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Sufficient Power (sufficient + power)
Selected AbstractsAssociation analysis of genes in the renin-angiotensin system with subclinical cardiovascular disease in families with Type 2 diabetes mellitus: The Diabetes Heart StudyDIABETIC MEDICINE, Issue 3 2006K. P. Burdon Abstract Aims Cardiovascular disease (CVD) is a major complication of Type 2 diabetes mellitus. The renin-angiotensin system (RAS) and nitric oxide production are both important regulators of vascular function and blood pressure. Genes encoding proteins involved in these pathways are candidates for a contribution to CVD in diabetic patients. We have investigated variants of the angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin type 1 receptor (AT1R) and endothelial nitric oxide synthase (NOS3) genes for association with subclinical measures of CVD in families with Type 2 diabetes mellitus (T2DM). Methods Atherosclerosis was measured by carotid intima-media thickness and calcification of the carotid and coronary arteries in 620 European Americans and 117 African Americans in the Diabetes Heart Study. Because of the role of these systems in blood pressure regulation, blood pressure was also investigated. Results Compelling evidence of association was not detected with any of the SNPs with any outcome measures after adjustments for covariates despite sufficient power to detect relatively small differences in traits for specific genotype combinations. Conclusions Genetic variation of the RAS and NOS3 genes do not appear to strongly influence subclinical cardiovascular disease or blood pressure in this diabetic population. [source] Self-monitoring in Type 2 diabetes mellitus: a meta-analysisDIABETIC MEDICINE, Issue 11 2000S. Coster SUMMARY Aims Self-monitoring of blood or urine glucose is widely used by subjects with Type 2 diabetes mellitus. This study evaluated the effectiveness of the technique at improving blood glucose control through a systematic review and meta-analysis. Methods Randomized controlled trials were identified that compared the effects of blood or urine glucose monitoring with no self-monitoring, or blood glucose self-monitoring with urine glucose self-monitoring, on glycated haemoglobin as primary outcome in Type 2 diabetes. Results , Eight reports were identified. These were rated for quality and data were abstracted. The mean (sd) quality score was 15.0 (1.69) on a scale ranging from 0 to 28. No study had sufficient power to detect differences in glycated haemoglobin (GHb) of less than 0.5%. One study was excluded because it was a cluster randomized trial of a complex intervention and one because fructosamine was used as the outcome measure. A meta-analysis was performed using data from four studies that compared blood or urine monitoring with no regular monitoring. The estimated reduction in GHb from monitoring was ,0.25% (95% confidence interval ,0.61 to 0.10%). Three studies that compared blood glucose monitoring with urine glucose monitoring were also combined. The estimated reduction in GHb from monitoring blood glucose rather than urine glucose was ,0.03% (,0.52 to 0.47%). Conclusions The results do not provide evidence for clinical effectiveness of an item of care with appreciable costs. Further work is needed to evaluate self-monitoring so that resources for diabetes care can be used more efficiently. [source] The 40-mg dose of eletriptan: comparative efficacy and tolerability versus sumatriptan 100 mgEUROPEAN JOURNAL OF NEUROLOGY, Issue 2 2004Hans-Christoph Diener Meta-analysis provides valuable information regarding relative efficacies of triptans, but head-to-head comparator studies remain the gold standard. Three similar head-to-head trials comparing eletriptan 40 mg (E40) with sumatriptan 100 mg (S100) provide a rare opportunity and sufficient power, for robust comparisons of efficacy. Data were combined from three double-blind, placebo-controlled, first-dose, first-attack acute migraine treatment studies comparing E40 (n = 1132), S100 (n = 1129), and placebo (n = 645). The primary outcome was headache response at 2 h. Secondary outcomes included headache response at 1 h, pain-free and functional responses, and sustained headache and pain-free responses. Odds ratios were calculated for summary estimates of probability of response. There were higher headache response rates with eletriptan versus sumatriptan at 2 h (67% vs. 57%; P < 0.0001) and 1 h (34% vs. 26%; P < 0.0001). Eletriptan also had higher 2 h pain-free (35% vs. 25%; P < 0.0001) and functional responses (67% vs. 58%; P < 0.0001). Sustained headache (42%) and pain-free (22%) response