The Current Relationship Between Surgeon Reimbursement and Patient Complexity in Arthroplasty-A Risk-Payment Analysis of All Primary Joint Replacements Billed to Medicare in 2019.

BACKGROUND: The purpose of this study was to assess surgeon reimbursement among total joint arthroplasty (TJA) patients who had differing risk profiles within the Medicare population. METHODS: The "2019 Medicare Physician and Other Provider" file was utilized. In 2019, 441,584 primary total hip and knee arthroplasty procedures were billed to Medicare Part B. All episodes were included. Patient demographics and comorbidity profiles were collected for all patients. Additionally, mean patient hierarchal condition category (HCC) risk scores and physician reimbursements were collected. All procedure episodes were split into 2 cohorts; those with an HCC risk score of 1.5 or greater, and those with patient HCC risk scores less than 1.5. Variables were averaged for each cohort and compared. RESULTS: The mean reimbursement across all procedures was $1,068.03. For the sicker patient cohort with a mean HCC risk score of 1.5 or greater, there was a significantly higher rate of all comorbidities compared to the cohort with HCC risk score under 1.5. The mean payment across the sicker cohort was $1,059.21, while the mean payment among the cohort with HCC risk score under 1.5 was 1,073.32 (P = .032). CONCLUSION: This study demonstrates that for Medicare patients undergoing primary TJA in 2019, the mean surgeon reimbursement was lower for primary TJA among sick patients in comparison to their healthier counterparts, although it is difficult to ascertain the impact of this discrepancy. As alternative payment models continue to undergo evaluation and development, these data will be important for the potential advancement of more equitable reimbursement models in arthroplasty care, specifically regarding surgeon reimbursement and possible risk adjustment within such models.

Gastroenterology Practice Consolidation Between 2012 and 2020.

INTRODUCTION: Multiple studies have indicated physicians are practicing medicine in increasingly larger groups. However, specialty-specific data on the extent of consolidation are lacking for many specialties, including gastroenterology. We aim to determine the extent of consolidation for gastroenterology in recent years. METHODS: The Physician Compare database was used to gather information at both an individual and group level. This information included location and number of providers for each group. Cochran-Armitage tests were used to test for differences between practice sizes in 2012 and 2020. RESULTS: Between 2012 and 2020, the number of physicians increased from 12,766 to 13,934, while the total number of practices decreased from 4517 to 3865. The total number of physicians who practice in groups of less than 9 physicians decreased by 23.9%, while the total number of physicians in practices of 100 + increased by 16.8%. DISCUSSION: Significant consolidation has occurred in the field of gastroenterology in every geographic region of the USA. The causes of consolidation are multi-faceted and include the legislative environment, private equity and hospital acquisition of private groups, individual physician lifestyle preferences, and economic benefits of economies of scale. However, the consequences of consolidation are still unclear. CONCLUSION: Over the last eight years, gastroenterologists have been practicing in increasingly larger groups. This trend has been consistent in each area of the country. Future research should focus on the impact of consolidation on patient care and physician wellbeing.

A Comprehensive Monetary Analysis of Inpatient Total Hip and Knee Arthroplasties Billed to Medicare by Hospitals: 2011-2017.

