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In EGFR-mutated lung cancer, the duration of response to tyrosine kinase inhibitors (TKIs) is limited by the development of acquired drug resistance. Despite the crucial role played by apoptosis-related genes in tumor cell survival, how their expression changes as resistance to EGFR-TKIs emerges remains unclear. Here, we conduct a comprehensive analysis of apoptosis-related genes, including BCL-2 and IAP family members, using single-cell RNA sequence (scRNA-seq) and spatial transcriptomics (ST). scRNA-seq of EGFR-mutated lung cancer cell lines captures changes in apoptosis-related gene expression following EGFR-TKI treatment, most notably BCL2L1 upregulation. scRNA-seq of EGFR-mutated lung cancer patient samples also reveals high BCL2L1 expression, specifically in tumor cells, while MCL1 expression is lower in tumors compared to non-tumor cells. ST analysis of specimens from transgenic mice with EGFR-driven lung cancer indicates spatial heterogeneity of tumors and corroborates scRNA-seq findings. Genetic ablation and pharmacological inhibition of BCL2L1/BCL-XL overcome or delay EGFR-TKI resistance. Overall, our findings indicate that BCL2L1/BCL-XL expression is important for tumor cell survival as EGFR-TKI resistance emerges.
Subject(s)
Apoptosis , ErbB Receptors , Lung Neoplasms , Mutation , Single-Cell Analysis , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Lung Neoplasms/drug therapy , ErbB Receptors/metabolism , ErbB Receptors/genetics , Humans , Apoptosis/genetics , Apoptosis/drug effects , Animals , Mice , Mutation/genetics , Gene Expression Regulation, Neoplastic , Cell Line, Tumor , RNA-Seq , Transcriptome/genetics , Drug Resistance, Neoplasm/genetics , Protein Kinase Inhibitors/pharmacology , Mice, Transgenic , Gene Expression Profiling , bcl-X Protein/metabolism , bcl-X Protein/genetics , Single-Cell Gene Expression AnalysisABSTRACT
Hospital CEO salaries have grown quickly over the past two decades. We investigate correlates of rising nonprofit hospital CEO pay between 2012 and 2019 by merging compensation data from Candid's IRS 990 forms with hospital data from the National Academy for State Health Policy Hospital Cost Tool. Almost half of the measured increase in CEO compensation (44.5%) accrued to a "base case" CEO, who was leading a non-teaching hospital system or independent hospital with fewer than 100 beds that earned 0 profits and provided no charity care. Another 28.5% of the measured salary increase resulted from changes in the generosity with which observable metrics were rewarded, particularly the reward for heading a system with 500 or more beds. The remaining 27% resulted mostly from hospital systems or single hospitals that increased their profits or bed size over time. The increase in CEO compensation associated with leading larger healthcare systems and earning greater profits may explain the increase in healthcare system consolidation which has occurred over the last several years.
Subject(s)
Chief Executive Officers, Hospital , Salaries and Fringe Benefits , Salaries and Fringe Benefits/statistics & numerical data , Chief Executive Officers, Hospital/economics , Humans , Hospitals, Voluntary/economics , Organizations, Nonprofit/economics , United StatesABSTRACT
Over the past 25 years, the gap between the increase in health insurance costs and workers' wages has significantly expanded. This trend has led to significant concerns about healthcare affordability, with surveys revealing conflicting opinions regarding whether hospitals or health insurance companies bear the blame for escalating costs. To better understand these dynamics, we examined consumer price indices for health insurance, hospital services, and professional services from 2006 to 2023 using Bureau of Labor Statistics data. Our analysis shows that the hospital price index rose steadily between 2006 and 2023, faster than insurance premiums or professional services. To examine whether differences in underlying costs are driving higher hospital price increases, we evaluated the profit margins of hospitals and health insurance companies using the National Academy for State Health Policy''s Hospital Cost Tool and National Association of Insurance Commissioners Industry Reports. Our findings reveal that hospitals (for-profit and nonprofit) have consistently maintained higher profit margins than insurance companies. As health insurance costs continue to weigh heavily on working Americans, our analysis suggests that high hospital prices drive insurance premiums.
