Estimation of Tax Benefit of US Nonprofit Hospitals.

Importance: Nonprofit hospitals are under increasing scrutiny to justify the generous tax benefit they receive due to their tax-exempt status. Quantifying the value of the tax benefit they receive at the federal, state, and local levels is critical for designing informed public health policies and ensuring nonprofit hospitals' taxpayer accountability. Objective: To estimate the financial benefit that nonprofit hospitals derive from their tax-exempt status and assess how the benefit is distributed across state and local communities. Design, Setting, and Participants: Using methodologies and measures consistent with current tax law and practice and data from 2021 Medicare Cost Reports, this study calculated the total financial benefit from nonprofit hospitals' tax-exempt status for all US nonprofit hospitals with the required Cost Reports data. Main Outcomes and Measures: Nonprofit hospitals' total tax benefit, which equals the sum of federal and state income tax, sales tax, property tax, the fair market value of charitable contributions from donors, savings from tax exemptions on issued bonds, and federal unemployment tax. Results: A total of 2927 US nonprofit hospitals received a $37.4 billion total tax benefit in 2021 from federal income tax ($11.5 billion; 31%), sales tax ($9.1 billion; 24%), property tax ($7.8 billion; 21%), state income tax ($3.7 billion; 10%), charitable contributions ($3.2 billion; 8%), bond financing ($2.1 billion; 6%), and federal unemployment tax ($200 million; <1%). Tax benefit varied substantially across states, from $25 098 (Delaware) to $159 464 (Massachusetts) per hospital bed and from $19 (Alabama) to $275 (Massachusetts) per capita. Tax benefit was highly concentrated, with 7% (n = 212) of hospitals accounting for half of the total amount. Conclusion and Relevance: This study highlights the wide variation of nonprofit hospitals' tax benefit across states, its high concentration among a small number of hospitals, and the primary role played by state and local taxes. Policy efforts to strengthen nonprofit hospitals' taxpayer accountability are likely to be more effective when pursued at the local level. The detailed standardized estimation road map can be used by various stakeholders to estimate tax benefit for external valuation and reporting purposes, updated as laws change, and improved upon as better data sources become available.

Spending on Dual Over-the-Counter and Prescription Drugs in the Medicare Part D Program.

This study compares Medicare and patient spending for dual over-the-counter and prescription drugs with their over-the-counter cash prices.

Evidence on the Effects of the Federal COVID-19 Vaccine Mandate on Nursing Home Staffing Levels.

OBJECTIVE: To assess the federal COVID-19 vaccine mandate's effects on nursing homes' nurse aide and licensed nurse staffing levels in states both with and without state-level vaccine mandates. DESIGN: Cross-sectional study using data from Centers for Medicare and Medicaid Services, Centers for Disease Control and Prevention, and Economic Innovation Group. Including nursing home facility fixed effects provides evidence on the intertemporal effects of the federal vaccine mandate within nursing homes. SETTING AND PARTICIPANTS: The sample contains 15,031 nursing homes, representing all US nursing homes with available data. METHODS: On January 13, 2022, the US Supreme Court upheld the federal COVID-19 vaccine mandate for health care workers in Medicare- and Medicaid-eligible facilities, with workers generally required to be vaccinated by March 20, 2022 (ie, the compliance date). We examined actual nursing home staffing levels in 3 time periods: (1) pre-Court decision; (2) precompliance date; and (3) postcompliance date. We separately examined staffing levels for nurse aides and licensed nursing staff. Because 28% of nursing homes were in states with state-imposed vaccine mandates that predated the Supreme Court's ruling, we divided the sample into 2 groups (nursing homes in mandate states vs nonmandate states) and performed all analyses separately. RESULTS: Staff vaccination rates and staffing levels were higher in mandate states than nonmandate states in all 3 time periods. After the Court's decision, staff vaccination rates increased 5% in nonmandate states and 1% in mandate states (on average). We find little evidence that the Court's vaccine mandate ruling materially affected nurse aide and licensed nurse staffing levels, or that nursing homes in mandate states and nonmandate states were differentially affected by the Court's ruling. Staffing levels over time were generally flat, with some evidence of a modestly greater increase for nurse aide staffing in mandate states than nonmandate states, and a modestly smaller decrease for licensed nurse staffing in mandate states than nonmandate states. Finally, regression results suggest that for both nurse aides and licensed nurses, staffing levels were lower in rural and for-profit nursing homes, and higher in Medicare-only, higher quality, and hospital-based nursing homes. CONCLUSIONS AND IMPLICATIONS: Results suggest the federal COVID-19 vaccine mandate has not caused clinically material changes in nursing home's nurse aide and licensed nurse staffing levels, which continue to be primarily associated with factors that are well-known to researchers and practitioners.

