State Priorities and Needs: The Role of Block Grants.

OBJECTIVES: Block grant funding provides federal financial support to states, with increased flexibility as to how those funds can be allocated at the community level. At the state level, block grant amounts and distributions are often based on outdated formulas that consider population measures and funding environments at the time of their creation. We describe variation in state-level funding allocations for 5 federal block grant programs and the extent to which funding aligns with the current needs of state populations. METHODS: We conducted an analysis in 2022 of state block grant allocations as a function of state-level characteristics for 2015-2019 for all 50 states. We provide descriptive statistics of state block grant allocations and multivariate regression models for each program. Models include base characteristics relevant across programs plus supplemental characteristics based on program-specific goals and state population needs. RESULTS: Mean state block grant allocations per 1000 population by program ranged from $618 to $21 528 during 2015-2019. Characteristics associated with state allocations varied across block grants. For example, for every 1-percentage-point increase in the percentage of the population living in nonmetropolitan areas, Preventive Health and Health Services Block Grant funding was approximately $7 per 1000 population higher and Community Services Block Grant funding was approximately $40 per 1000 population higher. Few supplemental characteristics were associated with allocations. CONCLUSIONS: Current block grant funding does not align with state characteristics and needs. Future research should consider how funds are used at the state level or allocated to local agencies or organizations and compare state block grant allocations with other types of funding mechanisms, such as categorical funding.

Nonmedical Prescription Drug Use Among Female Adolescents: The Relative Influence of Maternal Factors, Social Norms, and Perceptions of Risk and Availability.

Increasing understanding of the risk and protective factors for adolescent nonmedical use of prescription drugs (NMUPD) could inform prevention efforts. Several correlates have been identified, including parental factors, perceptions about use and accessibility, social norms, and age. However, these constructs have rarely been simultaneously examined using paired data from parents and adolescents. We aimed to examine the relative influence of these correlates among dyads (N=349) of mothers and adolescent daughters. Using multiple logistic regression, daughters' past NMUPD and inclination for future NMUPD were regressed onto descriptive norms for friend use, perceived drug accessibility and risk of harm from use, daughter age, mothers' disapproval about use, mothers' past NMUPD and inclination for future NMUPD, and the mother-daughter relationship quality. Akaike weights and lasso regressions were also estimated to evaluate the relative importance of each correlate. Higher descriptive norms for friend use, older age, and mothers' inclination for NMUPD were risk factors for daughters' NMUPD, while a closer mother-daughter relationship and mothers' disapproving attitudes towards NMUPD were protective factors. The three analysis approaches were corroborative. Results suggest friend descriptive norms, mother-daughter relationship quality, and mothers' attitudes about NMUPD are important prevention targets.

The association between grandparents as caregivers and overdose mortality in Appalachia and non-Appalachia counties.

Objective: To assess the association of drug overdose mortality with grandparents serving as caregivers of children in Appalachia and non-Appalachia in the U.S. Methods: This study used a cross-sectional design, with percent of grandparents as caregivers and overdose mortality rates being of primary interest. County-level data were combined, and descriptive, bivariate, and multivariable statistics were applied. Multiple sociodemographic and geographic variables were included: median age of the population, percent of the population that is uninsured, percent of the population that is non-Hispanic white, teen birth rate, percent of high school dropouts, and rurality. Results: The percent of grandparents as caregivers increased as the overdose mortality rate increased (p < 0.01). For every 1% increase in the overdose mortality rate, the percent of grandparents as caregivers increased by 56% in Appalachian counties compared to 24% in non-Appalachian counties. After adjusting for sociodemographic characteristics, the interaction between overdose mortality and Appalachian vs. non-Appalachian counties was no longer significant (p = 0.3). Conclusions: Counties with higher overdose mortality rates had greater rates of grandparents as caregivers, with Appalachian counties experiencing greater rates of grandparents as caregivers than non-Appalachian counties. Sociodemographic characteristics that are often more prevalent in Appalachia may be driving the observed differences. Policy implications: Policies and programs are needed to support grandparents providing caregiving for children impacted by substance use disorders including reform to federal child welfare financing to support children, parents, and grandparent caregivers such as kinship navigation, substance use treatment and prevention services, mental health services and in-home supports.

Machine learning-based improvement of MDS-CBC score brings platelets into the limelight to optimize smear review in the hematology laboratory.

