Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
1.
Frontline Gastroenterol ; 15(2): 124-129, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38486673

RESUMO

Objective: Patients hospitalised with decompensated cirrhosis have high rates of early unplanned readmission. Many readmissions are avoidable with secondary preventative strategies, but patients are often readmitted prior to outpatient review. To address this, we established a novel, nurse-led early postdischarge (EPD) clinic delivering goal-directed care for cirrhosis complications and evaluated the impact. Methods: Retrospective cohort study comparing outcomes in 78 patients seen in the EPD clinic with 91 phenotypically matched controls receiving standard, consultant hepatologist care. Follow-up for 12 months from index admission with endpoints including survival, time to readmission, number of readmissions and healthcare burden. Results: Median time to readmission was 51 days in controls and 98 days in the intervention group (p<0.01). The intervention cohort had significantly fewer readmissions at 30 days (12% vs 30%, p<0.01) and 90 days (27% vs 49%, p<0.01) but not significantly at 12 months (58% vs 68%, p=0.16) with an overall reduction in bed day usage of 29%. Mortality for the control group was 4% at 30 days with no deaths in the intervention group. There were significantly fewer deaths in the intervention group at 90 days (5% vs 15%, p<0.05) and 12 months (22% vs 41%, p<0.01). Conclusions: Following an index hospitalisation with decompensated cirrhosis, goal-directed postdischarge care can be effectively delivered by specialist nurses, prior to outpatient review by hepatologists. This model was associated with significantly fewer readmissions, lower bed day usage and a reduced mortality. Our data suggest such models of care deserve wider implementation and further evaluation.

2.
Cytopathology ; 35(2): 250-255, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38054566

RESUMO

OBJECTIVE: EBUS-TBNA is a method of acquiring tissue samples from intrathoracic lymph nodes and central intrathoracic tumours in patients suspected of having lung cancer. Rapid on-site evaluation (ROSE) denotes assessing tissue samples during EBUS (or bronchoscopy), providing instant feedback on sample adequacy and provisional cytomorphological diagnosis. Sector multidisciplinary team (MDT) discussion can then make informed treatment decisions, with confirmatory immunohistochemistry being finalised before provision of final treatment. Currently, impact of ROSE on length of time patients spend on the lung cancer diagnostic pathway remains unclear. METHODS: We retrospectively evaluated the impact of ROSE on the length of time between patients' EBUS/bronchoscopy procedures and discussion at sector MDT, referred to as time to treatment decision (TTD), at our institution. Additionally, we assessed impact of ROSE on number of passes (number of times nodes/masses were sampled) per procedure. RESULTS: The mean TTD was 77.9% shorter (p = 0.001) with ROSE present than when absent. Patients who received ROSE spend 34.3% less time (p = 0.028) on lung cancer diagnostic pathway overall. There was a significant reduction in number of passes in non-malignant nodes with ROSE present (2.23) than when absent (3.14) (p < 0.001). With ROSE present there was a significantly greater number of passes at malignant sites (5.07) than non-malignant sites (2.23) (p < 0.001). CONCLUSIONS: These findings support conclusions made in our institution's previous study, that utilisation of ROSE reduces TTD. ROSE also allows safe advancement through nodes with low suspicion of malignant involvement, focusing time on sampling nodes/masses of greater suspicion.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Avaliação Rápida no Local , Estudos Retrospectivos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Pulmão/patologia , Broncoscopia/métodos , Linfonodos/patologia
3.
Nat Commun ; 14(1): 1215, 2023 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-36869085

RESUMO

Diagnosis of drug-induced liver injury (DILI) and its distinction from other liver diseases are significant challenges in drug development and clinical practice. Here, we identify, confirm, and replicate the biomarker performance characteristics of candidate proteins in patients with DILI at onset (DO; n = 133) and follow-up (n = 120), acute non-DILI at onset (NDO; n = 63) and follow-up (n = 42), and healthy volunteers (HV; n = 104). Area under the receiver operating characteristic curve (AUC) for cytoplasmic aconitate hydratase, argininosuccinate synthase, carbamoylphosphate synthase, fumarylacetoacetase, fructose-1,6-bisphosphatase 1 (FBP1) across cohorts achieved near complete separation (range: 0.94-0.99) of DO and HV. In addition, we show that FBP1, alone or in combination with glutathione S-transferase A1 and leukocyte cell-derived chemotaxin 2, could potentially assist in clinical diagnosis by distinguishing NDO from DO (AUC range: 0.65-0.78), but further technical and clinical validation of these candidate biomarkers is needed.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Proteômica , Humanos , Argininossuccinato Sintase , Biomarcadores , Antígenos CD8 , Frutose
4.
Frontline Gastroenterol ; 12(2): 102-107, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613940