rates were higher for eletriptan versus sumatriptan (34%, P < 0.0001; 15%, P < 0.0001). The probability of response for eletriptan versus sumatriptan ranged from 36% higher (relief of nausea) to 64% higher (sustained pain-free rate). Combined analysis demonstrates that E40 has superior efficacy versus S100 across all clinically relevant outcomes. [source] Olfactory deficits in mice overexpressing human wildtype ,-synucleinEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2008Sheila M. Fleming Abstract Accumulation of ,-synuclein in neurons of the central and peripheral nervous system is a hallmark of sporadic Parkinson's disease (PD) and mutations that increase ,-synuclein levels cause familial PD. Transgenic mice overexpressing ,-synuclein under the Thy1 promoter (Thy1-aSyn) have high levels of ,-synuclein expression throughout the brain but no loss of nigrostriatal dopamine neurons up to 8 months, suggesting that they may be useful to model pre-clinical stages of PD. Olfactory dysfunction often precedes the onset of the cardinal motor symptoms of PD by several years and includes deficits in odor detection, discrimination and identification. In the present study, we measured olfactory function in 3- and 9-month-old male Thy1-aSyn mice with a buried pellet test based on latency to find an exposed or hidden odorant, a block test based on exposure to self and non-self odors, and a habituation/dishabituation test based on exposure to non-social odors. In a separate group of mice, ,-synuclein immunoreactivity was assessed in the olfactory bulb. Compared with wildtype littermates, Thy1-aSyn mice could still detect and habituate to odors but showed olfactory impairments in aspects of all three testing paradigms. Thy1-aSyn mice also displayed proteinase K-resistant ,-synuclein inclusions throughout the olfactory bulb. These data indicate that overexpression of ,-synuclein is sufficient to cause olfactory deficits in mice similar to that observed in patients with PD. Furthermore, the buried pellet and block tests provided sufficient power for the detection of a 50% drug effect, indicating their usefulness for testing novel neuroprotective therapies. [source] Association between smoking during radiotherapy and prognosis in head and neck cancer: A follow-up study ,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 12 2002George P. Browman MD Abstract Background. The study objective was to confirm a previous finding that patients with stage III/IV squamous head and neck cancer (SHNC) who smoke during radiotherapy (RT) experience reduced survival. Methods. An observational cohort study. Patients' smoking status was assessed weekly by questionnaire plus blood cotinine. Patients were assessed every 3 to 4 months for survival. Logistic regression and Cox proportional hazards analyses were used to detect the independent contribution of smoking on survival. Results. Of 148 patients, 113 smoked during RT. Blood cotinine and smoking questionnaire responses were highly correlated (Spearman R = .69; p < .0005). Abstainers and very light smokers experienced better survival than light, moderate, and heavy smokers (median, 42 vs 29 months; p = .07). Tumor and nodal status and years smoked were the most important prognostic factors. Smoking during RT was not an independent predictor of survival, but baseline smoking status was (p = .016). Conclusion. Smoking status should be documented in all future trials of RT in SHNC to allow for pooled analyses with sufficient power to address this question. © 2002 Wiley Periodicals, Inc. Head Neck 24: 1031,1037, 2002 [source] IBD international genetics consortium: International cooperation making sense of complex diseaseINFLAMMATORY BOWEL DISEASES, Issue 3 2003Juleen A. Cavanaugh Ph.D. Abstract The Inflammatory Bowel Disease International Genetic Consortium was formed in Oxford in 1997. Since then it has grown to include twelve groups from around the world that are each actively involved in identifying the genes that are involved in susceptibility to IBD. The approach of the IBDIGC is to attempt to overcome one of the major issues in complex disease analysis,that of obtaining sufficient power to analyze successfully the inheritance of IBD,by collaboratively studying large numbers of well documented families with multiple affected individuals. This strategy has been marked by considerable success with the publication of a paper authored by the IBDIGC substantiating the localization of IBD1 to chromosome 16. This publication served to encourage researchers and eventually resulted in the identification by several groups simultaneously of risk alleles in the NOD2 gene that