Molecular characterization and prognostic significance of FLT3 in CML progression

To characterize the molecular mechanisms involved in the transition from the chronic phase to blast crisis in chronic myelogenous leukemia (CML), gene expression profiles of leukemic cells from patients in the chronic and blast crisis phases were analyzed using an 8.7K cDNA chip and real-time PCR. A transient transfection analysis was conducted to evaluate the role of FLT3, which was significantly upregulated in the blast crisis patients. Abl and c-Kit induction was detected in K562 cells transfected with FLT3 cDNA (K562/FLT3), and Abl and c-Kit levels were reduced in K562/FLT3 cells transfected with FLT3-siRNA (K562/FLT3-siRNA). The induction of FLT3 in CML cells attenuated imatinib-induced apoptosis. The opposite effect was observed in K562/FLT3-siRNA cells. An increased level of cleaved PARP and decreased level of pro-caspase 3 were noted when K562/FLT3-siRNA cells were treated with imatinib. These findings indicate that FLT3 is associated with disease progression, despite imatinib therapy. These results may help in the prediction of disease progression in CML patients and the development of more appropriate therapeutic modalities. (C) 2009 Elsevier Ltd. All rights reserved.Hoshino K, 2009, LEUKEMIA RES, V33, P1361, DOI 10.1016/j.leukres.2009.03.044Volpe G, 2009, CANCER LETT, V274, P1, DOI 10.1016/j.canlet.2008.06.003Peng HL, 2008, CROAT MED J, V49, P650, DOI 10.3325/cmj.2008.5.650Matsumura I, 2008, CANCER SCI, V99, P479, DOI 10.1111/j.1349-7006.2007.00717.xKim BS, 2007, ANTI-CANCER DRUG, V18, P641Radich JP, 2006, P NATL ACAD SCI USA, V103, P2794, DOI 10.1073/pnas.0510423103Yong ASM, 2006, BLOOD, V107, P205, DOI 10.1182/blood-2005-05-2155Markovic A, 2005, INT J BIOCHEM CELL B, V37, P1168, DOI 10.1016/j.biocel.2004.12.005ILARIA RL, 2005, HEMATOLOGY AM SOC HE, P188Daub H, 2004, NAT REV DRUG DISCOV, V3, P1001, DOI 10.1038/nrd1579Schmidt-Arras D, 2004, CURR PHARM DESIGN, V10, P1867Kottaridis PD, 2003, BRIT J HAEMATOL, V122, P523Nowicki MO, 2003, ONCOGENE, V22, P3952, DOI 10.1038/sj.onc.1206620Marktel S, 2003, HAEMATOLOGICA, V88, P260Ohmine K, 2003, STEM CELLS, V21, P315Gilliland DG, 2002, CURR OPIN HEMATOL, V9, P274Sawyers CL, 2002, BLOOD, V99, P3530Ohmine K, 2001, ONCOGENE, V20, P8249Sawyers CL, 1999, NEW ENGL J MED, V340, P1330Savage DG, 1997, BRIT J HAEMATOL, V99, P30Carow CE, 1996, BLOOD, V87, P1089SILL H, 1995, BLOOD, V85, P2013BIRG F, 1992, BLOOD, V80, P2584AHUJA H, 1989, P NATL ACAD SCI USA, V86, P6783KANTARJIAN HM, 1987, AM J MED, V83, P445SOKAL JE, 1984, BLOOD, V63, P789

Community pharmacists' knowledge, perceptions, and practices about topical corticosteroid counseling: A real-world cross-sectional survey and focus group discussions in Korea.

Topical corticosteroids (TCs) are widely used to treat dermatological conditions such as eczema and psoriasis. It can be a safe and effective treatment when used appropriately. However, misguided information and corticosteroid phobia appear to contribute to inadequate adherence to therapy, leading to unsatisfactory treatment outcomes. Therefore, community pharmacists (CPs) are in a prime position to inform patients about the appropriate use of medicine. The aim of this study was to examine how the knowledge and perceptions of CPs, as well as other factors, associate CPs' patient counseling practice around the use of TCs. A structured, validated questionnaire was distributed to CPs in the Republic of Korea, and additional focus group discussions were implemented to obtain a deeper understanding of the survey findings. We analyzed the survey results by applying a modified knowledge-perception-practice model. In addition, we used path analysis to validate the model and assessed how knowledge level and perceptions of barriers affect CPs' counseling behavior. We ran a multiple regression to identify factors that associate CPs' practice levels. A total of 1018 surveys were analyzed. In general, respondents had sufficient knowledge to provide appropriate patient counseling on TC use. An increase in knowledge level positively associated the quality of practice, and more knowledge increased the perception of barriers that negatively associated patient counseling. Location in rural areas and pharmacists' perception of counseling barriers negatively associated the quality of practice. A higher level of knowledge, training in ADEs, higher proportion of OTC TC sales, and increased time for counseling positively associated the quality of practice. Therefore, minimizing barriers such as negative perceptions is very important in facilitating CPs' counseling practice around TC use

Predictive Factors of Spontaneous Reporting of Adverse Drug Reactions among Community Pharmacists.

