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1.
Clin Colorectal Cancer ; 23(1): 95-103.e3, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38242766

RESUMO

BACKGROUND: A substantial proportion of patients with stage III colorectal cancer (CRC) are older than 70 years. Optimal adjuvant chemotherapy (AC) for older patients (OP) continues to be debated, with subgroup analyses of randomized trials not demonstrating a survival benefit from the addition of oxaliplatin to a fluoropyrimidine backbone. PATIENTS AND METHODS: We analyzed the multisite Australian ACCORD registry, which prospectively collects patient, tumor and treatment data along with long term clinical follow-up. We compared OP (≥70) with stage III CRC to younger patients ([YP] <70), including the proportion recommended AC and any reasons for not prescribing AC. AC administration, regimen choice, completion rates, and survival outcomes were also examined. RESULTS: One thousand five hundred twelve patients enrolled in the ACCORD registry from 2005 to 2018 were included. Median follow-up was 57.0 months. Compared to the 827 YP, the 685 OP were less likely to be offered AC (71.5% vs. 96.5%, P < .0001) and when offered, were more likely to decline treatment (15.1% vs. 2.8%, P < .0001). Ultimately, 60.0% of OP and 93.7% of YP received AC (P < .0001). OP were less likely to receive oxaliplatin (27.5% vs. 84.7%, P < .0001) and to complete AC (75.9% vs. 85.7%, P < .0001). The probability of remaining recurrence-free was significantly higher in OP who received AC compared to those not treated (HR 0.73, P = .04) but not significantly improved with the addition of oxaliplatin (HR 0.75, P = .18). CONCLUSION: OP were less likely than YP to receive AC. Receipt of AC reduced recurrences in OP, supporting its use, although no significant benefit was observed from the addition of oxaliplatin.


Assuntos
Neoplasias Colorretais , Fluoruracila , Humanos , Oxaliplatina/uso terapêutico , Austrália/epidemiologia , Neoplasias Colorretais/patologia , Quimioterapia Adjuvante/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
2.
Asia Pac J Clin Oncol ; 19(3): 392-402, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36464923

RESUMO

BACKGROUND: The administration of adjuvant chemotherapy (AC) to colorectal cancer (CRC) patients in Australia and impact of recent trial data has not been well reported. We aim to evaluate temporal trends in AC treatment and outcomes in real-world Australian patients. METHODS: CRC patients were analyzed from 13 hospitals, stratified by stage (II or III) and three 5-year time periods (A: 2005-2009, B: 2010-2014, C: 2015-2019). Stage III was further stratified as pre- and post publication of the International Duration Evaluation of Adjuvant Therapy (IDEA) collaboration (March 2018). AC prescription, time-to-recurrence (TTR), and overall survival (OS) was compared across the time periods. RESULTS: Of 3977 identified patients, 1148 (stage II: 640, stage III: 508), 1525 (856 vs. 669), and 1304 (669 vs. 635) were diagnosed in Period A, B, and C, respectively. Fewer patients in Period C received AC compared to Period B in stage II (10% vs. 15%, p <.01) and III (70% vs. 79%, p <.01). Post-IDEA, the proportion of patients receiving ≤3 months of oxaliplatin-based AC increased (45% vs. 13%, p <.01). The proportion of patients who remained recurrence free at 3 years was similar between time periods in stage II (A: 89% vs. B: 88% vs. C: 90%, p = .53) and stage III (72% vs. 76% vs. 72%, p = .08). OS significantly improved for stage II (80%-85%, p = .04) and stage III (69%-77%, <.01) from period A to B. CONCLUSION: AC use has moderately decreased over time with no impact on recurrence rates. Improved survival in more recent years despite similar recurrence rates may be related to improved baseline staging, better postrecurrence treatment, and reduced noncancer-related mortality.


Assuntos
Neoplasias Colorretais , Fluoruracila , Humanos , Intervalo Livre de Doença , Estadiamento de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Austrália/epidemiologia , Quimioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/etiologia
3.
Cancers (Basel) ; 14(17)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36077668

RESUMO

Traditional cancer registries have often been siloed efforts, established by single groups with limited objectives. There is the potential for registry data to support a broad range of research, audit and education initiatives. Here, we describe the establishment of a series of comprehensive cancer registries across the spectrum of common solid cancers. The experience and learnings of each registry team as they develop, implement and then use collected data for a range of purposes, that informs the conduct and output of other registries in a virtuous cycle. Each registry is multi-site, multi-disciplinary and aims to collect data of maximal interest and value to a broad range of enquiry, which would be accessible to any researcher with a high-quality proposal. Lessons learnt include the need for careful and continuous curation of data fields, with regular database updates, and the need for a continued focus on data quality. The registry data as a standalone resource has supported numerous projects, but linkage with external datasets with patients in common has enhanced the audit and research potential. Multiple projects have linked registry data with matched tissue specimens to support prognostic and predictive biomarker studies, both validation and discovery. Registry-based biomarker trials have been successfully supported, generating novel and practice-changing data. Registry-based clinical trials, particularly randomised studies exploring the optimal use of available therapy options are now complementing the research conducted in traditional clinical trials. More recent projects supported by the registries include health economic studies, personalised patient education material, and increased consumer engagement, including consumer entered data.

