Real-world treatment patterns for palbociclib plus an aromatase inhibitor, or an aromatase inhibitor alone, for patients with metastatic breast cancer in the Flatiron Database.

There are limited real-world comparative effectiveness data for palbociclib plus an aromatase inhibitor (AI) as a first-line (1L) treatment examining endpoints that require long term follow-up and post 1L progression. The Flatiron Health Analytic Database was used to characterize treatment and dosing patterns in patients with hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) receiving palbociclib plus an AI vs an AI alone in routine US clinical practice. In addition, time to chemotherapy (TTC) and real-world progression-free survival (rwPFS) when combining 1L and second-line of therapy (rwPFS2) were assessed. Of 1324 patients who received palbociclib plus an AI between February 3, 2015 and March 31, 2020, 1110 (83.8%) started palbociclib at the recommended 125 mg/day dose. After stabilized inverse probability treatment-weighting (sIPTW), median TTC in patients treated with palbociclib plus an AI and AI alone was 37.4 months (95% confidence interval [CI], 33.7-40.7) and 29.2 months (95% CI, 26.8-33.5), respectively (hazard ratio [HR] = 0.77 [95% CI, 0.69-0.86], P < .0001); median rwPFS2 was 32.6 months (95% CI, 29.4-35.2) and 20.7 months (95% CI, 18.9-22.6), respectively (HR = 0.62 [95% CI, 0.54-0.70], P < .0001). Sensitivity analyses with propensity score matching showed similar results to sIPTW analyses. Results from this large real-world study examining additional effectiveness outcomes beyond 1L rwPFS and overall survival support the use of palbociclib plus an AI as a 1L treatment for patients with HR+/HER2- mBC.

Treatment outcomes in older patients with metastatic breast cancer receiving palbociclib plus an aromatase inhibitor: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This summary describes an article published in the medical journal Frontiers in Oncology in September 2023. The article reports results from a study that looked at breast cancer treatments for older patients aged 75 years or older. The study focused on a type of cancer called HR+/HER2- metastatic breast cancer. HR+/HER2- stands for hormone receptorpositive/human epidermal growth factor receptor 2-negative. This study evaluated whether older patients with this type of cancer benefited from the combination of two medicines - palbociclib and an aromatase inhibitor - compared with taking an aromatase inhibitor alone. HOW WAS THE STUDY IN THIS SUMMARY CARRIED OUT?: The Flatiron database contains medical records for people with cancer in the US. This study used deidentified health care information from this database. 'Deidentified' means that all information that could identify an individual was removed to protect individuals' privacy. People in this study received treatment in routine care and not in a clinical trial. WHAT DO THE RESULTS MEAN?: Older patients who took palbociclib plus an aromatase inhibitor lived longer than those who took an aromatase inhibitor alone. Older patients who took palbociclib plus an aromatase inhibitor also lived longer without their cancer getting worse and started chemotherapy later than those who took an aromatase inhibitor alone. These results support using palbociclib plus an aromatase inhibitor as the first treatment for patients aged 75 years or older with HR+/HER2- metastatic breast cancer.

This study evaluated outcomes in elderly patients with metastatic breast cancer treated in routine care. Overall, patients who took palbociclib plus an aromatase inhibitor (AI) lived longer, and lived longer without their cancer getting worse, than those who took an AI alone.

Prolonging the lives of African-Americans with metastatic breast cancer by adding palbociclib to an aromatase inhibitor in routine clinical practice: a plain language summary of a real-world database study.

