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1.
Diabetes Res Clin Pract ; 141: 156-167, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29763709

RESUMO

AIM: Dyslipidemia in type 2 diabetes contributes to an increased risk of cardiovascular disease. Fenofibrate, a lipid-regulating peroxisome proliferator-activated receptor-α (PPARα) agonist, has been shown to reduce vascular complications in adults with type 2 diabetes. The mechanisms for such benefit, however, are not yet well understood. We examined the effects of fenofibrate on carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis, in adults with type 2 diabetes. METHODS: In a prospectively designed substudy of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, we assessed carotid IMT in a subset of 422 representative adults. Traditional risk factors and IMT were assessed at 2 and 4 years after randomisation to fenofibrate (200 mg daily) or placebo. The prespecified primary study endpoint was the difference in IMT between treatment groups at 4 years. Post-hoc analyses were performed according to dyslipidemia and metabolic syndrome status. RESULTS: There was no difference in carotid IMT comparing those assigned to fenofibrate or placebo at 2 or 4 years, despite statistically significant improvement in lipid and lipoprotein parameters at 2 and 4 years, including TC, LDL-C and TG, and HDL-C at 4 months and 2 years. Similarly, there was no difference in carotid IMT on fenofibrate compared with placebo in those with dyslipidemia or metabolic syndrome. CONCLUSIONS: Fenofibrate was not associated with improved carotid IMT in adults with type 2 diabetes when compared with placebo, despite a statistically significant improvement in TC, LDL-C and TG at 2 and 4 years, and HDL-C at 4 months and 2 years.


Assuntos
Aterosclerose/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , Espessura Intima-Media Carotídea/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Fenofibrato/uso terapêutico , Dislipidemias/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
2.
Drug Alcohol Depend ; 181: 132-139, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29054032

RESUMO

BACKGROUND: Opioid substitution treatment (OST) is often continued long-term and, therefore, opioid-associated symptoms are of interest. Symptoms associated with methadone maintenance treatment (MMT) in men are well described, but there are fewer reports concerning symptoms associated with buprenorphine maintenance treatment (BMT) and very few reports among women. METHOD: Recipients of BMT (n=113) and MMT (n=184), non-opioid users (n=105) and opioid users not receiving OST (n=87) completed the Patient Assessment of Constipation (PAC-SYM) and a general symptom checklist. Multivariate analysis included other potential moderators of opioid-associated symptoms. FINDINGS: Opioid users reported a higher frequency and severity of symptoms than non-opioid users. Constipation, dry mouth, decreased appetite, sweating and fatigue were highly prevalent in the previous 30days (51-80%). Nausea, itchy skin, trouble urinating, menstrual problems, lightheadedness, blurred vision, heart racing were also common (30-50%). Non-OST opioid users had significantly higher frequency and severity than OST recipients of nausea, vomiting, diarrhoea, decreased appetite, sweating and itchy skin. Sweating was significantly more common in MMT than BMT. Constipation scores were higher in women, otherwise most sex differences were small. Higher PAC-SYM scores were associated with vomiting (OR=1.04) and sweating (OR=1.06). Cannabis use was associated with vomiting (OR=2.19). Constipation (OR=1.07), insomnia (OR=2.5) and depression (OR=2.82) were associated with fatigue. CONCLUSION: Men and women receiving OST report similarly high rates of somatic symptoms, though less than opioid users not receiving OST. There were few differences between BMT and MMT. Buprenorphine might be preferred where sweating is problematic. Several modifiable factors were identified.


Assuntos
Buprenorfina/efeitos adversos , Constipação Intestinal/induzido quimicamente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Metadona/efeitos adversos , Tratamento de Substituição de Opiáceos/efeitos adversos , Adulto , Analgésicos Opioides/uso terapêutico , Austrália/epidemiologia , Buprenorfina/uso terapêutico , Estudos de Casos e Controles , Constipação Intestinal/epidemiologia , Depressão , Feminino , Humanos , Masculino , Metadona/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Prevalência , Fatores Sexuais , Adulto Jovem
3.
Br J Cancer ; 115(10): 1179-1185, 2016 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-27764842

