Social vulnerability adversely affects emergency-department utilization but not patient-reported outcomes after total joint arthroplasty.

INTRODUCTION: Multiple studies demonstrate social deprivation is associated with inferior outcomes after total hip (THA) and total knee (TKA) arthroplasty; its effect on patient-reported outcomes is debated. The primary objective of this study evaluated the relationship between social vulnerability and the PROMIS-PF measure in patients undergoing THA and TKA. A secondary aim compared social vulnerability between patients who required increased resource utilization or experienced complications and those who didn't. MATERIALS AND METHODS: A retrospective review of 537 patients from March 2020 to February 2022 was performed. The Centers for Disease Control Social Vulnerability Index (SVI) were used to quantify socioeconomic disadvantage. The cohort was split into THA and TKA populations; univariate and multivariate analyses were performed to evaluate primary and secondary outcomes. Statistical significance was assessed at p < 0.05. RESULTS: 48.6% of patients achieved PROMIS-PF MCID at 1-year postoperatively. Higher levels of overall social vulnerability (0.40 vs. 0.28, p = 0.03) were observed in TKA patients returning to the ED within 90-days of discharge. Increased overall SVI (OR = 9.18, p = 0.027) and household characteristics SVI (OR = 9.57, p = 0.015) were independent risk factors for 90-day ED returns after TKA. In THA patients, increased vulnerability in the household type and transportation dimension was observed in patients requiring 90-day ED returns (0.51 vs. 0.37, p = 0.04). CONCLUSION: Despite an increased risk for 90-day ED returns, patients with increased social vulnerability still obtain good 1-year functional outcomes. Initiatives seeking to mitigate the effect of social deprivation on TJA outcomes should aim to provide safe alternatives to ED care during early recovery.

Outpatient physical therapy bundled payment models are feasible for total hip arthroplasty patients: an evaluation of utilization, cost and outcomes.

BACKGROUND: Various episode-of-care bundled payment models for patients undergoing total joint arthroplasty have been implemented. However, participation in bundled payment programs has dropped given the challenges of meeting continually lower target prices. The purpose of our study is to investigate the cost of outpatient physical therapy (PT) and the potential for stand-alone outpatient PT bundled payments for patients undergoing total hip arthroplasty (THA). METHODS: A retrospective review of 501 patients who underwent primary unilateral THA from November 2017 to February 2020 was performed. All patients included in this study received postoperative PT care at a single hospital-affiliated PT practice. Patients above the 75th percentile of therapy visits were then classified as high-PT utilizers and compared with the rest of the population using univariate statistics. Stepwise multivariate logistic regression was used to assess the predictors of high therapy utilization. RESULTS: Patients averaged 65 ± 10 years of age and a BMI of 29 ± 5 kg/m2. Overall, 80% of patients were white and 53% were female. The average patient had 11 ± 8 total therapy sessions in 42 days: one initial evaluation, one re-evaluation and 9 standard sessions. High-PT utilizers incurred estimated average costs of $1934 ± 431 per patient, compared to $783 ± 432 (P < 0.001) in the rest of the population. Further, no significant differences in 90-day outcomes including lower extremity functional scale scores, emergency department returns, readmissions, or returns to the operating room were observed between high utilizers and the rest of the population (all P > 0.08). In the multivariate analysis, women (OR = 1.68, P = 0.017) and those with sleep apnea (OR = 2.02, P = 0.012) were nearly twice as likely to be high utilizers, while white patients were 42% less likely to be high utilizers than patients of other races (OR = 0.58, P = 0.028). CONCLUSIONS: Outpatient PT utilization is highly variable in patients undergoing THA. However, despite using more services and incurring increased cost, patients in the top quartile of utilization experienced similar outcomes to the rest of the population. If outpatient therapy bundles are to be developed, 16 visits appear to be a reasonable target for pricing, given this provides adequate coverage for 75% of THA patients.

Racial Disparities in Outcomes of Total Joint Arthroplasty at a Single Institution: Have We Made Progress?

