartilage Damage on MRI at 2 Years After ACL Reconstruction: The MOON Nested Cohort.

BACKGROUND: Patients undergoing anterior cruciate ligament reconstruction (ACLR) are at an increased risk for posttraumatic osteoarthritis (PTOA). While we have previously shown that meniscal treatment with ACLR predicts more radiographic PTOA at 2 to 3 years postoperatively, there are a limited number of similar studies that have assessed cartilage directly with magnetic resonance imaging (MRI). HYPOTHESIS: Meniscal repair or partial meniscectomy at the time of ACLR independently predicts more articular cartilage damage on 2- to 3-year postoperative MRI compared with a healthy meniscus or a stable untreated tear. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A consecutive series of patients undergoing ACLR from 1 site within the prospective, nested Multicenter Orthopaedic Outcomes Network (MOON) cohort underwent bilateral knee MRI at 2 to 3 years postoperatively. Patients were aged <36 years without previous knee injuries, were injured while playing sports, and had no history of concomitant ligament surgery or contralateral knee surgery. MRI scans were graded by a board-certified musculoskeletal radiologist using the modified MRI Osteoarthritis Knee Score (MOAKS). A proportional odds logistic regression model was built to predict a MOAKS-based cartilage damage score (CDS) relative to the contralateral control knee for each compartment as well as for the whole knee, pooled by meniscal treatment, while controlling for sex, age, body mass index, baseline Marx activity score, and baseline operative cartilage grade. For analysis, meniscal injuries surgically treated with partial meniscectomy or meniscal repair were grouped together. RESULTS: The cohort included 60 patients (32 female; median age, 18.7 years). Concomitant meniscal treatment at the time of index ACLR was performed in 17 medial menisci (13 meniscal repair and 4 partial meniscectomy) and 27 lateral menisci (3 meniscal repair and 24 partial meniscectomy). Articular cartilage damage was worse in the ipsilateral reconstructed knee (P < .001). A meniscal injury requiring surgical treatment with ACLR predicted a worse CDS for medial meniscal treatment (medial compartment CDS: P = .005; whole joint CDS: P < .001) and lateral meniscal treatment (lateral compartment CDS: P = .038; whole joint CDS: P = .863). Other predictors of a worse relative CDS included age for the medial compartment (P < .001), surgically observed articular cartilage damage for the patellofemoral compartment (P = .048), and body mass index (P = .007) and age (P = .020) for the whole joint. CONCLUSION: A meniscal injury requiring surgical treatment with partial meniscectomy or meniscal repair at the time of ACLR predicted worse articular cartilage damage on MRI at 2 to 3 years after surgery. Further research is required to differentiate between the effects of partial meniscectomy and meniscal repair.

Can Patient-Reported Outcome Measurement Information System Measures Differentiate Patients Who Will Undergo Hip and Knee Total Joint Arthroplasty: A Retrospective Case-Control Study.

BACKGROUND: The Patient-Reported Outcome Measurement Information System (PROMIS) can be used to monitor patients in population-health-based programs. However, it is unknown which measures are most appropriate to differentiate patients who will undergo hip or knee total joint arthroplasty (TJA) in a cohort of patients with osteoarthritis. METHODS: A retrospective cohort of new patients consulting for treatment from November 17, 2017 to April 20, 2020 (cases: hip: n = 157, knee: n = 112; randomly selected nonsurgical controls: hip: n = 314, knee: n = 224) was extracted from the electronic health record. We recorded demographics, comorbidity, and PROMIS scores for 8 domains (physical function, pain interference, pain intensity, anxiety, depression, sleep disturbance, ability to participate in social roles and activities, and fatigue). We performed descriptive statistics to characterize the cohorts and baseline PROMIS scores and conducted logistic regression models to determine which PROMIS domains differentiated patients undergoing hip and knee TJA. RESULTS: In univariate comparisons of PROMIS domains, the hip and knee surgical cohorts differed from controls in physical function (P < .01), pain interference (P < .01), and ability to participate in social roles and activities (P < .02). In logistic regression models informed by univariate analyses, PROMIS physical function was the only PROMIS measure to differentiate undergoing surgery in both hip and knee cohorts (P < .01). CONCLUSION: PROMIS physical function can differentiate TJA cases from nonsurgical controls in both hip and knee patients. These findings have implications for considering which PROMIS measures to administer in patients with hip and knee osteoarthritis.