Poly(ADP-ribose) polymerase-1 (PARP-1) pharmacogenetics, activity and expression analysis in cancer patients and healthy volunteers.

There is a wide inter-individual variation in PARP-1 {PAR [poly(ADP-ribose)] polymerase 1} activity, which may have implications for health. We investigated if the variation: (i) is due to polymorphisms in the PARP-1 gene or PARP-1 protein expression; and (ii) affects patients' response to anticancer treatment. We studied 56 HV (healthy volunteers) and 118 CP (cancer patients) with supporting in vivo experiments. PARP activity ranged between 10 and 2600 pmol of PAR/106 cells and expression between 0.02-1.55 ng of PARP-1/µg of protein. PARP-1 expression correlated with activity in HV (R2=0.19, P=0.003) and CP (R2=0.06, P=0.01). A short CA repeat in the promoter was significantly associated with increased cancer risk [OR (odds ratio), 5.22; 95% CI (confidence interval), 1.79-15.24]. PARP activity was higher in men than women (P=0.04) in the HV. Male mice also had higher PARP activity than females or castrated males. Oestrogen supplementation activated PARP in PBMCs (peripheral blood mononuclear cells) from female mice (P=0.003), but inhibited PARP-1 in their livers by 80%. PARP activity and expression were not dependent on the investigated polymorphisms, but there was a modest correlation of PARP activity with expression. Studies in the HV revealed sex differences in PARP activity, which was confirmed in mice and shown to be associated with sex hormones. Toxic response to treatment was not associated with PARP activity and/or expression.

Nursing Home COVID Relief Under QIP's Performance-Based Formula: Does Performance Actually Matter, and Should It?

The Quality Incentive Program (QIP) distributed US$2 billion to nursing homes (NHs) that met performance goals primarily related to their COVID-19 infection rates. We examine how QIP affected 15,331 NHs with different facility and community attributes, and the extent to which QIP payments per resident-week (QIP$) were associated with NHs' COVID-related attributes. We find that QIP$ was primarily determined by county (not facility) infection rates. QIP distributed US$2 billion to NHs for months in which they experienced virtually no COVID-19 cases; US$0 was distributed for months in which they experienced more than 300,000 cases. We find that QIP$ was larger for smaller, nonprofit NHs located in more rural and economically distressed communities. Regression analyses reveal that recipients of larger QIP$ maintained greater supplies of personal protective equipment, conducted more staff testing, and limited admissions of infected residents, and that greater staff testing and limited admissions are also associated with NHs' sustained success in receiving QIP payments. Policymakers should consider whether performance-based payment systems are optimal for addressing public health emergencies.

Trends of Prescription Drug Manufacturer Rebates in Commercial Health Insurance Plans, 2015-2019.

This economic evaluation examines the magnitude and trend of prescription drug rebates in commercial markets from 2015 to 2019 and identifies insurance plan factors associated with rebates.

Targeting poly(ADP-ribose) polymerase: a two-armed strategy for cancer therapy.

