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1.
Pharm Pract (Granada) ; 18(4): 2141, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33343773

RESUMO

BACKGROUND: In Thailand, pharmacists are responsible for all activities to ensure access to medicines throughout pharmaceutical supply chain. Competency framework (CF) is an important guidance for professional development and workforce planning. OBJECTIVE: This study aimed to explore needs for pharmacy services in pharmaceutical supply chain and competencies of pharmacists to serve those needs. It was the first step for developing evidence-based pharmacy CF within the context of Thailand in 2026. METHODS: A qualitative method using in-depth interviews to gain rich data from practitioners and leaders in all area of practices. 99 key informants from 56 workplaces in Thailand were interviewed during January and March 2016. Data was transcribed verbatim, and thematic analysis was used. Competencies were extracted, followed by several rounds of group discussion among team members to develop an initial framework. The competencies and CF were presented, and recommendations were gained from professional leaders for refining the findings. RESULTS: The key informants agreed that pharmacist's works and responsibilities have gradually been drifted to support changes in healthcare and pharmaceutical systems. The upcoming pharmaceutical services call for higher standards of practice, larger number of personnel, and skillful pharmacists who have strong foundation in pharmaceutical knowledge as well as an ability to integrate knowledge into practices. Two sets of CFs were established. The general CF comprises five core domains: product focus, patient focus, healthcare system focus, community focus, and personal focus for self-improvement. These general competencies allow practitioners to perform basic professional tasks, including providing information, dispensing, and compounding. The service-specific competency is the integration of general competencies tailored into specific area of practice. CONCLUSIONS: Regarding the professional goal to evolve pharmacists from generalists to specialists for providing higher quality of professional services, the pharmacists are required to demonstrate general competencies and service-specific competencies. The findings serve as the need-based evidence for developing a national CF for pharmacists in Thailand.

2.
Pharm. pract. (Granada, Internet) ; 18(4): 0-0, oct.-dic. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-202376

RESUMO

BACKGROUND: In Thailand, pharmacists are responsible for all activities to ensure access to medicines throughout pharmaceutical supply chain. Competency framework (CF) is an important guidance for professional development and workforce planning. OBJECTIVE: This study aimed to explore needs for pharmacy services in pharmaceutical supply chain and competencies of pharmacists to serve those needs. It was the first step for developing evidence-based pharmacy CF within the context of Thailand in 2026. METHODS: A qualitative method using in-depth interviews to gain rich data from practitioners and leaders in all area of practices. 99 key informants from 56 workplaces in Thailand were interviewed during January and March 2016. Data was transcribed verbatim, and thematic analysis was used. Competencies were extracted, followed by several rounds of group discussion among team members to develop an initial framework. The competencies and CF were presented, and recommendations were gained from professional leaders for refining the findings. RESULTS: The key informants agreed that pharmacist's works and responsibilities have gradually been drifted to support changes in healthcare and pharmaceutical systems. The upcoming pharmaceutical services call for higher standards of practice, larger number of personnel, and skillful pharmacists who have strong foundation in pharmaceutical knowledge as well as an ability to integrate knowledge into practices. Two sets of CFs were established. The general CF comprises five core domains: product focus, patient focus, healthcare system focus, community focus, and personal focus for self-improvement. These general competencies allow practitioners to perform basic professional tasks, including providing information, dispensing, and compounding. The service-specific competency is the integration of general competencies tailored into specific area of practice. CONCLUSIONS: Regarding the professional goal to evolve pharmacists from generalists to specialists for providing higher quality of professional services, the pharmacists are required to demonstrate general competencies and service-specific competencies. The findings serve as the need-based evidence for developing a national CF for pharmacists in Thailand


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Assuntos
Humanos , Prática Clínica Baseada em Evidências , Competência Profissional , Assistência Farmacêutica , Educação em Farmácia , Farmacêuticos , Pesquisa Qualitativa , Entrevistas como Assunto , Tailândia
3.
Adv Med Educ Pract ; 9: 713-722, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30310347

