Environmental Scan on Consolidation Trends and Impacts in Health Care Markets.

The No Surprises Act (NSA) was created to help protect consumers with private insurance from surprise medical bills from out-of-network health care providers. The NSA requires the Department of Health and Human Services to prepare annual reports to Congress on the effects of the NSA's provisions. This article summarizes findings of an environmental scan on consolidation trends and impacts in health care markets. It describes the evidence on price, spending, quality of care, access, and wages in health care provider and insurance markets, as well as other market trends. The authors found strong evidence that hospital horizontal consolidation is associated with higher prices paid to providers and some evidence of the same for vertical consolidation of hospitals and physician practices. Health care spending is likely to increase in tandem with these price increases. Most studies find decreased or no change in quality of care associated with consolidation; however, findings differ by quality measures examined and setting. Horizontal consolidation of commercial insurers is associated with lower prices paid to providers as insurers gain market power in negotiations with providers, but the lower prices paid to providers do not appear to be passed onto consumers, who face higher premiums following insurer consolidation. There is insufficient evidence of the effects on patient access to care and health care wages. The few evaluations of state surprise billing laws have found heterogeneous effects on prices and have not directly examined effects on spending, quality, patient access, and wages.

Microsimulation projections of obesity interventions on cardiometabolic health disparities in the United States.

OBJECTIVE: The aim of this study was to estimate long-term impacts of health education interventions on cardiometabolic health disparities. METHODS: The model simulates how health education implemented in the United States throughout 2019 to 2049 would lead to changes in adult BMI and consequent hypertension and type 2 diabetes. Health outcome changes by sex, racial/ethnic (non-Hispanic White, non-Hispanic Black, and Hispanic), and weight status (normal: 18.5 ≤ BMI < 25; overweight: 25 ≤ BMI < 30; and obesity: 30 ≤ BMI) subpopulations were compared under a scenario with and one without health education. RESULTS: By 2049, the intervention would reduce average BMI of women with obesity to 27.7 kg/m2 (CI: 27.4-27.9), which would be 2.9 kg/m2 lower than the expected average BMI without an intervention. Education campaigns would reduce type 2 diabetes prevalence, but it would remain highest among women with obesity at 27.7% (CI: 26.2%-29.2%). The intervention would reduce hypertension prevalence among White women by 4.7 percentage points to 38.0% (CI: 36.4%-39.7%). For Black women in the intervention, the 2049 hypertension prevalence would be 52.6% (CI: 50.7%-54.5%). Results for men and women were similar. CONCLUSIONS: Long-term health education campaigns can reduce obesity-related disease. All population groups benefit, but they would not substantially narrow cardiometabolic health disparities.

Diet quality improvement and 30-year population health and economic outcomes: a microsimulation study.

OBJECTIVE: Diets closer aligned with nutritional guidelines could lower the risk of several chronic conditions and improve economic outcomes, such as employment and healthcare costs. However, little is known about the range, order of magnitude and timing of these potential effects. DESIGN: We used a microsimulation approach to predict US population changes over 30 years in health and economic outcomes that could result from a substantial (but not impossible) improvement in diet quality - an improvement from the third to the fifth quintile of US scores on the Alternate Healthy Eating Index, 2010 version. SETTING: Risk ratios from the literature for diabetes, heart disease and stroke were used to modify the Future Adult Model (FAM) to simulate outcomes from a higher-quality diet. Model parameter uncertainty was assessed using bootstrap and sensitivity analysis examined the variation in published risk ratios. PARTICIPANTS: FAM simulates outcomes for the US adult population aged 25 and older. RESULTS: Improved diet quality initially leads to very small changes in chronic disease prevalence, but these accumulate over time. If diets improved beginning in 2019, after 30 years diabetes prevalence could be reduced by 5·9 million cases (11·5 %), heart disease prevalence by 4·0 million cases (7·2 %) and stroke prevalence by 1·9 million cases (10·3 %). These reductions in disease prevalence would be accompanied that same year by fewer deaths (88 000) and healthcare cost savings of $144·0 billion (2019 USD). CONCLUSIONS: This microsimulation study suggests that improvements in diet are likely to improve health and economic population outcomes over time.

Cardiomyocytes are Protected from Antiretroviral Nucleoside Analog-Induced Mitochondrial Toxicity by Overexpression of PGC-1α.