Background: Health disparities disproportionately affect minority groups across the United States with respect to care access, quality, and outcomes. The aim of this study is to examine existing disparities between white and African American (AA) patients regarding postoperative outcomes following total joint arthroplasty and provide insight into disparity trends over a 9-year period. Methods: A retrospective review of 16,779 total joint arthroplasty patients at a single institution between January 2013 and December 2021 was performed. Patients were grouped by race as AA or white. Outcomes of interest included length of stay (LOS), home discharge, 30-day emergency department return, and 30-day readmission. Univariate statistics and multivariate regressions were utilized to analyze results. Results: Significant improvements in LOS and rates of home discharge occurred for both white and AA patients at our institution over a 9-year period, while rates of 30-day emergency department returns and readmissions demonstrated a downward but non-statistically significant trend. Despite these trends, AA patients continued to experience longer lengths of stay, less likelihood of 0- or 1-day LOS, and higher risk of nonhome discharge for most years examined. However, after controlling for demographic and comorbidity differences, the differences between groups narrowed over time resulting in no significant differences in the aforementioned 3 measures by 2021. Conclusions: Although racial disparities in outcomes are still apparent, over time, the differences in resource utilization between AA and white patients have narrowed. Initiatives aimed at creating healthier communities with increased access to care and the ultimate goal of equitable care must continue to be pursued.

Effect of a Biopsychosocial Intervention or Postural Therapy on Disability and Health Care Spending Among Patients With Acute and Subacute Spine Pain: The SPINE CARE Randomized Clinical Trial.

Importance: Low back and neck pain are often self-limited, but health care spending remains high. Objective: To evaluate the effects of 2 interventions that emphasize noninvasive care for spine pain. Design, Setting, and Participants: Pragmatic, cluster, randomized clinical trial conducted at 33 centers in the US that enrolled 2971 participants with neck or back pain of 3 months' duration or less (enrollment, June 2017 to March 2020; final follow-up, March 2021). Interventions: Participants were randomized at the clinic-level to (1) usual care (n = 992); (2) a risk-stratified, multidisciplinary intervention (the identify, coordinate, and enhance [ICE] care model that combines physical therapy, health coach counseling, and consultation from a specialist in pain medicine or rehabilitation) (n = 829); or (3) individualized postural therapy (IPT), a postural therapy approach that combines physical therapy with building self-efficacy and self-management (n = 1150). Main Outcomes and Measures: The primary outcomes were change in Oswestry Disability Index (ODI) score at 3 months (range, 0 [best] to 100 [worst]; minimal clinically important difference, 6) and spine-related health care spending at 1 year. A 2-sided significance threshold of .025 was used to define statistical significance. Results: Among 2971 participants randomized (mean age, 51.7 years; 1792 women [60.3%]), 2733 (92%) finished the trial. Between baseline and 3-month follow-up, mean ODI scores changed from 31.2 to 15.4 for ICE, from 29.3 to 15.4 for IPT, and from 28.9 to 19.5 for usual care. At 3-month follow-up, absolute differences compared with usual care were -5.8 (95% CI, -7.7 to -3.9; P < .001) for ICE and -4.3 (95% CI, -5.9 to -2.6; P < .001) for IPT. Mean 12-month spending was $1448, $2528, and $1587 in the ICE, IPT, and usual care groups, respectively. Differences in spending compared with usual care were -$139 (risk ratio, 0.93 [95% CI, 0.87 to 0.997]; P = .04) for ICE and $941 (risk ratio, 1.40 [95% CI, 1.35 to 1.45]; P < .001) for IPT. Conclusions and Relevance: Among patients with acute or subacute spine pain, a multidisciplinary biopsychosocial intervention or an individualized postural therapy intervention, each compared with usual care, resulted in small but statistically significant reductions in pain-related disability at 3 months. However, compared with usual care, the biopsychosocial intervention resulted in no significant difference in spine-related health care spending and the postural therapy intervention resulted in significantly greater spine-related health care spending at 1 year. Trial Registration: ClinicalTrials.gov Identifier: NCT03083886.

Patients From Medically Underserved Areas Are at Increased Risk for Nonhome Discharge and Emergency Department Return After Total Joint Arthroplasty.

