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1.
  • Abrahams, Harriët J. G., et al. (författare)
  • Moderators of the effect of psychosocial interventions on fatigue in women with breast cancer and men with prostate cancer : Individual patient data meta-analyses
  • 2020
  • Ingår i: Psycho-Oncology. - : Wiley. - 1057-9249 .- 1099-1611. ; 29:11, s. 1772-1785
  • Forskningsöversikt (refereegranskat)abstract
    • ObjectivePsychosocial interventions can reduce cancer‐related fatigue effectively. However, it is still unclear if intervention effects differ across subgroups of patients. These meta‐analyses aimed at evaluating moderator effects of (a) sociodemographic characteristics, (b) clinical characteristics, (c) baseline levels of fatigue and other symptoms, and (d) intervention‐related characteristics on the effect of psychosocial interventions on cancer‐related fatigue in patients with non‐metastatic breast and prostate cancer.MethodsData were retrieved from the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) consortium. Potential moderators were studied with meta‐analyses of pooled individual patient data from 14 randomized controlled trials through linear mixed‐effects models with interaction tests. The analyses were conducted separately in patients with breast (n = 1091) and prostate cancer (n = 1008).ResultsStatistically significant, small overall effects of psychosocial interventions on fatigue were found (breast cancer: β = −0.19 [95% confidence interval (95%CI) = −0.30; −0.08]; prostate cancer: β = −0.11 [95%CI = −0.21; −0.00]). In both patient groups, intervention effects did not differ significantly by sociodemographic or clinical characteristics, nor by baseline levels of fatigue or pain. For intervention‐related moderators (only tested among women with breast cancer), statistically significant larger effects were found for cognitive behavioral therapy as intervention strategy (β = −0.27 [95%CI = −0.40; −0.15]), fatigue‐specific interventions (β = −0.48 [95%CI = −0.79; −0.18]), and interventions that only targeted patients with clinically relevant fatigue (β = −0.85 [95%CI = −1.40; −0.30]).ConclusionsOur findings did not provide evidence that any selected demographic or clinical characteristic, or baseline levels of fatigue or pain, moderated effects of psychosocial interventions on fatigue. A specific focus on decreasing fatigue seems beneficial for patients with breast cancer with clinically relevant fatigue.
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2.
  • Adlard, Kirsten N, et al. (författare)
  • Peer support for the maintenance of physical activity and health in cancer survivors : the PEER trial - a study protocol of a randomised controlled trial.
  • 2019
  • Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407 .- 1471-2407. ; 19:1, s. 656-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Despite an overwhelming body of evidence showing the benefits of physical activity (PA) and exercise for cancer survivors, few survivors meet the exercise oncology guidelines. Moreover, initiating, let alone maintaining exercise programs with cancer survivors continues to have limited success. The aim of this trial is to evaluate the influence of peer support on moderate-to-vigorous PA (MVPA) and various markers of health 12 months following a brief supervised exercise intervention in cancer survivors.METHODS: Men and women previously diagnosed with histologically-confirmed breast, colorectal or prostate cancer (n = 226), who are >1-month post-treatment, will be invited to participate in this trial. Once enrolled, participants will complete 4 weeks (12 sessions) of supervised high intensity interval training (HIIT). On completion of the supervised phase, both groups will be provided with written recommendations and verbally encouraged to achieve three HIIT sessions per week, or equivalent exercise that meets the exercise oncology guidelines. Participants will be randomly assigned to receive 12 months of peer support, or no peer support (control). Primary and secondary outcomes will be assessed at baseline, after the 4-week supervised HIIT phase and at 3-, 6- and 12-months. Primary outcomes will include accelerometry-derived MVPA and prescribed HIIT session adherence; whilst secondary outcomes will include cardiorespiratory fitness ([Formula: see text]), body composition, quality of life and select cytokines, myokines and inflammatory markers. Random effects mixed modelling will be used to compare mean changes in outcomes between groups at each time point. A group x time interaction will be used to formally test for differences between groups (alpha =0.05); utilising intention-to-treat analyses.DISCUSSION: If successful, peer support may be proposed, adopted and implemented as a strategy to encourage cancer survivors to maintain exercise beyond the duration of a short-term, supervised intervention. A peer support-exercise model has the long-term potential to reduce comorbidities, improve physical and mental wellbeing, and significantly reduce the burden of disease in cancer survivors.ETHICS: Human Research Ethics Committee of Bellberry Ltd. (#2015-12-840).TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry 12618001855213 . Retrospectively registered 14 November 2018. Trial registration includes all components of the WHO Trial Registration Data Set, as recommended by the ICMJE.
