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1
Dowling, Karilynn, Nicholas E. Hagemeier, and Courtney Mospan. "Pharmacy Student Dispensing Behaviors in Practice-Based Dilemmas." Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/1438.
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Objectives: To examine the extent to which pharmacy students’ attitudes, subjective norm beliefs, and perceived behavioral control beliefs explain gray dispensing decisions, using the theory of planned behavior (TPB) as a framework. Method: Third professional year pharmacy students (n=159) from two academic cohorts were provided three written case scenarios: (1) a dentist prescribing outside of his scope of practice; (2) a physician prescribing for a family member; and (3) a patient who was out of refills on insulin. A brief questionnaire assessed TPB constructs, whether or not the student would dispense the medication, and the number of times the student would dispense in 10 similar situations. Composite scores were calculated for TPB constructs after analyzing internal consistency reliability. Linear regression techniques were used to analyze the influence of the constructs on mean intent to dispense in similar scenarios. Results: The percent of students who indicated they would dispense in each scenario was 68% in scenario 1, 74% in scenario 2, and 81% in scenario 3. For all case scenarios, mean intent to dispense in similar scenarios was explained by attitude scores (p≤0.006). For the insulin refill and family prescribing cases, mean intent to dispense was also explained by subjective norm beliefs (pImplications: Student attitudes consistently predicted intention to dispense across the gray scenarios. These findings can be used to develop and target upstream TPB construct interventions in pharmacy education that influence students’ downstream dispensing decisions. Additional research is warranted to determine if TBP constructs similarly explain the dispensing behaviors of practicing pharmacists.
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Waheedi, Salah. "Evaluation of a community pharmacy based cardiovascular risk assessment service." Thesis, Cardiff University, 2011. http://orca.cf.ac.uk/24738/.
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The aim of the study was to evaluate a community pharmacy-based cardiovascular risk assessment (VRA) service introduced into two pharmacies in south Wales. A longitudinal methodology was adopted where participants had an initial assessment with a follow-up after 12 months. Body mass index, waist circumference, blood pressure and total/HDL cholesterol levels were measured and the Framingham 10-year cardiovascular risk was estimated and communicated to patients. Demographic details and lifestyle information (smoking, alcohol, diet and exercise) were obtained via self-complete questionnaires at each consultation. A total of 172 individuals accessed the service and had either a brief assessment (n=26) without the calculation of the Framingham score or a full VRA (n=146). Mean age was 60 years (±10.3), 59% were female and 25% (37/146) were at high risk (>20%) of developing cardiovascular disease. High satisfaction with the VRA was obtained via an anonymous questionnaire provided immediately after the initial consultation (74% response rate). The short-term outcomes of the service (including recall of advice, lifestyle improvement and/or making the visit to their GP if they were referred) were reported through a semi-structured telephone interview two weeks after the initial assessment. In total 105/172 (61%) who attended the twelve-month follow-up had results of the two assessments compared using paired Student’s t-test. There was a statistically significant increase in mean HDL 0.08 mmol/L (95% CI 0.02 to 0.14) and a statically significant reduction in mean systolic BP -8.5 mmHg (95% CI -11.0 to -5.9), diastolic BP -7.7 mmHg (95% CI -10.4 to -5.0) and Framingham score -1.07 (95% CI -1.9 to -0.2). A comparison between Framingham and QRISK2 algorithms showed the importance of using the most accurate tool available in estimating cardiovascular risk. This is the first study to investigate short- and longer-term outcomes of a community pharmacy-based VRA service in Wales and provides a basis for future research.
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Li, Yanen. "Medicaid risk adjustment model with diagnosis and pharmacy-based adjusters : does it work?" [Tampa, Fla.] : University of South Florida, 2007. http://purl.fcla.edu/usf/dc/et/SFE0002215.
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Tweddell, Simon. "Evaluating the introduction of Team-Based Learning in a pharmacy consultation skills module." FIP, 2020. http://hdl.handle.net/10454/17838.
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YesThe learning and teaching strategy for a pharmacy consultation skills module was changed to Team-Based Learning (TBL) with the aim of motivating students to engage with course material pre-class and take deeper approaches to learning during class. Results from administering a validated TBL instrument suggests that students are more accountable and are satisfied with and have preference for TBL over traditional methods. Exam results show a 13% improvement in mean end-of-year examinations compared with pre-TBL results. Thematic analysis of written comments on the module evaluation survey suggest that they enjoyed learning using TBL and found it more engaging, stimulating and more effective for their learning; however, it could be improved through better management of workshop timings and more effective facilitation of discussion. TBL appears to have potential as a pedagogic approach in pharmacy education.
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Vargas, Linzee, Reema Patel, and Shelby Lehew. "The Impact of Pharmacy Mobile Application on Student Performance on NAPLEX-Based Questionnaire." The University of Arizona, 2017. http://hdl.handle.net/10150/624173.
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Class of 2017 AbstractObjectives: To determine if the use of RxSkills effectively improves student scores on the North American Pharmacist Licensure Examination (NAPLEX)-based questions among third and fourth-year pharmacy students at the University of Arizona (UA) College of Pharmacy. Methods: This is a pre-post interventional study using a survey of volunteer students from the classes of 2016 and 2017 at the UA College of Pharmacy. An email calling for volunteers was sent using the listserv to students providing information regarding the study. Once the pre-test was completed, instructions for downloading the mobile application were sent to the students. After six weeks of RxSkills use, a link to the post-test was sent to the students for completion. Student scores on the NAPLEX-based questions, use of the application (frequency and duration) and helpfulness, and demographic data were collected. Results: The number of participants in the study from each class was similar with 15 students from the Class of 2016 (52%) and 14 from the Class of 2017 (48%). There was no correlation between how often RxSkills was used and improvement in scores. Overall, student score on the NAPLEX-based questions were significantly improved post-RxSkills use (mean 10.48, SD 2.49) compared to pre-RxSkills use (mean 9.68, SD 2.24) with a p-value of 0.03. Conclusions: The use of RxSkills resulted in an improvement in student scores on the NAPLEX-based questions, indicating its usefulness in studying for the NAPLEX. Students would benefit from using the application when studying for this exam.
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Russell, Kathy, Marion Slack, Janet Cooley, and Kelly Mathews. "Impact of a Specialty Pharmacy-Based Oral Chemotherapy Adherence Program on Patient Adherence." The University of Arizona, 2016. http://hdl.handle.net/10150/614015.
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Class of 2016 AbstractObjectives: Patient medication adherence is a basic requirement for treating chronic myelogenous leukemia (CML) with oral tyrosine kinase inhibitors (TKIs). When imatinib adherence rates are less than 80 or 90 percent, major and complete molecular responses, respectively, do not happen. The purpose of this study was to determine the effect of a real-time medication monitoring (RTMM) reminder system adherence program on the medication possession ratio (MPR). Methods: This analytic study was a retrospective cohort study and used data extracted from chart reviews for patients who received services from 2011 to 2015. It was approved by the Institutional Review Board. The study consisted of an intervention group and a control group (50 patients each). MPRs, demographic, descriptive, and categorical variables were summarized using means, standard deviations (SD), and frequencies/percentages. Results: The study population consisted of adult patients (mean age=62.2, SD=2.7, 50% male) treated by Avella Specialty Pharmacy who received imatinib or nilotinib as treatment for CML, gastrointestinal stromal tumors (GIST), or a similar positive Philadelphia chromosome cancer. Only 4% of patients in the intervention group had an < 85% MPR, compared to 46% in the control group (p < 0.001). Conclusions: In those patients who had an MPR of ≥ 85%, the difference between the groups was statistically significant. As past studies have shown, adherence rates greater than 90% have a higher likelihood of a major or complete molecular response and a greatly reduced risk of disease progression.
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Barnes, Brenda. "Appointment Based Medication Synchronization: A Comparison of Three Model Designs in a Large Chain Community Pharmacy Setting." University of Cincinnati / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1470741101.
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Ascensio, Zona Josephine. "Pharmacy-Based Barriers to Adolescent Access to Over-the-Counter Emergency Contraception in Kentucky." TopSCHOLAR®, 2017. http://digitalcommons.wku.edu/theses/1939.
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Since June of 2013, Plan B and its generics have been available over-the-counter without age restriction nationwide. Even so, pharmacy-based economic, physical, and staff-associated barriers still exist, potentially leading adolescent customers to fail to obtain emergency contraception (EC) in a sufficiently timely manner to prevent pregnancy. This study explores these pharmacy-based barriers to EC in the state of Kentucky focusing on comparisons of urban and non-urban pharmacies and chain and private pharmacies. Using a secret-shopper survey technique, the researcher called 220 Kentucky pharmacies acting as a 15-year-old girl seeking information about EC. Among other findings, a logistic regression analysis revealed that private pharmacies were 97% less likely to carry EC compared to chain pharmacies (OR= .027; p
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Calhoun, McKenzie L. "The Journey to Team Based Healthcare: A Day in the Life." Digital Commons @ East Tennessee State University, 2010. https://dc.etsu.edu/etsu-works/6878.
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To offer an insight into the themes which will be explored at the Masterclass, in this short video Dr. McKenzie Calhoun and colleagues at the ETSU Family Physicians in Kingsport, Tennessee discuss how a model of interprofessional collaboration is typically applied and put into practice in the care of patients at the center. They highlight the importance and value of a team-based approach in enhancing the provision of primary healthcare.
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Hagemeier, Nicholas E., Sarah Blevins, Kyle Hagen, Emily Sorah, Richa Shah, and Kelly Ferris. "Integration of Rural Community Pharmacies into a Rural Family Medicine Practice-Based Research Network: A Descriptive Analysis." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etsu-works/1476.
