UNLABELLED: Orthopaedic surgeons are increasingly aware of deleterious effects of the opioid epidemic and the association between overprescription and diversion toward nonmedical opioid use or substance abuse. Opiate prescriptions at the time of hospital discharge have been identified as target for intervention. This study describes the successful outcome of a goal-directed intervention aimed at decreasing opioid overprescription by providing routine feedback to providers regarding their prescribing patterns. METHODS: The amount of opioid medications, quantified as oral morphine equivalents (OMEs), provided to opioid-naive adult patients on discharge after orthopaedic surgery was prospectively collected. As part of an institutional quality improvement initiative, medical providers received reports every 2 months detailing median discharge OMEs prescribed, trended over time. After 6 months, a retrospective comparison was done between preintervention and intervention patient cohorts. RESULTS: There were 401 patients in the preintervention cohort and 429 patients in the intervention cohort. Both groups were similar in regard to age, sex, rates of depression, surgical time, length of stay, orthopaedic subspecialty, and inpatient opioid requirement before discharge. Patients in the intervention cohort were prescribed markedly fewer opioid medications by 25%, equivalent to 20 tablets of 5-mg oxycodone IR (450 versus 600 OMEs, P < 0.001). Despite these opioid medications, opioid refill rates during the first 90 days after discharge did not markedly change between groups. DISCUSSION: It is critical to judiciously treat postoperative pain while avoiding opioid overprescription. This study demonstrated the outcome of a goal-directed initiative to decrease overprescription of opioid medications. The initiative reduced discharge opioid prescriptions yet did not increase the risk of requiring a prescription refill in the postoperative period. This indicates that such an approach can result in opioid reduction, while still providing appropriate care and pain control for patients.

BACKGROUND: Despite the pivotal role of clinical trials in advancing orthopaedic oncology knowledge and treatment strategies, the persistent issues of trial discontinuation and nonpublication are significant problems. This study conducted an analysis examining clinical trial discontinuation rates, associations between intervention types and discontinuation/nonpublication, and the role of funding, enrollment size, and their implications for trial success and completion. METHODS: This study, conducted on May 1, 2023, utilized a cross-sectional design to comprehensively analyze phase 3 and 4 randomized controlled trials within the realm of orthopaedic oncology. We specifically incorporated Phase 3 and 4 trials as they are designed to evaluate prolonged outcomes in human subjects and are more likely to reach publication. Study characteristics of interest included the intervention utilized in the clinical trial, presence of funding, whether the trial was published, completed, and trial enrollment size. The investigation involved an examination of ClinicalTrials.gov, a prominent online repository of clinical trial data managed by the National Library of Medicine of the USA. Descriptive statistics and multivariate logistic regressions were used to determine statistical significance. RESULTS: Among the cohort of 130 trials, 19.2% were prematurely discontinued. Completion rates varied based on intervention type; 111 pharmaceutical trials demonstrated a completion rate of 83.8%, whereas 19 non-pharmaceutical trials exhibited a completion rate of 8.0% (P < .001). Surgical trials, totaling 10, showed a completion rate of 90%. The overall trial publication rate was 86.15%, with pharmaceutical interventions achieving a publication rate of 91.96%. Larger-scale trials (≥ 261 participants) emerged as a protective factor against both discontinuation (Adjusted Odds Ratio [AOR]: 0.85, 95% Confidence Interval [CI] 0.42-0.95) and nonpublication (AOR: 0.19, 95% CI 0.13-.47), compared to smaller-scale trials. CONCLUSION: This study accentuates the heightened vulnerability of non-pharmaceutical interventions and trials exhibiting lower rates of enrollment to the issues of discontinuation and nonpublication. Moving forward, the advancement of clinical trials necessitates a concerted effort to enhance trial methodologies, especially concerning nonpharmaceutical interventions, along with a meticulous refinement of participant enrollment criteria.

