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1.
BMC Public Health ; 21(1): 2037, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34749704

RESUMO

BACKGROUND: Community-based mental health promotion programs focus on improving individual and community wellbeing by strengthening resilience and building capacity to support positive health outcomes. The Wheel of Wellbeing (WoW) is an example of such a program, promoting activities that support social engagement and positive emotions within a holistic framework underpinned by positive psychology. WoW is intended to be flexibly implemented in each community, training community members who implement behaviour change activities in their local community, workplace and educational settings. METHOD: This study aimed to understand the opinions and experiences of a sample of individuals who had participated in a range of WoW training programs; documenting the impact on participant behaviours and professional practices, and how the WoW framework was subsequently employed within their communities. Using Ripple Effects Mapping evaluation processes to guide a focus group, nine WoW training participants collectively reflected on the program impacts, generating consensus themes and a mind map. Mind map qualitative data were entered into XMIND mapping software and reviewed with the focus group transcription and field notes. RESULTS: Thematic analysis identified three themes: increased community involvement and engagement (strengthening community connections); improved health, emotions and behaviour (motivating change to health behaviours); and flexible resources which could be utilised in a range of settings (easily incorporated in the existing organisational cultures). CONCLUSIONS: The results of this study support the premise that the WoW framework can be an effective framework for guiding wellbeing promotion activities, with participants championing a 'ripple effect' across individual, family, friendship, professional and community networks.


Assuntos
Participação da Comunidade , Promoção da Saúde , Austrália , Grupos Focais , Humanos , Local de Trabalho
2.
Neurourol Urodyn ; 38(1): 338-345, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30350877

RESUMO

AIMS: We have developed a novel antimicrobial urinary catheter (AUC) impregnated with rifampicin, triclosan, and sparfloxacin and demonstrated that it has long-term (∼84 days) protection against bacterial colonization in vitro. This study aimed to assess the safety and patient acceptability of this device in long-term catheter users. METHODS: Adults who use long term (>28 days) indwelling urinary catheters with capacity to consent were invited to receive the AUC at their next catheter change. The primary outcome measure was adverse events (AE) attributable to antimicrobial impregnation of the catheter. Secondary outcome measures included severity of related AEs, patient acceptability, early removal of the trial catheter, and degree of microbial colonization of trial catheters. Except for the last, outcomes were assessed by telephone interviews. Original and trial catheters were collected, and the lumens and balloons were separated and analyzed for microbiological colonization. RESULTS: Thirty participants were recruited. Eighty four AEs were reported, and only one was rated as "probably" related to antimicrobial impregnation. The AE was mild and resolved within 48 h. A total of 82.14% of participants rated the catheter as no different or better than their usual catheter. Two participants chose to remove the AUC early due to it feeling shorter. There were significantly fewer bacterial isolates attached to the balloons of trial catheters compared to the matched original catheters. CONCLUSIONS: The AUC has an advantageous safety profile and was acceptable to the majority of participants. Information gained from this trial will support a larger randomized controlled study of efficacy.


Assuntos
Antibacterianos/uso terapêutico , Cateteres de Demora/microbiologia , Cateteres Urinários/microbiologia , Infecções Urinárias/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Cateteres de Demora/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Cateterismo Urinário/instrumentação , Cateteres Urinários/efeitos adversos , Infecções Urinárias/etiologia
3.
J Labelled Comp Radiopharm ; 57(4): 215-8, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24347378

RESUMO

Novel radiolabelling methods are important for the development of new tracers for positron emission tomography. Direct nucleophilic fluorination of aromatic rings with [(18) F]fluoride is limited to activated substrates, restricting the application of this approach. Inspired by transition metal-mediated transformations, a fluorine-18 synthon was prepared to supplement the radiolabelling methods available for molecules unsuitable for direct labelling. 2-Bromo-6-[(18) F]fluoropyridine (denoted [(18) F]1) was prepared in high yield, and palladium-mediated cross-coupling reactions were exemplified. High incorporation of fluoride and efficient cross-coupling reactions demonstrate that compound [(18) F]1 holds promise as a new synthon for construction of fluorine-18-labelled molecules via transition metal-mediated reactions.


