From monoclonal antibodies (mAbs) to Chimeric Antigen Receptor (CAR) T cells, immunotherapies have enhanced the efficacy of treatments against B cell malignancies. The same has not been true for ...Acute Myeloid Leukemia (AML). Hematologic toxicity has limited the potential of modern immunotherapies for AML at preclinical and clinical levels. Gemtuzumab Ozogamicin has demonstrated hematologic toxicity, but the challenge of preserving normal hematopoiesis has become more apparent with the development of increasingly potent immunotherapies. To date, no single surface molecule has been identified that is able to differentiate AML from Hematopoietic Stem and Progenitor Cells (HSPC). Attempts have been made to spare hematopoiesis by targeting molecules expressed only on later myeloid progenitors as well as AML or using toxins that selectively kill AML over HSPC. Other strategies include targeting aberrantly expressed lymphoid molecules or only targeting monocyte-associated proteins in AML with monocytic differentiation. Recently, some groups have accepted that stem cell transplantation is required to access potent AML immunotherapy and envision it as a rescue to avoid severe hematologic toxicity. Whether it will ever be possible to differentiate AML from HSPC using surface molecules is unclear. Unless true specific AML surface targets are discovered, stem cell transplantation could be required to harness the true potential of immunotherapy in AML.
Objectives
To examine the association between mental illness and chronic physical conditions in older adults and investigate whether co‐occurring substance use disorders (SUDs) are associated with ...greater risk of chronic physical conditions beyond mental illness alone.
Design
A retrospective cross‐sectional study.
Setting
Medicare and Medicaid programs in Massachusetts.
Participants
Massachusetts Medicare and Medicaid members aged 65 and older as of January 1, 2005 (N = 679,182).
Measurements
Diagnoses recorded on Medicare and Medicaid claims were used to identify mental illness, SUDs, and 15 selected chronic physical conditions.
Results
Community‐dwelling older adults with mental illness or SUDs had higher adjusted risk for 14 of the 15 selected chronic physical conditions than those without these disorders; the only exception was eye diseases. Moreover, those with co‐occurring SUDs and mental illness had the highest adjusted risk for 11 of these chronic conditions. For residents of long‐term care facilities, mental illness and SUDs were only moderately associated with the risk of chronic physical conditions.
Conclusion
Community‐dwelling older adults with mental illness or SUDs, particularly when they co‐occurred, had substantially greater medical comorbidity than those without these disorders. For residents of long‐term care facilities, the generally uniformly high medical comorbidity may have moderated this relationship, although their high prevalence of mental illness and SUDs signified greater healthcare needs. These findings strongly suggest the imminent need for integrating general medical care, mental health services, and addiction health services for older adults with mental illness or SUDs.
This study measured the impact of substance use disorders on Medicaid expenditures for behavioral and physical health care among beneficiaries with behavioral health disorders.
Claims for Medicaid ...beneficiaries with behavioral health diagnoses in 1999 from Arkansas, Colorado, Georgia, Indiana, New Jersey, and Washington were analyzed. Behavioral health and general medical expenditures for individuals with diagnoses of substance use disorders were compared with expenditures for those without such diagnoses. States were analyzed separately with adjustment for confounders.
A total of 148,457 beneficiaries met selection criteria, and 43,457 (29.3%) had a substance use diagnosis. Compared with other beneficiaries with behavioral health disorders, individuals with diagnoses of substance use disorders had significantly higher expenditures for physical health problems in five of six states. Approximately half of the additional care and expenditures were for treatment of physical conditions. Differences declined but remained statistically significant after adjustment for higher overall disease burden among beneficiaries with addictions. Medical expenditures for individuals with diagnoses of substance use disorders increased significantly with age in five of six states, whereas behavioral health expenditures were stable or declined. Hospital admissions for psychiatric and general medical reasons were higher for those with diagnoses of substance use disorders.
