Regional Differences in Primary Total Knee Arthroplasty Utilization, Physician Reimbursement, and Patient Characteristics.

Background: The primary purpose of this study was to evaluate how utilization, physician reimbursement, and patient populations have changed for primary total knee arthroplasty (TKA) from 2013 to 2021 at both a regional and national level within the Medicare population. Methods: The Medicare Physician and Other Practitioners database was queried for all episodes of primary TKA between years 2013 and 2021. TKA utilization per 10,000 beneficiaries, inflation-adjusted physician reimbursement per TKA, and patient demographics of each TKA surgeon were extracted each year. Data were stratified geographically, and Kruskal-Wallis tests were utilized. Results: Between 2013 and 2021, TKA utilization per 10,000 beneficiaries increased at the greatest rate in the Northeast (+15.1%). In 2021, TKA utilization was highest in the Midwest (97.6/10,000; P < .001). The Midwest had the greatest decline in average physician reimbursement per TKA between 2013 and 2021 (-26.3%) and the lowest average reimbursement ($988.70, P < .001) in 2021. Alternatively, the Northeast had the smallest decline in average TKA reimbursement (-22.6%). Nationally, the average number of beneficiaries per TKA surgeon declined (-6.8%), while the average number of TKAs per surgeon (+5.7%) and average services per beneficiary (+24.3%) both increased. The average number of patient comorbidities and proportion of patients with dual Medicare-Medicaid eligibility decreased over time across all regions. Conclusions: This study demonstrates that TKA utilization is increasing and average physician reimbursement per TKA is declining at varying rates across the country, with the Northeast and Midwest most affected. These findings should be addressed in policy discussions to ensure equitable arthroplasty care.

Medicaid Reimbursement for Total Hip and Knee Arthroplasty: A State-by-State Analysis Compared with Medicare.

BACKGROUND: Medicare reimbursement for arthroplasty procedures has been declining, but little has been reported on Medicaid reimbursement. We sought to determine Medicaid reimbursement rates using state Medicaid data for nine arthroplasty procedure codes and compare them to Medicare rates. METHODS: The Centers for Medicare & Medicaid Services physician fee schedule was used to collect Medicare reimbursement rates, and state Medicaid fee schedules were accessed to collect Medicaid rates for nine procedures encompassing primary and revision hip and knee arthroplasty surgery. State Medicare and Medicaid rates were compared to determine the mean dollar difference and dollar difference per relative value unit (RVU). A cost of living adjustment was performed using the Medicare Wage Index for each state. Coefficients of variation were calculated for each state to determine overall variability between the two systems. RESULTS: The mean reimbursement rates for Medicaid were lower for eight of the nine codes used in the study. Medicaid reimbursed physicians an average of 11.3% less overall and 23.1% less when adjusted for cost of living. The amount of variability in the Medicare rates was low with a consistent coefficient of variation of 0.06, but was higher in the Medicaid rates with a range of 0.26 to 0.29 in the unadjusted rates and 0.34 to 0.37 in the adjusted rates. There was a mean $6.73 decreased reimbursement per RVU for Medicaid procedures. CONCLUSION: For the most common arthroplasty procedures, Medicaid reimbursed physicians less than Medicare on average. Medicaid also demonstrated increased variability when compared to Medicare rates between states.

Simultaneous Optical Imaging of Gastric Slow Waves and Contractions in the In Vivo Porcine Stomach.

Gastric peristalsis is governed by electrical "slow waves" generally assumed to travel from proximal to distal stomach (antegrade propagation) in symmetric rings. While alternative slow wave patterns have been correlated with gastric disorders, their mechanisms and how they alter contractions remain understudied. Optical electromechanical mapping, a developing field in cardiac electrophysiology, images electrical and mechanical physiology simultaneously. Here, we translate this technology to the in-vivo porcine stomach. Stomachs were surgically exposed and a fluorescent dye (di-4-ANEQ(F)PTEA) that transduces the membrane potential (Vm) was injected through the right gastroepiploic artery. Fluorescence was excited by LEDs and imaged with one or two 256x256 pixel cameras. Motion artifact was corrected using a marker-based motion tracking method and excitation ratiometry, which cancels common-mode artifact. Tracking marker displacement also enabled gastric deformation to be measured. We validated detection of electrical activation and Vm morphology against alternative non-optical technologies. Non-antegrade slow waves and propagation direction differences between the anterior and posterior stomach were commonly present in our data. However, sham experiments suggest they were a feature of the animal preparation and not an artifact of optical mapping. In experiments to demonstrate the method's capabilities, we found that repolarization did not always follow at a fixed time behind activation "wavefronts," which could be a factor in dysrhythmia. Contraction strength and the latency between electrical activation and contraction differed between antegrade and non-antegrade propagation. In conclusion, optical electromechanical mapping, which simultaneously images electrical and mechanical activity, enables novel questions regarding normal and abnormal gastric physiology to be explored.