RESUMO

BACKGROUND: To determine the minimum survival benefits that patients, and their clinicians, judged sufficient to make adjuvant chemotherapy (ACT) worthwhile, in addition to pelvic radiotherapy, for women with high risk and advanced stage endometrial cancer. METHODS: Eighty-three participants in the PORTEC-3 trial completed a time trade-off questionnaire before and after adjuvant therapy; 44 of their clinicians completed it once only. The questionnaire used four hypothetical scenarios including baseline survival times without ACT of 5 and 8 years, and baseline survival rates at 5 years without ACT of 50 and 65%. RESULTS: Over 50% of patients judged an extra 1 year of survival time or an extra 5% in survival rate sufficient to make ACT worthwhile. Over 50% of clinicians judged an extra 1 year of survival time, or an extra 10% in survival rate, sufficient to make ACT worthwhile. Compared with patients, clinicians required similar survival time benefits (medians both 1 year, P=0.4), but larger survival rate benefits (medians 8.5% vs 5%, P=0.03), and clinicians' preferences varied less (IQR 0.5-1.5 years vs 0.4-2 years, P=0.0007; 5-10% vs 1-13%, P=0.004). Patients' preferences changed over time for the survival rate scenarios depending on whether they had ACT or not (change in median benefit - 3 months vs 2.5 months respectively, P=0.028). There were no strong predictors of patients' or clinicians' preferences. CONCLUSIONS: Patients and clinicians judged moderate survival benefits sufficient to make ACT worthwhile after pelvic radiotherapy for endometrial cancer. These benefits are larger than those judged sufficient by patients with breast or colon cancers, but similar to those judged sufficient by patients with lung or ovarian cancers.


Assuntos
Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/terapia , Pessoal de Saúde/psicologia , Preferência do Paciente/psicologia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Quimioterapia Adjuvante/métodos , Estudos de Coortes , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/mortalidade , Neoplasias do Colo/terapia , Terapia Combinada/métodos , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Satisfação do Paciente , Radioterapia/métodos , Inquéritos e Questionários , Taxa de Sobrevida
4.
Lung Cancer ; 95: 8-14, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27040845

RESUMO

BACKGROUND: People with cancer have varying preferences for involvement in decision-making between active, collaborative and passive roles. We sought the preferred and perceived involvement in decision-making among patients considering adjuvant chemotherapy (ACT) after resection of early non-small cell lung cancer (NSCLC). METHODS: Patients considering ACT for NSCLC were asked to complete a self-administered questionnaire at baseline and 6 months. Preferred and perceived decision-making roles were assessed by the Control Preferences Scale (CPS). We examined differences between preferred and perceived roles, differences in preferred roles over time, determinants of preferences, and differences in treatment preferences between patients preferring active and less active roles. RESULTS: 98 patients completed the baseline questionnaire; 75 completed the 6 month questionnaire. Most patients were male (55%) with a median age of 64 years (range, 43-79 years). Preferred role in decision-making at baseline (n=98) was active in 27%, collaborative in 47%, and passive in 27%. Perceived decision-making roles matched the preferred role in 79% of patients. Individuals' role preferences often varied between baseline and 6 months, but there was no consistent direction to the change (25% changed preference to more active involvement, 22% to less active). Preferring a more active role was associated with university education (OR 2.9, p=0.02), deciding not to have ACT (OR 5.0, p<0.01), and worse health-related quality of life (HRQL) during ACT: physical well-being (OR 4.4, p=0.05), overall well-being (OR 5.5, p=0.02), sleep (OR 8.4, p<0.01) and shortness of breath (OR 7.6, p=0.01). Patients who preferred an active decision-making role judged larger survival benefits necessary to make ACT worthwhile than those preferring a passive role. CONCLUSION: Most patients with resected NSCLC preferred and perceived a collaborative role in decision-making about ACT. Clinicians should elicit and consider patients' preferences for involvement in decision-making when discussing ACT for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Tomada de Decisões , Neoplasias Pulmonares/epidemiologia , Preferência do Paciente , Direitos do Paciente , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Retratamento , Fatores de Risco
5.
Radiother Oncol ; 118(2): 342-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26952933

RESUMO

BACKGROUND AND PURPOSE: This study aimed to examine the rate and type of p53 mutation in oropharyngeal cancer (OSCC). Relationships were sought between human papillomavirus (HPV) status and p53 mutation. The role of p53 mutation as a prognostic factor independent of HPV status and as a modifier of the effect of HPV on outcomes was also examined. METHODS: The HPV status of 202 cases was determined by HPV DNA by RT-PCR and p16 immunohistochemistry. P53 mutation in exon 5-8 was determined by pyrosequencing. Findings were correlated with known clinicopathological factors and outcomes. RESULTS: 48% of the cases were HPV positive and they were significantly less likely to have a p53 mutation than HPV-negative OSCCs (25.8% vs 46.7%, p=0.0021). Mutation was most common in exon 5. Among patients with HPV-positive OSCC, there was no significant difference in p53 mutation by smoking status (22.2% for never smokers and 30.8% for current or ex-smokers). Patients with p53 mutant OSCC had significantly worse overall survival (p=0.01). There was no statistical evidence that p53 mutation modified the effect of HPV status on outcomes. In the multivariate analysis, positive HPV status remained the strongest predictor of outcomes. p53 mutation status was not a significant predictor of outcome after adjusting for age, gender, T stage, N stage and HPV status. CONCLUSIONS: In summary, HPV-positive OSCC are less likely to have mutant p53 than HPV-negative OSCC. Our study did not show any evidence that p53 mutation could modify the effect of HPV status on outcomes.


