Affordability and adherence gains for Medicare Part D low-income subsidy recipients when low-income subsidy benefits expanded in 2024.

BACKGROUND: The lowest-income beneficiaries enrolled in the Medicare Part D prescription drug program receive "full subsidies" that waive the premium and deductible and impose minimal copayments. Those with slightly higher incomes and assets may be eligible for "partial subsidies." Prior to 2024, individuals receiving partial subsidies faced reduced Part D premiums and deductibles and paid 15% coinsurance. Under provisions of the Inflation Reduction Act, recipients of partial subsidies were upgraded to full subsidies beginning in 2024. The objective of this pilot study was to assess whether the new policy is likely to reduce cost-related nonadherence to prescribed medications- a common problem faced by older adults even among those receiving subsidies. OBJECTIVE: To compare cost-related nonadherence among partial- vs full-subsidy recipients with similar characteristics. METHODS: We used 2019 Medicare Current Beneficiary Survey data for the study. The Medicare Current Beneficiary Survey is uniquely suited for this work because it contains administrative data on low-income subsidy enrollment plus extensive survey-based information on financial resources necessary to establish program eligibility and rates of cost-related nonadherence. Explanatory variables included sociodemographic characteristics, economic resources, work status, and health variables. RESULTS: We found that the partial-subsidy group reported significantly more cost-related nonadherence (39% vs 22%; P = 0.01) arising both from a lower propensity to fill some prescriptions (23% vs 12%; P = 0.03) and to more delays in filling others (29% vs 8%; P = 0.03). The differences were more pronounced for women and racial and ethnic minority groups in contrast to men and majority populations, respectively. Because the study samples were small, we could not conduct a detailed regression analysis. CONCLUSIONS: The magnitude of cost-related nonadherence effects associated with partial-subsidy cost sharing suggests that the Inflation Reduction Act policy to expand low-income subsidies may boost medication adherence, most notably among women and racial and ethnic minority groups.

Medication adherence as a measure of the quality of care provided by physicians.

OBJECTIVES: To assess the extent to which medication adherence in congestive heart failure (CHF) and diabetes may serve as a measure of physician-level quality. STUDY DESIGN: A retrospective analysis of Medicare data from 2007 to 2009, including parts A (inpatient), B (outpatient), and D (pharmacy). METHODS: For each disease, we assessed the correlation between medication adherence and health outcomes at the physician level. We controlled for selection bias by first regressing patient-level outcomes on a set of covariates including comorbid conditions, demographic attributes, and physician fixed effects. We then classified physicians into 3 levels of average patient medication adherence-low, medium, and high-and compared health outcomes across these groups. RESULTS: There is a clear relationship between average medication adherence and patient health outcomes as measured at the physician level. Within the diabetes sample, among physicians with high average adherence and controlling for patient characteristics, 26.3 per 1000 patients had uncontrolled diabetes compared with 45.9 per 1000 patients among physicians with low average adherence. Within the CHF sample, also controlling for patient characteristics, the average rate of CHF emergency care usage among patients seen by physicians with low average adherence was 16.3% compared with 13.5% for doctors with high average adherence. CONCLUSIONS: This study's results establish a physician-level correlation between improved medication adherence and improved health outcomes in the Medicare population. Our findings suggest that medication adherence could be a useful measure of physician quality, at least for chronic conditions for which prescription medications are an important component of treatment.

Impact of early initiation of antihypertensive medications for patients with hypertension or elevated blood pressure.

