Safety Profile of Seven-Day Intra-articular Antibiotic Irrigation for the Treatment of Chronic Periprosthetic Joint Infection: A Prospective Randomized Phase II Comparative Study.

BACKGROUND: Systemic intravenous antimicrobials yield poor outcomes during treatment of periprosthetic joint infection due to the inability to obtain minimum biofilm eradication concentrations. This study evaluated the safety of a novel method of optimized local delivery of intra-articular antibiotics (IAAs). METHODS: This was a Phase II, multicenter, prospective randomized trial evaluating safety of a rapid (seven-day) two-stage exchange arthroplasty with IAA irrigation compared to standard two-stage exchange. The Experimental Group received irrigation using 80 mg tobramycin daily with a 2-hour soak, followed by hourly irrigation using 125 mg vancomycin with a 30-minute soak via an intramedullary irrigation device. The Control Group received an antibiotic-loaded cement spacer with vancomycin (average 8.4 g) and tobramycin (average 7.1 g, total 16 g antibiotics). Both groups received 12 weeks of systemic antibiotics following Stage 2. Safety measures included adverse events, peak vancomycin/tobramycin serum concentrations (Experimental Group), blood transfusion, and mortality. There were thirty-seven patients randomized to the Experimental Group and 39 to control. There was no difference in baseline demographics or comorbidities. RESULTS: There were no antibiotic medication-related adverse events and 2 serious adverse events related to antibiotic instillation. Of 188 vancomycin peak measurements, 69% had detectable serum level concentrations, with all concentrations well below the maximum acceptable trough threshold of 20 µg/mL. Of the 103 tobramycin peak measurements, 45% had detectable levels, with all below the maximum acceptable peak threshold of 18 to 24 µg/mL. There was no difference in blood transfused per subject (Experimental: 655 mL versus Control: 792 mL; P = .4188). There were two (2) deaths in the Experimental Group and four (4) in the control. CONCLUSIONS: The use of IAA is safe with minimal systemic antibiotic exposure. There was no difference in the rates or severity of serious adverse events between groups. Further research is being conducted to examine treatment efficacy.

Outpatient total hip and knee arthroplasty - Patient expectations versus experience.

Aims & objectives: With modern advancements in surgical techniques and rapid recovery protocols, incidence of outpatient total joint arthroplasty (TJA) is increasing. Previous literature has historically focused on cost, safety, and clinical outcomes, with few studies investigating patient expectations and experiences. The aim of this study was to survey preoperative patient expectations related to outpatient TJA surgery compared with perioperative perceptions and experience. Materials & methods: Prospective study of patients undergoing outpatient total hip or knee arthroplasty at a single Tertiary Academic center. Preoperative and postoperative surveys were administered during routine clinic visits. Results: One hundred and six patients completed preoperative surveys; 79 completed postoperative surveys and were included in the final data analysis. Fifty (63.3 %) patients reported being aware of outpatient TJA prior to undergoing the procedure. There was no difference between preoperative anticipated pain control and postoperative perceived pain control (6.64 vs. 6.88, p = 0.77). Most postoperative patients (N = 56, 70.9 %) rated outpatient surgery as "much better" or "better" than expected. Most postoperative patients (N = 68, 86 %) would opt to have outpatient surgery again. Fifty-two (65.8 %) of postoperative patients believed outpatient surgery sped up their postoperative rehabilitation. Conclusion: For most patients, the outpatient surgical experience met or exceeded expectations. Nearly 90 % of patients would prefer to have outpatient surgery in the future, further supporting the continued migration of elective arthroplasty away from inpatient sites of care.

Opioid Utilization After Primary Total Hip and Knee Arthroplasty Following Sequential Implementation of Statewide Legislation.