Assuntos
Carcinoma de Células Escamosas/genética , Genes p53/genética , Mutação/genética , Neoplasias Orofaríngeas/genética , Avaliação de Resultados em Cuidados de Saúde , Papillomaviridae/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real
6.
Br J Cancer ; 114(5): 505-9, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26867157

RESUMO

BACKGROUND: This randomised phase II study evaluated the efficacy and safety of panitumumab added to docetaxel-based chemotherapy in advanced oesophagogastric cancer. METHODS: Patients with metastatic or locally recurrent cancer of the oesophagus, oesophagogastric junction or stomach received docetaxel and a fluoropyrimidine with or without panitumumab for 8 cycles or until progression. The primary end point was response rate (RECIST1.1). We planned to enrol 100 patients, with 50% expected response rate for combination therapy. RESULTS: A total of 77 patients were enrolled. A safety alert from the REAL3 trial prompted a review of data that found no evidence of adverse outcomes associated with panitumumab but questionable efficacy, and new enrolment was ceased. Enrolled patients were treated according to protocol. Response rates were 49% (95% CI 34-64%) in the chemotherapy arm and 58% (95% CI 42-72%) in the combination arm. Common grade 3 and 4 toxicities included infection, anorexia, vomiting, diarrhoea and fatigue. At 23.7 months of median follow-up, median progression-free survival was 6.9 months vs 6.0 months and median overall survival was 11.7 months vs 10.0 months in the chemotherapy arm and the combination arm, respectively. CONCLUSIONS: Adding panitumumab to docetaxel-based chemotherapy for advanced oesophagogastric cancer did not improve efficacy and increased toxicities.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/secundário , Adulto , Idoso , Anorexia/induzido quimicamente , Anticorpos Monoclonais/administração & dosagem , Capecitabina/administração & dosagem , Carcinoma de Células Escamosas/secundário , Cisplatino/administração & dosagem , Diarreia/induzido quimicamente , Intervalo Livre de Doença , Docetaxel , Neoplasias Esofágicas/patologia , Fadiga/induzido quimicamente , Feminino , Fluoruracila/administração & dosagem , Humanos , Infecções/induzido quimicamente , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Panitumumabe , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/patologia , Taxoides/administração & dosagem , Resultado do Tratamento , Vômito/induzido quimicamente
7.
Cancer Biol Ther ; 17(2): 181-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26575468

RESUMO

BACKGROUND: The study aimed to identify prognostic markers to improve the management of patients with HPV positive OSCC Methods: We determined the ratio of HPV E6*I and E6*II splice variants by quantitative RT-PCR in 177 HPV positive OSCC and correlated the findings with other clinicopathological data Results: There was no significant difference in locoregional recurrence (HR 1.72 p = 0.24) and death (HR 1.65, p = 0.13) among patients whose tumors had an E6*I/*II ratio ≥1 compared with an E6*I/*II ratio of <1. Univariate analysis showed that patients with E6*I/*II ≥1 OSCC were more likely to have an event. In the multivariable analysis, there was a trend for more events in patients with E6*I/*II ratio ≥1 (HR 1.70, 95% CI 0.95-3.03, p = 0.07) CONCLUSION: Our data suggest that the use of HPV 16 spliced transcripts may help to predict for poorer outcomes in patients with HPV positive OSCC.


Assuntos
Carcinoma de Células Escamosas/genética , Proteínas Oncogênicas Virais/genética , Neoplasias Orofaríngeas/genética , Prognóstico , Proteínas Repressoras/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Papillomaviridae/genética , Papillomaviridae/patogenicidade , Sítios de Splice de RNA/genética , Fatores de Risco
8.
Head Neck ; 38(5): 743-50, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25521312

RESUMO

BACKGROUND: This study provides Australian data on the characteristics of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC) over the last 2 decades. METHODS: The HPV status of 515 patients with oropharyngeal SCC diagnosed between 1987 and 2010 was determined by HPV E6-targeted multiplex real time polymerase chain reaction assay (PCR) and p16 immunohistochemistry. RESULTS: The HPV positivity rate increased from 20.2% (1987-1995) to 63.5% (2006-2010). Among HPV-positive oropharyngeal SCC over the study period, the median age increased from 55.4 years to 59.8 years (p = .004) and there was a trend of an increasing proportion of never smokers (19.2% to 34.0%). The use of radiation therapy (RT) in patients with HPV-positive oropharyngeal cancer increased from 26.9% to 68.1% (p = .007) and we also observed a trend of improved outcomes. CONCLUSION: Our data show a rising prevalence of HPV-positive oropharyngeal SCC in Australia over the last 2 decades. These patients with HPV-positive oropharyngeal SCC are now presenting at an older age and about one third have never smoked.