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Purpose: Practice-based research networks (PBRN) seek to shorten the gap between research and application in primary patient care settings. Inclusion of community pharmacies in primary care PBRNs is relatively unexplored. Such a PBRN model could improve care coordination and community-based research, especially in rural and underserved areas. The objectives of this study were to: 1) evaluate rural Appalachian community pharmacy key informants’ perceptions of PBRNs and practice-based research; 2) explore key informants’ perceptions of perceived applicability of practice-based research domains; and 3) explore pharmacy key informant interest in PBRN participation.
Methods: The sample consisted of community pharmacies within city limits of all Appalachian Research Network (AppNET) PBRN communities in South Central Appalachia. A descriptive, cross-sectional, questionnaire-based study was conducted from November 2013 to February 2014. Bivariate and multivariate analyses were conducted to examine associations between key informant and practice characteristics, and PBRN interest and perceptions.
Findings: A 47.8% response rate was obtained. Most key informants (88%) were very or somewhat interested in participating in AppNET. Enrichment of patient care (82.8%), improved relationships with providers in the community (75.9%), and professional development opportunities (69.0%) were perceived by more than two-thirds of respondents to be very beneficial outcomes of PBRN participation. Respondents ranked time constraints (63%) and workflow disruptions (20%) as the biggest barriers to PBRN participation.
Conclusion: Key informants in rural Appalachian community pharmacies indicated interest in PBRN participation. Integration of community pharmacies into existing rural PBRNs could advance community level care coordination and promote improved health outcomes in rural and underserved areas.
Type: Original Research
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Coleman, David John. "An evaluation of the delivery of pharmaceutical care from a general practice surgery based pharmacy." Thesis, University of Portsmouth, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.311077.
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A longitudinal study was carried out on a population of 4,922 patients served by a general practice surgery with three doctors. The purpose was to investigate the opportunity which domiciliary care of elderly and infirm patients offers to UK pharmacists working in primary care. The aims of the study were: - 1) To identify indicators that could be used to identify patients in the community who might benefit from domiciliary pharmaceutical care, and which do not leave patients excluded. 2) To identify specific issues that would lead to better pharmaceutical care 3) To deliver a package of pharmaceutical care to these most "at risk" patients in the population over approximately a year. 4) To evaluate the interventions made considering the viewpoints of all parties found to be stakeholders. 5) To measure the scale of the challenge of domiciliary managed pharmaceutical care in relation to the population in the study. 6) To provide indicators for the development of pharmaceutical care including cost/ benefit and potential training requirements. A simple qualitative study design was pursued, based upon semi-structured interviews and field notes. A cohort of patients (n=149) identified as candidates for domiciliary visiting, represented 3% of the surgery population. After de-selection of unsuitable candidates, visits were made to 100 patients. Three concepts for the organisation of information and three clusters of criteria were identified and developed which would identify 94 out of 100 patients visited. A large number of indicators for pharmaceutical care were identified and described qualitatively under 14 headings. Though typical, these were not claimed as a comprehensive set of issues which could have been encountered. It was generally perceived that more of the pharmacist's interventions produced positive effects than those that were neutral or actually did harm. Some of the interventions were accepted by the GPs as very important, and developing the extended role to include for instance a cardiovascular review clinic; "in house" medication reviews was discussed. Domiciliary visits were deemed useful though the GPs pointed out that making visits was time consuming and, by implication, expensive. Patients reported a high level of satisfaction with the visiting programme. Satisfaction was explored in an attempt to differentiate sociometric issues from professional ones. Rating satisfaction with a domiciliary pharmaceutical service required that specific issues were identified and dealt with which reflected the main concerns of patients about their medicines. Most of the patients' concerns appeared to be centred around multiple medication, widely perceived (in this cohort) to have potential to cause harm. The author recommends that PCGs consider allocating part of the prescribing budget to fund a domiciliary pharmaceutical care service to a small targeted population through community pharmacies. This could be a first step in offering new professional opportunities through community pharmacies and might revitalise some which are currently in decline.
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Thompson, April, and Charity Olson. "Identifying inducements and barriers in developing a community health center pharmacy practice based research network." The University of Arizona, 2010. http://hdl.handle.net/10150/623757.
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Class of 2010 AbstractOBJECTIVES: To identify and describe practical incentives and barriers for community health center pharmacists in adopting a practice based research network (PBRN) that facilitates sustainable collaboration. METHODS: Directors of pharmacy at Community health centers listed as members of Arizona Association of Community Health Centers (AACHC), with on-site pharmacies, were contacted via telephone. During initial contact an IRB approved script was used to recruit the pharmacy director’s participation, at which time the subject’s disclaimer form was read and an appointment for a future phone interview was scheduled. Phone Interviews were conducted using a standardized questionnaire, and all results were manually recorded on a standardized data collection form. Data collected included, site specific information including the: educational background of the pharmacy director, and his or her perceived inducements and barriers to participating in a pharmacy based PBRN with the University of Arizona. RESULTS: Phone interviews were completed by 8 directors of pharmacy, 4 women (50%) and 4 men (50%). A total of 5 participants (62.5%) had a BS degree, 2 (25%) had PharmD degrees and 1 (12.5%) had both as BS and a PharmD degree. The mean length of time in current position was 5.56 yrs (SD= 4 yrs.). 75% of the participants indicated that they considered working with the University of Arizona (UofA) as an inducement, the same number of participants felt that their staff and practice as a whole would also consider it an inducement. Overall participants indicated that both their personal (75%) and staff‘s (87.5%) motivation to improve the pharmacy profession was considered an inducement, as well as their opportunity for professional growth (75%). All of the participants (100%) indicated they did not have adequate staffing to support research at this time and therefore felt it was a barrier to participation. When asked about resources as a whole, including staff, time and technology 87.5% of the participants felt this was a barrier. Other common barriers were; anticipated time requirements (75%), current schedule/time allowances (75%), staff’s outside commitments (75%). Out of the 8 participants only 2 (25%) are currently participating in PBRNS at this time, 3(37.5%) have research ideas that they are interested in working on, and 3(37.5%) indicated that they were not currently participating nor did they have any current interests. The major themes identified as inducements to participation were patient benefit, time/staffing involvement, and professional growth. CONCLUSIONS: The most common barriers to participating in a PBRN were: working with the UofA, motivation to improve the profession of pharmacy and the opportunity for professional growth. The most common inducements were staffing, current resources, anticipated time requirements, current schedules and outside commitments.
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Shah, Richa S., Sarah Blevins, Emily L. Sorah, Kelly M. Ferris, Kyle S. Hagen, and Nicholas E. Hagemeier. "Community Pharmacists' Willingness to Participate in a Rural Appalachian Practice-Based Research Network." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/1454.
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Practice-based research networks (PBRNs) are groups of health care practitioners who engage in translational research and quality improvement activities, with the overarching goal of improving patient care in primary care settings. The Appalachian Research Network (AppNET), a rural primary care PBRN, was created in 2009 and comprises 17 clinics in 16 rural communities in South Central Appalachia. Nationally, only 4 of 152 PBRNs registered with the Agency for Healthcare Research and Quality (AHRQ) place particular emphasis on community pharmacies and pharmacists in research efforts. Researchers at ETSU seek to integrate community pharmacies into AppNET, thereby establishing a novel interprofessional rural PBRN. The objective of this study was to assess pharmacist perceptions regarding practice-based research and interest in participating in AppNET. Barriers to participation in a PBRN, perceived benefits of participation, and practice-specific characteristics were also assessed. Contact information was obtained via telephone calls made to individual pharmacies in AppNET communities. Thereafter, paper-based surveys were mailed to 69 pharmacist contacts, along with a personalized cover letter and a stamped return envelope. A total of two mailings were used to recruit pharmacists to participate in the study. A response rate of 42% was obtained. Respondents were on average 44 years of age and had been licensed as a pharmacist for an average of 19 years. A large majority of respondents (86%) were very or somewhat interested in participating in AppNET. The majority of respondents felt that time constraints and workflow interruptions were the greatest barriers to participation. One hundred percent of respondents indicated that research on prescription drug abuse, medication adherence, and medication safety are very or somewhat applicable to their practice settings. Ninety-two percent felt that research on value-added services (e.g., immunizations, diabetes education) and medication therapy management was somewhat or very applicable to their practice. Overall, pharmacist respondents in AppNET communities indicated interest in research that benefits the care of their patients and interest in AppNET. Researchers are presently conducting a third recruitment attempt and will thereafter develop AppNET enrollment mechanisms that minimize barriers to participation of community pharmacies in practice-based research.
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Blackwelder, Reid B., and Brian Cross. "Team-based Care and Education." Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/6930.
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Tweddell, Simon. "Introducing team-based learning in a pharmacy curriculum : a qualitative study of staff and student experiences." Thesis, University of Huddersfield, 2018. http://eprints.hud.ac.uk/id/eprint/34528/.
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There is an increasing move towards an outcomes-based approach to educating healthcare professionals including the development of key skills such as problem-solving and critical thinking. Some healthcare regulators have changed accreditation criteria to ensure that graduates can apply knowledge and skills, analyse complex situations, and develop the skills to learn independently. There is a move to ensure that curricula are designed to take into account modern educational theory and research and promote active and deep approaches to learning. Accordingly, educators have redesigned curricula to be delivered by more learner-centred approaches involving active problem solving and peer and collaborative learning. These approaches require educators to adapt from the role of content deliverer to that of learning architect and facilitator of learning. This qualitative research study takes a phenomenological approach to consider the experiences of pharmacy educators and students in a pharmacy school that has designed its curriculum to be delivered predominantly by team-based learning (TBL). The findings of the study include: a dissatisfaction with traditional methods in engaging and motivating students; mixed feelings about the initial idea of TBL; the need for substantial resources for planning, staff training, designing and quality assuring resources when transitioning to TBL; improved student engagement and student preparation with TBL; staff benefits in working more collaboratively and enhanced enjoyment of teaching using TBL; perceived benefits of peer learning and transferable skills development; substantially higher staff workload during transition; challenges in writing effective application exercises, and developing the facilitation skills needed for a learner-centred classroom. In addition there is the need for substantial planning around timetabling, sourcing suitable rooms, ensuring consistency of approach across educators, and the development of bespoke quality assurance processes. Overall this research suggests that the majority of participants supported the implementation of TBL in the curriculum and that the benefits outweighed the challenges.