cosegregate with disease. The IBDIGC provides a model for studies in complex disease genetics, showing that research groups both large and small can participate equally in complex disease gene identification through the formation of large international consortia. [source] A randomisation program to compare species-richness valuesINSECT CONSERVATION AND DIVERSITY, Issue 3 2008JEAN M. L. RICHARDSON Abstract., 1Comparisons of biodiversity estimates among sites or through time are hampered by a focus on using mean and variance estimates for diversity measures. These estimators depend on both sampling effort and on the abundances of organisms in communities, which makes comparison of communities possible only through the use of rarefaction curves that reduce all samples to the lowest sample size. However, comparing species richness among communities does not demand absolute estimates of species richness and statistical tests of similarity among communities are potentially more straightforward. 2This paper presents a program that uses randomisation methods to robustly test for differences in species richness among samples. Simulated data are used to show that the analysis has acceptable type I error rates and sufficient power to detect violations of the null hypothesis. An analysis of published bee data collected in 4 years shows how both sample size and hierarchical structure in sample type are incorporated into the analysis. 3The randomisation program is shown to be very robust to the presence of a dominant species, many rare species, and decreased sample size, giving quantitatively similar conclusions under all conditions. This method of testing for differences in biodiversity provides an important tool for researchers working on questions in community ecology and conservation biology. [source] Effectiveness of arthroscopic versus open surgical stabilisation for the management of traumatic anterior glenohumeral instabilityINTERNATIONAL JOURNAL OF EVIDENCE BASED HEALTHCARE, Issue 2 2007Choong Ng BMedSci(Melb) Abstract Background, Anterior instability is a frequent complication following a traumatic glenohumeral dislocation. Frequently the underlying pathology associated with recurrent instability is a Bankart lesion. Surgical correction of Bankart lesions and other associated pathology is the key to successful treatment. Open surgical glenohumeral stabilisation has been advocated as the gold standard because of consistently low postoperative recurrent instability rates. However, arthroscopic glenohumeral stabilisation could challenge open surgical repair as the gold standard treatment for traumatic anterior glenohumeral instability. Objectives, Primary evidence that compared the effectiveness of arthroscopic versus open surgical glenohumeral stabilisation was systematically collated regarding best-practice management for adults with traumatic anterior glenohumeral instability. Search strategy, A systematic search was performed using 14 databases: MEDLINE, Cumulative Index of Nursing and Allied Health (CINAHL), Allied and Complementary Medicine Database (AMED), ISI Web of Science, Expanded Academic ASAP, Proquest Medical Library, Evidence Based Medicine Reviews, Physiotherapy Evidence Database, TRIP Database, PubMed, ISI Current Contents Connect, Proquest Digital Dissertations, Open Archives Initiative Search Engine, Australian Digital Thesis Program. Studies published between January 1984 and December 2004 were included in this review. No language restrictions were applied. Selection criteria, Eligible studies were those that compared the effectiveness of arthroscopic versus open surgical stabilisation for the management of traumatic anterior glenohumeral instability, which had more than 2 years of follow up and used recurrent instability and a functional shoulder questionnaire as primary outcomes. Studies that used non-anatomical open repair techniques, patient groups that were specifically 40 years or older, or had multidirectional instability or other concomitant shoulder pathology were excluded. Data collection and analysis, Two independent reviewers assessed the eligibility of each study for inclusion into the review, the study design used and its methodological quality. Where any disagreement occurred, consensus was reached by discussion with an independent researcher. Studies were assessed for homogeneity by considering populations, interventions and outcomes. Where heterogeneity was present, synthesis was undertaken in a narrative format; otherwise a meta-analysis was conducted. Results, Eleven studies were included in the review. Two were randomised controlled trials. Evidence comparing