Background: Following total hip arthroplasty (THA) and total knee arthroplasty (TKA), increased opioid use is associated with poor clinical outcomes. This study investigates implications of Florida legislative mandates on prescribing practices and opioid utilization following primary THA and TKA. Methods: We retrospectively reviewed patients undergoing primary TKA or THA between January 1, 2018, to December 31, 2020 at our academic medical center. Three groups were identified: procedures performed prior to mandates, after seven-day prescription limit, and after mandated electronic prescribing. A multivariate analyses of variance evaluated length of stay, morphine milligram equivalents (MMEs), age, body mass index and number of prescription refills. Chi-square tests compared preoperative opioid use, readmissions, and discharge disposition. Results: There were 198 patients in group one, 238 patients in group two, and 215 patients in group three (N = 651). Prior to any mandates, patients were prescribed 822.3 + 626.7 MMEs. Following a seven-day prescription limit this decreased to 465.0 + 296.0 MMEs (P < .001), which further decreased after mandated electronic prescribing (228.0 + 284.4 MMEs [P < 0.001]). Patients undergoing THA were prescribed less MME than those undergoing TKA. There was a 2.6% 90-day readmission rate, with no pain-related readmissions. Conclusions: Florida legislative mandates for opioid prescription quantities and electronic prescribing have effectively reduced average MMEs prescribed following primary arthroplasty. Despite a shift towards ambulatory surgery, opioid utilization decreased without compromising patient outcomes. These findings underscore the significance of both legislative and surgical practices influencing opioid prescribing habits among orthopaedic surgeons.

Perioperative Extracellular Brain Free-Water Changes for Older Adults Electing Total Knee Arthroplasty with General versus Spinal Anesthesia: A Pilot Study.

BACKGROUND: Recent research shows that older adults electing to undergo total knee arthroplasty with general anesthesia have a pre- to postoperative acute increase in molecular free-water within their cerebral white matter. It is unknown if this change is similar for individuals who elect spinal anesthesia methods. OBJECTIVE: To explore white matter microstructural changes in a pilot sample of older adults undergoing total knee arthroplasty and receiving general or spinal anesthesia. METHODS: We assessed acute perioperative changes in brain white matter free-water in a limited number of older adults electing total knee arthroplasty under spinal anesthesia (n = 5) and matched groups of older adults who received general anesthesia (n = 5) or had no surgery (n = 5). Patterns of free-water changes were also compared in the larger group of older adults electing total knee arthroplasty under general anesthesia (n = 61) and older adults with chronic knee pain who received no surgical intervention (n = 65). RESULTS: Our pilot results suggest older adults receiving general anesthesia had pre- to post-surgery free-water increases extensively throughout their white matter whereas those receiving spinal anesthesia appeared to have less consistent free-water increases. CONCLUSIONS: Our pilot results possibly suggest different patterns of perioperative brain white matter free-water changes based on anesthetic approach. We recommend future, larger studies to further examine the effects of anesthetic approach on perioperative brain free-water. The results of our study have potential implications for acute and chronic cognitive changes, perioperative complications, neurodegenerative processes including Alzheimer's disease, and understanding neuroinflammation.

A Physician-led Care Redesign Blunts Predictors of Length of Stay after Total Hip and Knee Arthroplasty.

We questioned to what extent traditional predictors of care team burden (via increased length of stay [LOS] after total joint arthroplasty [TJA]) were able to be mitigated through alteration of the care pathway. The impact on LOS of traditional patient risk factors, as well as encounter variables, were analyzed for a consecutive set of patients undergoing surgery before and after a physician-initiated arthroplasty care pathway redesign. We analyzed the impact of these variables on LOS, discharge disposition, and 90-day readmission; separate analyses were performed pre- and post-redesign for LOS. Several patient factors (Risk Assessment and Prediction Tool, body mass index, age, insurance type, smoking) predicted longer LOS in the pre-redesign cohort; post-redesign, only ambulation on the day of surgery and anticoagulation type were predictive. The redesign also lessened the aggregate impact of the patient-specific risk factors, resulting in reduced variation in LOS. Physician leadership of care pathways can reduce the impact of factors that have portended longer LOS, thereby reducing variability in LOS and costs for disparate patient populations while driving improvements in value-based care indices. (Journal of Surgical Orthopaedic Advances 32(2):097-101, 2023).

Lessons Learned From the Comprehensive Care for Joint Replacement Model at an Academic Tertiary Center: The Good, the Bad, and the Ugly.

