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1.
BMC Palliat Care ; 23(1): 173, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39010044

RESUMO

BACKGROUND: Therapeutic ceiling of care is the maximum level of care deemed appropiate to offer to a patient based on their clinical profile and therefore their potential to derive benefit, within the context of the availability of resources. To our knowledge, there are no models to predict ceiling of care decisions in COVID-19 patients or other acute illnesses. We aimed to develop and validate a clinical prediction model to predict ceiling of care decisions using information readily available at the point of hospital admission. METHODS: We studied a cohort of adult COVID-19 patients who were hospitalized in 5 centres of Catalonia between 2020 and 2021. All patients had microbiologically proven SARS-CoV-2 infection at the time of hospitalization. Their therapeutic ceiling of care was assessed at hospital admission. Comorbidities collected at hospital admission, age and sex were considered as potential factors for predicting ceiling of care. A logistic regression model was used to predict the ceiling of care. The final model was validated internally and externally using a cohort obtained from the Leeds Teaching Hospitals NHS Trust. The TRIPOD Checklist for Prediction Model Development and Validation from the EQUATOR Network has been followed to report the model. RESULTS: A total of 5813 patients were included in the development cohort, of whom 31.5% were assigned a ceiling of care at the point of hospital admission. A model including age, COVID-19 wave, chronic kidney disease, dementia, dyslipidaemia, heart failure, metastasis, peripheral vascular disease, chronic obstructive pulmonary disease, and stroke or transient ischaemic attack had excellent discrimination and calibration. Subgroup analysis by sex, age group, and relevant comorbidities showed excellent figures for calibration and discrimination. External validation on the Leeds Teaching Hospitals cohort also showed good performance. CONCLUSIONS: Ceiling of care can be predicted with great accuracy from a patient's clinical information available at the point of hospital admission. Cohorts without information on ceiling of care could use our model to estimate the probability of ceiling of care. In future pandemics, during emergency situations or when dealing with frail patients, where time-sensitive decisions about the use of life-prolonging treatments are required, this model, combined with clinical expertise, could be valuable. However, future work is needed to evaluate the use of this prediction tool outside COVID-19.


Assuntos
COVID-19 , Hospitalização , Humanos , COVID-19/epidemiologia , COVID-19/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Hospitalização/estatística & dados numéricos , Espanha/epidemiologia , Adulto , Idoso de 80 Anos ou mais , Estudos de Coortes , SARS-CoV-2 , Comorbidade
2.
J Card Fail ; 30(3): 425-435, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37678704

RESUMO

BACKGROUND: Treatment of patients with heart failure with reduced ejection fraction (HFrEF) and renal dysfunction (RD) is challenging owing to the risk of further deterioration in renal function, especially after acute decompensated HF (ADHF). METHODS AND RESULTS: We assessed the effect of RD (estimated glomerular filtration rate of ≥30 to <60 mL/min/1.73 m2) on initiation, up-titration, and tolerability of sacubitril/valsartan in hemodynamically stabilized patients with HFrEF admitted for ADHF (RD, n = 476; non-RD, n = 483). At week 10, the target dose of sacubitril/valsartan (97/103 mg twice daily) was achieved by 42% patients in RD subgroup vs 54% in non-RD patients (P < .001). Sacubitril/valsartan was associated with greater estimated glomerular filtration rate improvements in RD subgroup than non-RD (change from baseline least squares mean 4.1 mL/min/1.73 m2, 95% confidence interval 2.2-6.1, P < .001). Cardiac biomarkers improved significantly in both subgroups; however, compared with the RD subgroup, the improvement was greater in those without RD (N-terminal pro-brain natriuretic peptide, -28.6% vs -44.8%, high-sensitivity troponin T -20.3% vs -33.9%) (P < .001). Patients in the RD subgroup compared with those without RD experienced higher rates of hyperkalemia (16.3% vs 6.5%, P < .001), investigator-reported cardiac failure (9.7% vs 5.6%, P = .029), and renal impairment (6.4% vs 2.1%, P = .002). CONCLUSIONS: Most patients with HFrEF and concomitant RD hospitalized for ADHF tolerated early initiation of sacubitril/valsartan and showed significant improvements in estimated glomerular filtration rate and cardiac biomarkers. CLINICAL TRIAL REGISTRATION: NCT02661217.


