921 resultados para Drug Evaluation, Preclinical


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It is often argued that consumption of alcohol, tobacco and drugs is detrimental to the cognitive abilities of teenagers. In order to disentangle a possible causal effect of these substances use from a self-selection bias, we control for pupils previous performance and for their previous rate of progression applying a DiDiD strategy. Using the NELS 1988 panel dataset, we find that the effects of alcohol and tobacco on test scores disappear once the selection bias is controlled for (this does not preclude long term detrimental effects). However, we find reliable evidence that heavy use of drugs (marijuana and cocaine) has direct detrimental effects on educational achievements. Hence, our results may have significant policy implications.

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There is debate as to whether percutaneous coronary intervention (PCI) with drug-eluting stents or coronary artery bypass surgery (CABG) is the best procedure for subjects with type 2 diabetes and coronary artery disease requiring revascularization. There is some evidence that following these procedures there is less further revascularization with CABG than PCI in subjects with diabetes. Two recent studies; the FREEDOM (Future Revascularization Evaluation in patients with Diabetes mellitus: Optimal Management of Multivessel Disease) trial, and a trial using a real world diabetic population from a Registry, have shown that the benefits of CABG over PCI in subjects with type 2 diabetes extends to lower rates of death and myocardial infarct, in addition to lower rates of revascularization. However, the rates of stroke may be higher with CABG than PCI with drug-eluting stents in this population. Thus, if CABG is going to be preferred to PCI in subjects with type 2 diabetes and multivessel coronary disease, consideration should be given to how to reduce the rates of stroke with CABG.

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Recently, two landmark reports on antiangiogenic therapy were published: Paez-Ribes and colleagues and Ebos and colleagues . The Board of the Metastasis Research Society (MRS) congratulates the authors for their informative articles that help to explain the puzzle of why antiangiogenic agents have had a relatively minor or no significant impact on patient survival. Using four model systems and several different strategies, these researchers showed that inhibition of angiogenesis reduced primary tumor growth and microvessel density in keeping with many earlier reports, but strikingly, accelerated invasion and metastasis.

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Herein are reported the synthesis of a conjugate of chitosan with L-leucine, the preparation of nanoparticles from both chitosan and the conjugate for use in pulmonary drug delivery, and the in vitro evaluation of toxicity and inflammatory effects of both the polymers and their nanoparticles on the bronchial epithelial cell line, BEAS-2B. The nanoparticles, successfully prepared both from chitosan and the conjugate, had a diameter in the range of 10−30 nm. The polymers and their nanoparticles were tested for their effects on cell viability by MTT assay, on trans-epithelial permeability by using sodium fluorescein as a fluid phase marker, and on IL-8 secretion by ELISA. The conjugate nanoparticles had a low overall toxicity (IC50 = 2 mg/mL following 48 h exposure; no induction of IL-8 release at 0.5 mg/mL concentration), suggesting that they may be safe for pulmonary drug delivery applications.

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Estimating the prevalence of drink driving is a difficult task. Self‐reported drink driving indicates that drink driving is far more common than official statistics suggest. In order to promote a responsible attitude towards alcohol consumption and drink driving within the Queensland community, the Queensland Police Service, Queensland Health and Queensland Transport developed the ‘Drink Rite’ program (Queensland Police Service information sheet, 2009). However, the feasibility of the program is now in doubt as the National Health and Medical Research Council’s guidelines for alcohol consumption changed in 2009 to state “For healthy men and women, drinking no more than four standard drinks on a single occasion reduces the risk of alcohol‐related injury arising from that occasion” (NHMRC Publication, 2009, p. 51). As such, adhering to the NHMRC guidelines places restrictions on how the existing Drink Rite program can be operated (i.e. by reducing the number of standard drinks provided to participants from eight to four). It is arguable that a reduction in the number of alcoholic drinks provided to participants in the program will result in a large reduction in observed BAC readings. This, in turn, will lead to a potential loss of message content when discussing the variation in the effects of alcohol.