Commentary on Chen et al. (2022): The need for continued methodological research on leveraging information in secondary endpoints for more efficient RCTs.

Chen et al. (2022) recently proposed a set of estimating equations that incorporate data from secondary endpoints to improve precision in parameter estimates related to a primary endpoint. We were motivated to translate their methodology to the context of randomized controlled trials to gain precision in treatment effect estimation using data from secondary endpoints. Our results suggest that this estimator cannot gain efficiency in this context because of random treatment assignment, especially when there is a treatment effect on secondary endpoints, and that further methodological work in this area is needed.

Medicaid Reimbursement for Common Orthopedic Trauma Procedures is 16.0% Less Compared to Medicare with Substantial Variability Between States.

OBJECTIVES: This study seeks to evaluate the variability of Medicaid reimbursement and compare it to Medicare reimbursement using the 20 most commonly billed orthopedic trauma CPT codes nationwide. The authors anticipate significant variability between states and hypothesize that Medicaid payment will be significantly less than Medicare payment. METHODS: The top 20 most common orthopedic trauma surgery procedural codes were identified from a previous analysis performed by Haglin et al.1 The Centers for Medicare and Medicaid services physician fee schedule was used to determine reimbursement rates from Medicare, and state Medicaid fee schedules were used to determine reimbursement rates for Medicaid. State Medicaid rates were compared to their corresponding Medicare rates to determine a dollar difference. Additionally, the dollar difference for each CPT code was divided by its respective physician relative value unit (RVU). This was utilized to acknowledge the possible variability in the complexity of orthopedic procedures and the related physician effort. The Medicare Wage Index was used to adjust Medicaid rates based on the cost of living for the state as well. Coefficients of variation were calculated to represent overall variability in Medicaid and Medicare reimbursement rates. RESULTS: The mean reimbursement rates for Medicaid were lower for all 20 procedures compared to Medicare. On average, Medicaid reimbursed 16.0% less than Medicare, and 29.6% less when adjusting for cost-of-living. MCD reimbursed at a higher rate than MCR for all procedures in only nine states (Alaska, Arizona, Arkansas, Montana, Nebraska, New Jersey, New Mexico, and North Dakota, and South Dakota) while 38 states reimbursed at a lower rate than MCR, on average. The coefficient of variation ranged from 0.24 to 0.34 for the Medicaid unadjusted group and from 0.35 to 0.46 for the Medicare Wage-Index adjusted group. In contrast, the Medicare group was consistent at 0.06 for all 20 procedures. The average dollar difference across the 20 CPT codes for Medicaid reimbursement compared to Medicare ranged from -$76.89 to -$225.17, and the dollar difference per relative value unit ranged from -$5.96 to -$15.16. CONCLUSION: This study found a high amount of variation between state Medicaid reimbursement rates and average rates that were significantly lower than Medicare reimbursement rates for the top twenty most utilized orthopedic trauma CPT codes as identified by Haglin et al. The discrepancy in reimbursement was increased when Medicaid rates were adjusted for state cost-of-living. LEVEL OF EVIDENCE: Level III. See Instructions for Authors for a complete description of levels of evidence.

Tools and Resources at the Maize Genetics and Genomics Database (MaizeGDB).

