RESUMO
Background: Atrial Fibrillation (AF) increases the risk of stroke by a factor of five, leading a significant cost burdens on healthcare system. Pharmacists, especially those based in a primary care environment are well placed to support patients in this therapeutic area. Objectives: To assess primary care pharmacists' actual knowledge on the management of AF symptoms and anticoagulation. Furthermore, to investigate the resources used by pharmacists. Methods: A cross-sectional study using survey was conducted, targeting UK-based registered pharmacists employed within primary care settings. Quantitative data were analysed utilising descriptive univariate and bivariate statistics. Results: 349 pharmacists completed the adapted 19-questions of the pharmacists' knowledge. Out of a maximum of 19 points, the mean score was 14.34 ± 2.2 (75 ± 11.6%). The questionnaire revealed several significant gaps in pharmacists' knowledge. Most of the surveyed pharmacists (62.8%) reported that they used sources of information to support their consultations. Half reported that they used the National Institute for Health and Care Excellence (NICE) guidance (52.4%) and the British National Formulary (BNF) (50.7%). Conclusions: Primary care pharmacists are knowledgeable about AF and its management; however, some gaps exist which may require addressing. Although pharmacists use a variety of information resources, it is the traditional resources that remain the most frequently used.
RESUMO
BACKGROUND: Atrial fibrillation (AF) affects up to 2% of the UK population. AF is a potentially long-term condition that needs management, and as such primary care pharmacists may have a substantial role in supporting the management of AF. OBJECTIVES: This study aims to explore the role of primary care pharmacists, working in community pharmacies and general practices (GPs), in supporting the management of AF. Furthermore, this study investigates pharmacists' confidence in their knowledge and their attitudes towards incorporating AF-associated mobile apps use into their current practice. METHODS: A qualitative study was conducted, using one-to-one semi-structured, audio-recorded interviews with primary care pharmacists. The topic guide was developed based on pharmacy visits and included the most relevant constructs from the 'consolidated framework for implementation research (CFIR)'. All interviews were audio-recorded, transcribed verbatim and thematically analysed until saturation was achieved, guided by Braun and Clarke's 6-step research method. This study was given a favourable opinion on 5 September 2019 by the University of Birmingham (UOB) Research Ethics Committee (Reference ERN_19-0908). RESULTS: Thematic saturation was achieved after 11 interviews with primary care pharmacists (seven community pharmacists, and four GP pharmacists). Three main themes emerged relating to (1) the clinical role of pharmacists in the management of AF; (2) knowledge and awareness; and (3) prioritisation of resources. The first highlighted that primary care pharmacists were an underutilised resource within AF management. The second demonstrated that pharmacists, especially those based in the community, felt a lack of confidence in their knowledge of AF and its management, mainly community pharmacists due to other roles taking precedence over clinical roles. Both community and GP pharmacists expressed the need to have further training in this therapeutic area to be able to effectively support patients with AF. The third shed light on the pharmacists' views relating to the technological revolution in healthcare. Pharmacists expressed an interest in using apps to support their current practice. CONCLUSIONS: Primary care pharmacists supported an extended care to AF management from screening to consultations, yet the provision of such services remains limited and inconsistent. Future research should focus on understanding the ways in which pharmacists' role can be adapted toward greater involvement in clinical care.
RESUMO
Pharmacists deliver pharmaceutical care in many different healthcare settings and are well-placed to support the prevention of stroke. However, their role and impact in this area is ill-defined. This systematic review aims to explore the pharmacists' role in stroke prevention. Nine databases were searched for studies reporting pharmacist interventions in the management of primary and secondary ischaemic stroke prevention. Study quality was evaluated through Cochrane Risk of Bias and Joanna Briggs Institute (JBI) appraisal tools where possible. A narrative review was conducted and meta-analysis performed for studies with comparable outcomes. Of the 834 initial articles, 31 met inclusion criteria. Study designs were varied and included controlled trials, observational studies, audit reports and conference abstracts. Seven studies addressed the pharmacists' role in primary prevention and 24 in secondary prevention. Pharmacist interventions reported were diverse and often multifactorial. Overall, 20 studies reported significant improvement in outcomes. Meta-analysis showed pharmacist interventions in emergency care significantly improved the odds of achieving thrombolytic therapy door to needle (DTN) times ≤45 min, odds ratio: 2.69 (95% confidence interval (CI): 1.95−3.72); p < 0.001. The pharmacists' role is varied and spans the stroke treatment pathway, with the potential for a positive impact on a range of health-related outcomes.
