Outcomes and care quality metrics for people living with rheumatic heart disease and atrial fibrillation in Uganda.

Background: Atrial fibrillation (AF) is a common complication of rheumatic heart disease (RHD) and is challenging to treat in lower-resourced settings in which RHD remains endemic. Objective: We characterized demographics, treatment outcomes, and factors leading to care retention for participants with RHD and AF in Uganda. Methods: We conducted a retrospective analysis of the Uganda national RHD registry between June 2009 and May 2018. Participants with AF or atrial flutter were included. Demographics, survival, and care metrics were compared with participants without AF. Multivariable logistic regression was used to identify factors associated with retention in care among participants with AF. Results: A total of 1530 participants with RHD were analyzed and 293 (19%) had AF. The median age was 24 (interquartile range 14-38) years. Mortality was similar in both groups (adjusted hazard ratio 1.183, P = .77) over a median follow-up of 203 (interquartile range 98-275) days. A total of 79% of AF participants were prescribed anticoagulation, and 43% were aware of their target international normalized ratio. Retention in care was higher in participants with AF (18% vs 12%, P < .01). Factors associated with decreased retention in care include New York Heart Association functional class III/IV (adjusted odds ratio [OR] 0.48, 95% confidence interval [CI] 0.30-0.76) and distance to nearest health center (adjusted OR 0.94, 95% CI 0.90-0.99). Anticoagulation prescription was associated with enhanced care retention (adjusted OR 1.86, 95% CI 1.24-2.79). Conclusion: Participants with RHD and AF in Uganda do not experience higher mortality than those without AF. Anticoagulation prescription rates are high. Although retention in care is poor among RHD participants, those with concurrent AF are more likely to be retained.

Clinical Impact of Routine Assessment of Patient-Reported Health Status in Heart Failure Clinic: The PRO-HF Trial.

BACKGROUND: The impact of routine clinic use of patient-reported outcome (PRO) measures on clinical outcomes in patients with heart failure (HF) has not been well-characterized. We tested if clinic-based use of a disease-specific PRO improves patient-reported quality of life at 1 year. METHODS: The PRO-HF trial (Patient-Reported Outcome Measurement in Heart Failure Clinic) was an open-label, parallel, patient-level randomized clinical trial of routine PRO assessment or usual care at an academic HF clinic between August 30, 2021, and June 30, 2022, with 1 year of follow-up. In the PRO assessment arm, participants completed the Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) at each HF clinic visit, and results were shared with their treating clinician. The usual care arm completed the KCCQ-12 at randomization and 1 year later, which was not shared with the treating clinician. The primary outcome was the KCCQ-12 overall summary score (OSS) between 12 and 15 months after randomization. Secondary outcomes included domains of the KCCQ-12, hospitalization and emergency department visit rates, HF medication therapy, clinic visit frequency, and testing rates. RESULTS: Across 17 clinicians, 1248 participants were enrolled and randomized to PRO assessment (n=624) or usual care (n=624). The median age was 63.9 years (interquartile range [IQR], 51.8-72.8), 38.9% were women, and the median baseline KCCQ-12 OSS was 82.3 (IQR, 58.3-94.8). Final KCCQ-12 (available in 87.9% of the PRO arm and 85.1% in usual care; P=0.16) median OSS were 87.5 (IQR, 68.8-96.9) in the PRO arm and 87.6 (IQR, 69.7-96.9) in the usual care arm with a baseline-adjusted mean difference of 0.2 ([95% CI, -1.7 to 2.0]; P=0.85). The results were consistent across prespecified subgroups. A post hoc analysis demonstrated a significant interaction with greater benefit among participants with a baseline KCCQ-12 OSS of 60 to 80 but not in less or more symptomatic participants. No significant differences were found in 1-year mortality, hospitalizations, emergency department visits, medication therapy, clinic follow-up, or testing rates between arms. CONCLUSIONS: Routine PRO assessment in HF clinic visits did not impact patient-reported quality of life or other clinical outcomes. Alternate strategies and settings for embedding PROs into routine clinical care should be tested. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04164004.

