Alpha-2 agonists for sedation of mechanically ventilated adults in intensive care units: a systematic review

BACKGROUND: Care of critically ill patients in intensive care units (ICUs) often requires potentially invasive or uncomfortable procedures, such as mechanical ventilation (MV). Sedation can alleviate pain and discomfort, provide protection from stressful or harmful events, prevent anxiety and promote sleep. Various sedative agents are available for use in ICUs. In the UK, the most commonly used sedatives are propofol (Diprivan(®), AstraZeneca), benzodiazepines [e.g. midazolam (Hypnovel(®), Roche) and lorazepam (Ativan(®), Pfizer)] and alpha-2 adrenergic receptor agonists [e.g. dexmedetomidine (Dexdor(®), Orion Corporation) and clonidine (Catapres(®), Boehringer Ingelheim)]. Sedative agents vary in onset/duration of effects and in their side effects. The pattern of sedation of alpha-2 agonists is quite different from that of other sedatives in that patients can be aroused readily and their cognitive performance on psychometric tests is usually preserved. Moreover, respiratory depression is less frequent after alpha-2 agonists than after other sedative agents.

OBJECTIVES: To conduct a systematic review to evaluate the comparative effects of alpha-2 agonists (dexmedetomidine and clonidine) and propofol or benzodiazepines (midazolam and lorazepam) in mechanically ventilated adults admitted to ICUs.

DATA SOURCES: We searched major electronic databases (e.g. MEDLINE without revisions, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE and Cochrane Central Register of Controlled Trials) from 1999 to 2014.

METHODS: Evidence was considered from randomised controlled trials (RCTs) comparing dexmedetomidine with clonidine or dexmedetomidine or clonidine with propofol or benzodiazepines such as midazolam, lorazepam and diazepam (Diazemuls(®), Actavis UK Limited). Primary outcomes included mortality, duration of MV, length of ICU stay and adverse events. One reviewer extracted data and assessed the risk of bias of included trials. A second reviewer cross-checked all the data extracted. Random-effects meta-analyses were used for data synthesis.

RESULTS: Eighteen RCTs (2489 adult patients) were included. One trial at unclear risk of bias compared dexmedetomidine with clonidine and found that target sedation was achieved in a higher number of patients treated with dexmedetomidine with lesser need for additional sedation. The remaining 17 trials compared dexmedetomidine with propofol or benzodiazepines (midazolam or lorazepam). Trials varied considerably with regard to clinical population, type of comparators, dose of sedative agents, outcome measures and length of follow-up. Overall, risk of bias was generally high or unclear. In particular, few trials blinded outcome assessors. Compared with propofol or benzodiazepines (midazolam or lorazepam), dexmedetomidine had no significant effects on mortality [risk ratio (RR) 1.03, 95% confidence interval (CI) 0.85 to 1.24, I (2) = 0%; p = 0.78]. Length of ICU stay (mean difference -1.26 days, 95% CI -1.96 to -0.55 days, I (2) = 31%; p = 0.0004) and time to extubation (mean difference -1.85 days, 95% CI -2.61 to -1.09 days, I (2) = 0%; p < 0.00001) were significantly shorter among patients who received dexmedetomidine. No difference in time to target sedation range was observed between sedative interventions (I (2) = 0%; p = 0.14). Dexmedetomidine was associated with a higher risk of bradycardia (RR 1.88, 95% CI 1.28 to 2.77, I (2) = 46%; p = 0.001).

LIMITATIONS: Trials varied considerably with regard to participants, type of comparators, dose of sedative agents, outcome measures and length of follow-up. Overall, risk of bias was generally high or unclear. In particular, few trials blinded assessors.

CONCLUSIONS: Evidence on the use of clonidine in ICUs is very limited. Dexmedetomidine may be effective in reducing ICU length of stay and time to extubation in critically ill ICU patients. Risk of bradycardia but not of overall mortality is higher among patients treated with dexmedetomidine. Well-designed RCTs are needed to assess the use of clonidine in ICUs and identify subgroups of patients that are more likely to benefit from the use of dexmedetomidine.

