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High-risk Cohort (high-risk + cohort)
Selected AbstractsAssessing human germ-cell mutagenesis in the Postgenome Era: A celebration of the legacy of William Lawson (Bill) Russell,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2007Andrew J. Wyrobek Abstract Birth defects, de novo genetic diseases, and chromosomal abnormality syndromes occur in ,5% of all live births, and affected children suffer from a broad range of lifelong health consequences. Despite the social and medical impact of these defects, and the 8 decades of research in animal systems that have identified numerous germ-cell mutagens, no human germ-cell mutagen has been confirmed to date. There is now a growing consensus that the inability to detect human germ-cell mutagens is due to technological limitations in the detection of random mutations rather than biological differences between animal and human susceptibility. A multidisciplinary workshop responding to this challenge convened at The Jackson Laboratory in Bar Harbor, Maine. The purpose of the workshop was to assess the applicability of an emerging repertoire of genomic technologies to studies of human germ-cell mutagenesis. Workshop participants recommended large-scale human germ-cell mutation studies be conducted using samples from donors with high-dose exposures, such as cancer survivors. Within this high-risk cohort, parents and children could be evaluated for heritable changes in (a) DNA sequence and chromosomal structure, (b) repeat sequences and minisatellites, and (c) global gene expression profiles and pathways. Participants also advocated the establishment of a bio-bank of human tissue samples from donors with well-characterized exposure, including medical and reproductive histories. This mutational resource could support large-scale, multiple-endpoint studies. Additional studies could involve the examination of transgenerational effects associated with changes in imprinting and methylation patterns, nucleotide repeats, and mitochondrial DNA mutations. The further development of animal models and the integration of these with human studies are necessary to provide molecular insights into the mechanisms of germ-cell mutations and to identify prevention strategies. Furthermore, scientific specialty groups should be convened to review and prioritize the evidence for germ-cell mutagenicity from common environmental, occupational, medical, and lifestyle exposures. Workshop attendees agreed on the need for a full-scale assault to address key fundamental questions in human germ-cell environmental mutagenesis. These include, but are not limited to, the following: Do human germ-cell mutagens exist? What are the risks to future generations? Are some parents at higher risk than others for acquiring and transmitting germ-cell mutations? Obtaining answers to these, and other critical questions, will require strong support from relevant funding agencies, in addition to the engagement of scientists outside the fields of genomics and germ-cell mutagenesis. Environ. Mol. Mutagen., 2007. Published 2007 Wiley-Liss, Inc. [source] Effects of early cat or dog ownership on sensitisation and asthma in a high-risk cohort without disease-related modification of exposurePAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 2 2010Catarina Almqvist Summary Almqvist C, Garden F, Kemp AS, Li Q, Crisafulli D, Tovey ER, Xuan W, Marks GB for the CAPS investigators. Effects of early cat or dog ownership on sensitisation and asthma in a high-risk cohort without disease-related modification of exposure. Paediatric and Perinatal Epidemiology 2010; 24: 171,178. Variation in the observed association between pet ownership and allergic disease may be attributable to selection bias and confounding. The aim of this study was to suggest a method to assess disease-related modification of exposure and second to examine how cat acquisition or dog ownership in early life affects atopy and asthma at 5 years. Information on sociodemographic factors and cat and dog ownership was collected longitudinally in an initially cat-free Australian birth cohort based on children with a family history of asthma. At age 5 years, 516 children were assessed for wheezing, and 488 for sensitisation. Data showed that by age 5 years, 82 children had acquired a cat. Early manifestations of allergic disease did not foreshadow a reduced rate of subsequent acquisition of a cat. Independent risk factors for acquiring a cat were exposure to tobacco smoke at home odds ratio (OR) 1.92 [95% confidence interval (CI) 1.13, 3.26], maternal education ,12 years OR 1.95 [1.08, 3.51] and dog ownership OR 2.23 [1.23, 4.05]. Cat or dog exposure in the first 5 years was associated with a decreased risk of any allergen sensitisation, OR 0.50 [0.28, 0.88] but no association with wheeze OR 0.96 [0.57, 1.61]. This risk was not affected by age at which the cat was acquired or whether the pet was kept in- or outdoors. In conclusion, cat or dog ownership reduced the risk of subsequent atopy in this high-risk birth cohort. This cannot be explained by disease-related modification of exposure. Public health recommendations on the effect of cat and dog ownership should be based on birth cohort studies where possible selection bias has been taken into account. [source] Epidemiology of post-injury multiple organ failure in an Australian trauma systemANZ JOURNAL OF SURGERY, Issue 6 2009David C. Dewar Abstract Background:, The epidemiology of post-injury multiple organ failure (MOF) is reported internationally to have gone through changes over the last 15 years. The purpose of this study is to describe the epidemiology of post-injury MOF in Australia. Methods:, A 12-month prospective epidemiological study was performed at the John Hunter Hospital (Level-1 Trauma Centre). Demographics, injury severity (ISS), physiological parameters, MOF status and outcome data were prospectively collected on all trauma patients who met inclusion criteria (ICU admission; ISS > 15; age > 18, head Abbreviated Injury Scale (AIS) <3 and survival >48 h). MOF was prospectively defined by the Denver MOF score greater than 3 points. Data are presented as % or Mean+/,SEM. Univariate statistical comparison was performed (Student t -test, X2 test), P < 0.05 was considered significant. Results:, Twenty-nine patients met inclusion criteria (Age 40+/,4, ISS 29+/,3, Male 62%), five patients developed MOF. The incidence of MOF among trauma patients admitted to ICU was 2% (5/204) and 17% (5/29) in the high-risk cohort. The maximum average MOF score was 6.3 +/,1, with the average duration of MOF 5+/,2 days. Two patients had respiratory and cardiac failure, two patients had failure of respiratory, cardiac and hepatic systems, while