The Maize Genetics and Genomics Database (MaizeGDB) is the community resource for maize researchers, offering a suite of tools, informatics resources, and curated data sets to support maize genetics, genomics, and breeding research. Here, we provide an overview of the key resources available at MaizeGDB, including maize genomes, comparative genomics, and pan-genomics tools. This review aims to familiarize users with the range of options available for maize research and highlights the importance of MaizeGDB as a central hub for the maize research community. By providing a detailed snapshot of the database's capabilities, we hope to enable researchers to make use of MaizeGDB's resources, ultimately assisting them to better study the evolution and diversity of maize.

Integrating Phylogenies with Chronology to Assemble the Tree of Life.

Reconstructing the global Tree of Life necessitates computational approaches to integrate numerous molecular phylogenies with limited species overlap into a comprehensive supertree. Our survey of published literature shows that individual phylogenies are frequently restricted to specific taxonomic groups due to the expertise of investigators and molecular evolutionary considerations, resulting in any given species present in a minuscule fraction of phylogenies. We present a novel approach, called the chronological supertree algorithm (Chrono-STA), that can build a supertree of species from such data by using node ages in published molecular phylogenies scaled to time. Chrono-STA builds a supertree of organisms by integrating chronological data from molecular timetrees. It fundamentally differs from existing approaches that generate consensus phylogenies from gene trees with missing taxa, as Chrono-STA does not impute nodal distances, use a guide tree as a backbone, or reduce phylogenies to quartets. Analyses of simulated and empirical datasets show that Chrono-STA can combine taxonomically restricted timetrees with extremely limited species overlap. For such data, approaches that impute missing distances or assemble phylogenetic quartets did not perform well. We conclude that integrating phylogenies via temporal dimension enhances the accuracy of reconstructed supertrees that are also scaled to time.

CRF release from a unique subpopulation of accumbal neurons constrains action-outcome acquisition in reward learning.

BACKGROUND: The nucleus accumbens (NAc) mediates reward learning and motivation. Despite an abundance of neuropeptides, peptidergic neurotransmission from the NAc has not been integrated into current models of reward learning. The existence of a sparse population of neurons containing corticotropin releasing factor (CRF) has been previously documented. Here we provide a comprehensive analysis of their identity and functional role in shaping reward learning. METHODS: To do this, we took a multidisciplinary approach that included florescent in situ hybridization (Nmice ≥ 3), tract tracing (Nmice = 5), ex vivo electrophysiology (Ncells ≥ 30), in vivo calcium imaging with fiber photometry (Nmice ≥ 4) and use of viral strategies in transgenic lines to selectively delete CRF peptide from NAc neurons (Nmice ≥ 4). Behaviors used were instrumental learning, sucrose preference and spontaneous exploration in an open field. RESULTS: Here we show that the vast majority of NAc CRF-containing (NAcCRF) neurons are spiny projection neurons (SPNs) comprised of dopamine D1-, D2- or D1/D2-containing SPNs that primarily project and connect to the ventral pallidum and to a lesser extent the ventral midbrain. As a population, they display mature and immature SPN firing properties. We demonstrate that NAcCRF neurons track reward outcomes during operant reward learning and that CRF release from these neurons acts to constrain initial acquisition of action-outcome learning, and at the same time facilitates flexibility in the face of changing contingencies. CONCLUSION: We conclude that CRF release from this sparse population of SPNs is critical for reward learning under normal conditions.

CRF release from a unique subpopulation of accumbal neurons constrains action-outcome acquisition in reward learning.

Background: The nucleus accumbens (NAc) mediates reward learning and motivation. Despite an abundance of neuropeptides, peptidergic neurotransmission from the NAc has not been integrated into current models of reward learning. The existence of a sparse population of neurons containing corticotropin releasing factor (CRF) has been previously documented. Here we provide a comprehensive analysis of their identity and functional role in shaping reward learning. Methods: To do this, we took a multidisciplinary approach that included florescent in situ hybridization (N mice ≥ 3), tract tracing (N mice = 5), ex vivo electrophysiology (N cells ≥ 30), in vivo calcium imaging with fiber photometry (N mice ≥ 4) and use of viral strategies in transgenic lines to selectively delete CRF peptide from NAc neurons (N mice ≥ 4). Behaviors used were instrumental learning, sucrose preference and spontaneous exploration in an open field. Results: Here we show that the vast majority of NAc CRF-containing (NAc CRF ) neurons are spiny projection neurons (SPNs) comprised of dopamine D1-, D2- or D1/D2-containing SPNs that primarily project and connect to the ventral pallidum and to a lesser extent the ventral midbrain. As a population, they display mature and immature SPN firing properties. We demonstrate that NAc CRF neurons track reward outcomes during operant reward learning and that CRF release from these neurons acts to constrain initial acquisition of action-outcome learning, and at the same time facilitates flexibility in the face of changing contingencies. Conclusion: We conclude that CRF release from this sparse population of SPNs is critical for reward learning under normal conditions.