BACKGROUND: Our institution participated in the Comprehensive Care for Joint Replacement (CJR) model from 2016 to 2020. Here we review lessons learned from a total joint arthroplasty (TJA) care redesign at a tertiary academic center amid changing: (1) CJR rules; (2) inpatient only rules; and (3) outpatient trends. METHODS: Quality, financial, and patient demographic data from the years prior to and during participation in CJR were obtained from institutional and Medicare reconciled CJR performance data. RESULTS: Despite an increase in true outpatients and new challenges that arose from changing inpatient-only rules, there was significant improvement in quality metrics: decreased length of stay (3.48-1.52 days, P < .001), increased home discharge rate (70.2-85.5%, P < .001), decreased readmission rate (17.7%-5.1%, P < .001), decreased complication rate (6.5%-2.0%, P < .001), and the Centers for Medicare and Medicaid Services (CMS) Composite Quality Score increased from 4.4 to 17.6. Over the five year period, CMS saved an estimated $8.3 million on 1,486 CJR cases, $7.5 million on 1,351 non-CJR cases, and $600,000 from the voluntary classification of 371 short-stay inpatients as outpatient-a total savings of $16.4 million. Despite major physician time and effort leading to marked improvements in efficiency, quality, and large cost savings for CMS, CJR participation resulted in a net penalty of $304,456 to our institution, leading to zero physician gainsharing opportunities. CONCLUSION: The benefits of CJR were tempered by malalignment of incentives among payer, hospital, and physician as well as a lack of transparency. Future payment models should be refined based on the successes and challenges of CJR.

Anemia Recovery after Trauma: A Longitudinal Study.

Background: Post-injury inflammation and its correlation with anemia recovery after severe trauma is poorly described. Severe injury induces a systemic inflammatory response associated with critical illness and organ dysfunction, including disordered hematopoiesis, and anemia. This study sought to characterize the resolution of post-injury inflammation and anemia to identify risk factors associated with persistence of anemia. Patients and Methods: This single-institution study prospectively enrolled 73 trauma patients with an injury severity score >15, hemorrhagic shock, and a lower extremity long bone orthopedic injury. Blood was obtained at enrollment and after 14 days, one, three, and six months. Analytes were compared using Mann-Whitney U tests with correction for multiple comparisons. Results: Median age was 45 years and Injury Severity Score (ISS) was 27, with anemia rates of 97% at two weeks, 80% at one month, 52% at three months, and 30% at six months. Post-injury elevations in erythropoietin, interleukin-6, and C-reactive protein resolved by one month, three months, and six months, respectively. Median granulocyte colony-stimulating factor (G-CSF) and tumor necrosis factor (TNF)-α concentrations remained elevated throughout the six-month follow-up period. Patients with persistent anemia had longer intensive care unit and hospital lengths of stay, more infectious complications, and received more packed red blood cell transfusions compared to those with early anemia recovery. Conclusions: Severe trauma is associated with a prolonged inflammatory response, which is associated with increased transfusion requirements, lengths of stay, and persistent anemia. Further analysis is needed to identify correlations between prolonged inflammation and clinical outcomes after discharge.

Bone Marrow Adipokine Expression Was Associated With Decreased Erythroid Colony Growth After Trauma.

BACKGROUND: Proinflammatory and immunomodulatory adipokines are linked to inflammation in critically ill patients but are poorly studied after injury. We hypothesized that trauma would induce systemic adipokine release and influence erythroid suppression. METHODS: Blood and bone marrow (BM) were collected from trauma patients (ISS > 15, n = 90) and compared to patients undergoing elective hip replacement (n = 37). Plasma adipokine levels were measured, and BM was assayed for adipokine transcription and erythroid progenitor growth potential. Differences were detected using t-tests and correlations using simple linear regression. RESULTS: Trauma patients exhibited decreased adiponectin (1.8* vs 3.4 mg/mL) and increased leptin (7.8* vs 4.6 ng/mL) and resistin (3.1* vs 2.5 ng/mL), with sex- and age-specific differences. They also showed increased BM visfatin transcription. Adipokine transcription negatively correlated with erythroid progenitor growth. CONCLUSION: Adipose tissue activity is linked to inflammatory responses after injury, with variability by age and sex. Bone marrow adipose tissue may influence erythroid recovery after trauma.

Surgical Management of Tibial Bone Loss in Revision Total Knee Arthroplasty: Clinical Outcomes and Radiographic Analysis of Tantalum Cones, Titanium Cones and Titanium Sleeves.