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Omerza, Kevin Edward. "The Economic Impact of a Pharmacy-Based Hybrid Medication Adherence Model in Patients with Metabolic Syndrome." University of Toledo Health Science Campus / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=mco1430521410.
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Alsmadi, Mo'tasem Mohamed. "Physiologically based pharmacokinetic (PBPK) model of Ivermectin (IVM)." Diss., University of Iowa, 2014. https://ir.uiowa.edu/etd/5906.
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Purpose: Ivermectin (IVM) is a lipophilic BCS-II compound (molecular weight=875 g/mole, LogP=3.22, intrinsic solubility=700 ug/L). IVM is used as antiparasitic drug in both humans and animals. IVM is known to have a half-life of 12-56 hours in humans. Strongyloidiasis is a chronic parasitic infection of humans caused by Strongyloides stercoralis, with an estimated 30-100 million people infected worldwide. Infection may be severe and even life-threatening in cases of immunodeficiency. Patients with disseminated strongyloidiasis are usually bedridden hospitalized patients that show symptoms such as paralytic ileus and reduced plasma albumin and cholesterol. Oral IVM is the only FDA-approved treatment but may not be effective in patients with disseminated disease. Veterinary subcutaneous formulations have been used in severe infections. We hypothesized that IVM PK in patients with disseminated strongyloidiasis can be predicted using PBPK model originally built and refined in healthy human and animal species. This hypothesis was tested and shown to be valid.
Methods:A systematic method was used to build and refine different parts of the PBPK model. The process involved construction of models, parameterization of these models, evaluation of the effect of uncertainty in model parameters on model prediction via local and global sensitivity analyses and finally, refinement of model predictions.
Two disposition models that differ in the rate limiting step in drug distribution were constructed and include perfusion-limited and permeability-limited distribution models. The ability of each model to predict IVM disposition was evaluated using plasma PK data in rat after intra-arterial dosing and in dog after intravenous bolus dosing.
Then the disposition model was scaled to humans and an oral input model was constructed as a modification on the well-known ACAT model. The oral input model was coupled with the disposition model and used to predict IVM plasma concentration-time profile in healthy fasted human subject after oral dosing.
Two subcutaneous (SQ) input models were constructed and used to evaluate the effect of IVM precipitation at the injection site. Plasma PK data in dog after SQ dosing was used to refine the constructed SQ input models.
The refined disposition, oral input and SQ input physiologically-based models were used to predict IVM PK in patients with disseminated strongyloidiasis after a complex dosing regimen. The physiological parameters of the model were modified to account for the effect of the disease-induced pathophysiological changes on the body physiology and hence on the drug PK. Plasma PK data from hospitalized subjects with disseminated strongylidiasis was used in this part.
Results and conclusions:The disposition model with assumption of permeability-limited distribution was more capable of describing IVM disposition in rat after intra-arterial dosing compared to when perfusion-limited distribution was assumed. The model predicted that hepatic clearance is the most impactful parameter on model-predicted plasma concentration of the drug. Also, IVM was shown to have low hepatic extraction ratio along with high binding in plasma and large volume of distribution, which collectively may explain the long half-life in the plasma of 63 hours in rat after intra-arterial dosing.
The oral input model predicted that the oral input is limited by drug dissolution in the GI lumen and that a very small fraction of oral tablet dose (0.03) is available in the systemic circulation in healthy fasted human subjects. Both of the studied SQ input models predicted that majority of IVM absorption after SQ dosing is via the lymphatic route and that drug precipitation at the injection site can further slowdown the drug absorption after SQ administration.
The PBPK model was able achieve the main goal of this research which is to predict IVM pharmacokinetics in patients with disseminated strongyloidiasis after a complex dosing regimen of multiple oral and SQ dosing. This was achieved by modifying the most impactful physiological parameters of the model affected by the disease state and that are related to drug binding in the plasma (fraction unbound), the GI motility (gastric emptying rate) and the lymphatic flow rate. Based on our analysis, we recommend measurement of plasma IVM concentrations early after initiation of therapy to exclude treatment failure due to reduced oral and/or SQ absorption. Also, we recommend measurement of plasma lipoprotein levels and their composition in these patients to differentiate between low total plasma concentrations due to low binding plasma as opposed to low drug input. Finally, interventional procedures that enhance lymphatic flow rate to site of SQ injection are recommended to enhance SQ absorption.
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Blackwelder, Reid B., and Brian Cross. "Team-based Care and Education." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etsu-works/6932.
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Huang, Jian Hua 1970. "A randomized controlled trial to evaluate the clinical effectiveness of a community pharmacy based asthma education program /." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=82252.
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Objective. To evaluate the clinical effectiveness of a community pharmacy based education program for asthma patients.Design. A randomized controlled trial was conducted in 16 community pharmacies. Interventions: Patients in the intervention group (n=53) received three sessions of individualized asthma education from pharmacists. In addition, pharmacists also prepared a written action plan in consultation with patients' physicians. Patients in the control group (n=53) did not receive any asthma education during the study.
Outcome Measures. Asthma symptoms (the primary outcome), asthma knowledge, medication compliance, deep expiratory pressure percentage (DEP%), inhaler technique, quality of life (QOL), and heath resources utilization were measured.
Results. The mean score of asthma symptoms, the primary outcome, decreased more in the intervention group than in the control group (between group difference = -0.299, 95% CI, -0.71; 0.11), though this between group difference was not statistically significant (P=0.148). As to the secondary outcomes, patients in the intervention group had significant improvements in "overall mean score of QOL" (between group difference = 0.43, 95% CI, 0.023; 0.83), "symptom domain of QOL" (between group difference = 0.50, 95% CI, 0.04; 0.96), and "inhaler technique of Aerosol-dosing only" (between group difference = 1.77, 95% CI, 0.36; 3.18). Except for QOL and inhaler technique, the other four secondary outcomes did not achieve any significant differences between the two study groups.
Conclusions. Most of the study results were not statistically significant. One important reason for this was the lack of power due to the poor success in patient recruitment. The study also highlighted some of the limitations and difficulties in implementing a community pharmacy based asthma education program. Despite these difficulties, some benefits were found. Therefore, we suggest that future studies should focus on overcoming the limitations and difficulties observed in this study.
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Click, Ivy A., Thomas Bishop, Jodi Polaha, Reid Blackwelder, Beth Ann Bailey, and Beth Ann Fox. "Development and Implementation of a Team-Based Care Curriculum for Faculty, Residents, and Students." Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/6385.
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Chen, Jing, and 陈静. "Economic evaluation of community pharmacy based smoking cessation on burden of chronic obstructive pulmonary disease (COPD) in Hong Kong." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B47157252.
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Background: Chronic Obstructive Pulmonary Disease (COPD) poses a substantial
burden to Hong Kong. Smoking is the single most important risk factor for COPD.
Intensive smoking cessation in COPD patients slows disease progression. Community
pharmacy based smoking cessation in healthy smokers could forestall COPD onset. Each
of these programs has been proven effective and cost-effective worldwide. Currently
there are smoking cessation clinics in Hong Kong. But community pharmacy-based
smoking cessation services are not available. The present study firstly attempts to identify
the disease burden of COPD; secondly, to investigate if community pharmacy-based
smoking cessation services are applicable in Hong Kong; finally, to examine if
establishing the services would be cost effective in reducing the burden of COPD.
Methods: A series of data analysis of mortality, morbidity and cost of hospitalization
(length of stay × standard daily ward cost) was conducted to understand the burden of
COPD in Hong Kong. Cost effectiveness analysis based on a Markov model evaluated smoking cessation strategies against usual care: (1) minimal counseling in smoking
cessation clinics (MiniC) for COPD patients; (2) intensive counseling with
pharmacotherapy in smoking cessation clinics (IC_pharm) for COPD patients; (3)
community pharmacist-assisted service (CPA) for healthy smokers; (4) combination of
CPA and MiniC (CPA+MiniC); (5) combination of CPA and IC_pharm
(CPA+IC_Pharm). The Markov model was constructed by sex, smoking status and
COPD severity to calculate the lifetime cost of COPD, cost of smoking cessation
programs and QALYs. Both effectiveness and cost were discounted at 3%. Incremental
cost effectiveness ratios (ICERs), i.e. cost per one QALY gain, served as the decision
making rule. One way sensitivity analysis, threshold analysis and probabilistic sensitivity
analysis were performed to explore the uncertainty around the parameters.
Results: The overall age adjusted mortality of COPD increased from 28.8 per 100 000 in
1981 to 30.14 per 100 000 in 2008. Numbers of people aged 65+ with known COPD was
projected to be over 100 000 by 2036. There were 3.8 and 7.8 years of life lost (YLL) and
3.6 and 5.6 QALYs lost due to COPD for male and female smokers respectively. Medical
costs of hospitalization were estimated to be over HK$ one billion (US$132 million) in 2008.
Seventy one COPD cases could be avoided in the simulated cohort by CPA. If the
threshold value was HK$247 332 for one QALY gain, CPA was more cost effective than
IC_Pharm, with an ICER of HK$47 717. CPA+MiniC dominated CPA. CPA+IC_Pharm was more cost effective than CPA+MiniC (ICER, HK$36 000). The
probability of CPA+ IC_pharm being the most cost effective strategy was approaching
0.8 if one QALY was worth HK$96 000, and it was associated with the maximum
expected QALYs if societal value for one QALY was no less than HK$80 000.
