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1.
Gerontol Geriatr Educ ; 42(2): 207-223, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33349173

RESUMO

Fall-related injuries and mortality are increasing in older adults. Evidence suggests a need for a multifactorial, interprofessional approach to reducing falls. The Program for All-Inclusive Care for the Elderly (PACE) utilizes an interprofessional approach to care and serves a high-risk population. The purpose of this study was to investigate the effectiveness of an EBP falls prevention training program conducted at a PACE. The program was a revision of an established program and was led by an interprofessional team. The evaluation used a mixed-methods approach to assess program quality, learning and self-efficacy gains, and intended behavioral changes. Quantitative evaluation demonstrated program satisfaction and qualitative responses identified the depth and interprofessional delivery as favorable. Qualitative data identified opportunities to enhance content and learning design. Overall knowledge gains were statistically significant (mean difference 5%), with the greatest gains related to the evidence base (mean difference 2.67%). Self-efficacy ratings increased significantly after each session. Participants noted changes to team function and a willingness to consider practice changes as a result of the training. The findings support the effectiveness of this interprofessional, EBP training program on falls prevention practices in a PACE and highlight the value of a multifaceted assessment and iterative development.


Assuntos
Acidentes por Quedas , Geriatria , Acidentes por Quedas/prevenção & controle , Idoso , Geriatria/educação , Humanos , Fatores de Risco
2.
Gerontol Geriatr Educ ; 41(1): 63-84, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31488030

RESUMO

With increasing rates of polypharmacy among older adults, preparedness of current and future health care professionals to identify and deprescribe potentially inappropriate medications (PIMs) is critical. Medicine (n = 28), pharmacy (n = 35) and nursing (n = 11) trainees enrolled in an interprofessional course completed a survey assessing preparedness, confidence and attitudes toward deprescribing, and perception of interprofessional roles in the process. Pharmacy (p = .001) and nursing (p = .007) felt that their curriculum prepared them better to identify and deprescribe PIMs compared to medicine trainees. Pharmacy trainees perceived significantly more barriers to deprescribing compared to medicine (p = .003), but not nursing trainees. Physicians and pharmacists were perceived as the main drivers of the deprescribing process. Current curricular content should be modified to address lack of preparedness to deprescribe in clinical practice. Addressing such gaps as part of an interprofessional team may increase interprofessional role recognition and translate into changes in clinical practice as trainees move into the workforce.


Assuntos
Atitude do Pessoal de Saúde , Desprescrições , Relações Interprofissionais , Adulto , Estudos Transversais , Currículo , Feminino , Pessoal de Saúde/psicologia , Humanos , Masculino , Equipe de Assistência ao Paciente , Polimedicação , Inquéritos e Questionários
3.
Ann Pharmacother ; 52(7): 697-699, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29514464

RESUMO

The scope of practice for pharmacists in the United States increasingly includes elements of prescribing under collaborative practice agreements and statewide protocols. However, as a result of continued health care access concerns, we believe that pharmacists will be called on to serve as independent prescribers in the future. For this anticipated practice expansion to become a successful reality, the assurance of pharmacist preparedness and continuous professional development through profession-wide standards will be imperative.


Assuntos
Prescrições de Medicamentos/normas , Farmacêuticos/normas , Papel Profissional , Atitude do Pessoal de Saúde , Humanos , Estados Unidos
4.
Ann Pharmacother ; 50(7): 534-40, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27147704