4.
N Engl J Med ; 386(24): 2261-2272, 2022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35657320

RESUMO

BACKGROUND: The role of adjuvant chemotherapy in stage II colon cancer continues to be debated. The presence of circulating tumor DNA (ctDNA) after surgery predicts very poor recurrence-free survival, whereas its absence predicts a low risk of recurrence. The benefit of adjuvant chemotherapy for ctDNA-positive patients is not well understood. METHODS: We conducted a trial to assess whether a ctDNA-guided approach could reduce the use of adjuvant chemotherapy without compromising recurrence risk. Patients with stage II colon cancer were randomly assigned in a 2:1 ratio to have treatment decisions guided by either ctDNA results or standard clinicopathological features. For ctDNA-guided management, a ctDNA-positive result at 4 or 7 weeks after surgery prompted oxaliplatin-based or fluoropyrimidine chemotherapy. Patients who were ctDNA-negative were not treated. The primary efficacy end point was recurrence-free survival at 2 years. A key secondary end point was adjuvant chemotherapy use. RESULTS: Of the 455 patients who underwent randomization, 302 were assigned to ctDNA-guided management and 153 to standard management. The median follow-up was 37 months. A lower percentage of patients in the ctDNA-guided group than in the standard-management group received adjuvant chemotherapy (15% vs. 28%; relative risk, 1.82; 95% confidence interval [CI], 1.25 to 2.65). In the evaluation of 2-year recurrence-free survival, ctDNA-guided management was noninferior to standard management (93.5% and 92.4%, respectively; absolute difference, 1.1 percentage points; 95% CI, -4.1 to 6.2 [noninferiority margin, -8.5 percentage points]). Three-year recurrence-free survival was 86.4% among ctDNA-positive patients who received adjuvant chemotherapy and 92.5% among ctDNA-negative patients who did not. CONCLUSIONS: A ctDNA-guided approach to the treatment of stage II colon cancer reduced adjuvant chemotherapy use without compromising recurrence-free survival. (Supported by the Australian National Health and Medical Research Council and others; DYNAMIC Australian New Zealand Clinical Trials Registry number, ACTRN12615000381583.).


Assuntos
Antineoplásicos , Quimioterapia Adjuvante , DNA Tumoral Circulante , Neoplasias do Colo , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Austrália , Quimioterapia Adjuvante/métodos , DNA Tumoral Circulante/análise , DNA Tumoral Circulante/sangue , Neoplasias do Colo/sangue , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Neoplasias do Colo/terapia , Intervalo Livre de Doença , Fluoruracila/uso terapêutico , Humanos , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Oxaliplatina/uso terapêutico
5.
Nutrients ; 14(9)2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35565731

RESUMO

Resveratrol, a vasoactive phytoestrogen, has beneficial effects on cerebrovascular function. Previous research has shown that hormonal migraineurs have poorer cerebrovascular function than non-migraineur women. We aimed to investigate if resveratrol supplementation for three months could reduce the hormonal migraine burden index (HMBI: the number of days with menstrual migraine per month), reduce migraine-related disability and improve migraine-related quality of life. A randomised, double-blind, placebo-controlled, crossover, intervention trial was conducted in 62 hormonal migraineurs (mean age: 37.5 ± 0.8 years). Participants consumed 75 mg of resveratrol or matching placebo capsules twice daily for three months before crossing over to the other treatment arm. Participants completed a daily diary and the Headache Impact Test-6™, Migraine Disability Assessment and Migraine-Specific Quality of Life questionnaires at months 0, 3 and 6. The HMBI was the primary outcome and was calculated using data extracted from the participant's diary. No differences in the HMBI (p = 0.895), the Headache Impact Test-6™, the Migraine Disability Assessment and Migraine-Specific Quality of Life were found between the resveratrol and placebo treatments. Resveratrol supplementation for three months did not affect the HMBI, the migraine-related disability or quality of life measures in our cohort of hormonal migraineurs.


Assuntos
Transtornos de Enxaqueca , Qualidade de Vida , Adulto , Estudos Cross-Over , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Cefaleia , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controle , Resveratrol/uso terapêutico , Resultado do Tratamento
6.
Clin Nutr ; 40(3): 820-829, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32900519

