Differing Approaches to Pain Management for Intrauterine Device Insertion and Maintenance: A Scoping Review.

Intrauterine devices (IUDs) are considered a reliable contraceptive option for women, but they can come with side effects. There is a disconnect in standard guidelines for IUD insertion within and without the U.S. The objective of this review was to address a gap in the literature regarding official procedures for pain management during IUD implantation. This scoping review was initiated using keywords to extract relevant articles from multiple databases: U.S. National Library of Medicine National Institutes of Health (PubMed), MEDLINE (Ovid), and Excerpta Medica dataBASE (EMBASE, Ovid). Initially, 457 articles were identified and after a rigorous screening and selection process, 37 articles were chosen to be further assessed to ascertain if they met the study's inclusion criteria. Those 37 articles were further evaluated fully to check for relevancy. From that process, 19 articles were chosen for the review, and all passed quality assessment evaluations using the JB Appraisal Tools. To best address the research question, the data from the 19 articles were divided into three categories: 1) circumstantial factors, 2) non-pharmacological methods, and 3) pharmacological methods. Circumstantially, women with previous vaginal deliveries experienced the lowest pain during the procedure, and nulligravid (never pregnant) women experienced the most pain. Lower pain scores were reported by lactating women compared to non-lactating. Black women experienced the most anticipated pain compared to other races. Regarding non-pharmacological methods, different insertion techniques, tools, and the use of a cold compress were found to not affect the level of pain during IUD insertion. Lastly, it was shown that pharmacological methods such as lidocaine gel, lidocaine paracervical block, and lidocaine combined with either diclofenac or prilocaine decreased pain scores at different time stamps of the procedure. Also, oral ketorolac and a vaginal combination of misoprostol and dinoprostone helped reduce pain. Findings from this scoping review revealed a lack of uniformity across practices when performing IUD insertions, possibly due to differences in procedures across circumstantial factors, non-pharmacological methods, and pharmacological methods. More research is needed to investigate the intricacies of pain with IUD insertion. Moving forward, especially following a potential increase in the use of IUDs after the reversal of Roe v. Wade, establishing this gap may lead to a more refined standardized protocol to mitigate pain with IUD insertions.

Stochastic model of vesicular stomatitis virus replication reveals mutational effects on virion production.

We present the first complete stochastic model of vesicular stomatitis virus (VSV) intracellular replication. Previous models developed to capture VSV's intracellular replication have either been ODE-based or have not represented the complete replicative cycle, limiting our ability to understand the impact of the stochastic nature of early cellular infections on virion production between cells and how these dynamics change in response to mutations. Our model accurately predicts changes in mean virion production in gene-shuffled VSV variants and can capture the distribution of the number of viruses produced. This model has allowed us to enhance our understanding of intercellular variability in virion production, which appears to be influenced by the duration of the early phase of infection, and variation between variants, arising from balancing the time the genome spends in the active state, the speed of incorporating new genomes into virions, and the production of viral components. Being a stochastic model, we can also assess other effects of mutations beyond just the mean number of virions produced, including the probability of aborted infections and the standard deviation of the number of virions produced. Our model provides a biologically interpretable framework for studying the stochastic nature of VSV replication, shedding light on the mechanisms underlying variation in virion production. In the future, this model could enable the design of more complex viral phenotypes when attenuating VSV, moving beyond solely considering the mean number of virions produced.

Ten simple rules for managing laboratory information.

Information is the cornerstone of research, from experimental (meta)data and computational processes to complex inventories of reagents and equipment. These 10 simple rules discuss best practices for leveraging laboratory information management systems to transform this large information load into useful scientific findings.

The Opioid Epidemic: A Review of the Contributing Factors, Negative Consequences, and Best Practices.

