RESUMO
OBJECTIVE: There is a lack of robust data on significant gastrointestinal bleeding in older people using aspirin. We calculated the incidence, risk factors and absolute risk using data from a large randomised, controlled trial. DESIGN: Data were extracted from an aspirin versus placebo primary prevention trial conducted throughout 2010-2017 ('ASPirin in Reducing Events in the Elderly (ASPREE)', n=19 114) in community-dwelling persons aged ≥70 years. Clinical characteristics were collected at baseline and annually. The endpoint was major GI bleeding that resulted in transfusion, hospitalisation, surgery or death, adjudicated independently by two physicians blinded to trial arm. RESULTS: Over a median follow-up of 4.7 years (88 389 person years), there were 137 upper GI bleeds (89 in aspirin arm and 48 in placebo arm, HR 1.87, 95% CI 1.32 to 2.66, p<0.01) and 127 lower GI bleeds (73 in aspirin and 54 in placebo arm, HR 1.36, 95% CI 0.96 to 1.94, p=0.08) reflecting a 60% increase in bleeding overall. There were two fatal bleeds in the placebo arm. Multivariable analyses indicated age, smoking, hypertension, chronic kidney disease and obesity increased bleeding risk. The absolute 5-year risk of bleeding was 0.25% (95% CI 0.16% to 0.37%) for a 70 year old not on aspirin and up to 5.03% (2.56% to 8.73%) for an 80 year old taking aspirin with additional risk factors. CONCLUSION: Aspirin increases overall GI bleeding risk by 60%; however, the 5-year absolute risk of serious bleeding is modest in younger, well individuals. These data may assist patients and their clinicians to make informed decisions about prophylactic use of aspirin. TRIAL REGISTRATION NUMBER: ASPREE. NCT01038583.
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Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Método Duplo-Cego , Feminino , Humanos , Incidência , Vida Independente , Masculino , Prevenção Primária , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
The role of aspirin for primary prevention in older adults with chronic kidney disease (CKD) is unclear. Therefore, post hoc analysis of the randomized controlled trial ASPirin in Reducing Events in the Elderly (ASPREE) was undertaken comparing 100 mg of enteric-coated aspirin daily against matching placebo. Participants were community dwelling adults aged 70 years and older in Australia, 65 years and older in the United States, all free of a history of dementia or cardiovascular disease and of any disease expected to lead to death within five years. CKD was defined as present at baseline if either eGFR under 60mL/min/1.73m2 or urine albumin to creatinine ratio 3 mg/mmol or more. In 4758 participants with and 13004 without CKD, the rates of a composite endpoint (dementia, persistent physical disability or death), major adverse cardiovascular events and clinically significant bleeding in the CKD participants were almost double those without CKD. Aspirin's effects as estimated by hazard ratios were generally similar between CKD and non-CKD groups for dementia, persistent physical disability or death, major adverse cardiovascular events and clinically significant bleeding. Thus, in our analysis aspirin did not improve outcomes in older people while increasing the risk of bleeding, with mostly consistent effects in participants with and without CKD.
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Doenças Cardiovasculares , Insuficiência Renal Crônica , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Austrália , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Hemorragia/induzido quimicamente , Humanos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/tratamento farmacológico , Estados UnidosRESUMO
BACKGROUND: Aspirin is a well-established therapy for the secondary prevention of cardiovascular events. However, its role in the primary prevention of cardiovascular disease is unclear, especially in older persons, who have an increased risk. METHODS: From 2010 through 2014, we enrolled community-dwelling men and women in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability. Participants were randomly assigned to receive 100 mg of enteric-coated aspirin or placebo. The primary end point was a composite of death, dementia, or persistent physical disability; results for this end point are reported in another article in the Journal. Secondary end points included major hemorrhage and cardiovascular disease (defined as fatal coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal stroke, or hospitalization for heart failure). RESULTS: Of the 19,114 persons who were enrolled in the trial, 9525 were assigned to receive aspirin and 9589 to receive placebo. After a median of 4.7 years of follow-up, the rate of cardiovascular disease was 10.7 events per 1000 person-years in the aspirin group and 11.3 events per 1000 person-years in the placebo group (hazard ratio, 0.95; 95% confidence interval [CI], 0.83 to 1.08). The rate of major hemorrhage was 8.6 events per 1000 person-years and 6.2 events per 1000 person-years, respectively (hazard ratio, 1.38; 95% CI, 1.18 to 1.62; P<0.001). CONCLUSIONS: The use of low-dose aspirin as a primary prevention strategy in older adults resulted in a significantly higher risk of major hemorrhage and did not result in a significantly lower risk of cardiovascular disease than placebo. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583 .).
