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1.
J Orthop Res ; 42(7): 1545-1556, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38400619

ABSTRACT

Talonavicular (TN) fusion is a common treatment for TN arthritis or deformity correction. There is incongruous evidence regarding remaining motion at the talocalcaneal and calcaneocuboid joints after TN fusion. Additionally, the effects of a malaligned TN fusion are not well understood and alignment of the fusion may be important for overall foot integrity. This project assessed the kinematic and kinetic effects of neutral and malaligned TN fusions. Ten cadaveric feet were tested on a gait simulator in four conditions: unfused, fused in neutral, fused in varus, and fused in valgus. The fusions were simulated with external fixation hardware. An eight-camera motion analysis system and a 10-segment foot model generated kinematic data, and a pressure mat captured pressure data. Simulated TN fusion was achieved in eight feet. From unfused to fused-neutral, range of motion (ROM) was not eliminated in the adjacent joints, but the positions of the joints changed significantly throughout stance phase. Furthermore, the ROM increased at the tibiotalar joint. Plantar pressure and center of pressure shifted laterally with neutral fusion. The malalignments marginally affected the ROM but changed joint positions throughout stance phase. Pressure patterns were shifted laterally in varus malalignment and medially in valgus malalignment. The residual motion and the altered kinematics at the joints in the triple joint complex after TN fusion may subsequently increase the incidence of arthritis. Clinical significance: This study quantifies the effects of talonavicular fusion and malalignment on the other joints of the triple joint complex.


Subject(s)
Arthrodesis , Cadaver , Foot , Pressure , Humans , Biomechanical Phenomena , Aged , Female , Male , Range of Motion, Articular , Tarsal Joints , Middle Aged , Gait , Aged, 80 and over , Talus , Bone Malalignment/physiopathology , Tarsal Bones
2.
JMIR Med Inform ; 11: e44455, 2023 May 12.
Article in English | MEDLINE | ID: mdl-37171858

ABSTRACT

BACKGROUND: Hydroxychloroquine (HCQ) is commonly used for patients with autoimmune conditions. Long-term use of HCQ can cause retinal toxicity, but this risk can be reduced if high doses are avoided. OBJECTIVE: We developed and piloted an electronic health record-based dashboard to improve the safe prescribing of HCQ within the Veterans Health Administration (VHA). We observed pilot facilities over a 1-year period to determine whether they were able to improve the proportion of patients receiving inappropriate doses of HCQ. METHODS: Patients receiving HCQ were identified from the VHA corporate data warehouse. Using PowerBI (Microsoft Corp), we constructed a dashboard to display patient identifiers and the most recent HCQ dose and weight (flagged if ≥5.2 mg/kg/day). Six VHA pilot facilities were enlisted to test the dashboard and invited to participate in monthly webinars. We performed an interrupted time series analysis using synthetic controls to assess changes in the proportion of patients receiving HCQ ≥5.2 mg/kg/day between October 2020 and November 2021. RESULTS: At the start of the study period, we identified 18,525 total users of HCQ nationwide at 128 facilities in the VHA, including 1365 patients at the 6 pilot facilities. Nationwide, at baseline, 19.8% (3671/18,525) of patients were receiving high doses of HCQ. We observed significant improvements in the proportion of HCQ prescribed at doses ≥5.2 mg/kg/day among pilot facilities after the dashboard was deployed (-0.06; 95% CI -0.08 to -0.04). The difference in the postintervention linear trend for pilot versus synthetic controls was also significant (-0.06; 95% CI -0.08 to -0.05). CONCLUSIONS: The use of an electronic health record-based dashboard reduced the proportion of patients receiving higher than recommended doses of HCQ and significantly improved performance at 6 VHA facilities. National roll-out of the dashboard will enable further improvements in the safe prescribing of HCQ.

3.
Rheum Dis Clin North Am ; 48(3): 601-615, 2022 08.
Article in English | MEDLINE | ID: mdl-35953226

ABSTRACT

Quality measures (QMs) are tools that help measure or quantify health care processes, outcomes, patient perceptions, and organizational structures and systems associated with the ability to provide high-quality health care. QMs are often developed from clinical practice guidelines (CPGs), as they summarize the best available evidence to create standards for optimizing patient care. The authors provide a framework for learners to understand the relevance, development, and testing of QMs in rheumatology, touching on their relationship to CPGs and appropriate use criteria. They describe measure implementation across different health care settings and reflect on challenges and opportunities associated with this process.