Conclusion: The model-based economic evaluation demonstrated that CPA+IC_Pharm
would be the most cost-effective smoking cessation strategy. Community pharmacy
based (CPA) smoking cessation services could be applicable and should be proposed in
Hong Kong to reduce the burden of smoking related diseases.published_or_final_version
Public Health
Doctoral
Doctor of Philosophy
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Nel, Lindi. "Value-based management : an application in North West regional pharmacies / L. Nel." Thesis, North-West University, 2012. http://hdl.handle.net/10394/9807.
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Value based management is a process that can be used to determine a business’s value drivers. It attempts to determine how the drivers link to value creation, and then break down the value drivers into achievable activities that can be pursued by employees.
Due to strict medicine pricing regulations in the country, it is becoming increasingly difficult for pharmacy businesses to stay profitable. This study set out to develop a value based management framework that could be used by pharmacy management in order to maximise value creation in the business and help ensure its survival despite the strict pricing regulations. Secondary objectives were to contextualise the term “value based management”, to identify the value drivers in a pharmacy business and to determine the extent to which value based management and its principles are being applied in pharmacies in the North West region of South Africa.
The research study began in the literature where the term “value based management” was introduced and a literature study was done to conceptualise the term by investigating why value based management and value creation were important. Value based management metrics, the components of value based management; and key success factors for the implementation of value based management principles were investigated. A further literature study was done to identify possible value drivers in a pharmacy business.
An empirical study was conducted among registered pharmacists in the North West region of South Africa. Using the value drivers identified in the literature study as constructs, a questionnaire was designed to explore participants’ level of exposure to (and knowledge of) value based management as well as the extent to which the principles of value based management were being applied at the pharmacy businesses where participants were employed. Analysis of the responses showed the questionnaire to be reliable and valid. The results of the study highlighted that many respondents’ lack knowledge regarding the constructs (value drivers), cost price in the dispensary and cost of wages. Constructs (value drivers) that were better understood included product mix in the front shop and debtors’ control. Constructs (value drivers) that were best managed at the pharmacies where participants were employed, were cost price in the front shop and stock control. Constructs (value drivers) that were not as thoroughly managed were sales growth in the front shop and cost of wages.
Conclusions regarding the findings of the research study were presented and recommendations were made. The research study was evaluated opposite the primary and secondary objectives with the conclusion that both were achieved. Finally, recommendations for further research into value based management and the application of its principles in pharmacy businesses were proposed.Thesis (MBA)--North-West University, Potchefstroom Campus, 2013.
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Shi, Guqin. "Structure-based Computer-aided Drug Design and Analyses against Disease Target: Cytokine IL-6/IL-6R/GP130 Complex." The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu151197172881965.
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Nguyen, Quynh Hoa. "Risk assessment for drug degradation products using physiologically-based pharmacokinetic models." Diss., University of Iowa, 2014. https://ir.uiowa.edu/etd/1993.
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Degradation product toxicity is a critical quality issue for a small group of useful drug products--e.g. lidocaine, isoniazid, chlorhexidine, gabapentin. In the traditional risk assessment approaches, a no-observed-adverse-effect level (NOAEL) derived from animal data is determined with the use of generic (and arbitrary) uncertainty factors to obtain an acceptable daily intake. The effects of compound-specific biological complexities and pharmacokinetics are typically not part of the risk calculations. The selection of uncertainty factors that account for interspecies or intraspecies difference concerning biokinetics and biodynamics has also generally failed to consider chemical-specific mechanism information or pharmacokinetics data. The use of combining in-vitro biopharmaceutical characterization methods and physiologically-based pharmacokinetic modeling has undergone extensive study and validation for predicting clinical drug blood level time profiles. The rationale for the proposed research is that a PBPK modeling utilizing rat to human scaling for target tissue toxicity in combination with the Monte Carlo method for estimating human target exposure distributions provides a rational basis for assessing drug stability safety issues for drug substances that potentially degrade to toxic compounds.
PBPK models for rats and humans were developed to simulate drug exposure time profiles after oral administration of model compounds including aniline, p-chloroaniline, 2,6-dimethylaniline, o-toluidine and p-aminophenol. The PBPK models were parameterized using a combination of literature values, computational models and standard in vitro experiments. Microsomal and hepatocyte metabolism studies were used to estimate the metabolic constants, and ultrafiltration was used to measure protein binding. Intestinal permeability was predicted using a set of related compound data to correlate measured Caco-2 permeability with molecular descriptors by multivariate regression. Sensitivity analyses were conducted to evaluate the impact of PBPK model parameters on plasma level predictions. To evaluate patient population effects on exposure profiles, the PBPK model parameters were varied in meaningful ways using Monte Carlo methods. Based on population PBPK models, distributions of target tissue exposure in rats and humans were simulated and compared to derive human safe dose.
As results, rat PBPK model-predicted aniline concentration time profiles were in reasonable agreement with published profiles. Distributions of target tissue exposure in rats and humans were generated and compared based on a criterion. A human reference dose was then selected at a value of 1% criteria. This approach was compared to traditional risk assessment calculations. In conclusion, the PBPK modeling approach resulted in drug degradation product risk specifications that were less stringent than those estimated by conventional risk assessment approach. The PBPK modeling approach provides a rational basis for drug instability risk assessment by focusing on target tissue exposure and leveraging physiological, biochemical, biophysical knowledge of compounds and species.
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Al-Saeed, Eman. "A mixed methods study of the feasibility and acceptability of an opportunistic community pharmacy based CVD risk assessment service in Alexandria, Egypt." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.709157.
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Dan, Mo. "THE PHARMACOKINETICS OF METAL-BASED ENGINEERED NANOMATERIALS, FOCUSING ON THE BLOOD-BRAIN BARRIER." UKnowledge, 2013. http://uknowledge.uky.edu/pharmacy_etds/21.
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Metal-based engineered nanomaterials (ENMs) have potential to revolutionize diagnosis, drug delivery and manufactured products, leading to greater human ENM exposure. It is crucial to understand ENM pharmacokinetics and their association with biological barriers such as the blood-brain barrier (BBB). Physicochemical parameters such as size and surface modification of ENMs play an important role in ENM fate, including their brain association. Multifunctional ENMs showed advantages across the highly regulated BBB. There are limited reports on ENM distribution among the blood in the brain vasculature, the BBB, and brain parenchyma.
In this study, ceria ENM was used to study the effect of size on its pharmacokinetics. Four sizes of ceria ENMs were studied. Five nm ceria showed a longer half-life in the blood and higher brain association compared with other sizes and 15 and 30 nm ceria had a higher blood cell association than 5 or 55 nm ceria. Because of the long circulation and high brain association of 5 nm ceria compared with other sizes, its distribution between the BBB and brain parenchyma was studied. The in situ brain perfusion technique showed 5 nm ceria (99%) on the luminal surface of the BBB rather than the brain parenchyma.
For biomedical applications in the central nervous system (CNS), it is vital to develop stable and biocompatible ENMs and enhance their uptake by taking advantage of their unique properties. Cross-linked nanoassemblies entrapping iron oxide nanoparticles (CNA-IONPs) showed controlled particle size in biological conditions and less toxicity in comparison to Citrate-IONPs. CNA-IONPs considerably enhanced MRI T2 relaxivities and generated heat at mild hyperthermic temperatures (40 ~ 42°C) in the presence of alternating magnetic field (AMF). Numerous researchers showed mild whole body hyperthermia can increase BBB permeability for potential brain therapeutic application. Compared to conventional hyperthermia, AMF-induced hyperthermia increased BBB permeability with a shorter duration of hyperthermia and lower temperature, providing the potential to enhance IONP flux across the BBB with reduced toxicity.
Overall, ENMs with optimized physicochemical properties can enhance their flux across the BBB into the brain with desirable pharmacokinetics, which provide great potential for diagnosis and therapy in the CNS.
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Vaughn, L. Michelle, Brian Cross, Larissa Bossaer, Emily K. Flores, Jason Moore, and Ivy A. Click. "Analysis of an Interprofessional Home Visit Assignment: Student Perceptions of Team-Based Care, Home Visits, and Medication-Related Problems." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/6368.
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BACKGROUND AND OBJECTIVES: Interprofessional education (IPE) is recommended by many as a means by which to prepare clinicians for collaborative practice and a mechanism by which to improve the overall quality of health care. The objective of this study was to determine the impact of an interprofessional medicine-pharmacy student home visit experience on students’ self-assessments of skills and abilities related to team-based care and identification of medication-related problems. METHODS: Third-year medical and fourth-year pharmacy students completed an interprofessional home visit centered on identification of medication-related problems. Students were surveyed before and after the IPE assignment to assess changes in self-assessed skills and abilities. Survey items consisted of Likert-type statements on a 5-point scale (1=strongly disagree, 5=strongly agree) and free-text responses. Students also completed reflection papers regarding their experiences. RESULTS: Twenty-two medical and 20 pharmacy students conducted medication-focused interviews of 22 patients at home as interprofessional teams. Medical and pharmacy student self-assessments of skills and abilities related to team-based care and identification of medication-related problems improved after completion of the assignment. Both groups of students perceived an improvement in confidence regarding communication skills, both with patients and with other health professions students. Changes were reported on 12 survey items. Student feedback on the IPE experience was positive. CONCLUSIONS: Students’ self-perception of skills and abilities related to interprofessional team-based care and identification of medication-related problems are improved after IPE medication-focused home visit assignment. Student feedback supports the value of interprofessional patient care clinical experiences.
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Song, Lin. "STUDIES OF SOLUBILIZATION OF POORLY WATER-SOLUBLE DRUGS DURING IN VITRO LIPOLYSIS OF A MODEL LIPID-BASED DRUG DELIVERY SYSTEM AND IN MIXED MICELLES." UKnowledge, 2011. http://uknowledge.uky.edu/pharmacy_etds/1.