The opioid epidemic is a significant public health crisis that has caused extensive harm and devastation in the United States. This literature review aimed to identify the contributing factors and negative consequences of the epidemic, as well as best practices for healthcare providers in managing the epidemic. Overprescribing opiates and opioids, lack of education and opportunity, and being unmarried or divorced were some of the identified contributing factors to dependence on opioids. The epidemic's negative consequences are substantial, leading to increased access to opioids for vulnerable populations, which consequently cause accidental death among men and the degradation of rural community health services. As part of the literature review, we also analyzed the best practices for healthcare providers, including implementing prescription drug monitoring programs (PDMPs). However, we found that while PDMPs resulted in a decrease in opioid overprescription and an increase in provider confidence when prescribing medication, the evidence for their effectiveness in improving rural community health services or reducing opioid overdoses and opioid-related deaths was inconclusive. Our review highlights that the greatest challenge to overcome is a lack of legal mandates and proper education for healthcare providers on best practices for addressing the epidemic. To regulate and control opioids effectively, tracking and standardizing prescription models by federal agencies and medical institutions is necessary but not enough. Legal action is vital for the successful containment of the opioid crisis.

Liver Kinase B1 Regulates Remodeling of the Tumor Microenvironment in Triple-Negative Breast Cancer.

Liver kinase B1 (LKB1) is a potent tumor suppressor that regulates cellular energy balance and metabolism as an upstream kinase of the AMP-activated protein kinase (AMPK) pathway. LKB1 regulates cancer cell invasion and metastasis in multiple cancer types, including breast cancer. In this study, we evaluated LKB1's role as a regulator of the tumor microenvironment (TME). This was achieved by seeding the MDA-MB-231-LKB1 overexpressing cell line onto adipose and tumor scaffolds, followed by the evaluation of tumor matrix-induced tumorigenesis and metastasis. Results demonstrated that the presence of tumor matrix enhanced tumorigenesis in both MDA-MB-231 and MDA-MB-231-LKB1 cell lines. Metastasis was increased in both MDA-MB-231 and -LKB1 cells seeded on the tumor scaffold. Endpoint analysis of tumor and adipose scaffolds revealed LKB1-mediated tumor microenvironment remodeling as evident through altered matrix protein production. The proteomic analysis determined that LKB1 overexpression preferentially decreased all major and minor fibril collagens (collagens I, III, V, and XI). In addition, proteins observed to be absent in tumor scaffolds in the LKB1 overexpressing cell line included those associated with the adipose matrix (COL6A2) and regulators of adipogenesis (IL17RB and IGFBP4), suggesting a role for LKB1 in tumor-mediated adipogenesis. Histological analysis of MDA-MB-231-LKB1-seeded tumors demonstrated decreased total fibril collagen and indicated decreased stromal cell presence. In accordance with this, in vitro condition medium studies demonstrated that the MDA-MB-231-LKB1 secretome inhibited adipogenesis of adipose-derived stem cells. Taken together, these data demonstrate a role for LKB1 in regulating the tumor microenvironment through fibril matrix remodeling and suppression of adipogenesis.

Breast Cancer-Stromal Interactions: Adipose-Derived Stromal/Stem Cell Age and Cancer Subtype Mediated Remodeling.