Background: The use of metaphyseal cones and sleeves has improved the ability to manage tibial bone loss in revision total knee arthroplasty (TKA). The purpose of this study was to compare the outcomes of three systems used for tibial metaphyseal reconstruction in revision TKA. Methods: We performed a retrospective review of a consecutive series of 723 revision TKAs, including 145 (20%) knee revisions using tibial cones or sleeves. We compared porous tantalum (TM) cones, titanium (Ti) cones and titanium sleeves. The mean follow-up was 2.5 years. Results: The rate of revision for any reason was similar among all groups. Revision-free survival rates were similar among all systems studied at a mean follow-up of 2.5 years (TM cones 93%, Ti cones 94%, titanium sleeves 89%). Ti cones had a lower complication rate (6%) compared to TM cones (24%) and sleeves (29%). TM cones (15%) and titanium sleeves (13%) had higher reoperation rates (for any cause) than Ti cones (2%). Radiographic loosening was higher for sleeves (11%) than TM and Ti cones (2%). Conclusion: Metaphyseal reconstruction for tibial bone loss in revision TKA using tantalum cones, titanium cones and titanium sleeves showed successful and comparable early clinical outcomes at a mean follow-up of 2.5 years with higher rates of radiographic loosening for titanium sleeves. Level of Evidence: III.

Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators.

Opioid prescribing for postoperative pain management is challenging because of inter-patient variability in opioid response and concern about opioid addiction. Tramadol, hydrocodone, and codeine depend on the cytochrome P450 2D6 (CYP2D6) enzyme for formation of highly potent metabolites. Individuals with reduced or absent CYP2D6 activity (i.e., intermediate metabolizers [IMs] or poor metabolizers [PMs], respectively) have lower concentrations of potent opioid metabolites and potentially inadequate pain control. The primary objective of this prospective, multicenter, randomized pragmatic trial is to determine the effect of postoperative CYP2D6-guided opioid prescribing on pain control and opioid usage. Up to 2020 participants, age ≥8 years, scheduled to undergo a surgical procedure will be enrolled and randomized to immediate pharmacogenetic testing with clinical decision support (CDS) for CYP2D6 phenotype-guided postoperative pain management (intervention arm) or delayed testing without CDS (control arm). CDS is provided through medical record alerts and/or a pharmacist consult note. For IMs and PM in the intervention arm, CDS includes recommendations to avoid hydrocodone, tramadol, and codeine. Patient-reported pain-related outcomes are collected 10 days and 1, 3, and 6 months after surgery. The primary outcome, a composite of pain intensity and opioid usage at 10 days postsurgery, will be compared in the subgroup of IMs and PMs in the intervention (n = 152) versus the control (n = 152) arm. Secondary end points include prescription pain medication misuse scores and opioid persistence at 6 months. This trial will provide data on the clinical utility of CYP2D6 phenotype-guided opioid selection for improving postoperative pain control and reducing opioid-related risks.

Transcriptomic Changes Within Human Bone Marrow After Severe Trauma.

BACKGROUND: Severe trauma is associated with severe systemic inflammation and neuroendocrine activation that is associated with erythroid progenitor growth suppression and refractory anemia. Although distinct transcriptional profiles have been detected in numerous tissue types after trauma, no study has yet characterized this within the bone marrow. This study sought to identify a unique bone marrow transcriptomic response following trauma. METHODS: In a prospective observational cohort study, bone marrow was obtained from severely injured trauma patients with a hip or femur fracture (n = 52), elective hip replacement patients (n = 33), and healthy controls (n = 11). RNA was isolated from bone marrow using a Purelink RNA mini kit. Direct quantification of mRNA copies was performed by NanoString Technologies on a custom gene panel. RESULTS: Trauma patients displayed an upregulation of genes encoding receptors known to have inhibitory downstream effects on erythropoiesis, including ferroportin, interleukin-6 (IL-6) receptor, transforming growth factor-beta (TGF-ß) receptor, and IL-10, as well as genes involved in innate immunity including toll-like receptor 4 (TLR4)-mediated signaling factors. In contrast, hip replacement patients had downregulated transcription of IL-1ß, IL-6, TGF-ß, tumor necrosis factor alpha, and the HAMP gene with no change in TLR4-mediated signaling factors. CONCLUSIONS: A unique transcriptomic response within the bone marrow was identified following severe trauma compared to elective hip replacement. These transcriptomic differences were related to the innate immune response as well as known inhibitors of erythropoiesis. Although confined to just one time point, this differential transcriptional response may be linked to refractory anemia and inflammation after injury.