WHAT IS THIS SUMMARY ABOUT?: This summary is about a study that was published in the medical journal The Oncologist in July 2023. The combination of palbociclib with an aromatase inhibitor (AI) was approved by the FDA in 2015 as a treatment for people with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC). However, the effectiveness of palbociclib in African-Americans with MBC is not well studied. The goal of this study was to find out whether adding palbociclib to an AI helped African-Americans with HR+/HER2- MBC live longer. WHAT ARE THE KEY TAKEAWAYS?: This study used de-identified medical information from the Flatiron Database. This database contains healthcare information on people with cancer treated by doctors in the United States but personal information is removed to maintain privacy. Medical information for people who received certain treatments in routine clinical practice or real-world setting was included in the study.This study showed that in the real-world setting, African-Americans with HR+/HER2- MBC lived longer when receiving palbociclib with an AI than with an AI alone. Also, the study showed that African-Americans treated with palbociclib plus an AI lived longer without their cancer getting worse than those treated with an AI alone. WHAT WAS THE MAIN CONCLUSION REPORTED BY THE RESEARCHERS?: These results support the use of palbociclib with an AI as a first treatment for African-Americans with HR+/HER2- MBC.Clinical Trial Registration: NCT05361655 (ClinicalTrials.gov).

Effectiveness of palbociclib plus an aromatase inhibitor in African Americans with metastatic breast cancer in routine clinical practice: a plain language summary.

Real-world comparative effectiveness of palbociclib plus aromatase inhibitor in HR+/HER2- metastatic breast cancer.

Aim: Provide real-world data on palbociclib as evidence of effectiveness in patient populations from routine clinical practice. Methods: This was a retrospective, observational cohort study of patients with HR+/HER2- metastatic breast cancer treated with palbociclib plus aromatase inhibitor (AI) or AI alone as first-line therapy within the US Oncology Network. Results: Patients treated with palbociclib plus AI (n = 838) versus AI alone (n = 450) had a numerically longer median overall survival (42.1 vs 35.7 months; hazard ratio [HR] = 0.90 [95% CI: 0.75-1.07]; p = 0.117) and a significantly extended real-world progression-free survival (21.0 vs 15.7 months; HR = 0.75 [95% CI: 0.64-0.88]; p = 0.0002) after normalized inverse probability treatment weighting. Conclusion: These real-world results support the use of palbociclib plus AI as first-line treatment in routine clinical practice for patients with HR+/HER2- metastatic breast cancer.

What is this summary about? This summary describes how well palbociclib works when used with an aromatase inhibitor in the real-world setting for people with a certain type of breast cancer that has spread to other areas of the body. Palbociclib stops cancer cells from growing and dividing. An aromatase inhibitor prevents the body from making the hormone estrogen, which is needed for certain types of breast cancer cells to grow. Palbociclib with an aromatase inhibitor is a standard first treatment used for people with this type of breast cancer that needs estrogen to grow and has spread to other areas of the body. In clinics, doctors may not always prescribe the two treatments together. The study wanted to find out if using the two treatments together worked better than using an aromatase inhibitor alone in the real-world setting. What were the results? The results suggest that in this population of patients treated in a real-world setting, people with breast cancer that needs estrogen to grow and has spread to other areas of the body who were treated with palbociclib plus an aromatase inhibitor lived longer without their cancer getting worse than those treated with an aromatase inhibitor alone. What do the results of the study mean? The results support the use of palbociclib with an aromatase inhibitor as a first treatment for breast cancer that has spread to other areas of the body, rather than an aromatase inhibitor only.

Developing an educational "hub": impact of a distance-learning curriculum in a multinational cohort.

PURPOSE: To address a gap in radiation oncology education in low- and middle-income countries (LMICs), we sought to evaluate the effectiveness and generalizability of a refined curriculum on intensity modulated radiotherapy (IMRT) offered to existing radiation therapy (RT) clinics across Africa and Latin America (LATAM) at no cost. METHODS: A curriculum was created based on prior needs assessments and adapted for participating medical physicists, radiation oncologists, radiation therapists, and trainees in LMICs. English-speaking and Spanish-speaking teams of volunteer educators delivered 27 hour-long sessions 1-2 times weekly for 4 months using video conferencing to African and LATAM cohorts, respectively. Pre- and post-course multiple-choice examinations were administered to LATAM participants, and pre- and post-course self-confidence (1-5 Likert-scale) and open-ended feedback were collected from all participants. RESULTS: Twenty-five centers across Africa (13) and LATAM (12) participated, yielding a total of 332 enrolled participants (128 African, 204 LATAM). Sessions were delivered with a mean of 44 (22.5) and 85 (25.4) participants in the African and LATAM programs, respectively. Paired pre and post-course data demonstrated significant (p < 0.001) improvement in knowledge from 47.9 to 89.6% and self-confidence across four domains including foundations (+ 1.1), commissioning (+ 1.3), contouring (+ 1.7), and treatment planning (+ 1.0). Attendance was a significant predictor of change in self-confidence in "high attendance" participants only, suggesting a threshold effect. Qualitative data demonstrates that participants look forward to applying their knowledge in the clinical setting. CONCLUSION: A specialized radiation oncology curriculum adapted for LMIC audiences was effective for both African and LATAM participants. Participant feedback suggests that the refined IMRT course empowered clinics with knowledge and confidence to help train others. This feasible "Hub and Spokes" approach in which a distance-learning course establishes a hub to be leveraged by spokes (learners) may be generalizable to others aiming to reduce global health care disparities through training efforts.