STUDY REGISTRATION: This study is registered as PROSPERO CRD42014014101.

FUNDING: The National Institute for Health Research Health Technology Assessment programme. The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates.

Implications of divergences in Adult Protection legislation

Purpose – The purpose of this paper is to explore the similarities and differences of legal responses to older adults who may be at risk of harm or abuse in the UK, Ireland, Australia and the USA.
Design/methodology/approach – The authors draw upon a review of elder abuse and adult protection undertaken on behalf of the commissioner for older people in Northern Ireland. This paper focusses on the desk top mapping of the different legal approaches and draws upon wider literature to frame the discussion of the relative strengths and weaknesses of the different legal responses.
Findings – Arguments exist both for and against each legal approach. Differences in defining the scope and powers of adult protection legislation in the UK and internationally are highlighted.
Research limitations/implications – This review was undertaken in late 2013; while the authors have updated the mapping to take account of subsequent changes, some statutory guidance is not yet available. While the expertise of a group of experienced professionals in the field of adult safeguarding was utilized,
it was not feasible to employ a formal survey or consensus model.
Practical implications – Some countries have already introduced APL and others are considering doing so. The potential advantages and challenges of introducing APL are highlighted.
Social implications – The introduction of legislation may give professionals increased powers to prevent and reduce abuse of adults, but this would also change the dynamic of relationships within families and between families and professionals.
Originality/value – This paper provides an accessible discussion of APL across the UK and internationally
which to date has been lacking from the literature.

Active corrosion protection of AA2024 by sol-gel coatings with corrosion inhibitors

A indústria aeronáutica utiliza ligas de alumínio de alta resistência para o fabrico dos elementos estruturais dos aviões. As ligas usadas possuem excelentes propriedades mecânicas mas apresentam simultaneamente uma grande tendência para a corrosão. Por esta razão essas ligas necessitam de protecção anticorrosiva eficaz para poderem ser utilizadas com segurança. Até à data, os sistemas anticorrosivos mais eficazes para ligas de alumínio contêm crómio hexavalente na sua composição, sejam pré-tratamentos, camadas de conversão ou pigmentos anticorrosivos. O reconhecimento dos efeitos carcinogénicos do crómio hexavalente levou ao aparecimento de legislação banindo o uso desta forma de crómio pela indústria. Esta decisão trouxe a necessidade de encontrar alternativas ambientalmente inócuas mas igualmente eficazes. O principal objectivo do presente trabalho é o desenvolvimento de prétratamentos anticorrosivos activos para a liga de alumínio 2024, baseados em revestimentos híbridos produzidos pelo método sol-gel. Estes revestimentos deverão possuir boa aderência ao substrato metálico, boas propriedades barreira e capacidade anticorrosiva activa. A protecção activa pode ser alcançada através da incorporação de inibidores anticorrosivos no prétratamento. O objectivo foi atingido através de uma sucessão de etapas. Primeiro investigou-se em detalhe a corrosão localizada (por picada) da liga de alumínio 2024. Os resultados obtidos permitiram uma melhor compreensão da susceptibilidade desta liga a processos de corrosão localizada. Estudaram-se também vários possíveis inibidores de corrosão usando técnicas electroquímicas e microestruturais. Numa segunda etapa desenvolveram-se revestimentos anticorrosivos híbridos orgânico-inorgânico baseados no método sol-gel. Compostos derivados de titania e zirconia foram combinados com siloxanos organofuncionais a fim de obter-se boa aderência entre o revestimento e o substrato metálico assim como boas propriedades barreira. Testes industriais mostraram que estes novos revestimentos são compatíveis com os esquemas de pintura convencionais actualmente em uso. A estabilidade e o prazo de validade das formulações foram optimizados modificando a temperatura de armazenamento e a quantidade de água usada durante a síntese. As formulações sol-gel foram dopadas com os inibidores seleccionados durante a primeira etapa e as propriedades anticorrosivas passivas e activas dos revestimentos obtidos foram estudadas numa terceira etapa do trabalho. Os resultados comprovam a influência dos inibidores nas propriedades anticorrosivas dos revestimentos sol-gel. Em alguns casos a acção activa dos inibidores combinou-se com a protecção passiva dada pelo revestimento mas noutros casos terá ocorrido interacção química entre o inibidor e a matriz de sol-gel, de onde resultou a perda de propriedades protectoras do sistema combinado. Atendendo aos problemas provocados pela adição directa dos inibidores na formulação sol-gel procurou-se, numa quarta etapa, formas alternativas de incorporação. Na primeira, produziu-se uma camada de titania nanoporosa na superfície da liga metálica que serviu de reservatório para os inibidores. O revestimento sol-gel foi aplicado por cima da camada nanoporosa. Os inibidores armazenados nos poros actuam quando o substrato fica exposto ao ambiente agressivo. Numa segunda, os inibidores foram armazenados em nano-reservatórios de sílica ou em nanoargilas (halloysite), os quais foram revestidos por polielectrólitos montados camada a camada. A terceira alternativa consistiu no uso de nano-fios de molibdato de cério amorfo como inibidores anticorrosivos nanoparticulados. Os nano-reservatórios foram incorporados durante a síntese do sol-gel. Qualquer das abordagens permitiu eliminar o efeito negativo do inibidor sobre a estabilidade da matriz do sol-gel. Os revestimentos sol-gel desenvolvidos neste trabalho apresentaram protecção anticorrosiva activa e capacidade de auto-reparação. Os resultados obtidos mostraram o elevado potencial destes revestimentos para a protecção anticorrosiva da liga de alumínio 2024.