Medical Diagnoses in a University Athlete Training Room Clinic.

INTRODUCTION: Approximately 560 000 student-athletes participate in university athletic programs every year. These athletes develop a variety of medical injuries and illnesses during their time at the university. There is currently a paucity of data with regarding medical encounters in a dedicated university athlete training room clinic. OBJECTIVE: This study aims to provide data regarding medical diagnoses from a university athlete training room clinic. STUDY DESIGN: Descriptive epidemiology study. SETTING: University athlete training room clinic. PATIENTS: University athletes. METHODS: The electronic medical record for a year-round, athlete-only training room clinic at a private US university was reviewed. Athlete age, sex, sport, date of medical encounter, and encounter diagnoses across 5 calendar years were recorded; medical diagnoses were then manually stratified into diagnostic categories and subgroups. RESULTS: A total of 1258 university athletes were evaluated during 5303 medical encounters. Approximately two-thirds of athletes were evaluated one or more times per year. Average number of encounters per athlete per year was 2.2 (0.6-3.8, 95% confidence interval). The football team accounted for the greatest number of encounters (15.2% of total encounters). The most common medical diagnosis category was otorhinolaryngology (30.6% of total diagnoses). The most common diagnosis subgroup was upper respiratory infection (14.8% of total diagnoses). CONCLUSIONS: Approximately two-thirds of athletes were evaluated annually with an average of 2 encounters per athlete per year. Upper respiratory infection represented the most common individual diagnosis. The results reported in this study may be useful in directing future care and research of university athletes.

Protocol for a multicenter, randomised controlled trial of surgeon-directed home therapy vs. outpatient rehabilitation by physical therapists for reverse total shoulder arthroplasty: the SHORT trial.

BACKGROUND: Reverse total shoulder arthroplasty (RTSA) has emerged as a successful surgery with expanding indications. Outcomes may be influenced by post-operative rehabilitation; however, there is a dearth of research regarding optimal rehabilitation strategy following RTSA. The primary purpose of this study is to compare patient reported and clinical outcomes after RTSA in two groups: in one group rehabilitation is directed by formal, outpatient clinic-based physical therapists (PT group) as compared to a home therapy group, in which patients are instructed in their rehabilitative exercises by surgeons at post-operative appointments (HT group). Secondary aims include comparisons of complications, cost of care and quality of life between the two groups. METHODS: This randomised controlled trial has commenced at seven sites across the United States. Data is being collected on 200 subjects by clinical research assistants pre-operatively and post-operatively at 2, 6, and 12 weeks, 6 months, 1 and 2 year visits. The following variables are being assessed: American Shoulder and Elbow Surgeons (ASES), pain level using the numeric pain scale, the Single Assessment Numeric Evaluation (SANE) score, and shoulder active and passive range of motion for analysis of the primary aim. Chi square and t-tests will be used to measure differences in baseline characteristics of both groups. Repeated measures linear mixed effects modeling for measurement of differences will be used for outcomes associated with ASES and SANE and scores, and range of motion measures. Secondary aims will be analyzed for comparison of complications, cost, and quality of life assessment scores using data obtained from the PROMIS 29 v. 2, questionnaires administered at standard of care post-operative visits, and the electronic health record. Subjects will be allowed to crossover between the PT and HT groups, and analysis will include both intention-to-treat including patients who crossed over, and a second with cross-over patients removed, truncated to the time they crossed over. DISCUSSION: RTSA is being performed with increasing frequency, and the optimal rehabilitation strategy is unclear. This study will help clarify the role of formal physical therapy with particular consideration to outcomes, cost, and complications. In addition, this study will evaluate a proposed rehabilitation strategy. TRIAL REGISTRATION: This study is registered as NCT03719859 at ClincialTrials.gov .