BACKGROUND: Maryland Health Enterprise Zones (MHEZs) were introduced in 2012 and encompass underserved areas and those with reduced access to healthcare providers. Across the United States many underserved and minority populations experience poorer total joint arthroplasty (TJA) outcomes seemingly because they reside in underserved areas. The purpose of this study is to identify and quantify the relationship between living in an MHEZ and TJA outcomes. METHODS: Retrospective review of 11,451 patients undergoing primary TJA at a single institution from July 1, 2014 to June 30, 2020 was conducted. Patients were classified based on whether they resided in an MHEZ. Statistical analyses were used to compare outcomes for TJA patients who live in MHEZ and those who do not. RESULTS: Of the 11,451 patients, 1057 patients lived in MHEZ and 10,394 patients did not. After risk adjustment, patients who live in an MHEZ were more likely to return to the emergency department within 90 days postoperatively and were less likely to be discharged home than those patients who do not live in an MHEZ. CONCLUSION: Total joint arthroplasty patients residing in MHEZ appear to present with poorer overall health as measured by increased American Society of Anesthesiologists and Hierarchical Condition Categories scores, and they are less likely to be discharged home and more likely to return to the emergency department within 90 days. Several factors associated with these findings such as socioeconomic factors, household composition, housing type, disability, and transportation may be modifiable and should be targets of future population health initiatives.

A Comprehensive Assessment of Associations between Prenatal Phthalate Exposure and the Placental Transcriptomic Landscape.

BACKGROUND: Phthalates are commonly used endocrine-disrupting chemicals that are ubiquitous in the general population. Prenatal phthalate exposure may alter placental physiology and fetal development, leading to adverse perinatal and childhood health outcomes. OBJECTIVE: We examined associations between prenatal phthalate exposure in the second and third trimesters and the placental transcriptome at birth, including genes and long noncoding RNAs (lncRNAs), to gain insight into potential mechanisms of action during fetal development. METHODS: The ECHO PATHWAYs consortium quantified 21 urinary phthalate metabolites from 760 women enrolled in the CANDLE study (Shelby County, TN) using high-performance liquid chromatography-tandem mass spectrometry. Placental transcriptomic data were obtained using paired-end RNA sequencing. Linear models were fitted to estimate separate associations between maternal urinary phthalate metabolite concentration during the second and third trimester and placental gene expression at birth, adjusted for confounding variables. Genes were considered differentially expressed at a Benjamini-Hochberg false discovery rate (FDR) p<0.05. Associations between phthalate metabolites and biological pathways were identified using self-contained gene set testing and considered significantly altered with an FDR-adjusted p<0.2. RESULTS: We observed significant associations between second-trimester phthalate metabolites mono (carboxyisooctyl) phthalate (MCIOP), mono-2-ethyl-5-carboxypentyl phthalate, and mono-2-ethyl-5-oxohexyl phthalate and 18 genes in total, including four lncRNAs. Specifically, placental expression of NEAT1 was associated with multiple phthalate metabolites. Third-trimester MCIOP and mono-isobutyl phthalate concentrations were significantly associated with placental expression of 18 genes and two genes, respectively. Expression of genes within 27 biological pathways was associated with mono-methyl phthalate, MCIOP, and monoethyl phthalate concentrations. DISCUSSION: To our knowledge, this is the first genome-wide assessment of the relationship between the placental transcriptome at birth and prenatal phthalate exposure in a large and diverse birth cohort. We identified numerous genes and lncRNAs associated with prenatal phthalate exposure. These associations mirror findings from other epidemiological and in vitro analyses and may provide insight into biological pathways affected in utero by phthalate exposure. https://doi.org/10.1289/EHP8973.

Preoperative Education for Total Joint Arthroplasty: Does Reimbursement Reduction Threaten Improved Outcomes?