Assuntos
Radioisótopos de Flúor/química , Marcação por Isótopo/métodos , Paládio/química , Piridinas/química , Monóxido de Carbono/química
4.
Mol Imaging Biol ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38942967

RESUMO

PURPOSE: There is currently no ideal radiotracer for imaging bacterial infections. Radiolabelled D-amino acids are promising candidates because they are actively incorporated into the peptidoglycan of the bacterial cell wall, a structural feature which is absent in human cells. This work describes fluorine-18 labelled analogues of D-tyrosine and D-methionine, O-(2-[18F]fluoroethyl)-D-tyrosine (D-[18F]FET) and S-(3-[18F]fluoropropyl)-D-homocysteine (D-[18F]FPHCys), and their pilot evaluation studies as potential radiotracers for imaging bacterial infection. PROCEDURES: D-[18F]FET and D-[18F]FPHCys were prepared in classical fluorination-deprotection reactions, and their uptake in Staphylococcus aureus and Pseudomonas aeruginosa was evaluated over 2 h. Heat killed bacteria were used as controls. A clinically-relevant foreign body model of S. aureus infection was established in Balb/c mice, as well as a sterile foreign body to mimic inflammation. The ex vivo biodistribution of D-[18F]FPHCys in the infected and inflamed mice was evaluated after 1 h, by dissection and gamma counting. The uptake was compared to that of [18F]FDG. RESULTS: In vitro uptake of both D-[18F]FET and D-[18F]FPHCys was specific to live bacteria. Uptake was higher in S. aureus than in P. aeruginosa for both radiotracers, and of the two, higher for D-[18F]FPHCys than D-[18F]FET. Blocking experiments with non-radioactive D-[19F]FPHCys confirmed specificity of uptake. In vivo, D-[18F]FPHCys had greater accumulation in S. aureus infection compared with sterile inflammation, which was statistically significant. As anticipated, [18F]FDG showed no significant difference in uptake between infection and inflammation. CONCLUSIONS: D-[18F]FPHCys uptake was higher in infected tissues than inflammation, and represents a fluorine-18 labelled D-AA with potential to detect a S. aureus reference strain (Xen29) in vivo. Additional studies are needed to evaluate uptake of this radiotracer in clinical isolates.

5.
FASEB J ; 26(2): 907-16, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21990375

RESUMO

Macrophage migration inhibitory factor (MIF) is an abundantly expressed proinflammatory cytokine playing a critical role in innate immunity and sepsis and other inflammatory diseases. We examined whether functional MIF gene polymorphisms (-794 CATT(5-8) microsatellite and -173 G/C SNP) were associated with the occurrence and outcome of meningococcal disease in children. The CATT(5) allele was associated with the probability of death predicted by the Pediatric Index of Mortality 2 (P=0.001), which increased in correlation with the CATT(5) copy number (P=0.04). The CATT(5) allele, but not the -173 G/C alleles, was also associated with the actual mortality from meningoccal sepsis [OR 2.72 (1.2-6.4), P=0.02]. A family-based association test (i.e., transmission disequilibrium test) performed in 240 trios with 1 afflicted offspring indicated that CATT(5) was a protective allele (P=0.02) for the occurrence of meningococcal disease. At baseline and after stimulation with Neisseria meningitidis in THP-1 monocytic cells or in a whole-blood assay, CATT(5) was found to be a low-expression MIF allele (P=0.005 and P=0.04 for transcriptional activity; P=0.09 and P=0.09 for MIF production). Taken together, these data suggest that polymorphisms of the MIF gene affecting MIF expression are associated with the occurrence, severity, and outcome of meningococcal disease in children.