Assuntos
Aspirina/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Hemorragia/induzido quimicamente , Inibidores da Agregação Plaquetária/uso terapêutico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Austrália , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Método Duplo-Cego , Feminino , Hemorragia/epidemiologia , Humanos , Vida Independente , Masculino , Inibidores da Agregação Plaquetária/efeitos adversos , Falha de Tratamento , Estados UnidosRESUMO
BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) account for a large and growing proportion of liver disease burden globally. The burden of NAFLD/NASH manifests in increasing levels of advanced liver disease and primary liver cancer in Australia. A Markov model was used to forecast NAFLD burden in Australia through 2030. METHODS: A model was used to estimate fibrosis progression, primary liver cancer, and liver deaths among the Australian NAFLD population, with changes in incident NAFLD cases based on long-term trends for changes in the prevalence of obesity. Published estimates and surveillance data were applied to build and validate the model projections, including surveillance data for the incidence of liver cancer. RESULTS: Prevalent NAFLD cases were projected to increase 25% from the current burden (5 551 000 [4 748 000-6 306 000] cases in 2019) to 7 024 000 [5 838 000-7 886 000] cases in 2030. The projected increase in the number of NASH cases (40%) was greater than that of NAFLD cases. Incident cases of advanced liver disease are projected to increase up to 85% by 2030, and incident NAFLD liver deaths are estimated to increase 85% from 1900 (1100-3300) deaths in 2019 to 3500 (2100-6100) deaths in 2030. CONCLUSIONS: Restraining growth of the obese and diabetic populations, along with potential therapeutic options, will be essential for mitigating disease burden.
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Efeitos Psicossociais da Doença , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Austrália , Criança , Pré-Escolar , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Lactente , Falência Hepática/epidemiologia , Falência Hepática/etiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Transplante de Fígado , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Modelos Estatísticos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/mortalidade , Hepatopatia Gordurosa não Alcoólica/terapia , Obesidade/epidemiologia , Prevalência , Fatores de Tempo , Adulto JovemRESUMO
Non-alcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease in the Australian population, although precise estimates of prevalence are lacking. NAFLD may progress to liver fibrosis, cirrhosis, decompensated liver disease, and liver cancer and is becoming an increasingly common indication for liver transplantation in Australia and New Zealand. There is an extrahepatic burden of NAFLD extending beyond the liver, which is manifested by an increased risk of developing cardiovascular disease, diabetes, and chronic renal impairment, all of which are common causes of morbidity in the Australian population. Early recognition of those patients at high risk of developing advanced liver disease is essential in order to target those who will benefit from intensive lifestyle modification. In this review, we present data on the epidemiology of NAFLD within Australia, its associated health burden in terms of hepatic and extrahepatic complications, common clinical presentations, and indications for treatment. We also propose a research agenda that highlights knowledge needed to improve diagnosis and management specific to the Australian context.
