The Regulation of m6A Modification in Glioblastoma: Functional Mechanisms and Therapeutic Approaches.

Glioblastoma is the most prevalent primary brain tumour and invariably confers a poor prognosis. The immense intra-tumoral heterogeneity of glioblastoma and its ability to rapidly develop treatment resistance are key barriers to successful therapy. As such, there is an urgent need for the greater understanding of the tumour biology in order to guide the development of novel therapeutics in this field. N6-methyladenosine (m6A) is the most abundant of the RNA modifications in eukaryotes. Studies have demonstrated that the regulation of this RNA modification is altered in glioblastoma and may serve to regulate diverse mechanisms including glioma stem-cell self-renewal, tumorigenesis, invasion and treatment evasion. However, the precise mechanisms by which m6A modifications exert their functional effects are poorly understood. This review summarises the evidence for the disordered regulation of m6A in glioblastoma and discusses the downstream functional effects of m6A modification on RNA fate. The wide-ranging biological consequences of m6A modification raises the hope that novel cancer therapies can be targeted against this mechanism.

Use of Home and Community-Based Services After Implementation of Medicaid Managed Long Term Services and Supports in Virginia.

Many state Medicaid programs contract with managed care organizations to deliver long-term services and supports (LTSS) to seniors and persons with disabilities. Managed LTSS (MLTSS) programs are often intended to increase access to and utilization of home- and community-based services (HCBS), yet there are few empirical studies of their effects. In this retrospective observational study, we used administrative data from Virginia Medicaid to compare HCBS waiver enrollment and service utilization pre- and post-implementation of MLTSS. Compared to the prior fee-for-service system, Medicaid beneficiaries with long-term care needs who were enrolled in Virginia's MLTSS program were more likely to be enrolled in Virginia's 1915(c) waivers for home and community-based services. Further, the likelihood of using personal care increased by nearly 5%, and the likelihood of using respite care increased by about 10%. These findings are pertinent to ongoing policy changes that use private managed care organizations to deliver long-term services and supports to seniors and persons with disabilities. Policymakers in states and the federal government should note these initial increases in service use under Medicaid MLTSS, while supporting evaluations of the long-term impacts of MLTSS on HCBS use and beneficiary health and satisfaction.

Health plan switching and satisfaction in a Medicaid MLTSS program.

OBJECTIVES: This paper examines (1) the rate of plan switching among beneficiaries enrolled in a Medicaid managed long-term services and supports (MLTSS) program in Virginia, (2) barriers that prevent beneficiaries from changing plans, and (3) the extent to which a change in plans is associated with greater satisfaction with the current health plan. STUDY DESIGN: Survey data from a representative sample of 1048 members enrolled in Commonwealth Coordinated Care Plus, a Virginia Medicaid MLTSS program. METHODS: The survey ascertained whether beneficiaries changed plans at the previous open enrollment period, whether they wanted to change plans but did not, and reasons for not following through with a plan change. Logistic regression analysis examined the association between the intention to change plans and satisfaction with the current health plan. RESULTS: Seven percent of respondents changed plans during the previous open enrollment. However, twice as many respondents (15%) wanted to change plans but did not. The main reason for not changing plans was uncertainty about whether the new plan would meet their needs better than their current plan. Logistic regression analysis shows that an intention to change plans (realized or not) was associated with higher odds (3.5 times higher) of being dissatisfied with the current health plan compared with beneficiaries who had no intention to change plans. CONCLUSIONS: Greater dissatisfaction after a recent plan change may indicate that these members have specific needs beyond the scope of services offered by managed care organizations.

Virginia Medicaid Expansion: New Members Report Reduced Financial Concerns During The COVID-19 Pandemic.

Medicaid is a critical antipoverty program. Since the Affordable Care Act expanded Medicaid eligibility, millions of newly eligible people have enrolled, creating positive financial improvements for low-income families. We examined the association of Virginia's 2019 Medicaid expansion and changes in health care-related and non-health-care-related financial needs among newly eligible Medicaid enrollees. Our unique survey collected responses between December 2018 and April 2019 from newly enrolled members reporting on experiences in the year before enrollment and between July 2020 and May 2021 from members reporting on experiences one year after enrollment. The follow-up period coincided with the COVID-19 pandemic. Medicaid enrollment was associated with decreases in concern about all financial needs assessed: housing, food, monthly bills, credit card and loan payments, and health care costs. These reductions were broadly similar across demographic subgroups and across the months of the pandemic that overlapped with the follow-up period. We add to the evidence that Medicaid expansion is a social safety-net policy that could improve equity among low-income families, potentially encouraging states that have yet to expand to do so.

Medicaid participation among practitioners authorized to prescribe buprenorphine.

