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Selected AbstractsSNP Selection for Association Studies: Maximizing Power across SNP Choice and Study SizeANNALS OF HUMAN GENETICS, Issue 6 2005F. Pardi Summary Selection of single nucleotide polymorphisms (SNPs) is a problem of primary importance in association studies and several approaches have been proposed. However, none provides a satisfying answer to the problem of how many SNPs should be selected, and how this should depend on the pattern of linkage disequilibrium (LD) in the region under consideration. Moreover, SNP selection is usually considered as independent from deciding the sample size of the study. However, when resources are limited there is a tradeoff between the study size and the number of SNPs to genotype. We show that tuning the SNP density to the LD pattern can be achieved by looking for the best solution to this tradeoff. Our approach consists of formulating SNP selection as an optimization problem: the objective is to maximize the power of the final association study, whilst keeping the total costs below a given budget. We also propose two alternative algorithms for the solution of this optimization problem: a genetic algorithm and a hill climbing search. These standard techniques efficiently find good solutions, even when the number of possible SNPs to choose from is large. We compare the performance of these two algorithms on different chromosomal regions and show that, as expected, the selected SNPs reflect the LD pattern: the optimal SNP density varies dramatically between chromosomal regions. [source] Estimation of the burden of active and life-time epilepsy: A meta-analytic approachEPILEPSIA, Issue 5 2010Anthony K. Ngugi Summary Purpose:, To estimate the burden of lifetime epilepsy (LTE) and active epilepsy (AE) and examine the influence of study characteristics on prevalence estimates. Methods:, We searched online databases and identified articles using prespecified criteria. Random-effects meta-analyses were used to estimate the median prevalence in developed countries and in urban and rural settings in developing countries. The impact of study characteristics on prevalence estimates was determined using meta-regression models. Results:, The median LTE prevalence for developed countries was 5.8 per 1,000 (5th,95th percentile range 2.7,12.4) compared to 15.4 per 1,000 (4.8,49.6) for rural and 10.3 (2.8,37.7) for urban studies in developing countries. The median prevalence of AE was 4.9 per 1,000 (2.3,10.3) for developed countries and 12.7 per 1,000 (3.5,45.5) and 5.9 (3.4,10.2) in rural and urban studies in developing countries. The estimates of burden for LTE and AE in developed countries were 6.8 million (5th,95th percentile range 3.2,14.7) and 5.7 million (2.7,12.2), respectively. In developing countries these were 45 (14,145) million LTE and 17 (10,133) million AE in rural areas and 17 (5,61) million LTE and 10 (5,17) million AE in urban areas. Studies involving all ages or only adults showed higher estimates than pediatric studies. Higher prevalence estimates were also associated with rural location and small study size. Conclusions:, This study estimates the global burden of epilepsy and the proportions with AE, which may benefit from treatment. There are systematic differences in reported prevalence estimates, which are only partially explained by study characteristics. [source] Persistent Pain After Breast Cancer SurgeryPAIN MEDICINE, Issue 7 2007B Lau Purpose of the study:, To identify strengths and weaknesses in current studies with a view to carrying out a major multi-center study in Australia. Methods:, The literature was reviewed using standard Medline and Ovid methods. Bibliography of well known key recent papers were used to identify further papers. Results:, Studies evaluating persistent pain after breast cancer surgery have been small and few were prospective controlled studies with adequate power. Like Jung et al[1] we found that the literature was inconsistent in defining chronic pain and differentiating the breast cancer surgery pain syndromes. Marked variations in prior studies are due to differences in: study size (n = 22 to 282 patients), methodology, diagnostic criteria, pain assessment instruments, and distribution of demographic and clinical characteristics in the samples studied. Unfortunately the largest study to date, the ALMANAC Trial (n = 1031) which compared sentinel node biopsy vs "standard axillary dissection" evaluated arm and shoulder function and quality of life, but not pain[2]. From the current literature, it appears that neuropathic breast and arm pain are most common. Widely varying prevalence estimates of different neuropathic pain syndromes have been reported: phantom breast pain (3,44%); intercostobrachial neuralgia (ICBN) (16,39%); ICBN in breast conserving surgery (14,61%); and "neuroma pain" (23,49%). The most established risk factors for surgically related neuropathic pain syndromes are intraoperative nerve trauma, severe acute postoperative pain, and high use of postoperative analgesics[1]. Psychosocial distress is reported to be a risk factor and a consequence of chronic pain[1]. Conclusions:, Well-designed large multi-center studies are required to identify prevalences of various pain types, associated risk factors and treatment success for pain after breast cancer surgery. Such a study is in progress through the collaboration of our group with the Sentinel Node vs Axillary Clearance (SNAC) Study of 1000 women following breast surgery, conducted by the Royal Australian College of Surgeons (RACS). [source] SNP Selection for Association Studies: Maximizing Power across SNP Choice and Study SizeANNALS OF