Subject(s)
Quality Indicators, Health Care , Rheumatology , Delivery of Health Care , Health Facilities , Humans , Quality of Health Care
4.
Plast Reconstr Surg ; 150(3): 601-605, 2022 09 01.
Article in English | MEDLINE | ID: mdl-35791263

ABSTRACT

SUMMARY: Several surgical procedures have been described to treat thumb carpometacarpal osteoarthritis, including suture button suspensionplasty and ligament reconstruction and tendon interposition. To date, no single procedure has demonstrated clinical superiority. Suture button suspensionplasty has achieved favorable outcomes at 5 years in primary cases, but has not been validated in revision surgery. In this study, it was evaluated for revision of failed thumb carpometacarpal osteoarthritis surgery, and outcomes were compared to ligament reconstruction and tendon interposition outcomes. A retrospective chart review identified patients who underwent suture button suspensionplasty or ligament reconstruction and tendon interposition after failure of previous thumb carpometacarpal osteoarthritis surgery since 2010. Eighteen patients were included, with nine patients in each group. Eighteen patients had mean final follow-up of 35 months. There were two complications in the ligament reconstruction and tendon interposition group and none in the suture button suspensionplasty group. No patients required additional surgery. The suture button suspensionplasty group had an average visual analogue scale pain score improvement of 2.9, compared to 2.4 in the ligament reconstruction and tendon interposition group. Average final Quick Disabilities of the Arms, Shoulder and Hand questionnaire score was 15.1 in the suture button suspensionplasty group, compared to 22.6 in the ligament reconstruction and tendon interposition group. Mean operative time of 86.3 minutes in the suture button suspensionplasty group was significantly shorter than the 121-minute mean in the ligament reconstruction and tendon interposition group. Suture button suspensionplasty is an effective treatment option for revision of previous thumb carpometacarpal osteoarthritis surgery, with outcomes comparable to revision using ligament reconstruction and tendon interposition, and the added benefit of shorter operative times and early mobilization. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.


Subject(s)
Carpometacarpal Joints , Osteoarthritis , Trapezium Bone , Carpometacarpal Joints/surgery , Humans , Ligaments/surgery , Osteoarthritis/surgery , Reoperation , Retrospective Studies , Sutures , Tendons/surgery , Thumb/surgery , Trapezium Bone/surgery
5.
Hand (N Y) ; 17(3): 465-470, 2022 05.
Article in English | MEDLINE | ID: mdl-32674623

ABSTRACT

Background: Scaphoid nonunion advanced collapse (SNAC) is a common form of wrist arthritis, the treatment of which depends on the arthritic stage. The Vender classification serves to describe SNAC arthritis based on a single posteroanterior (PA) radiograph. The purpose of this study was to evaluate the intraobserver and interobserver agreement of the Vender classification, comparing multi versus single radiographic views. Methods: A retrospective review of patients with SNAC arthritis who underwent a proximal row carpectomy or a 4-corner fusion was performed. The included patients had 3 radiographic views of the pathologic wrist. Fifteen patients were analyzed by 5 blinded reviewers. Wrists were graded using the Vender classification first on the PA view and then using multiview radiographs. The intraobserver and interobserver agreement was determined using weighted kappa analysis. χ2 tests were calculated comparing the evaluation between single- versus multiview radiographs and determining a higher Vender stage. Results: Multiview radiographs demonstrated a higher intraobserver κw compared with single-view radiographs (0.72 vs 0.66), both representing substantial agreement. The average interobserver agreement was moderate (κw of 0.48) for single view and slight (κw of 0.30) for multiview evaluation. Evaluating multiview radiographs was 6.37 times more likely to demonstrate Vender stage 3 arthritis compared with single view (odds ratio = 6.37 [confidence interval, 3.81-10.64], P < .0001). Conclusion: Reviewing multiview radiographs more commonly yielded Vender stage 3 osteoarthritis classification. The decreased interrater reliability in the multiview analysis is likely related to the increased number of articular surfaces evaluated. Using a single PA view may underestimate the severity of arthritis present.


