Treating Hepatitis C Before Total Knee Arthroplasty is Cost-Effective: A Markov Analysis.

BACKGROUND: Patients who have the hepatitis C virus (HCV) have increased mortality and complication rates following total knee arthroplasty (TKA). Recent advances in HCV therapy have enabled clinicians to eradicate the disease using direct-acting antivirals (DAAs); however, its cost-effectiveness before TKA remains to be demonstrated. The aim of this study was to perform a cost-effectiveness analysis comparing no therapy to DAAs before TKA. METHODS: A Markov model using input values from the published literature was performed to evaluate the cost-effectiveness of DAA treatment before TKA. Input values included event probabilities, mortality, cost, and health state quality-adjusted life-year (QALY) values for patients who have and do not have HCV. Patients who have HCV were modeled to have an increased rate of periprosthetic joint infection (PJI) infection (9.9 to 0.7%). The incremental cost-effectiveness ratio (ICER) of no therapy versus DAA was compared to a willingness-to-pay threshold of $100,000/QALY. Sensitivity analyses were performed to investigate the effects of uncertainty associated with input variables. RESULTS: Total knee arthroplasty in the setting of no therapy and DAA added 8.1 and 13.5 QALYs at a cost of $25,000 and $114,900. The ICER associated with DAA in comparison to no therapy was $16,800/QALY, below the willingness-to-pay threshold of $100,000/QALY. Sensitivity analyses demonstrated that the ICER was affected by patient age, inflation rate, DAA cost and effectiveness, HCV-associated mortality, and DAA-induced reduction in PJI rate. CONCLUSION: Direct-acting antiviral treatment before TKA reduces risk of PJI and is cost-effective. Strong consideration should be given to treating patients who have HCV before elective TKA. LEVEL OF EVIDENCE: Cost-effectiveness Analysis; Level III.

What are the Trends in Racial Diversity Among Orthopaedic Applicants, Residents, and Faculty?

