55,738 research outputs found
Development of an exercise intervention for the prevention of musculoskeletal shoulder problems after breast cancer treatment : the prevention of shoulder problems trial (UK PROSPER)
Get PDFBackground
Musculoskeletal shoulder problems are common after breast cancer treatment. There is some evidence to suggest that early postoperative exercise is safe and may improve shoulder function. We describe the development and delivery of a complex intervention for evaluation within a randomised controlled trial (RCT), designed to target prevention of musculoskeletal shoulder problems after breast cancer surgery (The Prevention of Shoulder Problems Trial; PROSPER).
Methods
A pragmatic, multicentre RCT to compare the clinical and cost-effectiveness of best practice usual care versus a physiotherapy-led exercise and behavioural support intervention in women at high risk of shoulder problems after breast cancer treatment. PROSPER will recruit 350 women from approximately 15 UK centres, with follow-up at 6 and 12 months. The primary outcome is shoulder function at 12 months; secondary outcomes include postoperative pain, health related quality of life, adverse events and healthcare resource use. A multi-phased approach was used to develop the PROSPER intervention which was underpinned by existing evidence and modified for implementation after input from clinical experts and women with breast cancer. The intervention was tested and refined further after qualitative interviews with patients newly diagnosed with breast cancer; a pilot RCT was then conducted at three UK clinical centres.
Discussion
The PROSPER intervention incorporates three main components: shoulder-specific exercises targeting range of movement and strength; general physical activity; and behavioural strategies to encourage adherence and support exercise behaviour. The final PROSPER intervention is fully manualised with clear, documented pathways for clinical assessment, exercise prescription, use of behavioural strategies, and with guidance for treatment of postoperative complications. This paper adheres to TIDieR and CERT recommendations for the transparent, comprehensive and explicit reporting of complex interventions.
Trial registration: International Standard Randomised Controlled Trial Number: ISRCTN 35358984
Role of physiotherapy in supporting recovery from breast cancer treatment: a qualitative study embedded within the UK PROSPER trial
Get PDFObjectives To explore the experiences of women with breast cancer taking part in an early physiotherapy-led exercise intervention compared with the experiences of those receiving usual care. To understand physiotherapists' experience of delivering the trial intervention. To explore acceptability of the intervention and issues related to the implementation of the Prevention Of Shoulder Problems (PROSPER) programme from participant and physiotherapist perspective. Design Qualitative semistructured interviews with thematic analysis. Setting UK National Health Service. Participants Twenty participants at high risk of shoulder problems after breast cancer surgery recruited to the UK PROSPER trial (10 each from the intervention arm and control arm), and 11 physiotherapists who delivered the intervention. Trial participants were sampled using convenience sampling. Physiotherapists were purposively sampled from high and low recruiting sites. Results Participants described that the PROSPER exercise intervention helped them feel confident in what their body could do and helped them regain a sense of control in the context of cancer treatment, which was largely disempowering. Control arm participants expressed less of a sense of control over their well-being. Physiotherapists found the exercise intervention enjoyable to deliver and felt it was valuable to their patients. The extra time allocated for appointments during intervention delivery made physiotherapists feel they were providing optimal care, being the 'perfect physio'. Lessons were learnt about the implementation of a complex exercise intervention for women with breast cancer, and the issues raised will inform the development of a future implementation strategy. Conclusions A physiotherapist-delivered early supported exercise intervention with integrated behavioural strategies helped women at risk of shoulder problems following breast cancer treatment to feel more confident in their ability to mobilise their arm post-surgery. A physiotherapist-delivered early supported exercise intervention with integrated behavioural strategies may address the sense of powerlessness that many women experience during breast cancer treatment. Trial registration number ISRCTN35358984
Incident venous thromboembolic events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)