Subject(s)
Musculoskeletal Diseases , Osteoarthritis , Scaphoid Bone , Humans , Osteoarthritis/diagnostic imaging , Reproducibility of Results , Scaphoid Bone/diagnostic imaging , Wrist , Wrist Joint/diagnostic imaging
7.
J Bone Joint Surg Am ; 103(22): 2133-2140, 2021 11 17.
Article in English | MEDLINE | ID: mdl-34424868

ABSTRACT

BACKGROUND: Health-care expenditures in the U.S. are continually rising, prompting providers, patients, and payers to search for solutions to reduce costs while maintaining quality. The present study seeks to define the out-of-pocket price that patients undergoing hand surgery are willing to pay, and also queries the potential cost-cutting measures that patients are most and least comfortable with. We hypothesized that respondents would be less accepting of higher out-of-pocket costs. METHODS: A survey was developed and distributed to paid, anonymous respondents through Amazon Mechanical Turk. The survey introduced 3 procedures: carpal tunnel release, cubital tunnel release, and open reduction and internal fixation of a distal radial fracture. Respondents were randomized to 1 of 5 out-of-pocket price options for each procedure and asked if they would pay that price. Respondents were then presented with various cost-saving methods and asked to select the options that made them most uncomfortable, even if those would save them out-of-pocket costs. RESULTS: There were 1,408 respondents with a mean age of 37 years (range, 18 to 74 years). Nearly 80% of respondents were willing to pay for all 3 of the procedures regardless of which price they were presented. Carpal tunnel release was the most price-sensitive, with rejection rates of 17% at the highest price ($3,000) and 6% at the lowest ($250). Open reduction and internal fixation was the least price-sensitive, with rejection rates of 11% and 6% at the highest and lowest price, respectively. The use of older-generation implants was the least acceptable cost-cutting measure, at 50% of respondents. CONCLUSIONS: The present study showed that most patients are willing to pay a considerable amount of money out of pocket for hand surgery after the condition, treatment, and outcomes are explained to them. Furthermore, respondents are hesitant to sacrifice advanced technology despite increased costs.


Subject(s)
Consumer Behavior/statistics & numerical data , Hand/surgery , Health Expenditures/statistics & numerical data , Orthopedic Procedures/economics , Adolescent , Adult , Aged , Consumer Behavior/economics , Cost Savings/methods , Cost Savings/statistics & numerical data , Female , Humans , Male , Middle Aged , Orthopedic Procedures/methods , Surveys and Questionnaires/statistics & numerical data , Young Adult
8.
ACR Open Rheumatol ; 3(10): 690-698, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34288595

ABSTRACT

OBJECTIVE: Patient-reported outcomes (PROs) are an integral part of treat-to-target approaches in managing rheumatoid arthritis (RA). In clinical practice, however, routine collection, documentation, and discussion of PROs with patients are highly variable. The RISE LC (Rheumatology Informatics System for Effectiveness Learning Collaborative) was established to develop and share best practices in PRO collection and use across adult rheumatology practices in the United States METHODS: The goals of the RISE LC were developed through site surveys and in-person meetings. Participants completed a baseline survey on PRO collection and use in their practices. RISE LC learning sessions focused on improving communication around PROs with patients and enhancing shared decision-making in treatment plans. During the coronavirus disease 2019 (COVID-19) pandemic, the RISE LC pivoted to adapt PRO tools for telehealth. RESULTS: At baseline, all responding sites (n = 15) had established workflows for collecting PROs. Most sites used paper forms alone. PRO documentation in electronic health records was variable, with only half of the sites using structured data fields. To standardize and improve the use of PROs, participants iteratively developed a Clinical Disease Activity Index-based RA Disease Activity Communication Tool to solicit treatment goals and improve shared decision-making across sites. The COVID-19 pandemic necessitated developing a tool to gauge PROs via telehealth. CONCLUSION: The RISE LC is a continuous, structured method for implementing strategies to improve PRO collection and use in rheumatological care, initially adapting from the Learning Collaborative model and extending to include features of a learning network. Future directions include measuring the impact of standardized PRO collection and discussion on shared decision-making and RA outcomes.