PURPOSE:To evaluate the association between spontaneous reporting (SR) and the knowledge, attitude, and needs of community pharmacists (CPs), using a questionnaire following a conceptual model known as the mixed model of knowledge-attitude-practices and the satisfaction of needs. METHODS:Self-administered questionnaires were used with a nationwide convenience sample of CPs between September 1, 2014 and November 25, 2014 in Korea. The association between SR and the predictive factors was evaluated using multivariate logistic regression analysis. RESULTS:In total, 1,001 questionnaires were analyzed. The mean age of the respondents and the number of years spent in community pharmacy practice were 45.6 years and 15.3 years, respectively. CPs with experience of SR was 29.4%. Being older than 60 (ORadj, 0.16; 95% CI, 0.06-0.42), having prior experience with adverse drug reactions (ADR) (ORadj, 6.46; 95% CI, 2.46-16.98), having higher specific knowledge of SR (ORadj, 3.58; 95% CI, 1.96-6.56), and having less concern about the obstacles to SR (ORadj, 0.36; 95% CI, 0.23-0.57) were significant contributing factors to SR. The main obstacles to SR included perception of ADRs as 'not serious ADR' (77.9%), 'already well known ADR' (81.5%), and 'uncertain about causality' (73.3%). CPs without reporting experience had greater concerns related to the reporting method and the liability of the pharmacy than those with reporting experience (p<0.05). CONCLUSIONS:Findings from our study showed around one in three CPs had ADR reporting experience in Korea, while 87.1% had prior experience with ADR cases. The knowledge of SR, prior experience of ADR, and less concern about the obstacles to SR were contributing factors for reporting levels

Patterns of Adverse Drug Reactions in Different Age Groups: Analysis of Spontaneous Reports by Community Pharmacists

<div><p>Purpose</p><p>To evaluate the clinical manifestations and causative drugs associated with adverse drug reactions (ADRs) spontaneously reported by community pharmacists and to compare the ADRs by age.</p><p>Methods</p><p>ADRs reported to the Regional Pharmacovigilance Center of the Korean Pharmaceutical Association by community pharmacists from January 2013 to June 2014 were included. Causality was assessed using the WHO-Uppsala Monitoring Centre system. The patient population was classified into three age groups. We analyzed 31,398 (74.9%) ADRs from 9,705 patients, identified as having a causal relationship, from a total pool of 41,930 ADRs from 9,873 patients. Median patient age was 58.0 years; 66.9% were female.</p><p>Results</p><p>Gastrointestinal system (34.4%), nervous system (14.4%), and psychiatric (12.1%) disorders were the most frequent symptoms. Prevalent causative drugs were those for acid-related disorders (11.4%), anti-inflammatory products (10.5%), analgesics (7.2%), and antibacterials (7.1%). Comparisons by age revealed diarrhea and antibacterials to be most commonly associated with ADRs in children (p < 0.001), whereas dizziness was prevalent in the elderly (p < 0.001). Anaphylactic reaction was the most frequent serious event (19.7%), mainly associated with cephalosporins and non-steroidal anti-inflammatory drugs. Among 612 ADRs caused by nonprescription drugs, the leading symptoms and causative drugs were skin disorders (29.6%) and non-steroidal anti-inflammatory drugs (16.2%), respectively.</p><p>Conclusions</p><p>According to the community pharmacist reports, the leading clinical manifestations and causative drugs associated with ADRs in outpatients differed among age groups.</p></div

Causative drugs and clinical manifestation among the nonprescription drugs.^a

<p>ADRs, adverse drug reactions; GU, genito-urinary.</p><p>^a680 adverse drug reactions from 394 patients.</p><p>^bClinical manifestations reported for more than one adverse drug reaction and the number of adverse drug reactions.</p><p>^cCombinations of aluminum magnesium silicate/ranitidine/magnesium oxide/aluminum magnesium hydroxide.</p><p>Causative drugs and clinical manifestation among the nonprescription drugs.<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132916#t003fn002" target="_blank">^a</a></p

Patient demographics.

<p>Patient demographics.</p