RESUMO

PURPOSE: To serve the higher demands of pharmaceutical services, pharmacy education in Thailand has shifted from 5-year BPharm program to 6-year PharmD program with two specialization tracks: pharmaceutical care (PC) and industrial pharmacy (IP). This study aimed to compare the perceptions regarding professional competencies, pharmacy profession, and planned workplace between graduates with 5-year BPharm and 6-year PharmD and between those with PC and IP specialty. METHODS: A cross-sectional national survey using a paper-pencil self-administered questionnaire was distributed to all new graduates attending the pharmacy licensure examination in March 2015. RESULTS: Of all 1,937 questionnaires distributed, 1,744 were returned and completed (90% response rate). Pharmacy graduates rated highest on their competencies in professional ethics, followed by PC services and system management. They rated low confidence in medication selection procurement and pharmaceutical industry competencies. The 6-year PharmD graduates showed higher confidence in ethics and professional pride than the 5-year BPharm graduates. Graduates with PC specialty rated higher perceived competency in PC, system management, primary care, and consumer protection domains, while the IP graduates were superior in IP and medication selection and procurement domains, and most graduates (PC and IP) intended to work mainly in a hospital or a community pharmacy. Hospital was preferred for the PC graduates, and the IP graduates were more likely to work in pharmaceutical industry, regulation and consumer protection, sales and marketing, and academia. CONCLUSION: With some gaps still to be filled, the transition from 5-year BPharm to 6-year PharmD program with specialty tracks gave extra confidence to graduates in their specialty competencies and professional pride, leading to differences in preferred workplace. The findings of this study reflect that Thai pharmacy education continues to adjust to the needs of the society and the changing health care environments. Longitudinal monitoring to observe this transition is needed for both curriculum adjustment and competency of the graduates.

4.
J Geriatr Cardiol ; 15(6): 413-421, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30108613

RESUMO

BACKGROUND: Influenza vaccination has been clinically shown to reduce adverse cardiovascular outcomes in acute coronary syndrome (ACS) patients, but the economic perspectives can provide important data to make informed decisions. This study aimed to perform the economic evaluation of lifelong annual influenza vaccination for cardiovascular events and well-established pneumonia prevention. METHODS: Lifetime costs, life-expectancy, and quality-adjusted live years (QALYs) were estimated beyond one-year cycle length of a six-health states Markov model condition on whether a hospitalization for ACS, stroke, heart failure, pneumonia, no hospitalizations occurred, or death. The comparison of three age-groups of 40-49, 50-65, and > 65 years scenario was performed. Incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) were presented as a societal perspective in 2016. The model robustness was determined by one-way and probabilistic sensitivity analyses. RESULTS: The influenza vaccination was cost-effective in all age-groups, by dominant ICERs (lower cost with higher effectiveness) which was completely lower than acceptable willingness-to-pay threshold of Thailand [160,000 THB (4,466.8 USD) per QALYs], with a great incremental value of NMB. Especially, the 50-year-old-and-above scenario was shown as the most benefit at 129,092 THB (3,603.9 USD) for each patient. CONCLUSIONS: The annually additional influenza vaccination to standard treatment in ACS was cost-effective in all age-groups, which should be considered in clinical practice and health-policy making process.

5.
Int J Antimicrob Agents ; 48(2): 151-7, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27345269

RESUMO

This study aimed to describe the pharmacokinetic (PK) characteristics of meropenem in children with severe infections and to assess the pharmacokinetic/pharmacodynamic (PK/PD) profiles of various meropenem dosage regimens in these patients. Fourteen children with severe infections received intravenous (i.v.) bolus doses of meropenem (20 mg/kg/dose) every 8 h (q8h). Serum samples were obtained before and serially after the second dose of meropenem, and a population PK analysis was performed. The final model was used to simulate serum concentration-time profiles with various dosage regimens. The PK/PD target was to achieve a serum meropenem concentration higher than the minimum inhibitory concentration (MIC) of the causative organism (i.e. Pseudomonas aeruginosa and Enterobacteriaceae) for ≥40% of the dosing interval (40%T>MIC). The median age and weight of the children were 6.0 years and 20.0 kg, respectively. Meropenem serum concentration-time profiles were best described by a two-compartmental model with first-order elimination. The simulations showed that the probabilities of target attainment (PTAs) for organisms with an MIC of 1 mg/L were 0.678 and 1.000 following i.v. bolus and 3-h infusion of meropenem (20 mg/kg/dose), respectively. Using a 3-h infusion of a 20 mg/kg/dose, the PTA was 0.999 and 0.765 for organisms with MICs of 4 mg/L and 8 mg/L, respectively. Meropenem given as i.v. bolus doses of 20 mg/kg/dose q8h appeared to be inadequate for PK/PD target attainment for organisms with an MIC of 1 mg/L. The simulations showed that meropenem administration via a 3-h infusion using the same dose improved the PTA.