9.
Eur J Orthop Surg Traumatol ; 31(6): 1061-1067, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33389077

ABSTRACT

INTRODUCTION: Heterotopic ossification (HO) is a well-known sequela after an elbow injury and is widely studied given the associated morbidity. The anatomic location of HO development for specific elbow injuries has not been reported. The purpose of this study was to describe the precise, anatomic location of HO development after different peri-articular elbow injuries. METHODS: A retrospective chart review was performed for patients with peri-articular elbow fracture and/or dislocation who underwent an elbow contracture release. The injuries were grouped into coronal shear distal humerus/AO 13.B3 (CSDH), distal humerus/AO 13.A, 13.B1, B2 or 13.C (DH), olecranon/AO 21.B1 (OL), radial head/AO 21.B2 (RH), extra-articular proximal radius and ulna/AO 21.A (EAPRU) fractures and elbow dislocations (DL). The HO location was determined by reviewing elbow radiographs and CT scans and were classified as anterior capsule, medial or lateral collateral ligaments, and posterior capsule/triceps insertion. RESULTS: The study consisted of 49 patients, such as 6 CSDH, 13 DH, 6 OL, 21 RH, 4 EAPRU fractures and 20 elbow DL. All CSDH and RH fractures and 19/20 elbow DL developed HO in the collateral ligaments, while 12/13 DH fractures developed an anterior capsule HO. All 6 OL fractures developed HO posteriorly, and 3/4 EAPRU fractures developed a proximal radioulnar synostosis. CONCLUSIONS: Our findings suggest that the location of HO development is specific to the injury type and is influenced by the soft tissues involved. This is consistent with the understanding that HO is the abnormal ossification of normal structures.


Subject(s)
Elbow Joint , Fractures, Bone , Ossification, Heterotopic , Radius Fractures , Elbow/diagnostic imaging , Elbow Joint/diagnostic imaging , Humans , Ossification, Heterotopic/diagnostic imaging , Ossification, Heterotopic/etiology , Radius Fractures/complications , Radius Fractures/diagnostic imaging , Range of Motion, Articular , Retrospective Studies
10.
Hand (N Y) ; 16(6): 834-842, 2021 11.
Article in English | MEDLINE | ID: mdl-31847582

ABSTRACT

Background: Radiocarpal dislocations are rare injuries that result from high-energy forces across the wrist with the hallmark finding of radiocarpal ligament disruption. Published treatment methods are comprehensive with moderate-to-good outcomes. The purpose of this study was to review the treatment of radiocarpal dislocations with a dorsal wrist spanning plate. Methods: A retrospective review was conducted analyzing the radiographic and clinical outcomes of patients treated for a radiocarpal dislocation using a dorsal wrist spanning plate over a 10-year period. Outcomes assessed included radiographic joint incongruity and arthrosis, wrist range of motion, grip strength, Visual Analogue Scale (VAS) score, surgical complications, and Disabilities of the Arm, Shoulder, and Hand (DASH) score. Results: Thirteen patients were treated with a dorsal wrist spanning plate for radiocarpal dislocation with a mean follow-up of 615 days from the time of initial surgery. Six patients (46%) had associated distal radioulnar joint instability. The mean wrist range of motion at the final follow-up was: flexion 39°, extension 44°, pronation 79°, and supination 84°. One patient (8%) developed ulnar translation of the carpus, and 11 patients (85%) developed radiographic posttraumatic wrist arthrosis. Mean VAS and DASH scores were 4 and 18, respectively. Conclusions: Acute treatment with a dorsal wrist spanning plate in this series resulted in comparable outcomes to what have been previously reported in the literature. The dorsal wrist spanning plate offers the surgeon a reliable method of stabilization, with minimal additional surgical trauma to the wrist, while avoiding the potential for infections that develop with other treatment methods.


