PHA supports World No Tobacco Day

The Public Health Agency is taking the opportunity to highlight this year's World No Tobacco Day which takes place on Tuesday 31 May.In Northern Ireland, around 340,000 people aged 16 and over smoke. Smoking contributes not only to many cancers, heart disease, bronchitis and asthma, but to other illnesses, including stroke. In fact, smoking causes around 2,700 deaths per year here, all of them avoidable.The PHA is committed to saving lives by reducing the percentage of people who smoke. The PHA:works with councils to ensure smoking-related laws are enforced; funds a range of support to smokers who want to quit; educates young people to not start smoking, through programmes like 'Teenage Kicks' and 'Smokebusters'. In January this year, the PHA also launched its smoking campaign 'Things to do before you die' to encourage smokers, particularly those aged 20-49, to stop smoking.Health Minister Edwin Poots said:"Smoking is the greatest cause of preventable illness and premature death in Northern Ireland. While good progress has been made in the last number of years to reduce the number of people who smoke, more needs to be done."I would appeal to all smokers to use the wide range of support services available to make every effort to stop smoking - it is the single best step you can take to improve your health and quality of life."Mark Mc Bride, Health Improvement Manager, PHA, said "Smoking is the single greatest preventable cause of death in the world today. Across Northern Ireland there are over 600 support services for people who wish to stop smoking. These are based in GP surgeries, community pharmacies, hospitals, community centres and workplaces."From April 2010 to end March 2011 more than 1 in 10 of all adult smokers sought help from the support services and approximately half had quit after four weeks. This is a substantial - roughly 50% increase - on previous years and shows the benefit of the PHA campaigns and the dedication of the many specialists who help smokers quit."I would encourage everyone who is either thinking about quitting or ready to log on to our Want 2 Stop website www.want2stop.info or to contacting the Smokers' Helpline on 0808 812 8008 a Quit Kit free of charge."

Polymédication et personne agée: ni trop ni trop peu [Polypharmacy and the elderly: neither too much nor too little].

Elderly persons are at high risk of polypharmacy. Polypharmacy has been associated with numerous adverse outcomes, such as poorer quality of life, higher morbidity and mortality. However, deciding to stop or to continue a treatment is a difficult task, which confronts the physician to complex clinical and ethical choices. Such a decision requires a geriatric multidimensional assessment of the patient, an estimation of his or her prognosis, the definition of the goals of care and a careful assessment of the time to benefit of each drug. Diverse methods and tools to support the physician in this process are discussed in this article. However these can not replace a reflexive approach of the physician that integrates the values and representations of the patient with regard to his or her health and end of life, as well as his or her needs, fears and choices.