Real-World Effectiveness of Palbociclib Plus Aromatase Inhibitors in African American Patients With Metastatic Breast Cancer.

BACKGROUND: Disparities in survival and clinical outcomes between African American and White patients with breast cancer (BC) are well documented, but African American patients have not been well represented in randomized clinical trials of CDK4/6 inhibitors. Real-world studies can provide evidence for effective treatment strategies for underreported patient populations. PATIENTS AND METHODS: This retrospective analysis of African American patients with HR+/HER2- metastatic breast cancer (mBC) from the Flatiron Health longitudinal database evaluated treatments for patients with BC in routine clinical practice in the US. Patients initiated first-line therapy with palbociclib plus an aromatase inhibitor (AI) or AI alone between February 2015 and March 2020. Outcomes assessed included overall survival (OS) and real-world progression-free survival (rwPFS) until September 2020. RESULTS: Of 270 eligible patients, 127 (median age 64 years) were treated with palbociclib + AI, and 143 (median age 68 years) were treated with an AI. Median follow-up was 24.0 months for palbociclib + AI and 18.2 months for AI-treated patients. Median OS was not reached (NR; 95% CI, 38.2-NR) in the palbociclib + AI group versus 28.2 months (95% CI, 19.2-52.8) in the AI group (adjusted HR, 0.56; 95% CI, 0.36-0.89; P = .013). Median rwPFS was 18.0 months (95% CI, 12.4-26.7) in the palbociclib + AI group and 10.5 months (95% CI, 7.0-13.4) in the AI group (adjusted HR, 0.74; 95% CI, 0.47-1.17; P = .199). CONCLUSION: This comparative analysis of palbociclib + AI versus AI alone indicates that palbociclib combined with endocrine therapy in the first line is associated with improved effectiveness for African American patients with HR+/HER2- mBC in real-world settings. TRIAL NUMBER: NCT05361655.

Comparing a PD-L1 inhibitor plus chemotherapy to chemotherapy alone in neoadjuvant therapy for locally advanced ESCC: a randomized Phase II clinical trial : A randomized clinical trial of neoadjuvant therapy for ESCC.