Adipose tissue is characterized as an endocrine organ that acts as a source of hormones and paracrine factors. In diseases such as cancer, endocrine and paracrine signals from adipose tissue contribute to cancer progression. Young individuals with estrogen receptor-alpha positive (ER-α+) breast cancer (BC) have an increased resistance to endocrine therapies, suggesting that alternative estrogen signaling is activated within these cells. Despite this, the effects of stromal age on the endocrine response in BC are not well defined. To identify differences between young and aged ER-α+ breast tumors, RNA sequencing data were obtained from The Cancer Genome Atlas. Analysis revealed enrichment of matrix and paracrine factors in young (≤40 years old) patients compared to aged (≥65 years old) tumor samples. Adipose-derived stromal/stem cells (ASCs) from noncancerous lipoaspirate of young and aged donors were evaluated for alterations in matrix production and paracrine secreted factors to determine if the tumor stroma could alter estrogen signaling. Young and aged ASCs demonstrated comparable proliferation, differentiation, and matrix production, but exhibited differences in the expression levels of inflammatory cytokines (Interferon gamma, interleukin [IL]-8, IL-10, Tumor necrosis factor alpha, IL-2, and IL-6). Conditioned media (CM)-based experiments showed that young ASC donor age elevated endocrine response in ER-α+ BC cell lines. MCF-7 ER-α+ BC cell line treated with secreted factors from young ASCs had enhanced ER-α regulated genes (PGR and SDF-1) compared to MCF-7 cells treated with aged ASC CM. Western blot analysis demonstrated increased activation levels of p-ER ser-167 in the MCF-7 cell line treated with young ASC secreted factors. To determine if ER-α+ BC cells heightened the cytokine release in ASCs, ASCs were stimulated with MCF-7-derived CM. Results demonstrated no change in growth factors or cytokines when treated with the ER-α+ secretome. In contrast to ER-α+ CM, the ER-α negative MDA-MB-231 derived CM demonstrated increased stimulation of pro-inflammatory cytokines in ASCs. While there was no observed change in the release of selected paracrine factors, MCF-7 cells did induce matrix production and a pro-adipogenic lineage commitment. The adipogenesis was evident by increased collagen content through Sirius Red/Fast Green Collagen stain, lipid accumulation evident by Oil Red O stain, and significantly increased expression in PPARγ mRNA expression. The data from this study provide evidence suggesting more of a subtype-dependent than an age-dependent difference in stromal response to BC, suggesting that this signaling is not heightened by reciprocal signals from ER-α+ BC cell lines. These results are important in understanding the mechanisms of estrogen signaling and the dynamic and reciprocal nature of cancer cell-stromal cell crosstalk that can lead to tumor heterogeneity and variance in response to therapy.

Distinguishing Periprosthetic Crystalline Arthropathy from Infection in Total Knee Arthroplasty: A Systematic Review.

Distinguishing periprosthetic crystalline arthropathy from periprosthetic joint infection (PJI) remains a diagnostic challenge as both symptom presentation and diagnostic tests overlap. Accurate differentiation is important as treatment plans vary significantly. We sought to systematically review all cases of total knee arthroplasty (TKA) periprosthetic crystalline arthropathy reported in the literature and summarize clinical, diagnostic, and operative findings in the context of guidelines for diagnosing PJI. The goal of this systematic review is to determine the amount of diagnostic overlap and to identify best practices for differentiating between these two diagnoses. MEDLINE and Google Scholar were searched to identify cases of crystalline arthropathy following TKA. Case reports were reviewed for patient characteristics, clinical symptoms, physical exam, laboratory results, and treatment outcomes. These findings were summarized across patients and dichotomized based on current thresholds for diagnosing PJI according to Musculoskeletal Infection Society criteria. Twenty-six articles were identified which included 42 cases of periprosthetic crystalline arthropathy (17 gout, 16 pseudogout, one both, and eight not specified). Of these cases, 25 presented over 1 year after their index arthroplasty and 15 had no prior history of crystalline arthropathy. Only six cases had a superimposed infection based on aspiration or intraoperative cultures. For cases without a culture-positive infection, several diagnostic tests overlap with PJI thresholds: 95% of patients had C-reactive protein greater than 1 mg/dL, 76% had an erythrocyte sedimentation rate greater than 30 mm/hour, 91% had a synovial white blood cell greater than 3,000 cells, and 76% had a synovial polymorphonuclear cells percent greater than 80%. Patients without co-infection were managed with non-steroidal anti-inflammatory drugs, colchicine, allopurinol, steroids, or a combination of these treatments and most had complete resolution of symptoms within 1 week. Commonly used markers of PJI fail to reliably distinguish periprosthetic crystalline arthropathy from infection. Though clinical judgement and consideration of the implications of delayed treatment for acute PJI remain paramount, in the setting of synovial crystals, surgeons may wish to consider this alternate etiology as the source of the patient's clinical symptoms.