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Lipid-based drug delivery systems (LBDDSs) are becoming an increasingly popular approach to improve the oral absorption of poorly-water soluble drugs. Several possible mechanisms have been proposed to explain the means by which LBDDSs act in vivo to enhance absorption. The goal of the current dissertation is to provide a better understanding of one proposed mechanism; the capability of lipoidal components in LBDDS formulations to create and maintain a drug in a supersaturated state under simulated GI conditions. Moreover, molecular details of equilibrium solubilization of a drug in a series of model lipid assemblies were examined. The results of these studies will aid formulators in choosing the optimal LBDDS to improve oral absorption of poorly water-soluble drugs.
Time-dependent solubilization behavior of progesterone, 17β-estradiol and nifedipine in a simple model LBDDS composed of Polysorbate 80 was assessed employing the in vitro dynamic lipolysis model. The results illustrated the extent to which the supersaturated state was dependent on the extent of lipolysis of Polysorbate 80 and the initial drug concentration. Area-under-the curve-supersaturation was proposed as a means of quantifying the time-dependent extent of supersaturation in LBDDSs in simulated intestinal conditions.
Concurrently, a series of model mixed micellar solutions, composed of Polysorbate 80 and oleic acid, were prepared to represent the lipid assemblies produced during the lipolysis experiments. The ability of these aggregates to solubilize progesterone, 17β-estradiol and nifedipine were evaluated and the aggregate/water partition coefficients were determined. The Treinor model was found to successfully fit the partition coefficients of the drugs in a range of mixed micelles. The equilibrium solubility of drugs in the mixed micelles was calculated and compared to that found under lipolytic conditions. The best agreement between calculated and experimental conditions was observed for nifedipine. These studies have established a foundation for the evaluation of time-dependent extent of supersaturation with more complex LBDDS formulations exposed to lipolytic conditions.
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Alhaj-Suliman, Suhaila Omar. "Model-based meta-analysis to compare primary efficacy-endpoint, efficacy-time course, safety and tolerability of opioids used in the management of osteoarthritic pain in humans." Thesis, University of Iowa, 2018. https://ir.uiowa.edu/etd/6647.
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Osteoarthritis is a common degenerative disorder that affects joints. Despite recent therapeutic advances, osteoarthritis continues to be a challenging health problem, and elderly population is particularly at risk. Pain is the most unbearable symptom experienced by osteoarthritic patients. Currently, several pharmacological medications are available to manage osteoarthritic pain. Opioids, potent analgesics, have shown extraordinary ability to reduce intense pain in many osteoarthritic clinical trials. Although many clinical trials have investigated the efficacy and safety of opioids in osteoarthritic patients, there is an increased need for a study to integrate the reported outcomes and utilize them to achieve a better understanding of efficacy and safety profiles of opioids. Therefore, in our present study, efficacy, safety, and tolerability profiles of opioid compounds used to manage osteoarthritic pain were assessed and compared using a model-based meta-analysis (MBMA). To achieve our goal, a comprehensive database consisting of pain relief compounds with information on summary-level of efficacy over time, adverse events and dropout rates was compiled from multiple sources. MBMA was conducted using nonlinear mixed-effects modeling approach. The results showed that the selected models successfully captured the observed data, and primary efficacy endpoint estimations indicated that the ED50 of oxycodone, oxymorphone, and tramadol were 47, 84, and 247 mg per day, respectively. Efficacy-time course analysis showed that opioids had rapid time to efficacy onset, suggesting potential powerful pain relief effects. Also, it was found that gastrointestinal adverse events were the most opioid-associated and dose-dependent adverse effects. In addition, the analysis revealed that opioids are well-tolerable at low to moderate doses. The results presented here provided clinically meaningful insights into the efficacy and safety of oxycodone, oxymorphone, and tramadol. In addition, the presented framework analysis has a clinical impact on drug development where it can help in optimizing the dose of opioids to manage osteoarthritic pain, making precise key decisions for positioning of new drugs, and designing more efficient clinical trials.
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Mahasenan, Kiran V. "Discovery of novel small molecule enzyme inhibitors and receptor modulators through structure-based computational design." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1332367560.
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Tokosi, Oluwatoyin Iyabode Abiola. "An assessment of current practice patterns of TB/HIV at primary healthcare clinics in the Western Cape and a needs assessment for clinic-based training among final year Pharmacy students." Thesis, University of the Western Cape, 2010. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_6836_1378888818.
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Tuberculosis (TB) is a major contributor to the disease burden in developing countries resulting in deaths of approximately 2 million people a year. South Africa (SA) has one of the highest annual
TB incidences with an estimate of 558 per 100 000 population (2003) and the situation shows no sign of abating. TB remains the most common opportunistic infection and cause of death
amongst HIV- infected patients. Both TB and HIV treatment depend exclusively on multi-drug regimens that require close monitoring among health care professionals. With increasing workload
due to staff shortage and high patient load, the quality of care in nurse-led primary care clinics maybe compromised. Existing clinic staff may overlook drug-drug interactions, side effects and may
not be aware of the consequences when a formulation is modified during multi-drug therapy administration. As the custodian of medicines, pharmacists are ideally placed to monitor therapy.
Clinicbased training programmes which are offered to nurses provide an opportunity to work alongside clinic staff and engage in patient-centered care where the pharmacotherapeutic outcome of TB and HIV drug regimens could be closely monitored.
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Patterson, Brandon James. "A mixed methods investigation of leadership and performance in practice-based research networks." Diss., University of Iowa, 2013. https://ir.uiowa.edu/etd/5039.
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The objectives of this study were to: 1) create a measure of PBRN clinician member individual performance; 2) produce a rich description of PBRN directors' leadership behaviors and styles; and, 3) identify significant relationships between PBRN director leadership-PBRN clinician member performance. A sequential, exploratory mixed methods design was used to interview and survey PBRN directors and non-director participants. In Phase I, a semi-structured interview guide was used to identify PBRN director leadership behaviors, PBRN non-director performance behaviors and expectations, and decision making activities. A clinician member performance measure was created using a validated behavioral item extraction method. A thematic analysis was conducted on all other data. In Phase II, two quantitative surveys were administered to PBRN directors assessing demographics, membership activity, PBRN productivity, and clinician member performance. One survey was administered to PBRN clinician members assessing their demographics, activity level, and their perceptions of PBRN leadership behaviors. Clinician member performance within PBRNs is a multidimensional construct distinct from participation that is comprised of ownership and engagement aspects, although there is some evidence of a further division into leadership, awareness, follow-through, and communication factors. Collaborative leadership was reported as being distributed to all roles in the PBRN, but is primarily inculcated by a collaborative PBRN director. Time and funding were reported as important resources necessary for the completion of PBRN activities, and are increasingly becoming more limited in their availability. PBRNs engage in a variety of projects and other activities carried out and monitored through ongoing collaborative communication and consensus-based decision making efforts. Top-down decision making patterns by PBRNs have negative relationships with measures of productivity. Directive and participative leadership behaviors do not appear to have direct relationship with clinician member performance, but years of involvement in current PBRN does have a positive association. However, further investigation is necessary to replicate these findings in larger samples. Aiding busy clinicians with engagement through use of central staff may be beneficial. PBRN directors should focus on strengthening collaborative culture of their PBRN and minimizing barriers to effective communication and decision making.
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Flood, Michelle. "Shaping up for success : a qualitative case study on the impact of using interactive radar graphs on workplace-based assessment practices for pharmacy interns in Ireland." Thesis, Lancaster University, 2018. http://eprints.lancs.ac.uk/130523/.
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As competency-based health professions education is implemented more widely, the use of workplace-based assessment (WBA) has increased. WBA involves assessment of trainees in the workplace based on observation of performance against structured competency frameworks or using specific WBA tools. In Ireland, pharmacy interns are assessed against a 178-item behavioural checklist by a tutor as part of formative and summative assessments during training. This leads to the generation of large numbers of ratings which may prove challenging to interpret. This thesis aimed to explore how a novel information visualisation tool (Visualisation Tool) designed to support this process and explore how its introduction could impact on WBA practice. An activity theory-based methodology approach was used to first consider current WBA practice (using document analysis and focus groups) before exploring the potential of the Visualisation Tool to influence practice (using a double-stimulation user testing method). The findings indicated that current WBA practice is unexpectedly complex and many challenges were identified. Participants used technology to enter and record ratings, to review ratings, and as a point of reference during review meetings. Using the visualisation addressed problems relating to reductionism, allowed participants to more readily interpret the data, and allowed time in the review meeting to be used more efficiently so that the intern and tutor could prioritise discussion of specific areas of concern. The activity theory-based study design facilitated an in-depth analysis of the role of technology in practice. This study highlighted that technology is one of several, interrelated tools used in WBA and that while technology-based innovations may address some specific issues, a broader, system-level approach is required to address all issues identified as arising in WBA . These issues should be considered in the context of the overall WBA practice rather than in isolation, and researchers should avoid overestimating participants' estimation of the role of technology.
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Henningsson, Anja. "Mechanism-Based Pharmacokinetic and Pharmacodynamic Modelling of Paclitaxel." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5772.
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Dean, Sondra Faye. "Ligand-associated conformational changes of a flexible enzyme captured by harnessing the power of allostery." Thesis, University of Iowa, 2016. https://ir.uiowa.edu/etd/2201.
