30 research outputs found

    Methodological bias in cluster randomised trials

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    Background: Cluster randomised trials can be susceptible to a range of methodological problems. These problems are not commonly recognised by many researchers. In this paper we discuss the issues that can lead to bias in cluster trials. Methods: We used a sample of cluster randomised trials from a recent review and from a systematic review of hip protectors. We compared the mean age of participants between intervention groups in a sample of 'good' cluster trials with a sample of potentially biased trials. We also compared the effect sizes, in a funnel plot, between hip protector trials that used individual randomisation compared with those that used cluster randomisation. Results: There is a tendency for cluster trials, with evidence methodological biases, to also show an age imbalance between treatment groups. In a funnel plot we show that all cluster trials show a large positive effect of hip protectors whilst individually randomised trials show a range of positive and negative effects, suggesting that cluster trials may be producing a biased estimate of effect. Conclusion: Methodological biases in the design and execution of cluster randomised trials is frequent. Some of these biases associated with the use of cluster designs can be avoided through careful attention to the design of cluster trials. Firstly, if possible, individual allocation should be used. Secondly, if cluster allocation is required, then ideally participants should be identified before random allocation of the clusters. Third, if prior identification is not possible, then an independent recruiter should be used to recruit participants

    HR‐pQCT measures of bone microarchitecture predict fracture : systematic review and meta‐analysis

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    HR‐pQCT is a non‐invasive imaging modality for assessing volumetric bone mineral density (vBMD) and microarchitecture of cancellous and cortical bone. The objective was to (i) assess fracture‐associated differences in HR‐pQCT bone parameters and (ii) to determine if HR‐pQCT is sufficiently precise to reliably detect these differences in individuals. We systematically identified 40 studies that used HR‐pQCT (39/40 used XtremeCT scanners) to assess 1291‐3253 and 3389‐10,687 individuals with and without fractures, respectively, ranging in age from 10.9 to 84.7 years with no comorbid conditions. Parameters describing radial and tibial bone density, microarchitecture, and strength were extracted and percentage differences between fracture and control subjects were estimated using a random effects meta‐analysis. An additional meta‐analysis of short‐term in vivo reproducibility of bone parameters assessed by XtremeCT was conducted to determine whether fracture‐associated differences exceeded the least significant change (LSC) required to discern measured differences from precision error. Radial and tibial HR‐pQCT parameters, including failure load, were significantly altered in fracture subjects, with differences ranging from −2.6% (95% CI: −3.4 to −1.9) in radial cortical vBMD to −12.6% (95% CI: −15.0 to −10.3) in radial trabecular vBMD. Fracture‐associated differences reported by prospective studies were consistent with those from retrospective studies, indicating that HR‐pQCT can predict incident fracture. Assessment of study quality, heterogeneity and publication biases verified the validity of these findings. Finally, we demonstrated that fracture‐associated deficits in total and trabecular vBMD, and certain tibial cortical parameters, can be reliably discerned from HR‐pQCT‐related precision error and can be used to detect fracture‐associated differences in individual patients. Although differences in other HR‐pQCT measures, including failure load, were significantly associated with fracture, improved reproducibility is needed to ensure reliable individual cross‐sectional screening and longitudinal monitoring. In conclusion, our study supports the use of HR‐pQCT in clinical fracture prediction

    Losing the Ability in Activities of Daily Living in the Oldest Old: A Hierarchic Disability Scale from the Newcastle 85+ Study

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    Objectives: To investigate the order in which 85 year olds develop difficulty in performing a wide range of daily activities covering basic personal care, household care and mobility. Design: Cross-sectional analysis of baseline data from a cohort study. Setting: Newcastle upon Tyne and North Tyneside, UK. Participants: Individuals born in 1921, registered with participating general practices. Measurements: Detailed health assessment including 17 activities of daily living related to basic personal care, household care and mobility. Questions were of the form ‘Can you … ’ rather than ‘Do you… ’ Principal Component Analysis (PCA) was used to confirm a single underlying dimension for the items and Mokken Scaling was used to determine a subsequent hierarchy. Validity of the hierarchical scale was assessed by its associations with known predictors of disability. Results: 839 people within the Newcastle 85+ study for whom complete information was available on self-reported Activities of Daily Living (ADL). PCA confirmed a single underlying dimension; Mokken scaling confirmed a hierarchic scale where ‘Cutting toenails ’ was the first item with which participants had difficulty and ‘feeding ’ the last. The ordering of loss differed between men and women. Difficulty with ‘shopping ’ and ‘heavy housework ’ were reported earlier by women whilst men reported ‘walking 400 yards ’ earlier. Items formed clusters corresponding to strength, balance, lower and upper bod

    Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

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    BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials

    Discovery and Validation of Molecular Biomarkers for Colorectal Adenomas and Cancer with Application to Blood Testing

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    BACKGROUND & AIMS: Colorectal cancer incidence and deaths are reduced by the detection and removal of early-stage, treatable neoplasia but we lack proven biomarkers sensitive for both cancer and pre-invasive adenomas. The aims of this study were to determine if adenomas and cancers exhibit characteristic patterns of biomarker expression and to explore whether a tissue-discovered (and validated) biomarker is differentially expressed in the plasma of patients with colorectal adenomas or cancer. METHODS: Candidate RNA biomarkers were identified by oligonucleotide microarray analysis of colorectal specimens (222 normal, 29 adenoma, 161 adenocarcinoma and 50 colitis) and validated in a previously untested cohort of 68 colorectal specimens using a custom-designed oligonucleotide microarray. One validated biomarker, KIAA1199, was assayed using qRT-PCR on plasma extracted RNA from 20 colonoscopy-confirmed healthy controls, 20 patients with adenoma, and 20 with cancer. RESULTS: Genome-wide analysis uncovered reproducible gene expression signatures for both adenomas and cancers compared to controls. 386/489 (79%) of the adenoma and 439/529 (83%) of the adenocarcinoma biomarkers were validated in independent tissues. We also identified genes differentially expressed in adenomas compared to cancer. KIAA1199 was selected for further analysis based on consistent up-regulation in neoplasia, previous studies and its interest as an uncharacterized gene. Plasma KIAA1199 RNA levels were significantly higher in patients with either cancer or adenoma (31/40) compared to neoplasia-free controls (6/20). CONCLUSIONS: Colorectal neoplasia exhibits characteristic patterns of gene expression. KIAA1199 is differentially expressed in neoplastic tissues and KIAA1199 transcripts are more abundant in the plasma of patients with either cancer or adenoma compared to controls
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