BACKGROUND: Myelodysplastic syndromes (MDS) are clonal hematopoietic diseases of the elderly characterized by chronic cytopenias, ineffective and dysplastic haematopoiesis, recurrent genetic abnormalities and increased risk of progression to acute myeloid leukemia. A challenge of routine laboratory Complete Blood Counts (CBC) is to correctly identify MDS patients while simultaneously avoiding excess smear reviews. To optimize smear review, the latest generations of hematology analyzers provide new cell population data (CPD) parameters with an increased ability to screen MDS, among which the previously described MDS-CBC Score, based on Absolute Neutrophil Count (ANC), structural neutrophil dispersion (Ne-WX) and mean corpuscular volume (MCV). Ne-WX is increased in the presence of hypogranulated/degranulated neutrophils, a hallmark of dysplasia in the context of MDS or chronic myelomonocytic leukemia. Ne-WX and MCV are CPD derived from leukocytes and red blood cells, therefore the MDS-CBC score does not include any platelet-derived CPD. We asked whether this score could be improved by adding the immature platelet fraction (IPF), a CPD used as a surrogate marker of dysplastic thrombopoiesis. METHODS: Here, we studied a cohort of more than 500 individuals with cytopenias, including 168 MDS patients. In a first step, we used Breiman's random forests algorithm, a machine-learning approach, to identify the most relevant parameters for MDS prediction. We then designed Classification And Regression Trees (CART) to evaluate, using resampling, the effect of model tuning parameters on performance and choose the "optimal" model across these parameters. RESULTS: Using random forests algorithm, we identified Ne-WX and IPF as the strongest discriminatory predictors, explaining 37 and 33% of diagnoses respectively. To obtain "simplified" trees, which could be easily implemented into laboratory middlewares, we designed CART combining MDS-CBC score and IPF. Optimal results were obtained using a MDS-CBC score threshold equal to 0.23, and an IPF threshold equal to 3%. CONCLUSIONS: We propose an extended MDS-CBC score, including CPD from the three myeloid lineages, to improve MDS diagnosis on routine laboratory CBCs and optimize smear reviews.

Erythroblastic synartesis associated with lymphoproliferative disorder: There can be more than meets the eye.

Erythroblastic synartesis is a rare cause of acquired dyserythropoiesis. Only 9 cases have been previously reported. We hereby report 3 cases of patients diagnosed with erythroblastic synartesis associated with monoclonal immunoglobulin and an overt malignant lymphoid disorder. A different B-cell clone may produce the monoclonal immunoglobulin, forming a biclonal disorder. In light of these data and literature review, treatment targeting the paraprotein seems to be efficient to control synartesis and correct anemia. In the case of monoclonal gammapathy associated with chronic lymphocytic leukemia, therapeutics should be adapted to control both chronic lymphocytic leukemia and monitored monoclonal immunoglobulin titer.

Determinants of CD19-positive vs CD19-negative relapse after tisagenlecleucel for B-cell acute lymphoblastic leukemia.

Tisagenlecleucel therapy has shown promising efficacy for relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, relapses occur in 30-50% of patients. Determinants for CD19pos versus CD19neg relapses are poorly characterized. We report on 51 patients with R/R BCP-ALL (median age 17 years) infused with tisagenlecleucel after lymphodepletion. Complete remission rate at D28 was 96%. Prior blinatumomab increased the risk of early failure at D28. The 18-month cumulative incidence of relapse (CIR), event-free survival (EFS), and overall survival (OS) were 51%, 44%, and 74%, respectively, at a median follow-up of 15.5 months. Factors associated with a high tumor burden (occurrence of cytokine release syndrome) and prior blinatumomab were associated with an increased CIR, and a shorter EFS and OS. Pre-lymphodepletion high disease burden (MRD ≥ 10-2, SHR 10.4, p = 0.03) and detectable MRD at D28 (SHR 7.2, p = 0.006) correlated with an increased risk of CD19neg relapse. Low disease burden (SHR 5.3, p = 0.03) and loss of B-cell aplasia (BCA) (SHR 21.7, p = 0.004) predicted an increased risk of CD19pos relapses. These data highlight the impact of prior therapy on patient outcome. Finally, detectable MRD at D28 and loss of BCA both define patients at high risk of relapse for whom additional interventions are needed.

Community pharmacist engagement in HIV and HCV prevention: Current practices and potential for service uptake.