RESUMO
In response to the COVID-19 pandemic, Health Education England (HEE) and the University of Birmingham provided National Health Service (NHS) staff free access to SCRIPT, a national eLearning programme for safer prescribing and therapeutics. The eLearning was particularly for those returning to work or being redeployed. In the year March 2020-21, 3412 users registered to access portfolios and opened an aggregate of 17 198 modules. Each user completed a median of 2 (range 1-50, interquartile range [IQR] 1-7) assessed learning modules. Marks improved from pre-test to post-test by a median of 2 (IQR 0-3) marks out of 10. The most frequently selected modules were Adherence and Concordance (1109 users), Fluids (981 users) and Diabetic Emergencies (818 users). A total of 878 users accessed the unassessed COVID-19 module. The SCRIPT modules provided standardised education in core principles relating to prescribing and therapeutics, and were used by professionals from many healthcare disciplines.
Assuntos
COVID-19 , Pandemias , Adaptação Psicológica , Humanos , Aprendizagem , Medicina EstatalRESUMO
BACKGROUND: Adherence rates of preventative medication for cardiovascular disease (CVD) have been reported as 57%, and approximately 9% of all CVD events in Europe are attributable to poor medication adherence. Mobile health technologies, particularly mobile apps, have the potential to improve medication adherence and clinical outcomes. OBJECTIVE: The objective of this study is to assess the effects of mobile health care apps on medication adherence and health-related outcomes in patients with CVD. This study also evaluates apps' functionality and usability and the involvement of health care professionals in their use. METHODS: Electronic databases (MEDLINE [Ovid], PubMed Central, Cochrane Library, CINAHL Plus, PsycINFO [Ovid], Embase [Ovid], and Google Scholar) were searched for randomized controlled trials (RCTs) to investigate app-based interventions aimed at improving medication adherence in patients with CVD. RCTs published in English from inception to January 2020 were reviewed. The Cochrane risk of bias tool was used to assess the included studies. Meta-analysis was performed for clinical outcomes and medication adherence, with meta-regression analysis used to evaluate the impact of app intervention duration on medication adherence. RESULTS: This study included 16 RCTs published within the last 6 years. In total, 12 RCTs reported medication adherence as the primary outcome, which is the most commonly self-reported adherence. The duration of the interventions ranged from 1 to 12 months, and sample sizes ranged from 24 to 412. Medication adherence rates showed statistically significant improvements in 9 RCTs when compared with the control, and meta-analysis of the 6 RCTs reporting continuous data showed a significant overall effect in favor of the app intervention (mean difference 0.90, 95% CI 0.03-1.78) with a high statistical heterogeneity (I2=93.32%). Moreover, 9 RCTs assessed clinical outcomes and reported an improvement in systolic blood pressure, diastolic blood pressure, total cholesterol, and low-density lipoprotein cholesterol levels in the intervention arm. Meta-analysis of these clinical outcomes from 6 RCTs favored app interventions, but none were significant. In the 7 trials evaluating app usability, all were found to be acceptable. There was a great variation in the app characteristics. A total of 10 RCTs involved health care professionals, mainly physicians and nurses, in the app-based interventions. The apps had mixed functionality: 2 used education, 7 delivered reminders, and 7 provided reminders in combination with educational support. CONCLUSIONS: Apps tended to increase medication adherence, but interventions varied widely in design, content, and delivery. Apps have an acceptable degree of usability; yet the app characteristics conferring usability and effectiveness are ill-defined. Future large-scale studies should focus on identifying the essential active components of successful apps. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42019121385; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=121385.