BACKGROUND: Nurse navigation programs have been previously shown to reduce cost and improve outcomes after total joint arthroplasty (TJA). Medicare has proposed a 13.7% reduction in professional fee reimbursement for TJA procedures that may adversely impact providers' and health systems' ability to fund ancillary support resources such as nurse navigators. METHODS: A consecutive series of primary TJAs performed between April 2019 and February 2020 was retrospectively reviewed. Clinical and financial outcomes of patients attending a nurse navigator-led preoperative education class were compared with those who did not attend. RESULTS: There were 2057 TJAs identified during the study period. Most patients attended the preoperative education class (82.7%) and were discharged home (92.8%). Controlling for significant differences between groups, class attendance was associated with reduced length of stay (LOS), increased chance of 0- or 1-day LOS, reduced chance of discharge to a skilled nursing facility, and reduced hospital charges. For this patient sample, a proposed 13.7% reduction in nurse navigator-led classes was modeled to increase overall cost to payers by >$400,000 annually. Complete elimination of this class was estimated to increase the total annual cost by >$5,700,000 and cost per TJA by >$2700. CONCLUSION: The use of a nurse navigator-led preoperative education class was associated with shorter LOS, more frequent 0- and 1-day LOS, reduced discharge to skilled nursing facilities, and lower total hospital charges for those patients who attended. Potential reductions proposed by Medicare may interfere with the ability to support such services and negatively impact both clinical and financial outcomes.

Risk factors for severe illness in hospitalized Covid-19 patients at a regional hospital.

BACKGROUND: The Covid-19 pandemic threatens to overwhelm scarce clinical resources. Risk factors for severe illness must be identified to make efficient resource allocations. OBJECTIVE: To evaluate risk factors for severe illness. DESIGN: Retrospective, observational case series. SETTING: Single-institution. PARTICIPANTS: First 117 consecutive patients hospitalized for Covid-19 from March 1 to April 12, 2020. EXPOSURE: None. MAIN OUTCOMES AND MEASURES: Intensive care unit admission or death. RESULTS: In-hospital mortality was 24.8% and average total length of stay was 11.82 days (95% CI: 10.01 to 13.63 days). 30.8% of patients required intensive care unit admission and 29.1% required mechanical ventilation. Multivariate regression identified the amount of supplemental oxygen required at admission (OR: 1.208, 95% CI: 1.011-1.443, p = .037), sputum production (OR: 6.734, 95% CI: 1.630-27.812, p = .008), insulin dependent diabetes mellitus (OR: 11.873, 95% CI: 2.218-63.555, p = .004) and chronic kidney disease (OR: 4.793, 95% CI: 1.528-15.037, p = .007) as significant risk factors for intensive care unit admission or death. Of the 48 patients who were admitted to the intensive care unit or died, this occurred within 3 days of arrival in 42%, within 6 days in 71%, and within 9 days in 88% of patients. CONCLUSIONS: At our regional medical center, patients with Covid-19 had an average length of stay just under 12 days, required ICU care in 31% of cases, and had a 25% mortality rate. Patients with increased sputum production and higher supplemental oxygen requirements at admission, and insulin dependent diabetes or chronic kidney disease may be at increased risk for severe illness. A model for predicting intensive care unit admission or death with excellent discrimination was created that may aid in treatment decisions and resource allocation. Early identification of patients at increased risk for severe illness may lead to improved outcomes in patients hospitalized with Covid-19.

Preoperative Predictors of Patients Requiring Inpatient Admission for Total Hip Arthroplasty Following Removal From the Medicare Inpatient-Only List.