Characteristics of contemporary atrial fibrillation clinical trials and their association with industry sponsorship.

BACKGROUND: Industry sponsorship is an important source of funding for atrial fibrillation (AF) clinical trials, the implications of which have not been analyzed. OBJECTIVE: The purpose of this study was to determine the characteristics of contemporary AF clinical trials and to evaluate their association with funding source. METHODS: We systematically assessed all completed AF trials registered in the ClinicalTrials.gov database between conception to October 31, 2023, and extracted publicly available information including funding source, trial size, demographic distribution, intervention, location, and publication status. Trial characteristics were compared using the Wilcoxon rank-sum test and Fisher exact test for continuous and categorical variables, respectively. RESULTS: Of the 253 clinical trials assessed, 171 (68%) reported industry funding. Industry funding was associated with a greater median number of patients enrolled (172 vs 80; P <.001), publication rate (56.7% vs 42.7%; P = .04), probability of being product-focused (48.0% vs 24.4%; P <.001), and multicontinental recruitment location (25.2% vs 2.4%; P <.001) when compared to nonindustry-funded trials. However, industry funding was not associated with a significant difference in median impact factor (7.7 vs 7.7; P = .723). The overall proportion of industry-funded trials did not change over time (P = 1). CONCLUSION: Industry-funded clinical trials in AF often are larger, more frequently published, multicontinental, and product-focused. Industry funding was found to be associated with significant differences in study enrollment and publication metrics.

Opportunities to Increase Science of Diversity and Inclusion in Clinical Trials: Equity and a Lack of a Control.

The United States witnessed a nearly 4-fold increase in personal health care expenditures between 1980 and 2010. Despite innovations and obvious benefits to health, participants enrolled in clinical trials still do not accurately represent the racial and ethnic composition of patients nationally or globally. This lack of diversity in cohorts limits the generalizability and significance of results among all populations and has deep repercussions for patient equity. To advance diversity in clinical trials, robust evidence for the most effective strategies for recruitment of diverse participants is needed. A major limitation of previous literature on clinical trial diversity is the lack of control or comparator groups for different strategies. To date, interventions have focused primarily on (1) community-based interventions, (2) institutional practices, and (3) digital health systems. This review article outlines prior intervention strategies across these 3 categories and considers health policy and ethical incentives for substantiation before US Food and Drug Administration approval. There are no current studies that comprehensively compare these interventions against one another. The American Heart Association Strategically Focused Research Network on the Science of Diversity in Clinical Trials represents a multicenter, collaborative network between Stanford School of Medicine and Morehouse School of Medicine created to understand the barriers to diversity in clinical trials by contemporaneous head-to-head interventional strategies accessing digital, institutional, and community-based recruitment strategies to produce informed recruitment strategies targeted to improve underrepresented patient representation in clinical trials.

Impact of Patient-Reported Outcome Measurement in Heart Failure Clinic on Clinician Health Status Assessment and Patient Experience: A Substudy of the PRO-HF Trial.