Assuntos
Antibacterianos/farmacologia , Antibacterianos/farmacocinética , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Pseudomonas/tratamento farmacológico , Tienamicinas/farmacologia , Tienamicinas/farmacocinética , Administração Intravenosa , Antibacterianos/administração & dosagem , Antibacterianos/análise , Criança , Pré-Escolar , Simulação por Computador , Estado Terminal , Enterobacteriaceae/efeitos dos fármacos , Feminino , Humanos , Masculino , Meropeném , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Soro/química , Tienamicinas/administração & dosagem , Tienamicinas/análise , Fatores de Tempo
6.
Cardiol Res Pract ; 2016: 4097471, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27200206

RESUMO

Introduction. The prognosis of acute coronary syndrome (ACS) patients has been improved with several treatments such as antithrombotics, beta-blockers, and angiotensin-converting enzyme inhibitors (ACEI) as well as coronary revascularization. Influenza vaccination has been shown to reduce adverse outcomes in ACS, but no information exists regarding the interaction of other treatments. Methods. This study included 439 ACS patients from Phrommintikul et al. A single dose of inactivated influenza vaccine was given by intramuscular injection in the vaccination group. The cardiovascular outcomes were described as major cardiovascular events (MACEs) which included mortality, hospitalization due to ACS, and hospitalization due to heart failure (HF). The stratified and multivariable Cox's regression analysis was performed. Results. The stratified Cox's analysis by influenza vaccination for each cardiovascular outcome and discrimination of hazard ratios showed that beta-blockers had an interaction with influenza vaccination. Moreover, the multivariable hazard ratios disclosed that influenza vaccine is associated with a significant reduction of hospitalization due to HF in patients who received beta-blockers (HR = 0.05, 95% CI = 0.004-0.71, P = 0.027), after being adjusted for prognostic indicators (sex, dyslipidemia, serum creatinine, and left ventricular ejection fraction). Conclusions. The influenza vaccine was shown to significantly modify the effect of beta-blockers in ACS patients and to reduce the hospitalization due to HF. However, further study of a larger population and benefits to HF patients should be investigated.

7.
J Med Chem ; 56(5): 2097-109, 2013 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-23379514

RESUMO

Bacteria require iron for survival and virulence and employ several mechanisms including utilization of the host heme containing proteins. The final step in releasing iron is the oxidative cleavage of heme by HemO. A recent computer aided drug design (CADD) study identified several inhibitors of the bacterial HemOs. Herein we report the near complete HN, N, CO, Cα, and Cß chemical shift assignment of the P. aeruginosa HemO in the absence and presence of inhibitors (E)-3-(4-(phenylamino)phenylcarbamoyl)acrylic acid (3) and (E)-N'-(4-(dimethylamino)benzylidene) diazenecarboximidhydrazide (5). The NMR data confirm that the inhibitors bind within the heme pocket of HemO consistent with in silico molecular dynamic simulations. Both inhibitors and the phenoxy derivative of 3 have activity against P. aeruginosa clinical isolates. Furthermore, 5 showed antimicrobial activity in the in vivo C. elegans curing assay. Thus, targeting virulence mechanisms required within the host is a viable antimicrobial strategy for the development of novel antivirulants.