Subject(s)
Radius Fractures , Wrist Injuries , Humans , Retrospective Studies , Wrist , Wrist Injuries/diagnostic imaging , Wrist Injuries/surgery , Wrist Joint/diagnostic imaging , Wrist Joint/surgery
11.
Clin Sports Med ; 39(2): 401-422, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32115091

ABSTRACT

Metacarpal and phalangeal fractures are common injuries in athletes and occur frequently in contact and ball-handling sports. They usually result after direct hits from other players or athletic equipment. The fractures often are minimally displaced and require a short period of immobilization followed by early range of motion for expeditious return to play. Unstable or intra-articular fractures may require operative fixation. Open reduction and internal fixation afford the most stability while allowing for early rehabilitation. Athletes represent a unique population, and treatment of these fractures requires consideration of specific sport, timing of injury, and level of play.


Subject(s)
Athletic Injuries/therapy , Finger Phalanges/injuries , Fractures, Bone/therapy , Metacarpal Bones/injuries , Athletic Injuries/physiopathology , Athletic Injuries/surgery , Finger Phalanges/anatomy & histology , Fracture Fixation, Internal , Fractures, Bone/physiopathology , Fractures, Bone/surgery , Humans , Metacarpal Bones/anatomy & histology , Open Fracture Reduction , Range of Motion, Articular , Return to Sport
12.
J Pediatr Orthop ; 40(7): e609-e615, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32040065

ABSTRACT

BACKGROUND: The primary purpose of this study was to compare the number of pitches thrown by youth baseball players under the official league guidelines versus the number of "high-effort" throws recorded by a validated digital sensor worn by the players during a season. METHODS: In total, 11 and 12-year-old youth baseball players from a single league were provided an elbow sleeve and sensor to wear each time they threw a baseball for an entire baseball season. The sensor tracked total throws and pitch-equivalent high-effort throws for the season. Official pitch counts were collected at each game from the official scorekeepers. RESULTS: A total of 19 players participated in the study. The sensor-determined mean total throw count (1666.2±642.2) and mean high-effort throw count (576.9±329.3) per player were both significantly higher, P<0.0001 and P=0.02, respectively, than the mean official pitch count (168.1±122.4). CONCLUSIONS: Our findings demonstrate that youth players make significantly more total throws and high-effort, or pitch-equivalent, throws, than what is recorded by the official pitch counts. Further research is needed to determine a safe annual "throw count" for young throwing athletes and to determine which types of throws, in addition to pitches, put youth throwers at risk for injury. LEVEL OF EVIDENCE: Level IV.


Subject(s)
Athletic Injuries , Baseball , Elbow Injuries , Shoulder Injuries , Youth Sports , Athletic Injuries/physiopathology , Athletic Injuries/prevention & control , Baseball/injuries , Baseball/physiology , Baseball/standards , Biomechanical Phenomena/physiology , Child , Elbow Joint/physiology , Fitness Trackers , Humans , Male , Shoulder Injuries/etiology , Shoulder Injuries/prevention & control , Shoulder Joint/physiology , Youth Sports/physiology , Youth Sports/standards
13.
J Shoulder Elbow Surg ; 29(4): 736-742, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31784384

ABSTRACT

BACKGROUND AND HYPOTHESIS: Post-traumatic elbow contracture remains a common and challenging complication with often unsatisfactory outcomes. Although the etiology is unknown, elevated or abnormal post-fracture synovial fluid cytokine levels may result in the migration of fibroblasts to the capsule and contribute to capsular pathology. Thus, the purpose of this study was to characterize the cytokine composition in the synovial fluid fracture hematoma of patients with intra-articular elbow fractures. METHODS: The elbow synovial fluid fracture hematoma of 11 patients with intra-articular elbow fractures was analyzed for CTXII (C-terminal telopeptides of type II collagen [a cartilage breakdown product]) as well as 15 cytokines and matrix metalloproteinases (MMPs) including interferon γ, interleukin (IL) 1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor α, MMP-1, MMP-2, MMP-3, MMP-9, and MMP-10. The uninjured, contralateral elbow served as a matched control. Mean concentrations of each factor were compared between the fluid from fractured elbows and the fluid from control elbows. RESULTS: The levels of 14 of 15 measured cytokines and MMPs-interferon γ, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor α, MMP-1, MMP-3, MMP-9, and MMP-10-were significantly higher in the fractured elbows. In addition, post hoc power analysis revealed that 10 of 14 significant differences were detected with greater than 90% power. The mean concentration of CTXII was not significantly different between groups. CONCLUSIONS: These results demonstrate a proinflammatory environment after fracture that may be the catalyst to the development of post-traumatic elbow joint contracture. The cytokines with elevated levels were similar, although not identical, to the cytokines with elevated levels in studies of other weight-bearing joints, indicating the elbow responds uniquely to trauma.