Assuntos
Insuficiência Cardíaca , Nefropatias , Disfunção Ventricular Esquerda , Humanos , Aminobutiratos/efeitos adversos , Antagonistas de Receptores de Angiotensina , Biomarcadores , Compostos de Bifenilo , Combinação de Medicamentos , Volume Sistólico , Tetrazóis/efeitos adversos , Resultado do Tratamento , Valsartana , Disfunção Ventricular Esquerda/tratamento farmacológico
3.
Can Prosthet Orthot J ; 5(1): 37456, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37614483

RESUMO

BACKGROUND: Following amputation, patients with lower limb amputations (LLA) are classified into different functional mobility levels (K-levels) ranging from K0 (lowest) to K4 (highest). However, K-level classification is often based on subjective criteria. Objective measures that are able to differentiate between K-levels can help to enhance the objectivity of K-level classification. OBJECTIVES: The goal of this preliminary cross-sectional study was to investigate whether differences in hip muscle strength and balance parameters exist among patients with transfemoral amputations (TFA) assigned to different K-levels. METHODOLOGY: Twenty-two participants with unilateral TFA were recruited for this study, with four participants assigned to K1 or K2, six assigned to K3 and twelve assigned to K4. Maximum isometric hip strength of the residual limb was assessed in hip flexion, abduction, extension, and adduction using a custom-made diagnostic device. Static balance was investigated in the bipedal stance on a force plate in eyes open (EO) and eyes closed (EC) conditions. Kruskal-Wallis tests were used to evaluate differences between K-level groups. FINDINGS: Statistical analyses revealed no significant differences in the parameters between the three K-level groups (p>0.05). Descriptive analysis showed that all hip strength parameters differed among K-level groups showing an increase in maximum hip torque from K1/2-classified participants to those classified as K4. Group differences were also present in all balance parameters. Increased sway was observed in the K1/2 group compared to the K4 group, especially for the EC condition. CONCLUSION: Although not statistically significant, the magnitude of the differences indicates a distinction between K-level groups. These results suggest that residual limb strength and balance parameters may have the potential to be used as objective measures to assist K-level assignment for patients with TFA. This potential needs to be confirmed in future studies with a larger number of participants.

4.
J Mot Behav ; 53(6): 693-706, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33161890

RESUMO

Virtual reality (VR) is popular across many disciplines and has been increasingly used in sports as a training tool lately. However, it is not clear whether the spatial orientation of humans works equally within VR and in the real-world. In this paper, two studies are presented, in which natural body movements were allowed and demanded. Firstly, a series of verbal and walking distance estimation tests were conducted in both the virtual and the real environment. The non-parametric Friedman test with pairwise comparisons showed no significant differences neither in verbal nor in walking distance estimations between the conditions (all p > 0.05). However, shorter distances (0.9-1.5 m) were estimated more precisely than larger distances (2.6-2.8 m) in both environments. Secondly, a self-developed route recall test to examine the spatial orientation was performed in the virtual and the real environment. The participants visually perceived the predefined route and were instructed to follow these routes with their eyes blindfolded and afterward to return to their starting position. Between the ending and the starting position, no difference between the two environments was observed (p > 0.05). Based on these two studies, the performance of the human spatial orientation preliminarily verified the same in a virtual and real environment.


Assuntos
Orientação Espacial , Realidade Virtual , Humanos , Orientação , Percepção Espacial , Interface Usuário-Computador
6.
Ann R Coll Surg Engl ; 102(5): 383-390, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32233869