Assuntos
Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Infecções Meningocócicas/genética , Repetições de Microssatélites , Adolescente , Alelos , Sequência de Bases , Linhagem Celular , Criança , Pré-Escolar , Primers do DNA/genética , Feminino , Homozigoto , Humanos , Lactente , Masculino , Meningite Meningocócica/genética , Meningite Meningocócica/mortalidade , Infecções Meningocócicas/mortalidade , Países Baixos/epidemiologia , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Fatores de Risco , Sepse/genética , Sepse/mortalidade , Reino Unido/epidemiologia
6.
Am J Respir Crit Care Med ; 184(11): 1261-9, 2011 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-21868501

RESUMO

RATIONALE: Children with congenital heart disease are at risk of gut barrier dysfunction and translocation of gut bacterial antigens into the bloodstream. This may contribute to inflammatory activation and organ dysfunction postoperatively. OBJECTIVES: To investigate the role of intestinal injury and endotoxemia in the pathogenesis of organ dysfunction after surgery for congenital heart disease. METHODS: We analyzed blood levels of intestinal fatty acid binding protein and endotoxin (endotoxin activity assay) alongside global transcriptomic profiling and assays of monocyte endotoxin receptor expression in children undergoing surgery for congenital heart disease. MEASUREMENTS AND MAIN RESULTS: Levels of intestinal fatty acid binding protein and endotoxin were greater in children with duct-dependent cardiac lesions. Endotoxemia was associated with severity of vital organ dysfunction and intensive care stay. We identified activation of pathogen-sensing, antigen-processing, and immune-suppressing pathways at the genomic level postoperatively and down-regulation of pathogen-sensing receptors on circulating immune cells. CONCLUSIONS: Children undergoing surgery for congenital heart disease are at increased risk of intestinal mucosal injury and endotoxemia. Endotoxin activity correlates with a number of outcome variables in this population, and may be used to guide the use of gut-protective strategies.


Assuntos
Endotoxemia/microbiologia , Cardiopatias Congênitas/cirurgia , Enteropatias/microbiologia , Mucosa Intestinal/lesões , Mucosa Intestinal/microbiologia , Regulação para Baixo/imunologia , Endotoxemia/sangue , Endotoxemia/imunologia , Ensaio de Imunoadsorção Enzimática , Proteínas de Ligação a Ácido Graxo/sangue , Proteínas de Ligação a Ácido Graxo/imunologia , Feminino , Humanos , Lactente , Inflamação/sangue , Inflamação/imunologia , Inflamação/microbiologia , Enteropatias/sangue , Enteropatias/imunologia , Mucosa Intestinal/imunologia , Tempo de Internação/estatística & dados numéricos , Masculino , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/imunologia , Insuficiência de Múltiplos Órgãos/microbiologia , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/imunologia , Complicações Pós-Operatórias/microbiologia , Índice de Gravidade de Doença
7.
Nucl Med Biol ; 114-115: 71-77, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36242984

RESUMO

PURPOSE: From a series of fluorinated analogues of puromycin, we recently identified [18F]fluoroethylpuromycin (FEPURO) as a potential candidate for imaging the rate of protein synthesis in vivo. Herein, we describe the automation of the radiosynthesis, and evaluation of [18F]FEPURO in vivo. PROCEDURES: [18F]FEPURO was radiosynthesised in an automated module. PET imaging was conducted in Wistar rats under control and blocking conditions using the protein synthesis inhibitor cycloheximide. Biodistribution and metabolite studies at 30, 60 and 120 min were conducted in healthy rats. RESULTS: Automation of the radiosynthesis resulted in reduction of the synthesis time by half from the manual method. A steady increase in the SUV was observed in the time-activity curves for the whole brain as expected for a protein synthesis marker. However, rapid in vivo metabolism of [18F]FEPURO within 15 min in plasma as well as the brain (4 % of parent 30 min p.i.) indicated formation of the [18F]FET radio-metabolite in >90 % thus suggesting that observed increase in the brain uptake was due to the radiometabolite. CONCLUSIONS: [18F]FEPURO is not a suitable PET radiotracer for imaging protein synthesis rates in brain in vivo due to its rapid metabolism. Further structural modifications to prevent in vivo metabolism are underway.