A prospective observational cohort of 20 primary total hip arthroplasty (n = 12) and total knee arthroplasty (n = 8) patients (mean age: 63 ± 6 years) was passively monitored with a consumer-level wearable activity sensor before and 6 weeks after surgery. Patients were clustered by minimal change or decreased activity using sensor data. Decreased postoperative activity was associated with greater pain reduction (-5.5 vs -2.0, P = .03). All patients surpassed minimal clinical benefit thresholds of total joint arthroplasty (TJA) (Hip Disability and Osteoarthritis Score Junior 30.5 vs 20.8, P = .23; Knee Injury and Osteoarthritis Outcome Score Junior 23.3 vs 18.2, P = .77) within 6 weeks. Patients who objectively "take it easy" after TJA may experience less pain with no difference in early subjective outcome. Remote, passive analysis of outpatient wearable sensor data may permit real-time detection of early problems after TJA.

INTRODUCTION: In two-stage exchange for periprosthetic joint infection (PJI), adding antibiotics to cement spacers is the standard of care; however, little is known about optimal dosage. There is emphasis on using >3.6 g of total antibiotic, including ≥2.0 g of vancomycin, per 40 g of cement, but these recommendations lack clinical evidence. We examined whether recommended antibiotic spacer doses affect treatment success. METHODS: This was a retrospective review of 202 patients who underwent two-stage exchange for PJI from 2004 to 2020 with at least 1-year follow-up. Patients were separated into high (>3.6 g of total antibiotic per 40 g of cement) and low-dose spacer groups. Primary outcomes were overall and infectious failure. RESULTS: High-dose spacers were used in 80% (162/202) of patients. High-dose spacers had a reduced risk of overall (OR, 0.37; P = 0.024) and infectious (OR, 0.35; P = 0.020) failure for infected primary arthroplasties, but not revisions. In multivariate analysis, vancomycin dose ≥2.0 g decreased the risk of infectious failure (OR, 0.31; P = 0.016), although not overall failure (OR, 0.51; P = 0.147). CONCLUSION: During two-stage exchange for PJI, spacers with greater than 3.6 g of total antibiotic may reduce overall and infectious failure for infected primary arthroplasties. Furthermore, using at least 2.0 g of vancomycin could independently decrease the risk of infectious failure.

INTRODUCTION: There is no consensus on whether articulating or static spacers are superior during two-stage exchange arthroplasty for periprosthetic joint infection. We aimed to compare surgical time, need for extensile exposure, surgical costs, and treatment success for articulating and static spacers. METHODS: This was a retrospective review of 229 periprosthetic joint infections treated with two-stage exchange with a minimum of one-year follow-up. For articulating and static spacers, we compared the need for extensile exposure during reimplantation and treatment failure based on an updated definition. Surgical time and costs at both stages were also compared. Subgroup analysis was performed for total knee and hip arthroplasties. RESULTS: There was no difference in the surgical time for spacer insertion; however, articulating spacers demonstrated reduced surgical time during reimplantation (181 vs. 234 minutes, P < 0.001). In multivariate analysis, there was no difference in extensile exposures (odds ratio 2.20, P = 0.081), but treatment failure was more likely for static spacers (odds ratio 2.17, P = 0.009). Overall surgical costs for two-stage exchange were similar between groups (23,782 vs. 23,766, P = 0.495). CONCLUSION: Articulating spacers demonstrated shorter surgical times and a trend toward decreased extensile exposures during reimplantation. They also had higher treatment success rates and similar surgical costs for overall two-stage exchange.

Background

Complex revision total knee arthroplasty (TKA) often calls for endoprosthetic reconstruction to address bone loss, poor bone quality, and soft tissue insufficiency. Larger amounts of segmental bone loss in the setting of joint replacement may be associated with greater areas of devascularized tissue, which could increase the risk of complications and worsen functional results.

Questions/purposes

Are longer endoprosthetic reconstructions associated with (1) higher risk of deep infection; (2) increased risk of reoperation and decreased implant survivorship; or (3) poorer ambulatory status?

