Medicare Reimbursement for Total Joint Arthroplasty: The Driving Forces.

BACKGROUND: Total joint arthroplasty is a large and growing part of the U.S. Medicare budget, drawing attention to how much providers are paid for their services. The purpose of this study was to examine the variables that affect total joint arthroplasty reimbursement. Along with standard economic variables, we include unique health-care variables. Given the focus on value in the Affordable Care Act, the model examines the relationship of the quality of care to total joint arthroplasty reimbursement. We hoped to find that reimbursement patterns reward quality and reflect standard economic principles. METHODS: Multivariable regression was performed to identify variables that correlate with Medicare reimbursement for total joint arthroplasty. Inpatient charge or reimbursement data on Medicare reimbursements were available for 2,750 hospitals with at least 10 discharges for uncomplicated total joint arthroplasty from the Centers for Medicare & Medicaid Services (CMS) for fiscal year 2011. Reimbursement variability was examined by using the Dartmouth Atlas to group institutions into hospital referral regions and hospital service areas. Independent variables were taken from the Dartmouth Atlas, CMS, the WWAMI (Washington, Wyoming, Alaska, Montana, Idaho) Rural Health Research Center, and the United States Census. RESULTS: There were 427,207 total joint arthroplasties identified, with a weighted mean reimbursement of $14,324.84 (range,$9,103 to $38,686). Nationally, the coefficient of variation for reimbursements was 0.19. The regression model accounted for 52.5% of reimbursement variation among providers. The total joint arthroplasty provider volume (p \u3c 0.001) and patient satisfaction (p \u3c 0.001) were negatively correlated with reimbursement. Government ownership of a hospital (p \u3c 0.001) and higher Medicare costs (p \u3c 0.001) correlated positively with reimbursement. CONCLUSIONS: Medicare reimbursements for total joint arthroplasty are highly variable. Greater reimbursement was associated with lower patient volume, lower patient satisfaction, a healthier patient population, and government ownership of a hospital. As value-based reimbursement provisions of the Affordable Care Act are implemented, there will be dramatic changes in total joint arthroplasty reimbursements. To meet these changes, providers should expect qualities such as high patient volume, willingness to care for sicker patient populations, patient satisfaction, safe outcomes, and procedural demand to correlate with their reimbursement. CLINICAL RELEVANCE: Practicing orthopaedic surgeons and hospital administrators should be aware of discrepancies in inpatient reimbursement for total joint arthroplasty from Medicare. Furthermore, these discrepancies are not associated with typical economic factors. These findings warrant further investigation and collaboration between policymakers and providers to develop value-based reimbursement

Does international normalized ratio level predict pulmonary embolism?

BACKGROUND: Preventing pulmonary embolism is a priority after major musculoskeletal surgery. The literature contains discrepant data regarding the influence of anticoagulation on the incidence of pulmonary embolism after joint arthroplasty. The American College of Chest Physicians guidelines recommend administration of oral anticoagulants (warfarin), aiming for an international normalized ratio (INR) level between 2 and 3. However, recent studies show aggressive anticoagulation (INR \u3e 2) can lead to hematoma formation and increased risk of subsequent infection. QUESTIONS/PURPOSES: We asked whether an INR greater than 2 protects against pulmonary embolism. PATIENTS AND METHODS: We identified 9112 patients with 10,122 admissions for joint arthroplasty between 2004 and 2008. All patients received warfarin for prophylaxis, aiming for an INR level of 2 or lower. We assessed 609 of 10,122 admissions (6%) for pulmonary embolism using CT, ventilation/perfusion scan, or pulmonary angiography, and 163 of 10,122 admissions (1.6%) had a proven pulmonary embolism. RESULTS: Fifteen of 163 admissions (9%) had an INR greater than 2 before or on the day of workup compared to 35 of 446 admissions (8%) who were negative. We observed no difference between the INR values in patients with or without pulmonary embolism. CONCLUSIONS: We found no clinically relevant difference in the INR values of patients who did or did not develop pulmonary embolism. The risk of bleeding should be weighed against the risk of pulmonary embolism when determining an appropriate target INR for each patient, as an INR less than 2 may reduce the risk of bleeding while still protecting against pulmonary embolism. LEVEL OF EVIDENCE: Level III, therapeutic study. See Instructions to Authors for a complete description of levels of evidence