Subject(s)
Cytokines/metabolism , Elbow Injuries , Hematoma/metabolism , Intra-Articular Fractures/metabolism , Matrix Metalloproteinases/metabolism , Synovial Fluid/metabolism , Adult , Aged , Aged, 80 and over , Case-Control Studies , Collagen Type II/metabolism , Female , Hematoma/etiology , Humans , Inflammation/metabolism , Intra-Articular Fractures/complications , Male , Middle Aged , Peptide Fragments/metabolism , Prospective Studies
14.
Orthopedics ; 43(2): 76-82, 2020 Mar 01.
Article in English | MEDLINE | ID: mdl-31841608

ABSTRACT

Periprosthetic shoulder infection (PSI), although less common than prosthetic hip and knee infections, continues to be a devastating complication of shoulder arthroplasty. Unlike its counterparts in the hip and knee, infection with nonsuppurative bacteria is more common than infection with more virulent bacteria in periprosthetic shoulder infection. The diagnosis of PSI can be challenging because the traditional clinical and laboratory findings are not always present. The authors present a narrative review of the current methods used in the diagnosis of PSI, as well as recently developed tests that may hold promise for the diagnosis of PSI. [Orthopedics. 2020; 43(2):76-82.].


Subject(s)
Arthroplasty, Replacement, Shoulder/adverse effects , Prosthesis-Related Infections/diagnosis , Shoulder Joint/microbiology , Shoulder Joint/surgery , Biomarkers/blood , DNA, Bacterial/genetics , Fibrin Fibrinogen Degradation Products/analysis , High-Throughput Nucleotide Sequencing , Humans , Microbiological Techniques , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Specimen Handling/methods , alpha-Defensins/blood
15.
J Bone Joint Surg Am ; 101(4): e14, 2019 Feb 20.
Article in English | MEDLINE | ID: mdl-30801382

ABSTRACT

BACKGROUND: Elements of competency-based training are being incorporated into surgical training. The primary objective of this study was to determine how the orientation of the arthroscope and the instruments relative to the standing position of the surgeon affects basic arthroscopic performance. The secondary objective was to determine how arthroscopic level of training affects performance. METHODS: Participants from a single academic institution were recruited and divided by level of training into 2 groups: novice and advanced. The Fundamentals of Arthroscopic Surgery Training (FAST) Workstation (Sawbones) was used in this study. Performance on the ring transfer module was evaluated based on the total number of ring transfers that were completed and the errors that were made in timed sessions. All participants performed the task with the arthroscope facing away from (position A) and facing toward (position B) their standing position. Two trials were completed for each position, followed by a survey. RESULTS: Fifty-seven subjects participated in this study. Overall, position A showed 2.7 times the amount of transfers compared with position B (p < 0.001). The advanced group had 1.6 times more transfers in position A than the novice group (p = 0.007), and there was no significant difference in transfers between training level in position B. The advanced group had 3.6 times more transfers in position A compared with position B (p < 0.001), while the novice group had 2.0 times more transfers in position A than in position B (p < 0.001). CONCLUSIONS: Performing an arthroscopic simulator task with the arthroscope directed toward the operator was found to be more difficult. An understanding of how the orientation of the operator, the arthroscope, and the instruments can strongly influence performance may be important for the primary surgeon, trainees, or assistants who may be standing opposite the arthroscope, and to optimize training to overcome this discrepancy.