Public Policy and Ageing in Northern Ireland: Identifying Levers for Change

Public Policy and Ageing in Northern Ireland: Identifying Levers for Change Judith Cross, Policy Officer with the Centre for Ageing Research Development in Ireland (CARDI)��������Introduction Identifying a broad range of key public policy initiatives as they relate to age can facilitate discussion and create new knowledge within and across government to maximise the opportunities afforded by an ageing population. This article looks at how examining the current public policy frameworks in Northern Ireland can present opportunities for those working in this field for the benefit of older people. Good policy formulation needs to be evidence-based, flexible, innovative and look beyond institutional boundaries. Bringing together architects and occupational therapists, for example, has the potential to create better and more effective ways relevant to health, housing, social services and government departments. Traditional assumptions of social policy towards older people have tended to be medically focused with an emphasis on care and dependency. This in turn has consequences for the design and delivery of services for older people. It is important that these assumptions are challenged as changes in thinking and attitudes can lead to a redefinition of ageing, resulting in policies and practices that benefit older people now and in the future. Older people, their voices and experiences, need to be central to these developments. The Centre for Ageing Research and Development in Ireland The Centre for Ageing Research and Development in Ireland (CARDI) (1) is a not for profit organisation developed by leaders from the ageing field across Ireland (North and South) including age sector focused researchers and academics, statutory and voluntary, and is co-chaired by Professor Robert Stout and Professor Davis Coakley. CARDI has been established to provide a mechanism for greater collaboration among age researchers, for wider dissemination of ageing research information and to advance a research agenda relevant to the needs of older people in Ireland, North and South. Operating at a strategic level and in an advisory capacity, CARDI�۪s work focuses on promoting research co-operation across sectors and disciplines and concentrates on influencing the strategic direction of research into older people and ageing in Ireland. It has been strategically positioned around the following four areas: Identifying and establishing ageing research priorities relevant to policy and practice in Ireland, North and South;Promoting greater collaboration and co-operation on ageing research in order to build an ageing research community in Ireland, North and South;Stimulating research in priority areas that can inform policy and practice relating to ageing and older people in Ireland, North and South;Communicating strategic research issues on ageing to raise the profile of ageing research in Ireland, North and South, and its role in informing policy and practice. Context of Ageing in Ireland Ireland �۪s population is ageing. One million people aged 60 and over now live on the island of Ireland. By 2031, it is expected that Northern Ireland�۪s percentage of older people will increase to 28% and the Republic of Ireland�۪s to 23%. The largest increase will be in the older old; the number aged 80+ is expected to triple by the same date. However while life expectancy has increased, it is not clear that life without disability and ill health has increased to the same extent. A growing number of older people may face the combined effects of a decline in physical and mental function, isolation and poverty. Policymakers, service providers and older people alike recognise the need to create a high quality of life for our ageing population. This challenge can be meet by addressing the problems relating to healthy ageing, reducing inequalities in later life and creating services that are shaped by, and appropriate for, older people. Devolution and Structures of Government in Northern Ireland The Agreement (2) reached in the Multi-Party Negotiations in Belfast 1998 established the Northern Ireland Assembly which has full legislative authority for all transferred matters. The majority of social and economic public policy such as; agriculture, arts, education, health, environment and planning is determined by the Northern Ireland Assembly at Stormont. There are 11 Government Departments covering the main areas of responsibility with 108 elected Members of the Legislative Assembly (MLA�۪s). The powers of the Northern Ireland Assembly do not cover ��� reserved�۪ matters or ��� excepted�۪ matters . These are the responsibility of Westminster and include issues such as, tax, social security, policing, justice, defence, immigration and foreign affairs. Northern Ireland has 18 elected Members of Parliament (MP�۪s) to the House of Commons. Public Policy Context in Northern Ireland The economic, social and political consequence of an ageing population is a challenge for policy makers across government. Considering the complex and diverse causal factors that contribute to ageing in Northern Ireland, there are a number of areas of government policy at regional, national and international levels that are likely to impact in this area. International The Madrid International Plan of Action on Ageing (3) and the Research Agenda on Ageing for the 21st Century (4) provide important mechanisms for furthering research into ageing. The United Kingdom has signed up to these. The Madrid International Plan of Action on Ageing commits member states to a systematic review of the Plan of Action through Regional Implementation Strategies. The United Kingdom�۪s Regional Implementation Strategy covers Northern Ireland. National At National level, pension and social security are high on the agenda. The Pensions Act (5) became law in 2007 and links pensions increases with earnings as opposed to prices from 2012. Additional credits for people raising children and caring for older people to boost their pensions were introduced. Some protections are included for those who lost occupational pensions as a result of underfunded schemes being wound up before April 2005. In relation to State Pensions and benefits, this Act will bring changes to state pensions in future. The Act now places the Pension Credit element which is up-rated in line with or above earnings, on a permanent, statutory footing. Regional At regional level there are a number of age related public policy initiatives that have the potential to impact positively on the lives of older people in Northern Ireland. Some are specific to ageing such as the Ageing in an Inclusive Society (6) and others by their nature are cross-cutting such as Lifetime Opportunities: Governments Anti-Poverty Strategy for Northern Ireland (7). The main public policy framework in Northern Ireland is the Programme for Government: Building a Better Future, 2008-2011(PfG) (8) . The PfG, is the overarching high level policy framework for Northern Ireland and provides useful principles for ageing research and public policy in Northern Ireland. The PfG vision is to build a peaceful, fair and prosperous society in Northern