BACKGROUND: Total joint arthroplasty (TJA) has been a recent target of reimbursement reform. As such, the purpose of this study was to evaluate trends in Medicare reimbursement to hospitals for TJA patients from 2011 to 2017. METHODS: The Inpatient Utilization and Payment Public Use File was queried for all primary total hip and knee arthroplasty episodes. This file includes all services billed to Medicare via the Inpatient Prospective Payment System. Extracted data included hospital charges and amount paid by Medicare. All data were adjusted for inflation to 2017 US dollars. Multiple linear mixed-model regression analyses were conducted to assess change over time, and geo-modelling was used to represent reimbursement by location. RESULTS: A total of 3,368,924 primary TJA procedures were billed to Medicare by hospitals from 2011 to 2017 and included in the study. The mean inflation-adjusted Medicare payment to hospitals for DRG 469 decreased from $22,783.66 to $19,604.62 per procedure (-$3179.04; -14.0%; P < .001) and decreased from $13,290.79 to $11,771.54 for DRG 470 (-$1519.25; -11.4%, P = .011) from 2011 to 2017. Meanwhile, the mean charge submitted by hospitals increased by $6483.39 and $5115.60 for DRGs 469 and 470, respectively (+7.4% for 469, +9.3% for 470; P < .001). Medicare reimbursement to hospitals varied by state. CONCLUSION: During the study period, the mean Medicare reimbursement to hospitals decreased for TJA from 2011 to 2017. Meanwhile, the average charge submitted by hospitals increased. As alternative payment models continue to undergo evaluation and development, these data are important for the advancement of more agreeable reimbursement models in arthroplasty care.

A human fatty acid synthase inhibitor binds ß-ketoacyl reductase in the keto-substrate site.

Human fatty acid synthase (hFAS) is a complex, multifunctional enzyme that is solely responsible for the de novo synthesis of long chain fatty acids. hFAS is highly expressed in a number of cancers, with low expression observed in most normal tissues. Although normal tissues tend to obtain fatty acids from the diet, tumor tissues rely on de novo fatty acid synthesis, making hFAS an attractive metabolic target for the treatment of cancer. We describe here the identification of GSK2194069, a potent and specific inhibitor of the ß-ketoacyl reductase (KR) activity of hFAS; the characterization of its enzymatic and cellular mechanism of action; and its inhibition of human tumor cell growth. We also present the design of a new protein construct suitable for crystallography, which resulted in what is to our knowledge the first co-crystal structure of the human KR domain and includes a bound inhibitor.

Long-term Trends in Open vs Endoscopic Carpal Tunnel Release Among the Medicare Population in the United States.

BACKGROUND: Carpal tunnel release (CTR) surgery is the most common surgery billed to Medicare by hand surgeons. As such, the purpose of this study was to evaluate trends for CTR surgeries billed to Medicare from 2000 to 2020. METHODS: The publicly available Medicare Part B National Summary File from 2000 to 2020 was queried. For both open carpal tunnel release (OCTR) and endoscopic carpal tunnel release (ECTR), the number of procedures and total Medicare reimbursement were extracted. For year 2020, the specialty of the performing surgeon was recorded. Descriptive statistics were reported. RESULTS: A total of 3 429 471 CTR surgeries were performed in the Medicare population from 2000 to 2020. For these procedures, Medicare paid surgeons over $1.23 billion. During this period, there was a 101.8% increase in annual CTR procedures (91 130 in 2000, 183 911 in 2020). Further, annual volume of ECTR increased by 456.2%, and accounted for an increasing percentage of total CTR procedures (9.1% in 2012, 25.2% in 2020). The average adjusted Medicare reimbursement per procedure decreased by 1.5% for OCTR, and decreased by 11.6% for ECTR. In 2020, orthopedic surgeons performed 85.1% of CTR procedures. CONCLUSIONS: The volume of CTR surgeries among the Medicare population has increased from 2000 to 2020, and ECTR is accounting for a growing proportion of surgeries. When adjusted for inflation, average reimbursement has decreased, with a greater decrease among ECTR. Orthopedic surgeons perform most of such surgeries. These trends are important to assure adequate resource allocation as treating carpal tunnel becomes more common among the aging Medicare population.

Synthesis and structure-activity relationships of 1,2,4-triazolo[1,5-a]pyrimidin-7(3H)-ones as novel series of potent ß isoform selective phosphatidylinositol 3-kinase inhibitors.

A series of 1,2,4-triazolo[1,5-a]pyrimidin-7(3H)-ones with excellent enzyme inhibition, improved isoform selectivity, and excellent inhibition of downstream phosphorylation of AKT has been identified. Several compounds in the series demonstrated potent (∼ 0.100 µM IC(50)) growth inhibition in a PTEN deficient cancer cell line.