RESUMO

INTRODUCTION: Cardiopulmonary exercise testing (CPET) and transthoracic echocardiography (TTE) are common preparative investigations prior to elective endovascular aneurysm repair (EVAR). Whether these investigations can predict survival following EVAR and contribute to shared decision making is unknown. METHODS: Patients who underwent EVAR at a tertiary centre between June 2007 and December 2014 were identified from the National Vascular Registry. Variables obtained from preoperative investigations were assessed for their association with survival at three years. Regression analysis was used to determine variables that independently predicted survival at three years. RESULTS: A total of 199 patients underwent EVAR during the study period. Of these, 120 had preoperative CPET and 123 had TTE. Lower forced expiratory ventilation (FEV1), ratio of FEV1 to forced vital capacity, work at peak oxygen consumption and higher ventilatory equivalent for carbon dioxide were associated with increased mortality. Variables obtained from TTE were not associated with survival at three years although there was a low incidence of left ventricular systolic dysfunction and significant valvular disease in this cohort. CONCLUSIONS: CPET might be a useful adjunct to assist in shared decision making in patients undergoing elective EVAR and may influence anaesthetic technique. TTE does not appear to be able to discriminate between high and low risk individuals. However, a low rate of significant ventricular dysfunction and valvular disease in patients undergoing elective EVAR may account for these findings.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Teste de Esforço , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios/métodos , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/mortalidade , Ecocardiografia , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/normas , Sistema de Registros/estatística & dados numéricos , Medição de Risco/métodos , Medição de Risco/normas , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
7.
Mater Today Bio ; 2: 100011, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32159146

RESUMO

A one-step microfluidic system is developed in this study which enables the encapsulation of stem cells and genetically engineered non-pathogenic bacteria into a so-called three-dimensional (3D) pearl lace-like microgel of alginate with high level of monodispersity and cell viability. The alginate-based microgel constitutes living materials that control stem cell differentiation in either an autonomous or heteronomous manner. The bacteria (Lactococcus lactis) encapsulated within the construct surface display adhesion fragments (III7-10 fragment of human fibronectin) for integrin binding while secreting growth factors (recombinant human bone morphogenetic protein-2) to induce osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. We concentrate on interlinked pearl lace microgels that enabled us to prototype a low-cost 3D bioprinting platform with highly tunable properties.

8.
Mucosal Immunol ; 11(3): 846-860, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29186109

RESUMO

CD44 is a transmembrane molecule appearing in numerous isoforms generated by insertions of alternatively spliced variant exons (CD44v) and having various binding partners. CD44v7 on T cells was proposed to promote colitis by preventing T-cell apoptosis. Here we demonstrate that Cd44v7-deficient T cells - like Cd44 wild-type (Cd44WT) T cells - provoked disease in two different colitis models: the model induced by CD4+CD45RBhigh T-cell transfer into Rag2-deficient mice and a new model based on ovalbumin (OVA)-specific T-cell transfer into Rag-sufficient, OVA-challenged mice. In contrast, CD44v7 absence on macrophages in recipient mice prevented colitis. Prevention was associated with the downregulation of signal transducer and activator of transcription 3 (STAT3)-activating and Foxp3-counteracting interleukin-6 (IL-6), lower numbers of phospho-STAT3-containing lymphocytes, and higher Foxp3+ T-cell counts in the colon. Consequently, the protected colons showed lower IL-12, IL-1ß expression, and decreased interferon-γ levels. Importantly, stimulation of T cells by Cd44v7-deficient macrophages induced upregulation of Foxp3 in vitro, while cotransfer of Cd44WT macrophages into Cd44v7-deficient mice reduced Foxp3+ T-cell counts and caused colitis. Accordingly, the CD44v7 ligand osteopontin, whose levels were elevated in Crohn's disease, specifically induced IL-6 in human monocytes, a cytokine also increased in these patients. We suggest macrophage-specific targeting of the CD44v7 pathway as a novel therapeutic option for Crohn's disease.


Assuntos
Colite/imunologia , Doença de Crohn/imunologia , Receptores de Hialuronatos/metabolismo , Macrófagos/fisiologia , Subpopulações de Linfócitos T/fisiologia , Linfócitos T Reguladores/fisiologia , Adulto , Processamento Alternativo , Animais , Células Cultivadas , Técnicas de Cocultura , Citocinas/metabolismo , Modelos Animais de Doenças , Éxons/genética , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Receptores de Hialuronatos/genética , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Camundongos Transgênicos , Osteopontina/metabolismo
9.
Anal Chem ; 89(3): 1965-1971, 2017 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-28105807

