Methadone hydrochloride and leukemia cells: Effects on cell viability, DNA fragmentation and apoptotic proteins expression level.

Leukemia is a type of blood cancer where abnormal and immature leucocytes are produced in the bone marrow. Methadone hydrochloride is a man-made drug that is commonly used in the maintenance treatment for drug addiction. The objective of this research was to determine the cytotoxic activity and apoptotic effects of methadone hydrochloride treatment towards two leukemia cell lines which are CCRF-CEM and HL-60. CCRF-CEM and HL-60 cells were treated with methadone hydrochloride for 24 and 48 hours to determine the cytotoxic activity. IC50 at 24 hours obtained for CCRF-CEM was 121.6µmol/L while IC50 for HL-60 cells was 97.18µmol/L. Result obtained from DNA fragmentation assay showed no characteristic DNA ladder pattern in CCRF-CEM leukemia cells treated with methadone hydrochloride. Characteristics DNA ladder pattern was observed in methadone hydrochloride treated HL-60 cells. Formation of comets was seen in methadone hydrochloride treated CCRF-CEM and HL-60 cells with varying degree of DNA damage. The comets formed by methadone hydrochloride treated HL-60 cells were more prominent as compared to methadone-treated CCRF-CEM cells. The expression of apoptotic-related proteins in methadone-treated CCRF-CEM and HL-60 cells were checked by incubating the cell lysate with Raybio® Human Apoptosis Antibody Array. Significant alterations in expression level of apoptosis-related proteins in methadone hydrochloride treated CCRF-CEM cells were found involving upregulation of caspase-8 expression and downregulation of survivin expression. Methadone hydrochloride induced apoptosis in HL-60 cells involved upregulation of Bid and caspase-8 expression and downregulation of Bcl-2, p21 and survivin expression.

Pharmacy Student Learning During Advanced Pharmacy Practice Experiences in Relation to the CAPE 2013 Outcomes.

Outcomes from The Center for Advancement of Pharmacy Education (CAPE) are intended to represent the terminal knowledge, skills, and attitudes pharmacy students should possess and have guided delivery of pharmacy education for more than two decades. Advanced pharmacy practice experiences (APPEs) are the endpoint of pharmacy curricula where demonstration and assessment of terminal learning occurs. This review examines published literature in relation to the most recent CAPE outcomes to determine the extent to which they have been addressed during APPEs since 1996. Details related to the APPE focus, intervention(s)/learning setting(s), and assessments are summarized according to the 15 CAPE outcomes. Further, the assessments are categorized according to the level of learning achieved using an available method. Common CAPE outcomes are highlighted, as well as those for which published reports are lacking for APPEs. The range and quality of assessments are discussed and emphasize the need for continuous improvement of scholarly design and assessment.

Vascular protection with dipeptidyl peptidase-IV inhibitors in diabetes: experimental and clinical therapeutics.

The dipeptidyl peptidase-IV (DPP-IV) inhibitors, also known as gliptins, are widely used in clinical practice either as monotherapy or in combination with other agents for the management of type 2 diabetes mellitus (T2DM). The gliptins are effective, safe, well tolerated, and conveniently administered once/day. Moreover, these agents have a low risk for drug interactions and do not require initial dosage titrations to lessen adverse effects. They are not only clinically desirable, having the most favorable side-effect profile of all available antihyperglycemic medications, but they can also be used in any stage of renal or hepatic impairment. The antihyperglycemic effects of gliptins are attributed to inhibition of the DPP-IV enzyme, thereby prolonging the half-life (t1/2 ) of incretin hormones (substrates) to promote glucose-stimulated insulin secretion. Beyond their glucose-lowering effects, gliptins may also reduce the risk of cardiovascular disease by improving endothelial function, lowering blood pressure, reducing inflammation, and delaying the progression of atherosclerosis. Although the vascular protective effects of gliptins depend on incretins, the contributions of other biologically important endogenous vasoactive substrates of DPP-IV are worthy of consideration from a therapeutic standpoint. Future and ongoing studies should help determine whether these vascular protective effects contribute to improved cardiovascular outcomes in patients with T2DM. The experimental and clinical evidence supporting the vascular protective effects of gliptins is reviewed.

The WISEWOMAN program: smoking prevalence and key approaches to smoking cessation among participants, July 2008-June 2013.