one patient had failure of respiratory, hepatic and renal systems. One MOF patient died, all non MOF patients survived. MOF patients had longer ICU stays (20+/,4 versus 7+/,0.8 P= 0.01), tended to be older (60+/,11 versus 35+/,4 p=0.07). None of the previously described independent predictors (ISS, base deficit, lactate, transfusions) were different when the MOF patients were compared with the non-MOF patients. Conclusion:, The incidence of MOF in Australia is consistent with the international data. In Australia MOF continues to cause significant late mortality and morbidity in trauma patients. MOF patients have longer ICU stay than high-risk non MOF patients, and use significant resources. Our preliminary data challenges the timeliness of the 10-year-old independent predictors of post-injury MOF. The epidemiology, the clinical presentation and the independent predictors of post-injury MOF require larger scale reassessment for the Australian context. [source] Effectiveness of a community-directed ,healthy lifestyle' program in a remote Australian Aboriginal communityAUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 2 2000Kevin G. Rowley Objective: To assess the sustainability and effectiveness of a community-directed program for primary and secondary prevention of obesity, diabetes and cardiovascular disease in an Aboriginal community in north-west Western Australia. Method: Evaluation of health outcomes (body mass index, glucose tolerance, and plasma insulin and triglyceride concentrations) in a cohort of high-risk individuals (n=49, followed over two years) and cross-sectional community samples (n=200 at baseline, 185 at two-year and 132 at four-year follow-ups), process (interventions and their implementation) and impact (diet and exercise behaviour). Results: For the high-risk cohort, involvement in diet and/or exercise strategies was associated with protection from increases in plasma glucose and triglycerides seen in a comparison group; however, sustained weight loss was not achieved. At the community level, significant reductions were observed in fasting insulin concentration but no change in prevalence of diabetes, overweight or obesity. Weight gain remained a problem among younger people. Sustainable improvements were observed for dietary intake and level of physical activity. These changes were related to supportive policies implemented by the community council and store management. Conclusions: Community control and ownership enabled embedding and sustainability of program, in association with social environmental policy changes and long-term improvements in important risk factors for chronic disease. Implications: Developmental initiatives facilitating planning, implementation and ownership of interventions by community members and organisations can be a feasible and effective way to achieve sustainable improvements in health behaviours and selected health outcomes among Aboriginal people. [source] Should we screen for bladder cancer in a high-risk population?CANCER, Issue 5 2006A cost per life-year saved analysis Abstract BACKGROUND. The U.S. Food and Drug Administration recently approved screening high-risk patients for bladder cancer using urine-based markers. The cost and life-years saved associated with bladder cancer screening were evaluated. METHODS. A Markov model was created to estimate cumulative cancer-related costs and efficacy of screening (vs. no screening) of a high-risk population for bladder cancer using a urine-based tumor marker over a 5-year period. Assumptions were based on literature review of survival and progression rates for patients with bladder cancer and costs associated with different bladder cancer disease states. RESULTS. Screening for bladder cancer in a population with a 4% incidence of bladder cancer resulted in a gain of 3.0 life years per 1000 subjects at a cost savings of $101,000 for the population, assuming a 50% downstaging in the screened population from muscle-invasive to nonmuscle-invasive disease. One-way sensitivity analyses found that screening is the most cost-effective strategy if cancer incidence is >1.6%, tumor marker costs <$126, marker sensitivity is >26%, marker specificity is >54%, downstaging with screening is >20%, and office cystoscopy costs <$694. Varying costs of cystectomy, transurethral resection of bladder tumor (TURBT), chemotherapy, end-of-life care, costs of metastatic disease, and a computed tomography scan over a wide range did not affect the superiority of screening. CONCLUSIONS. The model found that urine-based markers are cost-effective in a high-risk population. Prospective randomized trials in a completely asymptomatic high-risk cohort are indicated before bladder cancer screening can be recommended. Cancer 2006. © 2006 American Cancer Society. [source] Breast magnetic resonance image screening and ductal lavage in women at high genetic risk for breast carcinomaCANCER, Issue 3 2004Anne-Renee Hartman M.D. Abstract BACKGROUND Intensive screening is an alternative to prophylactic mastectomy in women at high risk for developing breast carcinoma. The current article reports preliminary results from a screening protocol using high-quality magnetic resonance imaging (MRI), ductal lavage (DL), clinical breast examination, and mammography to identify early malignancy and high-risk lesions in women at increased genetic risk of breast carcinoma. METHODS Women with inherited BRCA1 or BRCA2 mutations or women with a > 10% risk of developing breast carcinoma at 10 years, as estimated by the Claus model, were eligible. Patients were accrued from September 2001 to May 2003. Enrolled patients underwent biannual clinical breast examinations and annual mammography, breast MRI, and DL. RESULTS Forty-one women underwent an initial screen. Fifteen of 41 enrolled women (36.6%) either had undergone previous bilateral oophorectomy and/or were on tamoxifen at the time of the initial screen. One patient who was a BRCA1 carrier had high-grade ductal carcinoma in situ (DCIS) that was screen detected by MRI but that was missed on mammography. High-risk lesions that were screen detected by MRI in three women included radial scars and atypical lobular hyperplasia. DL detected seven women with cellular atypia, including one woman who had a normal MRI and mammogram. CONCLUSIONS Breast MRI identified high-grade DCIS and high-risk lesions that were missed by mammography. DL detected cytologic atypia in a high-risk cohort. A larger screening trial is needed to determine which subgroups of high-risk women will benefit and whether the identification of malignant and high-risk lesions at an early stage will impact breast carcinoma incidence and mortality. Cancer 2004. © 2004 American Cancer Society. [source] | ||||||||||