Genome-wide association study of circulating folate one-carbon metabolites.

Experimental, observational, and clinical trials support a critical role of folate one-carbon metabolism (FOCM) in colorectal cancer (CRC) development. In this report, we focus on understanding the relationship between common genetic variants and metabolites of FOCM. We conducted a genome-wide association study of FOCM biomarkers among 1,788 unaffected (without CRC) individuals of European ancestry from the Colon Cancer Family Registry.

Clinical use of blinatumomab for B-cell acute lymphoblastic leukemia in adults.

Adults with relapsed or refractory B-cell acute lymphoblastic leukemia have a dismal prognosis with a short median overall survival that can be measured in months. Because most patients will have chemotherapy-resistant disease, allogeneic hematopoietic stem cell transplantation remains the only potentially curative treatment. Despite advances in current management, patients continue to have poor outcomes and lack of durable responses.

Emerging treatment options for myelofibrosis: focus on pacritinib.

Myelofibrosis (MF) is a myeloid malignancy associated with a heavy symptomatic burden that decreases quality of life and presents a risk for leukemic transformation. While there are limited curative treatments, the recent discovery of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway dysregulation has led to many clinical investigations for new treatment approaches. This review provides practical knowledge on the disease state, an overview of treatment options, and specifically focuses on the efficacy and safety of pacritinib in the management of MF.

Oral delivery of ivermectin using a fast dissolving oral film: Implications for repurposing ivermectin as a pharmacotherapy for alcohol use disorder.

Individuals suffering from an alcohol-use disorder (AUD) constitute a major health concern. Preclinical studies in our laboratory show that acute and chronic intraperitoneal (i.p.

Health care resource utilization and direct medical costs for patients with schizophrenia initiating treatment with atypical versus typical antipsychotics in Tianjin, China.

Background: It is uncertain whether the extra acquisition costs of atypical antipsychotics over typical antipsychotics are offset by their other reduced resource use especially in hospital services in China. This study compared the psychiatric-related health care resource utilization and direct medical costs for patients with schizophrenia initiating atypical or typical antipsychotics in Tianjin, China.

Methods: Data were obtained from the Tianjin Urban Employee Basic Medical Insurance database (2008-2010).

Manipulations of extracellular Loop 2 in α1 GlyR ultra-sensitive ethanol receptors (USERs) enhance receptor sensitivity to isoflurane, ethanol, and lidocaine, but not propofol.

We recently developed ultra-sensitive ethanol receptors (USERs) as a novel tool for investigation of single receptor subunit populations sensitized to extremely low ethanol concentrations that do not affect other receptors in the nervous system. To this end, we found that mutations within the extracellular Loop 2 region of glycine receptors (GlyRs) and γ-aminobutyric acid type A receptors (GABAARs) can significantly increase receptor sensitivity to micro-molar concentrations of ethanol resulting in up to a 100-fold increase in ethanol sensitivity relative to wild-type (WT) receptors. The current study investigated: (1) Whether structural manipulations of Loop 2 in α1 GlyRs could similarly increase receptor sensitivity to other anesthetics; and (2) If mutations exclusive to the C-terminal end of Loop 2 are sufficient to impart these changes.

Cost-effectiveness analysis of alternative screening and treatment strategies for heterozygous familial hypercholesterolemia in the United States.

Background/objectives: Familial hypercholesterolemia (FH) is a genetic disorder that leads to premature heart disease or stroke if untreated. Statins are effective for individuals with FH but less than 20% of actual cases are diagnosed in the US and many people are not adherent to treatment. Using new knowledge regarding mutations responsible for FH, some European countries have developed genetic FH screening strategies, many of which have been shown to be cost-effective.

Cost effectiveness of fingolimod, teriflunomide, dimethyl fumarate and intramuscular interferon-β1a in relapsing-remitting multiple sclerosis.