arthroscopic and open surgical glenohumeral stabilisation was of poor to fair methodological quality. Hence, the results of primary studies should be interpreted with caution. Observed clinical heterogeneity in populations and outcomes was highlighted and should be considered when interpreting the meta-analysis. Authors also used variable definitions of recurrent instability and a variety of outcome measures, which made it difficult to synthesise results. When comparable data were pooled, there were no significant differences (P > 0.05) between the arthroscopic and open groups with respect to recurrent instability rates, Rowe score, glenohumeral external rotation range and complication rates. Conclusions, Statistically, it appears that both surgical techniques are equally effective in managing traumatic anterior glenohumeral instability. In light of the methodological quality of the included studies, it is not possible to validate arthoscopic stabilisation to match open surgical stabilisation as the gold standard treatment. Further research using multicentred randomised controlled trials with sufficient power and instability-specific questionnaires with sound psychometric properties is recommended to build on current evidence. The choice of treatment should be based on multiple factors between the clinician and the patient. [source] An Expanded Evaluation of the Relationship of Four Alleles to the Level of Response to Alcohol and the Alcoholism RiskALCOHOLISM, Issue 1 2005Xianzhang Hu Background: Alcoholism is a complex, genetically influenced disorder the cause of which may be better understood through the study of genetically influenced phenotypes that mediate the risk. One such intermediate phenotype is the low level of response (LR) to alcohol. This project used a case-control approach to search for genes that may contribute to LR. Methods: Data were available from alcohol challenges at approximately age 20 and regarding the development of alcohol use disorders over the subsequent 20 years for 85 men, including 40 reported in a previous genetic analysis. LR was evaluated using oral consumption of 0.75 ml/kg of alcohol, after which changes in subjective feelings of intoxication and body sway were measured. Alcohol abuse and dependence were diagnosed by DSM-III-R criteria through structured interviews administered to both the participant and an informant (usually the spouse) 10, 15, and 20 years after initial testing. Four polymorphisms were evaluated, including the serotonin transporter HTTLPR promoter ins/del, GABAA,6 Pro385Ser, NPY Leu7Pro, and catalase 262C>T. Two of these, HTTLPR and GABAA,6 Pro385Ser, had been previously associated with LR and alcoholism in a preliminary study. Results: The HTTLPR L allele was significantly related to both the LR and alcoholism in an allele-dosage (stepwise) manner. Furthermore, the association remained when L alleles were subdivided into recently reported functional subtypes: the lowest LR was associated with genotypes correlated with the highest serotonin transporter expression. The GABAA,6 Ser385 allele showed a nonsignificant trend for association to a low LR, as had been previously observed, although the Ser385 allele is uncommon, and only 18 heterozygotes were in the current group. However, the six men with both LL and Pro385/Ser385 genotypes had the lowest LR, and each had developed alcoholism during follow-up. Neither NPY nor catalase was associated with either LR or alcoholic outcomes, although the sample did not have sufficient power for definitive conclusions. Conclusions: This report strengthens the support for a relationship between the HTTLPR L and GABAA,6 Ser385 alleles to low alcohol LR and to alcoholism in a prospectively studied cohort evaluated for LR in young adulthood and before the onset of alcohol dependence. [source] Association between the PD1.3A/G polymorphism of the PDCD1 gene and systemic lupus erythematosus in European populations: a meta-analysisJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 4 2009J-L Liu Abstract Background, Linkage studies suggest a locus, SLEB2, involved in susceptibility to systemic lupus erythematosus (SLE) and programmed cell death 1 (PDCD1) gene locates in this region. The association of PDCD1 polymorphism (PD1.3A/G) with SLE has been widely investigated, but there are no unambiguous conclusions. Objective, To assess the combined evidence for the association between PD1.3A/G polymorphism and SLE and to summarize the effect size of the polymorphism associated with susceptibility to SLE. Methods, We surveyed studies on the PD1.3A/G polymorphism and SLE using comprehensive PubMed search up to May 