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3.
  • Devin, James L, et al. (författare)
  • Cardiorespiratory Fitness and Body Composition Responses to Different Intensities and Frequencies of Exercise Training in Colorectal Cancer Survivors.
  • 2018
  • Ingår i: Clinical colorectal cancer. - : Elsevier BV. - 1938-0674 .- 1533-0028. ; 17:2, s. e269-e279
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Deteriorations in cardiorespiratory fitness (V˙o2peak) and body composition are associated with poor prognosis after colorectal cancer treatment. However, the optimal intensity and frequency of aerobic exercise training to improve these outcomes in colorectal cancer survivors is unknown.PATIENTS AND METHODS: This trial compared 8 weeks of moderate-intensity continuous exercise (MICE; 50 minutes; 70% peak heart rate [HRpeak]; 24 sessions), with high-intensity interval exercise (HIIE; 4 × 4 minutes; 85%-95% HRpeak) at an equivalent (HIIE; 24 sessions) and tapered frequency (HIIE-T; 16 sessions) on V˙o2peak and on lean and fat mass, measured at baseline, 4, 8, and 12 weeks.RESULTS: Increases in V˙o2peak were significantly greater after both 4 (+3.0 mL·kg-1·min-1, P = .008) and 8 (+2.3 mL·kg-1·min-1, P = .049) weeks of HIIE compared to MICE. After 8 weeks, there was a significantly greater reduction in fat mass after HIIE compared to MICE (-0.7 kg, P = .038). Four weeks after training, the HIIE group maintained elevated V˙o2peak (+3.3 mL·kg-1·min-1, P = .006) and reduced fat mass (-0.7 kg, P = .045) compared to the MICE group, with V˙o2peak in the HIIE-T also being superior to the MICE group (+2.8 mL·kg-1·min-1, P = .013).CONCLUSION: Compared to MICE, HIIE promotes superior improvements and short-term maintenance of V˙o2peak and fat mass improvements. HIIE training at a reduced frequency also promotes maintainable cardiorespiratory fitness improvements. In addition to promoting accelerated and superior benefits to the current aerobic exercise guidelines, HIIE promotes clinically relevant improvements even with a substantial reduction in exercise training and for a period after withdrawal.
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4.
  • Devin, James L, et al. (författare)
  • The influence of high-intensity compared with moderate-intensity exercise training on cardiorespiratory fitness and body composition in colorectal cancer survivors : a randomised controlled trial.
