866 resultados para Clinical analysis
Resumo:
OBJECTIVES: The aims of this study were to conduct a randomised controlled clinical trial (RCT) of partially dentate older adults comparing functionally orientated treatment based on the SDA concept with conventional treatment using RPDs to replace missing natural teeth. The two treatment strategies were evaluated according to their impact on nutritional status measured using haematological biomarkers.
METHODS: A randomised controlled clinical trial (RCT) was conducted of partially dentate patients aged 65 years and older (Trial Registration no. ISRCTN26302774). Each patient provided haematological samples which were screened for biochemical markers of nutritional status. Each sample was tested in Cork University Hospital for serum Albumin, serum Cholesterol, Ferritin, Folate, Vitamin B12 and 25-hydroxycholecalciferol (Vitamin D).
RESULTS: A mixed model analysis of covariance (ANCOVA) indicated that for Vitamin B12 (p=0.9392), serum Folate (p=0.5827), Ferritin (p=0.6964), Albumin (p=0.8179), Serum Total Cholesterol (p=0.3670) and Vitamin D (p=0.7666) there were no statistically significant differences recorded between the two treatment groups. According to the mixed model analysis of covariance (ANCOVA) for Vitamin D there was a significant difference between levels recorded at post-operative time points after treatment intervention (p=0.0470). There was an increase of 7% in 25-hydroxycholecalciferol levels recorded at 6 months compared to baseline (p=0.0172). There was no further change in recorded levels at 12 months (p=0.6482) and these increases were similar within the two treatment groups (p>0.05).
CONCLUSIONS: The only measure which illustrated consistent significant improvements in nutritional status for either group were Vitamin D levels. However no significant difference was recorded between the two treatment groups.
CLINICAL SIGNIFICANCE: Functionally orientated prosthodontic rehabilitation for partially dentate older patients was no worse than conventional removable partial dentures in terms of impact on nutritional status.
Resumo:
OBJECTIVE: To conduct a cost-effectiveness analysis comparing two different tooth replacement strategies for partially dentate older patients, namely partial removable dental prostheses (RDP) and functionally orientated treatment based on the shortened dental arch concept (SDA).
METHODS: Ninety-two partially dentate older patients completed a randomized controlled clinical trial. Patients were randomly allocated to two treatment groups: the RDP group and the SDA group. Treatment effect was measured using impact on oral health-related quality of life (OHrQOL), and the costs involved in providing and maintaining care were recorded for all patients. Patients were followed for 12 months after treatment intervention. All treatment was provided by a single operator.
RESULTS: The total cost of achieving the minimally important clinical difference (MID) in OHrQOL for an average patient in the RDP group was €464.64. For the SDA group, the cost of achieving the MID for an average patient was €252.00. The cost-effectiveness ratio was therefore 1:1.84 in favour of SDA treatment.
CONCLUSION: With an increasingly ageing population, many patients will continue to benefit from removable prostheses to replace their missing natural teeth. From a purely economic standpoint, the results from this analysis suggest that the treatment of partially dentate older adults should be focused on functionally orientated treatment because it is simply more cost-effective.
Resumo:
BACKGROUND: As the world population ages, the requirement for cost-effective methods of treating chronic disease conditions increases. In terms of oral health, there is a rapidly increasing number of dentate elderly with a high burden of maintenance. Population surveys indicate that older individuals are keeping their teeth for longer and are a higher caries risk group. Atraumatic Restorative Treatment (ART) could be suitable for patients in nursing homes or house-bound elderly, but very little research has been done on its use in adults.
OBJECTIVES: To compare the cost-effectiveness of ART and a conventional technique (CT) for restoring carious lesions as part of a preventive and restorative programme for older adults.
METHODS: In this randomized clinical trial, 82 patients with carious lesions were randomly allocated to receive either ART or conventional restorations. Treatment costs were measured based on treatment time, materials and labour. For the ART group, the cost of care provided by a dentist was also compared to the cost of having a hygienist to provide treatment. Effectiveness was measured using percentage of restorations that survived after a year.