The 50 Most Cited Papers Pertaining to American Football: Analysis of Studies From the Past 40 Years.

Background: Bibliometric citation analyses have been widely used in medicine to help researchers gain foundational knowledge about a topic and identify subtopics of popular interest for further investigations. Purpose: To identify the 50 most cited research publications related to American football. Study Design: Cross-sectional study. Methods: The Clarivate Analytics Web of Science database was used to generate a list of publications relating to football. Articles were filtered by the total number of citations, and the top 50 most cited articles studying the sport of football were selected for this analysis. Articles were analyzed by author, publication year, country of origin, institution affiliation, journal, article type, main research topic area, competitive level, and the level of evidence. A total of 247 articles were reviewed to reach the top 50 articles. Results: The most studied topic within the top 50 articles was concussion/chronic traumatic encephalopathy (n = 40). Collegiate football was the most studied level of competition (n = 25). The journal publishing the greatest number of top articles was Neurosurgery. Two institutions, the University of North Carolina at Chapel Hill and Boston University School of Medicine, produced over one-third of top 50 articles (n = 18). Conclusion: Our analysis indicated that most of the top 50 publications related to the sport of football focused on concussion and CTE, were observational, and were published during or after 2000. The most studied level of competition was collegiate football.

All-Soft Tissue Quadriceps Tendon Autograft in Revision Anterior Cruciate Ligament Reconstruction in Athletes: Comparison to Bone-Patellar Tendon-Bone Autograft With at Least a 2-Year Follow-up.

BACKGROUND: Revision anterior cruciate ligament (ACL) reconstruction is being performed at an increasing rate. Previous literature has suggested that autograft ACL reconstruction is a better option than allograft in revision surgery, although the optimal autograft choice remains unknown. The all-soft tissue quadriceps tendon (ASTQT) autograft has been found to be an effective option for primary ACL reconstruction. However, few studies have evaluated ASTQT autograft in revision ACL reconstruction. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate the ASTQT autograft in revision ACL reconstruction in athletes compared with bone-patellar tendon-bone (BTB) autograft. We hypothesized that the ASTQT autograft would lead to similar return to play, time to return to play, retear rate, and patient-reported outcomes compared with BTB autograft. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective study was performed on all athletes undergoing revision ACL reconstruction between August 2013 and December 2019 at a single institution. Patients participating in high school or college athletics undergoing first-time revision with either ASTQT or BTB autograft with ≥2 years of follow-up were included. Demographic variables, complications, return to sports, and outcome scores including the International Knee Documentation Committee (IKDC) and Lysholm were collected and compared between the 2 cohorts. RESULTS: A total of 58 revision ACL reconstructions were included, with 32 in the ASTQT cohort and 26 in the BTB cohort. Return to sports at the same level occurred in 62.5% of the ASTQT group and 53.8% of the BTB group. The ASTQT group returned to sports significantly faster than the BTB group (8.9 vs 10.3 months; P = .020). There was no difference in retear rates (3.1%, ASTQT; 7.7%, BTB) or other complications between the 2 groups. The IKDC scores were significantly higher at the 6- and 12-month follow-up for the ASTQT autograft group compared with the BTB group (6 months: ASTQT, 71.3; BTB, 61.7, P = .001; 12 months: ASTQT, 82.7; BTB, 78.6; P = .021). Lysholm scores were also greater in the ASTQT cohort at these time points (6 months: ASTQT, 75.1; BTB, 63.6; P < .001; 12 months: ASTQT, 82.0; BTB, 74.5; P < .001). However, IKDC and Lysholm scores were similar between both groups at final follow-up (IKDC: ASTQT, 82.9; BTB, 81.7; P = .344; Lysholm: ASTQT, 83.0; BTB, 81.0; P = .104) There was no significant clinical difference in the absolute difference in scores or rate of achieving clinical thresholds between the 2 cohorts. CONCLUSION: ASTQT autograft for revision ACL in athletes has similar outcomes compared with BTB autograft. However, the ASTQT may possibly afford quicker return to sports and better early improvements in patient-reported outcomes that normalize by 1 year. The soft tissue quadriceps autograft should be considered a viable graft option in revision ACL reconstruction in athletes.

