Comparing Common Risk Assessment Tools to Predict Outcomes in Total Knee Arthroplasty.

BACKGROUND: A number of tools exist to aid surgeons in risk assessment, including the Charlson Comorbidity Index (CCI), the Elixhauser Comorbidity Index (ECI), and various measures of frailty, such as the Hospital Frailty Risk Score (HFR). While all of these tools have been validated for general use, the best risk assessment tool is still debated. Risk assessment is particularly important in elective surgery, such as total joint arthroplasty. The aim of this study is to compare the predictive power of the CCI, ECI, and HFR in the setting of total knee arthroplasty (TKA). METHODS: All patients who underwent TKA were identified via International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code from the National Readmissions Database, years 2016 to 2019. Patient demographics, perioperative complications, and hospital-associated outcomes were recorded. Receiver operating characteristic (ROC) curves were created and area under the curves (AUCs) evaluated to gauge the predictive capabilities of each risk assessment tool (CCI, ECI, and HFR) across a range of outcomes. RESULTS: A total of 1,930,803 patients undergoing TKA were included in our analysis. For mortality, ECI was most predictive (0.95 AUC), while HFR and CCI were 0.75 and 0.74 AUC, respectively. For periprosthetic fractures, ECI was 0.78 AUC, HFR was 0.68 AUC, and CCI was 0.66 AUC. For joint infections, the ECI was 0.78 AUC, the HFR was 0.63 AUC, and the CCI was 0.62 AUC. For 30-day readmission, ECI was 0.79 AUC, while HFR and CCI were 0.6 AUC. For 30-day reoperation, ECI was 0.69 AUC, while HFR was 0.58 AUC and CCI was 0.56 AUC. CONCLUSIONS: Our analysis shows that ECI is superior to CCI and HFR for predicting 30-day postoperative outcomes following TKA. Surgeons should consider assessing patients using ECI prior to TKA.

3,4-Methylenedioxypyrovalerone High-Responder Phenotype as a Tool to Evaluate Candidate Medications for Stimulant Use Disorder.

Despite decades of research, there are no medications approved by the United States Food and Drug Administration to treat stimulant use disorders. Self-administration procedures are widely used to screen candidate medications for stimulant use disorder, although preclinical reductions in stimulant self-administration have not translated to meaningful reductions in stimulant use in humans. One possible reason for this discordance is that most preclinical studies evaluate candidate medications under conditions that promote predictable, and well-regulated patterns of drug-taking rather than the dysregulated and/or compulsive patterns of drug-taking characteristic of a stimulant use disorder. A subset of rats ("high-responders") that self-administer 3,4-methelyendioxypyrovalerone (MDPV), a monoamine uptake inhibitor, develop high levels of dysregulated drug-taking consistent with behaviors related to stimulant use disorders. Because MDPV acts on dopamine, serotonin (5-HT), and sigma receptor systems, the current studies compared the potency and effectiveness of a dopamine D3 receptor partial agonist (VK4-40) or antagonist (VK4-116), a sigma receptor antagonist (BD1063), a dopamine D2/D3/sigma receptor antagonist (haloperidol), and a 5-HT2C receptor agonist (CP-809,101) to reduce MDPV (0.0032-0.1 mg/kg/infusion) self-administration in high- and low-responding rats as well as rats self-administering cocaine (0.032-1 mg/kg/infusion). VK4-40, VK4-116, haloperidol, and CP-809,101 were equipotent and effective at reducing drug-taking in all three groups of rats, including the high-responders; however, VK4-116 and CP-809,101 were less potent at reducing drug-taking in female compared with male rats. Together, these studies suggest that drugs targeting dopamine D3 or 5-HT2C receptors can effectively reduce dysregulated patterns of stimulant use, highlighting their potential utility for treating stimulant use disorders. SIGNIFICANCE STATEMENT: There are no United States Food and Drug Administration-approved treatments for stimulant use disorder, perhaps in part because candidate medications are most often evaluated in preclinical models using male subjects with well-regulated drug-taking. In an attempt to better model aberrant drug taking, this study found compounds acting at dopamine D3 or 5-HT2C receptors can attenuate drug-taking in male and female rats that self-administered two different stimulants and exhibited either a high or low substance use disorder-like phenotype.