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OBJECTIVE: To measure key characteristics of the Veterans Health Administration's (VHA) Community Care (CC) referral network for screening colonoscopy and identify market and institutional factors associated with network size. DATA SOURCES: VHA electronic health records, CC claim data, and National Plan and Provider Enumeration System. STUDY DESIGN: In this retrospective cross-sectional study, we measure the size of the VHA's CC referral networks over time and by VHA parent facility (n = 137). We used a multivariable linear regression to identify factors associated with network size at the market-year level. Network size was measured as the number of physicians who performed at least one VHA-purchased screening colonoscopy per 1000 enrollees at baseline. DATA EXTRACTION: Data were extracted for all Veterans (n = 102,119) who underwent a screening colonoscopy purchased by the VHA from a non-VHA physician from 2018 to 2021. PRINCIPAL FINDINGS: From 2018 to 2021, median network volume of screening colonoscopies per 1000 enrollees grew from 1.6 (IQR: 0.6, 4.6) to 3.6 (IQR: 1.6, 6.6). The median network size grew from 0.63 (IQR: 0.30, 1.26) to 0.92 (IQR: 0.57, 1.63). Finally, the median procedures per physician increased from 2.5 (IQR: 1.6, 4.2) to 3.2 (IQR: 2.4, 4.7). After adjusting for baseline market characteristics, volume of screening colonoscopies was positively related to network size (ß = 0.15, 95% CI: [0.10, 0.20]), negatively related to procedures per physician (ß = -0.12, 95% CI: [-0.18, -0.05]), and positively associated with the percent of rural enrollees (ß = 0.01, 95% CI: [0.00, 0.01]). CONCLUSIONS: VHA facilities with a higher volume of VHA-purchased screening colonoscopies and more rural enrollees had more non-VHA physicians providing care. Geographic variation in referral networks may also explain differences in the effects of the MISSION Act on access to care and patient outcomes.
Subject(s)
Veterans Health , Veterans , United States , Humans , United States Department of Veterans Affairs , Retrospective Studies , Cross-Sectional Studies , ColonoscopyABSTRACT
PURPOSE: Understanding rural-urban disparities in patient satisfaction is critical to identify gaps for improvement in patient-centered care and tailor interventions to specific patient needs, especially those in the Frontier and Remote areas (FAR). This study aimed to examine disparities in patient perceptions of care between urban, rural non-FAR, and FAR hospitals between 2014 and 2019. METHODS: This is a retrospective longitudinal study using 2014-2019 Hospital Consumer Assessment of Healthcare Providers and Systems data linked to American Hospital Annual Survey data (3,524 hospitals in 2014 and 3,440 hospitals in 2019). Multivariable linear regression models were used to identify differential trends in patient perceptions of care by hospital rurality over 2014-2019, adjusting hospital- and county-level characteristics. FINDINGS: In 2014, patients at rural non-FAR and FAR hospitals had lower percentages of willingness to definitely recommend these hospitals than urban hospitals (average percentage difference, 95% CI: -4.0% [-4.5%, -3.5%]; -2.0% [-2.8%, -1.2%]); yet, over the study period, rural hospitals experienced steeper increases in patient willingness to recommend (0.2% [0.07%, 0.4%]; 0.4% [0.08%, 0.7%]). FAR hospitals also showed improvements in patient experience in a clean environment, communication with nurses, communication about medicines, and responsiveness of staff. Communication with doctors showed slight decreases across hospital locations. CONCLUSIONS: Patient perceptions of care were generally improved in all US hospitals from 2014 to 2019, except communications with doctors. These findings highlight the potential for enhancing patient satisfaction and experience in urban hospitals and suggest the need to improve patient willingness to recommend in rural FAR hospitals.