Assuntos
Difenilamina/análogos & derivados , Inibidores Enzimáticos/farmacologia , Fumaratos/farmacologia , Guanidinas/farmacologia , Heme Oxigenase (Desciclizante)/antagonistas & inibidores , Hidrazonas/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Virulência/efeitos dos fármacos , Animais , Apoenzimas/química , Caenorhabditis elegans , Difenilamina/farmacologia , Heme Oxigenase (Desciclizante)/química , Modelos Moleculares , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ressonância Magnética Nuclear Biomolecular , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/patogenicidade
8.
J Biol Chem ; 282(49): 35796-802, 2007 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-17925389

RESUMO

An essential component of heme transport in Gram-negative bacterial pathogens is the periplasmic protein that shuttles heme between outer and inner membranes. We have solved the first crystal structures of two such proteins, ShuT from Shigella dysenteriae and PhuT from Pseudomonas aeruginosa. Both share a common architecture typical of Class III periplasmic binding proteins. The heme binds in a narrow cleft between the N- and C-terminal binding domains and is coordinated by a Tyr residue. A comparison of the heme-free (apo) and -bound (holo) structures indicates little change in structure other than minor alterations in the heme pocket and movement of the Tyr heme ligand from an "in" position where it can coordinate the heme iron to an "out" orientation where it points away from the heme pocket. The detailed architecture of the heme pocket is quite different in ShuT and PhuT. Although Arg(228) in PhuT H-bonds with a heme propionate, in ShuT a peptide loop partially takes up the space occupied by Arg(228), and there is no Lys or Arg H-bonding with the heme propionates. A comparison of PhuT/ShuT with the vitamin B(12)-binding protein BtuF and the hydroxamic-type siderophore-binding protein FhuD, the only two other structurally characterized Class III periplasmic binding proteins, demonstrates that PhuT/ShuT more closely resembles BtuF, which reflects the closer similarity in ligands, heme and B(12), compared with ligands for FhuD, a peptide siderophore.


Assuntos
Proteínas de Transporte/química , Hemeproteínas/química , Proteínas Periplásmicas/química , Pseudomonas aeruginosa/química , Shigella dysenteriae/química , Sítios de Ligação , Proteínas de Transporte/metabolismo , Cristalografia por Raios X , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Hemeproteínas/metabolismo , Ligantes , Proteínas de Membrana Transportadoras/química , Proteínas de Membrana Transportadoras/metabolismo , Proteínas Periplásmicas de Ligação/química , Proteínas Periplásmicas de Ligação/metabolismo , Proteínas Periplásmicas/metabolismo , Estrutura Terciária de Proteína , Pseudomonas aeruginosa/metabolismo , Shigella dysenteriae/metabolismo , Homologia Estrutural de Proteína , Vitamina B 12/química , Vitamina B 12/metabolismo
9.
J Med Chem ; 50(16): 3804-13, 2007 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-17629261

RESUMO

The final step in heme utilization and iron acquisition in many pathogens is the oxidative cleavage of heme by heme oxygenase (HO), yielding iron, biliverdin, and carbon monoxide. Thus, the essential requirement for iron suggests that HO may provide a potential therapeutic target for antimicrobial drug development. Computer-aided drug design (CADD) combined with experimental assays identified small-molecule inhibitors of the Neisseria meningitidis HO (nm-HO). CADD virtual screening applied to 800 000 compounds identified 153 for biological assay. Several of the compounds were shown to have KD values in the micromolar range for nm-HO and the Pseudomonas aeruginosa HO (pa-HO). The compounds also inhibited the growth of P. aeruginosa as well as biliverdin formation in E. coli cells overexpressing nm-HO. Thus, CADD combined with experimental analysis has been used to identify novel inhibitors of the bacterial heme oxygenases that can cross the cell membrane and specifically inhibit HO activity.