BACKGROUND: A Phase II study was undertaken to evaluate the safety and efficacy of the neoadjuvant socazolimab, a novel PD-L1 inhibitor, in combination with nab-paclitaxel and cisplatin for locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Sixty-four patients were randomly divided between the Socazolimab + nab-paclitaxel + cisplatin (TP) arm (n = 32) and the control arm (n = 32), receiving either socazolimab (5 mg/kg intravenously (IV), day 1) or a placebo with nab-paclitaxel (125 mg/m2 IV, day 1/8) and cisplatin (75 mg/m2 IV, day 1) repeated every 21 days for four cycles before surgery. The primary endpoint was major pathological response (MPR), and the secondary endpoints were pathological complete response (pCR), R0 resection rate, event-free survival (EFS), overall survival (OS), and safety. RESULTS: A total of 29 (90.6%) patients in each arm underwent surgery, and 29 (100%) and 28 (98.6%) patients underwent R0 resection in the Socazolimab + TP and Placebo + TP arms, respectively. The MPR rates were 69.0 and 62.1% (95% Confidence Interval (CI): 49.1-84.0% vs. 42.4-78.7%, P = 0.509), and the pCR rates were 41.4 and 27.6% (95% CI: 24.1-60.9% vs. 13.5-47.5%, P = 0.311) in the Socazolimab + TP and Placebo + TP arms, respectively. Significantly higher incidence rates of ypT0 (37.9% vs. 3.5%; P = 0.001) and T downstaging were observed in the Socazolimab + TP arm than in the Placebo + TP arm. The EFS and OS outcomes were not mature. CONCLUSIONS: The neoadjuvant socazolimab combined with chemotherapy demonstrated promising MPR and pCR rates and significant T downstaging in locally advanced ESCC without increasing surgical complication rates. TRIAL REGISTRATION: Registration name (on clinicaltrials.gov): A Study of Anti-PD-L1 Antibody in Neoadjuvant Chemotherapy of Esophageal Squamous Cell Carcinoma. REGISTRATION NUMBER: NCT04460066.

Aging Alters the Aortic Proteome in Health and Thoracic Aortic Aneurysm.

BACKGROUND: Aging enhances most chronic diseases but its impact on human aortic tissue in health and in thoracic aortic aneurysms (TAA) remains unclear. METHODS: We employed a human aortic biorepository of healthy specimens (n=17) and those that underwent surgical repair for TAA (n=20). First, we performed proteomics comparing aortas of healthy donors to aneurysmal specimens, in young (ie, <60 years of age) and old (ie, ≥60 years of age) subjects. Second, we measured proteins, via immunoblotting, involved in mitophagy (ie, Parkin) and also mitochondrial-induced inflammatory pathways, specifically TLR (toll-like receptor) 9, STING (stimulator of interferon genes), and IFN (interferon)-ß. RESULTS: Proteomics revealed that aging transformed the aorta both quantitatively and qualitatively from health to TAA. Whereas young aortas exhibited an enrichment of immunologic processes, older aortas exhibited an enrichment of metabolic processes. Immunoblotting revealed that the expression of Parkin directly correlated to subject age in health but inversely to subject age in TAA. In TAA, but not in health, phosphorylation of STING and the expression of IFN-ß was impacted by aging regardless of whether subjects had bicuspid or tricuspid valves. In subjects with bicuspid valves and TAAs, TLR9 expression positively correlated with subject age. Interestingly, whereas phosphorylation of STING was inversely correlated with subject age, IFN-ß positively correlated with subject age. CONCLUSIONS: Aging transforms the human aortic proteome from health to TAA, leading to a differential regulation of biological processes. Our results suggest that the development of therapies to mitigate vascular diseases including TAA may need to be modified depending on subject age.

Prolonging the life of people with metastatic breast cancer in routine clinical practice by adding palbociclib to an aromatase inhibitor from a real-world database analysis: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of an article about a study called "P-REALITY X" that was published in the medical journal npj Breast Cancer in October 2022. "P-REALITY X" stands for Palbociclib REAl-world first-LIne comparaTive effectiveness studY eXtended. This study used information from a database to look at whether adding a second treatment (palbociclib) to an aromatase inhibitor (AI) helped people with a certain type of breast cancer to live longer. The type of breast cancer is metastatic hormone receptor-positive/human epidermal growth factor-negative breast cancer, also called HR-positive (or HR+)/HER2-negative (or HER2-) breast cancer. The study used information from the Flatiron Database. This database contains unidentified health care information collected from people seen by doctors in the USA. Only data from people who did not participate in a clinical trial were used. When people are treated outside of a clinical trial, this is called the real-world setting, or routine clinical practice. In clinical trials, people lived longer without their disease worsening if they were treated with palbociclib plus an AI versus being treated with an AI only. Based on the results of clinical trials, treatment with palbociclib plus an AI is already approved and recommended for people with HR+/HER2- breast cancer. This study looked at whether people lived longer if they were treated with palbociclib plus an AI versus being treated with an AI only in routine clinical practice as well. WHAT WERE THE RESULTS?: This study showed that, in routine clinical practice, people treated with the medicine palbociclib plus an AI lived longer than people treated with only an AI. WHAT DO THE RESULTS MEAN?: These results support the continued use of palbociclib plus an AI as the standard first medicine to be given to people with metastatic HR+/HER2- breast cancer. Clinical Trial Registration: NCT05361655 (ClinicalTrials.gov).