2008. The pooled odds ratio (OR) was calculated using a fixed- or a random-effects model. Heterogeneity was identified by sensitivity analysis and publication bias was examined by funnel plot and Egger's test. We also computed the power for a given number of samples. Results, A total of 20 datasets from eight studies that met our inclusion criteria were included. The studies comprised of a total of 2909 cases and 3995 controls. Stratified meta-analysis demonstrated a significant association between PD1.3A and SLE among non-Spanish European descents [OR, 1.290; 95% confidence interval (95% CI), 1.098,1.516; z = 3.10, P = 0.002], while PD1.3G is the risk allele in Spanish populations (OR = 1.414, 95% CI = 1.075,1.862; z = 2.48, P = 0.013). Both results have sufficient power to support these findings. No publication bias presented in the studies analysed. Conclusions, This meta-analysis demonstrates a significant association between PD1.3A and SLE among non-Spanish European descents, while a negative association was observed in Spanish population. Conflicts of interest None declared [source] A study of pre-registration house officers' clinical skillsMEDICAL EDUCATION, Issue 12 2000R A Fox Background Little is known about the ability of pre-registration house officers (PRHOs) to perform basic clinical skills just prior to entering the medical register. Objectives To find out whether PRHOs have deficiencies in basic clinical skills and to determine if the PRHOs themselves or their consultants are aware of them. Method All 40 PRHOs at the Chelsea and Westminster and Whittington Hospitals were invited to undertake a 17 station OSCE of basic clinical skills. Each station was marked by one examiner completing an overall global score after completing an itemised checklist. An adequate station performance was the acquisition of a pass/borderline pass grade. Prior to the OSCE, a questionnaire was given to each PRHO asking them to rate their own abilities (on a 5-point scale) in the skills tested. A similar questionnaire was sent to the educational supervisors of each PRHO asking them to rate their house officer's ability in each of the same skills. Results Twenty-two PRHOs participated. Each PRHO failed to perform adequately a mean of 2·4 OSCE stations (SD 1·8, range 1,8). There were no significant correlations between OSCE performance and either self- or educational supervisor ratings. The supervisor felt unable to give an opinion on PRHO abilities in 18% of the skills assessed. Discussion This study suggests that PRHOs may have deficiencies in basic clinical skills at the time they enter the medical register. Neither the PRHOs themselves nor their consultants identified these deficiencies. A large regional study with sufficient power is required to explore the generalizability of these concerns in more detail. [source] Polymorphic microsatellite markers for paternity assessment in southern calamari Sepioteuthis australis (Cephalopoda: Loliginidae)MOLECULAR ECOLOGY RESOURCES, Issue 4 2003L. M. Van Camp Abstract Recent decades have seen the fast growth of cephalopod fisheries but their management is compromised by the critical gaps in our knowledge of cephalopod life histories. Molecular markers are invaluable tools for studying the evolutionary significance and management implications of variation in mating systems. We have developed seven polymorphic microsatellite loci for mating system analysis in the southern calamari Sepioteuthis australis Quoy & Gaimard 1833 using magnetic enrichment and colony hybridization techniques. Observed heterozygosities range from 32% to 100% and will have sufficient power to examine the relative success of alternate mating strategies in S. australis. [source] TrkA expression is associated with an elevated level of apoptosis in classic medulloblastomasNEUROPATHOLOGY, Issue 3 2006Takashi Ohta Medulloblastomas represent the most common central nervous system malignancies in children. Despite intensive modality treatment with craniospinal irradiation and multiple drug chemotherapy, their prognosis remains dismal. In the present study, we examined the potential roles of cellular differentiation, proliferation and apoptosis in 21 pediatric patients with newly diagnosed classic medulloblastomas treated by conventional radiation therapy and adjuvant chemotherapy. The expression of glial fibrillary acidic protein, S-100, synaptophysin, TrkA and TrkC, and the proliferation index of MIB-1 were evaluated by immunohistochemistry and the apoptotic index was determined using terminal deoxytransferase-mediated deoxyuridine-5,-triphosphate nick-end labeling assay. The prognostic value of