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Importance: US hospitals are required to publicly post their prices for specified shoppable services online. However, the extent to which a hospital's prices posted online correlate with the prices they give to a telephone caller is unknown. Objective: To compare hospitals' online cash prices for vaginal childbirth and brain magnetic resonance imaging (MRI) with prices offered to secret shopper callers requesting price estimates by telephone. Design, Setting, and Participants: This cross-sectional study included cash online prices from each hospital's website for vaginal childbirth and brain MRI collected from representative US hospitals between August and October 2022. Thereafter, again between August and October 2022, simulated secret shopper patients called each hospital requesting their lowest cash price for these procedures. Main Outcomes and Measures: We calculated the difference between each hospital's online and phone prices for vaginal childbirth and brain MRI, and the Pearson correlation coefficient (r) between the online and phone prices for each procedure, among hospitals able to provide both prices. Results: A total of 60 representative US hospitals (20 top-ranked, 20 safety-net, and 20 non-top-ranked, non-safety-net hospitals) were included in the analysis. For vaginal childbirth, 63% (12 of 19) of top-ranked hospitals, 30% (6 of 20) of safety-net hospitals, and 21% (4 of 19) of non-top-ranked, non-safety-net hospitals provided both online and telephone prices. For brain MRI, 85% (17 of 20) of top-ranked hospitals, 50% (10 of 20) of safety-net hospitals, and 100% (20 of 20) of non-top-ranked, non-safety-net hospitals provided prices both online and via telephone. Online prices and telephone prices for both procedures varied widely. For example, online prices for vaginal childbirth posted by top-ranked hospitals ranged from $0 to $55â¯221 (mean, $23â¯040), from $4361 to $14â¯377 (mean $10â¯925) for safety-net hospitals, and from $1183 to $30â¯299 (mean $15â¯861) for non-top-ranked, non-safety-net hospitals. Among the 22 hospitals providing prices both online and by telephone for vaginal childbirth, prices were within 25% of each other for 45% (10) of hospitals, while 41% (9) of hospitals had differences of 50% or more (Pearson r = 0.118). Among the 47 hospitals providing both online and phone prices for brain MRI, prices were within 25% of each other for 66% (31) of hospitals), while 26% (n = 12) had differences of 50% or more (Pearson r = -0.169). Among hospitals that provided prices both online and via telephone, there was a complete match between the online and telephone prices for vaginal childbirth in 14% (3 of 22) of hospitals and for brain MRI in 19% (9 of 47) of hospitals. Conclusions and Relevance: Findings of this cross-sectional study suggest that there was poor correlation between hospitals' self-posted online prices and prices they offered by telephone to secret shoppers. These results demonstrate hospitals' continued problems in knowing and communicating their prices for specific services. The findings also highlight the continued challenges for uninsured patients and others who attempt to comparison shop for health care.
Subject(s)
Hospitals , Telephone , Female , Humans , Cross-Sectional StudiesABSTRACT
Recent studies document a substantial increase in emergency department (ED) spending in the past decade, even though the number of ED visits per capita has remained relatively stable. Price increases and upcoding are sometimes cited as possible explanations, but their relative impacts are not known. We analyzed Blue Cross Blue Shield claims for patients of all ages who received care in EDs in five states in 2012 and 2019. We used estimates from spending regressions and regressions explaining coding intensity to decompose changes in spending between 2012 and 2019 into components attributable to price increases, changes in patient characteristics or treatment intensity, and upcoding. Prices accounted for at least half of the increase in ED spending per visit for four of the five states we examined. Increases in spending attributable to upcoding were notable but generally not as large. Future research should explore the associations between local market conditions, such as consolidation and ownership type, and both price increases and upcoding.
Subject(s)
Emergency Service, Hospital , Ownership , Humans , United StatesABSTRACT
Rationale and Objective: Recent initiatives aim to improve patient satisfaction and autonomy by increasing the use of peritoneal dialysis (PD) in the United States. However, limited knowledge is available about the costs of different dialysis modalities, particularly those incurred by private insurers. In this study, we compared the costs of injectable dialysis drugs (and their oral equivalents) paid by insurers between privately insured patients receiving hemodialysis and PD. Study Design: A retrospective cohort study. Setting and Participants: From a private insurance claims database, we identified patients who started receiving PD or in-center hemodialysis between January 1, 2017, and December 31, 2020. Exposure: Patients started receiving PD. Outcomes: Average annual injectable drug and aggregate expenditures and expenditure subcategories. Analytical Approach: Patients who started receiving PD were propensity matched to similar patients who started receiving hemodialysis based on the year of dialysis initiation, patient demographics, health, geography, and comorbidities. Cost ratios (CRs) were estimated from generalized linear models. Results: We matched 284 privately insured patients who started receiving PD 1:1 with patients started receiving in-center hemodialysis. The average annual injectable drug expenditures for hemodialysis were 2-fold higher (CR: 1.99; 95% CI, 1.62-2.44) than that for PD. Compared those receiving PD, patients receiving hemodialysis incurred significantly lower nondrug dialysis-related expenditures (0.85; 95% CI, 0.76-0.94). The