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At least 415 records · Page 23Linked to original sources
PubMed2003

Alternative definitions of comparable case groups and estimates of lead time and benefit time in randomized cancer screening trials.

Randomized screening trials provide the optimal means of assessing the benefit of screening for cancer and other chronic diseases. Unlike therapy trials, however, where strict eligibility criteria assure the comparability of cases of disease in the arms of the trial, the cancer cases identified during follow-up are a subset of all randomized participants. Furthermore, those cases detected by screening tend to arise from length biased sampling which also can bias estimates of the screening benefit and of average lead time. To reduce or eliminate this bias, we propose several methods for defining comparable groups of cases from the trial arms. We examine, via simulation, these methods with respect to their effects on (i). point and interval estimates of average lead time and average benefit time and (ii). the logrank test statistic for a mortality effect of screening. The most successful new method for defining comparable case groups uses an estimate of the mean sojourn time (mean preclinical duration), and results in nearly unbiased estimates of average lead time and average benefit time as well as an unbiased logrank test statistic.

Adult↗
PubMed1995

High mortality from unidentified CVD in IDDM: time to start screening?

Mortality in insulin-dependent diabetes is markedly increased compared to the general population. Although strong associations have been found between renal disease and the risk of cardiovascular disease (CVD) the interaction between these two factors is not well understood. This study, which addresses risk factors for mortality in IDDM with a particular focus on the renal-CVD link, is based on the prospective Epidemiology of Diabetes Complications study. Thirty-seven (mean age 36 years, mean duration of IDDM 28 years at baseline) of the 658 IDDM individuals (mean age 28 years, mean duration of IDDM 20 years at baseline) have died in the first 4 years of follow up. A nested case-control study was performed, matching on sex and duration of diabetes. Twenty-two (59%) of the deaths were attributed to coronary heart disease, with an additional 16% attributed to diabetic coma. Only nine (41%) of the 22 individuals who died from cardiovascular disease had clinical evidence of coronary heart disease when seen for their last biennial exam. However, 54% of those who died of CVD without prior evidence did have evidence of lower extremity arterial disease. A strong link with renal disease was confirmed, with 81% of those with a coronary artery disease death having renal disease. Multivariate analyses suggest that smoking history, triglycerides and total platelet count are independent predictors of mortality, while LDL cholesterol best predicted CVD mortality. These results suggest a need for more intensive screening for cardiovascular disease, and correction of cardiovascular risk factors, in order to reduce the increased rate of mortality in this population. Efforts to prevent or delay the onset of renal disease may also be of benefit.

Adult↗
PubMed2005

Coeliac disease: is it time for mass screening?

Screening studies indicate a prevalence of coeliac disease (CD) of up to 1% in populations of European ancestry, yet the majority of cases remain undiagnosed. Serological markers for CD now available have high sensitivity and specificity, offering the option of mass population screening. The principles of disease screening as set out by Wilson and Jugner can be applied to CD to predict whether this is appropriate. CD is an important health problem for the individual and the community because of high prevalence, associated specific and non-specific morbidity, and long-term complications of which the most important are gut malignancy and osteoporosis. However, recent studies indicate that the prevalence of malignancy and the health impact of osteoporosis are much less than previously supposed, so the prophylactic benefits of early diagnosis through screening may be low. While CD has an accepted and effective treatment, dietary gluten exclusion, this is difficult for the individual and asymptomatic cases may be poorly motivated to comply. Diagnosis of CD is by histological confirmation on duodenal biopsy. We now recognise milder degrees of gluten sensitive enteropathy without villous atrophy (Marsh I, II lesions) and the benefits to the individual by identifying these early lesions through screening is unknown: whether to treat such individuals needs to be agreed before programmes commence. Screening with serum antibodies is relatively non-invasive but may have to be repeated during each individual's lifetime. HLA typing beforehand to identify the 30% of the population with DQ2 or DQ8, who are at potential risk of CD, will allow one-off exclusion of a large percentage of the population but like all genetic testing has ethical implications. The economic costs of screening and treatment versus morbidity prevented have not been calculated.

Celiac Disease↗
PubMed2006

Screening long-time plating effluent qualities by sorbent sorption with XRF analysis.

Long-term monitoring of plating effluent quality traditionally requires dense frequency sampling and analysis for multiple elements are needed. An effective and rapid approach was developed to monitor long-time plating effluent quality. The approach employs the placement of low-cost sorbents (chitosan, zeolite and granular activated carbon) in plating effluents followed by analysis of multiple-element X-ray fluorescence (XRF). Three plating effluents were selected in this study. Laboratory Freundlich isotherm sorption experiments were also conducted to describe the relationships of metal concentrations on sorbents and in effluents. Results indicated that chitosan was a suitable sorbent to estimate the Zn, Ni and Cr concentrations in plating effluents. Granular activated carbon was suitable for Cu concentration monitoring in effluents. The accumulation of metals onto sorbents with different sorption periods (1-3 days) was also investigated.

Adsorption↗
PubMed2001

Genetic hemochromatosis, a Celtic disease: is it now time for population screening?