BACKGROUND: Orthopaedic surgery has recruited fewer applicants from underrepresented in medicine (UIM) racial groups than many other specialties, and recent studies have shown that although applicants from UIM racial groups are competitive for orthopaedic surgery, they enter the specialty at lower rates. Although previous studies have measured trends in orthopaedic surgery applicant, resident, or attending diversity in isolation, these populations are interdependent and therefore should be analyzed together. It is unclear how racial diversity among orthopaedic applicants, residents, and faculty has changed over time and how it compares with other surgical and medical specialties. QUESTIONS/PURPOSES: (1) How has the proportion of orthopaedic applicants, residents, and faculty from UIM and White racial groups changed between 2016 and 2020? (2) How does representation of orthopaedic applicants from UIM and White racial groups compare with that of other surgical and medical specialties? (3) How does representation of orthopaedic residents from UIM and White racial groups compare with that of other surgical and medical specialties? (4) How does representation of orthopaedic faculty from UIM and White racial groups compare with that of other surgical and medical specialties? METHODS: We drew racial representation data for applicants, residents, and faculty between 2016 and 2020. Applicant data on racial groups was obtained for 10 surgical and 13 medical specialties from the Association of American Medical Colleges Electronic Residency Application Services report, which annually publishes demographic data on all medical students applying to residency through Electronic Residency Application Services. Resident data on racial groups were obtained for the same 10 surgical and 13 medical specialties from the Journal of the American Medical Association Graduate Medical Education report, which annually publishes demographic data on residents in residency training programs accredited by the Accreditation Council for Graduate Medical Education. Faculty data on racial groups were obtained for four surgical and 12 medical specialties from the Association of American Medical Colleges Faculty Roster United States Medical School Faculty report, which annually publishes demographic data of active faculty at United States allopathic medical schools. UIM racial groups include American Indian or Alaska Native, Black or African American, Hispanic or Latino, and Native American or Other Pacific Islander. Chi-square tests were performed to compare representation of UIM and White groups among orthopaedic applicants, residents, and faculty between 2016 and 2020. Further, chi-square tests were performed to compare aggregate representation of applicants, residents, and faculty from UIM and White racial groups in orthopaedic surgery to aggregate representation among other surgical and medical specialties with available data. RESULTS: The proportion of orthopaedic applicants from UIM racial groups increased between 2016 to 2020 from 13% (174 of 1309) to 18% (313 of 1699, absolute difference 0.051 [95% CI 0.025 to 0.078]; p < 0.001). The proportion of orthopaedic residents (9.6% [347 of 3617] to 10% [427 of 4242]; p = 0.48) and faculty (4.7% [186 of 3934] to 4.7% [198 of 4234]; p = 0.91) from UIM racial groups did not change from 2016 to 2020. There were more orthopaedic applicants from UIM racial groups (15% [1151 of 7446]) than orthopaedic residents from UIM racial groups (9.8% [1918 of 19,476]; p < 0.001). There were also more orthopaedic residents from UIM groups (9.8% [1918 of 19,476]) than orthopaedic faculty from UIM groups (4.7% [992 of 20,916], absolute difference 0.051 [95% CI 0.046 to 0.056]; p < 0.001). The proportion of orthopaedic applicants from UIM groups (15% [1151 of 7446]) was greater than that of applicants to otolaryngology (14% [446 of 3284], absolute difference 0.019 [95% CI 0.004 to 0.033]; p = 0.01), urology (13% [319 of 2435], absolute difference 0.024 [95% CI 0.007 to 0.039]; p = 0.005), neurology (12% [1519 of 12,862], absolute difference 0.036 [95% CI 0.027 to 0.047]; p < 0.001), pathology (13% [1355 of 10,792], absolute difference 0.029 [95% CI 0.019 to 0.039]; p < 0.001), and diagnostic radiology (14% [1635 of 12,055], absolute difference 0.019 [95% CI 0.009 to 0.029]; p < 0.001), and it was not different from that of applicants to neurosurgery (16% [395 of 2495]; p = 0.66), plastic surgery (15% [346 of 2259]; p = 0.87), interventional radiology (15% [419 of 2868]; p = 0.28), vascular surgery (17% [324 of 1887]; p = 0.07), thoracic surgery (15% [199 of 1294]; p = 0.94), dermatology (15% [901 of 5927]; p = 0.68), internal medicine (15% [18,182 of 124,214]; p = 0.05), pediatrics (16% [5406 of 33,187]; p = 0.08), and radiation oncology (14% [383 of 2744]; p = 0.06). The proportion of orthopaedic residents from UIM groups (9.8% [1918 of 19,476]) was greater than UIM representation among residents in otolaryngology (8.7% [693 of 7968], absolute difference 0.012 [95% CI 0.004 to 0.019]; p = 0.003), interventional radiology (7.4% [51 of 693], absolute difference 0.025 [95% CI 0.002 to 0.043]; p = 0.03), and radiation oncology (7.9% [289 of 3659], absolute difference 0.020 [95% CI 0.009 to 0.029]; p < 0.001), and it was not different from UIM representation among residents in plastic surgery (9.3% [386 of 4129]; p = 0.33), urology (9.7% [670 of 6877]; p = 0.80), dermatology (9.9% [679 of 6879]; p = 0.96), and diagnostic radiology (10% [2215 of 22,076]; p = 0.53). The proportion of orthopaedic faculty from UIM groups (4.7% [992 of 20,916]) was not different from UIM representation among faculty in otolaryngology (4.8% [553 of 11,413]; p = 0.68), neurology (5.0% [1533 of 30,871]; p = 0.25), pathology (4.9% [1129 of 23,206]; p = 0.55), and diagnostic radiology (4.9% [2418 of 49,775]; p = 0.51). Compared with other surgical and medical specialties with available data, orthopaedic surgery had the highest proportion of White applicants (62% [4613 of 7446]), residents (75% [14,571 of 19,476]), and faculty (75% [15,785 of 20,916]). CONCLUSION: Orthopaedic applicant representation from UIM groups has increased over time and is similar to that of several surgical and medical specialties, suggesting relative success with efforts to recruit more students from UIM groups. However, the proportion of orthopaedic residents and UIM groups has not increased accordingly, and this is not because of a lack of applicants from UIM groups. In addition, UIM representation among orthopaedic faculty has not changed and may be partially explained by the lead time effect, but increased attrition among orthopaedic residents from UIM groups and racial bias likely also play a role. Further interventions and research into the potential difficulties faced by orthopaedic applicants, residents, and faculty from UIM groups are necessary to continue making progress. CLINICAL RELEVANCE: A diverse physician workforce is better suited to address healthcare disparities and provide culturally competent patient care. Representation of orthopaedic applicants from UIM groups has improved over time, but further research and interventions are necessary to diversify orthopaedic surgery to ultimately provide better care for all orthopaedic patients.