Ireland, with respect for the rule of law. A number of Public Service Agreements (PSA) aligned to the PfG confirm key actions that will be taken to support the priorities that the Government aim to achieve over the next three years. For example objective 2 of PSA 7: Making Peoples�۪ Lives Better: Drive a programme across Government to reduce poverty and address inequality and disadvantage, refers to taking forward strategic action to promote social inclusion for older people; and to deliver a strong independent voice for older people. The Office of the First Minister and deputy First Minister (OFMDFM) have recently appointed an Interim Older People�۪s Advocate, Dame Joan Harbison to provide a focus for older peoples issues across Government. Ageing in an Inclusive Society is the cross-departmental strategy for older people in Northern Ireland and was launched in March 2005. It sets out the approach to be taken across Government to promote and support the inclusion of older people. The vision coupled with six strategic objectives form the basis of the action plans accompanying the strategy. The vision is: ���To ensure that age related policies and practices create an enabling environment, which offers everyone the opportunity to make informed choices so that they may pursue healthy, active and positive ageing.�۝ (Ageing in an Inclusive Society, Office of the First Minister and Deputy First Minister, 2005) Action planning and maintaining momentum across government in relation to this strategy has proved to be slower than anticipated. It is proposed to refresh this Strategy in line with Opportunity Age ��� meeting the challenges of ageing in the 21st Century (9). There are a number of policy levers elsewhere which can also be used to promote the positive aspects of an ageing society. The Investing for Health (10) and A Healthier Future:A 20 Year Vision for Health and Well-being in Northern Ireland (11), seek to ensure that the overall vision for health and wellbeing is achievable and provides a useful framework for ageing policy and research in the health area. These health initiatives have the potential to positively impact on the quality of life of older people and provide a useful framework for improving current policy and practice. In addition to public policy initiatives, the anti-discrimination frameworks in terms of employment in Northern Ireland cover age as well as a range of other grounds. Goods facilitates and services are currently excluded from the Employment Equality (age) Regulations (NI) 2006 (12). Supplementing the anti-discrimination measures, Section 75 of the Northern Ireland Act 1998 (13), unique to Northern Ireland, places a statutory obligation on public authorities in fulfilling their functions to promote equality of opportunity across nine grounds, one of which is age(14). This positive duty has the potential to make a real difference to the lives of older people in Northern Ireland. Those affected by policy decisions must be consulted and their interests taken into account. This provides an opportunity for older people and their representatives to participate in public policy-making, right from the start of the process. Policy and Research Interface ���Ageing research is vital as decisions in relation to policy and practice and resource allocation will be made on the best available information�۝. (CARDI�۪s Strategic Plan 2008-2011) As outlined earlier, CARDI has been established to bridge the gap to ensure that research reaches those involved in making policy decisions. CARDI is stimulating the ageing research agenda in Ireland through a specific research fund that has a policy and practice focus. My work is presently focusing on helping to build a greater awareness of the key policy levers and providing opportunities for those within research and policy to develop closer links. The development of this shared understanding by establishing these links between researchers and policy makers is seen as the best predictor for research utilization. It is important to acknowledge and recognise that researchers and policy makers operate in different institutional, political and cultural contexts. Research however needs to ���resonate�۪ with the contextual factors in which policy makers operate. Conclusions Those working within the public policy field recognise all too often that the development of government policies and initiatives in respect of age does not guarantee that they will result in changes in actual provision of services, despite Government recommendations and commitments. The identification of public policy initiatives as they relate to age has the potential to highlight persistent and entrenched difficulties that social policy has previously failed to address. Furthermore, the identification of these difficulties can maximise the opportunities for progressing these across government. A focus on developing effective and meaningful targets to ensure measurable outcomes in public policy for older people can assist in this. Access to sound, credible and up-to-date evidence will be vital in this respect. As well as a commitment to working across departmental boundaries to effect change. Further details: If you would like to discuss this paper or for further information about CARDI please contact: Judith Cross, Policy Officer, Centre for Ageing Research and Development in Ireland CARDI). t: +44 (0) 28 9069 0066; m: +353 (0) 867 904 171; e: judith@cardi.ie ; or visit our website at: www.cardi.ie References 1) Centre for Ageing Research and Development in Ireland (2008) Strategic Plan 2008-2011. Belfast. CARDI 2) The Agreement: Agreement Reached in the Multi-Party Negotiations. Belfast 1998 3) Madrid International Plan of Action on Ageing. http://www.un.org/ageing/ 4) UN Programme on Ageing (2007) Research Agenda on Ageing for the 21st Century: 2007 Update. New York. New York. UN Programme on Ageing and the International Association of Gerontology and Geriatrics. 5) The Pensions Act 2007 Chapter 22 6) Office of the First Minister and deputy First Minister (2005). Ageing in an Inclusive Society. Belfast. OFMDFM Central Anti-Poverty Unit. 7) Office of the First Minister and deputy First Minister (2005). Lifetime Opportunities: Government�۪s Anti-Poverty and Social Inclusion Strategy for Northern Ireland. Belfast. OFMDFM Central Anti-Poverty Unit. 8) Northern Ireland Executive (2008) Building a Better Future: Programme for Government 2008-2011. Belfast. OFMDFM Economic Policy Unit. 9) Department for Work and Pensions, (2005) Opportunity Age: Meeting the Challenges of Ageing in the 21 st Century. London. DWP. 10) Department of Health, Social Services and Public Safety (DHSS&PS) (2002) Investing for Health. Belfast. DHSS&PS. 11) Department of Health, Social Services and Public Safety (DHSS&PS) (2005) A Healthier Future:A 20 Year Vision for Health and Well-being in Northern Ireland Belfast. DHSS&PS. �� 12) The Employment Equality (Age) Regulations (Northern Ireland) 2006 SR2006 No.261 13) The Northern Ireland Act 1998, Part VII, S75 14) The nine grounds covered under S75 of the Northern Ireland Act are: gender, religion, race, sexual orientation, those with dependents, disability, political opinion, marital status and age.