RESUMO

Ageing and menopause contribute to endothelial dysfunction, causing impaired cerebral perfusion, which is in turn associated with accelerated cognitive decline. In a 14-week pilot study, we showed that supplementation with low-dose resveratrol, a phytoestrogen that can enhance endothelial function, improved cerebrovascular and cognitive functions in postmenopausal women. We sought to confirm these benefits in a larger, longer-term trial. A 24-month randomized, placebo-controlled crossover trial was undertaken in 125 postmenopausal women, aged 45-85 years, who took 75 mg trans-resveratrol or placebo twice-daily for 12 months and then crossover to the alternative treatment for another 12 months. We evaluated within individual differences between each treatment period in measures of cognition (primary outcome), cerebrovascular function in the middle cerebral artery (cerebral blood flow velocity: CBFV, cerebrovascular responsiveness: CVR) and cardio-metabolic markers as secondary outcomes. Subgroup analyses examined effects of resveratrol by life stages. Compared to placebo, resveratrol supplementation resulted a significant 33% improvement in overall cognitive performance (Cohen's d = 0.170, P = 0.005). Women ≥65 years of age showed a relative improvement in verbal memory with resveratrol compared to those younger than 65 years. Furthermore, resveratrol improved secondary outcomes including resting mean CBFV (d = 0.275, P = 0.001), CVR to hypercapnia (d = 0.307, P = 0.027), CVR to cognitive stimuli (d = 0.259, P = 0.032), fasting insulin (d = 0.174, P = 0.025) and insulin resistance index (d = 0.102, P = 0.034). Regular supplementation with low-dose resveratrol can enhance cognition, cerebrovascular function and insulin sensitivity in postmenopausal women. This may translate into a slowing of the accelerated cognitive decline due to ageing and menopause, especially in late-life women. Further studies are warranted to observe whether these cognitive benefits of resveratrol can reduce the risk of dementia.


Assuntos
Fenômenos Fisiológicos Cardiovasculares , Cognição , Suplementos Nutricionais , Resistência à Insulina , Pós-Menopausa , Resveratrol/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Circulação Cerebrovascular , Estudos Cross-Over , Método Duplo-Cego , Feminino , Envelhecimento Saudável , Humanos , Insulina/sangue , Memória , Pessoa de Meia-Idade , Resveratrol/efeitos adversos
7.
J Nutr ; 150(12): 3190-3199, 2020 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-33097947

RESUMO

BACKGROUND: Obesity accelerates age-related cognitive decline, which is partly mediated by vascular dysfunction. OBJECTIVE: The aim was to test the hypothesis that supplementation with fish oil and curcumin can enhance cognitive performance by improving cerebral circulatory function in overweight or obese middle-aged to older adults. METHODS: In a 16-wk double-blind, placebo-controlled intervention trial, adults [50-80 y; BMI (kg/m2): 25-40] were randomly assigned to either fish oil (2000 mg/d DHA + 400 mg/d EPA), curcumin (160 mg/d), or a combination. Effects on cerebrovascular function (primary outcome) and cardiovascular risk factors were reported previously. Effects on cognitive performance and cerebrovascular responsiveness (CVR) to cognitive stimuli are reported herein. One-factor ANOVA with post hoc analyses was conducted between groups in the whole cohort and in males and females separately. Two-factor ANOVA was conducted to assess independent effects of fish oil and curcumin and a potential interaction. Correlations between outcomes (those obtained herein and previously reported) were also examined. RESULTS: Compared with placebo, fish oil improved CVR to a processing speed test (4.4% ± 1.9% vs. -2.2% ± 2.1%; P = 0.023) and processing speed in males only (Z-score: 0.6 ± 0.2 vs. 0.1 ± 0.2; P = 0.043). Changes in processing speed correlated inversely with changes in blood pressure (R = -0.243, P = 0.006) and C-reactive protein (R = -0.183, P = 0.046). Curcumin improved CVR in a working memory test (3.6% ± 1.2% vs. -0.2% ± 0.2%, P = 0.026) and, in males only, performance of a verbal memory test compared with placebo (Z-score: 0.2 ± 0.1 vs. -0.5 ± 0.2, P = 0.039). Combining fish oil with curcumin did not produce additional benefits. CONCLUSIONS: Improvements in processing speed following fish-oil supplementation in middle-aged to older males might be mediated by improvements in circulatory function. Mechanisms underlying the cognitive benefit seen with curcumin are unknown. As cognitive benefits were found in males only, further evaluation of sex differences in responsiveness to supplementation is warranted. This trial was registered at the Australian and New Zealand Clinical Trial Register at https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370788 as ACTRN12616000732482p.


Assuntos
Cognição/efeitos dos fármacos , Curcumina/farmacologia , Suplementos Nutricionais , Óleos de Peixe/farmacologia , Sobrepeso/tratamento farmacológico , Idoso , Curcumina/administração & dosagem , Ácidos Docosa-Hexaenoicos/química , Ácidos Docosa-Hexaenoicos/farmacologia , Método Duplo-Cego , Quimioterapia Combinada , Ácido Eicosapentaenoico/química , Ácido Eicosapentaenoico/farmacologia , Feminino , Óleos de Peixe/administração & dosagem , Óleos de Peixe/química , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
8.
Menopause ; 28(1): 40-49, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32881835