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Flexible enzymes are notoriously a bane to structure-based drug design and discovery efforts. This is because no single structure can accurately capture the vast array of conformations that exist in solution and many are subject to ligand-associated structural changes that are difficult to predict. Glutamate racemase (GR) – an antibiotic drug discovery target involved in cell wall biosynthesis – is one such enzyme that has eluded basic structure-based drug design and discovery efforts due to these flexibility issues. In this study, our focus is on overcoming the impediment of unpredictable ligand-associated structural changes in GR drug discovery campaigns. The flexibility of the GR active site is such that it is capable of accommodating ligands with very different structures. Though these ligands may bind to the same pocket, they may associate with quite dissimilar conformations where some are more favorable for complexation than others. Knowledge of these changes is invaluable in guiding drug discovery efforts, indicating which compounds selectively associate with more favorable conformations and are therefore better suited for optimization and providing starting structures to guide structure-based drug design optimization efforts. In this study, we develop a mutant GR possessing a genetically encoded non-natural fluorescent amino acid in a region remote from the active site whose movement has been previously observed to correlate with active site changes. With this mutant GR, we observe a differential fluorescence pattern upon binding of two structurally distinct competitive inhibitors known to associate with unique GR conformations – one to a favorable conformation with a smaller, less solvated active site and the other to an unfavorable conformation with a larger, more solvated active site. A concomitant computational study ascribes the source of this differential fluorescence pattern to ligand-associated conformational changes resulting in changes to the local environment of the fluorescent residue. Therefore, this mutant permits the elucidation of valuable structural information with relative ease by simply monitoring the fluorescence pattern resulting from ligand binding, which indicates whether the ligand has bound to a favorable or unfavorable conformation and offers insight into the general structure of this conformation.
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Liu, Yuhong. "Fragment-based Excitonic Coupled-Cluster Theory for Large Chemical Systems." Scholarly Commons, 2017. https://scholarlycommons.pacific.edu/uop_etds/2980.
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Accurate energetic modeling of large molecular systems is always desired by chemists. For example, ligand-protein binding simulations and enzymatic catalysis studies all involve with a small energy difference. The energetic accuracy depends largely on a proper handling of electronic correlations. Molecular mechanics (MM) methods deliver a parameterized Newtonian treatment to these problems. They show great capability in handling large calculations but give only qualitatively good results. Quantum mechanics (QM) methods solve Schrödinger equations and exhibit much better energy accuracy, though the computational cost can be prohibitive if directly applied to very large systems.
Fragment-based methods have been developed to decompose large QM calculations into fragment calculations. However, most current schemes use a self- consistent field (SCF) method on fragments, in which no electronic correlation is accounted for. The super-system energy is computed as a sum of fragment energies plus two-body corrections and, possibly, three-body corrections (a "body" is a fragment). Higher order corrections can be added.
Nevertheless, many problems require the treatment of high order electronic correlations. The coupled-cluster (CC) theory is the state-of-the-art QM method for handling electronic correlations. The CC wavefunction contains correlated excitations up to a given truncated level and coincidental excitations for all possible electronic excitations. It is a brilliant way of including more electronic correlations while maintaining a low-order scaling. In the proposed excitonic coupled-cluster (X-CC) theory, substantial modifications have been made to allow CC algorithms to act on the collective coordinates of fragment fluctuations to obtain super-system energy.
The X-CC theory is designed to achieve accurate energetic modeling results for large chemical systems with much improved affordability and systematic improvability. The test system used in this work is a chain of beryllium atoms. A 30-fragment X-CCSD(2) calculation delivered matching accuracy with traditional CCSD method. An X-CCSD(2) calculation on a chain of 100 bonded fragments finished in 7 hours on a single 2.2 GHz CPU core. The X-CC scheme also demonstrates the ability in handling charge transfer problems. Due to the use of fluctuation basis in the test cases, the excitonic algorithms can be easily generalized to inhomogeneous systems. This will be investigated in future work.
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Anderson, Ryan, Nicole Lane, Matt Millward, and David Lee. "Comparing the Knowledge of Pharmacy Students at The University of Arizona Regarding Dangerous Critters of Southern Arizona Based on Pre and Post Testing with an Education Session in Between." The University of Arizona, 2011. http://hdl.handle.net/10150/614611.
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Class of 2011 AbstractOBJECTIVES: To determine if knowledge and confidence of third year pharmacy students would increase after an education session presented by the Poison Control Center about scorpions, snakes, Gila Monsters and spiders of the southwest. METHODS: A pre-test/post-test study design was implemented around the presentation from the Poison Control Center utilizing third year pharmacy students at The University of Arizona as the study population. The two tests were than analyzed to determine if there was any statistically significant improvement in quantifiable knowledge and comfort level associated with imparting knowledge regarding venomous stings and bites. RESULTS: Out of an available 95 students, 67 completed the pre and post-tests. Overall, the pharmacy student’s knowledge increased with statistical significance (p<0.05) by 10% with a corresponding statistically significant (p<0.05) increase in comfort level in talking to patients about bites and stings. CONCLUSION: Both knowledge and confidence increased in third year pharmacy students after an education session about scorpions, snakes, Gila monsters and spiders.
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Chang, Elizabeth H. "Implementation of the physician-pharmacist collaborative model in primary care clinics." Diss., University of Iowa, 2013. https://ir.uiowa.edu/etd/2190.
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In the modern society, chronic diseases have become the leading causes of death. With early recognition and proper management, however, many of the complications from chronic diseases could be prevented or delayed. Taking such a proactive approach in managing a population often requires the use of team-based approaches and delegation of certain clinical and nonclinical tasks to nonphysician team members. This three-study dissertation used a combination of methods to explore contextual factors that influence primary care teamwork and physician-pharmacist collaboration. The first study quantitatively examined baseline barriers and facilitators of physician-pharmacist collaboration in clinics participating in the Collaboration Among Pharmacists and Physicians To Improve Outcomes Now (CAPTION) Trial. Pharmacist expertise and clinic staff support were found to be the most important facilitators for physicians, while insurance reimbursement and task design factors were important for pharmacists. The second study characterized clinic personnel experience participating in the CAPTION trial and explored determinants of disease state control. Higher proportions of indigent and minority populations and higher baseline pharmacy structure scores were found to be associated with lower blood pressure control. The third study qualitatively examined organizational influences on primary care team effectiveness and the roles of pharmacists in a separate sample of primary care clinics. A lack of organizational rewards for teamwork in primary care was identified and pharmacists were integrated into clinic workflow in various degrees. These findings will be informative for practice managers and health care professionals seeking to redesign their practice to meet increasing needs of patients with chronic diseases.
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AbdulHameed, Mohamed Diwan Mohideen. "COMPUTATIONAL DESIGN OF 3-PHOSPHOINOSITIDE DEPENDENT KINASE-1 INHIBITORS AS POTENTIAL ANTI-CANCER AGENTS." UKnowledge, 2009. http://uknowledge.uky.edu/gradschool_diss/757.
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Computational drug design methods have great potential in drug discovery particularly in lead identification and lead optimization. 3-Phosphoinositide dependent kinase-1 (PDK1) is a protein kinase and a well validated anti-cancer target. Inhibitors of PDK1 have the potential to be developed as anti-cancer drugs. In this work, we have applied various novel computational drug design strategies to design and identify new PDK1 inhibitors with potential anti-cancer activity. We have pursued novel structure-based drug design strategies and identified a new binding mode for celecoxib and its derivatives binding with PDK1. This new binding mode provides a valuable basis for rational design of potent PDK1 inhibitors. In order to understand the structure-activity relationship of indolinone-based PDK1 inhibitors, we have carried out a combined molecular docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling study. The predictive ability of the developed 3D-QSAR models were validated using an external test set of compounds. An efficient strategy of the hierarchical virtual screening with increasing complexity was pursued to identify new hits against PDK1. Our approach uses a combination of ligand-based and structure-based virtual screening including shape-based filtering, rigid docking, and flexible docking. In addition, a more sophisticated molecular dynamics/molecular mechanics- Poisson-Boltzmann surface area (MD/MM-PBSA) analysis was used as the final filter in the virtual screening. Our screening strategy has led to the identification of a new PDK1 inhibitor. The anticancer activities of this compound have been confirmed by the anticancer activity assays of national cancer institute-developmental therapeutics program (NCI-DTP) using 60 cancer cell lines. The PDK1-inhibitor binding mode determined in this study may be valuable in future de novo drug design. The virtual screening approach tested and used in this study could also be applied to lead identification in other drug discovery efforts.
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Brito, Giselle de Carvalho. "Serviços clínicos farmacêuticos em unidades do programa Farmácia Popular do Brasil do estado de Sergipe: implantação, implementação e consolidação." Universidade Federal de Sergipe, 2015. https://ri.ufs.br/handle/riufs/3592.