Assuntos
Radioisótopos de Flúor , Compostos Radiofarmacêuticos , Animais , Ratos , Radioisótopos de Flúor/química , Compostos Radiofarmacêuticos/química , Distribuição Tecidual , Ratos Wistar , Tomografia por Emissão de Pósitrons/métodos
8.
Crit Care ; 15(3): R141, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21651808

RESUMO

INTRODUCTION: The aim was to investigate the prevalence of endotoxemia in children admitted to pediatric intensive care unit (PICU), and its association with disease severity and outcome. METHODS: We conducted a prospective, observational cohort study of children admitted to PICU at St. Mary's Hospital, London over a 6-month period. One hundred consecutive patients were recruited. Demographic and clinical data were collected. Severity of illness was assessed by the pediatric index of mortality 2 (PIM2) score. The pediatric logistic organ dysfunction (PELOD) score was performed daily for the first 4 days. Patients were categorized according to primary reason for PICU admission. Blood samples were taken within 24 hours of admission and endotoxemia was measured using the endotoxin activity assay (EAA). Patients were stratified according to EAA level (high, EAA > 0.4, low, EAA < 0.4) and categorized as septic, post-surgical, respiratory or other. Data were analyzed using appropriate non-parametric tests. RESULTS: EAA level was significantly lower in PICU controls versus other PICU admissions (P = 0.01). Fifty-five children had endotoxemia on admission. Forty-one (75%) of these were eventually diagnosed with an infectious cause of admission. Nine children without infection had elevated EAA on admission. An infectious cause of admission was significantly associated with endotoxemia (P < 0.005). Of 15 children with gram-negative infection, only 9 (60%) had endotoxemia on admission. Endotoxemia on admission was not associated with shock or death. However, there was a tendency for increased PELOD score and length of stay in endotoxemic children. CONCLUSIONS: Endotoxemia is common in children admitted to intensive care. Understanding the implications of endotoxemia and potential anti-endotoxin strategies may have the potential to reduce severity of illness and length of PICU stay in critically ill children.


Assuntos
Endotoxemia/epidemiologia , Infecções/epidemiologia , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde , Índice de Gravidade de Doença , Adolescente , Criança , Pré-Escolar , Estado Terminal , Endotoxemia/diagnóstico , Feminino , Humanos , Lactente , Londres/epidemiologia , Masculino , Projetos Piloto , Prevalência , Estudos Prospectivos
9.
BMC Pediatr ; 10: 5, 2010 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-20137090

RESUMO

BACKGROUND: There is increasing evidence that tight blood glucose (BG) control improves outcomes in critically ill adults. Children show similar hyperglycaemic responses to surgery or critical illness. However it is not known whether tight control will benefit children given maturational differences and different disease spectrum. METHODS/DESIGN: The study is an randomised open trial with two parallel groups to assess whether, for children undergoing intensive care in the UK aged

Assuntos
Hiperglicemia/tratamento farmacológico , Insulina/uso terapêutico , Unidades de Terapia Intensiva Pediátrica , Seleção de Pacientes , Adolescente , Fatores Etários , Criança , Pré-Escolar , Protocolos Clínicos , Estado Terminal/terapia , Monitoramento de Medicamentos , Inglaterra , Humanos , Hiperglicemia/sangue , Hiperglicemia/epidemiologia , Hiperglicemia/etiologia , Lactente , Recém-Nascido , Infusões Intravenosas , Insulina/administração & dosagem , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/terapia , Projetos de Pesquisa , Respiração Artificial , Resultado do Tratamento , Vasoconstritores/uso terapêutico , Desmame do Respirador/estatística & dados numéricos , Ferimentos e Lesões/sangue , Ferimentos e Lesões/terapia
10.
Stud Health Technol Inform ; 272: 28-32, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32604592

RESUMO

It is 200 years since the birth of Florence Nightingale. This keynote paper reviews some of her work relating to health statistics and outlines its continuing legacy to nursing informatics around the world and especially in poorer countries, like South Africa, in the 21st century.