The DNA repair pathways are protective of the host genome in normal cells; however, in cancer cells, these pathways may be disrupted and predispose to tumorigenesis or their activity may overcome the potentially cytotoxic damage caused by anticancer agents and be a mechanism of resistance. Poly(ADP-ribose) polymerase inhibitors, which block base excision repair of single-strand breaks, have entered the clinic in the last few years. This article discusses the interactions between the pathways of single- and double-strand break repair, which explain the two clinical development strategies for this class of drugs.

Trends in Premiums, Claims, and Enrollment for Fully Insured Large Group, Small Group, and Individual Health Plans From 2011 to 2021.

This economic evaluation compares trends in premiums, claims, and enrollment among fully insured large group, small group, and individual health plans in the US from 2001 to 2021.

Financial Characteristics of Nonprofit Social Welfare Organizations in the US Health Care System.

This cross-sectional study examines the purpose, revenues, profitability, and lobbying expenses of social welfare organizations in the US health care system.

Comparison of Commercial Negotiated Price and Cash Price Between Physician-Owned Hospitals and Other Hospitals in the Same Hospital Referral Region.

This cross-sectional study compares commercial negotiated prices and cash prices between physician-owned hospitals and other hospitals in the same hospital referral region (HRR) using price information available through the Hospital Price Transparency Rule.

Facility Fees for Colonoscopy Procedures at Hospitals and Ambulatory Surgery Centers.

This cross-sectional study investigates commercial facility fee differences for colonoscopy procedures between US hospitals and ambulatory surgery centers located within the same county and contracting with the same insurers.

Inhibition of poly(ADP-ribose) polymerase in cancer.

Inhibition of the DNA repair enzyme poly(ADP-ribose) polymerase-1 (PARP-1) has been extensively investigated in the pre-clinical setting as a strategy for chemo- or radio-potentiation. Recent evidence has suggested that PARP inhibitors might be active as single agents in certain rare inherited cancers that carry DNA repair defects. As a result, potent PARP-1 inhibitors have in the past three years entered early clinical trials in cancer patients, and the final results of these trials are eagerly awaited.

Safety and immunogenicity of new cell-cultured smallpox vaccine compared with calf-lymph derived vaccine: a blind, single-centre, randomised controlled trial.

BACKGROUND: US government organisations have identified the need for a new smallpox vaccine to replenish limited stocks of the approved, calf-lymph derived vaccine, the manufacture of which is no longer acceptable. We aimed to compare the safety and immunogenicity of the new cell-cultured smallpox vaccine (CCSV) to that of the calf-lymph derived vaccine (as a positive control) in 350 healthy, adult volunteers. METHODS: We did a randomised controlled study at the University of Kentucky Medical Center. We randomised 150 vaccinia-naive volunteers, aged 18-30 years, and 100 vaccinia-non-naive people, aged 32-65 years, to equivalent doses of either CCSV or test vaccine (2.5x10(5) plaque-forming units) by 15 puncture scarification in double-blind fashion. Immunogenicity was assessed by pock formation (take rate), humoral immune response by plaque-reduction neutralisation titres, and cellular immune response by vaccinia-specific, interferon-gamma T-cell quantification, cytotoxicity, and T-cell proliferation response. A further 100 vaccine-naive individuals, aged 18-30 years, received one of five doses of CCSV (undiluted, diluted 1 in 5, 1 in 10, 1 in 25, and 1 in 50) in single-blind fashion. Routine laboratory assessments, physical examinations, and recording of adverse events were done to assess vaccine safety. The primary endpoints were safety and reactogenicity (take rate) of CCSV. FINDINGS: 349 (99.7%) of 350 volunteers developed pock lesions; one vaccinia-naive individual who received a 1 in 25 dilution of CCSV did not. The rate of adverse events related to vaccine and the extent of humoral and cellular immune responses did not differ between the vaccine groups in vaccinia-naive or non-naive people. CCSV was immunogenic in vaccine-naive volunteers at a dose 50 times lower than that approved for Dryvax. INTERPRETATION: CCSV seems to be a safe and immunogenic alternative to calf-lymph derived vaccine for both vaccinia-naive and non-naive people.