Get PDF<p>Background: Venous thromboembolic events (VTE), including deep venous thrombosis and pulmonary embolism, are common in older age. It has been suggested that statins might reduce the risk of VTE however positive results from studies of middle aged subjects may not be generalisable to elderly people. We aimed to determine the effect of pravastatin on incident VTE in older people; we also studied the impact of clinical and plasma risk variables.</p>
<p>Methods: This study was an analysis of incident VTE using data from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), a randomized, double-blind, placebo-controlled trial of pravastatin in men and women aged 70-82. Mean follow-up was 3.2 years. Risk for VTE was examined in non-warfarin treated pravastatin (n = 2834) and placebo (n = 2865) patients using a Cox's proportional hazard model, and the impact of other risk factors assessed in a multivariate forward stepwise regression analysis. Baseline clinical characteristics, blood biochemistry and hematology variables, plasma levels of lipids and lipoproteins, and plasma markers of inflammation and adiposity were compared. Plasma markers of thrombosis and hemostasis were assessed in a nested case (n = 48) control (n = 93) study where the cohort was those participants, not on warfarin, for whom data were available.</p>
<p>Results: There were 28 definite cases (1.0%) of incident VTE in the pravastatin group recipients and 20 cases (0.70%) in placebo recipients. Pravastatin did not reduce VTE in PROSPER compared to placebo [unadjusted hazard ratio (95% confidence interval) 1.42 (0.80, 2.52) p = 0.23]. Higher body mass index (BMI) [1.09 (1.02, 1.15) p = 0.0075], country [Scotland vs Netherlands 4.26 (1.00, 18.21) p = 0.050 and Ireland vs Netherlands 6.16 (1.46, 26.00) p = 0.013], lower systolic blood pressure [1.35 (1.03, 1.75) p = 0.027] and lower baseline Mini Mental State Examination (MMSE) score [1.19 (1.01, 1.41) p = 0.034] were associated with an increased risk of VTE, however only BMI, country and systolic blood pressure remained significant on multivariate analysis. In a nested case control study of definite VTE, plasma Factor VIII levels were associated with VTE [1.52 (1.01, 2.28), p = 0.044]. However no other measure of thrombosis and haemostasis was associated with increased risk of VTE.</p>
<p>Conclusions: Pravastatin does not prevent VTE in elderly people at risk of vascular disease. Blood markers of haemostasis and inflammation are not strongly predictive of VTE in older age however BMI, country and lower systolic blood pressure are independently associated with VTE risk.</p>
The incidence and risk factors for new onset atrial fibrillation in the PROSPER study
Get PDFAims Atrial fibrillation/flutter (AF) is the most common arrhythmia in older people. It associates with reduced exercise capacity, increased risk of stroke, and mortality. We aimed to determine retrospectively whether pravastatin reduces the incidence of AF and whether any electrocardiographic measures or clinical conditions might be risk factors for its development. Methods and results The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) was a randomized, double-blind controlled trial that recruited 5804 individuals aged 70-82 years with a history of, or risk factors for, vascular disease. A total of 2891 were allocated to pravastatin and 2913 to placebo; mean follow-up was 3.2 years. Electrocardiograms (ECGs), which were recorded at baseline, annually thereafter, and at run-out, were processed by computer and reviewed manually. In all, 264 of 2912 (9.1%) of the placebo group and 283 of 2888 (9.8%) of the pravastatin-treated group developed AF [hazard ratio 1.08 (0.92,1.28), P = 0.35)]. Multivariate analysis showed that PR and QTc intervals, age, left ventricular hypertrophy, and ST-T abnormalities were related to development of AF after adjustment for many variables including alcohol consumption, which itself was univariately predictive of developing AF. Previous myocardial infarction on the ECG was not a risk factor. A history of vascular disease was strongly linked with developing AF but not diabetes and hypertension. Conclusion Pravastatin does not reduce the incidence of AF in older people at risk of vascular disease, at least in the short-medium term. Risk factors for AF include older age, prolongation of PR or QTc intervals, left ventricular hypertrophy, and ST-T abnormalities on the EC
The UN-SUSTAINABLE Match in HCV Recipients. Evidences from the Italian D-MELD Study on Balancing Donor-Recipient Risk Factors
No full textThe UN-SUSTAINABLE Match in HCV Recipients. Evidences from the Italian D-MELD Study on Balancing Donor-Recipient Risk Factor
C-Reactive protein and genetic variants and cognitive decline in old age: the PROSPER Study
Get PDFBackground: Plasma concentrations of C-reactive protein (CRP), a marker of chronic inflammation, have been associated with cognitive impairment in old age. However, it is unknown whether CRP is causally linked to cognitive decline.