Background: The central Appalachian region is at an elevated risk for HIV/HCV outbreaks, primarily due to injection drug use. Regional risk assessments highlight gaps in the evidence-based continuum of primary, secondary, and tertiary prevention strategies to minimize HIV/HCV transmission. One potential strategy for increasing the reach of HIV/HCV prevention efforts in rural areas is through provision of services at community pharmacies. Objective: To qualitatively describe community pharmacists' HIV/HCV-related prevention behaviors, attitudes, and beliefs in a 3-state central Appalachian region. Methods: Key informant interviews were conducted with 15 practicing community pharmacists. Theory of Planned Behavior-based questions probed for perceptions about the role of pharmacies in preventing and reducing HIV/HCV outbreaks in rural areas through activities such as syringe services, screening for HIV/HCV, and linking people to treatment when appropriate. Investigators applied thematic analysis to deductively and inductively generate themes from the interview transcripts. Results: Two overarching themes regarding pharmacist engagement in HIV/HCV-related prevention services were generated: 1) current approaches to primary prevention through nonprescription syringe sales (e.g., gatekeeping behaviors) and 2) potential for uptake of the continuum of HIV/HCV-related prevention services in community pharmacies. Future engagement of community pharmacists in the continuum of HIV/HCV-related prevention services comprised 2 subthemes as possible underlying factors: general and specific willingness to provide services and perceived fit within the pharmacy profession. Conclusions: Central Appalachian community pharmacists express a general willingness to help patients who may benefit from HIV/HCV-related prevention services, but current engagement, willingness, and perceived fit for offering specific prevention services in the community pharmacy setting is variable. This has potential immediate implications, such as prioritizing the introduction of more widely accepted services (e.g., provision of HIV/HCV-related prevention education) to community pharmacy practice, and longer-term implications, such as the integration and framing of HIV/HCV-related prevention services as helping behavior within the pharmacist professional identity.

"It's Took Over This Region": Patient Perspectives of Prescription Drug Abuse in Appalachia.

Background: Prescription drug abuse is a public health problem in the United States and the region of Appalachia, specifically. Primary care and addiction medicine-as possible points of access for prescription drugs with abuse potential and points of intervention for prescription drug abuse-are among the medical fields at its forefront. Little is known, however, about perceptions of prescription drug abuse across the two patient populations. Objectives: The objective of this qualitative analysis was to explore perceptions of the scale and context of prescription drug abuse among primary care and addiction medicine patients in Appalachia. Methods: As part of a mixed methods study, semi-structured interviews were conducted with 20 patients from primary care and addiction medicine in Central and South Central Appalachia from 2014 to 2015. The interviews were audio-recorded and transcribed verbatim. Thematic analysis was used to identify themes. Results: Three themes were identified: (1) pervasiveness of prescription drug abuse, describing perceptions of its high prevalence and negative consequences; (2) routes and routine practices for prescription drug acquisition and distribution, describing perceptions of routes of access to prescription drugs and behaviors exhibited to acquire and distribute prescription drugs; and (3) rationales for prescription drug acquisition and distribution, describing perceptions of the two underlying reasons for these processes-tolerance/addiction and revenue source. Conclusions/Importance: Perceptions of prescription drug abuse among primary care and addiction medicine patients in Appalachia are multifaceted, especially regarding prescription drug acquisition and distribution. Clinical practice implications for mitigating prescription drug abuse are discussed.

Communication Experiences of DATA-Waivered Physicians with Community Pharmacists: A Qualitative Study.

Background: Patients engaged in evidence-based opioid use disorder (OUD) treatment can obtain prescriptions for buprenorphine containing products from specially trained physicians that are subsequently dispensed by community pharmacists. Despite the involvement of physicians and community pharmacists in buprenorphine prescribing and dispensing, respectively, our understanding of their interactions in this context is limited. Objective: To qualitatively describe the communication and collaborative experiences between Drug Addiction Treatment Act 2000 (DATA)-waivered physicians and community pharmacists from the perspective of the physician. Methods: Ten key informant interviews were conducted with DATA-waivered physicians practicing in Northeast Tennessee. A semi-structured interview guide was used to explore communication and collaborative experiences between the physicians and community pharmacists. Interviews were audio recorded and transcribed verbatim. A coding frame was developed using concepts from the scientific literature and emerging codes from physician interviews. Interviews were coded using NVivo 11, with the data subsequently organized and evaluated for themes. Results: Four themes were identified: (1) mechanics of communication; (2) role specification and expectations; (3) education and understanding; and (4) climate of clinical practice. Physician-pharmacist communication primarily occurred indirectly through patients or staff and perceived challenges to collaboration included; lack of trust, stigma, and fear of regulatory oversight. Physicians also indicated the two professionals may lack clear roles and responsibilities as well as common expectations for treatment plans. Conclusions: Communication between DATA-waivered physicians and community pharmacists is influenced by multiple factors. Further research is warranted to improve physician-community pharmacist collaboration (PCPC) in the context of OUD pharmacotherapy and addiction treatment.