Body temperature regulation and outcome after cardiac arrest and therapeutic hypothermia.

OBJECTIVE: Therapeutic temperature modulation is recommended after cardiac arrest (CA). However, body temperature (BT) regulation has not been extensively studied in this setting. We investigated BT variation in CA patients treated with therapeutic hypothermia (TH) and analyzed its impact on outcome. METHODS: A prospective cohort of comatose CA patients treated with TH (32-34°C, 24h) at the medical/surgical intensive care unit of the Lausanne University Hospital was studied. Spontaneous BT was recorded on hospital admission. The following variables were measured during and after TH: time to target temperature (TTT=time from hospital admission to induced BT target <34°C), cooling rate (spontaneous BT-induced BT target/TTT) and time of passive rewarming to normothermia. Associations of spontaneous and induced BT with in-hospital mortality were examined. RESULTS: A total of 177 patients (median age 61 years; median time to ROSC 25 min) were studied. Non-survivors (N=90, 51%) had lower spontaneous admission BT than survivors (median 34.5 [interquartile range 33.7-35.9]°C vs. 35.1 [34.4-35.8]°C, p=0.04). Accordingly, time to target temperature was shorter among non-survivors (200 [25-363]min vs. 270 [158-375]min, p=0.03); however, when adjusting for admission BT, cooling rates were comparable between the two outcome groups (0.4 [0.2-0.5]°C/h vs. 0.3 [0.2-0.4]°C/h, p=0.65). Longer duration of passive rewarming (600 [464-744]min vs. 479 [360-600]min, p<0.001) was associated with mortality. CONCLUSIONS: Lower spontaneous admission BT and longer time of passive rewarming were associated with in-hospital mortality after CA and TH. Impaired thermoregulation may be an important physiologic determinant of post-resuscitation disease and CA prognosis. When assessing the benefit of early cooling on outcome, future trials should adjust for patient admission temperature and use the cooling rate rather than the time to target temperature.

Audio as medium for content distribution (providing access to knowledge)

Reaching and educating the masses to the benefit of all of mankind is the ultimate goal and through the use of this technology facility/tool many can be reached in their own language, in their own community, in their own time and at their own pace. Making this content available to those who will benefit from the information, is vital. These people who want to consume the content are not necessarily that interested in the qualification, they need the information. Making the content available in an auditory format may also help those who may not be as literate as others. The uses of audio/ recorded lessons have a number of uses and should not just be seen as a medium for content distribution to distant communities. Recording lectures makes it possible for a lecturer to present lectures to a vast number of students, while just presenting the lecture once.