RESUMO

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) affects approximately one in four adults of the general population, with an important minority of cases at high risk of developing cirrhosis. We evaluated the utility of a primary care NAFLD pathway incorporating a specialist nurse-led NAFLD clinic and a two-step testing approach for advanced liver fibrosis. DESIGN/METHOD: We performed a retrospective evaluation of prospectively collected demographic and clinical data on all patients diagnosed with NAFLD and intermediate NAFLD fibrosis score seen in our nurse-led NAFLD clinic between 1 May 2014 and 30 April 2017. Patients were assessed using a specific clerking pro forma and transient elastography (TE). Discharge to primary care with lifestyle advice was considered where TE<7.9 kPa. RESULTS: 904 patients were identified, 114 (12.6%) of whom did not meet NAFLD criteria. Among the NAFLD population (n=790 (87.4%)), TE<7.9 kPa was present in 558 patients (70.6%), 519 of whom were discharged to primary care. Selected patients were followed up in secondary care despite TE<7.9 kPa or discharged with TE≥7.9 kPa. TE was unreliable in 22 patients (2.7%). Overall, 559 (70.8%) of patients with confirmed NAFLD were discharged from the nurse-led clinic. Introduction of the new pathway was associated with increased screening for hepatitis B and C viruses in primary care, and 17 new cases of alpha-1-antitrypsin deficiency were identified. CONCLUSION: An integrated primary/secondary care NAFLD pathway, including a specialist nurse-led clinic may be a useful way of managing increasing demand on secondary care hepatology services.

5.
Gastroenterology ; 158(6): 1597-1610.e7, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31987796

RESUMO

BACKGROUND & AIMS: Dysbiosis of the intestinal microbiota has been associated with nonalcoholic fatty liver disease (NAFLD). We investigated whether administration of a synbiotic combination of probiotic and prebiotic agents affected liver fat content, biomarkers of liver fibrosis, and the composition of the fecal microbiome in patients with NAFLD. METHODS: We performed a double-blind phase 2 trial of 104 patients with NAFLD in the United Kingdom. Participants (mean age, 50.8 ± 12.6 years; 65% men; 37% with diabetes) were randomly assigned to groups given the synbiotic agents (fructo-oligosaccharides, 4 g twice per day, plus Bifidobacterium animalis subspecies lactis BB-12; n = 55) or placebo (n = 49) for 10-14 months. Liver fat content was measured at the start and end of the study by magnetic resonance spectroscopy, and liver fibrosis was determined from a validated biomarker scoring system and vibration-controlled transient elastography. Fecal samples were collected at the start and end of the study, the fecal microbiome were analyzed by 16S ribosomal DNA sequencing. RESULTS: Mean baseline and end-of-study magnetic resonance spectroscopy liver fat percentage values were 32.3% ± 24.8% and 28.5% ± 20.1% in the synbiotic group and 31.3% ± 22% and 25.2% ± 17.2% in the placebo group. In the unadjusted intention-to-treat analysis, we found no significant difference in liver fat reduction between groups (ß = 2.8; 95% confidence interval, -2.2 to 7.8; P = .30). In a fully adjusted regression model (adjusted for baseline measurement of the outcome plus age, sex, weight difference, and baseline weight), only weight loss was associated with a significant decrease in liver fat (ß = 2; 95% confidence interval, 1.5-2.6; P = .03). Fecal samples from patients who received the synbiotic had higher proportions of Bifidobacterium and Faecalibacterium species, and reductions in Oscillibacter and Alistipes species, compared with baseline; these changes were not observed in the placebo group. Changes in the composition of fecal microbiota were not associated with liver fat or markers of fibrosis. CONCLUSIONS: In a randomized trial of patients with NAFLD, 1 year of administration of a synbiotic combination (probiotic and prebiotic) altered the fecal microbiome but did not reduce liver fat content or markers of liver fibrosis. (ClinicalTrials.gov, Number: NCT01680640).


