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Disease Endpoints (disease + endpoint)
Selected AbstractsGenotype,phenotype studies in infantile spinal muscular atrophy (SMA) type I in Germany: implications for clinical trials and genetic counsellingCLINICAL GENETICS, Issue 2 2009S Rudnik-Schöneborn We reviewed the natural history and assessed the SMN2 copy number of 66 patients with infantile spinal muscular atrophy (SMA) type I born between 2000 and 2005 in Germany whose diagnosis was confirmed by a homozygous SMN1 deletion in the first 6 months of life. After excluding patients who had received valproic acid, the median/mean age at disease endpoint was 6.1/7.3 months (range 0.0,34.0). Four (6.1%) patients with one SMN2 copy had severe SMA type ,0' with joint contractures and respiratory distress from birth. Median/mean age at onset (months) in 57 (86.3%) patients with two SMN2 copies was 1.2/1.3, and 3.5/3.4 in 5 (7.6%) patients with three SMN2 copies. Median/mean age at disease endpoint was 6.5/7.8 months (range 0.5,30) in patients with two SMN2 copies. All patients with three SMN2 copies were still alive at 10,55 months, two of them under permanent ventilation. Our data are relevant for prognostication and genetic counselling. The observed clinical variability, especially in the group with two SMN2 copies, might be important for clinical trials in SMA I where a possible control group could be defined as follows: age at onset within 4,5 months, age at genetic diagnosis <6 months, two SMN2 copies present, head control in less than 10%, no respiratory distress from birth, disease endpoint either age at death or age at permanent ventilation. [source] Hemochromatosis genotypes and risk of 31 disease endpoints: Meta-analyses including 66,000 cases and 226,000 controls,HEPATOLOGY, Issue 4 2007Christina Ellervik Hemochromatosis genotypes have been associated with liver disease, diabetes mellitus, heart disease, arthritis, porphyria cutanea tarda, stroke, neurodegenerative disorders, cancer, and venous disease. We performed meta-analyses including 202 studies with 66,263 cases and 226,515 controls to examine associations between hemochromatosis genotypes C282Y/C282Y, C282Y/H63D, C282Y/wild type, H63D/H63D, and H63D/wild type versus wild type/wild type and 9 overall endpoints and 22 endpoint subgroups. We also explored potential sources of heterogeneity. For liver disease, the odds ratio for C282Y/C282Y versus wild type/wild type was 3.9 (99% confidence interval: 1.9,8.1) overall, 11 (3.7,34) for hepatocellular carcinoma, 4.1 (1.2,14) for hepatitis C, and 10 (2.1,53) for nonalcoholic steatohepatitis. For porphyria cutanea tarda, the odds ratios were 48 (24,95) for C282Y/C282Y, 8.1 (3.9,17) for C282Y/H63D, 3.6 (1.8,7.3) for C282Y/wild type, 3.0 (1.6,5.6) for H63D/H63D, and 1.7 (1.0,3.1) for H63D/wild type versus wild type/wild type. Finally, for amyotrophic lateral sclerosis, the odds ratio was 3.9 (1.2,13) for H63D/H63D versus wild type/wild type. These findings were consistent across individual studies. The hemochromatosis genotypes were not associated with risk for diabetes mellitus, heart disease, arthritis, stroke, cancer, or venous disease in the overall analyses; however, the odds ratio for C282Y/C282Y versus wild type/wild type was 3.4 (1.1,11) for diabetes mellitus among North Europeans. Conclusion: In aggregate, clinically ascertained cases who are homozygous for the C282Y mutation are associated with a 4,11,fold risk of liver disease, whereas all 5 hemochromatosis genotypes are associated with a 2,48,fold risk of porphyria cutanea tarda, and H63D/H63D is associated with a 4-fold risk of amyotrophic lateral sclerosis. These results, mainly from case-control studies, cannot necessarily be extrapolated to the general population. (HEPATOLOGY 2007.) [source] An Overview of the Design, Implementation, and Analyses of Longitudinal Studies on AgingJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 2010Anne B. Newman MD Longitudinal studies have contributed substantially to understanding of aging and geriatric syndromes. These efforts have provided a base of knowledge of the critical factors to consider in designing and implementing new longitudinal studies in older adults. This review highlights some of the major considerations in planning and implementing this type of study. Longitudinal studies can assess change over time and specific disease endpoints. Such projects require multidisciplinary teams with expertise in the many health and contextual factors that must be considered. Recent advances in study design include the use of imaging and biomarkers to assess mechanisms and approaches that raise the ceiling on measurement and integrate assessment of exposures over time. Study implementation requires careful planning and monitoring to maintain fidelity to the scientific goals. Analysis of longitudinal data requires approaches that account for inevitable missing data. New studies should take advantage of the experience obtained from longitudinal studies on aging already conducted. [source] Surrogate Alcohol: What Do We Know and Where Do We Go?ALCOHOLISM, Issue 10 2007Dirk W. Lachenmeier Background:, Consumption of surrogate alcohols (i.e., nonbeverage alcohols and illegally produced alcohols) was shown to impact on different causes of death, not only poisoning or liver disease, and appears to be a major public health problem in Russia and elsewhere. Methods:, A computer-assisted literature review on chemical composition and health consequences of "surrogate alcohol" was conducted and more than 70 references were identified. A wider definition of the term "surrogate alcohol" was derived, including both nonbeverage alcohols and illegally produced alcohols that contain nonbeverage alcohols. Results:, Surrogate alcohol may contain substances that cause severe health consequences including death. Known toxic constituents include lead, which may lead to chronic toxicity, and methanol, which leads to acute poisoning. On the other hand, the role of higher alcohols (e.g., propanol, isobutanol, and isoamyl alcohol) in the etiology of surrogate-associated diseases is currently unclear. Whether other constituents of surrogates have contributed to the high all-cause mortality over and above the effect of ethanol in recent studies also remains unclear. Conclusions:, Given the high public health importance associated with the consumption of surrogate alcohols, further knowledge on its chemical composition is required as well as research on its links to various disease endpoints should be undertaken with priority. Some interventions to reduce the harm resulting from surrogate alcohol could be undertaken already at this point. For example, the use of methanol or methanol-containing wood alcohol should be abolished in denatured alcohol. Other possible surrogates (e.g., automobile products) should be treated with bittering agents to avoid consumption. [source] | ||||||||||