Systematic review on infusion reactions associated with chemotherapies and monoclonal antibodies for metastatic colorectal cancer.

OBJECTIVE: The objective of this systematic review is to summarize the literature to date on the rates of infusion reactions (IR) associated with chemotherapies and monoclonal antibody (mAb) drug therapies used for the treatment of metastatic colorectal cancer (mCRC) and the associated clinical and economic impact. METHODS: This study searched Medline, Medline (R) In-Process, Embase and Cochrane Library databases for studies on IRs associated with chemotherapy and mAbs in mCRC patients from 2000-2011. RESULTS: For chemotherapy, the incidence of IRs ranged from 0-71% for all grades and 0-15% for grade 3-4. Rates of all grade IRs associated with cetuximab ranged from 7.6-33% and grade 3-4 IR rates were 0-22%. Rates of all grade IRs associated with panitumumab ranged from 0-4% and rates of grade 3-4 IRs ranged from 0-1%. The overall rate of IRs associated with bevacizumab ranged from 1.6-11%, with a rate of 0-4% for grade 3-4 IRs. A range of 50-100% of patients with grade 3-4 IRs terminated chemotherapy, and 34-100% of cetuximab patients with grade 3-4 IRs discontinued cetuximab therapy. No data were reported for bevacizumab or panitumumab. Only one study evaluated the economic impact of IRs. The study compared cetuximab administrations without an IR to those with an IR requiring resource utilization and found that mean costs were $9308 and $1725 higher for those with an IR requiring an emergency room visit or hospitalization and for those with an IR requiring outpatient treatment, respectively. CONCLUSIONS: The incidence of IRs varies among different mAbs; and IRs may cause treatment disruption and require costly medical interventions.

Disease-modifying drug initiation patterns in commercially insured multiple sclerosis patients: a retrospective cohort study.

BACKGROUND: The goal of this research was to compare the demographics, clinical characteristics and treatment patterns for newly diagnosed multiple sclerosis (MS) patients in a commercial managed care population who received disease-modifying drug (DMD) therapy versus those not receiving DMD therapy. METHODS: A retrospective cohort study using US administrative healthcare claims identified individuals newly diagnosed with MS (no prior MS diagnosis 12 months prior using ICD-9-CM 340) and ≥18 years old during 2001-2007 to characterize them based on demographics, clinical characteristics, and pharmacologic therapy for one year prior to and a minimum of one year post-index. The index date was the first MS diagnosis occurring in the study period. Follow-up of subjects was done by ICD-9-CM code identification and not by actual chart review. Multivariate analyses were conducted to adjust for confounding variables. RESULTS: Patients were followed for an average of 35.7±17.5 months after their index diagnosis. Forty-three percent (n=4,462) of incident patients received treatment with at least one of the DMDs during the post-index period. Treated patients were primarily in the younger age categories of 18-44 years of age, with DMD therapy initiated an average of 5.3±9.1 months after the index diagnosis. Once treatment was initiated, 27.7% discontinued DMD therapy after an average of 17.6±14.6 months, and 16.5% had treatment gaps in excess of 60 days. CONCLUSIONS: Nearly 60% of newly-diagnosed MS patients in this commercial managed care population remained untreated while over a quarter of treated patients stopped therapy and one-sixth experienced treatment gaps despite the risk of disease progression or a return of pre-treatment disease activity.

Evidence for substance abuse services and policy research: a systematic review of national databases.

We reviewed 39 national government- and nongovernment-sponsored data sets related to substance addiction policy. These data sets describe patients with substance use disorders (SUDs), treatment providers and the services they offer, and/or expenditures on treatment. Findings indicate the availability of reliable data on the prevalence of SUD and the characteristics of specialty treatment facilities, but meager data on financing and services. Gaps in information might be filled through agency collaboration to redesign, coordinate, and augment existing substance abuse and general health surveys. Despite noted gaps, these data sets represent an unusually rich set of resources for health services and policy research.

Alcohol and opioid dependence medications: prescription trends, overall and by physician specialty.

Over the past decade, advances in addiction neurobiology have led to the approval of new medications to treat alcohol and opioid dependence. This study examined data from the IMS National Prescription Audit (NPA) Plus database of retail pharmacy transactions to evaluate trends in U.S. retail sales and prescriptions of FDA-approved medications to treat substance use disorders. Data reveal that prescriptions for alcoholism medications grew from 393,000 in 2003 ($30 million in sales) to an estimated 720,000 ($78 million in sales) in 2007. The growth was largely driven by the introduction of acamprosate in 2005, which soon became the market leader ($35 million in sales). Prescriptions for the two buprenorphine formulations increased from 48,000 prescriptions ($5 million in sales) in the year of their introduction (2003) to 1.9 million prescriptions ($327 million in sales) in 2007. While acamprosate and buprenorphine grew rapidly after market entry, overall substance abuse retail medication sales remain small relative to the size of the population that could benefit from treatment and relative to sales for other medications, such as antidepressants. The extent to which substance dependence medications will be adopted by physicians and patients, and marketed by industry, remains uncertain.