Assuntos
Antibacterianos/química , Inibidores Enzimáticos/química , Heme Oxigenase (Desciclizante)/antagonistas & inibidores , Neisseria meningitidis/enzimologia , Pseudomonas aeruginosa/enzimologia , Antibacterianos/farmacologia , Biliverdina/biossíntese , Bases de Dados Factuais , Diaminas/química , Diaminas/farmacologia , Difenilamina/análogos & derivados , Difenilamina/química , Difenilamina/farmacologia , Inibidores Enzimáticos/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Escherichia coli/genética , Heme Oxigenase (Desciclizante)/química , Modelos Moleculares , Naftalenos/química , Naftalenos/farmacologia , Ligação Proteica , Pseudomonas aeruginosa/efeitos dos fármacos , Piridinas/química , Piridinas/farmacologia , Relação Estrutura-Atividade
10.
Biochemistry ; 44(39): 13179-91, 2005 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-16185086

RESUMO

The heme uptake systems by which bacterial pathogens acquire and utilize heme have recently been described. Such systems may utilize heme directly from the host's hemeproteins or via a hemophore that sequesters and transports heme to an outer membrane receptor and subsequently to the translocating proteins by which heme is further transported into the cell. However, little is known of the heme binding and release mechanisms that facilitate the uptake of heme into the pathogenic organism. As a first step toward elucidating the molecular level events that drive heme binding and release, we have undertaken a spectroscopic and mutational study of the first purified periplasmic heme-binding protein (PBP), ShuT from Shigella dysenteriae. On the basis of sequence identity, the ShuT protein is most closely related to the class of PBPs typified by the vitamin B(12) (BtuF) and iron-hydroxamate (FhuD) PBPs and is a monomeric protein having a molecular mass of 28.5 kDa following proteolytic processing of the periplasmic signaling peptide. ShuT binds one b-type heme per monomer with high affinity and bears no significant homology with other known heme proteins. The resonance Raman, MCD, and UV-visible spectra of WT heme-ShuT are consistent with a five-coordinate high spin heme having an anionic O-bound proximal ligand. Site-directed ShuT mutants of the absolutely conserved Tyr residues, Tyr-94 (Y94A) and Tyr-228 (Y228F), which are found in all putative periplasmic heme-binding proteins, were subjected to UV-visible, resonance Raman, and MCD spectroscopic investigations of heme coordination environment and rates of heme release. The results of these experiments confirmed Tyr-94 as the only axial heme ligand and Tyr-228 as making a significant contribution to the stability of heme-loaded ShuT, albeit without directly interacting with the heme iron.


Assuntos
Heme/metabolismo , Proteínas Periplásmicas de Ligação/metabolismo , Proteínas de Bactérias , Proteínas de Transporte/química , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Ligantes , Proteínas Periplásmicas de Ligação/química , Proteínas Periplásmicas de Ligação/genética , Proteínas Periplásmicas/química , Shigella dysenteriae/química , Análise Espectral
11.
Plant J ; 41(2): 231-42, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15634200

RESUMO

The Arabidopsis gene BIG (formerly DOC1/TIR3/UMB1/ASA1) is known to encode a huge calossin-like protein that is required for polar auxin transport (PAT). Mutations at this locus, in addition to reducing PAT, can alter the sensitivity of plants to several hormones and light. The tir3-1 allele of BIG reduces the response of plants to application of the gibberellin (GA) precursors ent-kaurenoic acid and GA12 and its semidwarf phenotype is partially reversed by C19-GAs. The effects of auxin transport inhibitors (ATIs) on GA 20-oxidation was examined in wild-type and tir3-1 seedlings. 1-N-naphthylphthalamic acid (NPA) and triiodobenzoic acid lead to overexpression of the GA-biosynthetic gene AtGA20ox1 comparable in magnitude to the overexpression observed in seedlings treated with paclobutrazol, a GA biosynthesis inhibitor. In contrast to that of AtGA20ox1, overexpression of AtGA20ox2 is pronounced only in paclobutrazol-treated Col and Ler, and is less in tir3-1 and in all NPA-treated seedlings. Thus the effects of BIG and ATIs on the expression of genes encoding GA 20-oxidases are complex, and suggest that at least in some tissues ATIs, directly or indirectly, may reduce the level of bioactive GA and/or alter GA signal transduction.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Proteínas de Ligação a Calmodulina/genética , Giberelinas/metabolismo , Ácidos Indolacéticos/metabolismo , Alelos , Arabidopsis/metabolismo , Retroalimentação Fisiológica , Regulação da Expressão Gênica de Plantas , Mutação , Fenótipo , Brotos de Planta/genética , Brotos de Planta/metabolismo
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