average annual expenditures for non-dialysis-dependent outpatient services were significantly higher among patients who underwent in-center hemodialysis (CR: 1.44; 95% CI, 1.10-1.90). Although aggregate and inpatient hospitalization expenditures were higher for in-center hemodialysis, these differences did not reach statistical significance. Limitations: Small sample sizes may have restricted our ability to identify differences in some cost categories. Conclusions: Compared with privately insured patients who started receiving PD, patients starting in-center hemodialysis incurred higher expenditures for injectable dialysis drugs, whereas differences in other expenditure categories varied. Recent increases in the use of PD may lead to reductions in injectable dialysis drug costs among privately insured patients. Plain Language Summary: Recent initiatives aim to improve patient satisfaction and autonomy by increasing the use of peritoneal dialysis (PD) in the United States. However, limited knowledge is available about the costs of different dialysis modalities, particularly those incurred by private insurers. In this study, we compared the costs of injectable dialysis drugs (and their oral equivalents) provided by insurers between privately insured patients receiving hemodialysis and PD. We found that the average annual injectable drug expenditures for hemodialysis were 2.0-fold higher compared with those for PD. These findings suggest that the recent increase in the use of PD may lead to reductions in injectable dialysis drug costs among privately insured patients.
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Using the National Academy of State Health Policy Hospital Cost Tool, we compared changes in hospital profits with changes in hospitals' charity care and cash reserves between 2012 and 2019. We estimated substantial growth in nonprofit hospital operating profits and cash reserves in this period but no corresponding increase in charity care.
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Charities , Hospitals, Voluntary , Humans , United States , Hospitals, Private , Hospital Costs , Health Policy , Organizations, NonprofitABSTRACT
Background: Pharmacists and allied health researchers need to ensure that their practice is supported by current, evidence-based information. Critical appraisal tools have been developed to aid in this process. Objectives: To analyze the current landscape of critical appraisal tools and to create an aid for pharmacists and other allied health researchers to use in comparing various tools and choosing the best one for each particular study design. Data Sources: A literature search of the PubMed, University of Toronto Libraries, and Cochrane Library databases was conducted in December 2021, to generate an up-to-date list of critical appraisal tools. The tools were then summarized in a descriptive table. Study Selection and Data Extraction: Review articles, original manuscripts, and tool webpages were examined to develop a comparison chart based on the user-friendliness, efficiency, comprehensiveness, and reliability of each tool. Results: Fourteen tools were found through the literature search. These tools were compared using the findings of included review articles, and a comparison chart was created to aid pharmacists and allied health researchers in selecting the appropriate tool for their practice. Conclusions: There are many standardized critical appraisal tools that can help in assessing the quality of evidence, and the summary list of tools developed and reported here can help health care researchers to compare among them and choose the best one. No tools were found that have been specifically adapted to serve the needs of pharmacists when assessing scientific articles. Future research should examine how existing critical appraisal tools can better identify common data elements that are essential to evidence-based decision-making in pharmacy practice.
Contexte: Les pharmaciens et les chercheurs en soins de la santé doivent faire en sorte que leur pratique soit étayée par des informations actualisées et fondées sur des données probantes. Des outils d'évaluation critique ont été développés pour faciliter ce processus. Objectifs: Analyser le paysage actuel des outils d'évaluation critique et créer une aide que les pharmaciens et les autres chercheurs paramédicaux peuvent utiliser pour comparer divers outils et choisir le meilleur pour chaque conception d'étude particulière. Sources des données: Une recherche documentaire dans trois bases de données (PubMed, les University of Toronto Libraries et la Cochrane Library) a été menée en décembre 2021 afin de générer une liste actualisée d'outils d'évaluation critique qui ont ensuite été résumés dans un tableau descriptif. Sélection des études et extraction des données: Des articles de synthèse, des manuscrits originaux et des pages Internet d'outils ont été examinés pour dresser un tableau comparatif basé sur la convivialité, l'efficacité, l'exhaustivité et la fiabilité de chaque outil. Résultats: Quatorze outils ont été trouvés grâce à la recherche documentaire. Ils ont été comparés à l'aide des résultats des articles de synthèse inclus, et un tableau comparatif a été créé pour aider les pharmaciens et les chercheurs en soins de la santé à sélectionner l'outil approprié pour leur pratique. Conclusions: De nombreux outils d'évaluation critique normalisés peuvent aider à évaluer la qualité des données probantes, et la liste récapitulative des outils développés et rapportés ici peut aider les chercheurs en soins de santé à les comparer et à choisir le meilleur. Aucun outil spécifiquement adapté pour répondre aux besoins des pharmaciens lors de l'évaluation d'articles scientifiques n'a été trouvé. Les recherches futures devraient se pencher sur la manière dont les outils d'évaluation critique existants peuvent mieux identifier les éléments de données communs qui sont essentiels à la prise de décision fondée sur des données probantes dans la pratique de la pharmacie.