Methods

This is a single-institution retrospective case series of nononcologic femoral endoprosthetic reconstructions for revision TKA from 1995 to 2013 (n = 32). Cases were categorized as distal (n = 17) or diaphyseal (n = 15) femoral reconstructions based on extension to or above the supracondylar metaphyseal-diaphyseal junction, respectively. Five patients from each group were lost to followup before 2 years (distal mean 4 years [range, 2-8 years]; diaphyseal mean = 6 years [range, 2-16 years]), and one of the 12 distal reconstructions and two of the 10 diaphyseal reconstructions had not been evaluated within the past 5 years. Clinical outcomes and ambulatory status (able to walk or not) were assessed through chart review by authors not involved in any cases. Prior incidence of periprosthetic joint infection was high in both groups (distal = seven of 12 versus diaphyseal = four of 10; p = 0.670).

Results

Patients with diaphyseal femoral replacements were more likely to develop postoperative deep infections than patients with distal femoral replacements (distal = three of 12 versus diaphyseal = nine of 10; p = 0.004). Implant survivorship (revision-free) for diaphyseal reconstructions was worse at 2 years (distal = 100%, 95% confidence interval [CI], 100%-100% versus diaphyseal = 40%, 95% CI, 19%-86%; p = 0.001) and 5 years (distal = 90%, 95% CI, 75%-100% versus diaphyseal = 30%, 95% CI, 12%-73%; p = 0.001). Infection-free, revision-free survival (retention AND no infection) was worse for diaphyseal femoral replacing reconstructions than for distal femoral replacements at 2 years (distal = 70%, 95% CI, 48%-100% versus diaphyseal = 20%, 95% CI, 6%-69%; p = 0.037) and 5 years (distal = 70%, 95% CI, 48%-100% versus diaphyseal = 10%, 95% CI, 2%-64%; p = 0.012). There was no difference with the small numbers available in proportion of patients able to walk (distal reconstruction = eight of 11 versus diaphyseal = seven of 10; p = 1.000), although all but one patient in each group required walking aids.

Conclusions

Endoprosthetic femoral reconstruction is a viable salvage alternative to amputation for treatment of failed TKA with segmental distal femoral bone loss. In our small series even with substantial loss to followup and likely best-case estimates of success, extension proximal to the supracondylar metaphyseal-diaphyseal junction results in higher infection and revision risk. In infection, limb salvage remains possible with chronic antibiotic suppression, which we now use routinely for all femoral replacement extending into the diaphysis.

Level of evidence

Level III, therapeutic study.

Introduction

Symptomatic hip osteoarthritis (OA) causes significant morbidity and functional limitations. While corticosteroid injections (CSI) are commonly offered and administered for OA pain relief, it is unknown if they offer any clinically meaningful long-term benefit or reduce the overall need for surgical intervention.

Methods

A cross-sectional retrospective cohort study was performed on primary hip osteoarthritis patients from a single academic tertiary-care center arthroplasty clinic from 2014 to 2019. Patients were divided into three groups. CSI + THA: hip CSI patients who underwent subsequent ipsilateral THA. CSI-noTHA: hip CSI who have not had ipsilateral THA to date. THA-noCSI: a control group of consecutive hip OA patients who underwent primary THA without prior CSI. Demographic variables, injection relief duration, and radiographic arthritis severity were recorded. Time from clinic presentation to injection and/or THA were compared.

Results

357 patients met inclusion criteria and underwent guided, arthroplasty provider-ordered CSI. Mean duration of relief was 6.7 weeks (SD 8.7). 244 injection patients (67.2%) subsequently underwent THA (CSI + THA). 150 of 390 patients have not undergone THA at mean of 25.5 months follow-up. Mean time from clinic presentation to THA was 8.6 months longer after CSI (16.3, SD 17.8) months in CSI patients compared to 7.7 (SD 10.6) months for patients without CSI (p < 0.001). Of 117 patients in the CSI-noTHA group at mean 25 months follow-up, only 43 (12% of all injection patients) had not had THA because they found injections effective. The remaining 74 (63%) of CSI-noTHA patients have been deemed medically unfit for surgery or are currently scheduled for THA.

