Breast cancers are complex ecosystems of malignant cells and the tumour microenvironment
. The composition of these tumour ecosystems and interactions within them contribute to responses to cytotoxic ...therapy
. Efforts to build response predictors have not incorporated this knowledge. We collected clinical, digital pathology, genomic and transcriptomic profiles of pre-treatment biopsies of breast tumours from 168 patients treated with chemotherapy with or without HER2 (encoded by ERBB2)-targeted therapy before surgery. Pathology end points (complete response or residual disease) at surgery
were then correlated with multi-omic features in these diagnostic biopsies. Here we show that response to treatment is modulated by the pre-treated tumour ecosystem, and its multi-omics landscape can be integrated in predictive models using machine learning. The degree of residual disease following therapy is monotonically associated with pre-therapy features, including tumour mutational and copy number landscapes, tumour proliferation, immune infiltration and T cell dysfunction and exclusion. Combining these features into a multi-omic machine learning model predicted a pathological complete response in an external validation cohort (75 patients) with an area under the curve of 0.87. In conclusion, response to therapy is determined by the baseline characteristics of the totality of the tumour ecosystem captured through data integration and machine learning. This approach could be used to develop predictors for other cancers.
This article investigates changes in the affordability of individual health plans (Marketplace plans) that were compliant with the Affordable Care Act following the termination of cost-sharing ...reduction subsidy payments in 2017. We examined how states’ and insurers’ responses to these cuts affected enrollees differently depending on whether they lived in rural or urban geographic areas and were or were not eligible for Advance Premium Tax Credits. Using data for 2014–19 from the Health Insurance Exchange Compare database and other sources, we found that subsidy-eligible enrollees in rural markets gained access to Marketplace plans that were more affordable than those available to their urban counterparts, after the cuts affected premiums in 2018. Average minimum net monthly premiums for subsidized enrollees in majority-rural geographic rating areas decreased from $288 in 2017 to $162 in 2019, while those of their urban counterparts decreased from $275 to $180. In contrast, rural enrollees without subsidies faced the least affordable premiums for Marketplace plans.
Objective
To investigate how changes in insurer participation and composition as well as state policies affect health plan affordability for individual market enrollees.
Data Sources
2014‐2019 ...Qualified Health Plan Landscape Files augmented with supplementary insurer‐level information.
Study Design
We measured plan affordability for subsidized enrollees using premium spreads, the difference between the benchmark plan and the lowest cost plan, and premium levels for unsubsidized enrollees. We estimated how premium spreads and levels varied with insurer participation, insurer composition, and state policies using log‐linear models for 15 222 county‐years.
Principal Findings
Increased insurer participation reduces premium levels, which is beneficial for unsubsidized enrollees. However, it also reduces premium spreads, leading to lower plan affordability for subsidized enrollees. States responding to cost‐sharing reduction subsidy payment cuts by increasing only silver plans' premiums increase premium spreads, particularly when premium increases are restricted to on‐Marketplace silver plans. The latter approach also protects unsubsidized, off‐Marketplace enrollees from experiencing premium shocks.
Conclusions
Insurer participation and insurer composition affect subsidized and unsubsidized enrollees' health plan affordability in different ways. Decisions by state regulators regarding health plan pricing can significantly affect health plan affordability for each enrollee segment.
Background
Over 15.3 million Americans relied on the individual health insurance market for health coverage in 2021. Yet, little is known about the relationships between the organizational ...characteristics of individual market health insurers and quality of coverage, particularly with respect to clinical outcomes.
Objective
To examine variation in marketplace insurers’ quality performance and investigate how performance varies by insurer organizational characteristics.
Design
Retrospective cohort study.
Participants
381 insurer products, representing 184 unique insurers in 50 states in 2019 and 2020.
Main Measures
Marketplace plan clinical quality measures reported in the 2019–2020 CMS Plan Quality Rating System dataset and insurer-product organizational attributes identified from several data sources, including non-profit ownership, Blue Cross Blue Shield Association membership, Medicaid focus and whether or not the insurer product is vertically integrated with a provider organization.
Key Results
Among the 381 insurer products in this study, 35% are part of a provider-sponsored health plan (PSHP) and 70% of these entities received four stars or above for overall quality performance. Overall, PSHPs exhibited higher quality than non-PSHPs for both clinical quality management (0.36 increased on a 5-point scale; 95% CI = 0.11 to 0.62;
P
= 0.005) and enrollee experience (0.27; 95% CI = 0.03 to 0.50;
P
= 0.03) summary indicators. Medicaid focused insurers were associated with lower performance on enrollee experience, plan administration, and various outcomes related to clinical quality.