Assuntos
Doenças Cardiovasculares , Aplicativos Móveis , Telemedicina , Pressão Sanguínea , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Humanos , Adesão à MedicaçãoRESUMO
Fundamental knowledge about the composition of intestinal fluids in paediatric populations is currently unavailable. This study aimed to characterise gastric and intestinal fluid from paediatric populations. Gastric and intestinal fluid samples were obtained during routine clinical endoscopy from paediatric patients at a large teaching hospital. These fluids were characterised to measure the pH; buffer capacity; osmolality; bile acid concentration and composition. A total of 55 children were recruited to the study aged from 11 months to 15 years of age where 53 gastric fluid samples and 40 intestinal fluid samples were obtained. pH values recorded ranged from pH 0.57 to 11.05 (median: 2.50) in gastric fluids and from 0.89 to 8.97 (median: 3.27) in intestinal fluids. The buffer capacity did not change significantly between gastric and intestinal fluids with median values of 12 mM/L/ΔpH for both fluids. Gastric fluid osmolality values ranged from 1 to 615 mOsm/kg, while intestinal fluid values ranged from 35 to 631 mOsm/kg. Gastric fluid bile acid concentrations ranged from 0.002 to 2.3 mM with a median value of 0.017 mM whilst intestinal fluid bile acid concentrations ranged from 0.0008 to 3.3 mM with a median value of 0.178 mM. Glycocholate; taurocholic acid; glycochenodeoxycholate and taurochenodeoxycholate were the most commonly identified bile acids within paediatric intestinal fluids. All compositional components were associated with large inter-individual variability. Further work is required to develop simulated paediatric media and to explore the impact of these media on drug solubility and dissolution.
Assuntos
Jejum/metabolismo , Mucosa Gástrica/metabolismo , Conteúdo Gastrointestinal/química , Mucosa Intestinal/metabolismo , Administração Oral , Adolescente , Fatores Etários , Criança , Pré-Escolar , Liberação Controlada de Fármacos/fisiologia , Endoscopia Gastrointestinal , Feminino , Absorção Gastrointestinal , Humanos , Concentração de Íons de Hidrogênio , Lactente , Recém-Nascido de Baixo Peso/metabolismo , Recém-Nascido , Recém-Nascido Prematuro/metabolismo , Masculino , Concentração Osmolar , SolubilidadeRESUMO
There is great interest in demonstrating acceptability of solid oral formulations in paediatric populations. This study investigated the acceptability of small, 7.5 mm, bitter-flavoured, coated tablets in healthy children and adults. A randomised, double-blind acceptability test was performed involving 101 children (4-12 years) and 52 adults (18-75 years). Acceptability was measured by participants as sensory assessment of taste, mouthfeel and hedonic perception, and by researcher observations of ability to swallow the tablet and negative facial expressions. Additionally, the taste-masking effect of film coatings was assessed based on the intensity of bitterness perception. At least one tablet was voluntarily swallowed by 35.7% of 4-6-year olds, 74% of 7-12-year olds and 98% of adults. The bitterness of the tablet did not affect participants' ability to swallow it. The sensory properties determined whether the tablet was acceptable. The following factors: low bitterness, high smoothness, high slipperiness and pleasant aftertaste had a positive impact on overall palatability in both populations. The paediatric scores during sensory evaluation of tablets differed from adults, showing lower acceptability. This study demonstrates the multifactorial nature of palatability of tablets and highlights that adults' palatability evaluation cannot be directly translated to a paediatric population.