RESUMO

Grazing incidence and grazing emission X-ray fluorescence spectroscopy (GI/GE-XRF) are techniques that enable nondestructive, quantitative analysis of elemental depth profiles with a resolution in the nanometer regime. A laboratory setup for soft X-ray GEXRF measurements is presented. Reasonable measurement times could be achieved by combining a highly brilliant laser produced plasma (LPP) source with a scanning-free GEXRF setup, providing a large solid angle of detection. The detector, a pnCCD, was operated in a single photon counting mode in order to utilize its energy dispersive properties. GEXRF profiles of the Ni-Lα,ß line of a nickel-carbon multilayer sample, which displays a lateral (bi)layer thickness gradient, were recorded at several positions. Simulations of theoretical profiles predicted a prominent intensity minimum at grazing emission angles between 5° and 12°, depending strongly on the bilayer thickness of the sample. This information was used to retrieve the bilayer thickness gradient. The results are in good agreement with values obtained by X-ray reflectometry, conventional X-ray fluorescence and transmission electron microscopy measurements and serve as proof-of-principle for the realized GEXRF setup. The presented work demonstrates the potential of nanometer resolved elemental depth profiling in the soft X-ray range with a laboratory source, opening, for example, the possibility of in-line or even in situ process control in semiconductor industry.

10.
Clin Microbiol Infect ; 22(2): 209.e5-209.e8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26482270

RESUMO

To evaluate the human herpes virus 6 (HHV-6) -specific immune response in individuals with chromosomally integrated HHV-6 (ciHHV-6), we measured HHV-6-antigen-specific cytokine responses (interferon-γ, interleukin-2, tumour necrosis factor-α) in T cells by flow cytometry in 12 and 16 individuals with and without ciHHV-6, respectively. All individuals with ciHHV-6 showed HHV-6-specific T cells with higher frequencies of HHV-6-specific CD8(+) cells (0.03-14.93, median 2.15% of CD8(+) cells) compared with non-ciHHV-6 (0.0-10.67, median 0.36%, p 0.026). The observed increased HHV-6-specific functionally active responses in individuals with ciHHV-6 clearly disprove speculations on immune tolerance in ciHHV-6 and indicate clinical and immunological implications of ciHHV-6.


Assuntos
Citocinas/metabolismo , Herpesvirus Humano 6/genética , Infecções por Roseolovirus/virologia , Linfócitos T/citologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Roseolovirus/genética , Infecções por Roseolovirus/imunologia , Linfócitos T/metabolismo , Integração Viral , Adulto Jovem
11.
Prev Vet Med ; 117(3-4): 533-41, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-25457134

RESUMO

An outbreak of foot and mouth disease in Australia would trigger a major disease control and eradication program that would include restriction of movement of live animals within defined disease control zones. Experiences from outbreaks in other countries show that restrictions that limit the ability to turn off stock can lead to animal welfare compromise on intensively managed farms that are not infected with the disease. Intensive pig farms are considered to be at high risk of developing welfare problems during a control program due to the imposed movement restrictions and limited space available to house growing pigs. This study was designed to investigate strategies that could be used to mitigate animal welfare problems on intensive pig farms during a simulated outbreak of foot and mouth disease in a livestock dense region of Australia. Three strategies for managing farms affected by animal welfare problems were assessed, including on-farm culling of grower and finisher pigs, on-farm culling of finisher pigs only, and permit-based movement of finisher pigs to slaughter at abattoir. Under traditional approaches of giving infected premises (IP) priority over culling of farms with welfare problems (WP), delays of up to 25 days were experienced prior to culling of WPs. Deployment of vaccination did little to reduce the delay to culling of WPs. These delays were sensitive to resources available for control, with reduced resources increasing the time until welfare problems were addressed. Assigning equal priority to all farms requiring culling regardless of status as IP or WP and culling each as they arose reduced the delay to culling of WPs to no more than 4 days without large increases in either the duration or the size of the outbreaks observed.