Software protection

A computer system's security can be compromised in many ways—a denial-of-service attack can make a server inoperable, a worm can destroy a user's private data, or an eavesdropper can reap financial rewards by inserting himself in the communication link between a customer and her bank through a man-in-the-middle (MITM) attack. What all these scenarios have in common is that the adversary is an untrusted entity that attacks a system from the outside—we assume that the computers under attack are operated by benign and trusted users. But if we remove this assumption, if we allow anyone operating a computer system—from system administrators down to ordinary users—to compromise that system's security, we find ourselves in a scenario that has received comparatively little attention.

Water use and conservation at the environmental protection area of Brilhante, Santa Catarina - Brazil

Dissertação mest., Gestão da Água e da Costa, Universidade do Algarve, 2008

Patient´s knowledge about radiation and radiological protection

Purpose: To obtain and analyse patient´s knowledge and perceptions regarding radiation exposure, from both natural and man-made radiation of medical procedures and interventions. Verify if patients worry about their exposure when undergoing medical exams, are aware of associated risks and means of radiological protection and if their knowledge on medical radiation exposure affects their own decisions. Methods and Materials: On a medical environment a self-applied questionnaire was used as instrument and assigned to patients who would undergo medical imaging exams involving ionising radiation. A total of 300 valid questionnaires were interpreted and statistically analysed through descriptive statistics and Phi & Cramer´s V correlation tests. Results: 44.3% of patients believe most of their exposure derives from electronic appliances and 25% from medical imaging exams, while patient´s with higher education levels tend to consider is comes from the environment. The great majority of patients (95%) consider that only certified personnel should operate medical imaging equipment, but 74% never ask for their qualifications. 66.3% of patients claim that Technologists have more education on radiological protection and about 60% of patients rarely or never worry about radiation exposure when undergoing medical imaging exams. Conclusion: Patients overestimate the risks of industrial radiation exposure while they underestimate the associated risks of medical radiation exposure and the Technologist´s ability to reduce the inherent radiation exposure of medical imaging exams. Patient´s knowledge on radiation and radiological protection is based more on perceptions and beliefs, rather than factual knowledge.