Assuntos
Deglutição/efeitos dos fármacos , Quinina/administração & dosagem , Comprimidos , Paladar/efeitos dos fármacos , Tecnologia Farmacêutica/métodos , Administração Oral , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção Gustatória , Adulto JovemRESUMO
OBJECTIVE: The aim of this study was to investigate the provision of community pharmacy services to children and young people with a focus on advanced services such as medicines use review. Perceptions and experiences of community pharmacists, pharmacy staff, young people and their parents or carers on the provision of such services were also explored. METHODS: Four different cross-sectional, self-administered questionnaires were distributed in parallel to pharmacists, pharmacy staff members, children and young people and parents in the United Kingdom. RESULTS: An outline of pharmacist's current involvement with children and young people was provided by 92 pharmacists. A different group of 38 community pharmacists and 40 non-pharmacist members of pharmacy staff from a total of 46 pharmacies provided information and views on the conduct of Medicines use review with children and young people. Experiences of advanced pharmacy service provision were collected from 51 children and young people and 18 parents. Most pharmacists offered public health advice to children and young people (73/92; 79.3%) and even more (83/92; 90.2%) reported that they often interacted with children and young people with long-term condition. Despite their high levels of interaction, and a majority opinion that medicines use reviews could benefit children (35/38; 92.1%), the number of pharmacies reporting to have conducted medicines use reviews with children was low (5/41). Pharmacists perceived the main barriers to recruitment as consent (17/29; 58.6%), guideline ambiguity (14/29; 48.3%) and training (13/29; 44.8%). A considerable proportion pharmacists (12/29; 41.4%) and other personnel (14/33; 42.4%) working in community pharmacies were unaware that children were potentially eligible for medicines use reviews. Only 29.4% of the 51 children and young people participants had received advice about their long-term condition from a pharmacist and the majority (46/51; 90.2%) had not taken part in an advanced service focused on adherence. CONCLUSIONS: While general engagement with children and young people appears high from the pharmacist's perspective, advice specific to children and young people with long-term conditions and the provision of advanced services in this group remains a challenge.
RESUMO
The volume and localization of fluid in the paediatric gastrointestinal tract is crucial to the design of in vitro and in silico models that predict the absorption of oral drugs administered to children. Previous studies have used magnetic resonance imaging (MRI) to quantify fluid volumes and localization in the intestines of adults; this study is the first to undertake similar analysis of pediatric participants. This study quantified the amount and distribution of fluid in fasted and fluid-fed children using MRI data captured during the routine clinical assessment. Data from 32 fasted children (aged 0-16 years) and 23 fluid-fed children (aged 8-16 years) were evaluated. The gastric volume ranged from 0 to 9 mL in the fasted and 19-423 mL in the fluid-fed state. The small intestinal volume was recorded to be 0-51 mL in the fasted and 6-91 mL in the fluid-fed state with an average number of 7.7 and 22.4 fluid pockets, respectively. The data showed significant differences in gastric volumes and the number of fluid pockets in the small intestine for age-matched fasted and fluid-fed children (p < 0.05). Both the number and the volume of pockets reported in children are much lower than those previously reported in adults. This study is the first to report intestinal volumes and localization in children and provides new information to achieve the design of biorelevant in vitro models and real values to update in silico models. The data available from both fluid-fed and fasted children show the extremes of fluid volumes that are present in the gastro-intestinal tract which is useful to understand the variability associated with drug absorption in children.
Assuntos
Mucosa Gástrica/metabolismo , Conteúdo Gastrointestinal/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Polietilenoglicóis/farmacocinética , Administração Oral , Adolescente , Criança , Pré-Escolar , Jejum , Feminino , Absorção Gastrointestinal , Humanos , Lactente , Recém-Nascido , Masculino , Polietilenoglicóis/administração & dosagem , Estudos RetrospectivosRESUMO
Recent evidence has shown that the incidence of long-term illnesses in young people aged 10-24 years is increasing. It is essential to highlight the importance of long-term health conditions in this age group and understand young people's health needs to be able to improve current support for young people. Pharmacists, as medicine experts, are in a unique position to promote young people's health. The role of primary care pharmacists in the management of chronic illnesses in young people has not been widely researched. The aim of this review was to explore the current role of primary care pharmacists in the management of chronic illnesses in young people aged 10-24 years. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement using Medical Subject Headings (MeSH) and Embase subject headings (Emtree) terms, covering three main themes: Pharmacists, young people and chronic illnesses. Articles were critically appraised using Critical Appraisal Skills Programme (CASP) tools. Eight articles were included in this review. Seven articles included original research studies (one observational study, two surveys, two qualitative interview studies and two interventions). The remaining article was a literature review. All of the articles made reference to community pharmacists, while there was no information about GP pharmacists. Roles that community pharmacists identified as high-priority in their practice when dealing with young people included supporting young people to develop generic healthcare skills, counselling and building trusted relationships directly with young people, helping young people to find credible health information and the provision of specialist services. Community pharmacists feel that they have a role to play in supporting young people with chronic illness and have identified many areas where they can provide services and support.