BACKGROUND: The Centers for Medicare and Medicaid Services has removed total hip arthroplasty from the inpatient-only (IO) list in January 2020. Given the confusion created when total knee arthroplasty came off the IO list in 2018, this study aims to develop a predictive model for guiding preoperative inpatient admission decisions based upon readily available patient demographic and comorbidity data. METHODS: This is a retrospective review of 1415 patients undergoing elective unilateral primary THA between January 2018 and October 2019. Multiple logistic regression was used to develop a model for predicting LOS ≥2 days based on preoperative demographics and comorbidities. RESULTS: Controlling for other demographics and comorbidities, increased age (odds ratio [OR], 1.048; P < .001), female gender (OR, 2.284; P < .001), chronic obstructive pulmonary disorder (OR, 2.249; P = .003), congestive heart failure (OR, 8.231; P < .001), and number of comorbidities (OR, 1.216; P < .001) were associated with LOS ≥2 days while patients with increased body mass index (OR, 0.964; P = .007) and primary hypertension (OR, 0.671; P = .008) demonstrated significantly reduced odds of staying in the hospital for 2 or more days. The area under the curve was found to be 0.731, indicating acceptable discriminatory value. CONCLUSION: For patients undergoing primary THA, increased age, female gender, chronic obstructive pulmonary disorder, congestive heart failure, and multiple comorbidities are risk factors for inpatient hospital LOS of 2 or more days. Our predictive model based on readily available patient presentation and comorbidity characteristics may aid surgeons in preoperatively identifying patients requiring inpatient admission with removal of THA from the Medicare IO list.

Prevalence of Spondylolysis in Symptomatic Adolescent Athletes: An Assessment of Sport Risk in Nonelite Athletes.

OBJECTIVE: To assess the risk of spondylolysis by sport in nonelite adolescent athletes with low back pain (LBP). DESIGN: Retrospective case series. SETTING: Hospital-based sports medicine clinic. PATIENTS: The medical charts of 1025 adolescent athletes with LBP (age 15 ± 1.8 years) were examined; 308 (30%) were diagnosed with a spondylolysis. ASSESSMENT OF RISK: Risk of spondylolysis was assessed in 11 sports for males and 14 sports for females. MAIN OUTCOME MEASURE: Relative risk of diagnosis of spondylolysis injury. RESULTS: The risk of spondylolysis differed by sex with baseball (54%), soccer (48%), and hockey (44%) having the highest prevalence in males and gymnastics (34%), marching band (31%), and softball (30%) for female athletes. Baseball was the only sport to demonstrate a significant increased risk of spondylolysis. CONCLUSIONS: The sports with the greatest risk of spondylolysis in adolescent athletes in this study were not consistent with published literature. Clinicians should be cautious generalizing high-risk sports to their practice, as geographic region and level of the athlete may significantly influence the incidence of spondylolysis in the population they are treating.

Human kidney on a chip assessment of polymyxin antibiotic nephrotoxicity.

Drug-induced kidney injury, largely caused by proximal tubular intoxicants, limits development and clinical use of new and approved drugs. Assessing preclinical nephrotoxicity relies on animal models that are frequently insensitive; thus, potentially novel techniques - including human microphysiological systems, or "organs on chips" - are proposed to accelerate drug development and predict safety. Polymyxins are potent antibiotics against multidrug-resistant microorganisms; however, clinical use remains restricted because of high risk of nephrotoxicity and limited understanding of toxicological mechanisms. To mitigate risks, structural analogs of polymyxins (NAB739 and NAB741) are currently in clinical development. Using a microphysiological system to model human kidney proximal tubule, we exposed cells to polymyxin B (PMB) and observed significant increases of injury signals, including kidney injury molecule-1 KIM-1and a panel of injury-associated miRNAs (each P < 0.001). Surprisingly, transcriptional profiling identified cholesterol biosynthesis as the primary cellular pathway induced by PMB (P = 1.22 ×10-16), and effluent cholesterol concentrations were significantly increased after exposure (P < 0.01). Additionally, we observed no upregulation of the nuclear factor (erythroid derived-2)-like 2 pathway, despite this being a common pathway upregulated in response to proximal tubule toxicants. In contrast with PMB exposure, minimal changes in gene expression, injury biomarkers, and cholesterol concentrations were observed in response to NAB739 and NAB741. Our findings demonstrate the preclinical safety of NAB739 and NAB741 and reveal cholesterol biosynthesis as a potentially novel pathway for PMB-induced injury. To our knowledge, this is the first demonstration of a human-on-chip platform used for simultaneous safety testing of new chemical entities and defining unique toxicological pathway responses of an FDA-approved molecule.

The Cost of Unnecessary Hospital Days for Medicare Joint Arthroplasty Patients Discharging to Skilled Nursing Facilities.