Phenotypic landscape of granulocytes and monocytes by multiparametric flow cytometry: A prospective study of a 1-tube panel strategy for diagnosis and prognosis of patients with MDS.

BACKGROUND: Multiparametric flow cytometry (MFC) was recently reported to be a helpful additional tool in the diagnosis of myelodysplastic syndromes (MDS). However, numerous aberrancies have been reported that makes their evaluation difficult as part of a routine diagnosis. METHODS: Here, we validated a 1-tube panel for the evaluation of granulocytic and monocytic maturation by MFC and correlated our findings with diagnosis and prognosis of MDS. A total of 251 samples with MDS suspicion were prospectively analyzed and compared to an internal reference database leading to the calculation of the Diff score. RESULTS: The associated specificity and sensitivity values of this scoring system were 92.1% and 60.4% in a first learning cohort and 96.7% and 65.2% in a second independent validation cohort. The combination of the Diff score with the concomitantly calculated Ogata score increased the sensitivity to 74.2% and 78.3% in the learning and validation cohorts, respectively. Finally, a normal Diff score in MDS patients was associated with a significant prolonged progression-free survival. CONCLUSIONS: Taken together, the present data indicate that our strategy is a sensitive and specific MFC tool for the diagnosis of MDS-related cytopenia(s) which could be also useful for predicting evolution of these diseases.

Provider-patient communication about prescription drug abuse: A qualitative analysis of the perspective of prescribers.

Background: Provider-patient communication underpins many initiatives aimed at reducing the public health burden associated with prescription drug abuse in the United States. The purpose of this qualitative analysis was to examine the characteristics of provider-patient communication about prescription drug abuse from the perspective of prescribers. Methods: From 2014 to 2015, 10 semi-structured interviews were conducted with a purposive sample of prescribers from multiple professions and medical fields in Central and South Central Appalachia. The interviews were conducted using a guide informed by Social Cognitive Theory and community theory research, audio-recorded, and transcribed verbatim. Thematic analysis, facilitated by NVivo 10 software, was used to generate themes. Results: Prescribers described 3 primary communication patterns with patients related to prescription drug abuse-informative, counteractive, and supportive. Prescribers also reported multiple factors-personal (e.g., education, experiences, and feelings of tension) and environmental (e.g., relationship with a patient, clinical resources, and policies on controlled prescription drugs)-that affect provider-patient communication and, by association, delivery of patient care related to prescription drug abuse. Conclusions: The findings suggest that provider-patient communication about prescription drug abuse is multidimensional and dynamic, characterized by multiple communication patterns and contributory factors. They have implications for (1) research aimed at advancing theoretical understanding of prescriber prescription drug abuse communication behaviors with patients and (2) interventions aimed at strengthening prescriber prescription drug abuse communication behaviors with patients.

The fraction of CD117/c-KIT-expressing erythroid precursors predicts ESA response in low-risk myelodysplastic syndromes.

BACKGROUND: Compelling evidence has emerged for the relevance of flow cytometry (FC) in the diagnostic work-up of myelodysplastic syndromes (MDS) but due to technical issues, the erythroid lineage has been under investigated, specifically in the therapeutic context. METHODS: Using the "no red cell lysis" method developed to set up the RED-score, we specifically quantified the fraction of CD117/c-KIT-expressing erythroid precursors in a cohort of 144 MDS patients and studied the correlation with response to erythropoiesis-stimulating agents (ESA) in a sub cohort of 63 low-risk MDS patients. RESULTS: We confirmed the previously reported increase in CD117/c-KIT-expressing erythroid precursors in a subset of MDS patients and demonstrated a strong association between a cut off of CD117/c-KIT-expressing erythroid precursors ≥3% and ESA response (P = 0.001), independent of red blood cell requirement. From our observations, we hypothesized that a decrease in CD117/c-KIT-expressing erythroid precursors could be a mechanism of ESA failure. Moreover, the fraction of CD117/c-KIT-expressing erythroid precursors was correlated with progression-free survival in low-risk MDS patients (P = 0.018). In vitro, we demonstrated in an EPO dependent cell line that CD117/c-KIT expression is necessary for cell survival under EPO stimulation. CONCLUSIONS: The quantification of the CD117/c-KIT-expressing erythroid precursors could be proposed as a new theranostic and prognostic marker in MDS treated by ESA. Future studies will be required to determine whether modulating CD117/c-KIT expression and signaling could be used to improve anemia in MDS. © 2019 International Clinical Cytometry Society.