Subject(s)
Arthroscopes , Arthroscopy/education , Clinical Competence/standards , Education, Medical/methods , Adult , Aged , Arthroscopy/instrumentation , Arthroscopy/standards , Competency-Based Education/methods , Humans , Internship and Residency , Middle Aged , North Carolina , Orthopedic Surgeons/education , Orthopedic Surgeons/standards , Sports Medicine/education , Young Adult
16.
Arthritis Rheumatol ; 71(1): 109-120, 2019 01.
Article in English | MEDLINE | ID: mdl-30009530

ABSTRACT

OBJECTIVE: High-expression alleles of macrophage migration inhibitory factor (MIF) are linked genetically to the severity of systemic lupus erythematosus (SLE). The U1 small nuclear RNP (snRNP) immune complex containing U1 snRNP and anti-U1 snRNP antibodies, which are found in patients with SLE, activates the NLRP3 inflammasome, comprising NLRP3, ASC, and procaspase 1, in human monocytes, leading to the production of interleukin-1ß (IL-1ß). This study was undertaken to investigate the role of the snRNP immune complex in up-regulating the expression of MIF and its interface with the NLRP3 inflammasome. METHODS: MIF, IL-1ß, NLRP3, caspase 1, ASC, and MIF receptors were analyzed by enzyme-linked immunosorbent assay, Western blotting, quantitative polymerase chain reaction, and cytometry by time-of-flight mass spectrometry (CytoF) in human monocytes incubated with or without the snRNP immune complex. MIF pathway responses were probed with the novel small molecule antagonist MIF098. RESULTS: The snRNP immune complex induced the production of MIF and IL-1ß from human monocytes. High-dimensional, single-cell CytoF analysis established that MIF regulates activation of the NLRP3 inflammasome, including findings of a quantitative relationship between MIF and its receptors and IL-1ß levels in the monocytes. MIF098, which blocks MIF binding to its cognate receptor, suppressed the production of IL-1ß, the up-regulation of NLRP3, which is a rate-limiting step in NLRP3 inflammasome activation, and the activation of caspase 1 in snRNP immune complex-stimulated human monocytes. CONCLUSION: The U1 snRNP immune complex is a specific stimulus of MIF production in human monocytes, with MIF having an upstream role in defining the inflammatory characteristics of activated monocytes by regulating NLRP3 inflammasome activation and downstream IL-1ß production. These findings provide mechanistic insight and a therapeutic rationale for targeting MIF in subgroups of lupus patients, such as those classified as high genotypic MIF expressers or those with anti-snRNP antibodies.


Subject(s)
Antigen-Antibody Complex/immunology , Autoantibodies/immunology , Inflammasomes/immunology , Intramolecular Oxidoreductases/immunology , Macrophage Migration-Inhibitory Factors/immunology , Monocytes/immunology , NLR Family, Pyrin Domain-Containing 3 Protein/immunology , Ribonucleoprotein, U1 Small Nuclear/immunology , Blotting, Western , CARD Signaling Adaptor Proteins/immunology , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Humans , Interleukin-1beta/immunology , Intramolecular Oxidoreductases/antagonists & inhibitors , Macrophage Migration-Inhibitory Factors/antagonists & inhibitors , Mass Spectrometry , Receptors, Immunologic
17.
Arthritis Care Res (Hoboken) ; 69(3): 338-346, 2017 03.
Article in English | MEDLINE | ID: mdl-27332620

ABSTRACT

OBJECTIVE: We assessed implementation of the 10-item Patient-Reported Outcomes Measurement Information System (PROMIS) physical function form (PF-10a) in routine practice in a racially and ethnically diverse population with rheumatoid arthritis (RA). Objectives were to determine feasibility of implementing PF-10a in the electronic health record (EHR) and PF-10a validity and longitudinal responsiveness. METHODS: Clinical and demographic data were abstracted from EHRs for all RA patients seen at a university-based rheumatology clinic between February 2013 and February 2015. We evaluated floor and ceiling (edge) effects and construct validity of PF-10a in a subgroup of patients with Health Assessment Questionnaire (HAQ) scores (n = 189). We used linear mixed-effects models to assess responsiveness of PF-10a to longitudinal changes in the Clinical Disease Activity Index (CDAI) for patients in the entire clinical cohort, with both scores recorded on at least 2 encounters (n = 326). RESULTS: Half of the patients were nonwhite, and 15% were non-English speakers. Over a 2-year period, PF10a was successfully implemented; 97% of patients and 89% of encounters had at least 1 measurement performed. PF-10a had fewer ceiling (defined as best) effects than the HAQ (8% versus 22%), and convergent validity was high (r = -0.85). PF-10a was sensitive to expected differences (older versus younger patients, more versus less active disease). Longitudinal changes in PF-10a were highly associated with changes in the CDAI score (P < 0.0001). CONCLUSION: PF-10a was feasible to implement in a diverse RA population. It strongly correlates with the HAQ but has fewer ceiling effects and is responsive to changes in RA disease activity, suggesting its validity for use in routine clinical practice.