Assuntos
Efeitos Psicossociais da Doença , Hepatopatia Gordurosa não Alcoólica , Austrália/epidemiologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/prevenção & controle , Progressão da Doença , Diagnóstico Precoce , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/prevenção & controle , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/prevenção & controle , Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Prevalência , RiscoRESUMO
BACKGROUND & AIMS: Noninvasive scoring systems for fibrosis are increasingly used in the clinic and in research because of their ease of use, accessibility, and low cost. However, test performance characteristics were established in groups of patients with a high prevalence of advanced fibrosis; little is known about diagnostic accuracy in low-risk populations. METHODS: In a cross-sectional study, 922 members of a general ambulatory population in Hong Kong (randomly selected; 18-70 years old) underwent clinical assessment from May 2008 through December 2010. All participants completed a standard questionnaire that collected information on age, sex, and history of smoking and alcohol use. Results of fasting blood tests and transient elastography were used as the reference standard to identify patients with advanced fibrosis. We assessed performance characteristics of 3 noninvasive fibrosis scoring systems: the nonalcoholic fatty liver disease fibrosis scoring system, the Fibrosis-4 scoring system, and aspartate transaminase to platelet ratio index, using standard thresholds. To calculate diagnostic test characteristics, we constructed a 2-by-2 table with the presence or absence of advanced fibrosis according to the transient elastography reading against the presence or absence of advanced fibrosis according to the scoring systems. Area under the receiver operating curve was calculated to assess overall diagnostic accuracy. RESULTS: Of the 922 individuals evaluated by transient elastography, 749 had a valid reading and 15 had advanced fibrosis (2%). The specificity of noninvasive scores in detection of advanced fibrosis approximated 100% (95% confidence interval [CI], 99%-100%), with a negative predictive value of 98% (95% CI, 97%-99%) for all systems. However, the scoring systems detected fibrosis with a low level of sensitivity, ranging from 7% (95% CI, 0%-32%) to 13% (95% CI, 2%-40%). Positive predictive values ranged from 50% (95% CI, 7%-93%) to 67% (95% CI, 9%-99%). Their negative likelihood ratios ranged from 0.87 (95% CI, 0.71%-1.06%) to 0.93 (95% CI, 0.82%-1.07%); positive likelihood ratios were uninformative because of the small number of people with positive scores. CONCLUSIONS: In low-risk populations, negative results from noninvasive scoring systems reliably exclude advanced fibrosis, without requirements for further tests. Positive test results are often a false-positive result and should prompt further testing.
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Análise Química do Sangue/métodos , Testes Diagnósticos de Rotina/métodos , Técnicas de Imagem por Elasticidade/métodos , Cirrose Hepática/diagnóstico , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto JovemRESUMO
AIM OF THE STUDY: The aim of the study was to determine the excess risk of all-cause and cardiovascular mortality in older people with elevated liver enzymes [alanine transaminase (ALT) and gamma glutamyltransferase (GGT)]. METHODS: We utilized data from a large, prospective, population based study of 2061 people aged 50 to 99 years with linkage to a National Death Registry. Participants were categorized as having elevated liver enzymes using standard thresholds (for males, GGT>51 and ALT>40 IU/L, and GGT>33 and ALT>31 IU/L for females). Adjusted Cox proportional hazards models assessed the association of elevated liver enzymes and mortality with long duration follow-up. RESULTS: Over a median follow-up of 10 years (20,145 person years), 701 people died, including 203 (34%) from cardiovascular disease. Cox regression models adjusted for sex, age, smoking, and alcohol intake indicated that people with elevated liver enzymes had an increased risk of all-cause mortality that was modified by age (test for interaction P=0.01). Age-stratified analyses demonstrated no increased risk at younger ages [age 59 y and below; hazard ratio (HR): 0.46; 95% confidence interval, 0.06-3.49], but increased risk with age; age 60 to 69, HR: 1.05 (0.53-2.07), age 70 to 79 years, HR: 1.54 (0.81 to 2.93), and age 80 years and above, HR: 3.53 (1.55 to 8.04). Similarly, the risk of cardiovascular mortality with elevated liver enzymes was also modified by, and increased with age (test for interaction P=0.02); age 70 to 79, HR: 3.15 (1.37 to 7.23), age 80 years and above, HR: 6.86 (2.44 to 19.30). CONCLUSIONS: In community-dwelling elderly persons, an elevation in both ALT and GGT are associated with an excess risk of all-cause and cardiovascular mortality which increases with age.
Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Doenças Cardiovasculares/mortalidade , Hepatopatias/mortalidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Causas de Morte , Ensaios Enzimáticos Clínicos , Feminino , Humanos , Hepatopatias/sangue , Hepatopatias/diagnóstico , Masculino , Pessoa de Meia-Idade , New South Wales , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores de Tempo , Regulação para CimaRESUMO
BACKGROUND AND AIM: Elevated alanine transaminase (ALT) is a strong predictor of metabolic syndrome, but there are few data from the Australian population. We aimed to determine the prevalence of elevated ALT and association with metabolic risk factors. METHODS: In this cross-sectional study including adult participants (N = 9,447) from a nationwide, population-based survey, we assessed the prevalence of elevated ALT [defined as ≥ 40 IU/L (men) and ≥ 30 IU/L (women) as baseline, and ALT as ≥ 30 IU/L (men) and ≥ 19 IU/L (women) as lower threshold], distribution of metabolic risk factors, and independent predictors of elevated ALT in logistic regression models. Analyses were weighted to the population with population weights. RESULTS: Elevated ALT levels were found in 11.2% of the Australian population. People with elevated ALT were younger (43 vs 46 yrs) with more truncal adiposity (100 vs 91 cm), higher pro-atherogenic lipids and glucose and exercised less (120 vs 160 min per week, P < 0.05 for all analyses). Regression analyses indicated that younger age, male sex, diabetes, triglycerides, apolipoprotein B, and waist circumference were independent predictors of elevated ALT. The population attributable fraction of elevated ALT due to truncal obesity was estimated at 47%. CONCLUSION: These data demonstrate a high prevalence of elevated ALT in the general population that is closely associated with metabolic risk factors. Individuals with elevated ALT should be evaluated for co-existent metabolic disorders.
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Alanina Transaminase/sangue , Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , Adulto , Austrália/epidemiologia , Estudos de Coortes , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Fatores de RiscoAssuntos
Hepatopatia Gordurosa não Alcoólica , China , França , Alemanha , Humanos , Itália , Japão , Espanha , Reino Unido , Estados UnidosRESUMO
UNLABELLED: Nonalcoholic steatohepatitis (NASH) is the commonest liver disease in developed countries. However, there are no current data on the cost-effectiveness of therapeutic options such as lifestyle modification, pioglitazone, or vitamin E. We undertook a cost utility analysis to compare these strategies. Using a third-party payer perspective, a deterministic Markov model was developed to compare costs and health benefits of lifestyle modification alone or with pioglitazone or vitamin E in a cohort of patients aged 50 years with biopsy-proven NASH and fibrosis level 3 or greater. We assumed an annual cycle length over a lifetime horizon. Probability and utility estimates were derived from a systematic literature review, and uncertainties in parameter estimates were tested using one- and two-way sensitivity analyses. Our outcome measure was the incremental cost-effectiveness ratio (ICER), with $A50,000 or less considered cost-effective. In comparison with lifestyle modification alone, treatment with either pioglitazone or vitamin E in addition to lifestyle modification was cost-effective, with incremental cost-effectiveness ratios of $A2748 and $A8475 per quality-adjusted life year (QALY) gained, respectively. In a direct comparison, pioglitazone was more cost-effective than vitamin E (ICER $A2,056/QALY gained). Sensitivity analyses indicated that pioglitazone was not cost-effective if either the total drug cost was greater than $A16,000 per annum, or the annual probability of developing cirrhosis in advanced fibrosis was less than 2%. CONCLUSION: Our modeled analyses suggest that in patients with advanced fibrosis due to NASH, pharmacological treatment in addition to standard lifestyle modification is likely to be cost-effective.