BACKGROUND: Clinicians typically estimate heart failure health status using the New York Heart Association Class, which is often discordant with patient-reported health status. It is unknown whether collecting patient-reported health status improves the accuracy of clinician assessments. METHODS: The PRO-HF trial (Patient-Reported Outcomes in Heart Failure Clinic) is a randomized, nonblinded trial evaluating routine Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) collection in heart failure clinic. Patients with a scheduled visit to Stanford heart failure clinic between August 30, 2021 and June 30, 2022 were enrolled and randomized to KCCQ-12 assessment or usual care. In this prespecified substudy, we evaluated whether access to the KCCQ-12 improved the accuracy of clinicians' New York Heart Association assessment or patients' perspectives on their clinician interaction. We surveyed clinicians regarding their patients' New York Heart Association Class, quality of life, and symptom frequency. Clinician responses were compared with patients' KCCQ-12 responses. We surveyed patients regarding their clinician interactions. RESULTS: Of the 1248 enrolled patients, 1051 (84.2%) attended a visit during the substudy. KCCQ-12 results were given to the clinicians treating the 528 patients in the KCCQ-12 arm; the 523 patients in the usual care arm completed the KCCQ-12 without the results being shared. The correlation between New York Heart Association Class and KCCQ-12 Overall Summary Score was stronger when clinicians had access to the KCCQ-12 (r=-0.73 versus r=-0.61, P<0.001). More patients in the KCCQ-12 arm strongly agreed that their clinician understood their symptoms (95.2% versus 89.7% of respondents [odds ratio' 2.27; 95% CI' 1.32-3.87]). However, patients in both arms reported similar quality of clinician communication and therapeutic alliance. CONCLUSIONS: Collecting the KCCQ-12 in heart failure clinic improved clinicians' accuracy of health status assessment; correspondingly, patients believed their clinicians better understood their symptoms. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04164004.

Disparities in Geographic Access to Cardiac Rehabilitation in Los Angeles County.

Background Exercise-based cardiac rehabilitation (CR) is known to reduce morbidity and mortality for patients with cardiac conditions. Sociodemographic disparities in accessing CR persist and could be related to the distance between where patients live and where CR facilities are located. Our objective is to determine the association between sociodemographic characteristics and geographic proximity to CR facilities. Methods and Results We identified actively operating CR facilities across Los Angeles County and used multivariable Poisson regression to examine the association between sociodemographic characteristics of residential proximity to the nearest CR facility. We also calculated the proportion of residents per area lacking geographic proximity to CR facilities across sociodemographic characteristics, from which we calculated prevalence ratios. We found that racial and ethnic minorities, compared with non-Hispanic White individuals, more frequently live ≥5 miles from a CR facility. The greatest geographic disparity was seen for non-Hispanic Black individuals, with a 2.73 (95% CI, 2.66-2.79) prevalence ratio of living at least 5 miles from a CR facility. Notably, the municipal region with the largest proportion of census tracts comprising mostly non-White residents (those identifying as Hispanic or a race other than White), with median annual household income <$60 000, contained no CR facilities despite ranking among the county's highest in population density. Conclusions Racial, ethnic, and socioeconomic characteristics are significantly associated with lack of geographic proximity to a CR facility. Interventions targeting geographic as well as nongeographic factors may be needed to reduce disparities in access to exercise-based CR programs. Such interventions could increase the potential of CR to benefit patients at high risk for developing adverse cardiovascular outcomes.

Seasonal COVID-19 surge related hospital volumes and case fatality rates.

BACKGROUND: Seasonal and regional surges in COVID-19 have imposed substantial strain on healthcare systems. Whereas sharp inclines in hospital volume were accompanied by overt increases in case fatality rates during the very early phases of the pandemic, the relative impact during later phases of the pandemic are less clear. We sought to characterize how the 2020 winter surge in COVID-19 volumes impacted case fatality in an adequately-resourced health system. METHODS: We performed a retrospective cohort study of all adult diagnosed with COVID-19 in a large academic healthcare system between August 25, 2020 to May 8, 2021, using multivariable logistic regression to examine case fatality rates across 3 sequential time periods around the 2020 winter surge: pre-surge, surge, and post-surge. Subgroup analyses of patients admitted to the hospital and those receiving ICU-level care were also performed. Additionally, we used multivariable logistic regression to examine risk factors for mortality during the surge period. RESULTS: We studied 7388 patients (aged 52.8 ± 19.6 years, 48% male) who received outpatient or inpatient care for COVID-19 during the study period. Patients treated during surge (N = 6372) compared to the pre-surge (N = 536) period had 2.64 greater odds (95% CI 1.46-5.27) of mortality after adjusting for sociodemographic and clinical factors. Adjusted mortality risk returned to pre-surge levels during the post-surge period. Notably, first-encounter patient-level measures of illness severity appeared higher during surge compared to non-surge periods. CONCLUSIONS: We observed excess mortality risk during a recent winter COVID-19 surge that was not explained by conventional risk factors or easily measurable variables, although recovered rapidly in the setting of targeted facility resources. These findings point to how complex interrelations of population- and patient-level pandemic factors can profoundly augment health system strain and drive dynamic, if short-lived, changes in outcomes.