Subject(s)
Arthritis, Rheumatoid/diagnosis , Outpatient Clinics, Hospital , Patient Reported Outcome Measures , Aged , Arthritis, Rheumatoid/ethnology , Arthritis, Rheumatoid/physiopathology , Electronic Health Records , Feasibility Studies , Female , Humans , Linear Models , Longitudinal Studies , Male , Middle Aged , Predictive Value of Tests , Reproducibility of Results , San Francisco/epidemiology , Severity of Illness Index
19.
Sci Rep ; 6: 36879, 2016 11 10.
Article in English | MEDLINE | ID: mdl-27830734

ABSTRACT

Hypoxia preconditioning of mesenchymal stem cells (MSCs) has been shown to promote wound healing through HIF-1α stabilization. Preconditioned MSCs can be applied to three-dimensional biomaterials to further enhance the regenerative properties. While environmentally induced hypoxia has proven difficult in clinical settings, this study compares the wound healing capabilities of adipose derived (Ad) MSCs seeded on a collagen-glycosaminoglycan (GAG) dermal substrate exposed to either environmental hypoxia or FDA approved deferoxamine mesylate (DFO) to stabilize HIF-1α for wound healing. The release of hypoxia related reparative factors by the cells on the collagen-GAG substrate was evaluated to detect if DFO produces results comparable to environmentally induced hypoxia to facilitate optimal clinical settings. VEGF release increased in samples exposed to DFO. While the SDF-1α release was lower in cells exposed to environmental hypoxia in comparison to cells cultured in DFO in vitro. The AdMSC seeded biomaterial was further evaluated in a murine model. The implants where harvested after 1 days for histological, inflammatory, and protein analysis. The application of DFO to the cells could mimic and enhance the wound healing capabilities of environmentally induced hypoxia through VEGF expression and promises a more viable option in clinical settings that is not merely restricted to the laboratory.


Subject(s)
Mesenchymal Stem Cells/metabolism , Neovascularization, Physiologic , Vascular Endothelial Growth Factor A/metabolism , Animals , Cells, Cultured , Collagen/chemistry , Culture Media/chemistry , Deferoxamine/pharmacology , Female , Glycosaminoglycans/chemistry , Humans , Male , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/drug effects , Mice, Hairless , Mice, Nude , Tissue Scaffolds/chemistry , Vascular Endothelial Growth Factor A/physiology , Wound Healing
20.
BMC Health Serv Res ; 16(a): 384, 2016 08 15.
Article in English | MEDLINE | ID: mdl-27527720

ABSTRACT

BACKGROUND: Treat-to-target is the recommended strategy for the management of rheumatoid arthritis (RA) and involves regular assessment of disease activity using validated measures and subsequent adjustment of medical therapy if patients are not in remission or low disease activity. Recommendations published in 2012 detailed the preferred disease activity measures but there have been few publications on implementation of disease activity measures in a real-world clinic setting. METHODS: Plan-Do-Study-Act (PDSA) methodology was used over two cycles with a goal of increasing provider measurement of disease activity during all RA patient visits. In PDSA cycle 1, we implemented a paper-based form to help providers assess disease activity in RA patients. PDSA cycle 2 included the creation of separate patient and physician forms for collection of information, identification of patients prior to their clinic visit and incorporation of medical assistants into the workflow. RESULTS: The first PDSA cycle improved the number of RA patients with documented disease activity measures from 24 % over a 4-week period, to an average of 44 % over an 8-week period. The second PDSA cycle showed a sustained and dramatic improvement, with 85 % of patients having a disease activity measure recorded over a 27-week period. CONCLUSIONS: Implementation of disease activity measurement in a typical academic rheumatology clinic can be achieved by standardizing workflow using a simple paper form.


Subject(s)
Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/physiopathology , Rheumatology , Aged , Arthritis, Rheumatoid/therapy , Disability Evaluation , Female , Humans , Male , Reproducibility of Results , San Francisco , Severity of Illness Index
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