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Objective: To establishing, implement and consolidate clinical pharmacy services in units of Farmácia Popular do Brasil program in state of Sergipe. Methods: Initially, systematic review was performed in the databases PubMed, Scopus, EMBASE using the key words "community pharmacy services", "quality assurance health care", "outcome assessment". A longitudinal study of three units of the Farmácia Popular do Brasil in the state of Sergipe on the establishment was carried out (2012), implementation (2013) and consolidation of clinical pharmacy services (2014). The structure of pharmacies was evaluated for physical structure, through the RDC 44/2009, and human resources, the technique of simulated patient. Then three focus groups were conducted (2012, 2013 and 2014) for the perceptions of pharmacists. Finally, we used the coaching technique for establishment, implementation and consolidation of services: dispensing, measurement of blood pressure and blood capillary glucose, medication review and medication therapy management. Results: In the systematic review 42 articles met the inclusion criteria. It was observed that the most valued results were glycosylated hemoglobin (clinical), quality of life (humanistic) and analysis of the cost-effectiveness of the service relationship (economic). In assessing the structure, interventions enabled improvements on all items that were considered non-compliant. However, the overall impression of the pharmaceutical skills for clinical services was considered regular (3) on a scale from 1 to 5. Regarding the focus groups, pharmacists reported expectations in technical support to develop skills, gain knowledge and have a constant monitoring of the researchers, also identified 13 types of barriers. Finally, was designed 520 hours of coaching in place to implement flows and processes, development of standard operating procedures and preparation of strategic plans. In the education training, pharmacists underwent 176 hours of theoretical and practical training and employees to 24h. After the coaching interventions the numbers of services were expanded: there was 767 dispensations in 2012, 1444 in 2013 and 2537 in 2014; 714 measurements of blood pressure and blood capillary glucose in 2012, 2375 in 2013 and 5039 to 2014; 49 consultations of medication review in 2012, 87 in 2013 and 355 in 2014; 15 consultations of medication therapy management in 2012, 33 in 2013 and 271 in 2014. Conclusion: From the good situational diagnosis, the coaching can be considered a technique that assists in establishment, implementation and consolidation of clinical pharmacy services. Combined with a professional training, it allows the individual follow-up in steps as: definition of services and processes, selection of indicators for the assessment and development of strategic plans. In this perspective, this results may support the construction of a differentiated and replicable model of clinical services in community pharmacies.Objetivo: Implantar, implementar e consolidar serviços clínicos farmacêuticos em unidades do programa Farmácia Popular do Brasil do Estado de Sergipe. Métodos: Inicialmente, foi realizada revisão sistemática da literatura nas bases de dados PubMed, SCOPUS, EMBASE utilizando os descritores community pharmacy services , quality assurance health care , outcome assessment . Foi realizado um estudo longitudinal em três unidades da Farmácia Popular do Brasil do estado de Sergipe sobre a implantação (2012), implementação (2013) e consolidação dos serviços clínicos farmacêuticos (2014). Foi avaliada a estrutura das farmácias quanto à estrutura física, por meio da RDC 44/2009, e aos recursos humanos, pela técnica do paciente simulado. Em seguida, foram realizados três grupos focais (2012, 2013 e 2014) para obter as percepções dos farmacêuticos. Por fim, foi utilizada a técnica de coaching para a implantação, implementação e consolidação dos serviços de: dispensação, aferição da pressão arterial e glicemia capilar, revisão da farmacoterapia e seguimento da farmacoterapia. Resultados: Na revisão sistemática 42 artigos preencheram os critérios de inclusão. Observou-se que os resultados mais avaliados foram hemoglobina glicosilada (clínico), qualidade de vida (humanístico) e análise da relação custo-eficácia do serviço (econômico). Na avaliação da estrutura, as intervenções possibilitaram melhorias em todos os itens que foram considerados inconformes. No entanto, a impressão geral sobre as competências farmacêuticas para serviços clínicos foi considerada regular (3) numa escala de 1 a 5. Com relação aos grupos focais, os farmacêuticos relataram expectativas quanto ter suporte técnico para desenvolver habilidades, adquirir conhecimentos e ter um acompanhamento constante dos pesquisadores, além disso, identificaram 13 tipos de barreiras. Por fim, foram destinadas 520 horas de coaching in loco para implantação de fluxos e processos, elaboração de procedimentos operacionais padrão e elaboração de planos estratégicos situacionais. Na etapa de treinamento, os farmacêuticos foram submetidos a 176h de treinamento teórico-prático e os colaboradores a 24h. Após as intervenções do coaching os números dos serviços foram ampliados: obteve-se 767 atendimentos de dispensação em 2012, 1444 em 2013 e 2537 em 2014; 714 aferições da pressão arterial e glicemia capilar em 2012, 2375 em 2013 e 5039 em 2014; 49 consultas da revisão da farmacoterapia em 2012, 87 em 2013 e 355 em 2014; 15 consultas de seguimento da farmacoterapia em 2012, 33 em 2013 e 271 em 2014. Conclusão:. A partir de um bom diagnóstico situacional o coaching pode ser considerado uma técnica que auxilia nas etapas de implantação, implementação e consolidação de serviços clínicos farmacêuticos. Aliado a um treinanamento profissional, ele permite o acompanhamento individualizado em etapas como: definição dos serviços e processos, seleção de indicadores para a avaliação e elaboração de planos estratégicos situacionais. Nesta perspectiva, os resultados observados poderão embasar a construção de um modelo diferenciado e replicável de serviços clínicos farmacêuticos em farmácias comunitárias.
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Amirthalingam, Amirthan Rajakumaran Selliah. "An evaluation of a community pharmacy based, pharmacist-led intervention package targeted to the patients' adherence status, to achieve and maintain target blood pressure (BP) control by optimising antihypertensive medicine adherence." Thesis, University of Birmingham, 2017. http://etheses.bham.ac.uk//id/eprint/7834/.
Full textAbstract:
Antihypertensive pharmacotherapy is associated with poor adherence. No validated method exists to establish patients’ likely adherence level. A systematic review and a single, Swedish community pharmacy practice-based pilot study were undertaken investigating blood pressure (BP) optimization from pharmacist-led, community pharmacy based antihypertensive adherence interventions titrated to individual patients. The systematic review showed generic interventions are often used for optimizing BP. Different intervention outcomes vary: positive, negative and no effect has been demonstrated. Pilot study participants (n=153) were categorised into adherence subgroups (A=Adherent, IR=Intentionally non adherent rational, II=Intentionally non-adherent irrational, U=Unintentionally non-adherent) based on responses to questionnaire format adherence screens. Interventions were designed intuitively to optimize adherence for each subgroup: changes in blood pressure and adherence attitudes were assessed. A significant reduction in mean systolic BP (SBP) (3 mmHg, P < 0.05), with no change in mean diastolic BP (DBP) was seen overall. However, outcomes varied with subgroup: adherence was enhanced in the U subgroup (decreased SBP: 3 mmHg; DBP: no change), but indications of a detrimental effect were observed in the II subgroup (SBP: no change; increased DBP: 3 mmHg). It is feasible to assign patients to different adherence subgroups in community pharmacy, which may optimize medicines adherence through personalization of interventions.
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Painter, Jacob T. "CHRONIC OPIOID USE IN FIBROMYALGIA SYNDROME: CHARACTERISTICS AND OUTCOMES." UKnowledge, 2012. http://uknowledge.uky.edu/pharmacy_etds/5.
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Fibromyalgia syndrome (FMS) is a chronic pain condition with significant societal and personal burdens of illness. Chronic opioid therapy in the treatment of chronic nonmalignant pain has increased drastically over the past decade. This is a worrisome trend in general, but specifically, given the pathophysiologic characteristics seen in fibromyalgia syndrome patients, the use of this class of medication deserves special scrutiny. Although the theoretical case against this therapy choice is strong, little empirical evidence exists. In order to supplement this literature, retrospective analysis methods are utilized to examine the association of state-, provider-, and patient level characteristics with the prevalence of chronic opioid use in this disease state. Data gathered through this analysis is then used to develop a propensity index for the identification of an appropriate control group for fibromyalgia patients, a task that has proven difficult in the literature to date. Using propensity stratification and matching techniques analysis of the impact of fibromyalgia, chronic opioid use, and the interaction of these two variables are undertaken.
Several key findings and updates to the understanding of chronic opioid use and fibromyalgia syndrome are reported. Wide geographic variation in chronic opioid utilization between states is seen. The role of diagnosing provider type in the rate of chronic opioid prescribing is significant and can be aggregated at various levels. Demographic characteristics, comorbid conditions, and concurrent medication use are all important associates of chronic opioid use in fibromyalgia syndrome. Additionally, chronic opioid use in fibromyalgia patients, independent of propensity to receive that therapy choice is a significant correlate with healthcare costs. A diagnosis of fibromyalgia is a statistically significant source of healthcare costs, though the clinical significance of its impact when compared to a closely matched control group is minimized. Despite the minimization of the role of this diagnosis the impact of the interaction of chronic opioid use with fibromyalgia, despite control for myriad regressors, is significant both statistically and clinically.
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Awasthi, Rakesh. "Application of modeling-based approaches to study the pharmacokinetics and pharmacodynamics of Delta-9-tetrahydrocannabinol (THC) and its active metabolite." Diss., University of Iowa, 2017. https://ir.uiowa.edu/etd/5410.
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The medical use of marijuana is increasing, yet little is known about the exposure-response relationships resulting in its psychoactive effects. Δ9-tetrahydrocannabinol (THC) and its active metabolite (11-hydroxy-THC; THC-OH) are the principal psychoactive components in marijuana. It is well known that the plasma concentrations of the psychoactive components of marijuana do not directly relate to the observed psychoactive effects. The presence of a counter-clockwise hysteresis in the plasma concentrations-effect plot demonstrates a temporal delay between the plasma concentrations and observed effect following the intravenous administration of THC. The overarching objective of this research was to better understand the relationship between the plasma and brain concentrations of the psychoactive components (THC and THC-OH) and the observable psychoactive effects after intravenous administration of THC, utilizing model-based approaches. Specifically, the pharmacokinetics were explored using population pharmacokinetic (Pop PK) and physiologically-based pharmacokinetic (PBPK) modeling whereas the pharmacodynamics (PD) of the psychoactive effect (“highness”) were explored using effect-compartment modeling and linking the PD to the PBPK-derived concentrations predicted in the brain and an assumed effect-site.
A “hypothetical” effect compartment model was developed to characterize the observed delay in peak “highness” ratings. A direct relationship was established between the reported psychoactive effects (“highness” or intoxication) and the predicted effect-site concentrations of both components (THC and THC-OH) using this effect-compartment modeling approach. The faster plasma to effect compartment equilibration for THC-OH indicated a more rapid equilibration of the active metabolite between plasma and the effect-site (biophase) than for the parent THC. In addition, a PBPK modeling approach was pursued to predict and relate the brain concentrations of THC and THC-OH to the psychoactive effect. The relationship between the effect and the predicted unbound brain concentration of THC indicated an indirect relationship, suggesting a temporal delay between brain concentrations of THC and observed effect. However, a direct relationship was observed between the observed effect and the unbound brain THC-OH concentrations. In addition, the unbound concentrations of THC-OH in the brain were predicted to be higher than the corresponding THC concentrations. These findings highlight the importance for the inclusion of THC-OH, in addition to THC, when relating the observed effect to the concentrations of the psychoactive components of marijuana.