RESUMO

OBJECTIVE: Following concerns about hormone therapy, postmenopausal women need alternative options to manage menopause-related symptoms and improve their well-being. A 14-week pilot study has shown that supplementation with resveratrol, a phytoestrogen with circulatory benefits, can improve aspects of well-being including chronic pain, which is a common complaint in postmenopausal women. We aimed to confirm these benefits in a larger, long-term study. METHODS: The Resveratrol for Healthy Ageing in Women study, a 24-month randomized, double-blind, placebo-controlled, two-period crossover intervention trial of resveratrol supplementation (75 mg BID) was conducted in 125 healthy postmenopausal women to evaluate effects on cognitive performance (results published elsewhere). Aspects of well-being including pain perception, mood and depressive symptoms, menopausal symptoms, sleep quality, and quality of life were assessed with questionnaires as secondary outcomes of the study. Cerebrovascular responsiveness to hypercapnia was measured as a surrogate marker of cerebrovascular function. RESULTS: Resveratrol supplementation reduced composite pain score (P < 0.001), especially in overweight individuals; this was associated with improvements in cerebrovascular responsiveness to hypercapnia (R = -0.329, P = 0.014). Somatic menopausal symptoms (P = 0.024) and general well-being (P = 0.010) were also improved after resveratrol supplementation. CONCLUSIONS: These results confirm the pilot study finding that resveratrol supplementation can reduce chronic pain in age-related osteoarthritis and improve menopause-related quality of life in postmenopausal women. These improvements are sustained by supplementation for at least 12 months and are associated with enhancement of circulatory function. CLINICAL TRIAL REGISTRATION: ACTRN12616000679482p.


Video Summary:http://links.lww.com/MENO/A638.


Assuntos
Pós-Menopausa , Qualidade de Vida , Estudos Cross-Over , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Menopausa , Percepção da Dor , Projetos Piloto , Resveratrol
9.
Rheumatol Adv Pract ; 4(2): rkaa036, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32968708

RESUMO

OBJECTIVES: OA is a leading cause of chronic pain and disability. Next to inflammation, vascular pathology has been hypothesized to play a role in its aetiology and progression. Owing to side effects and the low efficacy of pharmacological treatments, dietary supplements are popular as alternative treatments, but evidence of efficacy is limited. We tested whether fish oil and curcumin supplementation can reduce chronic pain and OA burden in older adults. METHODS: A 16-week randomized, double-blind, placebo-controlled, 2 × 2 factorial design supplementation trial with fish oil (2000 mg/day docosahexaenoic acid + 400 mg/day eicosapentaenoic acid), curcumin (160 mg/day) or a combination of both was undertaken in sedentary overweight/obese older adults. Secondary outcomes included treatment-induced changes in self-reported chronic pain and OA burden and whether changes were related to changes in small artery elasticity (surrogate marker for microvascular function), CRP (inflammatory marker) and well-being. RESULTS: The majority of participants (131 of 152) reported chronic pain, which was predominantly OA specific. Fish oil significantly reduced OA-specific pain (P = 0.002, Cohen's d = 0.56) and burden (P = 0.015, Cohen's d = 0.45) compared with no fish oil treatment; reductions were correlated with improvements in microvascular function and well-being. Curcumin, alone or in combination with fish oil, did not reduce pain measures. CONCLUSION: Our findings indicate potential for fish oil to alleviate OA pain and burden in overweight/obese older adults. Further investigations should be undertaken in patients with clinically diagnosed OA to evaluate fish oil alone and as an adjunct to conventional pharmacotherapy and to investigate underlying mechanisms. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Register, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370788, ACTRN12616000732482p.

10.
Nutrients ; 12(10)2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32977404

RESUMO

Curcumin has previously been shown to enhance mood in non-depressed older adults. However, observed benefits were limited to short-term supplementation (4 weeks). In a 16 week randomized, double-blind, placebo-controlled, 2 × 2 factorial design trial, we supplemented overweight or obese non-depressed adults (50-80 years) with curcumin (160 mg/day), fish oil (2000 mg docosahexaenoic acid +400 mg eicosapentaenoic acid/day), or a combination of both. Secondary outcomes included mental wellbeing measures (mood states and subjective memory complaints (SMCs)) and quality of life (QoL). Furthermore, plasma apolipoprotein E4 (APOE4) was measured to determine whether APOE4 status influences responses to fish oil. Curcumin improved vigour (p = 0.044) compared to placebo and reduced SMCs compared to no curcumin treatment (p = 0.038). Fish oil did not affect any mood states, SMCs or QoL; however, responses to fish oil were affected by APOE4 status. In APOE4 non-carriers, fish oil increased vigour (p = 0.030) and reduced total mood disturbances (p = 0.048) compared to placebo. Improvements in mental wellbeing were correlated with increased QoL. Combining curcumin with fish oil did not result in additive effects. This exploratory analysis indicates that regular supplementation with either curcumin or fish oil (limited to APOE4 non-carriers) has the potential to improve some aspects of mental wellbeing in association with better QoL.