Assuntos
Bem-Estar do Animal , Controle de Doenças Transmissíveis/métodos , Surtos de Doenças/veterinária , Febre Aftosa/epidemiologia , Febre Aftosa/prevenção & controle , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/prevenção & controle , Animais , Austrália/epidemiologia , Simulação por Computador , Surtos de Doenças/prevenção & controle , Febre Aftosa/transmissão , Modelos Teóricos , Suínos , Doenças dos Suínos/transmissão , Meios de Transporte
12.
Heart ; 100(12): 923-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24647052

RESUMO

OBJECTIVE: Acute heart failure syndrome (AHFS) is a major cause of hospitalisation and imparts a substantial burden on patients and healthcare systems. Tools to define risk of AHFS hospitalisation are lacking. METHODS: A prospective cohort study (n=628) of patients with stable chronic heart failure (CHF) secondary to left ventricular systolic dysfunction was used to derive an AHFS prediction model which was then assessed in a prospectively recruited validation cohort (n=462). RESULTS: Within the derivation cohort, 44 (7%) patients were hospitalised as a result of AHFS during 1 year of follow-up. Predictors of AHFS hospitalisation included furosemide equivalent dose, the presence of type 2 diabetes mellitus, AHFS hospitalisation within the previous year and pulmonary congestion on chest radiograph, all assessed at baseline. A multivariable model containing these four variables exhibited good calibration (Hosmer-Lemeshow p=0.38) and discrimination (C-statistic 0.77; 95% CI 0.71 to 0.84). Using a 2.5% risk cut-off for predicted AHFS, the model defined 38.5% of patients as low risk, with negative predictive value of 99.1%; this low risk cohort exhibited <1% excess all-cause mortality per annum when compared with contemporaneous actuarial data. Within the validation cohort, an identically applied model derived comparable performance parameters (C-statistic 0.81 (95% CI 0.74 to 0.87), Hosmer-Lemeshow p=0.15, negative predictive value 100%). CONCLUSIONS: A prospectively derived and validated model using simply obtained clinical data can identify patients with CHF at low risk of hospitalisation due to AHFS in the year following assessment. This may guide the design of future strategies allocating resources to the management of CHF.


Assuntos
Técnicas de Apoio para a Decisão , Insuficiência Cardíaca/etiologia , Hospitalização , Disfunção Ventricular Esquerda/complicações , Idoso , Distribuição de Qui-Quadrado , Doença Crônica , Diabetes Mellitus Tipo 2/complicações , Inglaterra , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Readmissão do Paciente , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Fatores de Tempo , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda
13.
Prev Vet Med ; 113(4): 436-46, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24412502

RESUMO

An outbreak of foot and mouth disease (FMD) could seriously impact Australia's livestock sector and economy. As an FMD-free country, an outbreak would trigger a major disease control and eradication program that would include the culling of infected and at risk animals ('stamping out'), movement restrictions and zoo-sanitary measures. Additional control measures may also include pre-emptive culling or vaccination. However, it is unclear what disease strategy would be most effective under Australian conditions and different resource levels. Using a stochastic simulation model that describes FMD transmission between farms in a livestock dense region of Australia, our results suggest that using current estimates of human resource capacity for surveillance, infected premises operations and vaccination, outbreaks were effectively controlled under a stamping out strategy. However, under more constrained resource allocations, ring vaccination was more likely to achieve eradication faster than stamping out or pre-emptive culling strategies.


Assuntos
Controle de Doenças Transmissíveis/métodos , Simulação por Computador , Surtos de Doenças/veterinária , Febre Aftosa/epidemiologia , Febre Aftosa/prevenção & controle , Criação de Animais Domésticos , Animais , Austrália/epidemiologia , Bovinos , Surtos de Doenças/prevenção & controle , Eutanásia Animal , Febre Aftosa/transmissão , Vacinação em Massa/veterinária , Modelos Teóricos , Processos Estocásticos
14.
Klin Monbl Augenheilkd ; 228(12): 1103-7, 2011 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-21847784