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BACKGROUND The current impetus for developing alcohol and/or other drugs (AODs) workplace policies in Australia is to reduce workplace AOD impairment, improve safety, and prevent AOD-related injury in the workplace. For these policies to be effective, they need to be informed by scientific evidence. Evidence to inform the development and implementation of effective workplace AOD policies is currently lacking. There does not currently appear to be conclusive evidence for the effectiveness of workplace AOD policies in reducing impairment and preventing AOD-related injury. There is also no apparent evidence regarding which factors facilitate or impede the success of an AOD policy, or whether, for example, unsuccessful policy outcomes were due to poor policy or merely poor implementation of the policy. It was the aim of this research to undertake a process, impact, and outcome evaluation of a workplace AOD policy, and to contribute to the body of knowledge on the development and implementation of effective workplace AOD policies. METHODS The research setting was a state-based power-generating industry in Australia between May 2008 and May 2010. Participants for the process evaluation study were individuals who were integral to either the development or the implementation of the workplace AOD policy, or both of these processes (key informants), and comprised the majority of individuals who were involved in the process of developing and/or implementing the workplace AOD policy. The sample represented the two main groups of interest—management and union delegates/employee representatives—from all three of the participating organisations. For the impact and outcome evaluation studies, the population included all employees from the three participating organisations, and participants were all employees who consented to participate in the study and who completed both the pre-and post-policy implementation questionnaires. Qualitative methods in the form of interviews with key stakeholders were used to evaluate the process of developing and implementing the workplace AOD policy. In order to evaluate the impact of the policy with regard to the risk factors for workplace AOD impairment, and the outcome of the policy in terms of reducing workplace AOD impairment, quantitative methods in the form of a non-randomised single group pre- and post-test design were used. Changes from Time 1 (pre) to Time 2 (post) in the risk factors for workplace AOD impairment, and changes in the behaviour of interest—(self-reported) workplace AOD impairment—were measured. An integration of the findings from the process, impact, and outcome evaluation studies was undertaken using a combination of qualitative and quantitative methods. RESULTS For the process evaluation study Study respondents indicated that their policy was developed in the context of comparable industries across Australia developing workplace AOD policies, and that this was mainly out of concern for the deleterious health and safety impacts of workplace AOD impairment. Results from the process evaluation study also indicated that in developing and implementing the workplace AOD policy, there were mainly ‗winners', in terms of health and safety in the workplace. While there were some components of the development and implementation of the policy that were better done than others, and the process was expensive and took a long time, there were, overall, few unanticipated consequences to implementing the policy and it was reported to be thorough and of a high standard. Findings also indicated that overall the policy was developed and implemented according to best-practice in that: consultation during the policy development phase (with all the main stakeholders) was extensive; the policy was comprehensive; there was universal application of the policy to all employees; changes in the workplace (with regard to the policy) were gradual; and, the policy was publicised appropriately. Furthermore, study participants' responses indicated that the role of an independent external expert, who was trusted by all stakeholders, was integral to the success of the policy. For the impact and outcome evaluation studies Notwithstanding the limitations of pre- and post-test study designs with regard to attributing cause to the intervention, the findings from the impact evaluation study indicated that following policy implementation, statistically significant positive changes with regard to workplace AOD impairment were recorded for the following variables (risk factors for workplace AOD impairment): Knowledge; Attitudes; Perceived Behavioural Control; Perceptions of the Certainty of being punished for coming to work impaired by AODs; Perceptions of the Swiftness of punishment for coming to work impaired by AODs; and Direct and Indirect Experience with Punishment Avoidance for workplace AOD impairment. There were, however, no statistically significant positive changes following policy implementation for Behavioural Intentions, Subjective Norms, and Perceptions of the Severity of punishment for workplace AOD impairment. With regard to the outcome evaluation, there was a statistically significant reduction in self-reported workplace AOD impairment following the implementation of the policy. As with the impact evaluation, these findings need to be interpreted in light of the limitations of the study design in being able to attribute cause to the intervention alone. The findings from the outcome evaluation study also showed that while a positive change in self-reported workplace AOD impairment following implementation of the policy did not appear to be related to gender, age group, or employment type, it did appear to be related to levels of employee general alcohol use, cannabis use, site type, and employment role. Integration of the process, impact, and outcome evaluation studies There appeared to be qualitative support for the relationship between the process of developing and implementing the policy, and the impact of the policy in changing the risk factors for workplace AOD impairment. That is, overall the workplace AOD policy was developed and implemented well and, following its implementation, there were positive changes in the majority of measured risk factors for workplace AOD impairment. Quantitative findings lend further support for a relationship between the process and impact of the policy, in that there was a statistically significant association between employee perceived fidelity of the policy (related to the process of the policy) and positive changes in some risk factors for workplace AOD impairment (representing the impact of the policy). Findings also indicated support for the relationship between the impact of the policy in changing the risk factors for workplace AOD impairment and the outcome of the policy in reducing workplace AOD impairment: positive changes in the risk factors for workplace AOD impairment (impact) were related to positive changes in self reported workplace AOD impairment (representing the main goal and outcome of the policy). CONCLUSIONS The findings from the research indicate support for the conclusion that the policy was appropriately implemented and that it achieved its objectives and main goal. The Doctoral research findings also addressed a number of gaps in the literature on workplace AOD impairment, namely: the likely effectiveness of AOD policies for reducing AOD impairment in the workplace, which factors in the development and implementation of a workplace AOD policy are likely to facilitate or impede the effectiveness of the policy to reduce workplace AOD impairment, and which employee groups are less likely to respond well to policies of this type. The findings from this research not only represent an example of translational, applied research—through the evaluation of the study industry's policy—but also add to the body of knowledge on workplace AOD policies and provide policy-makers with evidence which may be useful in the development and implementation of effective workplace AOD policies. Importantly, the findings espouse the importance of scientific evidence in the development, implementation, and evaluation of workplace AOD policies.