BACKGROUND: The 72-hour Medicare mandate (3-night stay rule) requires a 3-day inpatient stay for patients discharging to skilled nursing facilities (SNFs). Studies show that 48%-64% of Medicare total joint arthroplasty (TJA) patients are safe for discharge to SNFs on postoperative day (POD) #2. The purpose of this study was to extrapolate the financial impact of the 3-night stay rule. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for all primary TJAs performed in 2015. Discharge destination was recorded. Institutional cost accounting examined costs for patients discharging on POD #2 vs POD #3. RESULTS: A total of 42,423 TJAs (14,395 total hip arthroplasties [THAs] and 28,028 total knee arthroplasties [TKAs]) were performed in patients over the age of 65 years. Of these patients, 5252 THAs (36.5%) and 12,022 TKAs (42.9%) were discharged from the hospital on POD #3, with 2404 THAs (16.7%) and 5083 TKAs (18.1%) being discharged to SNFs. Institutional cost accounting revealed hospital costs for THA were $2014 more, whereas hospital costs for TKA were $1814 more for a 3-day length of stay when compared with a 2-day length of stay (P < .001). The mean charge per day for an SNF was $486. CONCLUSION: The National Surgical Quality Improvement Program database is a representative sample of all surgeries performed in the United States. Extrapolating our findings to all Medicare TJAs nationally gives an estimated $63 million in annual savings. Medicare mandated, but potentially medically unnecessary inpatient days at a higher level of care increase the total cost for TJAs. Policies regarding minimum stay requirements before discharge should be re-evaluated.

Treatment Satisfaction and Adherence to Oral Chemotherapy in Patients With Cancer.

PURPOSE: Although patients with cancer overwhelming prefer oral to intravenous chemotherapy, little is known about adherence to oral agents. We aimed to identify the rates and correlates of adherence in patients with diverse malignancies. MATERIALS AND METHODS: Ninety patients with chronic myeloid leukemia or metastatic renal cell carcinoma, non-small-cell lung cancer, or breast cancer enrolled in this prospective, single-group, observational study of medication-taking behaviors. Adherence was measured via self-report and with an electronic pill cap (Medication Event Monitoring System cap). Patients completed surveys regarding symptom distress, mood, quality of life, cancer-specific distress, and satisfaction with clinician communication and treatment at baseline and 12-week follow-up. RESULTS: As measured by the Medication Event Monitoring System, patients took, on average, 89.3% of their prescribed oral chemotherapy over the 12 weeks. One quarter of the sample was less than 90% adherent, and women were more adherent than men (mean difference, 9.59%; SE difference, 4.50%; 95% CI, -18.65 to -0.52; P = .039). Improvements in patient symptom distress (B = -0.79; 95% CI, -1.41 to -0.18), depressive symptoms (B = -1.57; 95% CI, -2.86 to -0.29), quality of life (B = 0.38; 95% CI ,0.07 to 0.68), satisfaction with clinician communication and treatment (B = 0.73; 95% CI, 0.49 to 0.98), and perceived burden to others (B = -1.28; 95% CI, -2.20 to -0.37) were associated with better adherence. In a multivariate model, improved treatment satisfaction (B = 0.71; 95% CI, 0.48 to 0.94) and reduced perceived burden (B = -0.92; 95% CI, -1.76 to -0.09) were the strongest indicators of better adherence. CONCLUSION: Women and patients who reported increased treatment satisfaction and reduced burden to others were more adherent to oral chemotherapy. Interventions that help patients improve communication with clinicians and reduce burden may optimize oral chemotherapy adherence.

Incidence, Risk Factors, and Costs for Hospital Returns After Total Joint Arthroplasties.