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Fígado Gorduroso/economia , Fígado Gorduroso/terapia , Hipoglicemiantes/economia , Tiazolidinedionas/economia , Vitamina E/economia , Vitaminas/economia , Terapia Combinada/economia , Análise Custo-Benefício , Fígado Gorduroso/complicações , Humanos , Hipoglicemiantes/uso terapêutico , Estilo de Vida , Cirrose Hepática/economia , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Cadeias de Markov , Hepatopatia Gordurosa não Alcoólica , Pioglitazona , Anos de Vida Ajustados por Qualidade de Vida , Índice de Gravidade de Doença , Tiazolidinedionas/uso terapêutico , Vitamina E/uso terapêutico , Vitaminas/uso terapêuticoRESUMO
Introduction: Data on the association between chronic kidney disease (CKD) and major hemorrhage in older adults are lacking. Methods: We used data from a double-blind randomized controlled trial of aspirin in persons aged ≥ 70 years with prospective capture of bleeding events, including hemorrhagic stroke and clinically significant bleeding. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m2 and/or urinary albumin-to-creatinine ratio (UACR) ≥ 3 mg/mmol (26.6 mg/g). We compared bleeding rates in those with and without CKD, undertook multivariable analyses, and explored effect modification with aspirin. Results: Of 19,114 participants, 17,976 (94.0%) had CKD status recorded, of whom 4952 (27.5%) had CKD. Participants with CKD had an increased rate of major bleeding events compared with those without CKD (10.4/1000 vs. 6.3/1000 person-years [py], respectively) and increased bleeding risk (risk ratio [RR] 1.60; 95% confidence interval [CI]: 1.40, 1.90 for eGFR < 60 ml/min per 1.73 m2) and RR (2.10; 95% CI: 1.70, 2.50) for albuminuria. In adjusted analyses, CKD was associated with a 35% increased risk of bleeding (hazard ratio [HR] 1.37; 95% CI: 1.15, 1.62; P < 0.001). Other risk factors were older age, hypertension, smoking, and aspirin use. There was no differential effect of aspirin on bleeding by CKD status (test of interaction P = 0.65). Conclusion: CKD is independently associated with an increased risk of major hemorrhage in older adults. Increased awareness of modifiable risk factors such as discontinuation of unnecessary aspirin, blood pressure control, and smoking cessation in this group is warranted.
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MUTYH carriers have an increased colorectal cancer risk in case-control studies, with loss of heterozygosity (LOH) as the presumed mechanism. We evaluated cancer risk among carriers in a prospective, population-based cohort of older adults. In addition, we assessed if cancers from carriers demonstrated mutational signatures (G:C>T:A transversions) associated with early LOH. We calculated incident risk of cancer and colorectal cancer among 13,131 sequenced study participants of the ASPirin in Reducing Events in the Elderly cohort, stratified by sex and adjusting for age, smoking, alcohol use, BMI, polyp history, history of cancer, and aspirin use. MUTYH carriers were identified among 13,033 participants in The Cancer Genome Atlas and International Cancer Genome Consortium, and somatic signatures of cancers were analyzed. Male MUTYH carriers demonstrated an increased risk for overall cancer incidence [multivariable HR, 1.66; 95% confidence interval (CI), 1.03-2.68; P = 0.038] driven by increased colorectal cancer incidence (multivariable HR, 3.55; 95% CI, 1.42-8.78; P = 0.007), as opposed to extracolonic cancer incidence (multivariable HR, 1.40; 95% CI, 0.81-2.44; P = 0.229). Female carriers did not demonstrate increased risk of cancer, colorectal cancer, or extracolonic cancers. Analysis of mutation signatures from cancers of MUTYH carriers revealed no significant contribution toward early mutagenesis from widespread G:C>T:A transversions among gastrointestinal epithelial cancers. Among cancers from carriers, somatic transversions associated with base-excision repair deficiency are uncommon, suggestive of diverse mechanisms of carcinogenesis in carriers compared with those who inherit biallelic MUTYH mutations. PREVENTION RELEVANCE: Despite absence of loss of heterozygosity in colorectal cancers, elderly male MUTYH carriers appeared to be at increased of colorectal cancer.