Assuntos
Carcinoma de Células Escamosas/epidemiologia , Neoplasias Orofaríngeas/epidemiologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Carcinoma de Células Escamosas/virologia , DNA Viral , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Proteínas Oncogênicas Virais/genética , Neoplasias Orofaríngeas/virologia , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Prevalência
9.
J Glaucoma ; 25(4): 390-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25836657

RESUMO

PURPOSE: Our aim was to compare changes in intraocular pressure (IOP) and management of glaucoma in patients undergoing either penetrating keratoplasty (PK) or Descemet stripping endothelial keratoplasty (DSEK). METHOD: A retrospective review of all patients who underwent primary corneal transplantation at Sydney Eye Hospital (Sydney, Australia) from January 2008 to December 2010 was performed. Eyes with comparable indications and either primary PK or DSEK with 12 months of follow-up were included. Data on IOP and antiglaucoma management postoperatively were collected. An IOP elevation of ≥30% from baseline or an absolute IOP of >24 at 1 year postoperatively was significant. RESULTS: Sixty-one eyes from 61 patients met the inclusion criteria. Comparable eyes had undergone either PK (n=28, 46%) or DSEK (n=33, 54%). In patients without prior glaucoma (n=39), 29% of those in the PK group and 28% in the DSEK group required a change in therapy to control IOP (P=0.970). If there was prior glaucoma (n=22), the PK group required a change in 71% of patients compared with the DSEK group, 63% (P=0.665). In both groups of patients, PK and DSEK, elevation of IOP of at least 30% from baseline to 1 year was seen in 39% (P=0.993) regardless of glaucoma status. CONCLUSIONS: Elevation of IOP is a serious consequence of both PK and DSEK, even despite maximal medical therapy in certain cases. DSEK has an equivalent incidence of IOP elevation to PK in comparable patients. Careful monitoring of IOP and appropriate therapy should be instituted to prevent progression to glaucoma.


Assuntos
Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Glaucoma/fisiopatologia , Pressão Intraocular/fisiologia , Ceratoplastia Penetrante , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Doenças da Córnea/cirurgia , Feminino , Glaucoma/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tonometria Ocular , Acuidade Visual , Adulto Jovem
10.
Atherosclerosis ; 242(1): 295-302, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26233916

RESUMO

OBJECTIVE: Dislipidaemia in type 2 diabetes mellitus contributes to arterial endothelial dysfunction and an increased risk of cardiovascular disease. Fenofibrate, a lipid-regulating peroxisome proliferator-activated receptor-α (PPARα) agonist, has been shown to reduce vascular complications in adults with type 2 diabetes. However, the mechanisms for such benefit are not well understood. We examined the effects of fenofibrate on brachial artery endothelial function in adults with type 2 diabetes. METHODS: In a prospectively designed substudy of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, we assessed arterial flow-mediated dilatation (FMD; endothelium-dependent dilatation) and dilator responses to glyceryl trinitrate (GTN, an endothelium-independent dilator) in a subset of 193 representative adults. Traditional risk factors were assessed at baseline, 4 months and 2 years after randomised treatment allocation to fenofibrate (200 mg daily) or placebo. The prespecified primary study endpoint was the difference in FMD between treatment groups at 4 months. RESULTS: Fenofibrate was associated with a significant improvement at 4 months compared with placebo (+1.05% (absolute); P=0.03); GTN-dilator responses were unchanged (P=0.77). After 2 years, FMD was similar in both groups (P=0.46). In multivariable models, none of the fenofibrate-related changes in lipoproteins and lipids were significantly associated with improved FMD on fenofibrate at 4 months. CONCLUSION: Treatment with fenofibrate significantly improved arterial endothelial function after 4 months. However, the effect was no longer apparent after 2 years. The long-term beneficial vascular effects of fenofibrate in type 2 diabetes are likely to be mediated via mechanisms other than improvement in endothelium-dependent dilatation of conduit arteries, and may differ for the microcirculation.


Assuntos
Artéria Braquial/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Fenofibrato/uso terapêutico , Hipolipemiantes/uso terapêutico , Vasodilatação/efeitos dos fármacos , Idoso , Austrália , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Método Duplo-Cego , Dislipidemias/sangue , Dislipidemias/diagnóstico , Endotélio Vascular/diagnóstico por imagem , Endotélio Vascular/fisiopatologia , Feminino , Finlândia , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Nitroglicerina/farmacologia , Estudos Prospectivos , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia , Vasodilatadores/farmacologia
11.
Eur J Cancer ; 51(12): 1529-37, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26059196