The impact of addiction on Medicaid populations with behavioral health disorders is greater than the direct cost of mental health and addictions treatment. Higher medical expenditures can be partly attributed to greater prevalence of co-occurring physical disorders, but expenditures remained higher after adjustment for disease burden. Spending estimates based only on behavioral health diagnoses may significantly underestimate addictions-related costs, particularly for older adults.
ObjectivesThis study had two aims: to measure the prevalence of long-term prescribing of high doses of antipsychotics and antipsychotic polypharmacy in a large Canadian province and to estimate the ...relative contributions of patient-, physician-, and hospital-level factors.MethodsGovernment hospital discharge, physician, and pharmaceutical claims data were linked to identify individuals with schizophrenia who in 2004 had antipsychotics available to them for at least 11 months. Individuals on a high dose throughout that period, as well as individuals on multiple concurrent antipsychotics (polypharmacy), were identified. Logistic and generalized linear mixed models using patient-, physician-, and hospital-level predictors were estimated.ResultsAmong the 12,150 individuals identified, 11.9% were on a high dose and 10.4% on antipsychotic polypharmacy continually, with 3.7% in both groups. After adjustment for potential confounders, analyses showed that systematic propensity for physicians to prescribe high doses accounted for 10.9% of the remaining unexplained variance, and physicians as a group who prescribed high doses across a hospital or psychiatry department accounted for 3.0%. For antipsychotic polypharmacy the corresponding percentages were 9.7% and 6.2%. Even after adjustment, the variation in high-dose prescribing and antipsychotic polypharmacy remained substantial.ConclusionsLong-term high-dose and antipsychotic polypharmacy prescribing appeared partly driven by some physicians’ and some hospitals’ propensities to prescribe in this way independently of patient characteristics. Given the weight of the evidence against high-dose prescribing and antipsychotic polypharmacy, measures addressed to physicians and hospitals most likely to prescribe high doses, antipsychotic polypharmacy, or both should be considered.
Antibody‐based therapy in acute myeloid leukemia (AML) has been marred by significant hematologic toxicity due to targeting of both hematopoietic stem and progenitor cells (HSPCs). Achieving greater ...success with therapeutic antibodies requires careful characterization of the potential target molecules on AML. One potential target is CD300f, which is an immunoregulatory molecule expressed predominantly on myeloid lineage cells. To confirm the value of CD300f as a leukemic target, we showed that CD300f antibodies bind to AML from 85% of patient samples. While one CD300f monoclonal antibody (mAb) reportedly did not bind healthy hematopoietic stem cells, transcriptomic analysis found that CD300f transcripts are expressed by healthy HSPC. Several CD300f protein isoforms exist as a result of alternative splicing. Importantly for antibody targeting, the extracellular region of CD300f can be present with or without the exon 4‐encoded sequence. This results in CD300f isoforms that are differentially bound by CD300f‐specific antibodies. Furthermore, binding of one mAb, DCR‐2, to CD300f exposes a structural epitope recognized by a second CD300f mAb, UP‐D2. Detailed analysis of publicly available transcriptomic data indicated that CD34+ HSPC expressed fewer CD300f transcripts that lacked exon 4 compared to AML with monocytic differentiation. Analysis of a small cohort of AML cells revealed that the UP‐D2 conformational binding site could be induced in cells from AML patients with monocytic differentiation but not those from other AML or HSPC. This provides the opportunity to develop an antibody‐based strategy to target AMLs with monocytic differentiation but not healthy CD34+ HSPCs. This would be a major step forward in developing effective anti‐AML therapeutic antibodies with reduced hematologic toxicity.
CD300f has an epitope encoded by exon 4 that is upregulated in AML with monocytic differentiation compared to hematopoietic stem and progenitor cells (HSPCs). A conformational epitope can be induced with an anti‐CD300f antibody in AML with monocytic differentiation but not HSPC. These epitopes are promising targets for antibody‐based AML therapies with reduced hematologic toxicity.