OBJECTIVES: The 2017 American College of Cardiology/American Heart Association High Blood Pressure Guidelines lowered high blood pressure (BP) threshold, recommending earlier treatment to prevent cardiovascular disease. This study estimated the impact of initiating early antihypertensive medications on the risk of acute myocardial infarction (AMI), stroke, death, and on healthcare costs in patients potentially qualifying for antihypertensive treatment under the 2017 guidelines. METHODS: High-risk patients qualifying for antihypertensive medications under the 2017 guidelines were identified using Optum data. Patients with a diagnosis of elevated BP were also assumed eligible for hypertension treatment under the new guidelines. Patients were defined to have initiated early treatment if they initiated treatment before experiencing a cardiovascular event postdiagnosis. RESULTS: A total of 916 633 patients met eligibility requirements and all other study inclusion criteria. Of those, 66% initiated treatment during 2007-2016. Initiating early antihypertensive treatment decreased the likelihood of having AMI by 59%, stroke by 60% and death by 9%. Patients with only an 'elevated BP' diagnosis experienced reduced risk of stroke once they initiated medications. Treatment reduced the risk of AMI or stroke for patients with diabetes, chronic renal disease and obesity and also significantly lowered all-cause healthcare costs in the first postindex year. CONCLUSION: Initiating antihypertensive medications before experiencing a cardiovascular disease-related clinical event was associated with reduced risk of AMI, stroke and death for all hypertensive patients identified in the new guidelines. However, early treatment had a significantly smaller effect for patients with only 'elevated' BP, who experienced just a lower risk of stroke once treated.

Primary Prevention Using Cholesterol-Lowering Medications in Patients Meeting New Treatment Guidelines: A Retrospective Cohort Analysis.

BACKGROUND: The American College of Cardiology and American Heart Association (ACC/AHA) issued new cholesterol treatment guidelines in 2013. Two of the groups designated for primary prevention were analyzed: patients with a low-density lipoprotein cholesterol (LDL-C) level ≥ 190 mg per dL and diabetic patients aged 40-75 years. OBJECTIVE: To estimate the effects of primary prevention as specified in the 2013 guidelines on cardiovascular event risk and cost. METHODS: Primary prevention patients were identified using laboratory and diagnostic data for Humana members from 2007 to 2013. Potential study patients were classified into 3 risk groups: elevated LDL-C, diabetes, and elevated LDL-C and diabetes. Patients receiving cholesterol-lowering medications before their index date were excluded. Eligible patients were divided into 2 treatment groups: (1) primary prevention patients who initiated treatment before experiencing any cardiovascular disease (CVD)-related event, and (2) patients who either did not initiate treatment until after experiencing a CVD event or never initiated treatment. The associations between initiating cholesterol-lowering medications for primary prevention and the risk for acute myocardial infarction, stroke, coronary angioplasty, or coronary artery bypass graft surgery were estimated using Cox proportional hazards models. The effect of primary prevention on health care costs was estimated using generalized linear models. RESULTS: 91,066 patients met study selection criteria. Primary prevention rates were the lowest in diabetic patients (35%), who were newly designated for treatment in the 2013 guidelines. Primary prevention rates were higher for patients designated for treatment under earlier guidelines: 65% for patients with elevated LDL-C and 78% for the combined LDL-C and diabetes group. Primary prevention treatment was associated with significant reductions in cardiovascular event risk (up to 37%) and lower total all-cause costs (by $673) in the first post-index year. CONCLUSIONS: Initiating cholesterol-lowering medications for primary prevention, as specified in the ACC/AHA 2013 guidelines, for patients with high LDL-C and diabetes is associated with reduced CVD event risks and lower health care costs. DISCLOSURES: No outside funding supported this study. Han received fellowship support from the Pharmaceutical Research and Manufacturers Association Foundation (PhRMA) during the conduct of this study. Dougherty is employed by PhRMA. The authors have nothing to disclose.

Medication Synchronization Programs Improve Adherence To Cardiovascular Medications And Health Care Use.