Conclusions
Provider-sponsored health plans in the health insurance marketplaces are associated with higher-quality care, as measured by CMS clinical quality measures.
Employers may respond to minimum wage increases by adjusting their health benefits. We examine the impact of state minimum wage increases on employer health benefit offerings using the 2002-2020 ...Medical Expenditure Panel Survey - Insurance/Employer Component data. Our primary regression specifications are difference-in-differences models that estimate the relationship between within-state changes in employer-sponsored insurance and minimum wage laws over time. We find that a $1 increase in minimum wages is associated with a 0.92 percentage point (p.p.) decrease in the percentage of employers offering health insurance, largely driven by small employers and employers with a greater share of low-wage employees. A $1 increase is also associated with a 1.83 p.p. increase in the prevalence of plans with a deductible requirement, but we do not find consistent evidence that other benefit characteristics are affected. We find no consequent change in uninsurance, likely explained by an increase in Medicaid enrollment.
Objectives
The United States is one of only three countries worldwide with no national policy guaranteeing paid leave to employed women who give birth. While maternity leave has been linked to ...improved maternal and child outcomes in international contexts, up-to-date research evidence in the U.S. context is needed to inform current policy debates on paid family leave.
Methods
Using data from
Listening to Mothers III
, a national survey of women ages 18–45 who gave birth in 2011–2012, we conducted multivariate logistic regression to predict the likelihood of outcomes related to infant health, maternal physical and mental health, and maternal health behaviors by the use and duration of paid maternity leave.
Results
Use of paid and unpaid leave varied significantly by race/ethnicity and household income. Women who took paid maternity leave experienced a 47% decrease in the odds of re-hospitalizing their infants (95% CI 0.3, 1.0) and a 51% decrease in the odds of being re-hospitalized themselves (95% CI 0.3, 0.9) at 21 months postpartum, compared to women taking unpaid or no leave. They also had 1.8 times the odds of doing well with exercise (95% CI 1.1, 3.0) and stress management (95% CI 1.1, 2.8), compared to women taking only unpaid leave.
Conclusions for Practice
Paid maternity leave significantly predicts lower odds of maternal and infant re-hospitalization and higher odds of doing well with exercise and stress management. Policies aimed at expanding access to paid maternity and family leave may contribute toward reducing socio-demographic disparities in paid leave use and its associated health benefits.
Objective
To understand US hospitals' initial strategic responses to the federal price transparency rule that took effect January 2021.
Data Sources and Study Setting
Primary interview data collected ...from 12 not‐for‐profit hospital organizations in six US metropolitan markets. All but one organization were multihospital systems; the 12 organizations represent a total of 81 hospitals.
Study Design
Exploratory, cross‐sectional, qualitative interview study of a convenience sample of hospital organizations across six geographically and compliance diverse markets.
Data Collection/Extraction Methods
In‐depth, semi‐structured, qualitative interviews with 16 key informants across sampled organizations between November 2021 and March 2022. Interviews solicited data about internal organizational factors and external market factors affecting strategic responses. Transcribed interviews were de‐identified, coded, and analyzed using the constant comparative method.
Principal Findings
Hospitals' strategic responses were influenced internally by the degree of the regulation's alignment with organizational values and goals, and task complexity vis‐a‐vis available resources. We found extensive variation in organizational capabilities to comply, and all but one organization relied on consultants and vendors to some degree. Key external factors driving strategic responses were hospitals' variable perceptions about how available price information would affect their competitive position, bottom line, and reputation. Organizations with more confidence in their interpretation of the environment, including how peers or purchasers would behave, and greater clarity in their own organization's position and goals, had more definitive initial strategic responses. In the first year, organizations' strategic responses skewed toward compliance, especially for the rule's consumer shopping requirements.
Conclusions
A deeper understanding of the realities of operationalizing price transparency policy for hospitals is needed to improve its impact.