  • 2016
  • Ingår i: Journal of cancer survivorship. - : Springer Science and Business Media LLC. - 1932-2259 .- 1932-2267. ; 10:3, s. 467-479
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Following colorectal cancer diagnosis and anti-cancer therapy, declines in cardiorespiratory fitness and body composition lead to significant increases in morbidity and mortality. There is increasing interest within the field of exercise oncology surrounding potential strategies to remediate these adverse outcomes. This study compared 4 weeks of moderate-intensity exercise (MIE) and high-intensity exercise (HIE) training on peak oxygen consumption (V̇O2peak) and body composition in colorectal cancer survivors.METHODS: Forty seven post-treatment colorectal cancer survivors (HIE = 27 months post-treatment; MIE = 38 months post-treatment) were randomised to either HIE [85-95 % peak heart rate (HRpeak)] or MIE (70 % HRpeak) in equivalence with current physical activity guidelines and completed 12 training sessions over 4 weeks.RESULTS: HIE was superior to MIE in improving absolute (p = 0.016) and relative (p = 0.021) V̇O2peak. Absolute (+0.28 L.min(-1), p < 0.001) and relative (+3.5 ml.kg(-1).min(-1), p < 0.001) V̇O2 peak were increased in the HIE group but not the MIE group following training. HIE led to significant increases in lean mass (+0.72 kg, p = 0.002) and decreases in fat mass (-0.74 kg, p < 0.001) and fat percentage (-1.0 %, p < 0.001), whereas no changes were observed for the MIE group. There were no severe adverse events.CONCLUSIONS: In response to short-term training, HIE is a safe, feasible and efficacious intervention that offers clinically meaningful improvements in cardiorespiratory fitness and body composition for colorectal cancer survivors.IMPLICATIONS FOR CANCER SURVIVORS: HIE appears to offer superior improvements in cardiorespiratory fitness and body composition in comparison to current physical activity recommendations for colorectal cancer survivors and therefore may be an effective clinical utility following treatment.
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5.
  • Flannick, Jason, et al. (författare)
  • Loss-of-function mutations in SLC30A8 protect against type 2 diabetes.
  • 2014
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 46:4, s. 357-357
  • Tidskriftsartikel (refereegranskat)abstract
    • Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ∼150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 × 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant (p.Lys34Serfs*50) demonstrated reduced glucose levels (-0.17 s.d., P = 4.6 × 10(-4)). The two most common protein-truncating variants (p.Arg138* and p.Lys34Serfs*50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk, and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.
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6.
  • Manning, Alisa, et al. (författare)
  • A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
  • 2017
  • Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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7.
  • Newton, Robert U, et al. (författare)
  • Exercise Mode Specificity for Preserving Spine and Hip Bone Mineral Density in Prostate Cancer Patients.
  • 2019
  • Ingår i: Medicine & Science in Sports & Exercise. - 0195-9131 .- 1530-0315. ; 51:4, s. 607-614
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Androgen deprivation therapy (ADT) in men with prostate cancer (PCa) is associated with an array of adverse effects, including reduced bone mineral density (BMD) predisposing patients to increased fracture risk. Our purpose was to examine the effects of targeted exercise modes on BMD in men with PCa undergoing ADT.METHODS: Between 2009 and 2012, 154 PCa patients 43-90 yr old on ADT were randomized to exercise targeting the musculoskeletal system (impact loading + resistance training [ImpRes], n = 57) supervised for 12 months, cardiovascular and muscular systems (aerobic + resistance training, n = 50) supervised for 6 months followed by a 6-month home-based program, or delayed aerobic exercise (DelAer, n = 47) received exercise information for 6 months followed by 6 months of supervised aerobic exercise (stationary cycling). End points were lumbar spine, hip and whole-body BMD measured by dual-energy x-ray absorptiometry with secondary end points of lean and fat mass, appendicular skeletal muscle mass, and neuromuscular strength. ANOVA was used to compare the exercise groups with DelAer at 6 and 12 months.RESULTS: There was a between-group difference in BMD for ImpRes and DelAer at the spine (6 months, P = 0.039; 12 months, P = 0.035) and femoral neck (6 months, P = 0.050), with decline attenuated in ImpRes (~-1.0% vs ~-2.0%). Compared with DelAer, ImpRes increased appendicular skeletal muscle at 6 months (0.3 kg, P = 0.045) and improved muscle strength at 6 and 12 months (P ≤ 0.012) by 9%-34%. A limitation was inclusion of well-functioning patients.CONCLUSION: Combined impact loading and resistance exercise attenuates bone loss at the spine and enhances overall musculoskeletal function in PCa patients undergoing ADT.
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8.
  • Skinner, Tina L, et al. (författare)
  • Impact of a brief exercise program on the physical and psychosocial health of prostate cancer survivors : A pilot study.