Medication synchronization programs based in pharmacies simplify the refill process by enabling patients to pick up all of their medications on a single visit. This can be especially important for improving medication adherence in patients with complex chronic diseases. We evaluated the impact of two synchronization programs on adherence, cardiovascular events, and resource use among Medicare beneficiaries treated between 2011 and 2014 for two or more chronic conditions-at least one of which was hypertension, hyperlipidemia, or diabetes. Among nearly 23,000 patients matched by propensity score, the mean proportion of days covered (a measure of medication adherence) for the control group of patients without a synchronization program was 0.84 compared to 0.87 for synchronized patients-a gain of 3 percentage points. Adherence improvement in synchronized versus control patients was three times greater in patients with low baseline adherence, compared to those with higher baseline adherence. Rates of hospitalization and emergency department visits and rates of outpatient visits were 9 percent and 3 percent lower in the synchronized group compared to the control group, respectively, while cardiovascular event rates were similar. Synchronization programs were associated with improved adherence for patients with cardiovascular disease, especially those with low baseline adherence.

Does the offer of free prescriptions increase generic prescribing?

OBJECTIVES: To test if offering zero generic co-pays for oral antidiabetic drugs (OADs) and statins increases generic dispensing for low-income subsidy (LIS) recipients with diabetes enrolled in Medicare Part D. STUDY DESIGN: We analyzed a natural experiment in which LIS recipients were randomized to Part D plans in 2008. Some plans placed selected generic OADs and statins on zero co-pay tiers whereas others did not. Randomization eliminated selection effects which could bias the study findings. METHODS: We analyzed a 5% random sample of Medicare beneficiaries with diabetes from the Chronic Condition Data Warehouse using Part D claims, formulary provisions, and co-pay tiers together with a special file prepared by CMS that identified all randomly assigned LIS recipients in 2008. We calculated proportions using generic drugs in the 2 classes and annual days' supply among users in plans with and without zero co-pay tiers for the country as a whole and California (where zero co-pay plans were particularly popular). RESULTS: We found that the demand for generic OADs was not significantly different in plans with and without zero co-pay tiers. By contrast, a large difference was observed in the percent of LIS recipients using generic statins in plans with zero co-pay tiers (61.4% vs 54.6%; P <.01). However, the difference disappeared once we controlled for formulary restrictions on the most popular brand statin at the time (Lipitor). CONCLUSIONS: This cautionary tale suggests that policy makers should give greater consideration to formulary provisions when evaluating the effects of free generics in value-based insurance designs.

Reducing out-of-pocket cost barriers to specialty drug use under Medicare Part D: addressing the problem of "too much too soon".

OBJECTIVES: Medicare Part D specialty drug users not qualifying for low-income subsidies (non-LIS beneficiaries) face high and variable cost sharing during the calendar year. We examined their out-of-pocket (OOP) cost patterns under the existing Part D cost-sharing policies and proposed changes to these policies. METHODS: Using 100% Medicare claims data from 2012, we examined mean annual and monthly OOP drug costs for Medicare Part D patients who were full-year users of Part D specialty drugs for rheumatoid arthritis (RA) (n = 1063), multiple sclerosis (MS) (n = 2256), or chronic myeloid leukemia (CML) (n = 1135) under existing policy. Using the same data, we simulated costs under both proposed Medicare Payment Advisory Commission (MedPAC) policy recommendations and our own recommendations. RESULTS: In 2012, our sample faced mean annual cumulative OOP drug costs (for all medications) of $3949 (RA), $5238 (MS), and $6322 (CML). Mean OOP costs were $977 (RA), $1613 (MS), and $2456 (CML) in January alone. A substantial proportion of total annual OOP prescription spending also occurred during the catastrophic coverage phase (RA: $1229 [31%]; MS: $2456 [47%]; CML: $3546 [56%]). Under proposed MedPAC changes, patients would have faced maximum annual OOP spending of $4700, but mean OOP costs in January and February would have been higher compared with the existing policy. Under our proposed strategy, OOP costs would have been spread evenly over 12 months (≤$392 per month). The potential incremental costs of our proposed strategy would have been $23.55 per non-LIS Part D beneficiary per year. CONCLUSIONS: The existing Part D cost-sharing structure creates a substantial financial burden for specialty drug users, especially early in the year. Implementing both annual and monthly OOP maximum spending limits would result in lower, more consistent OOP costs, potentially increasing patients' ability to access treatments for life-threatening, chronic, and rare diseases.