Outcome measures in total hip arthroplasty: have our metrics changed over 15 years?

INTRODUCTION: Consensus has not been reached regarding ideal outcome measures for total hip arthroplasty (THA) clinical evaluation and research. The goal of this review was to analyze the trends in outcome metrics within the THA literature and to discuss the potential impact of instrument heterogeneity on clinical practice. MATERIALS AND METHODS: A PubMed search of all manuscripts related to THA from January 2005 to December 2019 was performed. Statistical and linear regression analyses were performed for individual outcome metrics as a proportion of total THA publications over time. RESULTS: There was a statistically significant increase in studies utilizing outcomes metrics between 2005 and 2019 (15.1-29.5%; P < 0.001; R2 = 98.1%). Within the joint-specific subcategory, use of the Harris Hip Score (HHS) significantly decreased from 2005 to 2019 (82.8-57.3%; P < 0.001), use of the Hip Disability and Osteoarthritis Outcome Score (HOOS) significantly increased (0-6.7%; P < 0.001), and the modified HHS significantly increased (0-10.5%; P < 0.001). In the quality of life subcategory, EQ-5D demonstrated a significant increase in usage (0-34.8%; P < 0.001), while Short Form-36 significantly decreased (100% vs. 27.3%; P = 0.008). CONCLUSIONS: The utilization of outcome-reporting metrics in THA has continued to increase, resulting in added complexity within the literature. The utilization rates of individual instruments have shifted over the past 15 years. Additional study is required to determine which specific instruments are recommended.

Symptomology following mRNA vaccination against SARS-CoV-2.

Despite demonstrated efficacy of vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19), widespread hesitancy to vaccination persists. Improved knowledge regarding frequency, severity, and duration of vaccine-associated symptoms may help reduce hesitancy. In this prospective observational study, we studied 1032 healthcare workers who received both doses of the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine and completed post-vaccine symptom surveys both after dose 1 and after dose 2. We defined appreciable post-vaccine symptoms as those of at least moderate severity and lasting at least 2 days. We found that symptoms were more frequent following the second vaccine dose than the first (74% vs. 60%, P < 0.001), with >80% of all symptoms resolving within 2 days. The most common symptom was injection site pain, followed by fatigue and malaise. Overall, 20% of participants experienced appreciable symptoms after dose 1 and 30% after dose 2. In multivariable analyses, female sex was associated with greater odds of appreciable symptoms after both dose 1 (OR, 95% CI 1.73, 1.19-2.51) and dose 2 (1.76, 1.28-2.42). Prior COVID-19 was also associated with appreciable symptoms following dose 1, while younger age and history of hypertension were associated with appreciable symptoms after dose 2. We conclude that most post-vaccine symptoms are reportedly mild and last <2 days. Appreciable post-vaccine symptoms are associated with female sex, prior COVID-19, younger age, and hypertension. This information can aid clinicians in advising patients on the safety and expected symptomatology associated with vaccination.