RESUMO

BACKGROUND: Adjuvant chemotherapy (ACT) in non-small-cell lung cancer (NSCLC) improves overall survival, but the benefits must be weighed against its harms. We sought to determine the survival benefits that patients and their doctors judged sufficient to make ACT in NSCLC worthwhile. METHODS: 122 patients completed a self-administered questionnaire at baseline and 6 months (before & after ACT, if they had it); 82 doctors completed the questionnaire once only. The time trade-off method was used to determine the minimum survival benefits judged sufficient in four hypothetical scenarios. Baseline survival times were 3 years & 5 years and baseline survival rates (at 5 years) were 50% & 65%. RESULTS: At baseline, the median benefits judged sufficient by patients were an extra 9 months (Interquartile range (IQR) 1-12 months) beyond 3 years & 5 years and an extra 5% (IQR 0.1-10%) beyond 50% & 65%. At 6 months (n=91), patients' preferences had the same median benefit (9 months & 5%) but varied more (IQRs 0-18 months & 0-15%) than at baseline. Factors associated with judging smaller benefits sufficient were deciding to have ACT (P=0.01, 0.02) and better well-being (P=0.01, 0.006) during ACT. Doctors' preferences, compared with patients' preferences, had similar median benefits (9 months & 5%) but varied less (IQR 6-12 months versus 1-12 months, P<0.001; 5%-10% versus 0.1-10%, P<0.001). CONCLUSION: Most patients and doctors judged moderate survival benefits sufficient to make ACT in NSCLC worthwhile, but the preferences of doctors varied less than those of patients. Doctors should endeavour to elicit patients' preferences during discussions about ACT in NSCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Atitude do Pessoal de Saúde , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Preferência do Paciente , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Inquéritos e Questionários , Análise de Sobrevida
12.
Am J Ophthalmol ; 159(4): 788-96, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25634533

RESUMO

PURPOSE: To determine in primary congenital glaucoma whether age of presentation influences surgical success, the degrees of angle surgery needed to achieve glaucoma control, and whether there are critical ages where glaucoma progresses, requiring further surgical management. DESIGN: Retrospective cohort study. METHODS: The medical records of patients with primary congenital glaucoma over a 23-year period were reviewed: 192 procedures were performed on 117 eyes (70 patients). The number and age of angle procedures and final visual acuity was analyzed. Surgical success was defined as stable intraocular pressure and optic disc appearance. RESULTS: Procedures involving 83 of the 110 eyes (75.5%) undergoing angle surgery were successful, with 2-, 4-, 6-, and 10-year success rates of 92%, 86%, 84%, and 75%, respectively. Subgroup analysis (<3 months; 3-6 months; >6 months) comparing age of diagnosis to visual outcome (<20/200, 20/200-20/40, >20/40) was significant (P = .04). The age at first operation (P = .94), the number of angle operations (P = .43), and their effect on angle surgery success was not significant. Seven of 192 operations were performed after the age of 8 years (3.6%). After the initial angle surgeries within the first year of life, the third procedure occurred at a median age of 2.4 years (interquartile ratio [IQR] 0.6-3.8 years) and the fourth procedure occurred at a median age of 5.3 years (IQR 2.5-6.1 years). CONCLUSIONS: Children diagnosed at <3 months of age had a visual outcome of <20/200 despite successful glaucoma control. Age of presentation did not affect surgical success. A total of 78.9% of cases undergoing primary trabeculotomy were controlled with 1 operation: 4 clock hours of angle (120 degrees). Analysis of glaucoma progression suggests critical ages where further glaucoma surgery is required at around 2 and 5 years of age.


Assuntos
Hidroftalmia/diagnóstico , Hidroftalmia/cirurgia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Corpo Ciliar/cirurgia , Estudos de Coortes , Feminino , Seguimentos , Implantes para Drenagem de Glaucoma , Gonioscopia , Humanos , Hidroftalmia/fisiopatologia , Lactente , Pressão Intraocular/fisiologia , Fotocoagulação a Laser , Masculino , Estudos Retrospectivos , Fatores de Tempo , Tonometria Ocular , Trabeculectomia , Resultado do Tratamento , Acuidade Visual/fisiologia , Adulto Jovem
13.
J Diabetes ; 7(6): 809-19, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25350950