Treating Hepatitis C Prior to Total Hip Arthroplasty is Cost-effective: A Markov Analysis.

BACKGROUND: Patients infected with the hepatitis C virus (HCV) have high complication rates following total hip arthroplasty (THA). Advances in HCV therapy now enable clinicians to eradicate the disease; however, its cost-effectiveness from an orthopaedic perspective remains to be demonstrated. We sought to conduct a cost-effectiveness analysis comparing no therapy to direct-acting antiviral (DAA) therapy prior to THA among HCV-positive patients. METHODS: A Markov model was utilized to evaluate the cost-effectiveness of treating HCV with DAA prior to THA. The model was powered with event probabilities, mortality, cost, and quality-adjusted life year (QALY) values for patients with and without HCV that were obtained from the published literature. This included treatment costs, successes of HCV eradication, incidences of superficial or periprosthetic joint infection (PJI), probabilities of utilizing various PJI treatment modalities, PJI treatment success/failures, and mortality rates. The incremental cost-effectiveness ratio was compared to a willingness-to-pay threshold of $50,000/QALY. RESULTS: Our Markov model indicates that in comparison to no therapy, DAA prior to THA is cost-effective for HCV-positive patients. THA in the setting of no therapy and DAA added 8.06 and 14.39 QALYs at a mean cost of $28,800 and $115,800. The incremental cost-effectiveness ratio associated with HCV DAA in comparison to no therapy was $13,800/QALY, below the willingness-to-pay threshold of $50,000/QALY. CONCLUSION: Hepatitis C treatment with DAA prior to THA is cost-effective at all current drug list prices. Given these findings, strong consideration should be given to treating patients for HCV prior to elective THA. LEVEL OF EVIDENCE: Cost-effectiveness Analysis; Level III.

Distinct phases of adult microglia proliferation: a Myc-mediated early phase and a Tnfaip3-mediated late phase.

Microgliosis is a hallmark of many neurological diseases, including Alzheimer's disease, stroke, seizure, traumatic brain and spinal cord injuries, and peripheral and optic nerve injuries. Recent studies have shown that the newly self-renewed microglia have specific neurological functions. However, the mechanism of adult microglia proliferation remains largely unclear. Here, with single-cell RNA sequencing, flow cytometry, and immunohistochemistry, we demonstrate that the sciatic nerve injury induced two distinct phases of microglia proliferation in mouse spinal cord, each with different gene expression profiles. We demonstrate that the transcription factor Myc was transiently upregulated in spinal cord microglia after nerve injury to mediate an early phase microglia proliferation. On the other hand, we reveal that the tumor-necrosis factor alpha-induced protein 3 (Tnfaip3) was downregulated to mediate the Myc-independent late-phase microglia proliferation. We show that cyclin dependent kinase 1, a kinase with important function in the M phase of the cell cycle, was involved only in the early phase. We reveal that although the early phase was neither necessary nor sufficient for the late phase proliferation, the late-phase suppressed the early phase microglia proliferation in the spinal cord. Finally, we demonstrate that the termination of spinal cord microglia proliferation required both Myc and Tnfaip3 to resume their baseline expression. Thus, we have delineated an interactive signaling network in the proliferation of differentiated microglia.