Transitioning a Practice to Robotic Total Knee Arthroplasty Is Correlated with Favorable Short-Term Clinical Outcomes-A Single Surgeon Experience.

BACKGROUND: This study sought to evaluate the patient experience and short-term clinical outcomes associated with the hospital stay of patients who underwent robotic arm-assisted total knee arthroplasty (TKA). These results were compared with a cohort of patients who underwent TKA without robotic assistance performed by the same surgeon prior to the introduction of this technology. MATERIALS AND METHODS: A cohort of consecutive patients undergoing primary TKA for the diagnosis of osteoarthritis by a single fellowship trained orthopaedic surgeon over a 39-month period was identified. Patients who underwent TKA during the year that this surgeon transitioned his entire knee arthroplasty practice to robotic assistance were excluded to eliminate selection bias and control for the learning curve. All patients received the same prosthesis and postoperative pain protocol. Patients that required intubation for failed spinal anesthetic were excluded. A final population of 492 TKAs was identified. Of these, 290 underwent TKA without robotic assistance and 202 underwent robotic arm-assisted TKA. Patient demographic characteristics and short-term clinical data were analyzed. RESULTS: Robotic arm-assisted TKA was associated with shorter length of stay (2.3 vs. 2.6 days, p < 0.001), a 50% reduction in morphine milligram equivalent utilization (from 214 to 103, p < 0.001), and a mean increase in procedure time of 9.3 minutes (p < 0.001). There was one superficial infection in the nonrobotic cohort and there were no deep postoperative infections in either cohort. There were no manipulations under anesthesia in the robotic cohort while there were six in the nonrobotic cohort. Additionally, there were no significant differences in emergency department visits, readmissions, or return to the operating room. CONCLUSION: This analysis corroborates existing literature suggesting that robotic arm-assisted TKA can be correlated with improved short-term clinical outcomes. This study reports on a single surgeon's experience with regard to analgesic requirements, length of stay, pain scores, and procedure time following a complete transition to robotic arm-assisted TKA. These results underscore the importance of continued evaluation of clinical outcomes as robotic arthroplasty technology continues to grow.

Cholinergic neurons constitutively engage the ISR for dopamine modulation and skill learning in mice.

The integrated stress response (ISR) maintains proteostasis by modulating protein synthesis and is important in synaptic plasticity, learning, and memory. We developed a reporter, SPOTlight, for brainwide imaging of ISR state with cellular resolution. Unexpectedly, we found a class of neurons in mouse brain, striatal cholinergic interneurons (CINs), in which the ISR was activated at steady state. Genetic and pharmacological manipulations revealed that ISR signaling was necessary in CINs for normal type 2 dopamine receptor (D2R) modulation. Inhibiting the ISR inverted the sign of D2R modulation of CIN firing and evoked dopamine release and altered skill learning. Thus, a noncanonical, steady-state mode of ISR activation is found in CINs, revealing a neuromodulatory role for the ISR in learning.

Evaluation of Extracellular Matrix Composition to Improve Breast Cancer Modeling.