Retreatment with trastuzumab in Her2-positive metastatic breast cancer patients: a clinical study

Objective: To study the benefit of trastuzumab in monotherapy or combined with different chemotherapeutic agents in the treatment for Her2+ metastatic breast cancer (MBC) patients after progression on prior trastuzumab therapy.

Irinotecan loaded in eluting beads: preclinical assessment in a rabbit VX2 liver tumor model.

PURPOSE: The purpose of this study was to study the pharmacokinetics of irinotecan injected intravenously, intra-arterially, or loaded onto a delivery platform. MATERIAL AND METHODS: Fifty-four New Zealand White rabbits with VX2 liver tumor, divided in 3 groups of 17 rabbits, each received irinotecan either by intravenous (IV) route, intra-arterial hepatic (IA) route, or loaded on drug-eluting beads (DEBIRI). Animals were killed at 1, 6, and 24 h. Irinotecan and SN-38 concentrations were measured at different time points in serum, tumor, and normal liver. RESULTS: Twelve milligrams of irinotecan were injected IV and IA, whereas 6-16.5 mg were injected loaded onto DEBIRI. Normalized serum irinotecan reached a peak of 333 ng/ml (range 198.8-502.5) for IV, 327.1 ng/ml (range 277.1-495.6) for IA, and 189.7 ng/ml (range 111.1-261.9) for DEBIRI (P < 0.001) delivery. The area-under-the-curve value from 10 to 60 min of serum irinotecan concentration was significantly lower for DEBIRI (P = 0.0009). Tumor irinotecan levels for IV, IA, and DEBIRI (in ng/200 mg of tissue followed by ranges in parentheses) were, respectively, 23.6 (0.3-24.9), 36.5 (7.7-1914.1), and 20.2 (2.9-319) at 1 h; 4.2 (1-27.9), 99.3 (46.6-159.5), and 42.1 (11.3-189) at 6 h; and 2.7 (2.5-6.9), 18.3 (1.5-369.1), and 174.4 (3.4-5147.3) at 24 h (P = 0.02). At 24 h, tumor necrosis was 25% (10-30), 60% (40-91.25), and 95% (76.25-95) for IV, IA, and DEBIRI, respectively (P = 0.03). CONCLUSION: Compared with IV or IA, DEBIRI induces lower early serum levels of irinotecan, a high and prolonged intratumoral level of irinotecan, and a greater rate of tumor necrosis at 24 h. Further evaluation of the clinical benefit of DEBIRI is warranted.

Leucine supplementation protects from insulin resistance by regulating adiposity levels.

BACKGROUND Leucine supplementation might have therapeutic potential in preventing diet-induced obesity and improving insulin sensitivity. However, the underlying mechanisms are at present unclear. Additionally, it is unclear whether leucine supplementation might be equally efficacious once obesity has developed. METHODOLOGY/PRINCIPAL FINDINGS Male C57BL/6J mice were fed chow or a high-fat diet (HFD), supplemented or not with leucine for 17 weeks. Another group of HFD-fed mice (HFD-pairfat group) was food restricted in order to reach an adiposity level comparable to that of HFD-Leu mice. Finally, a third group of mice was exposed to HFD for 12 weeks before being chronically supplemented with leucine. Leucine supplementation in HFD-fed mice decreased body weight and fat mass by increasing energy expenditure, fatty acid oxidation and locomotor activity in vivo. The decreased adiposity in HFD-Leu mice was associated with increased expression of uncoupling protein 3 (UCP-3) in the brown adipose tissue, better insulin sensitivity, increased intestinal gluconeogenesis and preservation of islets of Langerhans histomorphology and function. HFD-pairfat mice had a comparable improvement in insulin sensitivity, without changes in islets physiology or intestinal gluconeogenesis. Remarkably, both HFD-Leu and HFD-pairfat mice had decreased hepatic lipid content, which likely helped improve insulin sensitivity. In contrast, when leucine was supplemented to already obese animals, no changes in body weight, body composition or glucose metabolism were observed. CONCLUSIONS/SIGNIFICANCE These findings suggest that leucine improves insulin sensitivity in HFD-fed mice by primarily decreasing adiposity, rather than directly acting on peripheral target organs. However, beneficial effects of leucine on intestinal gluconeogenesis and islets of Langerhans's physiology might help prevent type 2 diabetes development. Differently, metabolic benefit of leucine supplementation is lacking in already obese animals, a phenomenon possibly related to the extent of the obesity before starting the supplementation.