Papillary tumor of the pineal region: analysis of DNA methylation profiles and clinical outcomes in 76 cases.

Papillary tumor of the pineal region (PTPR) is an uncommon tumor of the pineal region with distinctive histopathologic and molecular characteristics. Experience is limited with respect to its molecular heterogeneity and clinical characteristics. Here, we describe 39 new cases and combine these with 37 previously published cases for a cohort of 76 PTPR's, all confirmed by methylation profiling. As previously reported, two main methylation groups were identified (PTPR-A and PTPR-B). In our analysis we extended the subtyping into three subtypes: PTPR-A, PTPR-B1 and PTPR-B2 supported by DNA methylation profile and genomic copy number variations. Frequent loss of chromosome 3 or 14 was found in PTPR-B1 tumors but not in PTPR-B2. Examination of clinical outcome showed that nearly half (14/30, 47%) of examined patients experienced tumor progression with significant difference among the subtypes (p value = 0.046). Our analysis extends the understanding of this uncommon but distinct neuroepithelial tumor by describing its molecular heterogeneity and clinical outcomes, including its tendency towards tumor recurrence.

Intimidating Attendings: The Importance of Near-Peer Mentorship During Third-Year Surgical Clerkship.

INTRODUCTION: Near-peer instruction has grown in popularity in medical education; however, limited data exist to support its effectiveness. This study investigates the perceptions of near-peer style instruction in third-y medical students undergoing a surgical clinical clerkship. We hypothesized that near-peer instruction would provide a beneficial educational experience to third-y medical students during their surgical clinical clerkship. METHODS: The authors anonymously surveyed third-y medical students undergoing their clinical clerkship in surgery on their perception of the near-peer instruction and mentorship they received from fourth-y medical students at the beginning of the clerkship. Near-peer instruction included teaching suturing techniques, surgical procedures and anatomy, operating room literacy, and sharing anecdotal experiences. Surveys were distributed 24 h after receiving the formal instruction. RESULTS: A total of 85 students completed the survey (78% response rate). Students reported a similar or increase in value of learning from near-peer mentors compared to attending physicians (less valuable: 1.2%; just as valuable: 52.9%; more valuable: 45.9%). The majority of students indicated they would like to experience more near-peer style instruction in medical school as demonstrated in surgical clerkship training (absolutely no: 0%; probably not: 0%; on the fence: 4.7%; probably yes: 25.9%; absolutely yes: 69.4%). After experiencing near-peer instruction and mentoring, students were more interested in becoming near-peer mentors (less interested: 1.2%; just as interested: 29.4%; more interested: 69.4%). CONCLUSIONS: Students appreciate and desire near-peer instruction, seeing it as an effective learning method. Mentees undergoing near-peer style instruction have an increased interest in becoming near-peer mentors.

Expanding the genetics and phenotypes of ocular congenital cranial dysinnervation disorders.

PURPOSE: To identify genetic etiologies and genotype/phenotype associations for unsolved ocular congenital cranial dysinnervation disorders (oCCDDs). METHODS: We coupled phenotyping with exome or genome sequencing of 467 probands (550 affected and 1108 total individuals) with genetically unsolved oCCDDs, integrating analyses of pedigrees, human and animal model phenotypes, and de novo variants to identify rare candidate single nucleotide variants, insertion/deletions, and structural variants disrupting protein-coding regions. Prioritized variants were classified for pathogenicity and evaluated for genotype/phenotype correlations. RESULTS: Analyses elucidated phenotypic subgroups, identified pathogenic/likely pathogenic variant(s) in 43/467 probands (9.2%), and prioritized variants of uncertain significance in 70/467 additional probands (15.0%). These included known and novel variants in established oCCDD genes, genes associated with syndromes that sometimes include oCCDDs (e.g., MYH10, KIF21B, TGFBR2, TUBB6), genes that fit the syndromic component of the phenotype but had no prior oCCDD association (e.g., CDK13, TGFB2), genes with no reported association with oCCDDs or the syndromic phenotypes (e.g., TUBA4A, KIF5C, CTNNA1, KLB, FGF21), and genes associated with oCCDD phenocopies that had resulted in misdiagnoses. CONCLUSION: This study suggests that unsolved oCCDDs are clinically and genetically heterogeneous disorders often overlapping other Mendelian conditions and nominates many candidates for future replication and functional studies.