Content and Functionality of United States Medical School Websites.

Introduction Most medical school applicants use the internet as a source of information when applying for medical school. Previous analyses have evaluated residency and fellowship websites; however, an in-depth analysis of medical school websites is lacking. Methods We evaluated 192 United States (US) medical school websites for presence or absence of 39 items relevant to medical school applicants. Items fell into seven general categories: curriculum, research, demographics of incoming class, admissions information, faculty, financial aid, and social. Results Of the 192 websites evaluated (152 allopathic and 40 osteopathic schools), websites contained a mean of 23 items (59%) with a standard deviation of 4.2 items. Conclusion Our study examining US medical school websites revealed a lack of online information for medical school applicants. As medical school interviews transition to being online during the COVID-19 pandemic, the importance of the medical school website to applicants becomes increasingly crucial. The information contained in our study could be used to improve the functionality and quality of information on medical school websites, which could help both applicants and the medical schools themselves.

M3 muscarinic acetylcholine receptor antagonists: SAR and optimization of bi-aryl amines.

Exploration of multiple regions of a bi-aryl amine template led to the identification of highly potent M(3) muscarinic acetylcholine receptor antagonists such as 14 (pA(2)=11.0) possessing good sub-type selectivity for M(3) over M(2). The structure-activity relationships (SAR) and optimization of the bi-aryl amine series are described.

Discovery of potent, selective sulfonylfuran urea endothelial lipase inhibitors.

Endothelial lipase (EL) activity has been implicated in HDL catabolism, vascular inflammation, and atherogenesis, and inhibitors are therefore expected to be useful for the treatment of cardiovascular disease. Sulfonylfuran urea 1 was identified in a high-throughput screening campaign as a potent and non-selective EL inhibitor. A lead optimization effort was undertaken to improve potency and selectivity, and modifications leading to improved LPL selectivity were identified. Radiolabeling studies were undertaken to establish the mechanism of action for these inhibitors, which were ultimately demonstrated to be irreversible inhibitors.

Muscarinic acetylcholine receptor antagonists: SAR and optimization of tyrosine ureas.

SAR exploration of multiple regions of a tyrosine urea template led to the identification of very potent muscarinic acetylcholine receptor antagonists such as 10b with good subtype selectivity for M(3) over M(1). The structure-activity relationships (SAR) and optimization of the tyrosine urea series are described.

Novel ATP-competitive kinesin spindle protein inhibitors.

Kinesin spindle protein (KSP), an ATPase responsible for spindle pole separation during mitosis that is present only in proliferating cells, has become a novel and attractive anticancer target with potential for reduced side effects compared to currently available therapies. We report herein the discovery of the first known ATP-competitive inhibitors of KSP, which display a unique activity profile as compared to the known loop 5 (L5) allosteric KSP inhibitors that are currently under clinical evaluation. Optimization of this series led to the identification of biphenyl sulfamide 20, a potent KSP inhibitor with in vitro antiproliferative activity against human cells with either wild-type KSP (HCT116) or mutant KSP (HCT116 D130V). In a murine xenograft model with HCT116 D130V tumors, 20 showed significant antitumor activity following intraperitoneal dosing, providing in vivo proof-of-principle of the efficacy of an ATP-competitive KSP inhibitor versus tumors that are resistant to the other known KSP inhibitors.

[3a,4]-Dihydropyrazolo[1,5a]pyrimidines: Novel, Potent, and Selective Phosphatidylinositol-3-kinase ß Inhibitors.