Hybrid Transtibial Femoral Preparation for Transphyseal Anterior Cruciate Ligament Reconstruction: A Radiographic Comparison With the Transtibial and Anteromedial Portal Techniques.

BACKGROUND: Transphyseal anterior cruciate ligament (ACL) reconstruction remains the most commonly used technique for pubescent patients. The transtibial (TT) drilling technique creates vertical and central femoral tunnels to minimize the physeal area of injury at the expense of a nonanatomic femoral tunnel. The hybrid TT (HTT) technique offers the potential of an anatomic femoral position with tunnel geometry similar to that using the TT technique. PURPOSE/HYPOTHESIS: The purpose was to perform a radiographic comparison of the HTT technique with TT and anteromedial portal (AM) techniques in adolescent patients undergoing transphyseal ACL reconstruction. It was hypothesized that femoral tunnels created during HTT would be similar to TT tunnels but significantly more vertical and central than AM tunnels. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: We retrospectively screened primary transphyseal ACL reconstructions performed in adolescents at our institution between 2013 and 2019. The youngest 20 eligible patients were selected from each technique cohort: TT, AM, and HTT. Postoperative radiographs were assessed for the coronal femoral tunnel angle, as well as the location of the tunnel-physis penetration on the anteroposterior and lateral views. Physeal lesion surface area was calculated. Data were compared among the 3 groups using 1-way analysis of variance followed by pairwise comparisons. RESULTS: Included were 47 patients with a mean ± SD age of 14.3 ± 1.2 years (n = 9 with TT, 18 with AM, and 20 with HTT techniques). The coronal tunnel angle was significantly more vertical in the TT (60.7° ± 7.2°) and HTT (54.4° ± 5.7) groups as compared with the AM group (48.8° ± 5.9; P = .0037 and P = .02, respectively). There was no significant difference between the TT and HTT groups (P = .066). The only significant finding regarding femoral tunnel location was that the HTT tunnels (28.9% ± 4.8%) penetrated the physis more centrally than did the AM tunnels (20.0% ± 5.1%; P = .00002) on lateral radiographs. CONCLUSION: The HTT technique presents an option for transphyseal ACL reconstruction, with femoral tunnel obliquity and estimated physeal disruption similar to that of the TT technique and significantly less than that of the AM technique. The HTT technique also results in the most central physeal perforation of all techniques, predominantly in the sagittal plane.

Use of Patient-Reported Outcomes Measurement Information System (PROMIS) measures to characterise health status for patients seeking care from an orthopaedic provider: a retrospective cohort study.

OBJECTIVES: Characterise the health status of patients newly consulting an orthopaedic specialist across eight clinical subspecialties. DESIGN: Retrospective cohort. SETTING: 18 orthopaedic clinics, including 8 subspecialties (14 ambulatory and 4 hospital based) within an academic health system. PARTICIPANTS: 14 910 patients consulting an orthopaedic specialist for a new patient consultation who completed baseline Patient-Reported Outcomes Measurement Information System (PROMIS) measures associated with their appointment from 17 November 2017 to 13 May 2019. Patients were aged 55.72±5.8 years old, and 61.3% were female and 79.3% were Caucasian and 13.4% were black or African American. Patients who did not complete PROMIS measures or cancelled their appointment were excluded from the study. PRIMARY OUTCOME: PROMIS domains of physical function, pain interference, pain intensity, depression, anxiety, fatigue, sleep disturbance and the ability to participate in social roles. RESULTS: Mean PROMIS scores for physical function were (38.1±9.2), pain interference (58.9±8.1), pain intensity (4.6±2.5), depression (47.9±8.9), anxiety (49.9±9.5), fatigue (50.5±10.3), sleep disturbance (51.1±9.8) and ability to participate in social roles (49.1±10.3) for the entire cohort. Across the clinical subspecialties, neurosurgery, spine and trauma patients were most profoundly affected across almost all domains and patients consulting with a hand specialist reported the least limitations or symptoms across domains. There was a moderate, negative correlation between pain interference and physical functioning (r=-0.59) and low correlations between pain interference with anxiety (r=0.36), depression (r=0.39) as well as physical function and anxiety (r=-0.32) and depression(r=-0.30) and sleep (r=-0.31). CONCLUSIONS: We directly compared clinically meaningful PROMIS domains across eight orthopaedic subspecialties, which would not have been possible with legacy measures alone. These results support PROMIS's utility as a common metric to assess and compare patient health status across multiple orthopaedic subspecialties.