The Affordable Care Act's Effects On The Formation, Expansion, And Operation Of Physician-Owned Hospitals.

The Affordable Care Act (ACA) imposed new restrictions on the formation and expansion of physician-owned hospitals. These restrictions provided incentives for the hospitals and their owners to take preemptive actions before the effective dates of ACA provisions and modify their operations thereafter. We studied 106 physician-owned hospitals in Texas to determine how they responded to ACA restrictions. We found that there were significant pre-ACA increases in the formation, physician ownership, and physical capacity of physician-owned hospitals, which suggests that they reacted quickly to the policy changes. After the ACA's provisions took effect, the hospitals improved the use of their assets to generate increased amounts of services, revenue, and profits. We found no evidence that existing physician-owned hospitals stopped accepting Medicare to avoid the ACA restrictions, although some investors adopted a seemingly unsuccessful strategy of not accepting Medicare at physician-owned hospitals formed after implementation of the ACA. We conclude that the ACA restrictions effectively eliminated the formation of new physician-owned hospitals, thus accomplishing what previous legislative efforts had failed to do.

Urticaria, exanthems, and other benign dermatologic reactions to smallpox vaccination in adults.

A phase 1 smallpox vaccine trial involving 350 adult volunteers was conducted. Of these subjects, 250 were naive to vaccinia virus vaccine (i.e., "vaccinia naive"). Volunteers received a new cell-cultured smallpox vaccine or a live vaccinia virus vaccine. Nine self-limiting rashes (3.6%) were observed in the vaccinia-naive group. None of the vaccinia-experienced patients had a rash. Rashes appeared 6-19 days after vaccination and had 5 different clinical presentations. Five volunteers had urticarial rashes that resolved within 4-15 days, 1 had an exanthem that lasted 20 days, and 1 each presented with folliculitis, contact dermatitis, and erythematous papules found only on the hands and fingers. Volunteers reported pruritus, tingling, and occasional headaches. Relief was obtained with antihistamine and acetaminophen therapy. No volunteer experienced fever or significant discomfort.

Clinicopathological features of homologous recombination-deficient epithelial ovarian cancers: sensitivity to PARP inhibitors, platinum, and survival.

Up to 50% of epithelial ovarian cancers (EOC) display defects in the homologous recombination (HR) pathway. We sought to determine the ramifications of the homologous recombination-deficient (HRD) status on the clinicopathologic features, chemotherapy response, and survival outcomes of patients with EOCs. HR status was determined in primary cultures from ascitic fluid in 50 chemotherapy-naïve patients by a functional RAD51 immunofluorescence assay and correlated with in vitro sensitivity to the PARP inhibitor (PARPi), rucaparib. All patients went on to receive platinum-based chemotherapy; platinum sensitivity, tumor progression, and overall survival were compared prospectively in HR-competent versus HRD patients. Compared with HR-competent patients, the HRD group was predominantly serous with a higher median CA125 at presentation. HRD was associated with higher ex vivo PARPi sensitivity and clinical platinum sensitivity. Median follow-up duration was 14 months; patients in the HRD group had lower tumor progression rates at 6 months, lower overall/disease-specific death rates at 12 months, and higher median survival. We therefore suggest that HRD as predicted by a functional RAD51 assay correlates with in vitro PARPi sensitivity, clinical platinum sensitivity, and improved survival outcome.

Therapeutic potential of poly(ADP-ribose) polymerase inhibitor AG014699 in human cancers with mutated or methylated BRCA1 or BRCA2.