RESUMO
The United States has experienced an unsustainable increase of the biomedical research workforce over the past 3 decades. This expansion has led to a myriad of consequences, including an imbalance in the number of researchers and available tenure-track faculty positions, extended postdoctoral training periods, increasing age of investigators at first U.S. National Institutes of Health R01 grant, and exodus of talented individuals seeking careers beyond traditional academe. Without accurate data on the biomedical research labor market, challenges will remain in resolving these problems and in advising trainees of viable career options and the skills necessary to be productive in their careers. We analyzed workforce trends, integrating both traditional labor market information and real-time job data. We generated a profile of the current biomedical research workforce, performed labor gap analyses of occupations in the workforce at regional and national levels, and assessed skill transferability between core and complementary occupations. We conclude that although supply into the workforce and the number of job postings for occupations within that workforce have grown over the past decade, supply continues to outstrip demand. Moreover, we identify practical skill sets from real-time job postings to optimally equip trainees for an array of careers to effectively meet future workforce demand.-Mason, J. L., Johnston, E., Berndt, S., Segal, K., Lei, M., Wiest, J. S. Labor and skills gap analysis of the biomedical research workforce.
Assuntos
Pesquisa Biomédica , Escolha da Profissão , Pesquisadores/educação , Pesquisadores/tendências , Animais , Pesquisadores/economia , Pesquisadores/provisão & distribuição , Salários e Benefícios , Fatores de Tempo , Estados Unidos , Recursos HumanosRESUMO
BACKGROUND: Diets rich in the n-3 fatty acid alpha-linolenic acid (ALA) have been shown to reduce breast tumor growth, enhance the effectiveness of the HER2-targeted drug trastuzumab (TRAS) and reduce HER2 signaling in mouse models. It is unclear whether this is due to direct effects of ALA or due to its long-chain n-3 fatty acids metabolites including docosahexaenoic acid (DHA). METHODS: The ability of HER2-overexpressing BT-474 human breast cancer cells to convert ALA to long-chain n-3 fatty acids was determined by measurement of phospholipid fatty acids by gas chromatography following treatment with 100 µM ALA. The effects of 96 h treatment with ALA or DHA, at serum levels seen in mice (50-100 µM), alone and combined with TRAS (10 µg/ml), on BT-474 cell growth measured by trypan blue exclusion, apoptosis measured by flow cytometric analysis of Annexin-V/7-AAD stained cells (ALA and TRAS treatment only) and protein biomarkers HER2 signaling measured by western blot were determined. RESULTS: ALA-treated BT-474 cells had higher phospholipid ALA but no increase in downstream n-3 metabolites including DHA. Both ALA and DHA reduced cell growth with and without TRAS. ALA had no effect on apoptosis. ALA and DHA showed opposite effects on Akt and MAPK phosphorylation; ALA increased and DHA decreased phosphorylation. CONCLUSIONS: Together these data suggest that, while both ALA and its DHA metabolite can reduce HER2-overexpressing breast cancer growth with and without TRAS, they demonstrate for the first time that DHA is responsible for the effects of ALA-rich diets on HER2 signaling pathways.
Assuntos
Antineoplásicos/farmacologia , Ácidos Docosa-Hexaenoicos/farmacologia , Receptor ErbB-2/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Trastuzumab/farmacologia , Ácido alfa-Linolênico/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quimioterapia Combinada , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Glândulas Mamárias Humanas , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Ácido alfa-Linolênico/metabolismoRESUMO
Flaxseed, rich in α-linolenic acid (ALA), is a complementary breast cancer (BC) therapy; however ALA effectiveness and mechanism are unclear. Variation in cellular expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and estrogen (E2) levels may alter ALA effectiveness. This research determined the effect of ALA on growth, apoptosis, and phospholipid fatty acids of 4 BC cell lines with varying receptor expression ± E2. MCF-7 (ER+/PR+/HER2-), BT-474 (ER+/PR+/HER2+), MDA-MB-231 (ER-/PR-/HER2-) and MDA-MB-468 (ER-/PR-/HER2-) cells were incubated with ALA (50-200 µM) ± 1 nM E2 for 48-72 h. ALA dose-dependently reduced growth, measured by trypan blue exclusion, of all cells (55-80% with 75 µM), and this effect was not altered by E2. ALA (75 µM)+E2 induced apoptosis, measured by flow cytometry (up to 111.2%). Decreased growth and increased apoptosis is related to increased cell phospholipid % ALA (up to 25.1%), measured by gas chromatography. ALA is shown for the first time to reduce cell growth and induce apoptosis regardless of receptor expression and E2 environment, by incorporating into BC phospholipids, supporting the use of ALA and ALA-rich foods as a safe, inexpensive complementary therapy for a wide range of BC.