Massive Osteolysis in a Modern Total Knee Prosthesis.

CASE: An 82-year-old woman underwent right total knee replacement with a sequentially irradiated and annealed highly cross-linked polyethylene insert. At 9 years, she was found to have a massive femoral osteolysis with an impending fracture. CONCLUSION: This case demonstrates a rare occurrence of massive femoral osteolysis, requiring revision surgery, with a sequentially irradiated and annealed highly cross-linked polyethylene.

Effects of Patient and Surgery Characteristics on Persistent Postoperative Pain: A Mediation Analysis.

OBJECTIVE: Acute postoperative pain intensity is associated with persistent postsurgical pain (PPP) risk. However, it remains unclear whether acute postoperative pain intensity mediates the relationship between clinical factors and persistent pain. MATERIALS AND METHODS: Participants from a mixed surgical population completed the Brief Pain Inventory and Pain Catastrophizing Scale before surgery, and the Brief Pain Inventory daily after surgery for 7 days and at 30 and 90 days after surgery. We considered mediation models using the mean of the worst pain intensities collected daily on each of postoperative days (PODs) 1 to 7 against outcomes of worst pain intensity at the surgical site endpoints reflecting PPP (POD 90) and subacute pain (POD 30). RESULTS: The analyzed cohort included 284 participants for the POD 90 outcome. For every unit increase of maximum acute postoperative pain intensity through PODs 1 to 7, there was a statistically significant increase of mean POD 90 pain intensity by 0.287 after controlling for confounding effects. The effects of female versus male sex (m=0.212, P=0.034), pancreatic/biliary versus colorectal surgery (m=0.459, P=0.012), thoracic cardiovascular versus colorectal surgery (m=0.31, P=0.038), every minute increase of anesthesia time (m=0.001, P=0.038), every unit increase of preoperative average pain score (m=0.012, P=0.015), and every unit increase of catastrophizing (m=0.044, P=0.042) on POD 90 pain intensity were mediated through acute PODs 1 to 7 postoperative pain intensity. DISCUSSION: Our results suggest the mediating relationship of acute postoperative pain on PPP may be predicated on select patient and surgical factors.

Blood flow restriction exercise to attenuate postoperative loss of function after total knee replacement: a randomized pilot study.

Aging well is directly associated with a healthy lifestyle. The focus of this paper is to relate that attenuation of postoperative loss of muscle function after a total knee arthroplasty (TKA) is an important consideration. Because patients usually do not tolerate standard high-resistance exercise in the preoperative or postoperative period, they often experience a decline in strength and function. Therefore, we tested the feasibility and acceptability of an alternative low-resistance exercise protocol with blood flow restriction (BFR) using a tourniquet in the preoperative period for patients awaiting TKA. We recruited patients undergoing a TKA and randomized six to the BFR exercise for 4 weeks prior to surgery and four to standard of care (no exercise). We measured physical function using the Short Physical Performance Battery (SPPB), the 6-Minute Walk Test (6MWT), leg strength (peak torque), and pain (numerical pain score) 4 to 5 weeks preoperatively and 2 weeks postoperatively. The clinical management, e.g., anesthetic management, did not differ between groups. No complications were observed. Our findings demonstrate the feasibility and acceptability of the BFR intervention. Although preliminary and not powered for comparison, the BFR group demonstrated less decline in SPPB following surgery (-2.2, 95%CI:-4.4,0.1) compared to the no exercise group (-4.8, 95%CI:-7.8,-1.7). No differences were noted for the 6MWT, leg strength, and pain measurements. We conclude that preoperative low-resistance exercise using the BFR is feasible and acceptable, and this test warrants investigation as an intervention to potentially attenuate the postoperative loss of physical function after TKA.

Assessing the feasibility of using the short physical performance battery to measure function in the immediate postoperative period after total knee replacement.

Measurements of physical function after total knee arthroplasty (TKA) are uncertain and require investments for special equipment, space, and staff. Therefore, we evaluated the Short Physical Performance Battery (SPPB) 4 to 6 weeks preoperatively and 2 weeks following TKA as this test battery addresses lower extremity strength, coordination, and balance, without additional special investments. For context, we also employed the Six-Minute Walk test (6MWT) and peak torque knee extension. Our analysis consisted of three women and one man, with average ages of 68.3±3.9 years. Patients showed a decrease in all functional measurements: SPPB (mean change: -4.8±1.9, 44% decrease), 6MWT (-0.37±.21 m/s, 34% decrease), and peak torque (-11.8±8.8°/s, 68% decrease). Our findings suggest the SPPB is feasible and can be integrated easily in daily clinical practice.