Assuntos
Neoplasias Colorretais , DNA Glicosilases , Idoso , Aspirina , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , DNA Glicosilases/genética , Feminino , Predisposição Genética para Doença , Genômica , Humanos , Masculino , Mutação , Estudos ProspectivosRESUMO
BACKGROUND & AIMS: Non alcoholic steatohepatitis (NASH) has no approved pharmacological therapy. Insulin sensitisers such as thiazolidinediones ameliorate insulin resistance and are a potential therapeutic option. We performed a systematic review and meta-analysis of the effect of thiazolidinediones on histological and biochemical variables in NASH. METHODS: Two reviewers searched Medline, Embase, Cochrane Central, international meeting abstracts, reference lists, and contacted experts. Inclusion criteria were randomized trials of people with NASH receiving thiazolidinediones, compared with placebo or other treatments. Methodological quality was assessed in domains suggested by the Cochrane Collaboration. The primary outcome was histological improvement (fibrosis, steatosis, inflammation, hepatocellular ballooning, and NAS score). Secondary outcomes included change in alanine transaminase, insulin resistance, body mass index, weight, and adverse events. Meta-analysis used random effects with dichotomous outcomes as relative risk (RR) and continuous outcomes as mean difference (MD), both with 95% confidence intervals (CI). RESULTS: Of seven randomized trials (n=489) with histological outcomes, four were placebo controlled (n=355). Methodological quality was variable although better for placebo controlled studies. Treated participants showed improvement in fibrosis (RR 1.38, CI 1.01-1.89), steatosis (RR 2.03, CI 1.57-2.62), inflammation (RR 1.71, CI 1.32-2.21), and hepatocellular ballooning (RR 1.62, CI 1.15-2.28). Treatment increased weight by an average of 4.4 kg (CI 2.6-5.2 kg). Adverse event reporting was inconsistent and only one trial assessed quality of life. CONCLUSIONS: Thiazolidinediones modestly improve histological variables including fibrosis and hepatocellular ballooning, but at the cost of significant weight gain. Trials of longer duration and reporting of patient oriented outcomes would be informative.
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Fígado Gorduroso/tratamento farmacológico , Tiazolidinedionas/uso terapêutico , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Ensaios Clínicos Controlados Aleatórios como Assunto , Tiazolidinedionas/efeitos adversos , Resultado do TratamentoRESUMO
Demographic changes among junior doctors are driving demand for increased flexibility in advanced physician training, but flexible training posts are lacking. Suitable flexible training models include flexible full-time, job-share and part-time positions. Major barriers to establishing flexible training positions include difficulty in finding job-share partners, lack of funding for creating supernumerary positions, and concern over equivalence of educational quality compared with full-time training. Pilot flexible training positions should be introduced across the medical specialties and educational outcomes examined prospectively.
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Atitude do Pessoal de Saúde , Capacitação em Serviço/organização & administração , Corpo Clínico Hospitalar/educação , Gerenciamento do Tempo , Tolerância ao Trabalho Programado , Austrália , Escolha da Profissão , Humanos , Satisfação no Emprego , Simplificação do TrabalhoRESUMO
BACKGROUND AND AIM: Locoregional therapies for hepatocellular carcinoma (HCC) are considered to confer a survival advantage, however, the patient group that should be targeted is not clearly defined. This study aimed to determine the impact on survival of locoregional therapies compared with supportive care, within prognostic categories as stratified by the Cancer of the Liver Italian Program (CLIP) scoring system. METHODS: A prospective database was used to identify those patients who were treated with either locoregional therapy (n = 128) or supportive care (n = 92). Survival analysis was performed for groups matched by CLIP score at presentation. Comparison of important prognostic factors was undertaken and univariate and multivariate analysis was performed to assess determinants of survival. RESULTS: Use of locoregional therapies was only associated with a survival benefit in patients with a CLIP score of 1 or 2. In this group, the median survival in patients who received locoregional therapies was 25.0 months (95% confidence interval 22.7-27.4) compared with 8.9 months (95% confidence interval 7.3-10.5) for supportive care (P = 0.001). For patients with CLIP scores of 3 or greater, no survival benefit of locoregional therapies was observed. Multivariate analysis revealed locoregional intervention, CLIP score, tumor symptoms, alpha-fetoprotein level, bilirubin and alkaline phosphatase level as independent prognostic indicators. CONCLUSION: Locoregional therapies should be targeted specifically to patients with non-advanced hepatocellular carcinoma as assessed by validated scoring systems. Use of these therapies in patients with advanced disease does not appear to be associated with a survival benefit and may expose patients to unnecessary harm.