Transforming mental health and substance abuse data systems in the United States.

State efforts to improve mental health and substance abuse service systems cannot overlook the fragmented data systems that reinforce the historical separateness of systems of care. These separate systems have discrete approaches to treatment, and there are distinct funding streams for state mental health, substance abuse, and Medicaid agencies. Transforming mental health and substance abuse services in the United States depends on resolving issues that underlie separate treatment systems--access barriers, uneven quality, disjointed coordination, and information silos across agencies and providers. This article discusses one aspect of transformation--the need for interoperable information systems. It describes current federal and state initiatives for improving data interoperability and the special issue of confidentiality associated with mental health and substance abuse treatment data. Some achievable steps for states to consider in reforming their behavioral health data systems are outlined. The steps include collecting encounter-level data; using coding that is compliant with the Health Insurance Portability and Accountability Act, including national provider identifiers; forging linkages with other state data systems and developing unique client identifiers among systems; investing in flexible and adaptable data systems and business processes; and finding innovative solutions to the difficult confidentiality restrictions on use of behavioral health data. Changing data systems will not in itself transform the delivery of care; however, it will enable agencies to exchange information about shared clients, to understand coordination problems better, and to track successes and failures of policy decisions.

Future funding for mental health and substance abuse: increasing burdens for the public sector.

Spending on mental health (MH) and substance abuse (SA) treatment is expected to double between 2003 and 2014, to $239 billion, and is anticipated to continue falling as a share of all health spending. By 2014, our projections of SA spending show increasing responsibility for state and local governments (45 percent); deteriorating shares financed by private insurance (7 percent); and 42 percent of SA spending going to specialty SA centers. For MH, Medicaid is forecasted to fund an increasingly larger share of treatment costs (27 percent), and prescription medications are expected to capture 30 percent of MH spending by 2014.

Imaging the addicted human brain.

Modern imaging techniques enable researchers to observe drug actions and consequences as they occur and persist in the brains of abusing and addicted individuals. This article presents the five most commonly used techniques, explains how each produces images, and describes how researchers interpret them. The authors give examples of key findings illustrating how each technique has extended and deepened our knowledge of the neurobiological bases of drug abuse and addiction, and they address potential clinical and therapeutic applications.

NF-kappaB p50-deficient mice show reduced anxiety-like behaviors in tests of exploratory drive and anxiety.

The ubiquitous transcription factor nuclear factor (NF)-kappaB plays a prominent role in regulation of inflammatory immune responses and in cell survival. Recently, it has been found to be active in neurons, and mice lacking NF-kappaB subunits p50 or p65 show deficits in specific cognitive tasks. Here we demonstrate a strikingly low level of anxiety-like behavior in the p50(-/-) mouse. In an open field, the mutant mice showed significantly less defecation, more rearing, and more time spent in the center compartment relative to wild type control mice. The p50(-/-) mice also spent more time investigating a novel object placed in the open field. On the elevated plus maze, p50(-/-) mice spent more time on the open arms and had increased numbers of open arm entries relative to wild type. In group housing conditions, they did not establish dominant-subordinate hierarchies, whereas wild type control animals did so, in part, by whisker barbering and conspecific allogrooming. In tests of general health, sensorimotor function, and daily activity on a circadian rhythm, p50(-/-) mice were normal. Thus, absence of the p50 subunit of the NF-kappaB transcription factor, which results in altered NF-kappaB transcriptional activity in cells throughout the body and brain, alters neuronal circuitry underlying manifestation of emotional behavior. The p50 subunit appears to play a role in normal expression of certain forms of anxiety.

Neurodegeneration in the rat hippocampus and striatum after middle cerebral artery occlusion.

Animal models of ischemia are in wide use to elucidate the molecular mechanisms of brain injury that result from cardiovascular disease in humans. We have used the fluorescent, anionic dye, Fluoro-Jade, to examine cellular degeneration that occurs in association with the middle cerebral artery occlusion (MCAO) model. MCAO results in cortical infarction as well as damage to the hippocampus leading to a delayed form of death of hippocampal neurons. We examined brain sections at 6 h, 12 h, 1, 4, 7, 14 and 21 days after injury. Fluoro-Jade labeling of the striatum was seen over a protracted time-course, with degeneration beginning by 6 h after injury. Neuronal degeneration in the hippocampus, in contrast, occurs between 12 h and 7 days after injury with neuronal death reaching a peak at 4 days. GFAP/Fluoro-Jade double labeling revealed that the Fluoro-Jade positive staining at late time-points in the striatum included astrocytic cells. Together, the results show Fluoro-Jade to be a useful marker of cellular degeneration following ischemic injury. Further, the use of this dye has enabled us to demonstrate previously undescribed events of cellular injury resulting from ischemia.