RESUMO

BACKGROUND: Intrahepatic expression of dipeptidyl peptidase-4 (DPP4), and circulating DPP4 (cDPP4) levels and its enzymatic activity, are increased in non-alcoholic fatty liver disease (NAFLD) and in type 2 diabetes mellitus and/or obesity. DPP4 has been implicated as a causative factor in NAFLD progression but few studies have examined associations between cDPP4 activity and NAFLD severity in humans. This study aimed to examine the relationship of cDPP4 activity with measures of liver disease severity in NAFLD in subjects with diabetes and/or obesity. METHODS: cDPP4 was measured in 106 individuals with type 2 diabetes who had transient elastography (Cohort 1) and 145 individuals with morbid obesity who had liver biopsy (Cohort 2). Both cohorts had caspase-cleaved keratin-18 (ccK18) measured as a marker of apoptosis. RESULTS: Natural log increases in cDPP4 activity were associated with increasing quartiles of ccK18 (Cohorts 1 and 2) and with median liver stiffness ≥10.3 kPa (Cohort 1) and significant fibrosis (F ≥ 2) on liver biopsy (Cohort 2). CONCLUSIONS: In diabetes and/or obesity, cDPP4 activity is associated with current apoptosis and liver fibrosis. Given the pathogenic mechanisms by which DPP4 may progress NAFLD, measurement of cDPP4 activity may have utility to predict disease progression and DPP4 inhibition may improve liver histology over time.


Assuntos
Apoptose , Diabetes Mellitus Tipo 2/enzimologia , Dipeptidil Peptidase 4/sangue , Hepatócitos/enzimologia , Cirrose Hepática/enzimologia , Hepatopatia Gordurosa não Alcoólica/enzimologia , Obesidade Mórbida/enzimologia , Adulto , Idoso , Biomarcadores/sangue , Biópsia , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Técnicas de Imagem por Elasticidade , Feminino , Hepatócitos/patologia , Humanos , Queratina-18/sangue , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade Mórbida/sangue , Obesidade Mórbida/patologia , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença
14.
Ann Surg Oncol ; 22(6): 1893-900, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25404475

RESUMO

BACKGROUND: Human papillomavirus (HPV) is the major predictor of outcome in oropharyngeal squamous cell carcinoma (OSCC) but the disease is heterogeneous and there is limited understanding of the prognostic significance of other molecular markers in relation to HPV. This multi-institutional, retrospective study examined the prognostic significance of Ki67 expression in association with HPV status in OSCC. METHODS: The 105 patients recruited had a median follow-up of 70 months. Tumor HPV status was determined by HPV E6-targeted multiplex real-time polymerase chain reaction/p16 semiquantitative immunohistochemistry and Ki67 expression by semiquantitative immunohistochemistry. Determinants of recurrence and mortality hazards were modelled using Cox regression with censoring at dates of last follow-up. RESULTS: HPV and Ki67 positivity rates were 46 and 44 %, respectively. HPV-positive cancers were more likely to be Ki67-positive. On multivariate analysis, both HPV and Ki67 were predictors of outcome. Ki67-positive cancers were associated with a 3.13-fold increased risk of disease-related death compared with Ki67-negative cancers. Among HPV-negative patients, Ki67-positive disease was associated with 5.6-fold increased risk of oropharyngeal cancer-related death (p = 0.002), 5.5-fold increased risk of death from any cause (p = 0.001), and 2.9-fold increased risk of any event (p = 0.013). The risk of locoregional failure was lowest in patients with HPV-positive/Ki67-positive cancers. CONCLUSIONS: Ki67 predicts disease-related death in oropharyngeal cancer independent of HPV status. A combination of Ki67 and HPV status provides improved prognostic information relative to HPV status alone. Our data suggest, for the first time, that Ki67 status has prognostic value, particularly in HPV-negative oropharyngeal cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Antígeno Ki-67/metabolismo , Recidiva Local de Neoplasia/metabolismo , Neoplasias Orofaríngeas/metabolismo , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , DNA Viral/genética , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/virologia , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Papillomaviridae/genética , Infecções por Papillomavirus/mortalidade , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Taxa de Sobrevida
15.
Diabetes Care ; 38(3): 521-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25524951

RESUMO

OBJECTIVE: People with diabetes frequently develop vascular disease. We investigated the relationship between blood 25-hydroxyvitamin D (25OH-D) concentration and vascular disease risk in type 2 diabetes. RESEARCH DESIGN AND METHODS: The relationships between blood 25OH-D concentration at baseline and the incidence of macrovascular (including myocardial infarction and stroke) and microvascular (retinopathy, nephropathy, neuropathy, and amputation) disease were analyzed with Cox proportional hazards models and logistic regression in an observational study of patients in the 5-year Fenofibrate Intervention and Event Lowering in Diabetes trial. RESULTS: A total of 50% of the patients had low vitamin D concentrations, as indicated by median blood 25OH-D concentration of 49 nmol/L. These patients with a blood 25OH-D concentration <50 nmol/L had a higher cumulative incidence of macrovascular and microvascular events than those with levels ≥50 nmol/L. Multivariate analysis, stratified by treatment and adjusted for relevant confounders, identified blood 25OH-D concentration as an independent predictor of macrovascular events. A 50 nmol/L difference in blood 25OH-D concentration was associated with a 23% (P = 0.007) change in risk of macrovascular complications during the study, and further adjustments for seasonality, hs-CRP, and physical activity level had little impact. The unadjusted risk of microvascular complications was 18% (P = 0.006) higher during the study, though the excess risk declined to 11-14% and lost significance with adjustment for HbA1c, seasonality, or physical activity. CONCLUSIONS: Low blood 25OH-D concentrations are associated with an increased risk of macrovascular and microvascular disease events in type 2 diabetes. However, a causal link remains to be demonstrated.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Angiopatias Diabéticas/diagnóstico , Vitamina D/análogos & derivados , Idoso , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/epidemiologia , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico , Prognóstico , Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia
16.
Emerg Med J ; 32(2): 130-3, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24022112