Methods and Findings: Within the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trial, with 5680 participants with a mean age of 75 years, we examined associations of CRP levels and its genetic determinants with cognitive performance and decline over 3.2 years mean follow-up. Higher plasma CRP concentrations were associated with poorer baseline performance on the Stroop test (P = 0.001) and Letter Digit Tests (P, 0.001), but not with the immediate and delayed Picture Learning Test (PLT; both P>0.5). In the prospective analyses, higher CRP concentrations associated with increased rate of decline in the immediate PLT (P = 0.016), but not in other cognitive tests (all p>0.11). Adjustment for prevalent cardiovascular risk factors and disease did not change the baseline associations nor associations with cognitive decline during follow-up. Four haplotypes of CRP were used and, compared to the common haplotype, carrierships associated strongly with levels of CRP (all P < 0.007). In comparison to strong associations of apolipoprotein E with cognitive measures, associations of CRP haplotypes with such measures were inconsistent.
Conclusion: Plasma CRP concentrations associate with cognitive performance in part through pathways independent of (risk factors for) cardiovascular disease. However, lifelong exposure to higher CRP levels does not associate with poorer cognitive performance in old age. The current data weaken the argument for a causal role of CRP in cognitive performance, but further study is warranted to draw definitive conclusions
Lack of effect of pravastatin on cerebral blood flow or parenchymal volume loss in elderly at risk for vascular disease
Get PDF<p><b>Background and Purpose:</b> Ageing is associated with a decline in cerebral blood flow. Animal studies have shown that cholesterol-lowering therapy with statins might preserve cerebral blood flow (CBF). We examined the effect of 40 mg pravastatin on the decline in CBF and brain volume in a subset of elderly subjects participating in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial.</p>
<p><b>Methods:</b> Randomization was not stratified according to whether or not subjects participated in the MRI substudy. In 391 men (n=226) and women (n=165) aged 70 to 82 years (mean±SD, 75±3.2), we measured total CBF (in mL/min) at baseline and after a mean±SD follow-up of 33±1.4 months with a gradient-echo phase-contrast MRI technique. Total CBF was defined as the summed flows in both internal carotid and vertebral arteries. Parenchymal volume (whole brain) was segmented with the use of in-house–developed semiautomatic software.</p>
<p><b>Results:</b> Total CBF significantly declined in the placebo-allocated group, from 521±83 to 504±92 mL/min (P=0.0036) and in the pravastatin-allocated group from 520±94 to 506±92 mL/min (P=0.018). This decline was not significantly different between treatment groups (P=0.56). There was also a significant reduction in brain volume over time (P<0.001), which was not different between the treatment groups (P=0.47). When expressed per unit of parenchymal volume, the decline in CBF over time was no longer statistically significant.</p>
<p><b>Conclusions:</b> Elderly people at risk for cerebral vascular disease had a significant decline in CBF with increasing age that was explained by a concomitant reduction in brain volume. Treatment with 40 mg pravastatin daily had no beneficial effect on total CBF.</p>
Circulating interleukin-10 and risk of cardiovascular events: a prospective study in the elderly at risk
Get PDF<p><b>Objective:</b> The goal of this study was to examine the association of the antiinflammatory interleukin-10 (IL-10) with risk of cardiovascular disease (CVD).</p>
<p><b>Methods and Results:</b> In the PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) cohort, we related baseline concentrations of circulating IL-10 to risk of CVD events in a nested case (n=819)-control (n=1618) study of 3.2 years of follow-up. Circulating IL-10 showed few strong associations with classical risk factors but was positively correlated with IL-6 and C-reactive protein. IL-10 was positively associated with risk of CVD events (odds ratio [OR] 1.17, 95% CI 1.05 to 1.31 per unit increase in log IL-10) after adjusting for classical risk factors and C-reactive protein. Furthermore, IL-10 was associated more strongly with CVD risk among those with no previous history of CVD (OR 1.42, 95% CI 1.18 to 1.70), compared with those with previous CVD (OR 1.04, 95% CI 0.90 to 1.19; P=0.018). Overall, IL-10 showed a modest ability to add discrimination to classical risk factors (C-statistic +0.005, P=0.002).</p>
<p><b>Conclusion:</b> Baseline circulating levels of the antiinflammatory IL-10 are positively associated with risk of CVD among the elderly without prior CVD events, although the association is less evident in those with a history of CVD. Additional epidemiological and mechanistic studies investigating the role of IL-10 in CVD are warranted.</p>
Genome-wide study of gene variants associated with differential cardiovascular event reduction by Pravastatin therapy
Get PDFStatin therapy reduces the risk of coronary heart disease (CHD), however, the person-to-person variability in response to statin therapy is not well understood. We have investigated the effect of genetic variation on the reduction of CHD events by pravastatin. First, we conducted a genome-wide association study of 682 CHD cases from the Cholesterol and Recurrent Events (CARE) trial and 383 CHD cases from the West of Scotland Coronary Prevention Study (WOSCOPS), two randomized, placebo-controlled studies of pravastatin. In a combined case-only analysis, 79 single nucleotide polymorphisms (SNPs) were associated with differential CHD event reduction by pravastatin according to genotype (P < 0.0001), and these SNPs were analyzed in a second stage that included cases as well as non-cases from CARE and WOSCOPS and patients from the PROspective Study of Pravastatin in the Elderly at Risk/PHArmacogenomic study of Statins in the Elderly at risk for cardiovascular disease (PROSPER/PHASE), a randomized placebo controlled study of pravastatin in the elderly. We found that one of these SNPs (rs13279522) was associated with differential CHD event reduction by pravastatin therapy in all 3 studies: P = 0.002 in CARE, P = 0.01 in WOSCOPS, P = 0.002 in PROSPER/PHASE. In a combined analysis of CARE, WOSCOPS, and PROSPER/PHASE, the hazard ratio for CHD when comparing pravastatin with placebo decreased by a factor of 0.63 (95% CI: 0.52 to 0.75) for each extra copy of the minor allele (P = 4.8x10(-7)). This SNP is located in DnaJ homolog subfamily C member 5B (DNAJC5B) and merits investigation in additional randomized studies of pravastatin and other statins
Genome-wide association study of genetic determinants of LDL-c response to atorvastatin therapy: importnace of Lp(a)
Get PDFWe carried out a genome-wide association study (GWAS) of LDL-c response to statin using data from participants in the Collaborative Atorvastatin Diabetes Study (CARDS; n = 1,156), the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT; n = 895), and the observational phase of ASCOT (n = 651), all of whom were prescribed atorvastatin 10 mg. Following genome-wide imputation, we combined data from the three studies in a meta-analysis. We found associations of LDL-c response to atorvastatin that reached genome-wide significance at rs10455872 (P = 6.13 x 10(-9)) within the LPA gene and at two single nucleotide polymorphisms (SNP) within the APOE region (rs445925; P = 2.22 x 10(-16) and rs4420638; P = 1.01 x 10(-11)) that are proxies for the epsilon 2 and epsilon 4 variants, respectively, in APOE. The novel association with the LPA SNP was replicated in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial (P = 0.009). Using CARDS data, we further showed that atorvastatin therapy did not alter lipoprotein(a) [Lp(a)] and that Lp(a) levels accounted for all of the associations of SNPs in the LPA gene and the apparent LDL-c response levels. However, statin therapy had a similar effect in reducing cardiovascular disease (CVD) in patients in the top quartile for serum Lp(a) levels (HR = 0.60) compared with those in the lower three quartiles (HR = 0.66; P = 0.8 for interaction). The data emphasize that high Lp(a) levels affect the measurement of LDL-c and the clinical estimation of LDL-c response.jlr Therefore, an apparently lower LDL-c response to statin therapy may indicate a need for measurement of Lp(a). However, statin therapy seems beneficial even in those with high Lp(a).-Deshmukh, H. A., H. M. Colhoun, T. Johnson, P. M. McKeigue, D. J. Betteridge, P. N. Durrington, J. H. Fuller, S. Livingstone, V. Charlton-Menys, A. Neil, N. Poulter, P. Sever, D. C. Shields, A. V. Stanton, A. Chatterjee, C. Hyde, R. A. Calle, D. A. DeMicco, S. Trompet, I. Postmus, I. Ford, J. W. Jukema, M. Caulfield, and G. A. Hitman on behalf of the CARDS, ASCOT, and PROSPER investigators. Genome-wide association study of genetic determinants of LDL-c response to atorvastatin therapy: importance of Lp(a). J. Lipid Res. 2012. 53: 1000-1011
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