Diet, nutrition, obesity and their role in arthritis

Obesity and poor nutrition, individually and together, have created costly musculoskeletal disease epidemic in the United States. Processed food, with abundant empty calories, has contributed greatly to our dietary woes. Much of the food consumed today is packed with calories but refined to the point that essential nutrients are lacking. Even worse, processed food may have ingredients added that are detrimental to good health. Abundant research has documented a close relationship between obesity, poor diet and orthopaedic problems. Dietary supplements have been proven to provide both disease prevention and therapeutic benefits. Unfortunately, many weight loss programs and methods are ineffective and possibly dangerous. Additionally, the FDA does not regulate the nutritional supplement industry and product quality is high variable. It is imperative that physicians treating patients with musculoskeletal complaints understand these disease producing relationships and have a network in place to refer patients to reputable weight loss entities and for high quality nutritional supplements

Does ‘excessive’ anticoagulation predispose to periprosthetic infection?

Background Although persistent drainage and hematoma formation are recognized risk factors for the development of periprosthetic infection, it is not known if excess anticoagulation is a predisposing factor. Methods We conducted a 2 to 1 case-control study with 78 cases who underwent revision for septic failure. The controls underwent the same index procedure but did not develop consequent infection. Patient comorbidities, medications, intraoperative, and postoperative factors were compared. Results Postoperative wound complications including development of hematoma and wound drainage were significant risk factors for periprosthetic infection. A mean international normalized ratio of greater than 1.5 was found to be more prevalent in patients who developed postoperative wound complications and subsequent periprosthetic infection. Conclusions Cautious anticoagulation to prevent hematoma formation and/or wound drainage is critical to prevent periprosthetic infection and its undesirable consequences

A multi-mRNA host-response molecular blood test for the diagnosis and prognosis of acute infections and sepsis: Proceedings from a clinical advisory panel

Current diagnostics are insufficient for diagnosis and prognosis of acute infections and sepsis. Clinical decisions including prescription and timing of antibiotics, ordering of additional diagnostics and level-of-care decisions rely on understanding etiology and implications of a clinical presentation. Host mRNA signatures can differentiate infectious from noninfectious etiologies, bacterial from viral infections, and predict 30-day mortality. The 29-host-mRNA blood-based InSe

Spatial and temporal clustering of dengue virus transmission in Thai villages.