Cyprocide selectively kills nematodes via cytochrome P450 bioactivation.

Left unchecked, plant-parasitic nematodes have the potential to devastate crops globally. Highly effective but non-selective nematicides are justifiably being phased-out, leaving farmers with limited options for managing nematode infestation. Here, we report our discovery of a 1,3,4-oxadiazole thioether scaffold called Cyprocide that selectively kills nematodes including diverse species of plant-parasitic nematodes. Cyprocide is bioactivated into a lethal reactive electrophilic metabolite by specific nematode cytochrome P450 enzymes. Cyprocide fails to kill organisms beyond nematodes, suggesting that the targeted lethality of this pro-nematicide derives from P450 substrate selectivity. Our findings demonstrate that Cyprocide is a selective nematicidal scaffold with broad-spectrum activity that holds the potential to help safeguard our global food supply.

Rural Surgery Preparedness After Graduation From a Surgical Residency.

BACKGROUND: General surgeons in rural communities face unique challenges due to broad scopes of practice with limited support and difficulties providing training. In 1998, this academic medical center initiated a rural program consisting of senior level rotations in rural communities. We surveyed past residents to determine scope of practice, level of preparedness, and recommendations. METHODS: The survey was sent to n = 89 residents and n = 34 surveys were completed. Of those, 85% took part in the rural program, 23.5% practice in a zip code defined as rural by HRSA, and 53% had fellowship training most commonly vascular (n = 5), critical care (n = 5), cardiothoracic (n = 3), and MIS (n = 3). Most common procedures reported were MIS (64.7%), vascular (38.2%), cardiothoracic (26.5%), hepatobiliary (23.5%), and pediatric (23.5%). RESULTS: Over 97% of participants were satisfied/very satisfied with their overall program, and 94% were satisfied/very satisfied with their preparedness for rural surgery. When prompted with, "A general surgery program must have some type of rural specific specialized curriculum and extended rotations to facilitate a career path in rural general surgery," 41.2% responded strongly agree, 47.1% agree, and 11.8% neutral. Recommendations for bolstering a rural program included urology (59%), MIS (59%), vascular (56%), OBGYN (47%), and pediatrics (38%). Regarding non-surgical education, residents felt underprepared for billing (79.4%) and administration (50.0%). DISCUSSION: Although satisfaction scores were high, improvements to better prepare surgeons for rural practice include increasing residents' exposure and training in OBGYN, MIS, vascular, urology, and billing and administration. These results should direct programs to prepare surgeons for effective rural practice.

Mechanochemical Synthesis of a Sodium Anion Complex [Na+(2,2,2-cryptand)Na-] and Studies of Its Reactivity: Two-Electron and One-Electron Reductions.

Group 1 metal molecular chemistry is dominated by a +1 oxidation state, while a 0 oxidation state is widespread in the metals. A more exotic, yet still available, oxidation state of group 1 metal is -1, i.e., alkalide. Reported as early as the 1970s, the alkalides appear in every modern inorganic chemistry textbook as an iconic chemical curiosity, yet their reactivity remains unexplored. This is due to their synthetic hurdles. In this work, we report the first facile synthesis of the archetypical alkalide complex, [Na+(2,2,2-cryptand)Na-], which allows us to unveil a versatile reactivity profile of this once exotic species.

Optimizing the timing of an end-of-outbreak declaration: Ebola virus disease in the Democratic Republic of the Congo.