Resident Involvement in Posterior Lumbar Interbody Fusion is Associated With Increased Readmissions and Operative Time, But No Increased Short-term Risks.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: The aim was to compare rates of adverse events and additional posterior lumbar interbody fusion (PLIF) cases assisted by residents versus cases performed solely by an orthopedic attending. SUMMARY OF BACKGROUND DATA: PLIF is a widely accepted surgical technique for the management of a variety of spinal conditions requiring spinal stabilization and fusion. However, no published studies have assessed the effects of resident involvement on intraoperative and postoperative outcomes in PLIF. METHODS: This retrospective study utilized the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) registry from 2007 to 2012 to identify patients who underwent PLIF procedures. A propensity score matching model was utilized to reduce patient cohort variances. The perioperative data and outcomes in the matched population were analyzed using paired t test and the McNemar test in order to assess, based on resident presence, the rates of postoperative adverse events, readmission, reoperation within 30 days, and operative time. RESULTS: In total, 1633 patients undergoing PLIF were included in the study, with 24.62% involving resident participation. The propensity score matching algorithm yielded 396 well-matched resident and nonresident pairs. Patients undergoing PLIF involving a resident were associated with a higher rate of readmission (1.77% vs. 0.00%; P=0.008), and longer operative time (245.7 vs. 197.7 min; P<0.001). However, these procedures were not associated with any significant difference in minor or severe adverse events. CONCLUSIONS: Resident involvement in PLIF was associated with an increased rate of readmissions, and operative time; however, was not associated with an increase in minor or severe adverse events. Further investigation is needed to characterize the role of resident involvement based on level of training experience, as well as methods to improve the learning curve to independence while reducing postoperative hospital length of stay. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Characterization of Clinical Symptoms by Race Among Women With Early-Stage, Hormone Receptor-Positive Breast Cancer Before Starting Chemotherapy.

Importance: Race disparities persist in breast cancer mortality rates. One factor associated with these disparities may be differences in symptom burden, which may reduce chemotherapy tolerance and increase early treatment discontinuation. Objectives: To compare symptom burden by race among women with early-stage breast cancer before starting chemotherapy and quantify symptom differences explained by baseline characteristics. Design, Setting, and Participants: A cross-sectional analysis of symptom burden differences by race among Black and White women with a diagnosis of stage I to III, hormone receptor-positive breast cancer who had a symptom report collected before chemotherapy initiation in a large cancer center in the southern region of the US from January 1, 2007, through December 31, 2015. Analyses were conducted from November 1, 2019, to March 31, 2021. Blinder-Oaxaca decomposition was used, adjusting for baseline sociodemographic and clinical characteristics. Main Outcomes and Measures: Four symptom composite scores with a mean (SD) of 50 (10) were reported before starting chemotherapy (baseline) and were derived from symptom items: general physical symptoms (11 items), treatment adverse effects (8 items), acute distress (4 items), and despair (7 items). Patients rated the severity of each symptom they experienced in the past week on a scale of 0 to 10 (where 0 indicates not a problem and 10 indicates as bad as possible). Results: A total of 1338 women (mean [SD] age, 54.6 [11.6] years; 420 Black women [31.4%] and 918 White women [68.6%]) were included in the study. Before starting chemotherapy, Black women reported a statistically significantly higher (ie, worse) symptom composite score than White women for adverse effects (44.5 vs 43.8) but a lower acute distress score (48.5 vs 51.0). Decomposition analyses showed that Black patients' characteristics were associated with higher symptom burden across all 4 scores. However, these differences were offset by relatively greater, statistically significant, unexplained physical, distress, and despair symptom reporting by White patients. Conclusions and Relevance: In this study, before starting chemotherapy, Black patients with early-stage breast cancer reported significantly higher burden for symptoms that may be exacerbated with chemotherapy and lower distress symptoms compared with White patients. Future studies should explore how symptoms change before and after treatment and differ by racial/ethnic groups and how they are associated with treatment adherence and mortality disparities.

Contemporary Outpatient Arthroplasty Is Safe Compared with Inpatient Surgery: A Propensity Score-Matched Analysis of 574,375 Procedures.