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Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Ablação por Cateter , Quimioembolização Terapêutica , Etanol/administração & dosagem , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Cuidados Paliativos , Seleção de Pacientes , Carcinoma Hepatocelular/patologia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/mortalidade , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/mortalidade , Distribuição de Qui-Quadrado , Bases de Dados como Assunto , Etanol/efeitos adversos , Feminino , Indicadores Básicos de Saúde , Humanos , Injeções , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , New South Wales , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Colorectal cancer is the third most commonly diagnosed cancer in Australia. Emerging evidence from several countries suggests increasing incidence in people aged <50 years. METHODS: We assessed colon and rectal cancer incidence trends in people aged 20+ in Australia from 1982 to 2014. We used data on 375,008 incident cases (248,162 colon and 126,846 rectal). We quantified the annual percentage change (APC) in rates by age group using Joinpoint regression. RESULTS: For people aged <50 years, colon cancer rates increased from the mid-2000s, with the increase in APCs ranging from 1.7% to 9.3% per annum (depending on specific age group); rectal cancer rates increased from the early 1990s, with APCs ranging from 0.9% to 7.1% per annum. For people aged 50 to 69 years, colon and rectal cancer rates decreased from the mid-1990s, with the decrease in APCs in specific age groups ranging from 0.8% to 4.8% per annum (except for colon cancer in those ages 65 to 69 years, where similar rate decreases were observed from 2007). An overall reduction in older persons (>70 years) was estimated at 1.9% to 4.9% per annum for colon cancer from 2010 onward and 1.1% to 1.8% per annum in rectal cancer from the early 2000s onward. CONCLUSIONS: Colon and rectal cancer incidence has increased in people aged <50 years in Australia over the last two decades. However, colon and rectal cancer rates decreased in people aged 50+, likely due to de facto and organized bowel cancer screening. IMPACT: Further research is needed to examine the cause of the increase and to quantify the impact of future trends on the cost-effectiveness of population-based screening for those <50 years.
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Neoplasias do Colo/epidemiologia , Neoplasias Retais/epidemiologia , Sistema de Registros/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Tempo , Adulto JovemAssuntos
Cólera/diagnóstico , Cólera/etiologia , Alimentos Marinhos , Vibrio cholerae , Idoso de 80 Anos ou mais , Austrália , Cólera/terapia , Humanos , MasculinoRESUMO
BACKGROUND: Bleeding is the major risk of aspirin treatment, especially in the elderly. A consensus definition for clinically significant bleeding (CSB) in aspirin primary prevention trials is lacking in the literature. METHODS: This paper details the development, modification, application, and quality control of a definition for clinically significant bleeding in the ASPirin in Reducing Events in the Elderly (ASPREE) trial, a primary prevention trial of aspirin in 19,114 community-dwelling elderly men and women. In ASPREE a confirmed bleeding event needed to meet criteria both for substantiated bleeding and clinical significance. Substantiated bleeding was defined as: 1) observed bleeding, 2) a reasonable report of symptoms of bleeding, 3) medical, nursing or paramedical report, or 4) imaging evidence. Bleeding was defined as clinically significant if it: 1) required transfusion of red blood cells, 2) required admission to the hospital for >24â¯h, or prolonged a hospitalization, with bleeding as the principal reason, 3) required surgery to stop the bleeding, or 4) resulted in death. Bleeding sites were subclassified as upper gastrointestinal, lower gastrointestinal, intracranial (hemorrhagic stroke, subarachnoid hemorrhage, subdural hematoma, extradural hematoma, or other), or other sites. Potential events were retrieved from medical records, self-report or notification from treating doctors. Two reviewers adjudicated each event using electronic adjudication software, and discordant cases were reviewed by a third reviewer. Adjudication rules evolved to become more strictly defined as the trial progressed and decision rules were added to assist with frequent scenarios such as post-operative bleeding. CONCLUSIONS: This paper provides a detailed methodologic description of the development of a standardized definition for clinically significant bleeding and provides a benchmark for development of a consensus definition for future aspirin primary prevention trials. TRIAL REGISTRATION: ASPREE is registered on the International Standard Randomized Controlled Trial Number Register (ISRCTN83772183) and on clinicaltrials.gov (NCT01038583).