A series of novel [3a,4]dihydropyrazolo[1,5a]pyrimidines were identified, which were highly potent and selective inhibitors of PI3Kß. The template afforded the opportunity to develop novel SAR for both the hinge-binding (R3) and back-pocket (R4) substitutents. While cellular potency was relatively modest due to high protein binding, the series displayed low clearance in rat, mouse, and monkey.

Discovery of biphenyl piperazines as novel and long acting muscarinic acetylcholine receptor antagonists.

A series of novel biphenyl piperazines was discovered as highly potent muscarinic acetylcholine receptor antagonists via high throughput screening and subsequent optimization. Compound 5c with respective 500- and 20-fold subtype selectivity for M3 over M2 and M1 exhibited excellent inhibitory activity and long duration of action in a bronchoconstriction in vivo model in mice via intranasal administration. The novel inhaled mAChR antagonists are potentially useful therapeutic agents for the treatment of chronic obstructive pulmonary disease.

Discovery of novel and long acting muscarinic acetylcholine receptor antagonists.

High throughput screening and subsequent optimization led to the discovery of novel quaternary ammonium salts as highly potent muscarinic acetylcholine receptor antagonists with excellent selectivity. Compounds 8a, 13a, and 13b showed excellent inhibitory activity and long duration of action in bronchoconstriction in vivo models in two species via intranasal or intratracheal administration. The novel inhaled muscarinic receptor antagonists are potentially useful therapeutic agents for the treatment of chronic obstructive pulmonary disease and other bronchoconstriction disorders.

Oxazolidinones as novel human CCR8 antagonists.

High-throughput screening of the corporate compound collection led to the discovery of a novel series of N-substituted-5-aryl-oxazolidinones as potent human CCR8 antagonists. The synthesis, structure-activity relationships, and optimization of the series that led to the identification of SB-649701 (1a), are described.

Aminoalkoxybenzyl pyrrolidines as novel human urotensin-II receptor antagonists.

High throughput screening of the corporate compound collection led to the discovery of a novel series of substituted aminoalkoxybenzyl pyrrolidines as human urotensin-II receptor antagonists. The synthesis, initial structure-activity relationships, and optimization of the initial hit that led to the identification of a truncated sub-series, represented by SB-436811 (1a), are described.

Experience with 109 cases of transvaginal hydrolaparoscopy.

We conducted a prospective review of our experience with 109 transvaginal hydrolaparoscopies (THLs) performed in 97 women. The THL was considered complete in 101 procedures (93%) and adequate for management in 105 (96%). Two complications occurred (1.8%), one failed entry and one perforation of a retroflexed uterus. Diagnoses for 67 infertile patients were normal pelvis in 34 (51%), endometriosis in 14 (21%), adhesions in 6 (9%), and tubal obstruction in 10 (15%); 3 THLs (4%) were considered incomplete. Of 17 women with dysmenorrhea, a normal pelvis was found in 8 (47%) and endometriosis in 9 (53%). In 11 patients with pelvic pain endometriosis was found in 4 (36%), normal pelvis in 3 (27%), and adhesions in 3 (27%); THL was incomplete in 1 (9%). Six infertile patients (9%) had operative laparoscopy and 10 (15%) operative THL; 6 (9%) were counseled to seek in vitro fertilization. Pregnancy occurred in 16 patients (24%). Analog pain scores (0 = no pain, 10 = worst pain) were tracked in 39 consecutive patients. Pain during trocar insertion averaged 4.2 +/- 0.5, 2.2 +/- 0.2 at midprocedure, and 1.1 +/- 0.1 at the end of THL. We believe that THL should be considered instead of hysterosalpingogram and laparoscopy in selected patients.

Transvaginal hydrolaparoscopy.

Transvaginal hydrolaparoscopy (THL) correlates well with standard laparoscopy for evaluation of the cul-de-sac in women with unexplained infertility. Office THL, chromopertubation, and hysteroscopy appear well tolerated, safe, and suitable for most patients, and may be more cost effective than hysterosalpingogram in the infertility work-up. Gynecologic and operative THLs are applicable for selected indications.