Following the apparent final case in an Ebola virus disease (EVD) outbreak, the decision to declare the outbreak over must balance societal benefits of relaxing interventions against the risk of resurgence. Estimates of the end-of-outbreak probability (the probability that no future cases will occur) provide quantitative evidence that can inform the timing of an end-of-outbreak declaration. An existing modeling approach for estimating the end-of-outbreak probability requires comprehensive contact tracing data describing who infected whom to be available, but such data are often unavailable or incomplete during outbreaks. Here, we develop a Markov chain Monte Carlo-based approach that extends the previous method and does not require contact tracing data. Considering data from two EVD outbreaks in the Democratic Republic of the Congo, we find that data describing who infected whom are not required to resolve uncertainty about when to declare an outbreak over.

EXPRESS: Increased Metamemory Accuracy with Practice Does Not Require Practice with Metamemory.

Given that learners do not always predict their future memory performance accurately, there is a need to better understand how metamemory accuracy can be improved. Prior research suggests that one way to improve is practice - participants tend to become better at predicting their future memory performance over the course of multi-trial learning experiments. However, it is currently unclear whether such improvements result from participants having practiced making metamemory judgments or whether comparable improvements occur even in their absence. This issue was investigated in three multi-trial, cued recall experiments wherein participants either did or did not receive practice making judgments of learning. Metamemory accuracy increased across study blocks but did so equally for the two groups. These results indicate that increased metamemory accuracy with practice is not due to participants having practiced explicit metamemory monitoring, but instead due to other factors associated with multi-trial learning such as retrieval practice and the availability of prior test performance as a metamemory cue.

The cochlear dose and the age at radiotherapy predict severe hearing loss after passive scattering proton therapy and cisplatin in children with medulloblastoma.

BACKGROUND: Hearing loss (HL) is associated with worse neurocognitive outcomes among patients with medulloblastoma. We aimed to identify risk factors associated with severe HL and to evaluate the generalizability of a published HL calculator among patients treated with passive scattering proton therapy (PSPT) and cisplatin. METHODS: We identified patients aged 3-21 years who were treated at our centers between 2007-2022. Audiograms were graded using the International Society of Pediatric Oncology-Boston scale. Time to grade 3-4 HL was evaluated using Kaplan-Meier and multivariable Cox models to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Seventy-nine patients were treated with PSPT at a median age of 7.5 years (range:3.1-21.1). The mean cochlear dose (Dmc) (±S.D.) was 31.5±8.5 Gy, and the cumulative cisplatin dose was 295±50 mg/m2. Fifty-nine patients (75%) received amifostine. Patients completed a median of 9 audiograms (range:4-22) with a median audiogram follow-up of 49 months (range:6-177). Twenty-seven patients (34%) had grade 3-4 HL. In adjusted Cox models, only higher Dmc (HR=1.12, 95% CI:1.06-1.18) was associated with grade 3-4 HL. The predicted 3-year incidence of grade 3-4 HL was 40.0% (95% CI: 21.3-66.3) and 66.7% (95% CI: 35.4-93.7) for children with Dmc ≥36 Gy and age at radiotherapy ≥7 and <7 years, respectively (p=0.042). It was 8.9% (95% CI: 2.3-31.6) and 15.6% (95% CI: 5.3-41.1) for children with Dmc <36 Gy and age at radiotherapy ≥7 and <7 years, respectively (p=0.78). CONCLUSIONS: Children <7 years at radiotherapy with a Dmc ≥36 Gy are at higher risk for HL.

Computational design of Periplasmic binding protein biosensors guided by molecular dynamics.

Periplasmic binding proteins (PBPs) are bacterial proteins commonly used as scaffolds for substrate-detecting biosensors. In these biosensors, effector proteins (for example fluorescent proteins) are inserted into a PBP such that the effector protein's output changes upon PBP-substate binding. The insertion site is often determined by comparison of PBP apo/holo crystal structures, but random insertion libraries have shown that this can miss the best sites. Here, we present a PBP biosensor design method based on residue contact analysis from molecular dynamics. This computational method identifies the best previously known insertion sites in the maltose binding PBP, and suggests further previously unknown sites. We experimentally characterise fluorescent protein insertions at these new sites, finding they too give functional biosensors. Furthermore, our method is sufficiently flexible to both suggest insertion sites compatible with a variety of effector proteins, and be applied to binding proteins beyond PBPs.