  • 2016
  • Ingår i: Asia-Pacific Journal of Clinical Oncology. - : Wiley. - 1743-7555 .- 1743-7563. ; 12:3, s. 225-234
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: It is well established that exercise is beneficial for prostate cancer survivors. The challenge for health professionals is to create effective strategies to encourage survivors to exercise in the community. Many community exercise programs are brief in duration (e.g. <5 exercise sessions); whilst evidence for the efficacy of exercise within the literature are derived from exercise programs ≥8 weeks in duration, it is unknown if health benefits can be obtained from a shorter program. This study examined the effect of a four-session individualized and supervised exercise program on the physical and psychosocial health of prostate cancer survivors.METHODS: Fifty-one prostate cancer survivors (mean age 69±7 years) were prescribed 1 h, individualized, supervised exercise sessions once weekly for 4 weeks. Participants were encouraged to increase their physical activity levels outside of the exercise sessions. Objective measures of muscular strength, exercise capacity, physical function and flexibility; and self-reported general, disease-specific and psychosocial health were assessed at baseline and following the intervention.RESULTS: Improvements were observed in muscle strength (leg press 17.6 percent; P < 0.001), exercise capacity (400-m walk 9.3 percent; P < 0.001), physical function (repeated chair stands 20.1 percent, usual gait speed 19.3 percent, timed up-and-go 15.0 percent; P < 0.001), flexibility (chair sit and reach +2.9 cm; P < 0.001) and positive well-being (P = 0.014) following the exercise program.CONCLUSION: A four-session exercise program significantly improved the muscular strength, exercise capacity, physical function and positive well-being of prostate cancer survivors. This short-duration exercise program is safe and feasible for prostate cancer survivors and a randomized controlled trial is now required to determine whether a similar individualized exercise regimen improves physical health and mental well-being over the short, medium and long term.
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9.
  • Taaffe, Dennis R, et al. (författare)
  • Effects of Different Exercise Modalities on Fatigue in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy : A Year-long Randomised Controlled Trial.
  • 2017
  • Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 72:2, s. 293-299
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Physical exercise mitigates fatigue during androgen deprivation therapy (ADT); however, the effects of different exercise prescriptions are unknown.OBJECTIVES: To determine the long-term effects of different exercise modes on fatigue in prostate cancer patients undergoing ADT.DESIGN, SETTING, AND PARTICIPANTS: Between 2009 and 2012, 163 prostate cancer patients aged 43-90 y on ADT were randomised to exercise targeting the musculoskeletal system (impact loading+resistance training; ILRT; n=58), the cardiovascular and muscular systems (aerobic+resistance training; ART; n=54), or to usual care/delayed exercise (DEL; n=51) for 12 mo across university-affiliated exercise clinics in Australia.INTERVENTION: Supervised ILRT for 12 mo, supervised ART for 6 mo followed by a 6-mo home program, and DEL received a printed booklet on exercise information for 6 mo followed by 6-mo stationary cycling exercise.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Fatigue was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 36 and vitality using the Short Form-36. Analysis of variance was used to compare outcomes for groups at 6 mo and 12 mo.RESULTS AND LIMITATIONS: Fatigue was reduced (p=0.005) in ILRT at 6 mo and 12 mo (∼5 points), and in ART (p=0.005) and DEL (p=0.022) at 12 mo. Similarly, vitality increased for all groups (p≤0.001) at 12 mo (∼4 points). Those with the highest levels of fatigue and lowest vitality improved the most with exercise (ptrend<0.001). A limitation was inclusion of mostly well-functioning individuals.CONCLUSIONS: Different exercise modes have comparable effects on reducing fatigue and enhancing vitality during ADT. Patients with the highest levels of fatigue and lowest vitality had the greatest benefits.PATIENT SUMMARY: We compared the effects of different exercise modes on fatigue in men on androgen deprivation therapy. All exercise programs reduced fatigue and enhanced vitality. We conclude that undertaking some form of exercise will help reduce fatigue, especially in those who are the most fatigued.
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10.
  • Wuttke, Matthias, et al. (författare)
  • A catalog of genetic loci associated with kidney function from analyses of a million individuals
  • 2019
  • Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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