HUMAN GENETICS, Issue 6 2005F. Pardi Summary Selection of single nucleotide polymorphisms (SNPs) is a problem of primary importance in association studies and several approaches have been proposed. However, none provides a satisfying answer to the problem of how many SNPs should be selected, and how this should depend on the pattern of linkage disequilibrium (LD) in the region under consideration. Moreover, SNP selection is usually considered as independent from deciding the sample size of the study. However, when resources are limited there is a tradeoff between the study size and the number of SNPs to genotype. We show that tuning the SNP density to the LD pattern can be achieved by looking for the best solution to this tradeoff. Our approach consists of formulating SNP selection as an optimization problem: the objective is to maximize the power of the final association study, whilst keeping the total costs below a given budget. We also propose two alternative algorithms for the solution of this optimization problem: a genetic algorithm and a hill climbing search. These standard techniques efficiently find good solutions, even when the number of possible SNPs to choose from is large. We compare the performance of these two algorithms on different chromosomal regions and show that, as expected, the selected SNPs reflect the LD pattern: the optimal SNP density varies dramatically between chromosomal regions. [source] Energy restriction early in life and colon carcinoma riskCANCER, Issue 1 2003Results of the Netherlands Cohort Study after 7.3 years of follow-up Abstract BACKGROUND This study evaluated the effects of severe undernutrition during adolescence and subsequent colon carcinoma risk. METHODS The authors evaluated The Netherlands Cohort Study on Diet and Cancer (NLCS) among 62,573 women and 58,279 men aged 55,69 years at baseline. Information on diet and risk factors was collected by questionnaire in 1986. Additional information was collected concerning residence during the hunger winter (1944,1945), the World War II years (1940,1944), and father's employment status during the economic depression of 1932,1940, which were used as indicators of exposure. After 7.3 years of follow-up, 807 colon carcinoma cases (388 females and 419 males) were available for analysis. RESULTS Multivariate analysis showed that both men and women who had lived in a western city in 1944,1945 had a decreased colon carcinoma risk (men: relative risk [RR] = 0.85, 95% confidence interval [CI] = 0.62,1.16; women: RR = 0.80, 95%CI = 0.59,1.09). No association between colon carcinoma risk and urban versus rural residence was found during the war years (1940,1944). Having an unemployed father during the economic depression (1932,1940) was also associated with a small decrease in colon carcinoma risk for men (RR = 0.90, 95% CI =0.62,1.31) and women (RR = 0.75, 95%CI 0.49-1.14). In subgroup analyses, a decreased colon carcinoma risk for men and women who were in their adolescent growth spurt and living in a western city during the hunger winter of 1944,1945 was noted (men: RR = 0.72, 95% CI = 0.31,1.65; women: RR = 0.88, 95% CI = 0.40,1.96). No associations were statistically significant because of the limited study size. CONCLUSIONS In the current study, a weak inverse relation was found between energy restriction early in life and subsequent colon carcinoma risk for men and women. However, these findings need replication in a larger study. Cancer 2003;97:46,55. © 2003 American Cancer Society. DOI 10.1002/cncr.11052 [source] Omega-3 Dietary Supplements and the Risk of Cardiovascular Events: A Systematic ReviewCLINICAL CARDIOLOGY, Issue 7 2009FCCM, Paul E. Marik MD Background Epidemiologic data suggest that omega-3 fatty acids derived from fish oil reduce cardiovascular disease. The clinical benefit of dietary fish oil supplementation in preventing cardiovascular events in both high and low risk patients is unclear. Objective To assess whether dietary supplements of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) decrease cardiovascular events across a spectrum of patients. Data Sources MEDLINE, Embase, the Cochrane Database of Systematic Reviews, and citation review of relevant primary and review articles. Study Selection Prospective, randomized, placebo-controlled clinical trials that evaluated clinical cardiovascular end points (cardiovascular death, sudden death, and nonfatal cardiovascular events) and all-cause mortality in patients randomized to EPA/DHA or placebo. We only included studies that used dietary supplements of EPA/DHA which were administered for at least 1 year. Data Extraction Data were abstracted on study design, study size, type and dose of omega-3 supplement, cardiovascular events, all-cause mortality, and duration of follow-up. Studies were grouped according to the risk of cardiovascular events (high risk and moderate risk). Meta-analytic techniques were used to analyze the data. Data Synthesis We identified 11 studies that included a total of 39 044 patients. The studies included patients after recent myocardial infarction, those with an implanted cardioverter defibrillator, and patients with heart failure, peripheral vascular disease, and hypercholesterolemia. The average dose of EPA/DHA was 1.8 ± 1.2 g/day and the mean duration of follow-up was 2.2 ± 1.2 years. Dietary supplementation with omega-3 fatty acids significantly reduced the risk of cardiovascular deaths (odds ratio [OR]: 0.87, 95% confidence interval [CI]: 0.79,0.95, p = 0.002), sudden cardiac death (OR: 0.87, 95% CI: 0.76,0.99, p = 0.04), all-cause mortality (OR: 0.92, 95% CI: 0.85,0.99, p = 0.02), and nonfatal cardiovascular events (OR: 0.92, 95% CI: 0.85,0.99, p = 