CD13 expression in B cell malignancies is a hallmark of plasmacytic differentiation.

The diagnosis of Waldenström Macroglobulinaemia (WM)/lymphoplasmacytic lymphoma (LPL) remains one of exclusion because other B-cell lymphoproliferative disorders (B-LPD), such as marginal zone lymphoma (MZL), can fulfil similar criteria, including MYD88 L265P mutation. It has been suggested that expression of the myeloid marker CD13 (also termed ANPEP) is more frequent in LPL than in other B-LPD and has also been described on normal and malignant plasma cells. Here, CD13 expression was tested in a cohort of 1037 B-LPD patients from 3 centres by flow cytometry. The percentage of CD13-expressing cells was found to be variable among B-LPD but significantly higher in WM/LPL (median 31% vs. 0% in non-WM/LPL, P < 0·001). In multivariate linear regression, CD13 expression remained significantly associated with a diagnosis of WM/LPL (P < 0·001). A cut-off value of 2% of CD19+ cells co-expressing CD13 yielded the best diagnostic performance for WM/LPL assertion. This was further improved by association with the presence or absence of IgM paraprotein. Finally, given that previously published transcriptomic data revealed no difference in CD13 (also termed ANPEP) mRNA between normal and pathological B-cells, the hypothesis of some post-transcriptional regulation must be favoured. These results suggest that testing for CD13 expression in routine flow cytometry panels could help to discriminate WM/LPL from other B-LPD.

Mutational and cytogenetic analyses of 188 CLL patients with trisomy 12: A retrospective study from the French Innovative Leukemia Organization (FILO) working group.

Trisomy 12 (tri12) is the second most frequent chromosomal aberration (15%-20%) in chronic lymphocytic leukemia (CLL). Tri12 confers an intermediate prognosis but is a heterogeneous entity. We examined whether additional mutational or chromosomal alterations might impact tri12 patient outcomes. This retrospective study, carried out by the French Innovative Leukemia Organization, included 188 tri12 patients with comprehensive information on immunoglobulin heavy chain (IGHV) gene status, karyotypic/FISH abnormalities, and NOTCH1, TP53, SF3B1, and MYD88 mutations. The main cytogenetic abnormalities associated with tri12 were del(13q) (25%), additional trisomies (14%) (including tri19 (10%) and tri18 (4%)), 14q32 translocations (10%), del(17p) (6.5%), del(14q) (4%), and del(11q) (4%). Unmutated (UM) IGHV, NOTCH1, and TP53, mutations were identified in respectively 66%, 25%, and 8.5% of cases. Multivariate analyses showed that additional trisomies (HR = 0.43, 95% CI = 0.23-0.78, P = .01) were associated with a significantly longer time to first treatment in Binet stage A patients and with a lower risk of relapse (HR = 0.37, 95% CI = 0.15-0.9, P = .03) in the overall tri12 population. Binet stage B/C, TP53 disruption, and UM IGHV status were associated with a shorter time to next treatment, while Binet stage B/C (HR = 4, 95% CI = 1.6-4.9, P = .002) and TP53 disruption (HR = 5, 95% CI = 1.94-12.66, P = .001) conferred shorter overall survival in multivariate comparisons. These data indicate that additional cytogenetic and mutational abnormalities, and particularly additional trisomies, IGHV status, and TP53 disruption, influence tri12 patient outcomes and could improve risk stratification in this population.

A Dissemination and Implementation Science Approach to the Epidemic of Opioid Use Disorder in the United States.

PURPOSE OF REVIEW: This review aims to (1) conceptualize the complexity of the opioid use disorder epidemic using a conceptual model grounded in the disease continuum and corresponding levels of prevention and (2) summarize a select set of interventions for the prevention and treatment of opioid use disorder. RECENT FINDINGS: Epidemiologic data indicate non-medical prescription and illicit opioid use have reached unprecedented levels, fueling an opioid use disorder epidemic in the USA. A problem of this magnitude is rooted in multiple supply- and demand-side drivers, the combined effect of which outweighs current prevention and treatment efforts. Multiple primary, secondary, and tertiary prevention interventions, both evidence-informed and evidence-based, are available to address each point along the disease continuum-non-use, initiation, dependence, addiction, and death. If interventions grounded in the best available evidence are disseminated and implemented across the disease continuum in a coordinated and collaborative manner, public health systems could be increasingly effective in responding to the epidemic.