Assuntos
Afeto/efeitos dos fármacos , Suplementos Nutricionais , Óleos de Peixe/administração & dosagem , Idoso , Apolipoproteína E4/sangue , Curcumina , Ácidos Docosa-Hexaenoicos/administração & dosagem , Método Duplo-Cego , Ácido Eicosapentaenoico/administração & dosagem , Feminino , Humanos , Masculino , Memória/efeitos dos fármacos , Saúde Mental , Pessoa de Meia-Idade , New South Wales , Obesidade , Sobrepeso , Qualidade de Vida
11.
J Bone Miner Res ; 35(11): 2121-2131, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32564438

RESUMO

Resveratrol, a naturally occurring polyphenol in red grapes and berries, can act as a phytoestrogen. It has been shown to improve both systemic and cerebral circulatory functions, possibly through activation of endothelial estrogen receptors. in vitro and in vivo studies in rodent models also indicate a bone-protective role for resveratrol, particularly in ovariectomized rat models that mimic postmenopausal osteoporosis caused by estrogen deficiency. Hypothesizing a circulatory benefit of resveratrol in bone tissue, we investigated whether resveratrol supplementation could improve bone health in postmenopausal women. The Resveratrol for Healthy Aging in Women (RESHAW) trial was a 24-month randomized, double-blind, placebo-controlled, two-period crossover intervention conducted to evaluate the effects of resveratrol (75 mg twice daily) on cognition, cerebrovascular function, bone health, cardiometabolic markers, and well-being in postmenopausal women. After 12 months of supplementation with resveratrol versus placebo, there were positive effects on bone density in the lumbar spine (+0.016 ± 0.003 g/cm2 ) and neck of femur (+0.005 ± 0.002 g/cm2 ), which were accompanied by a 7.24% reduction in C-terminal telopeptide type-1 collagen levels, a bone resorption marker, compared with placebo. The increase in bone mineral density in the femoral neck resulted in an improvement in T-score (+0.070 ± 0.018) and a reduction in the 10-year probability of major and hip fracture risk. The magnitude of improvement was higher in women with poor bone health biomarker status. Importantly, the improvement in femoral neck T-score with resveratrol correlated with improvement in perfusion. Our subanalysis also revealed that the bone-protective benefit of resveratrol was greater in participants who supplemented with vitamin D plus calcium. Regular supplementation with 75 mg of resveratrol twice daily has the potential to slow bone loss in the lumbar spine and femoral neck, common fracture sites in postmenopausal women without overt osteoporosis. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.


Assuntos
Densidade Óssea , Osteoporose Pós-Menopausa , Animais , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Colo do Fêmur , Humanos , Pós-Menopausa , Ratos , Resveratrol/farmacologia
12.
Nutr Metab Cardiovasc Dis ; 30(4): 625-633, 2020 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-32127335

RESUMO

BACKGROUND AND AIMS: Chronic conditions such as obesity, which contribute to endothelial dysfunction in older adults, can cause impairments in cerebrovascular perfusion, which is associated with accelerated cognitive decline. Supplementing the diet with bioactive nutrients that can enhance endothelial function, such as fish oil or curcumin, may help to counteract cerebrovascular dysfunction. METHODS AND RESULTS: A 16-week double-blind, randomized placebo-controlled trial was undertaken in 152 older sedentary overweight/obese adults (50-80 years, body mass index: 25-40 kg/m2) to investigate effects of fish oil (2000 mg docosahexaenoic acid + 400 mg eicosapentaenoic acid/day), curcumin (160 mg/day) or a combination of both on cerebrovascular function (measured by Transcranial Doppler ultrasound), systemic vascular function (blood pressure, heart rate and arterial compliance) and cardiometabolic (fasting glucose and blood lipids) and inflammatory (C-reactive protein) biomarkers. The primary outcome, cerebrovascular responsiveness to hypercapnia, was not affected by the interventions. However, cerebral artery stiffness was significantly reduced in males following fish oil supplementation (P = 0.007). Furthermore, fish oil reduced heart rate (P = 0.038) and serum triglycerides (P = 0.006) and increased HDL cholesterol (P = 0.002). Curcumin did not significantly affect these outcomes either alone or in combination with fish oil. CONCLUSION: Regular supplementation with fish oil but not curcumin improved biomarkers of cardiovascular and cerebrovascular function. The combined supplementation did not result in additional benefits. Further studies are warranted to identify an efficacious curcumin dose and to characterize (in terms of sex, BMI, cardiovascular and metabolic risk factors) populations whose cerebrovascular and cognitive functions might benefit from either intervention. CLINICAL TRIAL REGISTRATION: ACTRN12616000732482p.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Curcumina/administração & dosagem , Suplementos Nutricionais , Óleos de Peixe/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Obesidade/tratamento farmacológico , Rigidez Vascular/efeitos dos fármacos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Proteína C-Reativa/metabolismo , Sistema Cardiovascular/fisiopatologia , Curcumina/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Ácidos Docosa-Hexaenoicos/administração & dosagem , Método Duplo-Cego , Ácido Eicosapentaenoico/administração & dosagem , Feminino , Óleos de Peixe/efeitos adversos , Nível de Saúde , Humanos , Mediadores da Inflamação/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , New South Wales , Obesidade/diagnóstico , Obesidade/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
13.
Nutrients ; 10(10)2018 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-30279397