Assuntos
Estrogênios/metabolismo , Ácido alfa-Linolênico/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
SCOPE: Heterogeneity of breast cancer (BC) subtypes makes BC treatment difficult. α-linolenic acid (ALA), rich in flaxseed oil, has been shown to reduce growth and increase apoptosis in several BC cell lines, but the mechanism of action needs further understanding. METHODS AND RESULTS: Four BC cell lines (MCF-7, BT-474, MDA-MB-231 and MDA-MB-468) were incubated with 75 µM ALA+1 nM 17-ß estradiol (E2) or 1 nM E2 only (control) for 24 h. MDA-MB-231 cells were additionally incubated at 6 and 12 h. Viable cell number was measured, and expression of genes related to BC (signaling pathways, cell cycle, apoptosis) was quantified by real-time PCR array. There was a reduction in growth of all ALA treated cell lines after 24 h, and in MDA-MB-231 cells this was time-dependent. Many genes were altered after 24 h, and these differed between cell lines. In MDA-MB-231 cells, several gene expression changes were time-dependent. CONCLUSIONS: ALA reduces growth of BC cell lines, by modifying signaling pathways, which differ between BC molecular subtypes. The ALA effect on gene expression is dynamic and changes over time, indicating the significance of incubation period in detecting gene changes.
Assuntos
Antineoplásicos/farmacologia , Ácido alfa-Linolênico/farmacologia , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Neoplasias da Mama , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7RESUMO
BACKGROUND: Clarity and accuracy of the pharmacy aspects of cancer clinical trial protocols is essential. Inconsistencies and ambiguities in such protocols have the potential to delay research and jeopardise both patient safety and collection of credible data. The Chemotherapy and Pharmacy Advisory Service was established by the UK National Cancer Research Network, currently known as National Institute for Health Research Clinical Research Network, to improve the quality of pharmacy-related content in cancer clinical research protocols. This article reports the scope of Chemotherapy and Pharmacy Advisory Service, its methodology of mandated protocol review and pharmacy-related guidance initiatives and its current impact. METHODS: Over a 6-year period (2008-2013) since the inception of Chemotherapy and Pharmacy Advisory Service, cancer clinical trial protocols were reviewed by the service, prior to implementation at clinical trial sites. A customised Review Checklist was developed and used by a panel of experts to standardise the review process and report back queries and inconsistencies to chief investigators. Based on common queries, a Standard Protocol Template comprising specific guidance on drug-related content and a Pharmacy Manual Template were developed. In addition, a guidance framework was established to address 'ad hoc' pharmacy-related queries. The most common remarks made at protocol review have been summarised and categorised through retrospective analysis. In order to evaluate the impact of the service, chief investigators were asked to respond to queries made at protocol review and make appropriate changes to their protocols. Responses from chief investigators have been collated and acceptance rates determined. RESULTS: A total of 176 protocols were reviewed. The median number of remarks per protocol was 26, of which 20 were deemed clinically relevant and mainly concerned the drug regimen, support medication, frequency and type of monitoring and drug supply aspects. Further analysis revealed that 62% of chief investigators responded to the review. All responses were positive with an overall acceptance rate of 89% of the proposed protocol changes. CONCLUSION: Review of pharmacy content of cancer clinical trial protocols is feasible and exposes many undetected clinically relevant issues that could hinder efficient trial conduct. Our service audit revealed that the majority of suggestions were effectively incorporated in the final protocols. The refinement of existing and development of new pharmacy-related guidance documents by Chemotherapy and Pharmacy Advisory Service might aid in better and safer clinical research.