After 20 years of development and research, dual diagnosis services for clients with severe mental illness are emerging as an evidence-based practice. Effective dual diagnosis programs combine mental ...health and substance abuse interventions that are tailored for the complex needs of clients with comorbid disorders. The authors describe the critical components of effective programs, which include a comprehensive, long-term, staged approach to recovery; assertive outreach; motivational interventions; provision of help to clients in acquiring skills and supports to manage both illnesses and to pursue functional goals; and cultural sensitivity and competence. Many state mental health systems are implementing dual diagnosis services, but high-quality services are rare. The authors provide an overview of the numerous barriers to implementation and describe implementation strategies to overcome the barriers. Current approaches to implementing dual diagnosis programs involve organizational and financing changes at the policy level, clarity of program mission with structural changes to support dual diagnosis services, training and supervision for clinicians, and dissemination of accurate information to consumers and families to support understanding, demand, and advocacy.
Abstract Purpose To examine factors affecting prenatal and postpartum care for an insured, but vulnerable, population. Methods Individual-level data on three measures of care adequacy were obtained ...for Massachusetts Medicaid Managed Care women who met the National Committee on Quality Assurance’s Healthcare Effectiveness Data and Information Set denominator criteria for the prenatal and postpartum care measures in 2007 ( n = 1,882). We modeled individual compliance with each measure separately as a binomial logistic function with individual and neighborhood characteristics, provider type, and health plan as explanatory variables. Findings In our sample, 85% of women initiated care in the first trimester, but only 62% met the goal of receiving more than 80% of the recommended number of prenatal visits. Just 60% had a timely postpartum care visit. Having a diagnosis of substance abuse or dependence reduced the odds of meeting all measures. Women with disabilities were less likely to attain two of the three measures of adequate care, as were women with other children in the household. Women who enrolled in Medicaid in the first trimester were more likely to receive the recommended number of prenatal visits than those who were enrolled before pregnancy. Conclusion Given the importance of prenatal and postpartum care for maternal and child health and the recent national declining trend in timely care, initiatives to improve rates of timely and adequate care are crucial and must include components tailored toward particularly vulnerable subpopulations.
Substance use disorders have a profound impact on the course of severe mental illnesses and on the family, but little research has evaluated the impact of family intervention for this population. To ...address this question, a randomized controlled trial was conducted comparing a brief (2-3 mo) Family Education (ED) program with a longer-term (9-18 mo) program that combined education with teaching communication and problem-solving skills, Family Intervention for Dual Disorders (FIDD). A total of 108 clients (77% schizophrenia-spectrum) and a key relative were randomized to either ED or FIDD and assessed at baseline and every 6 months for 3 years. Rates of retention of families in both programs were moderate. Intent-to-treat analyses indicated that clients in both programs improved in psychiatric, substance abuse, and functional outcomes, as did key relatives in knowledge of co-occurring disorders, burden, and mental health functioning. Clients in FIDD had significantly less severe overall psychiatric symptoms and psychotic symptoms and tended to improve more in functioning. Relatives in FIDD improved more in mental health functioning and knowledge of co-occurring disorders. There were no consistent differences between the programs in substance abuse severity or family burden. The findings support the utility of family intervention for co-occurring disorders, and the added benefits of communication and problem-solving training, but also suggest the need to modify these programs to retain more families in treatment in order to provide them with the information and skills they need to overcome the effects of these disorders.
Assisted Outpatient Treatment (AOT) is a court-mandated program intended to engage adults with serious mental illness who have challenges with voluntary treatment adherence. AOT programs are designed ...to promote outpatient treatment participation, reduce emergency care, and decrease justice involvement. Research has found AOT programs to be effective in reducing hospitalizations and justice involvement. Yet, concerns have been raised, including limiting individual autonomy and self-determination and overrepresentation of individuals from BIPOC backgrounds. This article describes the evolution the AOT Houston Model. Through applying the social work lens, this innovative model builds on AOT strengths and addresses limitations. The Houston AOT Model has five goals guided by the core tenets of client empowerment and self-determination. This Model prioritizes six elements including housing, employment, access to public benefits, transportation, service continuity, and care coordination/communication. Implications for practice and policy are presented with strategies for successful implementation of comprehensive AOT programs in other jurisdictions.
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