RESUMO

AIM OF STUDY: In particular, in the quick ball and racket games a good dynamic seeing is required . The afferent dynamic seeing occurs via the retiina which mediates the stimuli for efferent dynamic seeing . The aim of this study was to examine the dynamic visual acuity of sportsmen from sports with different demands on their dynamic seeing (DS). METHODS: 19 sports students took part in the study. 10 subjects participated in coached team sports (group I) and 9 remaining performed individual sports (group II). The DS was assessed by means of the Düsseldorfer test for dynamic seeing of Wist which was performed twice on one day. RESULTS: The DS of the two groups in the first study did not differ (right eye 95.7 ± 10.6 % in group I vs. 94.3 ± 6.9 % in group II and left eye 97.6 ± 4.8 % vs. 95.3 ± 5.6 %; p ≥ 0.05). Also the second study there was no different in DS for the two groups (right eye 98.3 ± 2.6 % vs. 93.8 ± 8.0 % and left eye 99.3 ± 1.2 % vs. 95.6 ± 7.0 %; p ≥ 0.05). DISCUSSION: Our hypothesis about a different DS in players of ball games compared with non-ball sport players could not be proved. It is to be critically noted that a generalization is not possible due to the small sample numbers. Because DS is a necessary precondition in ball games further studies should be concentrated on its trainability.


Assuntos
Reconhecimento Visual de Modelos/fisiologia , Esportes/fisiologia , Acuidade Visual/fisiologia , Feminino , Humanos , Masculino , Testes Visuais , Adulto Jovem
15.
Health Technol Assess ; 14(24): 1-162, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20492762

RESUMO

BACKGROUND: Two aldosterone inhibitors are currently licensed for heart failure (HF) in the UK: spironolactone and eplerenone. Recent clinical guidelines recommend eplerenone after an acute myocardial infarction (MI) for patients with symptoms and/or signs of HF and left ventricular dysfunction. OBJECTIVES: The primary objective was to evaluate relative clinical effectiveness and cost-effectiveness of spironolactone and eplerenone in patients with postMI HF and explore the possibility of conducting an indirect comparison of spironolactone and eplerenone. A second objective was to undertake value-of-information (VOI) analyses to determine the need for further research to identify research questions critical to decision-making and to help inform the design of future studies. DATA SOURCES: Relevant databases including MEDLINE, EMBASE and CENTRAL were searched between September and December 2008. Randomised controlled trials (RCTs) of spironolactone, eplerenone, canrenone or potassium canrenoate were included if conducted in a postMI HF population. Trials of general HF patients with a subgroup of postMI HF patients were considered if they had at least 100 ischaemic participants per arm and the authors provided subgroup data when contacted. Adverse events summary data were sought from recognised reference sources and RCTs or observational studies in any population that recruited more than 100 participants. REVIEW METHODS: The comparative clinical effectiveness and cost-effectiveness of spironolactone and eplerenone was derived using Bayesian meta-regression drawing on a wider 'network' of aldosterone trials to those considered in the main clinical effectiveness review. An alternative scenario was also considered assuming a 'class effect' for the aldosterone antagonists in terms of major clinical events, but allowing for potential differences in side effect profiles. Cost-effectiveness was assessed using incremental cost-effectiveness ratios (ICERs) where appropriate. Uncertainty in cost-effectiveness results was also presented and used to inform future research priorities using VOI analyses based on expected value of perfect information (EVPI). A probabilistic decision analytic model was developed to estimate cost-effectiveness of spironolactone, eplerenone and standard care for management of postMI HF, provide estimates relevant to the NHS and explore alternative approaches to an indirect comparison between spironolactone and eplerenone. The model incorporated a lifetime horizon to estimate outcomes in terms of quality-adjusted life-years (QALYs) and costs from the NHS persepctive. In the base-case analysis, 2-year treatment duration was assumed, consistent with the follow-up in the main RCTs. Other scenarios were explored to examine the robustness of alternative assumptions including impact of different treatment durations. RESULTS: Searches yielded five RCTs: two spironolactone trials of poor methodological quality and three trials of which only one (of eplerenone) specifically examined postMI HF (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study, EPHESUS). One trial of spironolactone (Randomised Aldactone Evaluation Study, RALES) and one of canrenone (Antiremodelling Effect of Aldosterone receptors blockade with canrenone In mild Chronic Heart Failure, AREA IN-CHF) comprised general HF, but data were available for an ischaemic subgroup. Structural similarity of spironolactone and eplerenone suggests that they may be interchangeable, but formal indirect comparison between the three trials was severely limited by trial differences. Relative safety data were limited from RCTs and observational sources. Hyperkalaemia rates varied, but were generally higher than for placebo; data were insufficient to assess discontinuation because of hyperkalaemia.Gynaecomastia rates were higher with spironolactone. Adverse event data were sparse. Systematic review of economic evidence identified three main published studies but none used a UK perspective or attempted to compare cost-effectiveness in postMI HF. The new decision model indicated that eplerenone was the most cost-effective strategy for postMI HF (ICER of eplerenone compared with standard care was 4457 pounds per QALY, increasing to 7893 pounds per QALY if treatment continued over the patient's lifetime); in neither scenario did spironolactone appear cost-effective. The ICER of eplerenone was consistently under the 20,000-30,000 pounds per QALY threshold used to establish value for money in the NHS. Uncertainty resulted in EVPI estimates between 820M pounds (base-case) and 1265M pounds (lifetime treatment duration scenario). When class effect for mortality and hospitalisations was assumed spironolactone emerged as the most cost-effective treatment and EVPI estimates were negligible. If class effect is considered more plausible than the results of the evidence synthesis model then there would be limited value in additional research. LIMITATIONS: Exchangeability between trials was poor and there was a lack of robust data in RCTs. CONCLUSIONS: Only two good-quality trials of aldosterone inhibitors in the postMI HF population were found, but lack of exchangeability with respect to study populations, meant that a comparison between these drugs could not be done. It consistently emerged that, compared with usual care, use of an aldosterone antagonist appears to be a highly cost-effective strategy for the management of postMI HF patients in the NHS. An adequately powered, well-conducted RCT that directly compares spironolactone and eplerenone is required to provide more robust evidence on the optimal management of postMI HF patients.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/etiologia , Antagonistas de Receptores de Mineralocorticoides/economia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Infarto do Miocárdio/complicações , Teorema de Bayes , Ensaios Clínicos como Assunto , Análise Custo-Benefício , Eplerenona , Humanos , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Anos de Vida Ajustados por Qualidade de Vida , Espironolactona/análogos & derivados , Espironolactona/economia , Espironolactona/uso terapêutico , Medicina Estatal , Reino Unido
16.
Phys Rev Lett ; 104(8): 084802, 2010 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-20366938