RESUMO

BACKGROUND: Medication reconciliation to identify discrepancies is a National Patient Safety Goal. Increasing medication number and complex medication regimens are associated with discrepancies, nonadherence, and adverse events. The Medication Regimen Complexity Index (MRCI) integrates information about dosage form, dosing frequency, and additional directions. OBJECTIVE: This study evaluates the association of MRCI scores and medication number with medication discrepancies and commissions, a discrepancy subtype. METHODS: This was a retrospective cohort study of a convenience sample of 104 ambulatory care patients seen from April 2010 to July 2011 within the Department of Veterans Affairs. Primary outcomes included any medication discrepancy and commissions. Primary exposures included MRCI scores and medication number. Multivariable logistic regression models associated MRCI scores and medication number with discrepancies. Receiver operating characteristic (ROC) curves provided discrepancy thresholds. RESULTS: For the 104 patients analyzed, the median MRCI score was 25 (interquartile range [IQR] = 14-43), and the median medication number was 8 (IQR = 5-13); 60% of patients had any discrepancy, whereas 36% had a commission. In adjusted analyses, patients with MRCI scores ≥25 or medication number ≥8 were more likely to have commissions (odds ratio [OR] = 3.64, 95% CI = 1.41-9.41; OR = 4.51, 95% CI = 1.73-11.73, respectively). The unadjusted ROC threshold for commissions was 36 for MRCI (sensitivity, 59%; specificity, 82%) and 9 for medication number (sensitivity 68%; specificity 67%). CONCLUSION: Patients with either MRCI scores ≥25 or ≥8 medications were more likely to have commissions. Given equal performance in predicting discrepancies, the efficiency and simplicity of medication number supports its use in identifying patients for intensive medication review beyond medication reconciliation.


Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Prescrições de Medicamentos/estatística & dados numéricos , Revisão de Uso de Medicamentos/métodos , Reconciliação de Medicamentos/estatística & dados numéricos , Polimedicação , Idoso , Assistência Ambulatorial/métodos , Protocolos Clínicos , Prescrições de Medicamentos/classificação , Prescrições de Medicamentos/normas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Avaliação de Resultados da Assistência ao Paciente , Estudos Retrospectivos , Estados Unidos , United States Department of Veterans Affairs , Veteranos
5.
Palliat Med ; 28(4): 335-41, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24534725

RESUMO

BACKGROUND: Delirium may complicate the hospital course and adversely impact remaining quality of life for palliative care inpatients. Medications with anticholinergic properties have been linked to delirium within elderly populations via serum anticholinergic assays. AIM: The aim of this study is to determine whether increasing anticholinergic burden, as measured using a clinical assessment tool, is associated with an increase in delirium among palliative care inpatients. DESIGN: This study was completed as a retrospective, case-control study. SETTING/PARTICIPANTS: Veterans admitted to the Veterans Affairs Boston Healthcare System and consulted to the palliative care service were considered for inclusion. Increase in anticholinergic burden from admission through hospital day 14 was assessed using the Anticholinergic Risk Scale. Presence of delirium was determined by use of a validated chart review instrument. RESULTS: A total of 217 patients were analyzed, with a mean age of 72.9 (±12.8) years. The overall delirium rate was 31% (n = 67). Patients with an increase in Anticholinergic Risk Scale (n = 72 (33%)) were 40% more likely to experience delirium (odds ratio = 1.44, 95% confidence interval = 1.07-1.94) compared to those without increase (n = 145 (67%)). After adjustment for age, brain metastasis, intensive care unit admission, illness severity, opiate use, and admission Anticholinergic Risk Scale using multivariable modeling, delirium risk remained significantly higher in patients with an Anticholinergic Risk Scale increase compared to those without increase (adjusted odds ratio = 1.43, 95% confidence interval = 1.04-1.94). CONCLUSION: An increase in Anticholinergic Risk Scale from admission was associated with delirium in palliative care inpatients. While additional study is needed, anticholinergic burden should be increased cautiously in palliative inpatients, and those with increases should be closely followed for delirium.


Assuntos
Antagonistas Colinérgicos/efeitos adversos , Delírio/induzido quimicamente , Cuidados Paliativos/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Massachusetts , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Veteranos
6.
Curr Pharm Teach Learn ; 16(6): 445-452, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38631946