BackgroundTransmission of dengue viruses (DENV), the leading cause of arboviral disease worldwide, is known to vary through time and space, likely owing to a combination of factors related to the human host, virus, mosquito vector, and environment. An improved understanding of variation in transmission patterns is fundamental to conducting surveillance and implementing disease prevention strategies. To test the hypothesis that DENV transmission is spatially and temporally focal, we compared geographic and temporal characteristics within Thai villages where DENV are and are not being actively transmitted.Methods and findingsCluster investigations were conducted within 100 m of homes where febrile index children with (positive clusters) and without (negative clusters) acute dengue lived during two seasons of peak DENV transmission. Data on human infection and mosquito infection/density were examined to precisely (1) define the spatial and temporal dimensions of DENV transmission, (2) correlate these factors with variation in DENV transmission, and (3) determine the burden of inapparent and symptomatic infections. Among 556 village children enrolled as neighbors of 12 dengue-positive and 22 dengue-negative index cases, all 27 DENV infections (4.9% of enrollees) occurred in positive clusters (p < 0.01; attributable risk [AR] = 10.4 per 100; 95% confidence interval 1-19.8 per 100]. In positive clusters, 12.4% of enrollees became infected in a 15-d period and DENV infections were aggregated centrally near homes of index cases. As only 1 of 217 pairs of serologic specimens tested in positive clusters revealed a recent DENV infection that occurred prior to cluster initiation, we attribute the observed DENV transmission subsequent to cluster investigation to recent DENV transmission activity. Of the 1,022 female adult Ae. aegypti collected, all eight (0.8%) dengue-infected mosquitoes came from houses in positive clusters; none from control clusters or schools. Distinguishing features between positive and negative clusters were greater availability of piped water in negative clusters (p < 0.01) and greater number of Ae. aegypti pupae per person in positive clusters (p = 0.04). During primarily DENV-4 transmission seasons, the ratio of inapparent to symptomatic infections was nearly 1:1 among child enrollees. Study limitations included inability to sample all children and mosquitoes within each cluster and our reliance on serologic rather than virologic evidence of interval infections in enrollees given restrictions on the frequency of blood collections in children.ConclusionsOur data reveal the remarkably focal nature of DENV transmission within a hyperendemic rural area of Thailand. These data suggest that active school-based dengue case detection prompting local spraying could contain recent virus introductions and reduce the longitudinal risk of virus spread within rural areas. Our results should prompt future cluster studies to explore how host immune and behavioral aspects may impact DENV transmission and prevention strategies. Cluster methodology could serve as a useful research tool for investigation of other temporally and spatially clustered infectious diseases

Update to the Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) protocol: statistical analysis plan for a prospective, multicenter, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial.

BACKGROUND: Observational research suggests that combined therapy with Vitamin C, thiamine and hydrocortisone may reduce mortality in patients with septic shock. METHODS AND DESIGN: The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) trial is a multicenter, double-blind, adaptive sample size, randomized, placebo-controlled trial designed to test the efficacy of combination therapy with vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) given every 6 h for up to 16 doses in patients with respiratory or circulatory dysfunction (or both) resulting from sepsis. The primary outcome is ventilator- and vasopressor-free days with mortality as the key secondary outcome. Recruitment began in August 2018 and is ongoing; 501 participants have been enrolled to date, with a planned maximum sample size of 2000. The Data and Safety Monitoring Board reviewed interim results at N = 200, 300, 400 and 500, and has recommended continuing recruitment. The next interim analysis will occur when N = 1000. This update presents the statistical analysis plan. Specifically, we provide definitions for key treatment and outcome variables, and for intent-to-treat, per-protocol, and safety analysis datasets. We describe the planned descriptive analyses, the main analysis of the primary end point, our approach to secondary and exploratory analyses, and handling of missing data. Our goal is to provide enough detail that our approach could be replicated by an independent study group, thereby enhancing the transparency of the study. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03509350. Registered on 26 April 2018

Cell-Mediated Immunity Generated in Response to a Purified Inactivated Vaccine for Dengue Virus Type 1

Dengue is the most prevalent arboviral disease afflicting humans, and a vaccine appears to be the most rational means of control. Dengue vaccine development is in a critical phase, with the first vaccine licensed in some countries where dengue is endemic but demonstrating insufficient efficacy in immunologically naive populations. Since virus-neutralizing antibodies do not invariably correlate with vaccine efficacy, other markers that may predict protection, including cell-mediated immunity, are urgently needed. Previously, the Walter Reed Army Institute of Research developed a monovalent purified inactivated virus (PIV) vaccine candidate against dengue virus serotype 1 (DENV-1) adjuvanted with alum. The PIV vaccine was safe and immunogenic in a phase I dose escalation trial in healthy, flavivirus-naive adults in the United States. From that trial, peripheral blood mononuclear cells obtained at various time points pre- and postvaccination were used to measure DENV-1-specific T cell responses. After vaccination, a predominant CD4+ T cell-mediated response to peptide pools covering the DENV-1 structural proteins was observed. Over half (13/20) of the subjects produced interleukin-2 (IL-2) in response to DENV peptides, and the majority (17/20) demonstrated peptide-specific CD4+ T cell proliferation. In addition, analysis of postvaccination cell culture supernatants demonstrated an increased rate of production of cytokines, including gamma interferon (IFN-γ), IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Overall, the vaccine was found to have elicited DENV-specific CD4+ T cell responses as measured by enzyme-linked immunosorbent spot (ELISpot), intracellular cytokine staining (ICS), lymphocyte proliferation, and cytokine production assays. Thus, together with antibody readouts, the use of a multifaceted measurement of cell-mediated immune responses after vaccination is a useful strategy for more comprehensively characterizing immunity generated by dengue vaccines