The development of resistance to therapy is a significant obstacle to effective therapeutic regimens. Evaluating the effects of oncology drugs in the laboratory setting is limited by the lack of translational models that accurately recapitulate cell-microenvironment interactions present in tumors. Acquisition of resistance to therapy is facilitated, in part, by the composition of the tumor extracellular matrix (ECM), with the primary current in vitro model using collagen I (COL I). Here we seek to identify the prevalence of COL I-enhanced expression in the triple-negative breast cancer (TNBC) subtype. Furthermore, we identify if methods of response to therapy are altered depending on matrix composition. We demonstrated that collagen content varies in patient tumor samples across subtypes, with COL I expression dramatically increased in typically less aggressive estrogen receptor (ER)-positive(ER+)/progesterone receptor (PGR)-positive (PGR+) cancers irrespective of patient age or race. These findings are of significance considering how frequently COL I is implicated in tumor progression. In vitro analyses of ER+ and ER-negative (ER-) cell lines were used to determine the effects of ECM content (collagen I, collagen IV, fibronectin, and laminin) on proliferation, cellular phenotype, and survival. Neither ER+ nor ER- cells demonstrated significant increases in proliferation when cultured on these ECM substrates. ER- cells cultured on these substrates were sensitized to both chemotherapy and targeted therapy. In addition, MDA-MB-231 cells expressed different morphologies, binding affinities, and stiffness across these substrates. We also demonstrated that ECM composition significantly alters transcription of senescence-associated pathways across ER+ and ER- cell lines. Together, these results suggest that complex matrix composites should be incorporated into in vitro tumor models, especially for the drug-resistant TNBC subtype. Impact statement The importance of tumor extracellular matrix (ECM) in disease progression is often inadequately represented in models of breast cancer that rely heavily on collagen I and Matrigel. Through immunohistochemistry analysis of patient breast tumors, we show a wide variation in collagen content based on subtype, specifically a repression of fibril collagens in the receptor negative subtype, irrespective of age and race. We also demonstrated that tumor ECM composition alters cellular elasticity and oncogenic pathway activation demonstrating that physiologically relevant three-dimensional models of breast cancer should include an ECM that is subtype specific.

Opioid Naive Surgeons and Opioid-Tolerant Patients: Can Education Alter Prescribing Patterns to Total Knee Arthroplasty Patients?

Patterns of opioid overprescribing following arthroplasty likely developed given that poor pain control can diminish patient satisfaction, delay disposition, and lead to complications. Recently, interventions promoting responsible pain management have been described, however, most of the existing literature focuses on opioid naive patients. The aim of this study was to describe the effect of an educational intervention on opioid prescribing for opioid-tolerant patients undergoing primary total knee arthroplasty (TKA). As the start to a quality improvement initiative to reduce opioid overprescribing, a departmental grand rounds was conducted. Prescribing data, for the year before and after this intervention, were retrospectively collected for all opioid-tolerant patients undergoing primary TKA. Opioid prescribing data were standardized to mean morphine milligram equivalents (MME). Segmented time series regression was utilized to estimate the change in opioid prescribing associated with the intervention. A total of 508 opioid-tolerant patients underwent TKA at our institution during the study period. The intervention was associated with a statistically significant decrease of 468 mean MME (23%) from 2,062 to 1,594 (p = 0.005) in TKA patients. This study demonstrates that an educational intervention is associated with decreased opioid prescribing among opioid-tolerant TKA patients. While the effective management of these patients is challenging, surgeon education should be a key focus to optimizing their care.

Gout in primary total knee arthroplasty: Prevalent but not independently associated with complications.

BACKGROUND: Gout is a common synovial pathology, but its prevalence in patients undergoing total knee arthroplasty (TKA) and potential association with complications such as periprosthetic infection (PJI) and revision are unknown. METHODS: Medicare data from 2009 to 2013 was retrospectively reviewed using PearlDiver. All patients 65 years of age or older and undergoing primary TKA with at least 3 years of pre-TKA records were included. The prevalence of gout was based on ICD-9 codes. Univariable associations of gout with PJI and revision at 1 year were assessed using odds ratios with 95% confidence intrervals (C.I.). To control for potential confounding, patients with a history of gout were matched on age, gender, smoking history, and Elixhauser Comorbidity Index (ECI) to patients without gout and associations reassessed. RESULTS: The prevalence of gout in Medicare patients undergoing primary TKA was 5.7%. On univariable analysis, patients with a history of gout were more likely to develop PJI (O.R., 1.58; 95% C.I., 1.45-1.72) and undergo revision (O.R., 1.33; 95% C.I., 1.25-1.41) at 1 year. After matching for confounders, a history of gout was no longer associated with developing PJI (O.R., 0.98; 95% C.I., 0.90-1.06) or undergoing revision (O.R., 0.94; 95% C.I., 0.89-1.00) at 1 year. CONCLUSIONS: Gout is a relatively common pathology in patients undergoing TKA. While gout is associated with increased complications, this appears to be driven by confounding through its association with other medical comorbidities. Gout does not appear to be an independent risk factor for complications following TKA.