Using data envelopment analysis to assess the efficiency of social security systems: the case of income protection in old age

As the number of pensioners in Europe rises relative to the number of people in employment, the gap between the contributions and the benefit levels increases, and consequently ensuring adequate pensions on a sustainable basis has become a major challenge. This study aims to explore the potential of using the Data Envelopment Analysis (DEA) technique in order to access the efficiency of the income protection in old age, one of the most important branches of Social Security. To this effect, we collected data from the 27 European Union Member States regarding this branch. Our results show important differences among the Member States and stress the importance of identifying best practices to achieve more adequate, sustainable and modernised pension systems. Our results also highlight the importance of using DEA as a decision support tool for policy makers.

A global assessment of the effectiveness of different protection levels in marine protected areas of tropical waters, following a new categorization

Dissertação de mestrado, Biologia Marinha, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

On Investor Preferences and Mutual Fund Separation

We extend Cass and Stiglitz’s analysis of preference-based mutual fund separation. We show that high degrees of fund separation can be constructed by adding inverse marginal utility functions exhibiting lower degrees of separation. However, this method does not allow us to find all utility functions satisfying fund separation. In general, we do not know how to write the primal utility functions in these models in closed form, but we can do so in the special case of SAHARA utility defined by Chen et al. and for a new class of GOBI preferences introduced here. We show that there is money separation (in which the riskless asset can be one of the funds) if and only if there is a fund (which may not be the riskless asset) with a constant allocation as wealth changes.

Protection to farmers : speech of Hon. D. Wyatt Aiken, of South Carolina, in the House of Representatives, Tuesday, March 6, 1882, upon the Agricultural Appropriation Bill

This speech is about the Agricultural Appropriation Bill, which is a bill making appropriations for the Agricultural Department of the Government for the fiscal year ending in June 30,1883. Mr. Aiken is approved by the chairman to speak and he goes on to explain that he agrees with the majority of the bill with the exception of two or three clauses. He gives the reasoning behind his objections in the rest of the speech.

Radiological protection and nuclear engineering studies in multi-MW target systems

Tese de doutoramento, Física, Universidade de Lisboa, Faculdade de Ciências, 2014

In Protection of Whose “Wellbeing”? Considerations of “Clauses and A/Effects” in Athlete Contracts

Contractual agreements have become an accepted part of participation processes for athletes in a variety of sport contexts. Closer readings of these contracts,however, pose several questions regarding organizational intentions and motivations,the conceptualization of athletes as “workers,” and representation parity. In this article, we draw on four types of athlete contractual documents from both select international “amateur” and “professional” sport settings. Our key considerations include athletes’ ownership over their image and identities; medical and health disclosures; lifestyle, behavioral and body choices, and restrictions beyond sport; adherence to organizational philosophy and commitments; and social media and publicity constraints. Our exegesis here encourages sport researchers to deliberate whose “wellbeing” matters most when signing that seductive dotted line.

Identification of a Novel Recycling Sequence in the C-tail of FPR2/ALX Receptor: Association with Cell Protection from Apoptosis

Formyl-peptide receptor type 2 (FPR2; also called ALX because it is the receptor for lipoxin A4) sustains a variety of biological responses relevant to the development and control of inflammation, yet the cellular regulation of this G-protein-coupled receptor remains unexplored. Here we report that, in response to peptide agonist activation, FPR2/ALX undergoes β-arrestin-mediated endocytosis followed by rapid recycling to the plasma membrane. We identify a transplantable recycling sequence that is both necessary and sufficient for efficient receptor recycling. Furthermore, removal of this C-terminal recycling sequence alters the endocytic fate of FPR2/ALX and evokes pro-apoptotic effects in response to agonist activation. This study demonstrates the importance of endocytic recycling in the anti-apoptotic properties of FPR2/ALX and identifies the molecular determinant required for modulation of this process fundamental for the control of inflammation.