How Low-Income Subsidy Recipients Respond to Medicare Part D Cost Sharing.

OBJECTIVES: To determine the magnitude and mechanisms of response to Medicare Part D cost sharing by low-income subsidy (LIS) recipients using oral hypoglycemic agents (OHAs) and statins. DATA SOURCES: Medicare data for a 5 percent random sample of beneficiaries with diabetes enrolled in fee-for-service Part D drug plans in 2008. STUDY DESIGN: We evaluated the impact of differences between generic and brand cost sharing rates among cohorts of LIS and non-LIS recipients to determine if wider price spreads increased the generic dispensing rate (GDR) and reduced total drug use and cost. PRINCIPAL FINDINGS: We found little association between cost sharing and aggregate OHA and statin use. In adjusted analyses, non-LIS beneficiaries who paid 46 percent of total OHA costs had 2.5 percent fewer OHA days supply than full benefit dual eligibles who paid just 5 percent of their therapy costs. For statins, the difference in days supply between those facing the lowest and highest cost sharing was 4.6 percent. Higher cost sharing was associated with filling fewer but larger prescriptions for both generics and brands. CONCLUSIONS: Higher generic and brand copays had little association with OHA and statin use among LIS recipients. This implies that modest changes in required cost sharing for these medicines would have very little substantive impact on generic dispensing or utilization patterns among LIS recipients and thus would have little effect on total program spending. At the same time, any increases in out-of-pocket costs would be expected to shift costs and place greater financial burden on low-income beneficiaries, particularly those in poor health.

Eligibility For And Enrollment In Medicare Part D Medication Therapy Management Programs Varies By Plan Sponsor.

Medicare Part D prescription drug plans must offer medication therapy management to beneficiaries with multiple chronic conditions and high drug expenditures. However, plan sponsors have considerable latitude in setting eligibility criteria. Newly available data indicate that enrollment rates in medication therapy management among stand-alone prescription drug plans and Medicare Advantage drug plans averaged only 10 percent in 2012. The enrollment variation across plan sponsors-from less than 0.2 percent to more than 57.0 percent-was associated with the restrictiveness of their eligibility criteria. For example, enrollment was 16.4 percent in plans requiring two chronic conditions versus 9.2 percent in plans requiring three, and 12.7 percent in plans requiring the use of any Part D drug versus 4.4 percent in plans requiring the use of drugs in specific classes. This variation represents inequities in access to medication therapy management across plans and results in missed opportunities for interventions that might improve therapeutic outcomes and reduce spending. The new Part D Enhanced Medication Therapy Management model of the Centers for Medicare and Medicaid Services has the potential to significantly increase the impact of medication therapy management by aligning financial incentives with improvements in medication use and encouraging innovation.

An Official American Thoracic Society Clinical Practice Guideline: Pediatric Chronic Home Invasive Ventilation

"BACKGROUND: Children with chronic invasive ventilator dependence living at home are a diverse group of children with special health care needs. Medical oversight, equipment management, and community resources vary widely. There are no clinical practice guidelines available to health care professionals for the safe hospital discharge and home management of these complex children. PURPOSE: To develop evidence-based clinical practice guidelines for the hospital discharge and home/community management of children requiring chronic invasive ventilation. METHODS: The Pediatric Assembly of the American Thoracic Society assembled an interdisciplinary workgroup with expertise in the care of children requiring chronic invasive ventilation. The experts developed four questions of clinical importance and used an evidence-based strategy to identify relevant medical evidence. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to formulate and grade recommendations. RESULTS: Clinical practice recommendations for the management of children with chronic ventilator dependence at home are provided, and the evidence supporting each recommendation is discussed. CONCLUSIONS: Collaborative generalist and subspecialist comanagement is the Medical Home model most likely to be successful for the care of children requiring chronic invasive ventilation. Standardized hospital discharge criteria are suggested. An awake, trained caregiver should be present at all times, and at least two family caregivers should be trained specifically for the child's care. Standardized equipment for monitoring, emergency preparedness, and airway clearance are outlined. The recommendations presented are based on the current evidence and expert opinion and will require an update as new evidence and/or technologies become available."