these biological markers was also assessed. Immunoreactive glial fibrillary acidic protein, S-100, synaptophysin, TrkA and TrkC were observed in seven (33%), four (19%), 12 (57%), 14 (67%) and 11 (52%) of the 21 cases, respectively. TrkA expression was positively correlated with the MIB-1 staining index (P = 0.0228) and the apoptotic index (P = 0.0058). None of the immunohistochemical markers was found to be of value in predicting the prognosis. Although the present small sample size does not provide sufficient power to discount biological variables as prognostic markers, it was the well-established clinical prognostic factors, i.e. tumor stage and extent of surgery, that stood out as the most important predictors of survival. The close association between apoptosis and TrkA expression is consistent with in vitro data demonstrating the capacity of the NGF/TrkA signaling pathway to increase medulloblastoma apoptotic cell death, suggesting that this pathway may yield alternative therapeutic targets for novel therapies. [source] The BAMSE Project: presentation of a prospective longitudinal birth cohort studyPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 2002Magnus Wickman The aims of this prospective and longitudinal project are to establish crucial risk factors for asthma and other allergic diseases in childhood, and to study factors of importance for prognosis at already established allergic disease. Socio-economic factors, such as inequality in health, are also to be addressed. The project started in February 1994. To reach sufficient power, 4,000 children had to be included. In November 1996, this number was reached (4,093). Inclusion in the study was made at 3,4 months of age. At that time, and before induction of allergic disease/asthma of the child, a questionnaire focused on exposure, genetics and socio-economic factors was answered. Settled dust was sampled for later analysis of furred animal and mite allergens. When the children were aged both 1 and 2 years, their parents were asked to fill in new questionnaires focusing on respiratory and allergic (skin, gastrointestinal) symptoms, but also key variables of exposure. Cases with asthma are identified and, for every case, two matched controls drawn. During the following winter, the homes of cases and controls were investigated and the temperature, indoor humidity, air change rate and NO2 measured. Two hundred cases (5%) were expected to be identified during the first 2 years of the children's lives. Some 479 homes have now been investigated and 97.7% of the original 4,093 children still remain in the cohort. The 2-year symptom follow-up ended in November 1998. The 4-year follow-up started on 1 September 1998 and was planned to be finished in June 2000. Questionnaires (allergic and respiratory symptoms, key variables of exposure at home and day care) are sent out to all 4,093 families. All children are invited for examination, lung function tests (PEF, flow-volume, MVV and oxygen clearance) and physical performance. Blood is taken from all children (20 ml). Allergy screening is performed and specific IgE examined. Blood cells will be frozen to allow for later DNA extraction. In subsets (children with any allergic and/or respiratory manifestation and controls), markers of inflammation in blood and urine will be examined, as well as eosinophils in nasal smear. Interviews are carried out to assess the severity of asthma, type/periodicity of health care given, asthma medication and parental sick leave when appropriate. As a separate project, financed by the EU, outdoor pollution as risk factors for asthma and allergies are to be studied within the BAMSE cohort. A follow-up of 8,9 years is underway. [source] CALHM1 Polymorphism is not Associated with Late-onset Alzheimer DiseaseANNALS OF HUMAN GENETICS, Issue 3 2009Gary W. Beecham Summary Data suggests that the P86L polymorphism (rs2986017) in the calcium homeostasis modulator 1 (CALHM1) gene interferes with CALHM1 functionality, increases A, levels, and is associated with late-onset Alzheimer's disease (LOAD). Previous studies have demonstrated association with P86L and LOAD in three of five case-control cohorts, and a joint analysis of all datasets showed association with a p-value of 2 × 10,10 and an allele-specific odds ratio of 1.44 (2,043 cases, 1,361 controls total). In this short communication we attempt to replicate these results in our case-control cohort (510 cases, 524 controls). We show no association between P86L and LOAD despite having sufficient power to detect at the reported odds ratios, and briefly discuss potential reasons for the discrepancy. [source] | |||||||||||||