RESUMO

BACKGROUND AND PURPOSE: Effective communication skills are essential for all pharmacists, regardless of practice setting. An implicit need in pharmacy education is to emphasize direct application of these skills to future healthcare practice prior to experiential rotations. The aim of this article is to describe how we revised a required first professional year (P1) doctor of pharmacy course to achieve two main goals: 1) improve the course relevance by connecting content to real-world skills; and 2) qualify all pharmacy students at our institution as certified National Diabetes Prevention Program (DPP) lifestyle coaches upon course completion. EDUCATIONAL ACTIVITY AND SETTING: Lifestyle coach training approved by the Centers for Disease Control and Prevention (CDC) was integrated into a P1 communications course consisting of 14 modules that include: review of diabetes pathophysiology, group facilitation skills, social determinants of health, food tracking, action planning, participant retention and program administration. This content serves as a direct application of pre-existing course objectives related to knowledge (evidence-based theory) and skills (technical and counseling) required for effective communication with patients, families, and health professionals. FINDINGS: Between 2019 and 2022, the redesigned course was offered to 373 P1 students. Course evaluations during this time were consistently positive. The average evaluation score since DPP activities were integrated into the course was 3.41 (on a 4-point scale). Based upon course evaluations, students appreciated three main benefits of incorporating lifestyle coach certification into the pharmacy curriculum: 1) a certified skill that can differentiate them in the job market; 2) practice of skills on real patients under faculty supervision in the community setting; 3) early exposure to pharmacy patient care topics, thus contributing to professional identity. SUMMARY: Integration of lifestyle coach training into an existing core P1 pharmacy course increased application and assessment of communications skills and allowed wider availability of trained coaches to deliver DPP in the community.


Assuntos
Currículo , Diabetes Mellitus , Promoção da Saúde , Humanos , Promoção da Saúde/métodos , Promoção da Saúde/normas , Diabetes Mellitus/terapia , Currículo/tendências , Currículo/normas , Educação em Farmácia/métodos , Educação em Farmácia/normas , Estilo de Vida , Comunicação , Estudantes de Farmácia/estatística & dados numéricos
7.
Drugs Aging ; 40(12): 1123-1131, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37856064

RESUMO

BACKGROUND: A growing body of research supports the negative impact of anticholinergic drug burden on physical frailty. However, prior research has been limited to homogeneous white European populations, and few studies have evaluated how anticholinergic burden tools compare in their measurement function and reliability with minority community-dwelling adult populations. This study investigated the association between anticholinergic drug exposure and frailty by conducting a sensitivity analysis using multiple anticholinergic burden tools in a diverse cohort. METHODS: A comprehensive psychometric approach was used to assess the performance of five clinical Anticholinergic Burden Tools: Anticholinergic Cognitive Burden Scale (ACB), Anticholinergic Drug Scale (ADS), average daily dose, total standardized daily doses (TSDD), and Cumulative Anticholinergic Burden scale (CAB). Spearman correlation matrix and intraclass correlation coefficients (ICC) were used to determine the association among the variables. Ordinal logistic regression is used to evaluate the anticholinergic burden measured by each scale to determine the prediction of frailty. Model performance is determined by the area under the curve (AUC). RESULTS: The cohort included 80 individuals (mean age 69 years; 55.7% female, 71% African American). All anticholinergic burden tools were highly correlated (p < 0.001), ICC3 0.66 (p < 0.001, 95% confidence interval (CI) 0.53-0.73). Among individuals prescribed anticholinergics, 33% were robust, 44% were prefrail, and 23% were frail. All five tools predicted prefrail and frail status (p < 0.05) with low model misclassification rates for frail individuals (AUC range 0.78-0.85). CONCLUSION: Anticholinergic burden tools evaluated in this cohort of low-income African American older adults were highly correlated and predicted prefrail and frail status. Findings indicate that clinicians can select the appropriate instrument for the clinic setting and research question while maintaining confidence that all five tools will produce reliable results. Future anticholinergic research is needed to unravel the association between interventions such as deprescribing on incident frailty in longitudinal data.


Assuntos
Fragilidade , Humanos , Feminino , Idoso , Masculino , Fragilidade/induzido quimicamente , Fragilidade/epidemiologia , Reprodutibilidade dos Testes , Antagonistas Colinérgicos/efeitos adversos , Vida Independente
9.
J Am Geriatr Soc ; 69(9): 2619-2624, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33991423