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Ponte osteotomy is an increasingly popular technique for multiplanar correction of adolescent idiopathic scoliosis. Prior cadaveric studies have suggested that sequential posterior spinal releases increase spinal flexibility. Here we introduce a novel technique involving a sequential approach to the Ponte osteotomy that minimizes spinal canal exposure. One fresh-frozen adult human cadaveric thoracic spine specimen with 4 cm of ribs was divided into three sections (T1-T5, T6-T9, T10-L1) and mounted for biomechanical testing. Each segment was loaded with five Newton meters under four conditions: baseline inferior facetectomy with supra/interspinous ligament release, superior articular process (SAP) osteotomy in situ, spinous process (SP) osteotomy in situ, and complete posterior column osteotomy with SP/SAP excision and ligamentum flavum release (PCO). Compared to baseline, in situ SAP osteotomy alone provided 3.5%, 7.6%, and 7.2% increase in flexion/extension, lateral bending, and axial rotation, respectively. In situ SP osteotomy increased flexion/extension, lateral bending, and axial rotation by 15%, 18%, and 10.3%, respectively. PCO increased flexion/extension, lateral bending, and axial rotation by 19.6%, 28.3%, and 12.2%, respectively. Our report introduces a novel approach where incremental increases in range of motion can be achieved with minimal spinal canal exposure and demonstrates feasibility in a cadaveric model.
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BACKGROUND: Observations that peritoneal dialysis (PD) may be an effective, lower-cost alternative to hemodialysis for the treatment of ESKD have led to policies encouraging PD and subsequent increases in its use in the United States. METHODS: In a retrospective cohort analysis of Medicare beneficiaries who started dialysis between 2008 and 2015, we ascertained average annual expenditures (for up to 3 years after initiation of dialysis) for patients ≥67 years receiving in-center hemodialysis or PD. We also determined whether differences in Medicare expenditures across dialysis modalities persisted as more patients were placed on PD. We used propensity scores to match 8305 patients initiating PD with 8305 similar patients initiating hemodialysis. RESULTS: Overall average expenditures were US$108,656 (2017) for hemodialysis and US$91,716 for PD (proportionate difference, 1.11; 95% confidence interval [CI], 1.09 to 1.13). This difference did not change over time (P for time interaction term=0.14). Hemodialysis had higher estimated intravenous (iv) dialysis drug costs (1.69; 95% CI, 1.64 to 1.73), rehabilitation expenditures (1.35; 95% CI, 1.26 to 1.45), and other nondialysis expenditures (1.34; 95% CI, 1.30 to 1.37). Over time, initial differences in total dialysis expenditures disappeared and differences in iv dialysis drug utilization narrowed as nondialysis expenditures diverged. Estimated iv drug costs declined by US$2900 per patient-year in hemodialysis between 2008 and 2014 versus US$900 per patient-year in PD. CONCLUSIONS: From the perspective of the Medicare program, savings associated with PD in patients ≥67 years have remained unchanged, despite rapid growth in the use of this dialysis modality. Total dialysis expenditures for the two modalities converged over time, whereas nondialysis expenditures diverged.