Assuntos
Disbiose/dietoterapia , Microbioma Gastrointestinal/efeitos dos fármacos , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Simbióticos/administração & dosagem , Adulto , Bifidobacterium animalis , Biomarcadores/análise , Biópsia , Método Duplo-Cego , Disbiose/complicações , Técnicas de Imagem por Elasticidade , Fezes/microbiologia , Feminino , Humanos , Lipídeos/análise , Fígado/química , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/prevenção & controle , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Oligossacarídeos/administração & dosagem , Estudo de Prova de Conceito , Reino Unido
6.
Frontline Gastroenterol ; 8(4): 252-259, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29067150

RESUMO

OBJECTIVE: Guidelines for the assessment of non-alcoholic fatty liver disease (NAFLD) have been published in 2016 by National Institute for Health and Care Excellence and European Associations for the study of the Liver-European Association for the study of Diabetes-European Association for the study of Obesity. Prior to publication of these guidelines, we performed a cross-sectional survey of gastroenterologists and hepatologists regarding NAFLD diagnosis and management. DESIGN: An online survey was circulated to members of British Association for the Study of the Liver and British Society of Gastroenterology between February 2016 and May 2016. RESULTS: 175 gastroenterologists/hepatologists responded, 116 completing the survey, representing 84 UK centres. 22% had local NAFLD guidelines. 45% received >300 referrals per year from primary care for investigation of abnormal liver function tests (LFTs). Clinical assessment tended to be performed in secondary rather than primary care including body mass index (82% vs 26%) and non-invasive liver screen (86% vs 32%) and ultrasound (81% vs 37%). Widely used tools for non-invasive fibrosis risk stratification were aspartate transaminase (AST)/alanine transaminase (ALT) ratio (53%), Fibroscan (50%) and NAFLD fibrosis score (41%). 78% considered liver biopsy in selected cases. 50% recommended 10% weight loss target as first-line treatment. Delivery of lifestyle interventions was mostly handed back to primary care (56%). A minority have direct access to community weight management services (22%). Follow-up was favoured by F3/4 fibrosis (72.9%), and high-risk non-invasive fibrosis tests (51%). Discharge was favoured by simple steatosis at biopsy (30%), and low-risk non-invasive scores (25%). CONCLUSIONS: The survey highlights areas for improvement of service provision for NAFLD assessment including improved recognition of non-alcoholic steatohepatitis in people with type 2 diabetes, streamlining abnormal LFT referral pathways, defining non-invasive liver fibrosis assessment tools, use of liver biopsy, managing metabolic syndrome features and improved access to lifestyle interventions.

8.
BMJ Support Palliat Care ; 2(2): 150-5, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24654057

RESUMO

OBJECTIVES: The All Wales Care Pathway for the End of Life Pathway aims to ensure evidence-based end-of-life care is available across Wales. Implementation of end-of-life care processes was evaluated in a national audit of deaths between July 2007 and June 2009. METHODS: Up to 60 records of deceased patients were reviewed by two researchers from hospital (24), community localities (20), hospice and specialist inpatient (9) settings. Data extraction using a standard template was carried out at all sites to indicate whether end-of-life care processes had been implemented. A total of 1184 records were retrieved. 202 records were excluded due to sudden death (eg, cardiac arrest) or incomplete data. Sampling included 580 decedents (59%) who had received end-of-life care through the pathway. RESULTS: Pathway use was associated with improved implementation of all evidence-based clinical standards other than for daily review, where implementation was consistently high with (84.5%) or without the pathway (81%). Differences in achievement were most evident for the implementation of bereavement and spiritual support where the pathway was used. Implementation within hospice and specialist inpatient care settings was consistently high. CONCLUSION: Integrated care pathway use is associated with the implementation of best practice in end-of-life care. However, variation in implementation across sites and the influence of setting type highlights the mediating effect of organisational context which, together with different methods of feedback, may provide a useful agenda for implementation research within end-of-life care.


Assuntos
Assistência Terminal/organização & administração , Assistência Terminal/normas , Luto , Procedimentos Clínicos , Prestação Integrada de Cuidados de Saúde , Hospitais para Doentes Terminais/normas , Humanos , Auditoria Médica , Apoio Social , Fatores Socioeconômicos , País de Gales
9.
Gastroenterology ; 141(1): 320-5, 325.e1-2, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21600205