RESUMO

BACKGROUND/OBJECTIVES: Deprescribing is a strategy intended to reduce harms associated with potentially inappropriate medications. Reflective of the growing interest in deprescribing, there has been an increase in related research to better understand the landscape, opportunities for improvement, how best to develop and implement interventions, and remaining knowledge gaps that can be addressed with additional study. DESIGN: We conducted a narrative review of recent deprescribing literature. SETTING: As part of the US Deprescribing Network's inaugural conference in October 2020, we presented a narrative review of recent deprescribing literature to an audience with a range of clinical and research expertise. PARTICIPANTS: We searched four databases for English-language articles published between January 1, 2019 and August 31, 2020. MEASUREMENTS: We evaluated titles, abstracts, and full-length manuscripts for relevance, novelty, rigor and variety of methods; we also aimed for broad representation of authors, institutions, and nations. RESULTS: The initial search returned 199 citations, from which we reviewed 18 full-length manuscripts, selecting 10 articles to present. Salient themes included missed opportunities to deprescribe in potentially eligible patients, with variable impact of medication- and patient-level factors, along with differing perspectives and behaviors between geriatricians, internists, and cardiologists. Clinical, financial, and economic drivers were also evaluated. Finally, attention was given to issues applicable to deprescribing research, including difficulty recruiting trial participants, perspectives of investigators, and integration of findings into clinical practice. CONCLUSION: This narrative review summarizes key advances in the field while also identifying priority areas for additional research.


Assuntos
Pesquisa Biomédica , Desprescrições , Idoso , Humanos
10.
Clin Transl Sci ; 14(2): 437-444, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33026148

RESUMO

Older adults (i.e., 60 years and older), are the leading consumers of medications, and consequently are suffering the most from medication-related adverse events. Not only are older adults the largest consumers of medications, they are more likely to experience an adverse drug event contributing to increased hospitalization, utilization of emergency medical services, and mortality. Translational Approaches to Personalized Health (TAPH) is a transdisciplinary team of researchers conducting community-engaged participatory research focused on the discovery and translation of pharmacogenomic (PGx) data to improve health outcomes. Underserved and ethnically diverse older adults living in urban settings are significantly under-represented in PGx studies. To address the issue of under-representation, our study enrolls older African American adults into a community-based PGx study. Therefore, we will characterize the frequency of actionable PGx genotypes and identify novel PGx response genes in our cohort of older community dwelling African Americans. The translational component of our work is to use the PGx findings to improve therapeutic outcomes for medication management in older adults. Such findings will serve as a foundation for translational PGx studies aimed at improving medication efficacy and safety for older adults. In this article, we describe the process for launching the TAPH collaborative group, which includes the transdisciplinary team, community-engaged participatory research model, study measures, and the evaluation of PGx genes.


Assuntos
Negro ou Afro-Americano/genética , Pesquisa Participativa Baseada na Comunidade/organização & administração , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Colaboração Intersetorial , Pesquisa Translacional Biomédica/organização & administração , Fatores Etários , Idoso , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Humanos , Testes Farmacogenômicos/estatística & dados numéricos , Variantes Farmacogenômicos , Medicina de Precisão/métodos
11.
Pharmacogenomics ; 21(9): 627-635, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32425117

RESUMO

Older adults are at high risk for inappropriate prescribing, developing polypharmacy, adverse drug events and poor treatment outcomes due to multimorbidity and geriatric syndromes. Pharmacogenomics could allow healthcare professionals to provide optimal patient care while minimizing the risk of adverse drug events and simplifying complex medication regimens. The implementation of pharmacogenomics in geriatrics medicine requires a broad multilayered bottom-up approach. These include curriculum redesign, rethinking experiential education and patient and provider education. There are barriers associated with adopting pharmacogenomics into clinical practice. These barriers may include economic factors, workflow and informatics support. However, addressing these barriers primarily requires creating a culture of innovative practices in patient care, ongoing interprofessional continuing education and an interdisciplinary approach for patient care.


Assuntos
Prescrições de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Prescrição Inadequada/prevenção & controle , Educação de Pacientes como Assunto/métodos , Farmacogenética/métodos , Polimedicação , Idoso , Idoso de 80 Anos ou mais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Humanos , Prescrição Inadequada/tendências , Multimorbidade/tendências , Educação de Pacientes como Assunto/tendências , Farmacogenética/tendências
12.
Res Social Adm Pharm ; 16(2): 230-237, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31155477