Subject(s)
Kidney Failure, Chronic , Peritoneal Dialysis , Humans , Aged , United States , Medicare , Health Expenditures , Kidney Failure, Chronic/therapy , Retrospective Studies , Renal DialysisABSTRACT
Although private equity acquisition of short-term acute care hospitals purportedly improves efficiency and cost-effectiveness, financial performance after acquisition remains unexamined. We compared changes in the financial performance of 176 hospitals acquired during 2005-14 versus changes in matched control hospitals. Acquisition was associated with a $432 decrease in cost per adjusted discharge and a 1.78-percentage-point increase in operating margin. The majority of acquisitions-134 members of the Hospital Corporation of America, acquired in 2006-were associated with a $559 decrease in cost per adjusted discharge but no change in operating margin. Conversely, non-HCA hospitals exhibited a 3.27-percentage-point increase in operating margin without a concomitant change in cost per adjusted discharge. When we examined markers of hospital capacity, operational efficiency, and costs, we found that private equity acquisition was associated with decreases in total beds, ratio of outpatient to inpatient charges, and staffing (total personnel and nursing full-time equivalents and total full-time equivalents per occupied bed). Therefore, financial performance improved after acquisition, whereas patient throughput and inpatient utilization increased and staffing metrics decreased. Future research is needed to identify any unintended trade-offs with safety and quality.
Subject(s)
Hospitals , Humans , WorkforceABSTRACT
We present a case of pericardial amyloidosis with associated lymphoplasmacytic lymphoma in a patient with chronic worsening shortness of breath and cough. This case highlights the wide variation in the presentation of cardiac amyloidosis, and the rare occurrence of clinically significant light-chain and heavy-chain amyloidosis in the pericardium. (Level of Difficulty: Advanced.).
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PURPOSE: Retrospective case series evaluating the efficacy and safety of implanting XtraFocus™ pinhole device in pseudophakic patients with irregular corneal astigmatism with concurrent or standalone iris defect. METHODS: Electronic case records were searched for: uncorrected distance visual acuities (UDVA) and corrected distance visual acuities (CDVA), automatic or manifest refraction and spherical equivalent (SE). All main outcomes were evaluated preoperatively and postoperatively at 1, 3, 6, 9 and 12 months, along with patients' satisfactory outcome and complications. RESULTS: Eleven pseudophakic eyes of 11 patients with a mean age of 54 (range 27-81) years were included. Median UDVA improved significantly from logMAR 0.7 (range 0.1-1.22) pre-operatively to 0.4 (range 0-1.3) at 1-month (p = 0.002); median CDVA remained unchanged at logMAR 0.4 (range 0-0.1) pre-operatively and 0.4 (range 0-0.8) at 1-month (p = 0.36). There were no significant statistical differences in both UDVA and CDVA between the post-operative periods. Ten patients (90.9%) had initial UDVA improvement at 1-month post op. Eight (72.7%) patients expressed satisfaction with improved vision or reduction of glare/halos. Three (27.3%) patients had unsatisfactory visual outcome resulting in 2 requested for implant explantation due to worsening of glare and distressing floaters. CONCLUSIONS: XtraFocus™ is effective in improving vision or reducing glare in pseudophakic patients with irregular corneal astigmatism or intragenic iris trauma, with over 70% expressed satisfactory outcome. Disturbing floaters and glare preclude its use in some resulting in implant explantation.
Subject(s)
Astigmatism , Corneal Diseases , Eye Injuries , Adult , Aged , Aged, 80 and over , Astigmatism/etiology , Astigmatism/surgery , Corneal Diseases/surgery , Eye Injuries/surgery , Eye, Artificial/adverse effects , Humans , Iris/surgery , Lens Implantation, Intraocular/methods , Middle Aged , Refraction, Ocular , Retrospective Studies , Treatment OutcomeABSTRACT
Private equity firms have increased their participation in the US health care system, raising questions about incentive alignment and downstream effects on patients. However, there is a lack of systematic characterization of private equity acquisition of short-term acute care hospitals. We present an overview of the scope of private equity-backed hospital acquisitions over the course of 2003-17, comparing the financial and operational differences between those hospitals and hospitals that remained unacquired through 2017. A total of 42 private equity deals occurred, involving 282 unique hospitals across 36 states. In unadjusted analyses, hospitals that were acquired had larger bed sizes, more discharges, and more full-time-equivalent staff positions in 2003 relative to nonacquired hospitals; private equity-acquired hospitals also had higher charge-to-cost ratios and higher operating margins, and this gap widened during our study period. These findings motivate evaluations by policy makers and researchers on the impact, if any, of private equity acquisition on health care access, spending, and risk-adjusted outcomes.