Discussion/conclusion

The results of this study suggest the utilization of intra-articular CSI as conservative treatment in an arthroplasty clinic does not prolong time to THA for a clinically important duration. The use of CSI should be reserved for diagnostic purposes and/or short-term pain relief in poor surgical candidates.

Level of evidence

III.

Purpose

Non-invasive imaging is a key clinical tool for detection and treatment monitoring of infections. Existing clinical imaging techniques are frequently unable to distinguish infection from tumors or sterile inflammation. This challenge is well-illustrated by prosthetic joint infections that often complicate joint replacements. D-methyl-¹¹C-methionine (D-¹¹C-Met) is a new bacteria-specific PET radiotracer, based on an amino acid D-enantiomer, that is rapidly incorporated into the bacterial cell wall. In this manuscript, we describe the biodistribution, radiation dosimetry, and initial human experience using D-¹¹C-Met in patients with suspected prosthetic joint infections.

Methods

614.5 ± 100.2 MBq of D-¹¹C-Met was synthesized using an automated in-loop radiosynthesis method and administered to six healthy volunteers and five patients with suspected prosthetic joint infection, who were studied by PET/MRI. Time-activity curves were used to calculate residence times for each source organ. Absorbed doses to each organ and body effective doses were calculated using OLINDA/EXM 1.1 with both ICRP 60 and ICRP 103 tissue weighting factors. SUV_max and SUV_peak were calculated for volumes of interest (VOIs) in joints with suspected infection, the unaffected contralateral joint, blood pool, and soft tissue background. A two-tissue compartment model was used for kinetic modeling.

Results

D-¹¹C-Met was well tolerated in all subjects. The tracer showed clearance from both urinary (rapid) and hepatobiliary (slow) pathways as well as low effective doses. Moreover, minimal background was observed in both organs with resident micro-flora and target organs, such as the spine and musculoskeletal system. Additionally, D-¹¹C-Met showed increased focal uptake in areas of suspected infection, demonstrated by a significantly higher SUV_max and SUV_peak calculated from VOIs of joints with suspected infections compared to the contralateral joints, blood pool, and background (P < 0.01). Furthermore, higher distribution volume and binding potential were observed in suspected infections compared to the unaffected joints.

Conclusion

D-¹¹C-Met has a favorable radiation profile, minimal background uptake, and fast urinary extraction. Furthermore, D-¹¹C-Met showed increased uptake in areas of suspected infection, making this a promising approach. Validation in larger clinical trials with a rigorous gold standard is still required.

Asthma is a heterogeneous disease, with multiple underlying inflammatory pathways and structural airway abnormalities that impact disease persistence and severity. Recent progress has been made in developing targeted asthma therapeutics, especially for subjects with eosinophilic asthma. However, there is an unmet need for new approaches to treat patients with severe and exacerbation-prone asthma, who contribute disproportionately to disease burden. Extensive deep phenotyping has revealed the heterogeneous nature of severe asthma and identified distinct disease subtypes. A current challenge in the field is to translate new and emerging knowledge about different pathobiologic mechanisms in asthma into patient-specific therapies, with the ultimate goal of modifying the natural history of disease. Here, we describe the Precision Interventions for Severe and/or Exacerbation-Prone Asthma (PrecISE) Network, a groundbreaking collaborative effort of asthma researchers and biostatisticians from around the United States. The PrecISE Network was designed to conduct phase II/proof-of-concept clinical trials of precision interventions in the population with severe asthma, and is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Using an innovative adaptive platform trial design, the PrecISE Network will evaluate up to 6 interventions simultaneously in biomarker-defined subgroups of subjects. We review the development and organizational structure of the PrecISE Network, and choice of interventions being studied. We hope that the PrecISE Network will enhance our understanding of asthma subtypes and accelerate the development of therapeutics for severe asthma.