Slow Dynamics of Acute Postoperative Pain Intensity Time Series Determined via Wavelet Analysis Are Associated With the Risk of Severe Postoperative Day 30 Pain.

BACKGROUND: Evidence suggests that increased early postoperative pain (POP) intensities are associated with increased pain in the weeks following surgery. However, it remains unclear which temporal aspects of this early POP relate to later pain experience. In this prospective cohort study, we used wavelet analysis of clinically captured POP intensity data on postoperative days 1 and 2 to characterize slow/fast dynamics of POP intensities and predict pain outcomes on postoperative day 30. METHODS: The study used clinical POP time series from the first 48 hours following surgery from 218 patients to predict their mean POP on postoperative day 30. We first used wavelet analysis to approximate the POP series and to represent the series at different time scales to characterize the early temporal profile of acute POP in the first 2 postoperative days. We then used the wavelet coefficients alongside demographic parameters as inputs to a neural network to predict the risk of severe pain 30 days after surgery. RESULTS: Slow dynamic approximation components, but not fast dynamic detailed components, were linked to pain intensity on postoperative day 30. Despite imbalanced outcome rates, using wavelet decomposition along with a neural network for classification, the model achieved an F score of 0.79 and area under the receiver operating characteristic curve of 0.74 on test-set data for classifying pain intensities on postoperative day 30. The wavelet-based approach outperformed logistic regression (F score of 0.31) and neural network (F score of 0.22) classifiers that were restricted to sociodemographic variables and linear trajectories of pain intensities. CONCLUSIONS: These findings identify latent mechanistic information within the temporal domain of clinically documented acute POP intensity ratings, which are accessible via wavelet analysis, and demonstrate that such temporal patterns inform pain outcomes at postoperative day 30.

Patient and Procedural Determinants of Postoperative Pain Trajectories.

BACKGROUND: The primary goal of this study was to evaluate patterns in acute postoperative pain in a mixed surgical patient cohort with the hypothesis that there would be heterogeneity in these patterns. METHODS: This study included 360 patients from a mixed surgical cohort whose pain was measured across postoperative days 1 through 7. Pain was characterized using the Brief Pain Inventory. Primary analysis used group-based trajectory modeling to estimate trajectories/patterns of postoperative pain. Secondary analysis examined associations between sociodemographic, clinical, and behavioral patient factors and pain trajectories. RESULTS: Five distinct postoperative pain trajectories were identified. Many patients (167 of 360, 46%) were in the moderate-to-high pain group, followed by the moderate-to-low (88 of 360, 24%), high (58 of 360, 17%), low (25 of 360, 7%), and decreasing (21 of 360, 6%) pain groups. Lower age (odds ratio, 0.94; 95% CI, 0.91 to 0.99), female sex (odds ratio, 6.5; 95% CI, 1.49 to 15.6), higher anxiety (odds ratio, 1.08; 95% CI, 1.01 to 1.14), and more pain behaviors (odds ratio, 1.10; 95% CI, 1.02 to 1.18) were related to increased likelihood of being in the high pain trajectory in multivariable analysis. Preoperative and intraoperative opioids were not associated with postoperative pain trajectories. Pain trajectory group was, however, associated with postoperative opioid use (P < 0.001), with the high pain group (249.5 oral morphine milligram equivalents) requiring four times more opioids than the low pain group (60.0 oral morphine milligram equivalents). CONCLUSIONS: There are multiple distinct acute postoperative pain intensity trajectories, with 63% of patients reporting stable and sustained high or moderate-to-high pain over the first 7 days after surgery. These postoperative pain trajectories were predominantly defined by patient factors and not surgical factors.

A hybrid implementation-effectiveness randomized trial of CYP2D6-guided postoperative pain management.