Objective: The aim of the study was to compare the cost effectiveness of fingolimod, teriflunomide, dimethyl fumarate, and intramuscular (IM) interferon (IFN)-β(1a) as first-line therapies in the treatment of patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: A Markov model was developed to evaluate the cost effectiveness of disease-modifying drugs (DMDs) from a US societal perspective. The time horizon in the base case was 5 years.

Glycine and GABA(A) ultra-sensitive ethanol receptors as novel tools for alcohol and brain research.

A critical obstacle to developing effective medications to prevent and/or treat alcohol use disorders is the lack of specific knowledge regarding the plethora of molecular targets and mechanisms underlying alcohol (ethanol) action in the brain. To identify the role of individual receptor subunits in ethanol-induced behaviors, we developed a novel class of ultra-sensitive ethanol receptors (USERs) that allow activation of a single receptor subunit population sensitized to extremely low ethanol concentrations. USERs were created by mutating as few as four residues in the extracellular loop 2 region of glycine receptors (GlyRs) or γ-aminobutyric acid type A receptors (GABA(A)Rs), which are implicated in causing many behavioral effects linked to ethanol abuse.

A review of the economic burden of glioblastoma and the cost effectiveness of pharmacologic treatments.

Grade IV glioma (glioblastoma) is one of the most common brain/central nervous system cancers. In 2005, the standard of care for adjuvant treatment was significantly changed with the approval of temozolomide. Carmustine wafers have also gained some popularity.

P2X4 receptors (P2X4Rs) represent a novel target for the development of drugs to prevent and/or treat alcohol use disorders.

Alcohol use disorders (AUDs) have a staggering socioeconomic impact. Few therapeutic options are available, and they are largely inadequate. These shortcomings highlight the urgent need to develop effective medications to prevent and/or treat AUDs.

Multiday administration of ivermectin is effective in reducing alcohol intake in mice at doses shown to be safe in humans.

Ivermectin (IVM), an FDA approved anthelmintic agent, can significantly reduce ethanol intake in mice following acute administration. The current study evaluates the sustainability and safety of multiday IVM administration in reducing 10% v/v ethyl alcohol (10E) intake in mice at a dose shown to be safe in humans. We tested the effect of 10-day administration of IVM (3.

Access to oral osteoporosis drugs among female Medicare Part D beneficiaries.

Background: For women living with osteoporosis, high out-of-pocket (OOP) drug costs may prevent drug therapy initiation. We investigate the association between oral osteoporosis OOP medication costs and female Medicare beneficiaries' initiation of osteoporosis drug therapy.

Methods: We used 2007 and 2008 administrative claims and enrollment data for a 5% random sample of Medicare beneficiaries.

Avermectins differentially affect ethanol intake and receptor function: implications for developing new therapeutics for alcohol use disorders.

Our laboratory is investigating ivermectin (IVM) and other members of the avermectin family as new pharmaco-therapeutics to prevent and/or treat alcohol use disorders (AUDs). Earlier work found that IVM significantly reduced ethanol intake in mice and that this effect likely reflects IVM's ability to modulate ligand-gated ion channels. We hypothesized that structural modifications that enhance IVM's effects on key receptors and/or increase its brain concentration should improve its anti-alcohol efficacy.

Microbicidal effects of α- and θ-defensins against antibiotic-resistant Staphylococcus aureus and Pseudomonas aeruginosa.

Antibiotic-resistant bacterial pathogens threaten public health. Because many antibiotics target specific bacterial enzymes or reactions, corresponding genes may mutate under selection and lead to antibiotic resistance. Accordingly, antimicrobials that selectively target overall microbial cell integrity may offer alternative approaches to therapeutic design.

The risk of long-term morbidity and mortality in patients with chronic hepatitis C: results from an analysis of data from a Department of Veterans Affairs Clinical Registry.