RESUMO

BACKGROUND: Schools of Pharmacy are important contributors to pharmacy practice research and several have created research centers focusing on this area. OBJECTIVES: To identify and characterize pharmacy practice research centers in the United States. METHODS: A comprehensive list of research centers was gathered using three sources: 1) websites of Schools of Pharmacy obtained from the American Association of Colleges of Pharmacy website; 2) Google; and 3) department chairs. Two independent reviewers applied the following exclusion criteria to the list: 1) no affiliation with a School of Pharmacy; 2) no focus on research; 3) not an independent unit recognized at the school or university levels; and 4) research not focused on advancing pharmacy practice. Inter-rater reliability was calculated using a prevalence-adjusted bias-adjusted kappa (PABAK). A questionnaire was developed comprising 24 questions grouped into three sections - overall structure of the center, research and educational activities - and disseminated through center directors. Descriptive statistics of survey data were obtained. RESULTS: Twenty centers across 20 different states were identified. Survey response rate was 100%. Three-quarters of centers were at public institutions and half had an advisory board. Full-time equivalents ranged from 0.2 to 21. Areas of research primarily focused on medication and disease-state management and interprofessional collaboration in the ambulatory/outpatient setting. Few centers (35%) conducted experimental studies. Despite 85% centers conducting multi-site studies, the median number of sites engaged was low (range 1-3). Seven centers received over USD 1 million in total funding since inception. A majority of centers (90%) offered educational activities for both students and professionals. CONCLUSIONS: Pharmacy practice research centers are relatively small, received low funding and few conduct multi-site experimental studies. Collaboration among centers could be a means to overcome these issues.


Assuntos
Centros Médicos Acadêmicos/tendências , Docentes de Farmácia , Pesquisa em Farmácia/tendências , Faculdades de Farmácia/tendências , Inquéritos e Questionários , Centros Médicos Acadêmicos/métodos , Estudos Transversais , Humanos , Pesquisa em Farmácia/métodos , Estados Unidos
13.
J Contin Educ Health Prof ; 40(1): 49-57, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32149948

RESUMO

INTRODUCTION: De-prescribing is a complex behavior that benefits from a multifaceted approach to learning. We sought to create and deliver a 1-day interprofessional workshop to enhance de-prescribing knowledge and skills among health care professionals. METHODS: Workshop development was based on the Adult Learning Theory and the Theoretical Domains Framework. The workshop addressed provider-related barriers, was created and delivered by an interprofessional team, and combined didactic and active learning techniques. Targeted participants included physicians, advanced practice providers (nurse practitioners and physician's assistants), pharmacists, and clinic staff. Interprofessional workgroups were created a priori. Participants were asked to complete a postprogram evaluation, including whether they would implement changes to practice, teaching, research, or administrative duties after participation. RESULTS: We created an in-person, 5.5 credit hour, interprofessional de-prescribing workshop that comprised six sessions: (1) polypharmacy and de-prescribing overview; (2) identification of potentially inappropriate medications; (3) prioritization of medications for de-prescribing; (4) design and implementation of a de-prescribing plan; (5) principles for a patient-centered approach; and (6) suggestions for successful collaboration. Forty-one participants attended the workshop, and 38 (92.7%) completed the postprogram assessment. Participants felt they were likely to implement changes in practice, teaching, research, or administrative duties, rating themselves with a mean of 9.2 (SD = 1.06) on a 1 to 10 scale. Ultimately, 96.6% would recommend the workshop to others. DISCUSSION: Based on participant feedback, the workshop catalyzed intention to change practice, teaching, research, or administrative duties. Other institutions seeking to change the complex behavior of de-prescribing may wish to model this development and delivery strategy.


Assuntos
Desprescrições , Educação/métodos , Pessoal de Saúde/educação , Padrões de Prática Médica/tendências , Humanos , Padrões de Prática Médica/normas , Inquéritos e Questionários
14.
Bioorg Med Chem Lett ; 19(17): 5158-61, 2009 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-19646866

RESUMO

This Letter describes the discovery and key structure-activity relationship (SAR) of a series of 2-aminobenzimidazoles as potent Aurora kinase inhibitors. 2-Aminobenzimidazole serves as a bioisostere of the biaryl urea residue of SNS-314 (1c), which is a potent Aurora kinase inhibitor and entered clinical testing in patients with solid tumors. Compared to SNS-314, this series of compounds offers better aqueous solubility while retaining comparable in vitro potency in biochemical and cell-based assays; in particular, 6m has also demonstrated a comparable mouse iv PK profile to SNS-314.