Evolving practice in global healthcare: Remote physics support for low- and middle-income countries.

The COVID-19 pandemic has disrupted traditional onsite support for radiotherapy clinics in low- and middle-income countries (LMIC). Clinics there have struggled to commission new techniques and receive onsite training for their staff. We sought to evaluate whether an offsite approach could fill this gap at a clinic in Jordan by requesting a clinical audit and attempting to commission volumetric modulated arc therapy (VMAT). Over 13 months, a consultant provided remote support for a radiotherapy center that had already obtained treatment equipment and licenses. The consultant began by conducting a virtual audit, using a remote login to the center's R&V and TPS, to identify any gaps in the clinical workflow. Suggestions for improving the clinical workflow were proposed, and change implementation was tracked through emails, social media apps, and video conferencing. An extensive table outlined the commissioning process, including all measurements to be done. Social media apps and shared documents were used to track measurements and analysis. The lack of person-to-person interaction in this new remote-support ecosystem created conflicts; we have highlighted some of these, as well as their resolution and the lessons learned from them. The virtual audit identified gaps categorized as machine QA, treatment plan review, and treatment delivery processes. Following the implementation of the proposals, motion management was added, and machine QA became more comprehensive. VMAT was commissioned using the reports of the AAPM and the IAEA. The main challenges for remote support were time difference, establishing an appropriate form and frequency of communication, tone of voice used in messages, and buy-in from local staff. This evolving practice will enable medical physicists to use modern, multimodal remote communication pathways to effectively transfer knowledge to centers in LMICs. The audit-proposal-improvement pathway for remote support can be incorporated to help others while avoiding the pitfalls we faced.

Dichlorodiphenyltrichloroethane for Malaria and Agricultural Uses and Its Impacts on Human Health.

Pesticides are widely used in agriculture and disease control, and dichlorodiphenyltrichloroethane (DDT) is one of the most used pesticides in human history. Besides its significant contributions in pest control in agriculture, DDT was credited as having saved millions of human lives for controlling malaria and other deadly insect-transmitted diseases. Even today, the use of DDT in some countries for malaria control cannot be replaced without endangering people who live there. The recent COVID-19 pandemic has changed our lives and reminded us of the challenges in dealing with infectious diseases, especially deadly ones including malaria. However, DDT and its metabolites are stable, persist long, are found in almost every corner of the world, and their persistent effects on humans, animals, and the environment must be seriously considered. This review will focus on the history of DDT use for agriculture and malaria control, the pathways for the spread of DDT, benefits and risks of DDT use, DDT exposure to animals, humans, and the environment, and the associated human health risks. These knowledge and findings of DDT will benefit the selection and management of pesticides worldwide.

Case Series: Cariprazine for treatment of methamphetamine use disorder.

BACKGROUND AND OBJECTIVES: Methamphetamine use is a major source of morbidity and mortality but has no reliably effective interventions. We identified cariprazine as an option for treatment of methamphetamine use disorder (MUD) and present two cases. METHODS: Two patients with MUD and psychotic disorders were treated with cariprazine. Abstinence and cravings were assessed using urine drug screens and the Brief Substance Craving Scale, respectively. RESULTS: Both patients reported global functional improvement, reduction in methamphetamine cravings and use with cariprazine, confirmed with negative urine drug screens. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Cariprazine's unique pharmacodynamic profile conveys potential efficacy for MUD. It would be a novel treatment that targets multiple psychiatric symptoms seen in MUD.

Temporal associations between emergency department and telehealth volumes during the COVID-19 pandemic: A time-series analysis from 2 academic medical centers.