RESUMO

BACKGROUND & AIMS: Polymorphisms in the interleukin-28B (IL28B) gene are associated with outcomes from infection with hepatitis C virus (HCV). However, the role of these polymorphisms in protecting injection drug users who are at high risk for HCV infection but do not have detectable antibodies against HCV or HCV RNA (exposed uninfected) has not been demonstrated. We investigated whether these individuals have the IL28B genotype rs12979860-CC, which protects some individuals against HCV infection. METHODS: Seventy-four exposed uninfected individuals, 89 spontaneous resolvers, and 234 chronically infected individuals were genotyped to determine single nucleotide polymorphisms at IL28B.rs12979860. RESULTS: Exposed, uninfected individuals had a significantly lower frequency of the protective genotype (rs12979860-CC) than anti-HCV-positive spontaneous resolvers (41.9% vs 69.7%, respectively; P=.0005; odds ratio [OR], 0.31; 95% confidence interval [CI]: 0.16-0.60) but a similar frequency to patients who were chronically infected (41.9% vs 43.6%, respectively; P=ns). However, exposed, uninfected individuals had a significantly higher frequency of homozygosity for killer cell immunoglobulin-like receptor 2DL3:group 1 HLA-C (KIR2DL3:HLA-C1) than those with chronic infection (31.1% vs 13.3%, respectively; P=.0008; OR, 2.95; 95% CI: 1.59-5.49). For patients who spontaneously resolved infection, IL28B and KIR:HLA protected, independently, against chronic HCV infection, based on logistic regression and synergy analyses (synergy factor, 1.3; 95% CI: 0.37-4.75; P synergy=.6). CONCLUSIONS: IL28B and KIR2DL3:HLA-C1 are independently associated with spontaneous resolution of viremia following HCV exposure. Resistance to HCV infection in exposed uninfected cases is associated with homozygosity for KIR2DL3:HLA-C1 but not the single nucleotide polymorphism IL28B.rs12979860. Uninfected individuals are therefore a distinct population from patients who spontaneously resolve HCV infection. Distinct, nonsynergistic innate immune mechanisms can determine outcomes of HCV exposure.


Assuntos
Hepatite C Crônica/genética , Hepatite C Crônica/prevenção & controle , Hepatite C/genética , Hepatite C/prevenção & controle , Imunidade Inata/genética , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Progressão da Doença , Feminino , Frequência do Gene , Predisposição Genética para Doença , Antígenos HLA-C/genética , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite C/diagnóstico , Hepatite C/imunologia , Anticorpos Anti-Hepatite C/sangue , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/imunologia , Humanos , Interferons , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , RNA Viral/sangue , Receptores KIR2DL3/genética , Remissão Espontânea , Medição de Risco , Fatores de Risco , Reino Unido , Carga Viral
10.
Biochem Biophys Res Commun ; 407(2): 277-82, 2011 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-21300026

RESUMO

Myofibroblastic, activated hepatic stellate cells (HSC) play a pivotal role in the development of liver fibrosis through the secretion of fibrillar collagens and the tissue inhibitors of metalloproteinase (TIMP)-1 and -2. TIMPs are believed to promote hepatic fibrosis by inhibiting both matrix degradation and apoptosis of HSC. In other cell types, there is evidence that TIMP-1 has effects on proliferation, however the role of TIMPs in the regulation of HSC proliferation remains unexplored. Therefore, we have used short interfering RNA (siRNA) to investigate the effects of autocrine TIMP-1 and -2 on HSC proliferation. TIMP-1 and -2 siRNA were highly effective, producing peak target protein knockdown compared to negative control siRNA of 92% and 63%, respectively. Specific silencing of TIMP-1, using siRNA, significantly reduced HSC proliferation. TIMP-1 was localised in part to the HSC nucleus and TIMP-1 siRNA resulted in loss of both cytoplasmic and nuclear TIMP-1. Attenuated proliferation was associated with reduced Akt phosphorylation and was partially rescued by addition of recombinant TIMP-1. We have revealed a novel autocrine mitogenic effect of TIMP-1 on HSC, which may involve Akt-dependent and specific nuclear mechanisms of action. We suggest that TIMP-1 might promote liver fibrosis by means other than its previously described anti-apoptotic effect on HSC. Moreover, these findings, together with our previous reports and the emerging data from in vivo studies of TIMP inhibition, provide strong evidence that TIMP-1 is mechanistically central to liver fibrosis and an important potential therapeutic target.