Establishing Age- and Sex-Specific Norms for Pediatric Return-to-Sports Physical Performance Testing.

BACKGROUND: Graft tears and contralateral anterior cruciate ligament (ACL) tears are common in pediatric athletes after ACL reconstruction. Use of objective return-to-sports (RTS) criteria, in particular physical performance tests (PPTs), is believed to reduce the incidence of secondary injury; however, pediatric norms for these tests are unknown. PURPOSE: To establish a proof of concept for the creation of age- and sex-based norms for commonly used RTS PPTs in healthy pediatric athletes, allowing the creation of growth curves for clinical referencing. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A total of 100 healthy people who were between the ages of 6 and 18 years and involved in organized sports were enrolled, with even distributions of age and sex. All participants underwent 9 common RTS PPTs: stork test, stork test on Bosu, single-leg squat, single-leg squat on Bosu, clockwise and counterclockwise quadrant hops, single-leg hop for distance, 6-m timed hop, and triple crossover hop for distance. Mean performance across limbs was calculated for each individual. Chronological age, height, weight, sex, and self-reported Pubertal Maturational Observational Scale (PMOS) score were recorded. Univariable and multivariable models were created for each PPT, assessing the importance of the recorded descriptive variables. Quantile regression was used to create growth curves for each PPT. RESULTS: The cohort was 52% female, and the mean ± standard deviation age was 11.7 ± 3.6 years. PMOS was highly correlated with age (r = 0.86) and was excluded from the regressions. In univariable regression, age, height, and weight were strong predictors of performance for all PPTs, whereas sex was a predictor of performance on the single-leg and triple crossover hops for distance (with males outperforming females). Height and weight were excluded from multivariable regression because of multicollinearity with age. Multivariable regression showed predictive patterns for age and sex that were identical to those shown in the univariable analysis. Given ceiling effects, quantile regression for the stork tests was not possible, but quantile regression growth curves were successfully created for the 7 remaining PPTs. CONCLUSION: Chronological age and sex accurately predicted performance on common RTS PPTs in pediatric patients. The growth curves presented herein could assist clinicians with benchmarking pediatric patients postoperatively against a healthy athletic cohort.

Can PROMIS measures be used to create subgroups for patients seeking orthopaedic care?

AIMS: Patient-reported outcome measures have become an important part of routine care. The aim of this study was to determine if Patient-Reported Outcomes Measurement Information System (PROMIS) measures can be used to create patient subgroups for individuals seeking orthopaedic care. METHODS: This was a cross-sectional study of patients from Duke University Department of Orthopaedic Surgery clinics (14 ambulatory and four hospital-based). There were two separate cohorts recruited by convenience sampling (i.e. patients were included in the analysis only if they completed PROMIS measures during a new patient visit). Cohort #1 (n = 12,141; December 2017 to December 2018,) included PROMIS short forms for eight domains (Physical Function, Pain Interference, Pain Intensity, Depression, Anxiety, Sleep Quality, Participation in Social Roles, and Fatigue) and Cohort #2 (n = 4,638; January 2019 to August 2019) included PROMIS Computer Adaptive Testing instruments for four domains (Physical Function, Pain Interference, Depression, and Sleep Quality). Cluster analysis (K-means method) empirically derived subgroups and subgroup differences in clinical and sociodemographic factors were identified with one-way analysis of variance. RESULTS: Cluster analysis yielded four subgroups with similar clinical characteristics in Cohort #1 and #2. The subgroups were: 1) Normal Function: within normal limits in Physical Function, Pain Interference, Depression, and Sleep Quality; 2) Mild Impairment: mild deficits in Physical Function, Pain Interference, and Sleep Quality but with Depression within normal limits; 3) Impaired Function, Not Distressed: moderate deficits in Physical Function and Pain Interference, but within normal limits for Depression and Sleep Quality; and 4) Impaired Function, Distressed: moderate (Physical Function, Pain Interference, and Sleep Quality) and mild (Depression) deficits. CONCLUSION: These findings suggest orthopaedic patient subgroups differing in physical function, pain, and psychosocial distress can be created from as few as four different PROMIS measures. Longitudinal research is necessary to determine whether these subgroups have prognostic validity. Cite this article: Bone Jt Open 2021;2(7):493-502.