RESUMO

Laser-plasma wakefield-based electron accelerators are expected to deliver ultrashort electron bunches with unprecedented peak currents. However, their actual pulse duration has never been directly measured in a single-shot experiment. We present measurements of the ultrashort duration of such electron bunches by means of THz time-domain interferometry. With data obtained using a 0.5 J, 45 fs, 800 nm laser and a ZnTe-based electro-optical setup, we demonstrate the duration of laser-accelerated, quasimonoenergetic electron bunches [best fit of 32 fs (FWHM) with a 90% upper confidence level of 38 fs] to be shorter than the drive laser pulse, but similar to the plasma period.

17.
Genes Immun ; 10(8): 702-14, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19798076

RESUMO

Interferon (IFN)-lambda1, -2 and -3 (also designated as interleukin (IL)-29, IL-28alpha and IL-28beta) represent a new subfamily within the class II cytokine family. They show type I IFN-like antiviral and cytostatic activities in affected cells forming the basis for IFN-lambda1 therapy currently under development for hepatitis C infection. However, many aspects of IFN-lambdas are still unknown. This study aimed at identifying the target cells of IFN-lambdas within the immune system and the skin. Among skin cell populations, keratinocytes and melanocytes, but not fibroblasts, endothelial cells or subcutaneous adipocytes turned out to be targets. In contrast to these target cells, blood immune cell populations did not clearly respond to even high concentrations of these cytokines, despite an IFN-lambda receptor expression. Interestingly, immune cells expressed high levels of a short IFN-lambda receptor splice variant (sIFN-lambdaR1/sIL-28R1). Its characterization revealed a secreted, glycosylated protein that binds IFN-lambda1 with a moderate affinity (K(D) 73 nM) and was able to inhibit IFN-lambda1 effects. Our study suggests that IFN-lambda therapy should be suited for patients with verrucae, melanomas and non-melanoma skin cancers, apart from patients with viral hepatitis, and would not be accompanied by immune-mediated complications known from type I IFN application.