The anatomical distribution of genetic associations.

Deeper understanding of the anatomical intermediaries for disease and other complex genetic traits is essential to understanding mechanisms and developing new interventions. Existing ontology tools provide functional, curated annotations for many genes and can be used to develop mechanistic hypotheses; yet information about the spatial expression of genes may be equally useful in interpreting results and forming novel hypotheses for a trait. Therefore, we developed an approach for statistically testing the relationship between gene expression across the body and sets of candidate genes from across the genome. We validated this tool and tested its utility on three applications. First, we show that the expression of genes in associated loci from GWA studies implicates specific tissues for 57 out of 98 traits. Second, we tested the ability of the tool to identify novel relationships between gene expression and phenotypes. Specifically, we experimentally confirmed an underappreciated prediction highlighted by our tool: that white blood cell count--a quantitative trait of the immune system--is genetically modulated by genes expressed in the skin. Finally, using gene lists derived from exome sequencing data, we show that human genes under selective constraint are disproportionately expressed in nervous system tissues.

Increased Use Of Prescription Drugs Reduces Medical Costs In Medicaid Populations.

We used data on more than 1.5 million Medicaid enrollees to examine the impact of changes in prescription drug use on medical costs. For three distinct groups of enrollees, we estimated the effects of aggregate prescription drug use-and, more specifically, the use of medications to treat eight chronic noncommunicable diseases-on total nondrug, inpatient, outpatient, and other Medicaid spending. We found that a 1 percent increase in overall prescription drug use was associated with decreases in total nondrug Medicaid costs by 0.108 percent for blind or disabled adults, 0.167 percent for other adults, and 0.041 percent for children. Reductions in combined inpatient and outpatient spending from increased drug utilization in Medicaid were similar to an estimate for Medicare by the Congressional Budget Office. Moving forward, policy makers evaluating proposed changes that alter medication use among the nearly seventy million Medicaid recipients should consider the net effects on program spending to ensure that scarce federal and state health care dollars are allocated efficiently.

Medication adherence and measures of health plan quality.

OBJECTIVES: Medication adherence is increasingly being considered as a measure for performance-based reimbursement contracts in healthcare systems. However, the association between health outcomes and adherence at the plan level is unknown. STUDY DESIGN: Retrospective analysis of medical and pharmacy claims from a large private sector claims database from 2000 to 2009. METHODS: We compared plan-level measures of medication adherence and health outcomes for patients with diabetes and congestive heart failure (CHF). Plan performance was based on average rates of disease complications. Medication adherence was calculated as the percent of patients having 80% of days covered for medications treating diabetes or CHF. Both adherence and outcomes were adjusted for patient differences using multivariate regression. Plans were stratified into low, moderate, and high adherence, based on adherence in the bottom quartile, middle 2 quartiles, and top quartile, respectively. RESULTS: Average adherence varied significantly across plans. Plans with low adherence to diabetes medications had adjusted rates of uncontrolled diabetes admissions of 13.2 per 1000 patients, compared with 11.2 in moderate adherence plans and 8.3 in high adherence plans (P < .001). The adjusted rate of CHF-related hospitalization was 15.3% in low adherence plans, compared with 12.4% in moderate adherence plans and 12.2% in high adherence plans (P < .001). These patterns were consistent across different types of complications for both diabetes and CHF. CONCLUSIONS: Private health plans vary considerably in average adherence to medications treating chronic diseases. Plans with higher average adherence had lower rates of disease complications, suggesting that medication adherence measures are potentially useful tools for improving the performance of health plans.