Neither Residual Anterior Knee Laxity Up to 6 mm nor a Pivot Glide Predict Patient-Reported Outcome Scores or Subsequent Knee Surgery Between 2 and 6 Years After ACL Reconstruction.

BACKGROUND: A primary goal of anterior cruciate ligament reconstruction (ACLR) is to reduce pathologically increased anterior and rotational laxity of the knee, but the effects of residual laxity on patient-reported outcomes (PROs) after ACLR remain unclear. HYPOTHESIS: Increased residual laxity at 2 years postoperatively is predictive of a higher risk of subsequent ipsilateral knee surgery and decreases in PRO scores from 2 to 6 years after surgery. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: From a prospective multicenter cohort, 433 patients aged <36 years were identified at a minimum 2 years after primary ACLR. These patients underwent a KT-1000 arthrometer assessment and pivot-shift test and completed PRO assessments with the Knee injury and Osteoarthritis Outcome Score and International Knee Documentation Committee (IKDC) scores. Patients completed the same PROs at 6 years postoperatively, and any subsequent ipsilateral knee procedures during this period were recorded. Subsequent surgery risk and change in PROs from 2 to 6 years postoperatively were compared based on residual side-to-side KT-1000 arthrometer differences (<-1 mm, -1 to 2 mm, 2 to 6 mm, and >6 mm) in laxity at 2 years postoperatively. Multiple linear regression models were built to determine the relationship between 2-year postoperative knee laxity and 2- to 6-year change in PROs while controlling for age, sex, body mass index, smoking status, meniscal and cartilage status, and graft type. RESULTS: A total of 381 patients (87.9%) were available for follow-up 6 years postoperatively. There were no significant differences in risk of subsequent knee surgery based on residual knee laxity. Patients with a difference >6 mm in side-to-side anterior laxity at 2 years postoperatively were noted to have a larger decrease in PROs from 2 to 6 years postoperatively (P < .05). No significant differences in any PROs were noted among patients with a difference <6 mm in side-to-side anterior laxity or those with pivot glide (IKDC B) versus no pivot shift (IKDC A). CONCLUSION: The presence of a residual side-to-side KT-1000 arthrometer difference <6 mm or pivot glide at 2 years after ACLR is not associated with an increased risk of subsequent ipsilateral knee surgery or decreased PROs up to 6 years after ACLR. Conversely, patients exhibiting a difference >6 mm in side-to-side anterior laxity were noted to have significantly decreased PROs at 6 years after ACLR.

Electronic health record-integrated approach for collection of patient-reported outcome measures: a retrospective evaluation.