Assuntos
Antineoplásicos/normas , Protocolos Clínicos/normas , Consultores , Neoplasias/tratamento farmacológico , Projetos de Pesquisa/normas , Humanos , Garantia da Qualidade dos Cuidados de Saúde/organização & administração , Estudos Retrospectivos , Reino UnidoRESUMO
Flaxseed oil (FSO) reduces breast tumorigenesis and HER2 expression in animal models of luminal breast cancer. The primary treatment for HER2-overexpressing tumors is trastuzumab (TRAS). We aimed to determine the effect of 4% FSO alone and combined with TRAS on HER2-overexpressing tumor (BT-474) growth and to explore potential mechanisms with a specific focus on HER2, mitogen-activated protein kinase (MAPK) and Akt signaling and fatty acid profile. Athymic mice with established tumors were fed the basal diet (control) or 4% FSO diet, with or without TRAS (1 or 2.5 mg/kg) treatment for 4 weeks. Tumor growth, HER2 signaling biomarkers (mRNA and protein) and fatty acid profile were measured. Tumors treated with FSO alone showed no difference in tumor growth compared to control; however, compared to TRAS2.5 and other groups, FSO+TRAS2.5 caused significantly lower tumor growth and cell proliferation and higher apoptosis and the greatest lowering of signaling biomarker expressions (MAPK2, HER2 mRNA; pHER2 protein). Both TRAS and FSO had main effects of reducing the phosphorylated/total expression of Akt and MAPK protein expression. Dietary FSO altered the tumor fatty acid profile. In conclusion, 4% dietary FSO alone does not affect BT-474 tumor growth but enhances the tumor-reducing effect of TRAS (2.5 mg/kg). FSO×TRAS interactive effect may be modulated by their combined reductions of HER2 signaling through the Akt and MAPK pathways leading to reduced cell proliferation and increased apoptosis. FSO alters tumor fatty acid profile that likely contributes to effects on signaling pathways. This supports FSO as a complementary treatment for HER2+ breast cancer treated with TRAS.
Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Neoplasias da Mama/patologia , Óleo de Semente do Linho/farmacologia , Receptor ErbB-2/metabolismo , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Sinergismo Farmacológico , Feminino , Humanos , Camundongos , Camundongos Nus , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Transplante de Neoplasias , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor ErbB-2/genética , Transdução de Sinais , TrastuzumabRESUMO
Docosahexaenoic acid (DHA) is considered to be important for cardiac and brain function, and 17ß-estradiol (E2) appears to increase the conversion of α-linolenic acid (ALA) into DHA. However, the effect of varying ALA intake on the positive effect of E2 on DHA synthesis is not known. Therefore, the objective of this study was to investigate the effects of E2 supplementation on tissue and serum fatty acids in mice fed a low-ALA corn oil-based diet (CO, providing 0.6 % fatty acids as ALA) or a high ALA flaxseed meal-based diet (FS, providing 11.2 % ALA). Ovariectomized mice were implanted with a slow-release E2 pellet at 3 weeks of age and half the mice had the pellet removed at 7 weeks of age. Mice were then randomized onto either the CO or FS diet. After 4 weeks, the DHA concentration was measured in serum, liver and brain. A significant main effect of E2 was found for liver and serum DHA, corresponding to 25 and 15 % higher DHA in livers of CO and FS rats, respectively, and 19 and 13 % in serum of CO and FS rats, respectively, compared to unsupplemented mice. There was no effect of E2 on brain DHA. E2 results in higher DHA in serum and liver, at both levels of dietary ALA investigated presently, suggesting that higher ALA intake may result in higher DHA in individuals with higher E2 status.