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We present the development of a drug-loaded triple-layer platform consisting of thin film biodegradable polymers, in a properly designed form for the desired gradual degradation. Poly(dl-lactide-co-glycolide) (PLGA (65:35), PLGA (75:25)) and polycaprolactone (PCL) were grown by spin coating technique, to synthesize the platforms with the order PCL/PLGA (75:25)/PLGA (65:35) that determine their degradation rates. The outer PLGA (65:35) layer was loaded with dipyridamole, an antiplatelet drug. Spectroscopic ellipsometry (SE) in the Vis-far UV range was used to determine the nanostructure, as well as the content of the incorporated drug in the as-grown platforms. In situ and real-time SE measurements were carried out using a liquid cell for the dynamic evaluation of the fibrinogen and albumin protein adsorption processes. Atomic force microscopy studies justified the SE results concerning the nanopores formation in the polymeric platforms, and the dominant adsorption mechanisms of the proteins, which were defined by the drug incorporation in the platforms. © 2013 Elsevier B.V. All rights reserved.

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Osteoarthritis (OA) is a degenerative joint disease that can result in joint pain, loss of joint function, and deleterious effects on activity levels and lifestyle habits. Current therapies for OA are largely aimed at symptomatic relief and may have limited effects on the underlying cascade of joint degradation. Local drug delivery strategies may provide for the development of more successful OA treatment outcomes that have potential to reduce local joint inflammation, reduce joint destruction, offer pain relief, and restore patient activity levels and joint function. As increasing interest turns toward intra-articular drug delivery routes, parallel interest has emerged in evaluating drug biodistribution, safety, and efficacy in preclinical models. Rodent models provide major advantages for the development of drug delivery strategies, chiefly because of lower cost, successful replication of human OA-like characteristics, rapid disease development, and small joint volumes that enable use of lower total drug amounts during protocol development. These models, however, also offer the potential to investigate the therapeutic effects of local drug therapy on animal behavior, including pain sensitivity thresholds and locomotion characteristics. Herein, we describe a translational paradigm for the evaluation of an intra-articular drug delivery strategy in a rat OA model. This model, a rat interleukin-1beta overexpression model, offers the ability to evaluate anti-interleukin-1 therapeutics for drug biodistribution, activity, and safety as well as the therapeutic relief of disease symptoms. Once the action against interleukin-1 is confirmed in vivo, the newly developed anti-inflammatory drug can be evaluated for evidence of disease-modifying effects in more complex preclinical models.