Early Cretaceous life, climate and anoxia

Early Cretaceous life and the environment were strongly influenced by the accelerated break up of Pangaea, which was associated with the formation of a multitude of rift basins, intensified spreading, and important volcanic activity on land and in the sea. These processes likely interacted with greenhouse conditions, and Early Cretaceous climate oscillated between "normal" greenhouse, predominantly arid conditions, and intensified greenhouse, predominantly humid conditions. Arid conditions were important during the latest Jurassic and early Berriasian, the late Barremian, and partly also during the late Aptian. Humid conditions were particularly intense and widespread during shorter episodes of environmental change (EECs): the Valanginian Weissert, the latest Hauterivian Faraoni, the latest Barremian earliest Aptian Taxy, the early Aptian Selli, the early late Aptian Fallot and the late Aptian-early Albian Paquier episodes. Arid conditions were associated with evaporation, low biogeochemical weathering rates, low nutrient fluxes, and partly stratified oceans, leading to oxygen depletion and enhanced preservation of laminated, organic-rich mud (LOM). Humid conditions enabled elevated biogeochemical weathering rates and nutrient fluxes, important runoff and the buildup of freshwater lids in proximal basins, intensified oceanic and atmospheric circulation, widespread upwelling and phosphogenesis, important primary productivity and enhanced preservation of LOM in expanded oxygen-minimum zones. The transition of arid to humid climates may have been associated with the net transfer of water to the continent owing to the infill of dried-out groundwater reservoirs in internally drained inland basins. This resulted in shorter-term sea-level fall, which was followed by sea-level rise. These sea-level changes and the influx of freshwater into the ocean may have influenced oxygen-isotope signatures. Climate change preceding and during the Early Cretaceous EECs may have been rapid, but in general, the EECs had a "pre"-history, during which the stage was set for environmental change. Negative feedback on the climate through increased marine LOM preservation was unlikely, because of the low overall organic-carbon accumulation rates during these episodes. Life and climate co-evolved during the Early Cretaceous. Arid conditions may have affected continental life, such as across the Tithonian/Berriasian boundary. Humid conditions and the corresponding tendency to develop dys- to anaerobic conditions in deeper ocean waters led to phases of accelerated extinction in oceans, but may have led to more luxuriant vegetation cover on continents, such as during the Valanginian, to the benefit of herbivores. During Early Cretaceous EECs, reef systems and carbonate platforms in general were particularly vulnerable. They were the first to disappear and the last to recover, often only after several million years. (C) 2011 Elsevier Ltd. All rights reserved.

Iron metabolism, inflammation and anemia in critically ill patients. A cross-sectional study.

INTRODUCTION For critically patients, enteral immunonutrition results in notable reductions in infections and in length of stay in hospital, but not on mortality, raising the question as to whether this relate to the heterogeneous nature of critically ill patients or to the absence of the altered absorption of specific nutrients within the immunonutrient mix (e.g. iron). Immune-associated functional iron deficiency (FID) is not only one of the many causes or anaemia in the critically ill, but also a cause of inappropriate immune response, leading to a longer duration of episodes of systemic inflammatory response syndrome and poor outcome. OBJECTIVE This prospective cross-sectional study was undertaken to assess the prevalence of FID in critically ill patients during their stay in intensive care (ICU) in order to find the more appropriate population of patients that can benefit from iron therapy. METHOD Full blood cell counts, including reticulocytes (RETIC), serum iron (SI), transferring levels (TRF) and saturation (satTRF), serum TFR receptor (sTfR), ferritin (FRT) and C-reactive protein (CRP) were measured in venous blood samples from 131 random patients admitted to the ICU for at least 24 h (Length of ICU stay, LIS; min: 1 day; max: 38 days). RESULTS Anaemia (Hb < 12 g/dL) was present in 76% of the patients (Hb < 10 g/dL in 33%), hypoferremia (SI < 45 microg/dl) in 69%; satTRF < 20% in 53%; FRT < 100 ng/mL in 23%; sTfR > 2.3 mg/dL in 13%; and CRP > 0.5 mg/dL in 88%. Statistically significant correlations (r of Pearson; *p < 0.05, **p < 0.01) were obtained for serum CRP levels and WBC**, Hb*, TRF**, satTRF*, and FRT**. There was also a strong correlation between TRF and FRT (-0.650**), but not between FRT and satTRF or SI. LIS correlated with Hb*, CRP**, TRF*, satTRF* and FRT**. CONCLUSIONS A large proportion of critically ill patients admitted to the ICU presented the typical functional iron deficiency (FID) of acute inflammation-related anaemia (AIRA). This FID correlates with the inflammatory status and the length of stay at the ICU. However, 21% of the ICU patients with AIRA had an associated real iron deficiency (satTRF < 20; FRT < 100 and sTfR > 2.3). Since oral supplementation of iron seems to be ineffective, all these patients might benefit of iv iron therapy for correction of real or functional iron deficiency, which in turn might help to ameliorate their inflammatory status.

Hypothermie thérapeutique en traumatologie crânienne grave [Therapeutic hypothermia for severe traumatic brain injury].

Therapeutic hypothermia (TH) is considered a standard of care in the post-resuscitation phase of cardiac arrest. In experimental models of traumatic brain injury (TBI), TH was found to have neuroprotective properties. However, TH failed to demonstrate beneficial effects on neurological outcome in patients with TBI. The absence of benefits of TH uniformly applied in TBI patients should not question the use of TH as a second-tier therapy to treat elevated intracranial pressure. The management of all the practical aspects of TH is a key factor to avoid side effects and to optimize the potential benefit of TH in the treatment of intracranial hypertension. Induction of TH can be achieved with external surface cooling or with intra-vascular devices. The therapeutic target should be set at a 35°C using brain temperature as reference, and should be maintained at least during 48 hours and ideally over the entire period of elevated intracranial pressure. The control of the rewarming phase is crucial to avoid temperature overshooting and should not exceed 1°C/day. Besides its use in the management of intracranial hypertension, therapeutic cooling is also essential to treat hyperthermia in brain-injured patients. In this review, we will discuss the benefit-risk balance and practical aspects of therapeutic temperature management in TBI patients.

β-Lactam Monotherapy vs β-Lactam-Macrolide Combination Treatment in Moderately Severe Community-Acquired Pneumonia: A Randomized Noninferiority Trial.

IMPORTANCE: The clinical benefit of adding a macrolide to a β-lactam for empirical treatment of moderately severe community-acquired pneumonia remains controversial. OBJECTIVE: To test noninferiority of a β-lactam alone compared with a β-lactam and macrolide combination in moderately severe community-acquired pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Open-label, multicenter, noninferiority, randomized trial conducted from January 13, 2009, through January 31, 2013, in 580 immunocompetent adult patients hospitalized in 6 acute care hospitals in Switzerland for moderately severe community-acquired pneumonia. Follow-up extended to 90 days. Outcome assessors were masked to treatment allocation. INTERVENTIONS: Patients were treated with a β-lactam and a macrolide (combination arm) or with a β-lactam alone (monotherapy arm). Legionella pneumophila infection was systematically searched and treated by addition of a macrolide to the monotherapy arm. MAIN OUTCOMES AND MEASURES: Proportion of patients not reaching clinical stability (heart rate <100/min, systolic blood pressure >90 mm Hg, temperature <38.0°C, respiratory rate <24/min, and oxygen saturation >90% on room air) at day 7. RESULTS: After 7 days of treatment, 120 of 291 patients (41.2%) in the monotherapy arm vs 97 of 289 (33.6%) in the combination arm had not reached clinical stability (7.6% difference, P = .07). The upper limit of the 1-sided 90% CI was 13.0%, exceeding the predefined noninferiority boundary of 8%. Patients infected with atypical pathogens (hazard ratio [HR], 0.33; 95% CI, 0.13-0.85) or with Pneumonia Severity Index (PSI) category IV pneumonia (HR, 0.81; 95% CI, 0.59-1.10) were less likely to reach clinical stability with monotherapy, whereas patients not infected with atypical pathogens (HR, 0.99; 95% CI, 0.80-1.22) or with PSI category I to III pneumonia (HR, 1.06; 95% CI, 0.82-1.36) had equivalent outcomes in the 2 arms. There were more 30-day readmissions in the monotherapy arm (7.9% vs 3.1%, P = .01). Mortality, intensive care unit admission, complications, length of stay, and recurrence of pneumonia within 90 days did not differ between the 2 arms. CONCLUSIONS AND RELEVANCE: We did not find noninferiority of β-lactam monotherapy in patients hospitalized for moderately severe community-acquired pneumonia. Patients infected with atypical pathogens or with PSI category IV pneumonia had delayed clinical stability with monotherapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00818610.

Imatinib plasma concentrations variability in oncologic patients

The anticancer drug imatinib has transformed the treatment and prognosis of chronic myeloid leukemia and gastrointestinal stromal tumor. However, the treatment must be taken indefinitely and is not devoid of inconveniences and toxicity. Moreover, resistance or escape from disease control are occurring. Considering the large interindividual differences in the function of the enzymatic and transport systems involved in imatinib disposition, exposure to this drug can be expected to vary widely among patients. This book describes an observational clinical trial aiming at exploring the influence of these covariates on imatinib pharmacokinetics and assessing the interindividual variability of the pharmacokinetic parameters of the drug. A large interindividual variability was observed, together with some preliminary concentration-effect relationships. These elements are arguments to further investigate the potential benefit of a therapeutic drug monitoring program to optimize the use of imatinib in patients. Such results should be especially useful to clinical oncologists or scientists involved in clinical oncology research.

Suivi thérapeutique des médicaments (II). La pratique clinique [Therapeutic drug monitoring: clinical practice].

When requesting a blood level measurement in the context of "Therapeutic drug monitoring" (TDM), numerous aspects have to be considered in the pre-analytical and analytical area, as in the integration of associated clinical data. This review presents therapeutic classes for which a clinical benefit of TDM is established or suggested, at least in some settings. For each class of drugs, the main pharmacokinetic, pre-analytical, analytical and clinical aspects are evaluated in the scope of such a monitoring. Each step of the TDM process is important and none should be neglected. Additional clinical trials are however warranted to better establish the exact conditions of use for such a monitoring.

Simulation methods with extended stability for stiff biochemical kinetics

Background: With increasing computer power, simulating the dynamics of complex systems in chemistry and biology is becoming increasingly routine. The modelling of individual reactions in (bio)chemical systems involves a large number of random events that can be simulated by the stochastic simulation algorithm (SSA). The key quantity is the step size, or waiting time, τ, whose value inversely depends on the size of the propensities of the different channel reactions and which needs to be re-evaluated after every firing event. Such a discrete event simulation may be extremely expensive, in particular for stiff systems where τ can be very short due to the fast kinetics of some of the channel reactions. Several alternative methods have been put forward to increase the integration step size. The so-called τ-leap approach takes a larger step size by allowing all the reactions to fire, from a Poisson or Binomial distribution, within that step. Although the expected value for the different species in the reactive system is maintained with respect to more precise methods, the variance at steady state can suffer from large errors as τ grows. Results: In this paper we extend Poisson τ-leap methods to a general class of Runge-Kutta (RK) τ-leap methods. We show that with the proper selection of the coefficients, the variance of the extended τ-leap can be well-behaved, leading to significantly larger step sizes.Conclusions: The benefit of adapting the extended method to the use of RK frameworks is clear in terms of speed of calculation, as the number of evaluations of the Poisson distribution is still one set per time step, as in the original τ-leap method. The approach paves the way to explore new multiscale methods to simulate (bio)chemical systems.