Use of and spending on supportive care medications among Medicare beneficiaries with cancer.

PURPOSE: The study objective was to provide population-based estimates of supportive care medication (SCM) use among Medicare beneficiaries with cancer and determine factors related to SCM receipt. METHODS: This retrospective cohort study of community-based Medicare beneficiaries used the Medicare Current Beneficiary Survey (1997­2007). Dependent variables comprised use and spending on SCMs for three medication classes: opioids, antidepressants/sedative/hypnotics (ASH), and antiemetics. Independent variables of interest were supplemental insurance coverage, cancer site, and treatment. Multivariate models determined factors affecting receipt of, and spending on, SCMs. We also compared SCM use and spending among beneficiaries with and without cancer in order to understand what portion of SCM use and spending could be attributed to cancer as opposed to other comorbid conditions. RESULTS: A total of 1,836 Medicare beneficiaries with cancer and 9,898 beneficiaries without cancer were eligible for the study. Beneficiaries with cancer were more likely to receive opioids, ASH, and antiemetics compared to non-cancer beneficiaries. Adjusted annual payments for antiemetics were on average $637 higher in with cancer versus without cancer (p<0.01), while ASH payments were $184 lower (p<0.01). Opioid spending was similar among cancer and non-cancer users. Relative to colon cancer, beneficiaries with prostate cancer were least likely to receive any of the three SCM classes. Receipt of antineoplastic treatment increased the probability of use of all three classes of SCMs. Insurance coverage did not influence the use of or spending on opioids or antiemetics, but was associated with both outcomes for ASH. The use of all three SCM classes was significantly lower during years before Part D implementation of the new Medicare Part D prescription drug benefit and was higher after implementation of Part D. CONCLUSION: This study provides population-based information on SCM use among Medicare beneficiaries with cancer. Cancer site and treatment modality were important predictors of SCM use.

The effect of supplemental medical and prescription drug coverage on health care spending for Medicare beneficiaries with cancer.

OBJECTIVES: To examine whether patients with newly diagnosed cancer respond differently to supplemental coverage than the general Medicare population. METHODS: A cohort of newly diagnosed cancer patients (n = 1,799) from the 1997-2007 Medicare Current Beneficiary Survey and a noncancer cohort (n = 9,726) were identified and matched by panel year. Two-year total medical care spending was estimated by using generalized linear models with gamma distribution and log link-including endogeneity-corrected models. Interactions between cancer and type of insurance allowed testing for differential effects of a cancer diagnosis. RESULTS: The cancer cohort spent an adjusted $15,605 more over 2 years than did the noncancer comparison group. Relative to those without supplemental coverage, beneficiaries with employer-sponsored insurance, other private with prescription drug coverage, and public coverage had significantly higher total spending ($3,510, $2,823, and $4,065, respectively, for main models). For beneficiaries with cancer, supplemental insurance effects were similar in magnitude yet negative, suggesting little net effect of supplemental insurance for cancer patients. The endogeneity-corrected models produced implausibly large main effects of supplemental insurance, but the Cancer × Insurance interactions were similar in both models. CONCLUSIONS: Medicare beneficiaries with cancer are less responsive to the presence and type of supplemental insurance than are beneficiaries without cancer. Proposed restrictions on the availability of supplemental insurance intended to reduce Medicare spending would be unlikely to limit expenditures by beneficiaries with cancer, but would shift the financial burden to those beneficiaries. Policymakers should consider welfare effects associated with coverage restrictions.

Equine rhabdomyolysis.

A 1.5-year-old Quarter Horse gelding with a history of chronic nasal discharge and leukocytosis presented with signs of increased lethargy and muscular pain. The horse quickly became recumbent and unable to rise and was euthanized due to a poor prognosis. At necropsy, severe bilateral guttural pouch empyema was observed, as well as numerous well-demarcated areas of pallor within the skeletal muscles of all major muscle groups. Polymerase chain reaction testing of the guttural pouch exudate confirmed an infection with Streptococcus equi subsp. equi, and an S. equi-associated immune-mediated rhabdomyolysis was initially considered to be the most likely diagnosis. This report briefly discusses the various etiologies that should be considered in cases of equine myopathy, and it demonstrates the complexity of these poorly understood muscular disorders.