RESUMO

OBJECTIVE: To investigate factors associated with emergency physician perception of the shift and to determine whether these perceptions were predictors of overall daily emergency department (ED) performance indicators. METHODS: This was an observational study conducted at an inner city ED in New South Wales. Shift reports completed by the emergency physician in charge at clinical handover times between February and July 2012 were included. Variables collected by the shift report included (1) total number of patients in ED, (2) number of patients in the ED with length of stay (LOS) greater than 4 h, (3) number of admitted patients, (4) number of patients waiting to be seen by a doctor and (5) medical staffing levels. Outcomes of interest for this study were shift perception scores (1=very poor to 5=very good) and daily ED performance measures. Performance measures were the proportion of patients admitted or discharged from ED within 4 h (National Emergency Access Target, NEAT) and the percentage of inpatient admissions leaving ED within 8 h of ED arrival time. RESULTS: The number of patients in ED with LOS >4 h (OR 0.83, 95% CI 0.79 to 0.87, p value <0.001) and number of patients waiting to be seen (OR 0.92, 95% CI 0.88 to 0.95, p value <0.001) were the factors most strongly associated with shift perception score. After adjustment, the mean NEAT performance improved 6% for each incremental increase in average shift perception score (ß=0.06 95% CI 0.04 to 0.07, p<0.001). CONCLUSIONS: Shift reports and shift perceptions by emergency physicians may be used to predict overall ED performance.


Assuntos
Atitude do Pessoal de Saúde , Serviço Hospitalar de Emergência/normas , Adulto , Medicina de Emergência , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , New South Wales , Admissão do Paciente/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Transferência da Responsabilidade pelo Paciente/estatística & dados numéricos , Indicadores de Qualidade em Assistência à Saúde , Fatores de Tempo
17.
Diabetes Res Clin Pract ; 106(2): 328-36, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25301035

RESUMO

AIM: Impaired arterial function has been implicated in diabetes-related atherosclerosis, but its determinants in high-risk adults have not been well characterised. We investigated factors associated with impaired arterial function in adults with type 2 diabetes. METHODS: Flow-mediated dilatation (a marker of endothelial function) and dilator response to glyceryl trinitrate (to assess smooth muscle function) of the brachial artery were assessed at baseline in 193 patients with type 2 diabetes from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Traditional risk factors were assessed and a multivariable model was constructed to identify factors independently associated with impaired arterial function. RESULTS: Median age was 64 years (interquartile range, 58-69; 61% male) and duration of diabetes was 4 years (interquartile range, 2-9). Flow-mediated dilatation (3.06 ± 0.25%, mean ± SEM) was severely impaired but not significantly associated with other risk factors. Dilator responses to glyceryl trinitrate (10.56 ± 0.52%) were significantly and independently impaired in past and present cigarette smokers (P = 0.005) and in subjects with increased urinary albumin/creatinine ratio (P = 0.01). CONCLUSIONS: In adults with type 2 diabetes and known or suspected atherosclerosis, arterial smooth muscle-dependent dilatation was shown to be significantly impaired in cigarette smokers and those with elevated urinary albumin levels.


Assuntos
Albuminúria/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/epidemiologia , Músculo Liso Vascular/fisiopatologia , Fumar/epidemiologia , Idoso , Albuminúria/fisiopatologia , Artéria Braquial/efeitos dos fármacos , Artéria Braquial/fisiopatologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/complicações , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Feminino , Fenofibrato/uso terapêutico , Humanos , Hipolipemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Músculo Liso Vascular/efeitos dos fármacos , Nitroglicerina/farmacologia , Fatores de Risco , Fumar/fisiopatologia , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia
18.
Emerg Med Australas ; 26(4): 343-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24935075