0.02). The mortality benefit was largely due to the studies which enrolled high risk patients, while the reduction in nonfatal cardiovascular events was noted in the moderate risk patients (secondary prevention only). Meta-regression failed to demonstrate a relationship between the daily dose of omega-3 fatty acid and clinical outcome. Conclusions Dietary supplementation with omega-3 fatty acids should be considered in the secondary prevention of cardiovascular events. Copyright © 2009 Wiley Periodicals, Inc. [source] Epidemiologic critique of literature on post-transplant neoplasms in solid organ transplantationCLINICAL TRANSPLANTATION, Issue 5 2009Lee L. Lanza Abstract:, As survival of transplant recipients improves, long-term complications become more important. We reviewed epidemiologic literature on real-world risks of de novo neoplasia post-transplant. We searched the Medline/PubMed, Cochrane, and Embase databases for population-based studies on risk of neoplasia from 1998 to 2005. Selection criteria included: solid organ transplants, neoplastic outcomes, n > 500 subjects, age ,18 yr, and study design. Of 187 abstracts, 64 met criteria for study size, age range, topic, and design. We classified the articles by quality of reporting on components of cohort studies. Twelve of 64 studies reported cohort eligibility and exclusion criteria, defined time at risk, and ascertained incident neoplasms. Twenty-one studies reported prevalence of neoplasms for unspecified time periods, and only eight incidence studies reported person yr at risk. Three studies of all types of neoplasms in kidney recipients reported incidence ranging from 11.0 to 17.3 cases per 1000 person yr. Two studies of post-transplant lymphoproliferative disorders reported incidence of 0.4 to 2.5 cases per 1000 person yr in kidney recipients. More precise estimation of risks and rates, better description of study population, and more attention to confounding in comparisons of rates would make studies more meaningful. Reports should adhere to established guidelines for presenting methods and results in epidemiologic studies. [source] Pulsatile machine perfusion vs. cold storage of kidneys for transplantation: a rapid and systematic reviewCLINICAL TRANSPLANTATION, Issue 4 2003Jeremy P Wight Abstract: Objective: To identify and prioritize key areas for further research in kidney preservation systems. Materials and methods: We conducted a systematic review and meta-analysis of the effectiveness of machine perfusion and cold storage techniques in reducing delayed graft function (DGF) and improving graft survival in recipients of kidneys from beating and non-heart-beating donors. Literature quantifying the link between DGF and graft survival was used to evaluate the potential long-term impact of machine perfusion and cold storage systems. Cox proportional hazards modelling was used to predict graft survival and graft years gained over 10 yr. Monte Carlo sensitivity analysis was conducted to evaluate stochastic uncertainties within the model. Results: Machine perfusion leads to a relative risk of DGF of approximately 80% (67%, 96%) compared with cold storage, although the evidence base is limited in quality and study size. Direct evidence on graft survival at 1 yr demonstrates no statistically significant difference between machine perfusion and cold storage. Predictions based upon quantifying the link between DGF and graft survival suggest potential improvements of between 0 and 6% at 10 yr. Discussion: Studies of high methodological quality and sufficient size are required to determine whether machine preservation leads to reduce rates of DGF. Predicted impact on graft survival implies that direct evidence would require a large population followed up over a long period of time. Registry database analysis supported by validation of the link between DGF and graft survival may be preferable and more feasible than randomized controlled trials. [source] Does a late evening meal reduce the risk of hepatocellular carcinoma among patients with chronic hepatitis C?HEPATOLOGY RESEARCH, Issue 9 2008Satoko Ohfuji Aim:, Some studies have suggested that nutritional support might protect against the recurrence of hepatocellular carcinoma (HCC) among postoperative HCC patients. However, no epidemiological studies have evaluated the effect of nutritional support on HCC incidence. This study aimed to investigate the association between a late evening meal and HCC. Methods:, We conducted a hospital-based, case-control study comparing 73 cases with HCC to 253 matched controls among patients with chronic hepatitis C. A questionnaire elicited information on the consumption of a late evening meal, which was defined as a snack or meal within 2 h before bedtime. The odds ratios (OR) and 95% confidence intervals (CI) were calculated by the conditional logistic regression model. Results:, After adjustment for potential confounders, patients who consumed a late evening meal had a lower OR as compared to those who did not consume one (OR, 0.08; 95% CI, 0.01,0.48). In terms of frequency of intake, a clear inverse exposure,response relationship was observed (trend P = 0.009). In addition, a negative association between a late evening meal and HCC was more pronounced among patients with an ,-fetoprotein level of less than 20 ng/mL and those with a body mass index of less than 25 kg/m2. Conclusion:, A late evening meal might protect against HCC, particularly among patients with a normal ,-fetoprotein level and who are not obese, although these relations might be accounted for other factors, including total energy intake. Further studies with larger study sizes are needed to corroborate these findings. [source] |