PURPOSE: Cytochrome P450 2D6 (CYP2D6) genotype-guided opioid prescribing is limited. The purpose of this type 2 hybrid implementation-effectiveness trial was to evaluate the feasibility of clinically implementing CYP2D6-guided postsurgical pain management and determine that such an approach did not worsen pain control. METHODS: Adults undergoing total joint arthroplasty were randomized 2:1 to genotype-guided or usual pain management. For participants in the genotype-guided arm with a CYP2D6 poor (PM), intermediate (IM), or ultrarapid (UM) metabolizer phenotype, recommendations were to avoid hydrocodone, tramadol, codeine, and oxycodone. The primary endpoints were feasibility metrics and opioid use; pain intensity was a secondary endpoint. Effectiveness outcomes were collected 2 weeks postsurgery. RESULTS: Of 282 patients approached, 260 (92%) agreed to participate. In the genotype-guided arm, 20% had a high-risk (IM/PM/UM) phenotype, of whom 72% received an alternative opioid versus 0% of usual care participants (p < 0.001). In an exploratory analysis, there was less opioid consumption (200 [104-280] vs. 230 [133-350] morphine milligram equivalents; p = 0.047) and similar pain intensity (2.6 ± 0.8 vs. 2.5 ± 0.7; p = 0.638) in the genotype-guided vs. usual care arm, respectively. CONCLUSION: Implementing CYP2D6 to guide postoperative pain management is feasible and may lead to lower opioid use without compromising pain control.

The role of bone marrow microRNA (miR) in erythropoietic dysfunction after severe trauma.

BACKGROUND: Previous data has shown that severe traumatic injury is associated with bone marrow dysfunction, which manifests as persistent injury-associated anemia. This study sought to identify whether the expression of erythropoiesis-related microRNAs were altered in the bone marrow of trauma patients to determine if these microRNAs play a role in persistent injury-associated anemia. METHODS: Bone marrow was collected from severely injured trauma patients who underwent fracture fixation as well as patients who underwent elective hip replacement. There were 27 trauma patients and 10 controls analyzed. Total RNA and microRNA were isolated from CD34-positive cells using the RNeasy Plus Mini kit, and genome-wide microRNA expression patterns were assayed. Genes with significant expression differences were found using BRB-ArrayTools with a significance of P < .01. RESULTS: There were marked differences in expression of 108 microRNAs in the trauma group when compared with hip replacement patients. Four of these microRNAs play a role in regulating erythropoiesis: microRNA-150, microRNA-223, microRNA15a, and microRNA-24. These microRNAs were all upregulated significantly, with trauma/hip replacement fold changes of 1.7, 1.8, 1.2, and 1.2 respectively, and all act to suppress or regulate erythropoiesis. CONCLUSION: Assessment of the bone marrow microRNA profile in trauma patients compared to those undergoing elective hip replacement revealed the differential expression of microRNA-150, microRNA-223, microRNA-15a, and microRNA-24. These microRNAs all play a role in decreased erythroid progenitor cell growth and provide important insight to the erythropoietic dysfunction seen after trauma.

A Randomized Controlled Trial of Music for Pain Relief after Arthroplasty Surgery.

PURPOSE: Effective pain management for patients undergoing orthopedic surgery, using pharmacological and nonpharmacological strategies, is essential. This pilot study evaluated music as an adjuvant therapy with prescribed analgesics to reduce acute pain and analgesic use among patients undergoing arthroplasty surgery. DESIGN: Prospective randomized controlled trial of 50 participants scheduled for arthroplasty surgery at a large university-affiliated hospital. METHODS: Participants were randomly assigned to treatment (music and analgesic medication; n = 25) or control (analgesic medication only; n = 25) groups. The intervention consisted of listening to self-selected music for 30 minutes, three times per day postoperatively in hospital and for 2 days postdischarge at home. Participants rated pain intensity and distress before and after music listening (treatment group) or meals (control group). Analgesic medication use was assessed via medical records in hospital and self-report logs postdischarge. RESULTS: Forty-seven participants completed the study. Participants who listened to music after surgery reported significantly lower pain intensity and distress in hospital and postdischarge at home. There were no statistically significant differences in analgesic medication use after surgery between groups. CONCLUSIONS: Study findings provide further evidence for the effectiveness of music listening, combined with analgesics, for reducing postsurgical pain, and extend the literature by examining music listening postdischarge. Music listening is an effective adjuvant pain management strategy. It is easy to administer, accessible, and affordable. Patient education is needed to encourage patients to continue to use music to reduce pain at home during the postoperative recovery period.