INTRODUCTION: This study examines Medicaid participation among buprenorphine waivered providers in Virginia in 2019, with a particular focus on the prescribing differences between different physician specialties, nurse practitioners and physicians assistants (NP and PA). METHODS: Secondary data sources include the 2019 DEA list of buprenorphine waivered prescribers, Virginia Medicaid claims for buprenorphine, physician characteristics from the Virginia Department of Health Professions, SAMHSA Behavioral Treatment Services Locator, and area level characteristics. This cross-sectional study is based on a linkage of Medicaid claims data to a list of Virginia practitioners authorized to prescribe buprenorphine in 2019. Using a two-part logistic regression, we assess prescriber license type and local area factors that are associated with: (1) the probability of prescribing buprenorphine to any Medicaid patients in 2019; (2) the number of Medicaid patients treated by each prescriber in 2019. RESULTS: Adjusted odds ratios show that nurse practitioners with buprenorphine waivers are more likely to treat any Medicaid patients compared to physicians (odds ratio (OR), 2.016; p = 0.000). Among prescribers who treated any Medicaid patients, the probability of treating a large number of Medicaid patients was higher among nurse practitioners relative to physicians (OR, 2.869, p = 0.002). Medicaid participation was much higher among prescribers with patient limits of 100 and 275 compared to prescribers with patient limits of 30 (OR, 6.66, p = 0.000 and 29.40, p = 0.000, respectively). CONCLUSIONS: State Medicaid programs have been at the forefront of addressing their state's opioid epidemic, including expanding access to buprenorphine treatment. This study provides evidence that targeted outreach efforts should include NP license types as well as physicians, and is consistent with prior studies showing that NP are especially important in filling treatment gaps for underserved areas and populations.

Hospital Use Declines After Implementation Of Virginia Medicaid's Addiction And Recovery Treatment Services.

Medicaid programs responded to the opioid crisis by expanding treatment coverage and reforming delivery systems. We assessed whether Virginia's Addiction and Recovery Treatment Services (ARTS) program, implemented in April 2017, influenced emergency department and inpatient use. Using claims for January 2016-June 2018 and difference-in-differences models, we compared beneficiaries with opioid use disorder before and after ARTS implementation to beneficiaries with no substance use disorder. After program implementation, the likelihood of having an emergency department visit in a quarter declined by 9.4 percentage points (a 21.1 percent relative decrease) among beneficiaries with opioid use disorder, compared to 0.9 percentage points among beneficiaries with no substance use disorder. Similarly, the likelihood of having an inpatient hospitalization declined among beneficiaries with opioid use disorder. In contrast to other states, Virginia has a new Medicaid expansion population whose beneficiaries enter a delivery system in which reforms of the addiction treatment system are well under way.

Mandatory minimum sentencing policies and cocaine use in the U.S., 1985-2013.

BACKGROUND: As of May 2017, the United States federal government renewed its prioritization for the enforcement of mandatory minimum sentences for illicit drug offenses. While the effect of such policies on racial disparities in incarceration is well-documented, less is known about the extent to which these laws are associated with decreased drug use. This study aims to identify changes in cocaine use associated with mandatory minimum sentencing policies by examining differential sentences for powder and crack cocaine set by the Anti-Drug Abuse Act (ADAA) (100:1) and the Fair Sentencing Act (FSA), which reduced the disparate sentencing to 18:1. METHODS: Using data from National Survey on Drug Use and Health, we examined past-year cocaine use before and after implementation of the ADAA (1985-1990, N = 21,296) and FSA (2009-2013, N = 130,574). We used weighted logistic regressions and Z-tests across models to identify differential change in use between crack and powder cocaine. Prescription drug misuse, or use outside prescribed indication or dose, was modeled as a negative control to identify underlying drug trends not related to sentencing policies. RESULTS: Despite harsher ADAA penalties for crack compared to powder cocaine, there was no decrease in crack use following implementation of sentencing policies (odds ratio (OR): 0.72, p = 0.13), although both powder cocaine use and misuse of prescription drugs (the negative control) decreased (OR: 0.59, p < 0.01; OR: 0.42, p < 0.01 respectively). Furthermore, there was no change in crack use following the FSA, but powder cocaine use decreased, despite no changes to powder cocaine sentences (OR: 0.81, p = 0.02), suggesting that drug use is driven by factors not associated with sentencing policy. CONCLUSIONS: Despite harsher penalties for crack versus powder cocaine, crack use declined less than powder cocaine and even less than drugs not included in sentencing policies. These findings suggest that mandatory minimum sentencing may not be an effective method of deterring cocaine use.

The effect of primary care visits on other health care utilization: A randomized controlled trial of cash incentives offered to low income, uninsured adults in Virginia.

We conducted a randomized controlled trial, enrolling low-income uninsured adults in Virginia (United States), to determine whether cash incentives are effective at encouraging a primary care provider (PCP) visit, and at lowering utilization and costs. Subjects were randomized to four groups: untreated controls, and one of three incentive arms with incentives of $0, $25, or $50 for visiting a PCP within six months of group assignment. We used the exogenous variation generated by the experiment to obtain causal evidence on the effects of a PCP visit. We observed modest reductions in non-urgent emergency department visits and increased outpatient visits, but no reductions in overall costs. These findings in utilization are consistent with the expectation that PCPs offer an alternative to the emergency department for non-emergent conditions. Total costs did not decline because any savings from avoiding the emergency department were offset by increased outpatient utilization.