BACKGROUND: Tobacco use is a major risk factor for cardiovascular disease (CVD) and is the leading preventable cause of death, disease, and disability in the United States. The CDC's Well-Integrated Screening and Evaluation for Women Across the Nation (WISEWOMAN) program addresses the heart health of low-income under- or uninsured women between the ages of 40 and 64 years. This article discusses WISEWOMAN's key approaches to smoking cessation and their impact on WISEWOMAN participants' cardiovascular health. METHODS: A longitudinal retrospective analysis was conducted using data from 21 funded CDC programs from July 2008 to June 2013. Data were collected on 149,767 women to assess CVD risk, smoking status, and utilization of programs related to tobacco cessation. RESULTS: The overall prevalence of smoking among the WISEWOMAN population during this period was 28%. Increases in referrals to tobacco quitlines, tobacco-cessation counseling, lifestyle interventions, and other community-based tobacco-cessation programs contributed to a 15% smoking-cessation rate among smokers who returned for a rescreening assessment over the 5-year program period. CONCLUSION: The WISEWOMAN program has observed a smoking-cessation rate of 15% over the 5-year program period. WISEWOMAN's key approaches include continuous technical assistance that highlights quitline referrals, motivational interviewing done by program staff, and professional-development strategies for WISEWOMAN healthcare providers. WISEWOMAN will continue its programmatic emphasis on smoking cessation by partnering with state tobacco-cessation programs to work toward a lower smoking-prevalence rate among program participants.

Implementation of computerized prescriber order entry in four academic medical centers.

PURPOSE: Lessons learned through the transition to computerized prescriber order entry (CPOE) at four academic medical centers are reviewed. SUMMARY: CPOE is an important strategy in efforts to improve medication and patient safety and achieve compliance with federal health care information technology objectives. Pharmacy-led CPOE implementation teams at Brigham and Women's Hospital, Georgia Health Sciences Health System, UC Health University Hospital, and University of Utah Hospitals and Clinics were challenged to overcome different types of resource, staffing, and hardware-software constraints. Their collective experience points to a number of factors that are essential to successful CPOE implementation, including (1) involvement by all ancillary personnel in system planning, development, implementation, and refinement, (2) selection of CPOE equipment that offers a high level of interoperability with existing information systems and automated dispensing machines, (3) development of electronic order sets and clinical decision support (CDS) tools that are designed for ease of use and tailored to the hospital's clinical workflows, and (4) dedication of adequate resources and time for staff training, technical support, and system troubleshooting and maintenance. In particular, facilities transitioning to CPOE must secure initial and ongoing physician input and feedback to ensure patient safety and reduce CDS-related problems and other barriers to broad system acceptance. CONCLUSION: Before implementing CPOE, addressing institutional considerations pertaining to system selection, preimplementation preparation, staff training, necessary equipment, program rollout, and postimplementation maintenance can increase the likelihood of a smooth transition to CPOE and optimal system performance.

Adverse drug reaction deaths reported in United States vital statistics, 1999-2006.

BACKGROUND: Adverse drug reactions (ADRs) are an important source of morbidity and mortality during medical care. OBJECTIVE: To examine the trends in mortality related to ADRs reported through the US vital statistics system since January 1999. METHODS: Demographic characteristics of people reported as dying as a result of ADRs from 1999 to 2006 were evaluated. The National Mortality Statistics database was queried for International Classification of Diseases, Tenth Revision, codes Y40-Y59, which are specific for deaths due to adverse effects of drugs in therapeutic use. The data were subgrouped based on demographic factors to identify important trends. Crude rates were calculated based on incidents per 100,000 population. Odds ratios and 95% confidence intervals for subgroups were calculated by logistical regression. RESULTS: During the 8-year study period 2,313,902,748 person years were evaluated and 2341 ADR-related deaths were identified. Annual rates ranged from 0.08/100,000 to 0.12/100,000, and rates increased significantly over time at a rate of 0.0058 per year. ADR deaths were significantly more likely in persons older than 55 years. The risk was greatest in those aged 75 years or older (OR 6.96, 95% CI 6.30 to 7.69). ADR deaths were higher among men than women. Rates varied by race and ethnicity and were highest among blacks (OR 1.38, 95% CI 1.23 to 1.54). Geographically, rates varied widely between states. Based on urbanization, rates were highest in extremely rural (non-core) areas (OR 2.05, 95% CI 1.76 to 2.38). The most common drug classes associated with death were anticoagulants, opioids, and immunosuppressants. CONCLUSIONS: ADR death rates have a clear association with age, race, and urbanization subgroups. Older individuals, males, blacks, and individuals residing in extremely rural areas experienced higher ADR death rates; these findings warrant further study to develop prevention strategies.