BACKGROUND: Outpatient joint arthroplasty is a potential modality for increased case throughput and is rising in demand. However, we are aware of no study that has compared outcomes between risk-matched outpatient and inpatient procedures within the last 7 years. The aims of this study were to compare matched patient cohorts who underwent outpatient or inpatient joint arthroplasty in terms of 30-day adverse events and readmission rates. METHODS: From the National Surgical Quality Improvement Program database, we identified patients who underwent primary total hip arthroplasty (THA), primary total knee arthroplasty (TKA), and primary unicompartmental knee arthroplasty (UKA) from 2009 to 2018. Using 10 perioperative variables, patients who underwent an outpatient procedure were 1:4 propensity score-matched with patients who underwent an inpatient procedure. The rates of 30-day adverse events and readmission were compared using the McNemar test. The risk factors for adverse events and readmissions were identified using multivariate regression. RESULTS: Of 574,375 patients identified, 21,506 (3.74%) underwent an outpatient procedure. After propensity score matching, an outpatient joint arthroplasty was associated with a lower rate of adverse events (3.18% compared with 7.45%; p < 0.001). When assessed individually, outpatient TKA (3.15% compared with 8.11%; p < 0.001), THA (4.94% compared with 10.05%; p < 0.001), and UKA (1.78% compared with 3.39%; p < 0.001) were all associated with fewer adverse events overall and there was no difference in the rate of 30-day readmission, when compared with inpatient analogs. Outpatient joint arthroplasty was an independent factor for lower adverse events (odds ratio [OR], 0.407 [95% confidence interval (CI), 0.369 to 0.449]; p < 0.001), with no increase in the risk of readmission (OR, 1.004 [95% CI, 0.878 to 1.148]; p = 0.951). CONCLUSIONS: Contemporary outpatient joint arthroplasty demonstrated lower rates of adverse events with no increased rate of 30-day readmission when compared with risk-matched inpatient counterparts. Although multiple factors should guide the decision for the site of care, outpatient arthroplasty may be a safe alternative to inpatient arthroplasty. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

How Are We Measuring Cost-Effectiveness in Total Joint Arthroplasty Studies? Systematic Review of the Literature.

BACKGROUND: As volumes of total hip arthroplasty (THA) and total knee arthroplasty (TKA) continue to rise, it is important to understand their economic impact. No systematic review on cost-effectiveness of THA/TKA has been performed since 2016 despite recent changes in the healthcare environment. The purpose of the study is to provide a contemporary analysis of the cost-effectiveness of total joint arthroplasty and the use of quality-adjusted life years (QALYs). METHODS: A systematic review was performed from 2005 to 2020. Online databases (OVID Medline, PubMed, Cost-Effectiveness Analysis Registry, Google Scholar, Elton B. Stephens Co) were queried to identify economic analyses that evaluated the cost-effectiveness of THA/TKA. RESULTS: In total, 38 studies met the screening criteria. Study designs were primarily Markov models (68%), cohort studies (16%), and randomized trials (8%). Most studies adopted either a societal perspective (45%) or a health system perspective (39%). Analysis revealed that THA/TKA was strongly cost-effective compared to nonsurgical treatment. THA/TKA procedures that were not delayed were more cost-effective than delayed intervention. The majority of studies used QALYs as the primary quality metric (82%); in all these studies there was a significant improvement in QALYs gained. CONCLUSION: Given the high economic impact of arthroplasty, ongoing assessment of cost-effectiveness is needed. Twenty-four percent of studies included in this systematic review were published in the last 4 years of this 15-year study period, highlighting the need for continuous assessment of aggregate data. Future studies should incorporate the cost-effectiveness of THA and TKA with respect to the work-value provided by surgeon providers to support health policy and reimbursement.

Evolving Outcome Measures in Total Knee Arthroplasty: Trends and Utilization Rates Over the Past 15 Years.