RESULTS: Eighty-two patients received 260 restorations, that is, 128 ART and 132 conventional restorations. 91.1% of the restorations were on one surface only. After a year, 252 restorations were assessed in 80 patients. The average cost for ART and conventional restorations was €16.86 and €28.71 respectively; the restoration survival percentages were 91.1% and 97.7%, respectively. This resulted in a cost-effectiveness ratio of 0.18 (ART) and 0.29 (CT). When the cost of a hygienist to provide ART was inserted in the analysis, the resulting ratio was 0.14.
CONCLUSIONS: Atraumatic restorative treatment was found to be a more cost-effective alternative to treat older adults after 1 year, compared to conventional restorations, especially in out of surgery facilities and using alternative workforce such as hygienists. Atraumatic restorative treatment can be a useful tool to provide dental care for frail and fearful individuals who might not access dental treatment routinely.
Resumo:
The oncogenic role of WNT is well characterized. Wntless (WLS) (also known as GPR177, or Evi), a key modulator of WNT protein secretion, was recently found to be highly overexpressed in malignant astrocytomas. We hypothesized that this molecule may be aberrantly expressed in other cancers known to possess aberrant WNT signaling such as ovarian, gastric, and breast cancers. Immunohistochemical analysis using a TMA platform revealed WLS overexpression in a subset of ovarian, gastric, and breast tumors; this overexpression was associated with poorer clinical outcomes in gastric cancer (P=0.025). In addition, a strong correlation was observed between WLS expression and human epidermal growth factor receptor 2 (HER2) overexpression. Indeed, 100% of HER2-positive intestinal gastric carcinomas, 100% of HER2-positive serous ovarian carcinomas, and 64% of HER2-positive breast carcinomas coexpressed WLS protein. Although HER2 protein expression or gene amplification is an established predictive biomarker for trastuzumab response in breast and gastric cancers, a significant proportion of HER2-positive tumors display resistance to trastuzumab, which may be in part explainable by a possible mechanistic link between WLS and HER2.
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Digital pathology and the adoption of image analysis have grown rapidly in the last few years. This is largely due to the implementation of whole slide scanning, advances in software and computer processing capacity and the increasing importance of tissue-based research for biomarker discovery and stratified medicine. This review sets out the key application areas for digital pathology and image analysis, with a particular focus on research and biomarker discovery. A variety of image analysis applications are reviewed including nuclear morphometry and tissue architecture analysis, but with emphasis on immunohistochemistry and fluorescence analysis of tissue biomarkers. Digital pathology and image analysis have important roles across the drug/companion diagnostic development pipeline including biobanking, molecular pathology, tissue microarray analysis, molecular profiling of tissue and these important developments are reviewed. Underpinning all of these important developments is the need for high quality tissue samples and the impact of pre-analytical variables on tissue research is discussed. This requirement is combined with practical advice on setting up and running a digital pathology laboratory. Finally, we discuss the need to integrate digital image analysis data with epidemiological, clinical and genomic data in order to fully understand the relationship between genotype and phenotype and to drive discovery and the delivery of personalized medicine.
Resumo:
Analysis of colorectal carcinoma (CRC) tissue for KRAS codon 12 or 13 mutations to guide use of anti-epidermal growth factor receptor (EGFR) therapy is now considered mandatory in the UK. The scope of this practice has been recently extended because of data indicating that NRAS mutations and additional KRAS mutations also predict for poor response to anti-EGFR therapy. The following document provides guidance on RAS (i.e., KRAS and NRAS) testing of CRC tissue in the setting of personalised medicine within the UK and particularly within the NHS. This guidance covers issues related to case selection, preanalytical aspects, analysis and interpretation of such RAS testing.
Resumo:
Marginal zone B-cell lymphomas (MZLs) have been divided into 3 distinct subtypes (extranodal MZLs of mucosa-associated lymphoid tissue [MALT] type, nodal MZLs, and splenic MZLs). Nevertheless, the relationship between the subtypes is still unclear. We performed a comprehensive analysis of genomic DNA copy number changes in a very large series of MZL cases with the aim of addressing this question. Samples from 218 MZL patients (25 nodal, 57 MALT, 134 splenic, and 2 not better specified MZLs) were analyzed with the Affymetrix Human Mapping 250K SNP arrays, and the data combined with matched gene expression in 33 of 218 cases. MALT lymphoma presented significantly more frequently gains at 3p, 6p, 18p, and del(6q23) (TNFAIP3/A20), whereas splenic MZLs was associated with del(7q31), del(8p). Nodal MZLs did not show statistically significant differences compared with MALT lymphoma while lacking the splenic MZLs-related 7q losses. Gains of 3q and 18q were common to all 3 subtypes. del(8p) was often present together with del(17p) (TP53). Although del(17p) did not determine a worse outcome and del(8p) was only of borderline significance, the presence of both deletions had a highly significant negative impact on the outcome of splenic MZLs.