Assuntos
História da Enfermagem , Informática em Enfermagem , Feminino , História do Século XIX , Humanos , África do Sul
11.
Stud Health Technol Inform ; 146: 91-5, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19592815

RESUMO

As nurses around the world prepare to celebrate the centenary of the death of Florence Nightingale in 2010 this paper reviews her work on using information, especially statistics, to analyze and manage patient care and links that to current developments in informatics. It then examines assistive technologies and how they may impact on nursing practice in the future and links these developments to the writings of Florence Nightingale. The paper concludes by suggesting that in progressing towards sustainable and ubiquitous healthcare informatics we need to study history in order to learn from the lessons of Florence Nightingale and other healthcare pioneers.


Assuntos
Cuidados de Enfermagem/organização & administração , Feminino , História da Enfermagem , História do Século XIX , História do Século XX , Humanos , Informática em Enfermagem
12.
Stud Health Technol Inform ; 150: 963-7, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19745456

RESUMO

Free/Libre and Open Source Software (FLOSS) is a process of software development, a method of licensing and a philosophy. Although FLOSS plays a significant role in several market areas, the impact in the health care arena is still limited. FLOSS is promoted as one of the most effective means for overcoming fragmentation in the health care sector and providing a basis for more efficient, timely and cost effective health care provision. The 2008 European Federation for Medical Informatics (EFMI) Special Topic Conference (STC) explored a range of current and future issues related to FLOSS in healthcare (FLOSS-HC). In particular, there was a focus on health records, ubiquitous computing, knowledge sharing, and current and future applications. Discussions resulted in a list of main barriers and challenges for use of FLOSS-HC. Based on the outputs of this event, the 2004 Open Steps events and subsequent workshops at OSEHC2009 and Med-e-Tel 2009, a four-step strategy has been proposed for FLOSS-HC: 1) a FLOSS-HC inventory; 2) a FLOSS-HC collaboration platform, use case database and knowledge base; 3) a worldwide FLOSS-HC network; and 4) FLOSS-HC dissemination activities. The workshop will further refine this strategy and elaborate avenues for FLOSS-HC from scientific, business and end-user perspectives. To gain acceptance by different stakeholders in the health care industry, different activities have to be conducted in collaboration. The workshop will focus on the scientific challenges in developing methodologies and criteria to support FLOSS-HC in becoming a viable alternative to commercial and proprietary software development and deployment.


Assuntos
Acesso à Informação , Software , Educação , Europa (Continente) , Disseminação de Informação , Informática Médica
13.
Nucl Med Commun ; 40(1): 73-78, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30371605

RESUMO

BACKGROUND: Radical chemoradiotherapy is the primary treatment for head and neck cancers in many hospitals. Tumour hypoxia causes radiotherapy resistance and is an indicator of poor prognosis for patients. Identifying hypoxia to select patients for intensified or hypoxia-modified treatment regimens is therefore of high clinical importance. PATIENTS AND METHODS: We evaluated hypoxia in a group of patients with newly diagnosed squamous cell head and neck cancer using the hypoxia-selective radiotracer [F]HX4. Patients underwent a single [F]HX4 PET/computed tomography scan prior to beginning chemoradiotherapy. RESULTS: Three out of eight patients recruited were scanned with [F]HX4. Two out of three had pretreatment [F]FDG PET/computed tomography scans available for review. [F]HX4 tumour uptake varied between patients, with tumour to mediastinal ratios ranging from 1 to 3.5. CONCLUSION: The spectrum of [F]HX4 uptake in this small series of patients exemplifies the difference in oxygenation profiles between histologically similar tumours. Performing an additional PET scan with [F]HX4 prior to chemoradiotherapy treatment was logistically challenging in a routine setting, and therefore validation of its clinical impact should be the focus of future studies [EudraCT number 2013-003563-58].