Importance: The impact of viral load suppression, genotype, race, and other factors on the risk of late-stage liver-related events in patients with hepatitis C (HCV) has been assessed previously using data from small observational cohorts or clinical trials. Data from large real-world practice samples are needed to improve risk factor estimates for late-stage liver events and death in HCV.

Objective: To describe the natural history of HCV in real-world clinical practice.

Effect of exenatide, pen insulin, and vial insulin on patient outcomes: a retrospective database analysis of persistence and first-year costs in a commercially insured population.

Objective: We compared health care costs and medication persistence for patients with type 2 diabetes initiating treatment using exenatide, pen insulin, or vial insulin.

Methods: Commercial health plan data (2004-2008) were used to identify episodes of antidiabetic drug therapy, which were then classified according to treatment history: first observed treatment, restarting a previous therapy (90-day gap in all treatment), switching therapy, and augmentation therapy. Three time periods were defined for each episode: the month in which the episode was initiated (index month), 6 months before the index month (preindex period), and 12 months after the index month (postindex period).

Comparative effectiveness of statin plus fibrate combination therapy and statin monotherapy in patients with type 2 diabetes: use of propensity-score and instrumental variable methods to adjust for treatment-selection bias.

Purpose: Type 2 diabetes is associated with increased cardiovascular risk. The comparative effectiveness of statin plus fibrate combination therapy and statin monotherapy in reducing risk of cardiovascular disease in real-world settings is unknown.

Methods: A retrospective database analysis was performed using a large managed care claims database of patients identified with type 2 diabetes based on diagnosis codes from January 2002 through December 2003 and continuously enrolled for the entire study period, 5.

Self-reported barriers to hemophilia care in people with factor VIII deficiency.

Background: In 1975, a national network of hemophilia treatment centers (HTCs) was created to increase access to healthcare services for individuals with hemophilia. Studies demonstrate that care in HTCs improves outcomes and reduces costs.

Purpose: The objective of the study was to assess the association of demographic, insurance, and clinical characteristics with self-reported barriers to HTC utilization.

Behind-the-counter statins: a silver bullet for reducing costs and increasing access?

Objective: To examine how the 2004 introduction of behind-the-counter (BTC) simvastatin in the United Kingdom affected utilization, prices, and expenditures.

Data Sources/study Setting: Secondary data on simvastatin utilization, prices, and expenditures between 1997 and 2007 in the United Kingdom and four other countries.

Study Design: We used a difference-in-differences approach to estimate how the introduction of BTC simvastatin affected utilization, prices, and expenditures.

Cost-effectiveness of Prostate Health Index for prostate cancer detection.

Objective: • To evaluate the cost-effectiveness of early prostate cancer detection with the Beckman Coulter Prostate Health Index (phi) (not currently available in the USA) adding to the serum prostate-specific antigen (PSA) test compared with the PSA test alone from the US societal perspective.

Patients And Methods: • Phi was developed as a combination of PSA, free PSA, and a PSA precursor form [-2]proPSA to calculate the probability of prostate cancer and was used as an aid in distinguishing prostate cancer from benign prostatic conditions for men with a borderline PSA test (e.g.

Impact of drug treatment history on comparative effectiveness research in schizophrenia.

Objectives: Randomized clinical trials frequently attract volunteer patients who were either non-compliant or seeking to switch therapies. Patients on active therapies often undergo a washout period after which a single medication is initiated. Observational research has the potential to compare alternative treatments under a wider range of clinical situations if care is taken to document each patient's treatment history.

Budget impact analysis of a new prostate cancer risk index for prostate cancer detection.

The objective of this study was to evaluate the budget impact of a new prostate cancer risk index for detecting prostate cancer. The index is calculated as the combination of serum prostate-specific antigen (PSA), free PSA and a precursor form p2PSA. We constructed two budget impact models using PSA cutoff values of ≥2 ng ml(-1) (model #1) and ≥4 ng ml(-1) (model #2) for recommending a prostate biopsy in a hypothetical health plan with 100 000 male members aged 50-75 years old.