BACKGROUND: The COVID-19 pandemic compelled healthcare systems to rapidly adapt to changing healthcare needs as well as identify ways to reduce COVID transmission. The relationship between pandemic-related trends in emergency department (ED) visits and telehealth urgent care visits have not been studied. METHODS: We performed an interrupted time series analysis to evaluate trends between ED visits and telehealth urgent medical care visits at two urban healthcare system in Colorado. We performed pairwise comparisons between baseline versus each COVID-19 surge and all three surges combined, for both ED and telehealth encounters at each site and used Wilcoxon rank sum test to compare median values. RESULTS: During the study period, 595,350 patient encounters occurred. We saw ED visits decline in correlation with rising telehealth visits during each COVID surge. CONCLUSIONS: During initial COVID surges, ED visits declined while telehealth visits rose in inverse correlation with falling ED visits, suggesting that some patients shifted their preferred location for clinical care. As EDs cope with future staffing during the ongoing COVID pandemic, telehealth represents an opportunity for emergency physicians and a means to align patients desires for virtual care with ED volumes and staffing.

Finite Mixture Models, a Flexible Alternative to Standard Modeling Techniques for Extrapolated Mean Survival Times Needed for Cost-Effectiveness Analyses.

OBJECTIVES: To compare finite mixture models with common survival models with respect to how well they fit heterogenous data used to estimate mean survival times required for cost-effectiveness analysis. METHODS: Publicly available overall survival (OS) and progression-free survival (PFS) curves were digitized to produce nonproprietary data. Regression models based on the following distributions were fit to the data: Weibull, lognormal, log-logistic, generalized F, generalized gamma, Gompertz, mixture of 2 Weibulls, and mixture of 3 Weibulls. A second set of analyses was performed based on data in which patients who had not experienced an event by 30 months were censored. Model performance was compared based on the Akaike information criterion (AIC). RESULTS: For PFS, the 3-Weibull mixture (AIC = 479.94) and 2-Weibull mixture (AIC = 488.24) models outperformed other models by more than 40 points and produced the most accurate estimates of mean survival times. For OS, the AIC values for all models were similar (all within 4 points). The means for the mixture 3-Weibulls mixture model (17.60 months) and the 2-Weibull mixture model (17.59 months) were the closest to the Kaplan-Meier mean estimate of (17.58 months). The results and conclusions from the censored analysis of PFS were similar to the uncensored PFS analysis. On the basis of extrapolated mean OS, all models produced estimates within 10% of the Kaplan-Meier mean survival time. CONCLUSIONS: Finite mixture models offer a flexible modeling approach that has benefits over standard parametric models when analyzing heterogenous data for estimating survival times needed for cost-effectiveness analysis.

Elevated bone morphogenic protein 4 expression implicated in site-specific adipogenesis in thyroid associated orbitopathy.

Periorbital adipose tissue expansion is a key pathological change in thyroid associated orbitopathy (TAO). Bone morphogenic protein 4 (BMP4) is instrumental in adipogenesis. We compared site-specific BMP4 expression and its effect on adipogenesis using donor-matched adipose tissue-derived stromal cells (ADSC) from TAO patients. In this study, ADSC were generated from periorbital (eyelid, orbital) and subcutaneous (abdominal) adipose tissue. BMP4 expression was characterized by RT-PCR and immunofluorescent staining and compared among ADSC from the three anatomic depots. Effects on adipogenesis after knocking down endogenous BMP4 were quantified by adipogenic markers PPARγ and perilipin. Exogenous BMP4 protein was added after BMP4 knockdown to study the role of BMP4 in adipogenesis. Our results showed that BMP4 staining in periorbital adipose tissue was stronger than those in subcutaneous. BMP4 mRNA expression was higher in eyelid (4.4-2489.4-fold) and orbital (6.9-1811-fold) than that of subcutaneous ADSC, whereas expression fell during induced adipogenesis. After BMP4 knockdown, both adipogenic markers PPARγ (eyelid: 1.7-fold, p = 0.038; orbital: 1.4-fold, p = 0.126) and perilipin (eyelid:1.7-fold, p = 0.001; orbital:2.6-fold, p = 0.066) increased in periorbital ADSC upon induction. These increased expression fell after adding exogenous BMP4 protein. Our findings demonstrated higher BMP4 expression was found in periorbital ADSC and adipose tissue compared to donor-matched subcutaneous counterparts, which fell during adipogenic induction. Knocking down BMP4 expression further enhanced adipogenesis in periorbital ADSC. This effect was reversed by adding exogenous BMP4 protein. We suggested a novel role of BMP4 in modulating site-specific adipogenesis in TAO patients.