BACKGROUND: Unplanned hospital returns after total joint arthroplasty (TJA) reduce any cost savings in a bundled reimbursement model. We examine the incidence, risk factors, and costs for unplanned emergency department (ED) visits and readmissions within 30 days of index TJA. METHODS: We retrospectively reviewed a consecutive series of 655 TJAs (382 total knee arthroplasty and 273 total hip arthroplasty) performed between April 2014 and March 2015. Preoperative diagnosis was osteoarthritis of the hip or knee (97%) or avascular necrosis of the hip (3%). Hospital costs were recorded for each ED visit and readmission episode. RESULTS: Of the 655 TJAs reviewed, 55 (8.4%) returned to the hospital. Of these hospital returns, 35 patients (5.3%) returned for a total of 36 unplanned ED visits whereas the remaining 20 patients (3.1%) presented 22 readmissions within 30 days of index TJA. The 2 most common reasons for unplanned ED visits were postoperative pain/swelling (36%) and medication-related side effects (22%). Avascular necrosis of the hip was a significant risk factor for an unplanned ED visit (7.27 odds ratio [OR], 95% confidence interval [CI] 1.67-31.61, P = .008). Multiple logistic regression analysis revealed the following risk factors for readmission: body mass index (1.10 OR, 95% CI 1.02-1.78, P = .013), comorbidity >2 (2.07 OR, 95% CI 1.06-6.95, P = .037), and prior total knee arthroplasty (2.61 OR, 95% CI 1.01-6.72, P = .047). Ambulating on the day of surgery trended toward a lower risk for readmission (0.13 OR, 95% CI 0.02-1.10, P = .061). The 2 most common reasons for readmission were ileus (23%) and cellulitis (18%). The total cost associated with unplanned ED visits were $15,427 whereas costs of readmissions totaled $142,654. CONCLUSION: Unplanned ED visits and readmissions in the forthcoming bundled payments reimbursement model will reduce cost savings from rapid recovery protocols for TJA. Identifying and mitigating preventable causes of unplanned visits and readmissions will be critical to improving care and controlling costs.

Cytoreduction with hyperthermic intraperitoneal chemotherapy: an appraisal of outcomes and cost at a newly established peritoneal malignancy program.

BACKGROUND: Outcome measures after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for peritoneal carcinomatosis in established centers are well defined. However, results from newly emerging US centers have not been reported. METHODS: This is a retrospective review of a prospectively maintained database of patients with peritoneal malignancies undergoing CRS/HIPEC. RESULTS: Fifty-six patients underwent exploratory laparotomy with 36 receiving CRS/HIPEC over 36 months. The median peritoneal cancer index score was 18, and the cytoreduction 0/1 rate was 92%. Postoperative major morbidity was 16.7% with one perioperative death. The median length of hospital stay and intensive care unit days were 9 and 3 days, respectively. Disease-free survival in high-grade vs low-grade tumors was 12.6 and 31.0 months (P, .03), respectively. Average direct cost for patients undergoing CRS/HIPEC was $25,917. CONCLUSIONS: Our emerging center's short-term results are comparable with established programs with a trend toward more selective intraoperative judgment on who undergoes CRS/HIPEC.

Top 10 research questions related to exercise deficit disorder (EDD) in youth.

Exercise deficit disorder (EDD) is a pediatric medical condition characterized by reduced levels of moderate-to-vigorous physical activity (MVPA) that are below current recommendations and inconsistent with positive health outcomes. At present, a majority of children and adolescents meet the diagnostic criteria for EDD because they are not accumulating minimum thresholds of daily MVPA. The purpose of this article is to highlight 10 important research questions related to EDD in youth. The critical research needs to better define the clinical spectrum of EDD to include an assessment of physical activity behaviors to determine the age or stage of maturation at which EDD first emerges; an examination of the kinesiogenesis of movement skills and physical abilities; and an evaluation of lifestyle factors that can influence the MVPA trajectory in youth. Research questions about interventions and policies to treat EDD include evaluating the education and training of health care providers on the importance of exercise medicine; determining the effectiveness of strategies to identify and treat youth with EDD in clinical practice; developing sensitive, specific, and cost-effective methods to diagnose youth with EDD; and assessing methods to promote health care reimbursement for the treatment of this condition. Without future research to optimize identification, treatment, and management strategies for youth with EDD, new health care concerns with significant biomedical, psychosocial, economic, and political ramifications will continue to emerge.

R2oDNA designer: computational design of biologically neutral synthetic DNA sequences.