Assuntos
Nitroimidazóis , Tomografia por Emissão de Pósitrons , Planejamento da Radioterapia Assistida por Computador , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Triazóis , Hipóxia Tumoral , Idoso , Quimiorradioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
14.
J Nucl Med ; 49(11): 1862-8, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18927340

RESUMO

UNLABELLED: A water-soluble glucose conjugate of the hypoxia tracer 64Cu-diacetyl-bis(N4-methylthiosemicarbazone) (64Cu-ATSM) was synthesized and radiolabeled (64Cu-ATSE/A-G). Here we report our initial biological experiments with 64Cu-ATSE/A-G and compare the results with those obtained for 64Cu-ATSM and 18F-FDG. METHODS: The uptake of 64Cu-ATSE/A-G and 64Cu-ATSM into HeLa cells in vitro was investigated at a range of dissolved oxygen concentrations representing normoxia, hypoxia, and anoxia. Small-animal PET with 64Cu-ATSE/A-G was performed in male BDIX rats implanted with P22 syngeneic carcinosarcomas. Images of 64Cu-ATSM and 18F-FDG were obtained in the same model for comparison. RESULTS: 64CuATSE/A-G showed oxygen concentration-dependent uptake in vitro and, under anoxic conditions, showed slightly lower levels of cellular uptake than 64Cu-ATSM; uptake levels under hypoxic conditions were also lower. Whereas the normoxic uptake of 64Cu-ATSM increased linearly over time, 64Cu-ATSE/A-G uptake remained at low levels over the entire time course. In the PET study, 64CuATSE/A-G showed good tumor uptake and a biodistribution pattern substantially different from that of each of the controls. In marked contrast to the findings for 64Cu-ATSM, renal clearance and accumulation in the bladder were observed. 64Cu-ATSE/A-G did not display the characteristic brain and heart uptake of 18F-FDG. CONCLUSION: The in vitro cell uptake studies demonstrated that 64Cu-ATSE/A-G retained hypoxia selectivity and had improved characteristics when compared with 64Cu-ATSM. The in vivo PET results indicated a difference in the excretion pathways, with a shift from primarily hepatointestinal for 64Cu-ATSM to partially renal with 64Cu-ATSE/A-G. This finding is consistent with the hydrophilic nature of the glucose conjugate. A comparison with 18F-FDG PET results revealed that 64Cu-ATSE/A-G was not a surrogate for glucose metabolism. We have demonstrated that our method for the modification of Cu-bis(thiosemicarbazonato) complexes allows their biodistribution to be modified without negating their hypoxia selectivity or tumor uptake properties.


Assuntos
Radioisótopos de Cobre/química , Glucose/química , Hipóxia/diagnóstico por imagem , Tiossemicarbazonas/química , Tiossemicarbazonas/metabolismo , Animais , Carcinossarcoma/diagnóstico por imagem , Fluordesoxiglucose F18 , Células HeLa , Humanos , Hipóxia/metabolismo , Masculino , Oxigênio/metabolismo , Tomografia por Emissão de Pósitrons , Ratos , Tiossemicarbazonas/sangue
15.
Pediatr Crit Care Med ; 9(6): 636-40, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18838926

RESUMO

OBJECTIVE: To determine the association between hyperglycemia and outcome in children ventilated for meningococcal sepsis. DESIGN: Retrospective case notes review. SETTING: Eight bedded pediatric intensive care unit in London. PATIENTS: Consecutive children ventilated for meningococcal sepsis 2001-2004. INTERVENTIONS: None. MEASUREMENTS: Peak glucose for the entire admission was determined and mean glucose was calculated for the following three epochs: 1) first 24 hrs, 2) second 24 hrs, and 3) the entire pediatric intensive care unit admission. Patients were also grouped according to whether their blood glucose rose to >7 mmol/L (126 mg/dL), >10 mmol/L (180 mg/dL), or remained below these levels during the pediatric intensive care unit admission. Outcome measures were predicted mortality (based on pediatric risk of mortality score), ventilator free days at 30 days, nosocomial infection, use of renal replacement therapy, use of inotropes, and skin necrosis. MAIN RESULTS: Ninety-seven patients were identified with a median age of 2.1 yrs and a median length of stay of 4 days. Four patients died. Peak glucose significantly correlated with predicted mortality and negatively correlated with ventilator free days at 30 days (p < 0.001 and p < 0.001, respectively). Patients who received renal replacement therapy or inotropic support, or developed a nosocomial infection or skin necrosis had significantly higher peak glucose than those who did not (p = 0.006, p < 0.0001, p = 0.022, and p < 0.0001, respectively). Patients who received renal replacement therapy or who developed skin necrosis had significantly higher mean blood glucose in the second 24 hrs of admission (p = 0.017 and p = 0.004, respectively). However, mean blood glucose in the first 24 hrs and over the entire admission did not correlate with outcome. Patients defined as hyperglycemic with blood glucose either >7 mmol/L or >10 mmol/L also had a significantly worse outcome than those who maintained blood glucose below these levels. CONCLUSIONS: There was a significant association between hyperglycemia and outcome. Our results support a trial of tight glycemic control in this group of critically ill children.