Periprosthetic Hip Fractures Outside the Initial Postoperative Period: Does Time from Diagnosis to Surgery Matter?

BACKGROUND: Despite an increasing incidence and associated morbidity, the optimal timing for the surgical management of periprosthetic hip fractures remains unknown. This study sought to explore whether time to surgery was associated with medical or surgical complications. METHODS: A retrospective review of Medicare data from 2010 to 2014 was performed using PearlDiver. All patients with a periprosthetic hip fracture greater than 90 days from surgery and undergoing open reduction internal fixation (ORIF) or revision total hip arthroplasty (RTHA) were included. Time to surgery was measured from diagnosis and dichotomized at 48 hours. RESULTS: Of 342 patients undergoing ORIF, 269 (79%) had surgery within 48 hours. Of 255 patients undergoing RTHA, 142 (56%) had surgery within 48 hours. For ORIF, surgery more than 48 hours after diagnosis was associated with an increased rate of 30-day deep vein thrombosis or pulmonary embolism (15% vs 7%, P = .03), which remained after adjustment (odds ratio [OR]: 2.71, 95% confidence interval [CI]: 1.11-6.45). A similar association was seen for RTHA (12% vs 6%, P = .09 and OR: 2.61, 95% CI 1.01-7.24). For RTHA, surgery more than 48 hours after diagnosis was associated with an increased rate of 90-day periprosthetic joint infection (12% vs 4%, P = .007), which remained after adjustment (OR: 3.86, 95% CI: 1.36-12.72). A similar but not significant association was seen for ORIF (7% vs 3%, P = .18 and OR: 2.65, 95% CI: 0.73-8.91). CONCLUSIONS: Among Medicare patients with a periprosthetic hip fracture, time to surgery greater than 48 hours was associated with increased medical and surgical complications.

ERK5 Is Required for Tumor Growth and Maintenance Through Regulation of the Extracellular Matrix in Triple Negative Breast Cancer.

Conventional mitogen-activated protein kinase (MAPK) family members regulate diverse cellular processes involved in tumor initiation and progression, yet the role of ERK5 in cancer biology is not fully understood. Triple-negative breast cancer (TNBC) presents a clinical challenge due to the aggressive nature of the disease and a lack of targeted therapies. ERK5 signaling contributes to drug resistance and metastatic progression through distinct mechanisms, including activation of epithelial-to-mesenchymal transition (EMT). More recently a role for ERK5 in regulation of the extracellular matrix (ECM) has been proposed, and here we investigated the necessity of ERK5 in TNBC tumor formation. Depletion of ERK5 expression using the CRISPR/Cas9 system in MDA-MB-231 and Hs-578T cells resulted in loss of mesenchymal features, as observed through gene expression profile and cell morphology, and suppressed TNBC cell migration. In vivo xenograft experiments revealed ERK5 knockout disrupted tumor growth kinetics, which was restored using high concentration Matrigel™ and ERK5-ko reduced expression of the angiogenesis marker CD31. These findings implicated a role for ERK5 in the extracellular matrix (ECM) and matrix integrity. RNA-sequencing analyses demonstrated downregulation of matrix-associated genes, integrins, and pro-angiogenic factors in ERK5-ko cells. Tissue decellularization combined with cryo-SEM and interrogation of biomechanical properties revealed that ERK5-ko resulted in loss of key ECM fiber alignment and mechanosensing capabilities in breast cancer xenografts compared to parental wild-type cells. In this study, we identified a novel role for ERK5 in tumor growth kinetics through modulation of the ECM and angiogenesis axis in breast cancer.