RESUMO

Purported benefits of long chain omega-3 polyunsaturated fatty acid (LCn-3PUFA) for brain function may be attributable, at least in part, to improved cerebral perfusion. A pilot randomised controlled trial was undertaken to investigate effects of taking a DHA-rich fish oil supplement for 20 weeks on cerebrovascular function, mood and cognitive performance. Borderline hypertensives aged 40⁻85 years with low habitual LCn-3PUFA intake took four capsules/day of EPAX (1600 mg DHA + 400 mg EPA) or placebo (corn oil). Cerebrovascular function was assessed at baseline and after 20 weeks in 38 completers (19 on each supplement) using transcranial Doppler ultrasound of blood flow in the middle cerebral artery at rest and whilst performing a battery of cognitive tasks (neurovascular coupling). The primary outcome, cerebrovascular responsiveness (CVR) to hypercapnia, increased 26% (p = 0.024) in women; there was no change in men. In contrast, neurovascular coupling increased significantly (p = 0.01 for the overall response) in men only; the latter correlated with an increase of EPA in erythrocytes (r = 0.616, p = 0.002). There was no associated improvement of mood or cognition in either men or women. These preliminary observations indicate that LCn-3PUFA supplementation has the potential to enhance blood flow in the brain in response to both hypercapnic and cognitive stimuli. Future studies should examine differential effects of EPA and DHA and take account of the gender differences in responsiveness to supplementation.


Assuntos
Encéfalo/efeitos dos fármacos , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Hipertensão/fisiopatologia , Hipertensão/psicologia , Adulto , Afeto/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Circulação Cerebrovascular/efeitos dos fármacos , Cognição/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Hipertensão/terapia , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
14.
Ageing Res Rev ; 48: 79-86, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30355506

RESUMO

Menopause is a critical period during which, without timely interventions, increased risks of cardiovascular and metabolic diseases, osteoporosis, sexual dysfunction and premature cognitive decline will contribute to diminished quality-of-life in women. Hormone therapy (HT) used to be the standard of care for managing vasomotor symptoms and prevention of chronic diseases until publication of the Women's Health Initiative (WHI) in 2002. Concerned about risks highlighted in WHI publications, many symptomatic women promptly ceased HT which resulted in increased vasomotor symptoms, osteoporosis-related-fractures and insomnia. Data from post-hoc WHI analyses and newer clinical trials consistently show reductions in coronary heart disease and mortality when estrogen therapy is initiated soon after menopause, whereas administration in later years and/or in combination with progesterone carries increased risks. However, no validated primary preventive strategies are available for younger postmenopausal women (<60 years), highlighting the need to re-evaluate the use of estrogen alone for which the risk-benefit balance appears positive. In contrast, in older women (>60 years), risks associated with oral HT exceed benefits; however transdermal estrogen may offer a safer alternative and should be further evaluated. Alternative therapies such as phytoestrogens and non-hormonal prescriptions may be beneficial for older women or those who are unsuitable for HT. Long-term head-to-head comparisons of HT with alternative interventions are warranted to confirm their efficacy for chronic disease prevention.


Assuntos
Terapia de Reposição de Estrogênios/tendências , Pós-Menopausa/metabolismo , Saúde da Mulher/tendências , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos como Assunto , Doença das Coronárias/metabolismo , Doença das Coronárias/prevenção & controle , Demência/metabolismo , Demência/prevenção & controle , Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios/efeitos adversos , Feminino , Humanos , Menopausa/efeitos dos fármacos , Menopausa/metabolismo , Pessoa de Meia-Idade , Fitoestrógenos/administração & dosagem , Pós-Menopausa/efeitos dos fármacos , Resveratrol/administração & dosagem , Medição de Risco/tendências , Fatores de Tempo
15.
Adv Nutr ; 9(2): 105-113, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29659685

RESUMO

The rate of cognitive decline in the elderly is highly variable. One potential factor contributing to accelerated cognitive decline is chronic systemic inflammation, because it has been linked to cognitive impairment and increased dementia risk. Certain lifestyle factors, such as excess body weight and sedentary behavior, can exacerbate a proinflammatory state in older adults, resulting in chronic low-grade inflammation. Supplementing the diet with curcumin, an anti-inflammatory polyphenolic compound from the curry spice turmeric, is a potential approach to prevent accelerated cognitive decline by counteracting chronic inflammatory processes. Although the anti-inflammatory effects of curcumin are well established, the potential cognitive benefits of curcumin were discovered more recently. Several animal and epidemiologic studies on the effect of curcumin supplementation on cognition showed promising results; however, randomized controlled trials in humans are limited. In this review, we identified 5 randomized controlled trials, of which only 2 observed a beneficial effect of curcumin supplementation on cognition by improving working memory. By critically examining the methodologies of those studies, we identified some limitations, one of which is that none of the studies explored the possibility that anti-inflammatory mechanisms were mediating cognitive benefits (i.e., no study tested participants with low-grade inflammation or measured inflammatory biomarkers). Other factors influencing the likelihood of conclusive outcomes include choice of study population (cognitively unimpaired compared with impaired), study duration, curcumin dose and its bioavailability, and neurocognitive test battery. On the basis of these findings, we offer recommendations for future studies to examine the potential cognitive benefits of curcumin in humans, which include evaluating its effects on cerebral endothelial vasodilator function and boosting its cognitive effects by combining it with long-chain omega-3 (n-3) fatty acids.