Assuntos
Ácidos Docosa-Hexaenoicos/sangue , Estradiol/administração & dosagem , Fígado/metabolismo , Ácido alfa-Linolênico/administração & dosagem , Administração Oral , Animais , Encéfalo/metabolismo , Óleo de Milho/administração & dosagem , Suplementos Nutricionais , Estrogênios/administração & dosagem , Feminino , Linho/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Sementes/metabolismoRESUMO
Flaxseed (FS), rich in the phytoestrogen lignans and α-linolenic acid-rich oil, has been suggested to have an anticancer effect. Questions remain whether FS and its lignan and oil components are effective in reducing breast cancer risk and tumour growth, and can interact beneficially with breast cancer drugs. To find answers, in vitro, animal, observational, and clinical studies on FS and its lignan and oil components were reviewed. The majority of studies in various rodent models show that 2.5%-10% FS diet or the equivalent amount of lignan or oil reduces tumour growth. Ten percent FS and equivalent lignans do not interfere with but rather increase the effectiveness of tamoxifen (80 mg/day) while the 4% FS oil increases trastuzumab/Herceptin (2.5 mg/kg) effectiveness. Observational studies show that FS and lignan intake, urinary excretion, or serum levels are associated with reduced risk, particularly in postmenopausal women. Lignans reduce breast cancer and all-cause mortality by 33%-70% and 40%-53%, respectively, without reducing tamoxifen effectiveness. Clinical trials show that FS (25 g/day with 50 mg lignans; 32 days) reduces tumour growth in breast cancer patients and lignans (50 mg/day; 1 year) reduces risk in premenopausal women. Mechanisms include decreased cell proliferation and angiogenesis and increased apoptosis through modulation of estrogen metabolism and estrogen receptor and growth factor receptor signalling pathways. More clinical trials are needed but current overall evidence indicates that FS and its components are effective in the risk reduction and treatment of breast cancer and safe for consumption by breast cancer patients.
Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/dietoterapia , Neoplasias da Mama/tratamento farmacológico , Linho , Lignanas/farmacologia , Fitoestrógenos/farmacologia , Ácido alfa-Linolênico/farmacologia , Animais , Modelos Animais de Doenças , Interações Medicamentosas , Feminino , Humanos , Fatores de RiscoRESUMO
Flaxseed (FS) reduces breast tumorigenesis and human epidermal growth factor receptor 2 (HER2) expression in postmenopausal patients and animal models. The primary treatment for HER2-overexpressing tumors is trastuzumab (TRAS). FS oil enhances TRAS effectiveness in athymic mice but the FS effect is unknown and was therefore determined. Athymic mice with established BT-474 tumors were fed the basal diet (control), or 10% FS diet, with or without TRAS (2.5mg/kg) treatment for 5 wk. After 2 wk, TRAS and FS reduced tumor size with a trend for an FS × TRAS interaction; however, after 5 wk, only TRAS reduced tumor size and increased tumor apoptosis. FS did not further improve TRAS effect but increased overall survival. TRAS reduced signaling biomarkers [phosphorylated HER2 and mitogen-activated protein kinase (MAPK) proteins; Akt1, Akt2, MAPK, and estrogen receptor-α mRNA], FS reduced phosphorylated-Akt1 protein, and FS × TRAS interactions were seen for HER2 mRNA and phosphorylated-Akt1 protein. FS, with and without TRAS, increased tumor n-3 PUFA levels and serum lignans indicating potential roles in the observed effect. In conclusion, TRAS reduces tumor growth by influencing HER2 signaling. Dietary FS has minimal tumor-reducing effect, does not interfere with TRAS action, but improves overall survival in athymic mice.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos , Neoplasias da Mama/genética , Linho , Genes erbB-2/genética , Animais , Apoptose , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Ácidos Graxos/análise , Feminino , Humanos , Antígeno Ki-67/análise , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Proteínas Proto-Oncogênicas c-akt/genética , RNA Mensageiro/análise , Receptores de Estrogênio/análise , Receptores de Fatores de Crescimento/análise , Transdução de Sinais/efeitos dos fármacos , Trastuzumab , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The National Cancer Institute (NCI) career development (K) awards program supports investigators to develop their cancer research programs and achieve independence. The NCI Center for Cancer Training conducted a K program evaluation by analyzing outcomes of awardees and individuals who applied to the program but were not funded. The evaluation covered seven NCI mechanisms (K01, K07, K08, K11, K22, K23, and K25) between 1980 and 2008. Descriptive statistics and regression modeling were performed on the full cohort (n = 2,893 individuals, 4,081 K applications) and a comparison cohort described herein. K awardees proportionately received more subsequent NIH grants and authored more publications, and time to first R01 grant was unaffected. Of those not pursuing research, K awardees were more likely to participate in activities signaling continued scientific engagement. The NCI K program had a positive impact, not only on participants' biomedical research careers but also on achieving outcomes significant to the scientific enterprise.