Assuntos
Proliferação de Células , Células Estreladas do Fígado/fisiologia , Cirrose Hepática/genética , RNA Interferente Pequeno/genética , Inibidor Tecidual de Metaloproteinase-3/fisiologia , Animais , Células Cultivadas , Inativação Gênica , Células Estreladas do Fígado/citologia , Masculino , Camundongos , Camundongos Knockout , Ratos , Ratos Sprague-Dawley , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidor Tecidual de Metaloproteinase-2/fisiologia , Inibidor Tecidual de Metaloproteinase-3/genética
11.
Adv Ther ; 27(8): 512-22, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20652658

RESUMO

More than 180 million people worldwide have chronic hepatitis C (CHC) virus infection, a major cause of liver cirrhosis and its life-threatening complications including liver failure, portal hypertension, and hepatocellular carcinoma. With the current standard of care of pegylated interferon-alpha and ribavirin (PEG-IFN-alpha/RBV), the chances of sustained viral clearance or "cure" are only 40%-50% for genotype 1 infection, which is the most common genotype in western populations. Consequently, there has been a drive to develop new agents specifically targeting essential components of the viral life cycle, such as the hepatitis C virus (HCV) NS3/4A serine protease. Perhaps the most advanced HCV protease inhibitor in clinical development is telaprevir, which has been shown to improve treatment outcomes when combined with PEG-IFN-alpha/RBV in genotype 1 infection, and is currently undergoing phase 3 study. In this review, we summarize the pharmacology, pharmacokinetics, and results of phase 1 and 2 clinical trials of telaprevir, and discuss the likely role of this agent in the future management of CHC.


Assuntos
Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Oligopeptídeos , Antivirais/uso terapêutico , Ensaios Clínicos como Assunto , Sinergismo Farmacológico , Predisposição Genética para Doença , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/genética , Hepatite C Crônica/fisiopatologia , Humanos , Interferon-alfa/uso terapêutico , Cirrose Hepática/etiologia , Oligopeptídeos/farmacologia , Ribavirina/uso terapêutico , Inibidores de Serina Proteinase/genética , Inibidores de Serina Proteinase/uso terapêutico , Resultado do Tratamento
12.
Hepatology ; 51(4): 1168-75, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20077564

RESUMO

UNLABELLED: Natural killer cells are a key component in the immune control of viral infections. Their functions are controlled by inhibitory receptors for major histocompatability complex (MHC) class I, including the killer cell immunoglobulin-like receptors (KIR). KIR2DL3 in combination with its cognate human leukocyte antigen (HLA)-C ligand has been shown to be associated with spontaneous resolution of viremia following hepatitis C virus (HCV) infection. In order to determine if this gene combination is advantageous across all potential outcomes following HCV exposure, we studied individuals with apparent resistance to HCV infection who remain seronegative and aviremic despite long-term injection drug use and also individuals chronically infected with HCV who successfully clear HCV with treatment. Homozygosity for KIR2DL3 in combination with group 1 HLA-C allotypes was more frequent in exposed seronegative aviremic individuals as compared to those with chronic HCV (25.0% versus 9.7%, P = 0.003, odds ratio [OR] = 3.1, 95% confidence interval [CI] = 1.3-7.1) in a model similar to that found for those spontaneously resolving HCV. In individuals undergoing treatment for HCV, those with KIR2DL3 and group 1 HLA-C were more likely to make a sustained virological response (SVR) (P = 0.013, OR = 2.3, 95% CI = 1.1-4.5). KIR and HLA-C protection in both treatment response and spontaneously resolving HCV was validated at the allelic level, in which KIR2DL3-HLA-Cw*03 was associated with SVR (P = 0.004, OR = 3.4, 95% CI = 1.5-8.7) and KIR2DL3/KIR2DL3-HLA-Cw*03 was associated with spontaneous resolution of HCV infection (P = 0.01, OR = 2.3, 95% CI = 1.2-4.4). CONCLUSION: KIR and HLA-C genes are consistently beneficial determinants in the outcome of HCV infection. This advantage extends to the allelic level for both gene families.


Assuntos
Antígenos HLA-C/fisiologia , Hepatite C/imunologia , Receptores KIR2DL3/fisiologia , Adulto , Feminino , Antígenos HLA-C/genética , Humanos , Masculino , Pessoa de Meia-Idade , Receptores KIR2DL3/genética
13.
Liver Int ; 28(6): 889-91, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18647143

RESUMO

We report an apparently unique case where hepatitis C virus (HCV) RNA was identified in renal tissue from a patient with membranoproliferative glomerulonephritis and treated chronic hepatitis C, despite the absence of detectable virus in the serum or liver (COBAS Amplicor qualitative assay, lower limit of detection 50 IU/ml). The implications of this finding are discussed, with particular reference to current concepts regarding 'occult' hepatitis C infection.