Resumo:
Retrospective clinical datasets are often characterized by a relatively small sample size and many missing data. In this case, a common way for handling the missingness consists in discarding from the analysis patients with missing covariates, further reducing the sample size. Alternatively, if the mechanism that generated the missing allows, incomplete data can be imputed on the basis of the observed data, avoiding the reduction of the sample size and allowing methods to deal with complete data later on. Moreover, methodologies for data imputation might depend on the particular purpose and might achieve better results by considering specific characteristics of the domain. The problem of missing data treatment is studied in the context of survival tree analysis for the estimation of a prognostic patient stratification. Survival tree methods usually address this problem by using surrogate splits, that is, splitting rules that use other variables yielding similar results to the original ones. Instead, our methodology consists in modeling the dependencies among the clinical variables with a Bayesian network, which is then used to perform data imputation, thus allowing the survival tree to be applied on the completed dataset. The Bayesian network is directly learned from the incomplete data using a structural expectation–maximization (EM) procedure in which the maximization step is performed with an exact anytime method, so that the only source of approximation is due to the EM formulation itself. On both simulated and real data, our proposed methodology usually outperformed several existing methods for data imputation and the imputation so obtained improved the stratification estimated by the survival tree (especially with respect to using surrogate splits).
Resumo:
Brain tissue from so-called Alzheimer's disease (AD) mouse models has previously been examined using H-1 NMR-metabolomics, but comparable information concerning human AD is negligible. Since no animal model recapitulates all the features of human AD we undertook the first H-1 NMR-metabolomics investigation of human AD brain tissue. Human post-mortem tissue from 15 AD subjects and 15 age-matched controls was prepared for analysis through a series of lyophilised, milling, extraction and randomisation steps and samples were analysed using H-1 NMR. Using partial least squares discriminant analysis, a model was built using data obtained from brain extracts. Analysis of brain extracts led to the elucidation of 24 metabolites. Significant elevations in brain alanine (15.4 %) and taurine (18.9 %) were observed in AD patients (p ≤ 0.05). Pathway topology analysis implicated either dysregulation of taurine and hypotaurine metabolism or alanine, aspartate and glutamate metabolism. Furthermore, screening of metabolites for AD biomarkers demonstrated that individual metabolites weakly discriminated cases of AD [receiver operating characteristic (ROC) AUC <0.67; p < 0.05]. However, paired metabolites ratios (e.g. alanine/carnitine) were more powerful discriminating tools (ROC AUC = 0.76; p < 0.01). This study further demonstrates the potential of metabolomics for elucidating the underlying biochemistry and to help identify AD in patients attending the memory clinic
Resumo:
This study combined high resolution mass spectrometry (HRMS), advanced chemometrics and pathway enrichment analysis to analyse the blood metabolome of patients attending the memory clinic: cases of mild cognitive impairment (MCI; n = 16), cases of MCI who upon subsequent follow-up developed Alzheimer's disease (MCI_AD; n = 19), and healthy age-matched controls (Ctrl; n = 37). Plasma was extracted in acetonitrile and applied to an Acquity UPLC HILIC (1.7μm x 2.1 x 100 mm) column coupled to a Xevo G2 QTof mass spectrometer using a previously optimised method. Data comprising 6751 spectral features were used to build an OPLS-DA statistical model capable of accurately distinguishing Ctrl, MCI and MCI_AD. The model accurately distinguished (R2 = 99.1%; Q2 = 97%) those MCI patients who later went on to develop AD. S-plots were used to shortlist ions of interest which were responsible for explaining the maximum amount of variation between patient groups. Metabolite database searching and pathway enrichment analysis indicated disturbances in 22 biochemical pathways, and excitingly it discovered two interlinked areas of metabolism (polyamine metabolism and L-Arginine metabolism) were differentially disrupted in this well-defined clinical cohort. The optimised untargeted HRMS methods described herein not only demonstrate that it is possible to distinguish these pathologies in human blood but also that MCI patients 'at risk' from AD could be predicted up to 2 years earlier than conventional clinical diagnosis. Blood-based metabolite profiling of plasma from memory clinic patients is a novel and feasible approach in improving MCI and AD diagnosis and, refining clinical trials through better patient stratification.