Assuntos
Hiperglicemia/complicações , Infecções Meningocócicas/complicações , Sepse/complicações , Glicemia/análise , Pré-Escolar , Infecção Hospitalar/sangue , Humanos , Hiperglicemia/tratamento farmacológico , Insulina/uso terapêutico , Morbidade , Respiração Artificial , Estudos Retrospectivos
16.
Intensive Care Med ; 33(2): 364-7, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17115131

RESUMO

OBJECTIVE: To compare plasma levels of thioredoxin (Trx), TNF-alpha and IL-1 beta in children during the acute phase of meningococcal septic shock (MSS) and in convalescence. DESIGN AND SETTING: Retrospective, observational study in the paediatric intensive care unit of a postgraduate teaching hospital. PATIENTS: Thirty-five children requiring intensive care for meningococcal sepsis; paired convalescent samples from 30 survivors (median interval between samples 62 days); 25 healthy control children. MEASUREMENTS AND RESULTS: Plasma Trx levels were significantly lower in the children with MSS, both during the acute illness (5.5 ng/ml, IQR 1.4-11.4) and in convalescence (2.5 ng/ml, IQR 0.4-6.9) than controls (18.8 ng/ml, IQR 7.9-25.0). Levels of IL-1 beta and TNF-alpha were higher in patients with acute MSS (30.3 pg/ml, IQR 3.6-63.6, and 145.9 pg/ml, IQR 31.8-278.1 respectively) than controls (3.7 pg/ml, IQR 0-36.9, and 23.8 pg/ml, IQR 0-124.3, respectively). Levels fell in convalescence (3.7 pg/ml, IQR 0-25.5, 3.7 pg/ml, IQR 0-304.8, respectively). Plasma Trx was higher in non-survivors, albeit a small group (n=5), than in survivors (n=30). Trx, IL-1 beta, and TNF-alpha levels were not correlated with predicted mortality as assessed by the paediatric risk of mortality (PRISM) score. CONCLUSIONS: Children with MSS exhibit persistently low plasma levels of Trx during acute illness and in convalescence.


Assuntos
Infecções Meningocócicas/sangue , Choque Séptico/sangue , Síndrome de Resposta Inflamatória Sistêmica/sangue , Tiorredoxinas/sangue , Estudos de Casos e Controles , Pré-Escolar , Humanos , Unidades de Terapia Intensiva Pediátrica , Interleucina-1beta/sangue , Infecções Meningocócicas/mortalidade , Estudos Retrospectivos , Choque Séptico/mortalidade , Análise de Sobrevida , Síndrome de Resposta Inflamatória Sistêmica/mortalidade , Fator de Necrose Tumoral alfa/sangue
17.
Stud Health Technol Inform ; 122: 153-7, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17102238

RESUMO

Open Learning has been offered by the University of Winchester since 1991 in a partnership with the publishing company Emap Healthcare. A new on-line module for Independent, Extended and Supplementary Nurse Prescribing was developed by Emap Healthcare to meet a Government initiative to develop the role of nurses. The on-line module was created because of the wide spread national requirement, the need to keep the learning material contemporary and to revise it easily as required. Fourteen students completed the course and this paper reports the preliminary evaluation of the first cohort. Two questionnaires were analysed quantitatively and qualitatively and both the course management and the e-learning materials evaluations demonstrate the success of this first cohort. Various minor changes to the course management have subsequently been implemented following this analysis.