RESUMO

OBJECTIVE: To evaluate the impact of a senior early assessment model of care on performance measures in a single ED. METHODS: A pragmatic single-blinded randomised control trial with day of ED presentation randomised to one of three study arms: senior work-up assessment and treatment (SWAT) model of care intervention, non-SWAT control or control. PRIMARY OUTCOME: The primary outcomes were the proportion of patients meeting National Emergency Access Target (NEAT) criteria (ED length of stay less than 4 h) and ED length of stay. Secondary outcome measured was time to decision to admit in the subgroup of admitted patients. RESULTS: A total of 1737 patients were analysed. There was no overall difference in NEAT performance (48% [95% CI 44, 51] vs 41% ([95% CI 37, 45] vs 46% [95% CI 41, 50], P = 0.09) or ED length of stay (P = 0.65) between SWAT, non-SWAT and standard of care control groups, respectively. In the subgroup of patients discharged from ED (non-admitted), the SWAT intervention group was associated with higher NEAT performance (P = 0.004) compared with non-SWAT and control. CONCLUSION: A senior early assessment model of care was not associated with improved overall NEAT performance and ED length of stay. However, there is evidence that improvements were made in the subgroup of discharged patients. There was no difference in overall NEAT performance among the three study groups.


Assuntos
Serviço Hospitalar de Emergência/organização & administração , Adulto , Idoso , Austrália , Eficiência Organizacional/normas , Serviço Hospitalar de Emergência/normas , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Fatores de Tempo
19.
Emerg Med Australas ; 26(4): 356-60, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24931459

RESUMO

OBJECTIVE: To describe trends in population-based rates of ED presentations in the Greater Sydney Area (GSA) and compare these between the elderly and non-elderly age groups. METHODS: This was a retrospective study using ED presentation data from all public hospitals in the GSA and population data from the Australian Bureau of Statistics between 2001 and 2011. Age-specific ED presentation rates stratified by age group (<65 years, 65-79 years and ≥80 years of age) were presented and compared using negative binomial regression and generalised linear regression models. RESULTS: Over 11 million ED presentations were analysed. The annualised rate of increase in ED presentations per 1000 population was 1.8% per annum. The adjusted incidence rate ratio for patients aged 80 years and over was 3.6 times higher than patients younger than 65 years (95% CI 2.8, 4.7, P < 0.001) and 1.6 times higher for patients between 65 and 79 years of age (95% CI 1.4, 1.8, P < 0.001). There was an increase of 40 patients per 1000 population per year admitted to hospital from ED (ß = 40, 95% CI 29, 52 P < 0.001) in patients aged 80 years or older compared with those aged less than 65 years of age. CONCLUSIONS: A disproportionate increase in ED presentation rates and in-patient admission rates in patients aged 80 years and over was demonstrated over 11 years in the GSA. ED models of care and system wide strategies to address these demographic changes are required.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Necessidades e Demandas de Serviços de Saúde/tendências , Serviços de Saúde para Idosos/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitalização/estatística & dados numéricos , Hospitalização/tendências , Humanos , Masculino , Pessoa de Meia-Idade , New South Wales , Vigilância da População/métodos , Estudos Retrospectivos
20.
Emerg Med Australas ; 25(5): 457-63, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24099376

RESUMO

OBJECTIVES: Describe the level of agreement between prehospital (emergency medical service [EMS]) and ED vital signs in a group of trauma patients transported to an inner city Major Trauma Centre. We also sought to determine factors associated with differences in recorded vital sign measurements. METHODS: All adult patients meeting trauma triage criteria and transported directly from scene of injury by New South Wales Ambulance to our institution were included. The primary outcome was the difference in vital signs: heart rate (HR), systolic blood pressure (SBP), respiratory rate (RR) and Glasgow Coma Scale (GCS), between ED and EMS recorded measurements. Agreement was assessed using intraclass correlation coefficients and enhanced Bland-Altman plots. Multivariable linear regression models were used to determine factors associated with vital sign differences. RESULTS: The 1181 trauma patients met inclusion criteria. Intraclass correlation coefficients were as follows: GCS 0.74 (95% confidence interval [CI], 0.37, 1.12); HR 0.41 (95% CI, 0.30, 0.53); SBP 0.37 (95% CI, 0.27, 0.46); and RR 0.29 (95% CI, 0.06, 0.51). Bland-Altman derived 95% limits of agreement lay outside a priori limits of clinical agreement for SBP and RR and were within limits of clinical agreement for GCS and HR. SBP and HR differences were associated with prehospital airway and fluid intervention. CONCLUSIONS: Agreement was demonstrated between EMS and ED GCS scores but not RR and SBP recordings. Discrepancies appeared to reflect physiological changes in response to EMS initiated interventions. Trauma triage algorithms and risk models might need to take these measurement differences, and factors associated with them, into account.


Assuntos
Serviços Médicos de Emergência/estatística & dados numéricos , Sinais Vitais , Ferimentos e Lesões/classificação , Adolescente , Adulto , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Escala de Coma de Glasgow/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , New South Wales , Variações Dependentes do Observador , Estudos Retrospectivos , Ferimentos e Lesões/diagnóstico , Adulto Jovem
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