Resumo:
The novel long-acting β2-agonist olodaterol demonstrated an acceptable safety profile in short-term phase II clinical studies. This analysis of four randomized, double-blind, placebo-controlled, parallel-group, phase III studies (1222.11, NCT00782210; 1222.12, NCT00782509; 1222.13, NCT00793624; 1222.14, NCT00796653) evaluated the long-term safety of olodaterol once daily (QD) in a large cohort of patients with moderate to very severe (Global initiative for chronic Obstructive Lung Disease 2-4) chronic obstructive pulmonary disease (COPD). The studies compared olodaterol (5 or 10 μg) QD via Respimat®, formoterol 12 μg twice daily (BID) via Aerolizer® (1222.13 and 1222.14), and placebo for 48 weeks. Patients continued receiving background maintenance therapy, with ∼60% receiving concomitant cardiovascular therapy and 25% having a history of concomitant cardiac disease. Pre-specified analyses of pooled data assessed the adverse events (AEs) and serious AEs in the whole population, and in subgroups with cardiac disease, along with in-depth electrocardiogram and Holter monitoring. In total, 3104 patients were included in the safety analysis: 876 received olodaterol 5 μg, 883 received olodaterol 10 μg, 885 received placebos, and 460 received formoterol 12 μg BID. Overall incidence of on-treatment AEs (71.2%), serious AEs (16.1%), and deaths (1.7%) were balanced across treatment groups. Respiratory and cardiovascular AEs, including major adverse cardiac events, were reported at similar frequencies in placebo and active treatment groups. The safety profiles of both olodaterol 5 μg (marketed and registered dose) and 10 μg QD delivered via Respimat® are comparable to placebo and formoterol BID in this population, with no safety signals identified.
Resumo:
Introduction
Despite excellent first year outcomes in kidney transplantation, there remain significant long-term complications related to new-onset diabetes after transplantation (NODAT). The purpose of this study was to validate the findings of previous investigations of candidate gene variants in patients undergoing a protocolised, contemporary immunosuppression regimen, using detailed serial biochemical testing to identify NODAT development.
Methods
One hundred twelve live and deceased donor renal transplant recipients were prospectively followed-up for NODAT onset, biochemical testing at days 7, 90, and 365 after transplantation. Sixty-eight patients were included after exclusion for non-white ethnicity and pre-transplant diabetes. Literature review to identify candidate gene variants was undertaken as described previously.
Results
Over 25% of patients developed NODAT. In an adjusted model for age, sex, BMI, and BMI change over 12 months, five out of the studied 37 single nucleotide polymorphisms (SNPs) were significantly associated with NODAT: rs16936667:PRDM14 OR 10.57;95% CI 1.8–63.0;p = 0.01, rs1801282:PPARG OR 8.5; 95% CI 1.4–52.7; p = 0.02, rs8192678:PPARGC1A OR 0.26; 95% CI 0.08–0.91; p = 0.03, rs2144908:HNF4A OR 7.0; 95% CI 1.1–45.0;p = 0.04 and rs2340721:ATF6 OR 0.21; 95%CI 0.04–1.0; p = 0.05.
Conclusion
This study represents a replication study of candidate SNPs associated with developing NODAT and implicates mTOR as the central regulator via altered insulin sensitivity, pancreatic β cell, and mitochondrial survival and dysfunction as evidenced by the five SNPs.
General significance
1) Highlights the importance of careful biochemical phenotyping with oral glucose tolerance tests to diagnose NODAT in reducing time to diagnosis and missed cases.
2)This alters potential genotype:phenotype association.
3)The replication study generates the hypothesis that mTOR signalling pathway may be involved in NODAT development.