BACKGROUND: Patient-reported outcome metrics and reporting are important for demonstrating value associated with total knee arthroplasty (TKA). This review studied the patient-reported outcome utilization trends as reported within the TKA literature over a 15-year period. METHODS: A PubMed search of all manuscripts related to TKA from January 2005 to December 2019 was performed. Descriptive statistics were used for individual outcome metrics as proportions of total article publications focusing on TKA outcomes. Linear regressions analysis was performed to demonstrate significant changes in utilization rates over time. RESULTS: There was a significant overall increase in studies utilizing outcome metrics between 2005 and 2019 (16.1%-45.0%; P < .001; R2 = 98.7%). Within joint-specific metrics (2005-2019), use of Knee Disability and Osteoarthritis Outcome score increased (0%-14.8%; P < .001); while use of Knee Society Knee Scoring System decreased (55.2%-35.4%; P = .007). Of the studies reporting general health, use of the Forgotten Joint Score-12 decreased (100%-66.7% from 2014 to 2019; P = .006), and Patient-Reported Outcome Measurement Information System Global-10 increased (0%-21.4% from 2005 to 2019; P < .001). In the quality of life subcategory (2005-2019), EuroQol 5-Dimension Health Outcome Survey increased in usage (14.3%-28.0%; P < .001), while Short Form-36 use decreased (85.7%-36.6%; P < .001). CONCLUSION: Although utilization of outcome metrics has significantly increased over the last 15 years in the TKA literature, there still exists considerable heterogeneity of outcome metrics. This lack of consensus may impede comparisons of studies for clinical and research purposes, as well as hinder cross-walk of outcome tools over time. Further study is needed to identify ideal global and joint-specific tools, while balancing issues like ease of use and utility in specific populations such as the young and highly active.

IRE1α RNase-dependent lipid homeostasis promotes survival in Myc-transformed cancers.

Myc activation is a primary oncogenic event in many human cancers; however, these transcription factors are difficult to inhibit pharmacologically, suggesting that Myc-dependent downstream effectors may be more tractable therapeutic targets. Here, we show that Myc overexpression induces endoplasmic reticulum (ER) stress and engages the inositol-requiring enzyme 1α (IRE1α)/X-box binding protein 1 (XBP1) pathway through multiple molecular mechanisms in a variety of c-Myc- and N-Myc-dependent cancers. In particular, Myc-overexpressing cells require IRE1α/XBP1 signaling for sustained growth and survival in vitro and in vivo, dependent on elevated stearoyl-CoA-desaturase 1 (SCD1) activity. Pharmacological and genetic XBP1 inhibition induces Myc-dependent apoptosis, which is alleviated by exogenous unsaturated fatty acids. Of note, SCD1 inhibition phenocopies IRE1α RNase activity suppression in vivo. Furthermore, IRE1α inhibition enhances the cytotoxic effects of standard chemotherapy drugs used to treat c-Myc-overexpressing Burkitt's lymphoma, suggesting that inhibiting the IRE1α/XBP1 pathway is a useful general strategy for treatment of Myc-driven cancers.

Post-acute care disparities in total joint arthroplasty.

BACKGROUND: Understanding the socioeconomic factors that influence hospitalization and post-discharge metrics after joint replacement is important for identifying key areas of improvement in the delivery of orthopaedic care. METHODS: An institutional administrative data set of 2869 patients from an academic arthroplasty referral center was analyzed to quantify the relationship between socioeconomic factors and post-acute rehabilitation care received, length of stay, and cost of care. The study used International Classification of Disease, ninth edition coding in order to identify cohorts of patients who received joint arthroplasty of the knee and hip between January 2007 and May 2015. RESULTS: The study found that females (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.74-2.46), minorities (OR, 2.11; 95% CI, 1.78-2.51), and non-private insurance holders (OR, 1.56; 95% CI, 1.26-1.94) were more likely to be assigned to institutional care after discharge. The study also found that minorities (OR, 1.45; 95% CI, 1.24-1.70) and non-private insurance holders (OR, 1.43; 95% CI, 1.16-1.77) are more likely to exhibit longer length of stay. Mean charges were higher for males when compared to females ($80,010 vs $74,855; P < .001), as well as total costs ($19,910 vs $18,613; P = .001). CONCLUSIONS: Socioeconomic factors such as gender, race, and insurance status should be further explored with respect to healthcare policies seeking to influence quality of care and health outcomes.