Altered Gene Expression in Pulmonary Tissue of Tryptophan Hydroxylase-1 Knockout Mice: Implications for Pulmonary Arterial Hypertension

The use of fenfluramines can increase the risk of developing pulmonary arterial hypertension (PAH) in humans, but the mechanisms responsible are unresolved. A recent study reported that female mice lacking the gene for tryptophan hydroxylase-1 (Tph1(−/−) mice) were protected from PAH caused by chronic dexfenfluramine, suggesting a pivotal role for peripheral serotonin (5-HT) in the disease process. Here we tested two alternative hypotheses which might explain the lack of dexfenfluramine-induced PAH in Tph1(−/−) mice. We postulated that: 1) Tph1(−/−) mice express lower levels of pulmonary 5-HT transporter (SERT) when compared to wild-type controls, and 2) Tph1(−/−) mice display adaptive changes in the expression of non-serotonergic pulmonary genes which are implicated in PAH. SERT was measured using radioligand binding methods, whereas gene expression was measured using microarrays followed by quantitative real time PCR (qRT-PCR). Contrary to our first hypothesis, the number of pulmonary SERT sites was modestly up-regulated in female Tph1(−/−) mice. The expression of 51 distinct genes was significantly altered in the lungs of female Tph1(−/−) mice. Consistent with our second hypothesis, qRT-PCR confirmed that at least three genes implicated in the pathogenesis of PAH were markedly up-regulated: Has2, Hapln3 and Retlna. The finding that female Tph1(−/−) mice are protected from dexfenfluramine-induced PAH could be related to compensatory changes in pulmonary gene expression, in addition to reductions in peripheral 5-HT. These observations emphasize the intrinsic limitation of interpreting data from studies conducted in transgenic mice that are not fully characterized

Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications

Background—Serotonergic medications with various mechanisms of action are used to treat psychiatric disorders and are being investigated as treatments for drug dependence. The occurrence of fenfluramine-associated valvular heart disease (VHD) has raised concerns that other serotonergic medications might also increase the risk of developing VHD. We hypothesized that fenfluramine or its metabolite norfenfluramine and other medications known to produce VHD have preferentially high affinities for a particular serotonin receptor subtype capable of stimulating mitogenesis. Methods and Results—Medications known or suspected to cause VHD (positive controls) and medications not associated with VHD (negative controls) were screened for activity at 11 cloned serotonin receptor subtypes by use of ligand-binding methods and functional assays. The positive control drugs were (±)-fenfluramine; (+)-fenfluramine; (−)-fenfluramine; its metabolites (±)-norfenfluramine, (+)-norfenfluramine, and (−)-norfenfluramine; ergotamine; and methysergide and its metabolite methylergonovine. The negative control drugs were phentermine, fluoxetine, its metabolite norfluoxetine, and trazodone and its active metabolite m-chlorophenylpiperazine. (±)-, (+)-, and (−)-Norfenfluramine, ergotamine, and methylergonovine all had preferentially high affinities for the cloned human serotonin 5-HT2B receptor and were partial to full agonists at the 5-HT2B receptor. Conclusions—Our data imply that activation of 5-HT2B receptors is necessary to produce VHD and that serotonergic medications that do not activate 5-HT2B receptors are unlikely to produce VHD. We suggest that all clinically available medications with serotonergic activity and their active metabolites be screened for agonist activity at 5-HT2B receptors and that clinicians should consider suspending their use of medications with significant activity at 5-HT2B receptors