Assuntos
Glomerulonefrite Membranoproliferativa/virologia , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Rim/virologia , Glomerulonefrite Membranoproliferativa/sangue , Glomerulonefrite Membranoproliferativa/patologia , Hepacivirus/genética , Hepatite C Crônica/sangue , Hepatite C Crônica/patologia , Humanos , Rim/patologia , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue
17.
Dig Dis ; 24(1-2): 174-83, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16699275

RESUMO

Liver fibrosis occurs as a result of a wide range of injurious processes and in its end-stage results in cirrhosis. This gross disruption of liver architecture is associated with impaired hepatic function, portal hypertension and significant resultant morbidity and mortality. Indeed, liver fibrosis and cirrhosis represent a major worldwide healthcare burden. Recent progress in liver transplantation, the management of portal hypertension and the treatment of chronic viral hepatitis have had an important impact. However, these approaches are not without their limitations - in particular, issues regarding organ availability for transplantation - and serve to highlight the urgent requirement to influence pharmacologically the underlying fibrotic process in many patients. Liver fibrosis has been shown to be a bidirectional process and increasing data from laboratory and clinical studies reveal that even advanced fibrosis and cirrhosis are potentially reversible. Exploration of the molecular mechanisms underlying this bi-directionality will lead to char acterisation of the essential attributes of an antifibrotic therapy. In this review, these mechanisms are highlighted and the growing number of emerging antifibrotic agents discussed.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Humanos , Cirrose Hepática/patologia , Resultado do Tratamento
18.
BMC Palliat Care ; 3(1): 1, 2004 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-15113420

RESUMO

BACKGROUND: Although guidelines for the care of the dying patient exist the evidence base to support the guidelines is poor. Some of the factors contributing to this include failure to recruit to trials, protective healthcare professionals and subsequent attrition from trials due to the death of the patients. Recent studies report favourably on the use of cluster randomisation as an appropriate methodology for use in this patient group. METHODS/DESIGN: A feasibility study, exploring two types of randomisation as appropriate methodology for trials involving dying patients. Cluster randomisation and randomised consent will be utilised following a crossover design at two sites, one oncology ward and one Macmillan unit within the Northwest Wales NHS Trust. All patients commencing on the Integrated Care Pathway (ICP) for the Last Days of Life will be eligible for inclusion in the study. Using the hypothesis that it is not necessary to prescribe an anti-emetic medication when setting up a syringe driver for the dying patient, the study will evaluate different models of research methodology. DISCUSSION: The identification of the most appropriate methodology for use in studies concerning this patient group will inform the development of future clinical studies. Furthermore, the outcomes of this feasibility study will inform the development, of a proposal seeking funding for Wales-wide trials in palliative care. The identification of an appropriate methodology will provide a starting point for the establishment of a robust evidence base for the care of the dying patient.

19.
Int J Palliat Nurs ; 8(12): 566-73, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12560798

RESUMO

Functional benchmarking assesses performance and practice across a broad range of settings and carries the potential to effect change in practice. An integrated care pathway (ICP) can assist in the benchmarking process, defining desired outcomes for specific patient groups over a designated time frame. Any variations to the agreed course of care are documented using the 'variance sheet'. This article describes the Wales-wide implementation of an ICP for the last two days of life. The project has enabled an ongoing centralized collection and analysis of variance sheets, which reflect the care of the dying patient in four different care settings crossing the voluntary and statutory sectors. Initial analysis of the first 500 variance sheets to be generated by the ICP for the last two days of life indicates that the management of pain, agitation, excess respiratory secretions and mouth care may be problematic. The same problems were experienced across acute, hospice, specialist inpatient units and community care. Closing the audit cycle involves incorporating the information from the variance analysis into clinical practice.


Assuntos
Benchmarking/organização & administração , Procedimentos Clínicos/organização & administração , Auditoria de Enfermagem/organização & administração , Cuidados Paliativos/normas , Assistência Terminal/normas , Análise de Variância , Educação Continuada em Enfermagem/organização & administração , Medicina Baseada em Evidências , Humanos , Pesquisa em Avaliação de Enfermagem , Recursos Humanos de Enfermagem/educação , Projetos Piloto , Gestão da Qualidade Total/organização & administração , País de Gales
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA