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- Dent, E., et al.
(författare)
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Physical Frailty : ICFSR International Clinical Practice Guidelines for Identification and Management
- 2019
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Ingår i: The Journal of Nutrition, Health & Aging. - : SPRINGER FRANCE. - 1279-7707 .- 1760-4788. ; 23:9, s. 771-787
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) developed these clinical practice guidelines to overview the current evidence-base and to provide recommendations for the identification and management of frailty in older adults.Methods: These recommendations were formed using the GRADE approach, which ranked the strength and certainty (quality) of the supporting evidence behind each recommendation. Where the evidence-base was limited or of low quality, Consensus Based Recommendations (CBRs) were formulated. The recommendations focus on the clinical and practical aspects of care for older people with frailty, and promote person-centred care.Recommendations for Screening and Assessment: The task force recommends that health practitioners case identify/screen all older adults for frailty using a validated instrument suitable for the specific setting or context (strong recommendation). Ideally, the screening instrument should exclude disability as part of the screening process. For individuals screened as positive for frailty, a more comprehensive clinical assessment should be performed to identify signs and underlying mechanisms of frailty (strong recommendation).Recommendations for Management: A comprehensive care plan for frailty should address polypharmacy (whether rational or nonrational), the management of sarcopenia, the treatable causes of weight loss, and the causes of exhaustion (depression, anaemia, hypotension, hypothyroidism, and B12 deficiency) (strong recommendation). All persons with frailty should receive social support as needed to address unmet needs and encourage adherence to a comprehensive care plan (strong recommendation). First-line therapy for the management of frailty should include a multi-component physical activity programme with a resistance-based training component (strong recommendation). Protein/caloric supplementation is recommended when weight loss or undernutrition are present (conditional recommendation). No recommendation was given for systematic additional therapies such as cognitive therapy, problem-solving therapy, vitamin D supplementation, and hormone-based treatment. Pharmacological treatment as presently available is not recommended therapy for the treatment of frailty.
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- Bath, PMW, et al.
(författare)
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Baseline characteristics of the 4011 patients recruited into the ‘Efficacy of Nitric Oxide in Stroke’ (ENOS) trial
- 2014
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Ingår i: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 9:6, s. 711-720
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is common in acute stroke and associated with a worse functional outcome. Many patients who present with acute stroke are taking prescribed antihypertensive therapy before their stroke. Aims ENOS tested whether lowering blood pressure and continuing pre-stroke antihypertensive therapy are each safe and effective. Methods This study is an international multi-centre prospective randomized single-blind blinded-endpoint parallel-group partial-factorial controlled trial of transdermal glyceryl trinitrate (a nitric oxide donor, given for seven-days) vs. no glyceryl trinitrate, and of continuing vs. stopping (temporarily for seven-days) pre-stroke antihypertensive drugs if relevant, in patients with acute ischaemic stroke or intracerebral haemorrhage and high systolic blood pressure (140–220 mmHg). Results Recruitment ran from July 2001 to October 2013. Four thousand eleven patients [2097 (52·3%) in the continue/stop arm] were recruited from 173 sites across 23 countries in 5 continents (Asia 14%, Continental Europe 16%, UK 64%). Baseline characteristics include: mean age 70 (standard deviation 12) years; male 57%; mean time from stroke to recruitment 26 ( 13 ) h; mean severity (Scandinavian Stroke Scale) 34 ( 13 ) of 58; mean blood pressure 167 ( 19 )/90 ( 13 ) mmHg; ischaemic stroke 83%; and intracerebral haemorrhage 16%. The main trial results will be presented in May 2014. The results will also be presented in updated Cochrane systematic reviews and included in individual patient data meta-analyses of all relevant randomized controlled trials. Conclusion ENOS is a large completed international trial of blood pressure management in acute stroke and includes patients representative of many stroke services worldwide.
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- Grann, Martin, et al.
(författare)
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Methodological development : structured outcome assessment and community risk monitoring (SORM)
- 2005
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Ingår i: International Journal of Law and Psychiatry. - : Elsevier BV. - 0160-2527 .- 1873-6386. ; 28:4, s. 442-456
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes an effort to develop a clinical tool for the continuous monitoring of risk for violence in forensic mental health clients who have left their institutions and who are dwelling in the community on a conditional release basis. The model is called Structured Outcome Assessment and Community Risk Monitoring (SORM). The SORM consists of 30 dynamic factors and each factor in SORM is assessed in two ways: The current absence, presence or partial och intermittent presence of the factors, which is an actuarial (systematized and 'objective') assessment. Secondly, the risk effect, i.e. whether the presence/absence of factors currently increases, decreases or is perceived as unrelated to violence risk, is a clinical (or impressionistic) assessment. Thus, the factors considered via the SORM can be coded as risk factors or protective factors (or as factors unimportant to risk of violence) depending on circumstances that apply in the individual case. Further, the SORM has a built-in module for gathering idiographical information about risk-affecting contextual factors. The use of the SORM and its potential as a risk monitoring instrument is illustrated via preliminary data and case vignettes from an ongoing multicenter project. In this research project, patients leaving any of the 9 participating forensic hospitals in Sweden is assessed at release on a variety of static background factors, and the SORM is then administered every 30 days for 2 years.
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- Haim-Vilmovsky, Liora, et al.
(författare)
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Mapping Rora expression in resting and activated CD4+ T cells
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:5
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Tidskriftsartikel (refereegranskat)abstract
- The transcription factor Rora has been shown to be important for the development of ILC2 and the regulation of ILC3, macrophages and Treg cells. Here we investigate the role of Rora across CD4+ T cells in general, but with an emphasis on Th2 cells, both in vitro as well as in the context of several in vivo type 2 infection models. We dissect the function of Rora using overexpression and a CD4-conditional Rora-knockout mouse, as well as a RORA-reporter mouse. We establish the importance of Rora in CD4+ T cells for controlling lung inflammation induced by Nippostrongylus brasiliensis infection, and have measured the effect on downstream genes using RNA-seq. Using a systematic stimulation screen of CD4 + T cells, coupled with RNA-seq, we identify upstream regulators of Rora, most importantly IL-33 and CCL7. Our data suggest that Rora is a negative regulator of the immune system, possibly through several downstream pathways, and is under control of the local microenvironment. Copyright: © 2021 Haim-Vilmovsky et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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- Mann, G. W., et al.
(författare)
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Intercomparison and evaluation of global aerosol microphysical properties among AeroCom models of a range of complexity
- 2014
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 14:9, s. 4679-4713
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Tidskriftsartikel (refereegranskat)abstract
- Many of the next generation of global climate models will include aerosol schemes which explicitly simulate the microphysical processes that determine the particle size distribution. These models enable aerosol optical properties and cloud condensation nuclei (CCN) concentrations to be determined by fundamental aerosol processes, which should lead to a more physically based simulation of aerosol direct and indirect radiative forcings. This study examines the global variation in particle size distribution simulated by 12 global aerosol microphysics models to quantify model diversity and to identify any common biases against observations. Evaluation against size distribution measurements from a new European network of aerosol supersites shows that the mean model agrees quite well with the observations at many sites on the annual mean, but there are some seasonal biases common to many sites. In particular, at many of these European sites, the accumulation mode number concentration is biased low during winter and Aitken mode concentrations tend to be overestimated in winter and underestimated in summer. At high northern latitudes, the models strongly underpredict Aitken and accumulation particle concentrations compared to the measurements, consistent with previous studies that have highlighted the poor performance of global aerosol models in the Arctic. In the marine boundary layer, the models capture the observed meridional variation in the size distribution, which is dominated by the Aitken mode at high latitudes, with an increasing concentration of accumulation particles with decreasing latitude. Considering vertical profiles, the models reproduce the observed peak in total particle concentrations in the upper troposphere due to new particle formation, although modelled peak concentrations tend to be biased high over Europe. Overall, the multimodel-mean data set simulates the global variation of the particle size distribution with a good degree of skill, suggesting that most of the individual global aerosol microphysics models are performing well, although the large model diversity indicates that some models are in poor agreement with the observations. Further work is required to better constrain size-resolved primary and secondary particle number sources, and an improved understanding of nucleation and growth (e. g. the role of nitrate and secondary organics) will improve the fidelity of simulated particle size distributions.
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- Laxminarayan, Ramanan, et al.
(författare)
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Antibiotic resistance-the need for global solutions
- 2013
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Ingår i: The Lancet - Infectious diseases. - 1473-3099 .- 1474-4457. ; 13:12, s. 1057-1098
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Tidskriftsartikel (refereegranskat)abstract
- The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed.
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- Ulloa, Jose L, et al.
(författare)
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Assessment of gadoxetate DCE-MRI as a biomarker of hepatobiliary transporter inhibition
- 2013
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Ingår i: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 26:10, s. 1258-1270
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Tidskriftsartikel (refereegranskat)abstract
- Drug-induced liver injury (DILI) is a clinically important adverse drug reaction, which prevents the development of many otherwise safe and effective new drugs. Currently, there is a lack of sensitive and specific biomarkers that can be used to predict, assess and manage this toxicity. The aim of this work was to evaluate gadoxetate-enhanced MRI as a potential novel biomarker of hepatobiliary transporter inhibition in the rat. Initially, the volume fraction of extracellular space in the liver was determined using gadopentetate to enable an estimation of the gadoxetate concentration in hepatocytes. Using this information, a compartmental model was developed to characterise the pharmacokinetics of hepatic uptake and biliary excretion of gadoxetate. Subsequently, we explored the impact of an investigational hepatobiliary transporter inhibitor on the parameters of the model in vivo in rats. The investigational hepatobiliary transporter inhibitor reduced both the rate of uptake of gadoxetate into the hepatocyte, k 1 , and the Michaelis-Menten constant, V max , characterising its excretion into bile, whereas K M values for biliary efflux were increased. These effects were dose dependent and correlated with effects on plasma chemistry markers of liver dysfunction, in particular bilirubin and bile acids. These results indicate that gadoxetate-enhanced MRI provides a novel functional biomarker of inhibition of transporter-mediated hepatic uptake and clearance in the rat. Since gadoxetate is used clinically, the technology has the potential to provide a translatable biomarker of drug-induced perturbation of hepatic transporters that may also be useful in humans to explore deleterious functional alterations caused by transporter inhibition. © 2013 John Wiley & Sons, Ltd.
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