Assuntos
Interferons/imunologia , Leucócitos/imunologia , Receptores de Interferon/imunologia , Sequência de Aminoácidos , Células Cultivadas , Regulação da Expressão Gênica , Humanos , Queratinócitos/imunologia , Melanócitos/imunologia , Dados de Sequência Molecular , Receptores de Interferon/química , Receptores de Interferon/genética
18.
Hum Mov Sci ; 28(3): 394-405, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19443066

RESUMO

As a consequence of the three interacting systems of horse, saddle, and rider, horseback riding is a very complex movement that is difficult to characterize by a limited number of biomechanical parameters or characteristic curves. Principal Component Analysis (PCA) is a technique for reducing multidimensional datasets to a minimal (i.e., optimally economic) set of dimensions. To apply PCA to horseback riding data, a "pattern vector" composed of the horizontal velocities of a set of body markers was determined. PCA was used to identify the major dynamic constituents of the three natural gaits of the horse: walk, trot, and canter. It was found that the trot is characterized by only one major component accounting for about 90% of the data's variance. Based on a study involving 13 horses with the same rider, additional phase plane analyses of the order parameter dynamics revealed a potential influence of the saddle type on movement coordination for the majority of horses.


Assuntos
Fenômenos Biomecânicos/fisiologia , Marcha/fisiologia , Cavalos/fisiologia , Suporte de Carga/fisiologia , Animais , Teste de Esforço/veterinária , Humanos , Modelos Biológicos , Movimento/fisiologia , Condicionamento Físico Animal/métodos , Postura , Pressão , Esportes
19.
Pneumologie ; 63(2): 86-92, 2009 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-19219769

RESUMO

We report two patients admitted to our hospital suspected to suffer from cancer in the lung or mediastinum, respectively. Both patients had a diagnosis of thoracic actinomycosis. A 76 year old man revealed pulmonary and endobronchial actinomycosis associated with broncholithiasis. Diagnosis was achieved by bronchoscopy. Therapy with ampicillin/sulbactam was successful. A 36 year old patient presented with bilateral pleural effusions, extended pericardial, mediastinal and pulmonary actinomycosis with pericarditis constrictiva and superior vena cava syndrome. Diagnosis was finally made by cardiac surgery with therapeutic pericardectomy. Prolonged therapy with ampicillin/sulbactam was administered with satisfactory result. Here we discuss the importance to include actinomycosis in the differential diagnosis of pulmonary affections and mediastinal masses in order to avoid diagnostic errors and to limit invasive procedures to the necessary amount. We illustrate the need of an individualized treatment approach.


Assuntos
Actinomicose/diagnóstico , Actinomicose/terapia , Doenças Torácicas/diagnóstico , Doenças Torácicas/terapia , Adulto , Idoso , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Masculino , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/terapia
20.
Scott Med J ; 53(4): 26-30, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19051661

RESUMO

OBJECTIVE: To determine, using a consensus based methodology, the rate and nature of adverse events (AEs) among patients admitted to acute medicine, acute surgery and obstetrics in a large teaching hospital in Scotland. METHODS: Retrospective case-note review of 450 medical, nursing and medication records to identify and classify adverse events. For 354 patients whose length of stay was greater than 24 hours, the overall adverse event rate was 7.9% which ranged from 0% in obstetrics, 7.2% in acute medicine to 13% in acute surgery. Among all AEs, 43% were deemed preventable by a consensus group and 59% of the AEs contributed to a proportion of the patients' hospital stay or led to hospital readmission. Whilst nurse identification of adverse events was highly specific (94%), its sensitivity was poor (43%). Only 10% of the identified AEs were identified by the hospital's voluntary reporting system for adverse events. The estimated additional cost of adverse events in terms of bed days was l69,189 which if extrapolated Scotland-wide could cost l297 million per annum. CONCLUSIONS: This study supports the need to continue the traditional retrospective record review to identify adverse events. The current hospital-based reporting of adverse events does not provide a complete measure of adverse events and needs to be complemented by other measures.


Assuntos
Consenso , Auditoria Médica , Erros Médicos , Adulto , Feminino , Hospitalização , Hospitais , Humanos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Estudos Retrospectivos , Escócia
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