Characterising 'bounce-back' readmissions after radical cystectomy.

OBJECTIVE: To examine predictors of early readmissions after radical cystectomy (RC). Factors associated with preventable readmissions may be most evident in readmissions that occur within 3 days of discharge, commonly termed 'bounce-back' readmissions, and identifying such factors may inform efforts to reduce surgical readmissions. PATIENTS AND METHODS: We utilised the Healthcare Cost and Utilization Project's State Inpatient Databases to examine 1867 patients undergoing RC in 2009 and 2010, and identified all patients readmitted within 30 days of discharge. We assessed differences between patients experiencing bounce-back readmission compared to those readmitted 8-30 days after discharge using logistic regression models and also calculated abbreviated LACE scores to assess the utility of common readmissions risk stratification algorithms. RESULTS: The 30-day and bounce-back readmission rates were 28.4% and 5.6%, respectively. Although no patient or index hospitalisation characteristics were significantly associated with bounce-back readmissions in adjusted analyses, bounce-back patients did have higher rates of gastrointestinal (14.3% vs 6.7%, P = 0.02) and wound (9.5% vs 3.0%, P < 0.01) diagnoses, as well as increased index and readmission length of stay (5 vs 4 days, P = 0.01). Overall, the median abbreviated LACE score was 7, which fell into the moderate readmission risk category, and no difference was observed between readmitted and non-readmitted patients. CONCLUSION: One in five readmissions after RC occurs within 3 days of initial discharge, probably due to factors present at discharge. However, sociodemographic and clinical factors, as well as traditional readmission risk tools were not predictive of this bounce-back. Effective strategies to reduce bounce-back readmission must identify actionable clinical factors prior to discharge.

Role of Post-Acute Care on Hospital Readmission After High-Risk Surgery.

BACKGROUND: Payment models, including the Hospital Readmissions Reduction Program and bundled payments, place pressures on hospitals to limit readmissions. Against this backdrop, we sought to investigate the association of post-acute care after major surgery and readmission rates. METHODS: We identified patients undergoing high-risk surgery (abdominal aortic aneurysm repair, coronary bypass grafting, aortic valve replacement, carotid endarterectomy, esophagectomy, pancreatectomy, lung resection, and cystectomy) from 2005 to 2010 using the Healthcare Cost and Utilization Project's State Inpatient Database. The primary outcome was readmission rates after major surgery. Secondary outcome was readmission length of stay. RESULTS: We identified 135,523 patients of whom 56,720 (42%) received post-acute care. Patients receiving post-acute care had higher readmission rates than those who were discharged home (16% versus 10%, respectively; P < 0.001). The risk-adjusted readmission length of stay was greatest for patients who received care from a skilled nursing facility, followed by those who received home care, and lowest for those who did not receive post-acute care (7.1 versus 5.4 versus 4.8 d, respectively; P < 0.001). CONCLUSIONS: The use of post-acute care was associated with higher readmission rates and higher readmission lengths of stay. Improving the support of patients in post-acute care settings may help reduce readmissions and readmission intensity.

Uterine Artery Embolization following Cesarean Delivery but prior to Hysterectomy in the Management of Patients with Invasive Placenta.