Resumo:
Clinical studies in patients with cystic fibrosis and G551D-CFTR showed that the group treated with ivacaftor had improved clinical outcomes. To better understand the effect of ivacaftor therapy across the distribution of individual FEV1 responses, data from Phase 3 studies (STRIVE/ENVISION) were re-examined. In this post-hoc analysis of patients (n=209) who received 48 weeks of ivacaftor or placebo, patients were assigned to tertiles according to FEV1 response. These groups were then used to evaluate response (FEV1, sweat chloride, weight, CFQ-R, and pulmonary exacerbation). The number needed to treat (NNT) was calculated for specific thresholds for each outcome. Across all tertiles, numerical improvements in FEV1, sweat chloride, CFQ-R and the frequency of pulmonary exacerbations were observed in ivacaftor-treated patients: the treatment difference versus placebo was statistically significant for all outcomes in the upper tertile and for some outcomes in the lower and middle tertiles. The NNT for a≥5% improvement in %predicted FEV1 was 1.90, for a≥5% body weight increase was 5.74, and to prevent a pulmonary exacerbation was 3.85. This analysis suggests that the majority of patients with clinical characteristics similar to STRIVE/ENVISION patients have the potential to benefit from ivacaftor therapy.
Resumo:
INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a common clinical syndrome with high mortality and long-term morbidity. To date there is no effective pharmacological therapy. Aspirin therapy has recently been shown to reduce the risk of developing ARDS, but the effect of aspirin on established ARDS is unknown.
METHODS: In a single large regional medical and surgical ICU between December 2010 and July 2012, all patients with ARDS were prospectively identified and demographic, clinical, and laboratory variables were recorded retrospectively. Aspirin usage, both pre-hospital and during intensive care unit (ICU) stay, was included. The primary outcome was ICU mortality. We used univariate and multivariate logistic regression analyses to assess the impact of these variables on ICU mortality.
RESULTS: In total, 202 patients with ARDS were included; 56 (28%) of these received aspirin either pre-hospital, in the ICU, or both. Using multivariate logistic regression analysis, aspirin therapy, given either before or during hospital stay, was associated with a reduction in ICU mortality (odds ratio (OR) 0.38 (0.15 to 0.96) P = 0.04). Additional factors that predicted ICU mortality for patients with ARDS were vasopressor use (OR 2.09 (1.05 to 4.18) P = 0.04) and APACHE II score (OR 1.07 (1.02 to 1.13) P = 0.01). There was no effect upon ICU length of stay or hospital mortality.
CONCLUSION: Aspirin therapy was associated with a reduced risk of ICU mortality. These data are the first to demonstrate a potential protective role for aspirin in patients with ARDS. Clinical trials to evaluate the role of aspirin as a pharmacological intervention for ARDS are needed.
Resumo:
IMPORTANCE Systematic reviews and meta-analyses of individual participant data (IPD) aim to collect, check, and reanalyze individual-level data from all studies addressing a particular research question and are therefore considered a gold standard approach to evidence synthesis. They are likely to be used with increasing frequency as current initiatives to share clinical trial data gain momentum and may be particularly important in reviewing controversial therapeutic areas.
OBJECTIVE To develop PRISMA-IPD as a stand-alone extension to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Statement, tailored to the specific requirements of reporting systematic reviews and meta-analyses of IPD. Although developed primarily for reviews of randomized trials, many items will apply in other contexts, including reviews of diagnosis and prognosis.
DESIGN Development of PRISMA-IPD followed the EQUATOR Network framework guidance and used the existing standard PRISMA Statement as a starting point to draft additional relevant material. A web-based survey informed discussion at an international workshop that included researchers, clinicians, methodologists experienced in conducting systematic reviews and meta-analyses of IPD, and journal editors. The statement was drafted and iterative refinements were made by the project, advisory, and development groups. The PRISMA-IPD Development Group reached agreement on the PRISMA-IPD checklist and flow diagram by consensus.
FINDINGS Compared with standard PRISMA, the PRISMA-IPD checklist includes 3 new items that address (1) methods of checking the integrity of the IPD (such as pattern of randomization, data consistency, baseline imbalance, and missing data), (2) reporting any important issues that emerge, and (3) exploring variation (such as whether certain types of individual benefit more from the intervention than others). A further additional item was created by reorganization of standard PRISMA items relating to interpreting results. Wording was modified in 23 items to reflect the IPD approach.
CONCLUSIONS AND RELEVANCE PRISMA-IPD provides guidelines for reporting systematic reviews and meta-analyses of IPD.