Personalised approaches to the management of all solid tumours are increasing rapidly, along with wider accessibility for clinicians. Advances in tumour characterisation and targeted therapies have ...placed triple-negative breast cancers (TNBC) at the forefront of this approach. TNBC is a highly heterogeneous disease with various histopathological features and is driven by distinct molecular alterations. The ability to tailor individualised and effective treatments for each patient is of particular importance in this group due to the high risk of distant recurrence and death. The mainstay of treatment across all subtypes of TNBC has historically been cytotoxic chemotherapy, which is often associated with off-target tissue toxicity and drug resistance. Neoadjuvant chemotherapy is commonly used as it allows close monitoring of early treatment response and provides valuable prognostic information. Patients who achieve a complete pathological response after neoadjuvant chemotherapy are known to have significantly improved long-term outcomes. Conversely, poor responders face a higher risk of relapse and death. The identification of those subgroups that are more likely to benefit from breakthroughs in the personalised approach is a challenge of the current era where several targeted therapies are available. This review presents an overview of contemporary practice, and promising future trends in the management of early TNBC. Platinum chemotherapy, DNA damage response (DDR) inhibitors, immune checkpoint inhibitors, inhibitors of the PI3K-AKT-mTOR, and androgen receptor (AR) pathways are some of the increasingly studied therapies which will be reviewed. We will also discuss the growing evidence for less-developed agents and predictive biomarkers that are likely to contribute to the forthcoming advances in this field. Finally, we will propose a framework for the personalised management of TNBC based upon the integration of clinico-pathological and molecular features to ensure that long-term outcomes are optimised.
In clinical practice, differentiating Bipolar Disorder (BD) from unipolar depression is a challenge due to the depressive symptoms, which are the core presentations of both disorders. This ...misdiagnosis during depressive episodes results in a delay in proper treatment and a poor management of their condition. In a first step, using A-to-I RNA editome analysis, we discovered 646 variants (366 genes) differentially edited between depressed patients and healthy volunteers in a discovery cohort of 57 participants. After using stringent criteria and biological pathway analysis, candidate biomarkers from 8 genes were singled out and tested in a validation cohort of 410 participants. Combining the selected biomarkers with a machine learning approach achieved to discriminate depressed patients (n = 267) versus controls (n = 143) with an AUC of 0.930 (CI 95% 0.879-0.982), a sensitivity of 84.0% and a specificity of 87.1%. In a second step by selecting among the depressed patients those with unipolar depression (n = 160) or BD (n = 95), we identified a combination of 6 biomarkers which allowed a differential diagnosis of bipolar disorder with an AUC of 0.935 and high specificity (Sp = 84.6%) and sensitivity (Se = 90.9%). The association of RNA editing variants modifications with depression subtypes and the use of artificial intelligence allowed developing a new tool to identify, among depressed patients, those suffering from BD. This test will help to reduce the misdiagnosis delay of bipolar patients, leading to an earlier implementation of a proper treatment.
To compare direct-to-consumer (DTC) telemedicine and in-person visits in rates of testing, follow-up health care use, and quality for urinary tract infections (UTIs) and sinusitis.
The Minnesota All ...Payer Claims Data provided 2008-2015 administrative claims data.
Using a difference-in-differences approach, we compared episodes of care for UTIs and sinusitis among enrollees of health plans introducing coverage for DTC telemedicine relative to those without DTC telemedicine coverage. Primary outcomes included number of laboratory tests, antibiotics filled, office and outpatient visits, emergency department (ED) visits, and standardized spending, based on standardized prices of health services.
The study sample included non-elderly enrollees of commercial health insurance plans. We constructed 30-day episodes of care initiated by a DTC telemedicine or in-person visit.
The UTI and sinusitis samples were comprised of 215,134 and 624,630 episodes of care, respectively. Following the introduction of coverage for DTC telemedicine, 15.7% of UTI episodes and 8.9% of sinusitis episodes were initiated with DTC telemedicine. Compared to episodes without coverage for DTC telemedicine, UTI episodes with coverage had 0.25 fewer lab tests (95% CI: -0.33, -0.18; p < 0.001), lower standardized spending for the first UTI visit (-$11.18 95% CI: -$21.62, -$0.75; p < 0.05), and no change in office and outpatient visits, ED visits, antibiotics filled, or standardized medical spending. Sinusitis episodes with coverage for DTC telemedicine had fewer antibiotics filled (-0.08 95% CI: -0.14, -0.01; p < 0.05) and a very small increase in ED visits (0.001 95% CI: 0.001, 0.010; p < 0.05), but no change in lab tests, office and outpatient visits, or standardized medical spending.
Among commercially insured patients, coverage of DTC telemedicine was associated with reductions in antibiotics for sinusitis and laboratory tests for UTI without changes in downstream total office and outpatient visits or changes in ED visits.
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