Assuntos
Antineoplásicos/química , Benzimidazóis/química , Inibidores de Proteínas Quinases/química , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacocinética , Aurora Quinases , Benzimidazóis/síntese química , Benzimidazóis/farmacocinética , Linhagem Celular Tumoral , Humanos , Camundongos , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/farmacocinética , Proteínas Serina-Treonina Quinases/metabolismo , Relação Estrutura-Atividade
15.
Am J Pharm Educ ; 83(1): 6976, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30894774

RESUMO

Objective. To identify programmatic components and structural features associated with success of mentoring programs within the health sciences. Findings. Thirty-eight manuscripts representing 34 individual programs were reviewed. Of the institutions represented, 68% were public. Sixty-eight percent of programs included single disciplines only, with four focused in pharmacy, 13 in medicine, and six in nursing. Of the 34 individual programs, all programs reporting participant confidence and self-efficacy reported success in that domain. Eighteen programs reported outcomes related to scholarly activity that included publications or funding/grantsmanship; 16 reported success. Eleven of 16 programs reporting promotion/tenure and/or faculty retention rates reported success. Program components associated with successful programs included frequent meetings (at least monthly) and delivering content within formal curricula. Content categories common within programs reporting success were content related to research, funding/grantsmanship and networking/collaboration. In addition, specific for the promotion/retention domain, content related to curriculum/teaching was commonly found within successful programs. Summary. Although somewhat dependent on the program's specific goals, curriculum most commonly associated with success contained content on research, grantsmanship/funding, curriculum/teaching, and networking/collaboration. Among many programs, the reporting lacked objective, standardized metrics and often included only generalized descriptions/categorization of course content. The incomplete and inconsistent reporting limited our ability to draw conclusions regarding individual topics important for each program component. Proper planning, execution, and assessment of faculty mentoring programs is critical to the identification of additional program characteristics for optimal faculty success.


Assuntos
Docentes de Medicina/educação , Tutoria/estatística & dados numéricos , Desenvolvimento de Pessoal , Currículo , Educação em Farmácia , Humanos , Tutoria/organização & administração , Mentores , Avaliação de Programas e Projetos de Saúde
16.
Bioorg Med Chem Lett ; 18(17): 4880-4, 2008 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-18678489

RESUMO

This communication describes the discovery of a novel series of Aurora kinase inhibitors. Key SAR and critical binding elements are discussed. Some of the more advanced analogues potently inhibit cellular proliferation and induce phenotypes consistent with Aurora kinase inhibition. In particular, compound 21 (SNS-314) is a potent and selective Aurora kinase inhibitor that exhibits significant activity in pre-clinical in vivo tumor models.


Assuntos
Neoplasias Experimentais/tratamento farmacológico , Compostos de Fenilureia/química , Compostos de Fenilureia/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Quinazolinas/farmacologia , Tiazóis/química , Tiazóis/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Aurora Quinases , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Humanos , Camundongos , Transplante de Neoplasias , Neoplasias Experimentais/enzimologia , Quinazolinas/química , Relação Estrutura-Atividade
17.
Int J Radiat Biol ; 84(2): 107-25, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18246480

RESUMO

PURPOSE: Human diseases associated with acute radiation responses are rare genetic disorders with common clinical and biological features including radiosensitivity, genomic instability, chromosomal aberrations, and frequently immunodeficiency. To determine what molecular assays are predictive of cellular radiosensitivity whatever the genes mutations, the existence of a quantitative correlation between cellular radiosensitivity and unrepaired DNA double-strand breaks (DSB) repair defects was examined in a collection of 40 human fibroblasts representing 8 different syndromes. MATERIALS AND METHODS: A number of techniques such as pulsed-field gel electrophoresis, plasmid assay and immunofluorescence with antibodies against MRE11, MDC1, 53BP1 and phosphorylated forms of H2AX, DNA-PK were applied systematically. RESULTS AND CONCLUSIONS: Survival fraction at 2 Gy was found to be inversely proportional to the amount of unrepaired DSB, whatever the genes mutations and the assay applied. However, no single assay discriminates the full range of human radiosensitivity. Particularly, nuclear foci formed by the phosphorylation of H2AX do not predict well moderate radiosensitivities. Our findings suggest the existence of an ATM-dependent interplay between the activation of DNA-PK and MRE11. A classification of diseases according their cellular radiosensitivity, their molecular response to radiation and the functional assays permitting their evaluation is proposed.