BACKGROUND: The integration of Patient Reported Outcome Measures (PROMs) into clinical care presents many challenges for health systems. PROMs provide quantitative data regarding patient-reported health status. However, the most effective model for collecting PROMs has not been established. Therefore the purpose of this study is to report the development and preliminary evaluation of the standardized collection of PROMs within a department of orthopedic surgery at a large academic health center. METHODS: We utilized the Users' Guide to Integrating Patient-Reported Outcomes in Electronic Health Records by Gensheimer et al., 2018 as a framework to describe the development of PROMs collection initiative. We framed our initiative by operationalizing the three aspects of PROM collection development: Planning, Selection, and Engagement. Next, we performed a preliminary evaluation of our initiative by assessing the response rate of patients completing PROMs (no. of PROMs completed/no. of PROMs administered) across the entire department (18 clinics), ambulatory clinics only (14 clinics), and hospital-based clinics only (4 clinics). Lastly, we reported on the mean response rates for the top 5 and bottom 5 orthopaedic providers to describe the variability across providers. RESULTS: We described the development of a fully-integrated, population health based implementation strategy leveraging the existing resources of our local EHR to maximize clinical utility of PROMs and routine collection. We collected a large volume of PROMs over a 13 month period (n = 10,951) across 18 clinical sites, 7 clinical specialties and over 100 providers. The response rates varied across the department, ranging from 29 to 42%, depending on active status for the portal to the electronic health record (MyChart). The highest single provider mean response rate was 52%, and the lowest provider rate was 13%. Rates were similar between hospital-based (26%) and ambulatory clinics (29%). CONCLUSIONS: We found that our standardized PROMs collection initiative, informed by Gensheimer et al., achieved scope and scale, but faced challenges in achieving a high response rate commensurate with existing literature. However, most studies reported a targeted recruitment strategy within a narrow clinical population. Further research is needed to elucidate the trade-off between scalability and response rates in PROM collection initiatives.

Composite psychosocial risk based on the fear avoidance model in patients undergoing anterior cruciate ligament reconstruction: Cluster-based analysis.

OBJECTIVES: To examine associations between preoperative fear-avoidance model (FAM) risk subgroup status and patient expectation of surgical success with postoperative outcomes at 6 and 12 months after anterior cruciate ligament reconstruction (ACLR). DESIGN: Cohort study. SETTING: Academic medical center. PARTICIPANTS: 54 patients (25 females) undergoing unilateral ACLR. MAIN OUTCOME MEASURES: Cluster analysis distinguished FAM risk subgroups based on preoperative fear of movement/reinjury, self-efficacy, and pain catastrophizing. Preoperative expectation for surgical success was assessed with a numeric rating scale. Six and 12-month outcomes included Subjective Patient Outcomes for Return to Sport, Knee Injury and Osteoarthritis Outcome Score (KOOS) sports/recreation and quality of life, and International Knee Documentation Committee (IKDC) Subjective Knee Form. RESULTS: Thirteen (24%) patients were "moderate-to-high FAM risk." Moderate-to-high FAM risk patients had lower odds of return to sport at 12 months (OR = 0.3, p = .05) and lower KOOS sports/recreation at 6 months (st. beta = -0.27, p = .05), KOOS quality of life at 12 months (st. beta = -0.42, p = .007), and IKDC at 6 (st. beta = -0.29, p = .04) and 12 months (st. beta = -0.47, p = .001). Higher expectation was associated with lower 6-month IKDC (st. beta = -0.36, p = .008) and 12-month KOOS quality of life (st. beta = -0.29, p = .05). CONCLUSIONS: Preoperative FAM risk influences patient-reported outcomes and return to sport at 6 and 12 months.

The Clinical Radiographic Incidence of Posttraumatic Osteoarthritis 10 Years After Anterior Cruciate Ligament Reconstruction: Data From the MOON Nested Cohort.