Assuntos
Prescrições de Medicamentos , Educação em Enfermagem , Internet , Inglaterra , Inquéritos e Questionários
18.
J Med Chem ; 59(20): 9422-9430, 2016 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-27690460

RESUMO

There is currently no ideal radiotracer for imaging of protein synthesis rate (PSR) by positron emission tomography (PET). Existing fluorine-18-labeled amino acid-based radiotracers predominantly visualize amino acid transporter processes, and in many cases they are not incorporated into nascent proteins at all. Others are radiolabeled with the short-half-life positron emitter carbon-11, which is rather impractical for many PET centers. Based on the puromycin (6) structural manifold, a series of 10 novel derivatives of 6 was prepared via Williamson ether synthesis from a common intermediate. A bioluminescence assay was employed to study their inhibitory action on protein synthesis, which identified the fluoroethyl analogue 7b as a lead compound. The fluorine-18 analogue was prepared via nucleophilic substitution of the corresponding tosylate precursor in a modest radiochemical yield of 2 ± 0.6% with excellent radiochemical purity (>99%) and showed complete stability over 3 h at ambient temperature.


Assuntos
Proteínas de Bactérias/análise , Proteínas de Bactérias/biossíntese , Tomografia por Emissão de Pósitrons/métodos , Biossíntese de Proteínas , Puromicina/análogos & derivados , Puromicina/análise , Relação Dose-Resposta a Droga , Marcação por Isótopo , Medições Luminescentes , Estrutura Molecular , Puromicina/síntese química , Puromicina/química , Radioisótopos/química , Staphylococcus aureus/metabolismo , Relação Estrutura-Atividade
19.
Trends Microbiol ; 12(11): 476-82, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15488386

RESUMO

Chromobacterium violaceum is an environmental Gram-negative bacterium that is common in soil and water in tropical and sub-tropical regions. It is also a model organism for studying quorum-sensing and is a rare but deadly human pathogen. Recent completion of the genome sequence of C. violaceum strain ATCC 12472 revealed the presence of genes associated with type-III secretion systems (TTSSs). One of these systems resembles the Spi-1 system found in Salmonella enterica, whereas another is similar to the Spi-2 system from the same organism. Here, we present a detailed analysis and a fresh annotation of the two gene clusters. Moreover, we highlight the presence of several genes encoding putative type-III effector proteins that lead us to predict that this organism can manipulate vesicular trafficking, the actin cytoskeleton and apoptotic pathways within mammalian cells to its own advantage.


Assuntos
Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Chromobacterium/genética , Genes Bacterianos , Proteínas de Bactérias/química , Chromobacterium/fisiologia , Família Multigênica , Transporte Proteico , Salmonella enterica/genética , Homologia de Sequência de Aminoácidos
20.
Stud Health Technol Inform ; 216: 525-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26262106

RESUMO

Since 2011, the Regional e-Health Center of Excellence in Rwanda (REHCE) has run an MSc in Health Informatics programme (MSc HI). A programme review was commissioned in February 2014 after 2 cohorts of students completed the post-graduate certificate and diploma courses and most students had started preparatory activity for their master dissertation. The review developed a method for mapping course content on health informatics competences and knowledge units. Also the review identified and measured knowledge gaps and content redundancy. Using this method, we analyzed regulatory and programme documents combined with stakeholder interviews, and demonstrated that the existing MSc HI curriculum did not completely address the needs of the Rwandan health sector. Teaching strategies did not always match students' expectations. Based on a detailed Rwandan health informatics needs assessment, International Medical Informatics Association (IMIA)'s Recommendations on Education in Biomedical and Health Informatics and the IMIA Health Informatics Knowledge Base, a new curriculum was developed and provided a better competences match for the specifics of healthcare in the Central African region. The new approved curriculum will be implemented in the 2014/2015 academic year and options for regional extension of the programme to Eastern DRC (Bukavu) and Burundi (Bujumbura) are being investigated.


Assuntos
Currículo/normas , Educação de Pós-Graduação/normas , Avaliação Educacional/normas , Bases de Conhecimento , Informática Médica/educação , Internacionalidade , Ruanda
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