The nucleoside reverse transcriptase inhibitors (NRTIs), used for treatment of the human immunodeficiency virus-1, compromise mitochondria in cardiomyocytes and other host cells, limiting the clinical use of these drugs. To explore underlying mechanisms, we overexpressed PGC-1α, a master regulator of mitochondrial biogenesis, twofold in H9c2 rat cardiomyocyte cultures, hypothesizing that this might protect the mitochondria from damage induced by the NRTI combination zidovudine (AZT) and didanosine (ddI). The experimental groups, evaluated during 16 passages (P) of drug exposure, included: PGC-1α-overexpressing cells with no exposure, or exposure to 50 µM AZT plus 50 µM ddI; and control cells with no exposure or exposure to the same doses of AZT and ddI. The AZT/ddI combination caused a growth inhibition of 15-20% in control cells, but none in PGC-1α cells. Apoptosis was highest in AZT/ddI-exposed control cells, and PGC-1α overexpression protected cells from AZT/ddI-induced apoptosis. At P3, P6, P8, and P12, uncoupled mitochondrial oxygen consumption rate, determined by Seahorse 24 XF Analyzer, as higher in AZT/ddI-exposed PGC-1α cells, compared to AZT/ddI-exposed control cells (p < 0.05 at all P). Complex I activity was higher in AZT/ddI-exposed PGC-1α overexpressing cells than that in AZT/ddI-exposed control cells (p < 0.05), and reactive oxygen species levels were lower in PGC-1α overexpressing cells than that in control cells (p < 0.05) when both were exposed to AZT/ddI. Taken together, these experiments show proof of concept that overexpression of PGC-1α protects cardiomyocytes from NRTI-induced toxicity, and suggest that a pharmaceutical agent with similar activity may protect against NRTI-induced mitochondrial toxicity.

Tempol protects cardiomyocytes from nucleoside reverse transcriptase inhibitor-induced mitochondrial toxicity.

Nucleoside reverse transcriptase inhibitors (NRTIs), essential components of combinational therapies used for treatment of human immunodeficiency virus-1, damage heart mitochondria. Here, we have shown mitochondrial compromise in H9c2 rat cardiomyocytes exposed for 16 passages (P) to the NRTIs zidovudine (AZT, 50µM) and didanosine (ddI, 50µM), and we have demonstrated protection from mitochondrial compromise in cells treated with 200µM 1-oxyl-2,2,6,6-tetramethyl-4-hydroxypiperidine (Tempol) or 200µM 1-hydroxy-4-[2-triphenylphosphonio)-acetamido]-2,2,6,6-tetramethylpiperidine (Tempol-H), along with AZT/ddI, for 16P. Exposure to AZT/ddI caused a moderate growth inhibition at P3, P5, P7, and P13, which was not altered by addition of Tempol or Tempol-H. Mitochondrial oxidative phosphorylation capacity was determined as uncoupled oxygen consumption rate (OCR) by Seahorse XF24 Analyzer. At P5, P7, and P13, AZT/ddI-exposed cells showed an OCR reduction of 8.8-57.2% in AZT/ddI-exposed cells, compared with unexposed cells. Addition of Tempol or Tempol-H, along with AZT/ddI, resulted in OCR levels increased by about 300% above the values seen with AZT/ddI alone. The Seahorse data were further supported by electron microscopy (EM) studies in which P16 cells exposed to AZT/ddI/Tempol had less mitochondrial pathology than P16 cells exposed to AZT/ddI. Western blots of P5 cells showed that Tempol and Tempol-H upregulated expression of mitochondrial uncoupling protein-2 (UCP-2). However, Complex I activity that was reduced by AZT/ddI, was not restored in the presence of AZT/ddI/Tempol. Superoxide levels were increased in the presence of AZT/ddI and significantly decreased in cells exposed to AZT/3TC/Tempol at P3, P7, and P10. In conclusion, Tempol protects against NRTI-induced mitochondrial compromise, and UCP-2 plays a role through mild uncoupling.

Molecular analysis of mitochondrial compromise in rodent cardiomyocytes exposed long term to nucleoside reverse transcriptase inhibitors (NRTIs).

Despite the highly effective impact of NRTI therapy in patients infected with the human immunodeficiency virus type 1 (HIV-1), long-term treatment has revealed cardiotoxicity, considered to be due to mitochondrial dysfunction. To evaluate mitochondrial damage, and design therapeutic interventions, we established cultures of rat H9c2 and mouse HL-1 cardiomyocytes and exposed them to the NRTIs zidovudine (AZT), and AZT plus didanosine (ddI). Proliferation assays showed that H9c2 cells grew well in 50 µM AZT and 50 µM AZT/50 µM ddI and that HL-1 cells grew well in 10 µM AZT and 10 µM AZT/10 µM ddI. Both types of cells were exposed to the drugs for 39 passages (P), and mitochondrial integrity in the form of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) was examined by Seahorse XF24 analyzer. In NRTI-exposed H9c2 cells at most passages, OCR was reduced, in both the basal and uncoupled states, compared to unexposed controls (P < 0.05). NRTI-exposed HL-1 cells showed a different pattern of mitochondrial compromise, with inhibition of OCR, in basal and uncoupled cells, occurring largely before P14 and after P17 (P < 0.05). The ECAR response in uncoupled cells of both types was unchanged at early passages, but increased after P18 (P < 0.05). Evaluation of mitochondrial biogenesis in H9c2 cells revealed reduction before P29, no change at P29, and reduction at P39 in NRTI-exposed cells, compared to unexposed cells (P < 0.05). Western blotting of transcription factors critical for mitochondrial biogenesis, PGC-1α, Nrf-1 and mtTFA, showed downregulation in NRTI-exposed H9c2 cells compared to unexposed controls. In addition, electron microscopy (EM) revealed increasing mitochondrial morphological damage in H9c2 cells over passages. For both cell types, AZT/ddI was more damaging than AZT alone. These studies demonstrate progressive mitochondrial compromise in cardiomyocytes-exposed long term, and the model will be used to evaluate potentially protective intervention strategies.