Assuntos
Anti-Inflamatórios/farmacologia , Cognição/efeitos dos fármacos , Disfunção Cognitiva/etiologia , Curcuma/química , Curcumina/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Memória/efeitos dos fármacos , Animais , Anti-Inflamatórios/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Curcumina/uso terapêutico , Demência/tratamento farmacológico , Suplementos Nutricionais , Ácidos Graxos Ômega-3/uso terapêutico , Feminino , Humanos , Inflamação/complicações , Inflamação/tratamento farmacológico , Masculino , Fitoterapia , Polifenóis/farmacologia , Polifenóis/uso terapêutico
16.
Ann N Y Acad Sci ; 1403(1): 150-163, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28945939

RESUMO

Recent evidence indicates that resveratrol, a phytoestrogen, can improve cognitive function in postmenopausal women by enhancing cerebral vasodilator responsiveness. We examine the effects of phytoestrogen supplementation on cognition and compare resveratrol with other phytoestrogens. Databases were searched for reports of randomized controlled trials (RCTs) containing terms describing phytoestrogens together with terms relating to cognition. Effect sizes were determined for changes in cognition. We identified 23 RCTs, 15 with isoflavone and eight with resveratrol or grape formulations. Six soy isoflavone studies showed positive cognitive effects of medium size. Greater benefits were seen in women who were <10 years postmenopausal and supplemented for <6 months. Small-to-medium effect-size cognitive benefits of resveratrol were seen in four studies of older adults of mixed gender and in postmenopausal women who took 150-200 mg resveratrol daily for at least 14 weeks. No benefits were seen in three studies using red clover or grape formulations. Supplementation with either soy isoflavone or resveratrol improved executive function and memory domains of cognitively normal older adults in half of the included studies, mostly with medium effect sizes. The cognitive benefit of resveratrol was related to improved cerebral perfusion.


Assuntos
Cognição/efeitos dos fármacos , Suplementos Nutricionais , Fitoestrógenos/farmacologia , Estilbenos/farmacologia , Humanos , Resveratrol
17.
Nutrients ; 9(5)2017 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-28498345

RESUMO

Long-chain omega-3 polyunsaturated fatty acids (LCn-3 PUFA) may improve brain functions by acting on endothelial cells in the cerebrovasculature to facilitate vasodilatation and perfusion. The aim of this review is to explore this hypothesis by analyzing the effect of LCn-3 PUFA supplementation on systemic vasodilator and cognitive function and finding evidence to link LCn-3 PUFA intake, vasodilator function and cognition. Forty randomized controlled trials examining the effect of LCn-3 PUFA supplementation in humans on either endothelial vasodilator function or cognition were identified and pooled effects measured with a weighted analysis. Compared to placebo, LCn-3 PUFA tended to increase flow-mediated dilatation and significantly improved cognitive function. Emerging evidence links vasodilator dysfunction to cognitive impairment, but evidence that LCn-3 PUFA can improve cognition through enhancements of vasodilator function is still lacking. Further research is needed to determine: (1) whether LCn-3 PUFA can enhance dilatation of cerebral vessels; (2) if improvements in cerebrovascular responsiveness by LCn-3 PUFA are accompanied by cognitive benefits; and (3) the target population groups.


Assuntos
Cognição/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Ácidos Graxos Ômega-3/administração & dosagem , Circulação Cerebrovascular/efeitos dos fármacos , Suplementos Nutricionais , Endotélio Vascular/metabolismo , Humanos , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Vasodilatadores/administração & dosagem
18.
Menopause ; 24(8): 916-922, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28350759