MSH1 is required for maintenance of the low mutation rates in plant mitochondrial and plastid genomes.

Mitochondrial and plastid genomes in land plants exhibit some of the slowest rates of sequence evolution observed in any eukaryotic genome, suggesting an exceptional ability to prevent or correct mutations. However, the mechanisms responsible for this extreme fidelity remain unclear. We tested seven candidate genes involved in cytoplasmic DNA replication, recombination, and repair (POLIA, POLIB, MSH1, RECA3, UNG, FPG, and OGG1) for effects on mutation rates in the model angiosperm Arabidopsis thaliana by applying a highly accurate DNA sequencing technique (duplex sequencing) that can detect newly arisen mitochondrial and plastid mutations even at low heteroplasmic frequencies. We find that disrupting MSH1 (but not the other candidate genes) leads to massive increases in the frequency of point mutations and small indels and changes to the mutation spectrum in mitochondrial and plastid DNA. We also used droplet digital PCR to show transmission of de novo heteroplasmies across generations in msh1 mutants, confirming a contribution to heritable mutation rates. This dual-targeted gene is part of an enigmatic lineage within the mutS mismatch repair family that we find is also present outside of green plants in multiple eukaryotic groups (stramenopiles, alveolates, haptophytes, and cryptomonads), as well as certain bacteria and viruses. MSH1 has previously been shown to limit ectopic recombination in plant cytoplasmic genomes. Our results point to a broader role in recognition and correction of errors in plant mitochondrial and plastid DNA sequence, leading to greatly suppressed mutation rates perhaps via initiation of double-stranded breaks and repair pathways based on faithful homologous recombination.

The Association of Opioid Utilization and Patient Satisfaction Following Outpatient Orthopaedic Surgery: More May Not Be Better.

Postoperative analgesia remains an important area of research in orthopaedics. There remains a lack of information on the complex interplay between opioid utilization postoperatively, pain and patient satisfaction. This study aims to describe the relationship between opioid utilization, postoperative pain, and patient satisfaction following outpatient orthopaedic surgery in a multispecialty orthopaedic practice. As a part of an ongoing quality control project at our institution patients were instructed to monitor utilization of postoperative opioids. The results of a convenience sample of 139 patients representing a 53% response rate among eligible patients that completed the survey following outpatient orthopaedic surgery are reported. Among patients undergoing outpatient orthopaedic surgery, there was no clinically significant association between opioid utilization and patient satisfaction. This association appeared largely independent of the patient's actual pain. While lower pain scores were associated with increasing patient satisfaction, this appeared to be independent of opioid utilization. (Journal of Surgical Orthopaedic Advances 29(2):88-93, 2020).

Stratifying Venous Thromboembolism Risk in Arthroplasty: Do High-Risk Patients Exist?

BACKGROUND: While there are many possible complications associated with total joint arthroplasty (TJA), venous thromboembolism (VTE) is both frequent and potentially severe. Despite this importance, there are inconsistent recommendations for prophylaxis based on patient risk factors. METHODS: A predictive model was constructed to compare low-molecular-weight heparin(LMWH) and aspirin (ASA) for prevention of VTE-associated complications following TJA.The model used risks from prior prophylaxis studies to estimate the risk of developing a symptomatic deep vein thrombosis, pulmonary embolism, thrombocytopenia, and operative or nonoperative site bleeding. We also evaluated the progression to 4 possible final health states: postphlebitis syndrome, intracranial hemorrhage, death, or baseline health. Within published ranges, we selected assumptions that were favorable to LMWH such that these analyses represent a best case scenario for LMWH or an alternative more aggressive low-molecular-weight heparin alternative (LMWHA). Events and outcomes were assigned quality-adjusted life-year (QALY) losses according to prior studies to determine the effect on patients' outcomes for ASA and LMWHA prophylaxis. RESULTS: Assessing VTE risk populations from 0.2% to 2% with life expectancies ranging from 5 to 40 years postoperatively, patients with a risk ratio less than 3.7 showed increased expected QALY with ASA compared to LMWHA. For patients with a baseline VTE risk of 1% and a 15 year life expectancy, a risk ratio of 13.4 was needed to identify patients that would benefit from LMWHA. With life expectancy increased to 30 years, the risk ratio needed to idetify these patients was 7.4. CONCLUSION: Patients undergoing TJA should receive ASA chemoprophylaxis in nearly all situations, unless the patient has a significantly increased VTE risk compared to the baseline population and a long life expectancy.