PURPOSE: To evaluate outcomes of patients with placenta accreta spectrum (PAS) disorders who underwent uterine artery embolization (UAE) following cesarean delivery but before hysterectomy. MATERIALS AND METHODS: A retrospective review of patients with PAS treated with cesarean-hysterectomy (C-hyst) was performed. Patients in the UAE group underwent UAE after cesarean delivery but before hysterectomy; patients in the control group underwent C-hyst alone. Estimated blood loss (EBL), transfusion requirements, length of intensive care unit (ICU) stay, and adverse events were evaluated. RESULTS: The study included 31 patients, 7 in the UAE group and 24 in the control group. Median EBL, transfusion requirements, and length of ICU stay in the UAE group compared with control group were 1,500 mL (range, 500-2,000 mL) vs 2,000 mL (range, 1,000-4,500 mL) (P = .04), 150 mL (range, 0-650 mL) vs 550 mL (range, 0-3,125 mL) (P = .10), and 0 d (range, 0-1 d) vs 0.5 d (range, 0-2 d) (P = .07). All patients in the UAE group had placenta increta; patients in the control group had placenta accreta (29%), increta (54%), and percreta (17%) (P = .10). Subgroup analysis of patients with placenta increta demonstrated that the UAE group had a significant decrease in median EBL (P = .004), transfusion requirements (P = .009), and length of ICU stay (P = .04). No adverse events following UAE were noted. CONCLUSIONS: UAE following cesarean delivery but before hysterectomy in patients with placenta increta appears to be safe and effective in decreasing EBL, transfusion requirements, and length of ICU stay compared with C-hyst alone.

RNA polymerase II senses obstruction in the DNA minor groove via a conserved sensor motif.

RNA polymerase II (pol II) encounters numerous barriers during transcription elongation, including DNA strand breaks, DNA lesions, and nucleosomes. Pyrrole-imidazole (Py-Im) polyamides bind to the minor groove of DNA with programmable sequence specificity and high affinity. Previous studies suggest that Py-Im polyamides can prevent transcription factor binding, as well as interfere with pol II transcription elongation. However, the mechanism of pol II inhibition by Py-Im polyamides is unclear. Here we investigate the mechanism of how these minor-groove binders affect pol II transcription elongation. In the presence of site-specifically bound Py-Im polyamides, we find that the pol II elongation complex becomes arrested immediately upstream of the targeted DNA sequence, and is not rescued by transcription factor IIS, which is in contrast to pol II blockage by a nucleosome barrier. Further analysis reveals that two conserved pol II residues in the Switch 1 region contribute to pol II stalling. Our study suggests this motif in pol II can sense the structural changes of the DNA minor groove and can be considered a "minor groove sensor." Prolonged interference of transcription elongation by sequence-specific minor groove binders may present opportunities to target transcription addiction for cancer therapy.

Predictors and Cost of Readmission in Total Knee Arthroplasty.

BACKGROUND: The Comprehensive Care for Joint Replacement bundle was created to decrease total knee arthroplasty (TKA) cost. To help accomplish this, there is a focus on reducing TKA readmissions. However, there is a lack of national representative sample of all-payer hospital admissions to direct strategy, identify risk factors for readmission, and understand actual readmission cost. METHODS: We used the Nationwide Readmission Database to examine national readmission rates, predictors of readmission, and associated readmission costs for elective TKA procedures. We fit a multivariable logistic regression model to examine factors associated with readmission. Then, we determined mean readmission costs and calculated the readmission cost when distributed across the entire TKA population. RESULTS: We identified 224,465 patients having TKA across all states participating in the Nationwide Readmission Database. The mean unadjusted 30-day TKA readmission rate was 4%. The greatest predictors of readmission were congestive heart failure (odds ratio [OR] 2.51, 95% confidence interval [CI] 2.62-2.80), renal disease (OR 2.19, 95% CI 2.03-2.37), and length of stay greater than 4 days (OR 2.4, 95% CI 2.25-2.61). The overall median cost for each readmission was $6753 ± 175. Extrapolating the readmission cost for the entire TKA population resulted in the readmission cost being 2% of the overall 30-day procedure cost. CONCLUSIONS: A major focus of the Comprehensive Care for Joint Replacement bundle is improving cost and quality by limiting readmission rates. TKA readmissions are low and comprise a small percentage of total TKA cost, suggesting that they may not be the optimal measure of quality care or a significant driver of overall cost.