RESUMO

OBJECTIVE: Pain is a common complaint among postmenopausal women. It has been postulated that vascular dysfunction caused by estrogen decline at menopause plays a key role in the initiation and progression of degradative joint disease, namely age-related osteoarthritis. We evaluated whether supplementation with resveratrol, a phytoestrogen, could improve aspects of well-being such as chronic pain that is commonly experienced by postmenopausal women. METHODS: A 14-week randomized, double-blind, placebo-controlled intervention with trans-resveratrol (75 mg, twice daily) was conducted in 80 healthy postmenopausal women. Aspects of well-being, including pain, menopausal symptoms, sleep quality, depressive symptoms, mood states, and quality of life were assessed by Short form-36 at baseline and at the end of treatment. Rating scales were averaged to provide a composite score representing overall well-being. Cerebral vasodilator responsiveness to hypercapnia was also assessed as a surrogate marker for cerebrovascular function. RESULTS: Compared with placebo treatment, there was a significant reduction in pain and an improvement in total well-being after resveratrol supplementation. Both benefits, including measures of quality of life, correlated with improvements in cerebrovascular function. CONCLUSIONS: Our preliminary findings indicate potential for resveratrol treatment to reduce chronic pain in age-related osteoarthritis. Resveratrol consumption may also boost perceptions of well-being in postmenopausal women. Further investigation to elucidate underlying mechanisms is warranted.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Osteoartrite , Dor/prevenção & controle , Pós-Menopausa , Estilbenos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/administração & dosagem , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Medição da Dor , Fitoestrógenos/administração & dosagem , Fitoestrógenos/uso terapêutico , Resveratrol , Estilbenos/administração & dosagem , Resultado do Tratamento
19.
Nutrients ; 9(1)2017 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-28054939

RESUMO

We tested whether chronic supplementation with resveratrol (a phytoestrogen) could improve cerebrovascular function, cognition and mood in post-menopausal women. Eighty post-menopausal women aged 45-85 years were randomised to take trans-resveratrol or placebo for 14 weeks and the effects on cognitive performance, cerebral blood flow velocity and pulsatility index (a measure of arterial stiffness) in the middle cerebral artery (using transcranial Doppler ultrasound), and cerebrovascular responsiveness (CVR) to both cognitive testing and hypercapnia were assessed. Mood questionnaires were also administered. Compared to placebo, resveratrol elicited 17% increases in CVR to both hypercapnic (p = 0.010) and cognitive stimuli (p = 0.002). Significant improvements were observed in the performance of cognitive tasks in the domain of verbal memory (p = 0.041) and in overall cognitive performance (p = 0.020), which correlated with the increase in CVR (r = 0.327; p = 0.048). Mood tended to improve in multiple measures, although not significantly. These results indicate that regular consumption of a modest dose of resveratrol can enhance both cerebrovascular function and cognition in post-menopausal women, potentially reducing their heightened risk of accelerated cognitive decline and offering a promising therapeutic treatment for menopause-related cognitive decline.


Assuntos
Afeto/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Cognição/efeitos dos fármacos , Pós-Menopausa/sangue , Estilbenos/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Fitoestrógenos/farmacologia , Resveratrol , Inquéritos e Questionários
20.
Clin Colorectal Cancer ; 16(2): e45-e54, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27825672

RESUMO

BACKGROUND: Recent data has created uncertainty regarding the benefit of adjuvant fluoropyrimidine-containing chemotherapy following preoperative chemoradiotherapy and surgical resection for locally advanced rectal cancer (LARC). In particular, patients with a pathologic complete response (pCR) may derive no benefit from adjuvant chemotherapy. PATIENTS AND METHODS: This is a retrospective analysis of patients with LARC, diagnosed between January 1, 2003 and December 31, 2014 at 3 Melbourne health services. Patients were identified from the Australian Comprehensive Cancer Outcomes and Research Database, where a defined data set is prospectively collected on consecutive patients. Patient demographics, pCR rates, postoperative treatment, recurrence, and survival were analyzed. RESULTS: A total of 717 patients with LARC were identified, of whom 555 (77%) had received preoperative long-course chemoradiation followed by surgery. Four hundred fifty-two of 555 patients (81%) subsequently received adjuvant fluoropyrimidine-based chemotherapy. At a median follow-up of 45.9 months, 95 (21%) patients in the adjuvant chemotherapy group and 20 (19%) in the surveillance group had relapsed. Five-year relapse-free survival was 77% in the adjuvant chemotherapy group and 71% in the surveillance group with no significant difference on univariate analysis (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.58-1.51; P = .780). No significant impact on relapse-free survival was seen for either pCR or non-pCR patients. Five-year overall survival (OS) was 85% in the adjuvant chemotherapy group and 74% in the surveillance group with a nonsignificant trend towards OS benefit (HR, 0.62; 95% CI, 0.37-1.05; P = .074). A significant OS benefit favoring adjuvant chemotherapy was seen in the non-pCR subset of patients (HR, 0.49; 95% CI, 0.28-0.86; P = .014). CONCLUSION: A high proportion of patients in this routine practice cohort received adjuvant chemotherapy following preoperative treatment and surgery for LARC. Adjuvant chemotherapy administration was associated with a significant improvement in 5-year OS only in the patients with a non-pCR.


Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Retais/terapia , Adenocarcinoma/patologia , Idoso , Austrália , Quimioterapia Adjuvante/métodos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Recidiva Local de Neoplasia , Modelos de Riscos Proporcionais , Neoplasias Retais/patologia , Estudos Retrospectivos , Taxa de Sobrevida
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