BACKGROUND: The incidence of posttraumatic osteoarthritis (PTOA) based on clinical radiographic grading criteria at 10 years after anterior cruciate ligament (ACL) reconstruction (ACLR) has not been well-defined in a prospective cohort of young athletic patients. HYPOTHESIS: Among young athletic patients, there is a high incidence of clinical radiographic PTOA at 10 years after ACLR. Additionally, there is a significant difference in clinical radiographic osteoarthritis (OA) changes (joint space narrowing and osteophyte formation) between ACL-reconstructed and contralateral knees at 10 years. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The first 146 patients in an ongoing nested cohort study of the Multicenter Orthopaedic Outcomes Network (MOON) prospective cohort presented for a minimum 10-year follow-up. Included patients had a sports-related ACL injury, were aged <33 years at the time of ACLR, had no history of ipsilateral or contralateral knee surgery, and did not undergo revision ACLR before follow-up. Bilateral knee metatarsophalangeal view radiographs were obtained and graded according to International Knee Documentation Committee (IKDC), Osteoarthritis Research Society International (OARSI), and modified Kellgren-Lawrence (KL) criteria by 2 blinded reviewers. The incidence and severity of ipsilateral and contralateral radiographic OA were determined among patients without a contralateral ACL injury before 10-year follow-up (N = 133). RESULTS: Interrater reliability was substantial for the IKDC (Gwet Agreement Coefficient [AC] 1 = 0.71), moderate for the KL (0.48), and almost perfect for the OARSI (0.84) grading systems. Among patients with a contralateral radiographically normal knee, the 10-year incidence of clinical radiographic PTOA after ACLR was 37% as defined by osteophytes and 23% as defined by joint space narrowing. The maximum side-to-side difference in the OARSI osteophyte grade in the medial or lateral compartment was 0 in 65% of patients, 1 in 20%, and ≥2 in 15%. The maximum side-to-side difference in the OARSI joint space narrowing grade was 0 in 77% of patients, 1 in 19%, and ≥2 in 4%. CONCLUSION: In young active patients, the 10-year incidence of clinical radiographic PTOA after ACLR was 37% as defined by osteophytes and 23% as defined by joint space narrowing. The mean difference in the degree of osteophyte formation (≤1 grade in 85%) and joint space narrowing (≤1 grade in 96%) between the ACL-reconstructed and contralateral knees was small. REGISTRATION: NCT02717559 (ClinicalTrials.gov identifier).

Healthy Pediatric Athletes Have Significant Baseline Limb Asymmetries on Common Return-to-Sport Physical Performance Tests.

BACKGROUND: Return to sport (RTS) after anterior cruciate ligament (ACL) reconstruction in children is associated with a much higher risk (∼30%) of subsequent ACL injury than in adults. Most RTS testing protocols use a limb symmetry index (LSI) ≥90% on physical performance tests (PPTs) to assess an athlete's readiness for sport. This assumes that, in a healthy state, the physical performances across both lower extremities are and should be equal. PURPOSE: To determine the prevalence of limb asymmetries >10% in the uninjured pediatric population on common PPTs as well as to explore the relationship between athlete variables, limb preference, and LSI values. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: This study included healthy volunteers (N = 100) evenly distributed between the ages of 6 and 18 years (mean age, 11.7 ± 3.6 years; 52% female). Participants performed 9 common PPTs. For analysis, we developed a composite score for each limb by averaging trials. We then calculated the LSI for each test. Univariable and multivariable linear regression analyses were performed to assess the relationship between athlete variables (age, sex, height, and weight) and LSI for each PPT. RESULTS: Instances of poor baseline limb symmetry (<90% LSI) were common across all PPTs. The single-leg timed hop had the highest percentage of participants, with LSI ≥90% at 73%, while the stork on a Bosu ball had the lowest percentage at 23%. After adjusting for age, female sex showed a significant association with LSI for the stork test (P = .010) and the quadrant hop-counterclockwise (P = .021). Additionally, after adjusting for sex, increasing age showed a significant association with LSI for the stork test (P < .001), single-leg squat on a Bosu ball (P = .010), quadrant hop-clockwise (P = .016), and quadrant hop-counterclockwise (P = .009). CONCLUSION: The majority of healthy athletes 18 years and younger demonstrated significant (<90%) limb asymmetries. Limb symmetry was not consistently affected by participant age or sex, and the effect sizes of these relationships were small. These findings should encourage clinicians and coaches to exercise caution in using the LSI as an isolated measure of RTS readiness after injury in pediatric athletes.