R2oDNA Designer is a web application that stochastically generates orthogonal sets of synthetic DNA sequences designed to be biologically neutral. Biologically neutral sequences may be used for directing efficient DNA assembly by overlap-directed methods, as a negative control for functional DNA, as barcodes, or potentially as spacer regions to insulate biological parts from local context. The software creates optimized sequences using a Monte Carlo simulated annealing approach followed by the elimination of sequences homologous to host genomes and commonly used biological parts. An orthogonal set is finally determined by using a network elimination algorithm. Design constraints can be defined using either a web-based graphical user interface (GUI) or uploading a file containing a set of text commands.

Validating a Coarse-Grained Potential Energy Function through Protein Loop Modelling.

Coarse-grained (CG) methods for sampling protein conformational space have the potential to increase computational efficiency by reducing the degrees of freedom. The gain in computational efficiency of CG methods often comes at the expense of non-protein like local conformational features. This could cause problems when transitioning to full atom models in a hierarchical framework. Here, a CG potential energy function was validated by applying it to the problem of loop prediction. A novel method to sample the conformational space of backbone atoms was benchmarked using a standard test set consisting of 351 distinct loops. This method used a sequence-independent CG potential energy function representing the protein using [Formula: see text]-carbon positions only and sampling conformations with a Monte Carlo simulated annealing based protocol. Backbone atoms were added using a method previously described and then gradient minimised in the Rosetta force field. Despite the CG potential energy function being sequence-independent, the method performed similarly to methods that explicitly use either fragments of known protein backbones with similar sequences or residue-specific [Formula: see text]/[Formula: see text]-maps to restrict the search space. The method was also able to predict with sub-Angstrom accuracy two out of seven loops from recently solved crystal structures of proteins with low sequence and structure similarity to previously deposited structures in the PDB. The ability to sample realistic loop conformations directly from a potential energy function enables the incorporation of additional geometric restraints and the use of more advanced sampling methods in a way that is not possible to do easily with fragment replacement methods and also enable multi-scale simulations for protein design and protein structure prediction. These restraints could be derived from experimental data or could be design restraints in the case of computational protein design. C++ source code is available for download from http://www.sbg.bio.ic.ac.uk/phyre2/PD2/.

Analytic markovian rates for generalized protein structure evolution.

A general understanding of the complex phenomenon of protein evolution requires the accurate description of the constraints that define the sub-space of proteins with mutations that do not appreciably reduce the fitness of the organism. Such constraints can have multiple origins, in this work we present a model for constrained evolutionary trajectories represented by a markovian process throughout a set of protein-like structures artificially constructed to be topological intermediates between the structure of two natural occurring proteins. The number and type of intermediate steps defines how constrained the total evolutionary process is. By using a coarse-grained representation for the protein structures, we derive an analytic formulation of the transition rates between each of the intermediate structures. The results indicate that compact structures with a high number of hydrogen bonds are more probable and have a higher likelihood to arise during evolution. Knowledge of the transition rates allows for the study of complex evolutionary pathways represented by trajectories through a set of intermediate structures.

A data-based assessment of alternative strategies for identification of potential human cancer hazards.

The two-year cancer bioassay in rodents remains the primary testing strategy for in-life screening of compounds that might pose a potential cancer hazard. Yet experimental evidence shows that cancer is often secondary to a biological precursor effect, the mode of action is sometimes not relevant to humans, and key events leading to cancer in rodents from nongenotoxic agents usually occur well before tumorigenesis and at the same or lower doses than those producing tumors. The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) hypothesized that the signals of importance for human cancer hazard identification can be detected in shorter-term studies. Using the National Toxicology Program (NTP) database, a retrospective analysis was conducted on sixteen chemicals with liver, lung, or kidney tumors in two-year rodent cancer bioassays, and for which short-term data were also available. For nongenotoxic compounds, results showed that cellular changes indicative of a tumorigenic endpoint can be identified for many, but not all, of the chemicals producing tumors in two-year studies after thirteen weeks utilizing conventional endpoints. Additional endpoints are needed to identify some signals not detected with routine evaluation. This effort defined critical questions that should be explored to improve the predictivity of human carcinogenic risk.