These models contribute to the understanding of the PK-PD relationships associated with marijuana use and are important steps in the prediction of the pharmacodynamic effects related to the psychoactive components in marijuana and establish an approach for investigating other THC-related effects.
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Cao, Yichen. "APPLICATION OF LINEAR FREE ENERGY RELATIONSHIPS IN THE PREDICTION OF TRIGLYCERIDE/WATER PARTITION COEFFICIENTS AND LIPID BILAYER PERMEABILITY COEFFICIENTS OF SMALL ORGANIC MOLECULES AND PEPTIDES." UKnowledge, 2008. http://uknowledge.uky.edu/gradschool_diss/655.
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Computational methods such as linear free energy relationships (LFERs) offer a useful high-throughput solution to quickly evaluate drug developability, e.g. membrane permeability, organic solvent/water partition coefficients, and solubility. LFERs typically assume the contribution of structural components/functional groups to the overall properties of a given molecule to be constant and independent. This dissertation describes a series of studies in which linear free energy relationships were developed to predict solvation of small organic molecules in lipid formulations, specifically, triglyceride containing solvents and phospholipid-based liposomes. The formation of intermolecular HBs in triglyceride solvents (homogenous with H-bond accepting ability) and intramolecular HBs within the bilayer barrier domain (hydrocarbon-like) proved to be the major factors to consider in developing LFERs to account for the increased oil/water partition coefficients and enhanced bilayer permeability of small organic molecules.
The triglyceride solvent/water partition coefficients of a series of model compounds varying in polarity and H-bond donating/accepting capability were used to establish a correlation between the solvent descriptors and the ester concentration in these solvents using the Abraham LFER approach. The LFER analyses showed that the descriptors representing the polarizability and H-bond basicity of the solvents vary systematically with the ester concentration.
A fragment-based LFER to predict membrane permeability or 1,9- decadiene/water partition coefficients of small organic molecules including small peptides was systematically constructed using a total of 47 compounds. Significant nonadditivity was observed in peptides in that the contribution of the peptide backbone amide to the apparent transfer free energy from water into the bilayer barrier domain is considerably smaller than that of a “well-isolated” amide and greatly affected by adjacent polar substituents on the C-termini.
In order to explain the phenomenon of nonadditivity, the formation of intramolecular HBs and inductive effects of neighboring polar groups on backbone amide, were investigated using FTIR and MD simulations. Both spectroscopic and computational results provided supportive evidence for the hypothesis that the formation of intramolecular HBs in peptides is the main reason for the observed nonadditivity of Δ(ΔG°)-CONH-. The MD simulation results showed that the inductive effect of neighboring groups is not as important as the effect of intramolecular HBs.
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Folly, da Silva Constantino Laura. "An effective layered workflow of virtual screening for identification of active ligands of challenging protein targets." Thesis, University of Iowa, 2017. https://ir.uiowa.edu/etd/5754.
Full textAbstract:
Docking is a computer simulation method used to predict the preferred orientation of two interacting chemical species that has been successfully applied to numerous macromolecules over the years. However, non-traditional targets have inherent difficulties associated with their screening. Large interfaces, lack of obvious binding sites, and transient pockets are some examples. Additionally, most natural ligands of challenging targets are inadequate models for identifying or designing new ligands. Therefore, it is not surprising that customary techniques of structure-based virtual screening are incompatible with these non-traditional targets.
We hypothesized that an integrative virtual screening campaign comprised of docking followed by refinement of best receptor–ligand complexes would effectively identify small-molecule ligands of challenging receptors. We targeted the single-stranded DNA (ssDNA) binding groove of the human RAD52, and a cryptic allosteric pocket of the Helicobacter pylori Glutamate Racemase (GR). In this project, we first determined which docking method was more appropriate for each studied non-traditional target, and then examined how good our two-step docking workflow was in finding novel active ligand scaffolds.
This research developed a powerful layered virtual screening workflow for the discovery of lead compounds against challenging protein targets. Furthermore, we successfully applied a statistical analysis method, which used receiver operating characteristic (ROC) curves, to validate the selected docking protocol that would be used in the screening campaigns. Using the validated workflow, we identified a natural compound that competes with ssDNA to bind to RAD52. The performed screening campaigns also provided new insights into the studied binding pockets, as well as structure-activity relationships (SAR) and binding determinants of the ligands. Our achievements reinforce the power of the ROC curve analysis approach in directing the search for the most appropriate docking protocol and helping to speed up drug discovery in pharmaceutical research.
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Li, Mengyao. "USING SEMIPHYSIOLOGICALLY-BASED PHARMACOKINETIC (SEMI-PBPK) MODELING TO EXPLORE THE IMPACT OF DIFFERENCES BETWEEN THE INTRAVENOUS (IV) AND ORAL (PO) ROUTE OF ADMINISTRATION ON THE MAGNITUDE AND TIME COURSE OF CYP3A-MEDIATED METABOLIC DRUG-DRUG INTERACTIONS (DDI) USING MIDAZOLAM (MDZ) AS PROTOTYPICAL SUBSTRATE AND FLUCONAZOLE (FLZ) AND ERYTHROMYCIN (ERY) AS PROTOTYPICAL INHIBITORS." VCU Scholars Compass, 2016. http://scholarscompass.vcu.edu/etd/4402.
Full textAbstract:
The purpose of the project was to investigate the impact of IV and PO routes difference for MDZ, a prototypical CYP3A substrate, and two CYP3A inhibitors (CYP3AI) -FLZ and ERY-, on the magnitude and time course of their inhibitory metabolic DDI.
Individual semi-PBPK models for MDZ, FLZ and ERY were developed and validated separately, using pharmacokinetic (PK) parameters from clinical/in-vitro studies and published physiological parameters. Subsequently, DDI sub-models between MDZ and CYP3AIs incorporated non-competitive and mechanism-based inhibition (MBI) for FLZ and ERY, respectively, on hepatic and gut wall (GW) CYP3A metabolism of MDZ, using available in-vitro/in-vivo information. Model-simulated MDZ PK profiles were compared with observed data from available clinical PK and DDI studies, by visual predictive check and exposure metrics comparison. DDI magnitude and time course for CYP3AI (IV vs. PO) followed by MDZ (IV vs. PO) at various time points were predicted by the validated semi-PBPK-DDI models. Two hypothetical CYP3A substrates and four CYP3AI (derived from MDZ, FLZ and ERY, with GW metabolism removed, hepatic metabolism reduced, or oral bioavailability (Foral) and/or elimination half-life (t1/2) modified) were also simulated to generalize conclusions.
The final semi-PBPK-DDI models predict well the PK profiles for IV/PO MDZ in absence/presence of IV/PO CYP3AI, with deviations between model-predicted and observed exposure metrics within 30%. Prospective simulations demonstrate that:
1) CYP3A substrates, e.g., MDZ, are consistently more sensitive to metabolic inhibition after PO than after IV administration, due to pre-systemic hepatic and/or GW metabolism. For substrates without GW metabolism and limited hepatic metabolism, only a marginal route difference for substrate administration is observed.
2) For high-Foral CYP3AIs, e.g., FLZ, no inhibitor IV-PO route DDI differences are expected, unless they are given simultaneously with PO MDZ.
3) For low-Foral CYP3AIs, e.g., ERY, greater inhibition is expected after IV than after PO administration for IV MDZ, but is difficult to predict for PO MDZ.
4) In addition to Foral and plasma t1/2 of CYP3AIs, the DDI onset, peak and duration are determined by their oral absorption rate and by the resulting hepatic and/or GW concentration profiles relative to Ki for noncompetitive CYP3AIs, but by CYP3A kinetics (synthesis, degradation rate) for MBI CYP3AIs.
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Beechey, Riley Tegan Anne. "Pharmacist Utilization of Opioid Misuse and Abuse Interventions: Acceptability Among Pharmacists and Patients in Detox." Kent State University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=kent1499974262218499.
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Karlsson, Kristin E. "Benefits of Pharmacometric Model-Based Design and Analysis of Clinical Trials." Doctoral thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-133104.
Full textAbstract:
Quantitative pharmacokinetic-pharmacodynamic and disease progression models are the core of the science of pharmacometrics which has been identified as one of the strategies that can make drug development more effective. To adequately develop and utilize these models one needs to carefully consider the nature of the data, choice of appropriate estimation methods, model evaluation strategies, and, most importantly, the intended use of the model. The general aim of this thesis was to investigate how the use of pharmacometric models can improve the design and analysis of clinical trials within drug development. The development of pharmacometric models for clinical assessment scales in stroke and graded severity events, in this thesis, show the benefit of describing data as close to its true nature as possible, as it increases the predictive abilities and allows for mechanistic interpretations of the models. Performance of three estimation methods implemented in the mixed-effects modeling software NONMEM; 1) Laplace, 2) SAEM, and 3) Importance sampling, applied when modeling repeated time-to-event data, was investigated. The two latter methods are to be preferred if less than approximately half of the individuals experience events. In addition, predictive performance of two validation procedures, internal and external validation, was explored, with internal validation being preferred in most cases. Model-based analysis was compared to conventional methods by the use of clinical trial simulations and the power to detect a drug effect was improved with a pharmacometric design and analysis. Throughout this thesis several examples have shown the possibility of significantly reducing sample sizes in clinical trials with a pharmacometric model-based analysis. This approach will reduce time and costs spent in the development of new drug therapies, but foremost reduce the number of healthy volunteers and patients exposed to experimental drugs.
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Kumari, Vandana. "Structure-Based Computer Aided Drug Design and Analysis for Different Disease Targets." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1311612599.
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Wang, Nick X. "Controlled Delivery of Protein Therapeutics for HIV Prevention." Case Western Reserve University School of Graduate Studies / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=case1327614039.
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