Assuntos
Quebras de DNA de Cadeia Dupla/efeitos da radiação , Dano ao DNA/efeitos da radiação , Reparo do DNA/efeitos da radiação , Fibroblastos/efeitos da radiação , Tolerância a Radiação/efeitos da radiação , Bioensaio/métodos , Linhagem Celular , Sobrevivência Celular/fisiologia , Sobrevivência Celular/efeitos da radiação , Dano ao DNA/fisiologia , Reparo do DNA/fisiologia , Eletroforese em Gel de Campo Pulsado/métodos , Fibroblastos/citologia , Fibroblastos/metabolismo , Imunofluorescência/métodos , Previsões , Humanos , Tolerância a Radiação/fisiologia , Fatores de Tempo , Raios X
18.
19.
Drugs Aging ; 35(1): 27-41, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29350336

RESUMO

BACKGROUND: Case reports have demonstrated that dual use of cholinesterase inhibitors (ChIs) and urinary anticholinergics (UAChs) in older adults may be associated with delusions, aggression, changes in cognition, and anxiety, which typically resolve on drug discontinuation. Despite opposing mechanisms of action, these drugs continue to be co-prescribed. OBJECTIVE: This systematic review evaluates cognitive and functional outcomes of dual use of ChIs and UAChs and describes its prevalence. PATIENTS AND METHODS: A literature search using terms related to ChIs and UAChs was conducted. Observational or interventional studies evaluating cognitive or functional outcomes in subjects receiving dual therapy were included for the primary aim. Articles describing prevalence of dual use were included for the secondary aim. RESULTS: Of 1340 unique results, five studies met the inclusion criteria for the primary aim. Four of the studies assessed cognitive outcomes-three failed to identify a significant difference in cognitive function with dual use and the fourth study observed a statistically significant improvement in cognition with dual use of high-dose donepezil and solifenacin when compared with baseline. Three studies assessed functional outcomes-one revealed a 50% greater quarterly decline in activities of daily living (p = 0.01) among dual users functioning in the top quartile, another revealed significant functional improvement in dual users, and the final study did not demonstrate a significant difference. Seventeen articles were included for the secondary aim. Prevalence of dual use ranged from 1.2 to 40.5%. CONCLUSION: This systematic review revealed a high prevalence of dual use of ChIs and UAChs; however, there are mixed results for cognitive and functional outcomes. Results were limited by methodological flaws. Observational or interventional studies assessing dual users are lacking and further study of cognitive and functional risks of dual ChI and UACh use is needed.


Assuntos
Antagonistas Colinérgicos/administração & dosagem , Antagonistas Colinérgicos/efeitos adversos , Inibidores da Colinesterase/administração & dosagem , Inibidores da Colinesterase/efeitos adversos , Transtornos Cognitivos/induzido quimicamente , Cognição/efeitos dos fármacos , Atividades Cotidianas , Fatores Etários , Demência/tratamento farmacológico , Interações Medicamentosas , Humanos , Incontinência Urinária/tratamento farmacológico
20.
Clin Pharmacol ; 9: 113-117, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29042822

RESUMO

OBJECTIVES: Detection of delirium in hospitalized patients remains challenging. The objective was to determine if the prescription of antipsychotic medications was associated with delirium. PATIENTS AND METHODS: Two patient cohorts were utilized from a tertiary Veterans Affairs hospital: a palliative care retrospective cohort and a prospective medical cohort. Patients prescribed outpatient antipsychotics were excluded. Retrospectively, delirium was identified using a validated medical record-review instrument. Prospectively, a clinical expert assessed patients for delirium daily using a standardized interview. Acute antipsychotic medication administration was recorded from the electronic medical record. RESULTS: In the retrospective cohort (n=217), delirium was found in 31% (n=67) and antipsychotic use in 18% (n=40) of patients. Acute antipsychotic use indicated delirium with 54% sensitivity and 97% specificity. In the prospective cohort (n=100), delirium developed in 23% (n=23) and antipsychotics were used in 5% (n=5) of patients. The sensitivity and specificity of acute antipsychotic use was 22% and 100%, respectively. CONCLUSION: Hospitalized patients who are acutely prescribed antipsychotics are likely to have delirium, but not all patients with delirium will be identified with this method. In health systems, utilization of the prescription of acute antipsychotics can be an efficient and specific method to identify delirious patients for targeted intervention.

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