An interesting case of adenoviral hepatitis in a cardiac transplant recipient.

Adenoviral infections are commonly described in pediatric transplant populations. However, much less information is available regarding the incidence of infection and clinical spectrum of disease in adult transplant recipients. Moreover, this infection usually manifests as involvement of the transplanted organ in one pathologic form or the other, in addition to other systemic manifestations. We present a case of adenoviral infection of a nontransplanted organ in a solid organ transplant recipient.

The CASE adherence index: A novel method for measuring adherence to antiretroviral therapy.

The Center for Adherence Support Evaluation (CASE) Adherence Index, a simple composite measure of self-reported antiretroviral therapy (ART) adherence, was compared to a standard three-day self-reported adherence measure among participants in a longitudinal, prospective cross-site evaluation of 12 adherence programs throughout the United States. The CASE Adherence Index, consisting of three unique adherence questions developed for the cross-site study, along with a three-day adherence self-report were administered by interviews every three months over a one-year period. Data from the three cross-site adherence questions (individually and in combination) were compared to three -day self-report data and HIV RNA and CD4 outcomes in cross-sectional analyses. The CASE Adherence Index correlated strongly with the three-day self-reported adherence data (p < 0.001) and was more strongly associated with HIV outcomes, including a 1-log decline in HIV RNA level (maximum OR = 2.34; p < 0.05), HIV RNA < 400 copies/ml (maximum OR = 2.33; p < 0.05) and performed as well as the three-day self-report when predicting CD4 count status. Participants with a CASE Index score >10 achieved a 98 cell mean increase in CD4 count over 12 months, compared to a 41 cell increase for those with scores < or =10 (p < 0.05). The CASE Adherence Index is an easy to administer instrument that provides an alternative method for assessing ART adherence in clinical settings.

PBK/TOPK, a proliferating neural progenitor-specific mitogen-activated protein kinase kinase.

We performed genomic subtraction coupled to microarray-based gene expression profiling and identified the PDZ (postsynaptic density-95/Discs large/zona occludens-1)-binding kinase/T-LAK (lymphokine-activated killer T cell) cell originating protein kinase (PBK/TOPK) as a gene highly enriched in neural stem cell cultures. Previous studies have identified PBK/TOPK as a mitogen-activated protein kinase (MAPK) kinase that phosphorylated P38 MAPK but with no known expression or function in the nervous system. First, using a novel, bioinformatics-based approach to assess cross-correlation in large microarray datasets, we generated the hypothesis of a cell-cycle-related role for PBK/TOPK in neural cells. We then demonstrated that both PBK/TOPK and P38 are activated in a cell-cycle-dependent manner in neuronal progenitor cells in vitro, and inhibition of this pathway disrupts progenitor proliferation and self-renewal, a core feature of progenitors. In vivo, PBK/TOPK is expressed in rapidly proliferating cells in the adult subependymal zone (SEZ) and early postnatal cerebellar external granular layer. Using an approach based on transgenically targeted ablation and lineage tracing in mice, we show that PBK/TOPK-positive cells in the SEZ are GFAP negative but arise from GFAP-positive neural stem cells during adult neurogenesis. Furthermore, ablation of the adult stem cell population leads to concomitant loss of PBK/TOPK-positive cells in the SEZ. Together, these studies demonstrate that PBK/TOPK is a marker for transiently amplifying neural progenitors in the SEZ. Additionally, they suggest that PBK/TOPK plays an important role in these progenitors, and further implicates the P38 MAPK pathway in general, as an important regulator of progenitor proliferation and self-renewal.