BACKGROUND: Mutations in BRCA1 and BRCA2 (BRCA1/2), components of the homologous recombination DNA repair (HRR) pathway, are associated with hereditary breast and ovarian cancers. Poly(ADP-ribose) polymerase (PARP) inhibitors are selectively cytotoxic to animal cells with defective HRR, but results in human cancer cells have been contradictory. We undertook, to our knowledge, the first comprehensive in vitro and in vivo investigations of the antitumor activity of the PARP inhibitor AG014699 in human cancer cells carrying mutated or epigenetically silenced BRCA1/2. METHODS: We used nine human cell lines, four with nonmutated BRCA1/2 (MCF7, MDA-MB-231, and HCC1937-BRCA1 [breast cancer] and OSEC-2 [ovarian surface epithelial]), two with mutated BRCA1 (MDA-MB-436 and HCC1937 [breast cancer]), one with mutated BRCA2 (CAPAN-1 [pancreatic cancer]), one that was heterozygous for BRCA2 (OSEC-1 [ovarian surface epithelial]), and one with epigenetically silenced BRCA1 (UACC3199 [breast cancer]), and two Chinese hamster ovary cell lines, parental AA8 and XRCC3 mutated IRS 1SF. We assessed cytotoxicity, DNA damage, and HRR function. Antitumor activity of AG014699 was determined by growth of xenograft tumors (five mice per treatment group). Long-term safety of AG014699 was assessed. RESULTS: AG014699 (≤10 µM) was cytotoxic to cells with mutated BRCA1/2 or XRCC3 and to UACC3199 cells with epigenetically silenced BRCA1 but not to cells without BRCA1/2 or XRCC3 mutations or that were heterozygous for BRCA2 mutation. AG014699 induced DNA double-strand breaks in all nine cell lines studied. HRR was observed only in cells with functional BRCA1/2 proteins. Growth of xenograft tumors with BRCA1/2 mutations or with epigenetically silenced BRCA1 was reduced by AG014699 treatment, and combination treatment with AG014699 plus carboplatin was more effective than either drug alone. AG014699 was not toxic in mice with nonmutated or heterozygous BRCA2. CONCLUSION: Human cancer cells or xenograft tumors with mutated or epigenetically silenced BRCA1/2 were sensitive to AG014699 monotherapy, indicating a potential role for PARP inhibitors in sporadic human cancers.

Doxorubicin-induced suppression of poly(ADP-ribose) polymerase-1 (PARP-1) activity and expression and its implication for PARP inhibitors in clinical trials.

PURPOSE: Monozygotic twins provide an excellent tool to study environmental effects on human health. Poly(ADP-ribose) polymerase-1 (PARP-1) is an important enzyme primarily involved in DNA repair and genomic stability and is under clinical investigation as a target for anticancer therapy. As a part of a PARP pharmacogenetics study, elderly male monozygotic twins, one healthy and the other with a Trojani grade 3 sarcoma treated with doxorubicin (DOX: 142.5 mg/m(2)), were recruited for the study. METHODS: PARP activity and expression were measured in peripheral blood mononuclear cells (PBMCs) by methods validated to GCLP standard and used as a pharmacodynamic endpoint for clinical trials. RESULTS: The mean PARP activity for the patient before treatment was 160 pmol PAR/10(6) cells and was similar to that of his brother (130 pmol PAR/10(6) cells). There was approximately ninefold decrease (P = 0.001) in PARP activity in a second sample from the patient taken 21 days after the first DOX administration (17 pmol PAR/10(6) cells) and a decrease in PARP-1 expression. Investigations into BALB/C mice revealed that DOX treatment (5 mg/kg) resulted in a significant transient decrease in PARP activity after 1 h (63% control, P << 0.05) and 24 h (53% control, P << 0.05) but that PARP activity was restored 1 week after DOX treatment (86% control, P = 0.24). CONCLUSIONS: We showed here that administration of DOX can have a profound effect on the measured level of PARP activity and expression in PBMCs from patients and animals. Results obtained in clinical trials where PARP activity is used as a pharmacodynamic marker of PARP inhibition could reflect the effect of a chemotherapeutic on PBMCs rather than the effectiveness of a tested PARP inhibitor.