Targeted Intervention to Increase Awareness of Opioid Overprescribing Significantly Reduces Narcotic Prescribing Within an Academic Orthopaedic Practice.

OBJECTIVE: To evaluate the impact of a targeted intervention focused on increasing awareness of opioid overprescribing within an academic orthopaedic practice. DESIGN: Retrospective prescribing data was collected through an electronic chart review. A single time point, a departmental grand rounds titled "Opioid Use, Misuse, & Abuse in Orthopaedics," was conducted on February 8, 2017. Opioid prescribing data was analyzed for the year preceding and year immediately following this targeted intervention. Narcotics were standardized using milligram morphine equivalents (MME) for comparison, and patients were categorized as opioid naive or non-naive based on whether an opioid prescription was written within 90 days prior to surgery. A segmented time series regression model was utilized to determine statistical significance of the educational intervention. SETTING: Academic Medical Center. PARTICIPANTS: All patients undergoing orthopaedic procedures at our institution between January 2016 and March 2018. RESULTS: A total of 5882 patients underwent orthopaedic procedures at our institution during the study period. Of these, 2887 were in the year preceding and 2995 were in the year immediately following the targeted intervention to increase awareness of opioid overprescribing. The interve.ntion was associated with an acute decrease of 167 mean MME from 780 to 613 in opioid naive (p = 0.028) and 154 mean MME from 1,015 to 861 in opioid non-naive patients (p = 0.010). The intervention was also associated with a favorable change in the overall mean MME prescribing trend over time in both naive (p = 0.011) and non-naive (p = 0.064) patients. CONCLUSIONS: This study demonstrates decreased opioid prescribing within an academic orthopaedic department after a targeted intervention focused on raising the awareness of opioid overprescribing. Ongoing provider education and awareness are critical parts of any plan to continue curtail opioid overprescribing among surgeons.

Varus-Valgus Constraint in Primary Total Knee Arthroplasty: A Short-Term Solution but Will It Last?

BACKGROUND: Prostheses with varus-valgus constraint (VVC) are increasingly utilized in primary total knee arthroplasty (TKA) to address coronal malalignment and instability though little is known regarding the association between added constraint and aseptic loosening. We sought to systematically review the literature for reports of VVC in primary TKA and meta-analyze clinical results and implant survival. METHODS: PubMed was searched using broad terms to identify articles reporting VVC in primary TKA. Any article reporting clinical or survival outcomes was included. Clinical scores, close to 2 years postoperatively were converted to standardized mean differences, and the latest survival estimates were weighted using the inverse of their variance and meta-analyzed. RESULTS: Three hundred ninety-two search results were reviewed identifying 30 relevant articles reporting on 3620 knees in total. The estimate for the improvement in clinical scores postoperatively was 3.1 standard deviations (95% confidence interval 2.6-3.6). The estimate for implant revision slowly increased from 1% at 2 years to 2% at 6 years and then began to increase more rapidly beyond this point. The estimated revision rate was 9% by 12 years and 28% by 20 years. This revision rate estimate was stable with and without the inclusion of outlying studies. CONCLUSION: VVC in primary TKA is associated with significant clinical improvement without significant risk of early failure. Meta-regression estimates raise concerns for significant revision risk with extended follow-up, especially beyond 5 years. In the absence of new data, VVC should continue to be used cautiously in the primary TKA.