In populations of northern European ancestry, hereditary hemochromatosis (HH) is tightly linked to mutations within the hemochromatosis gene (HFE gene). Over 93% of Irish HH patients are homozygous for the HFE gene C282Y mutation, providing a reliable diagnostic marker of the disease in this population. However, the prevalence of the C282Y mutation and that of the second HFE gene mutation, H63D, have yet to be determined within the Irish population. The objective of this study was to identify the true prevalence of the genetic form of HH in the Irish population. DNA was extracted from 1002 randomly selected newborn screening cards and analyzed for the C282Y and H63D mutations within the HFE gene. Complete results were obtained from 800 cards. Mutations were identified in 364 (46%) neonates. Eight (1%) neonates were homozygous for C282Y and 8 (1%) were homozygous for H63D. One hundred and fifty-five (19%) neonates were C282Y heterozygous and 226 (28%) were H63D heterozygous. Of these, 33 (4%) carried one copy of both C282Y and H63D mutations, i.e., compound heterozygous. Allele frequencies for C282Y and H63D were 11% and 15%, respectively. The high C282Y allele frequency in the Irish population together with its close linkage to HH indicate that C282Y genotyping is the preferred screening strategy for this disease in Ireland.

Ethnicity↗
PubMed1989

Predictive value of a short dietary questionnaire for changes in serum lipids in high-risk Utah families.

Dietary questionnaires and serum cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol determinations were completed for 1239 subjects aged greater than or equal to 20 at each of two separate screenings. The mean time between screenings was 2.5 y. After correcting for potential confounding variables, reduction of a measure of dietary cholesterol and saturated fatty acids assessed by two simple questions was a significant independent predictor of reduction in total cholesterol in serum (p less than 0.005). Initial body mass index (BMI) and change in BMI were highly significant predictors of initial values and changes in total cholesterol, triglycerides, and HDL cholesterol in serum. Reduction of dietary saturated fatty acid and cholesterol was significantly correlated with initial serum cholesterol levels, which suggest that serum cholesterol screening may be an important motivating factor for dietary change. Important public health and research implications of these findings are discussed.

Adult↗
PubMed2000

Soda bread provocation test for subjects with transient serology for coeliac disease 3 years after a population screening survey.

BACKGROUND: We have previously reported that IgA antigliadin antibodies (IgA-AGA) in the majority of healthy subjects are transient and do not indicate enteropathy, and also that an increased intake of gluten in the form of soda bread may be part of the explanation for this phenomenon. OBJECTIVE: The aim of the study was to determine whether gluten challenge with soda bread in subjects with transiently positive IgA-AGA could induce a significant titre of IgA-AGA. DESIGN: Food challenge study. METHODS: All subjects with positive IgA-AGA on screening at the time of the MONICA project in 1991 (T0) who developed negative serology at 3-year follow-up (T1) were invited to participate in a 'soda bread challenge' (1 loaf per day) for 1 month. Analysis of food intake was carried out prior to the challenge (T2) and compared to the analysis at the time of screening (T0). IgA-AGA and IgA antiendomysial antibodies (EMA) were checked pre- (T2) and post-challenge (T3). RESULTS: Ten subjects agreed to participate. Quantities of food ingested for the various categories did not differ significantly from T0 to T2. IgA-AGA titres did not differ significantly from T1 to T2 (20.2 versus 35.0, P=0.085). Mean IgA-AGA titres rose significantly between T2 and T3 (35.0 versus 40.3, P=0.005), although none of the subjects developed a significant titre of IgA-AGA. None of the subjects were positive for IgA-EMA. CONCLUSIONS: Intake of soda bread does not appear to be an important explanation as to why subjects may have a transient rise in IgA-AGA titre since none of the subjects developed a significant titre of IgA-AGA.

Bread↗
PubMed2006

Electrocardiography and the preparticipation physical examination: is it time for routine screening?

The preparticipation physical examination (PPE) is a screening tool endorsed by numerous organizations and used to evaluate young athletes prior to competition for both medical and musculoskeletal conditions that may predispose them to injury. The cardiac portion of the examination, as recommended by the American Heart Association, is detailed specifically to detect signs or symptoms consistent with certain congenital heart conditions that may increase a young athlete's risk of sudden cardiac death (SCD). Much controversy has erupted over the years as to whether this examination has the diagnostic sensitivity to detect these conditions and prevent SCD, and whether additional modalities, such as the 12-lead electrocardiograph (ECG), should be incorporated. Given the rarity of SCD events, the large population of young athletes that would qualify yearly for the examination, and the limitations that an ECG would present, it would not be efficient to add the ECG to the standard PPE on the symptomatic athlete. More efforts should be spent in standardizing the PPE on a national level to further improve its efficiency.

Adolescent↗
PubMed2025

RESTRICT-seq enables time-gated CRISPR screens and uncovers novel epigenetic dependencies of SCC resistance.

Cancer cell evasion of therapy is a highly adaptive process that undermines the efficacy of many treatment strategies. A significant milestone in the study of these mechanisms has been the advent of pooled CRISPR knockout screens, which enable high-throughput, genome-wide interrogations of tumor dependencies and synthetic lethal interactions, advancing our understanding of how cancer cells adapt to and evade therapies. However, the utility of this approach diminishes when applied to dynamic biological contexts, where processes are transient and sensitivity to routine cell culture manipulations that introduce noise and limit meaningful discoveries. To overcome these limitations, we present RESTRICT-seq, a next-generation pooled screening methodology that restricts Cas9 nuclear activation in controlled, repeated cycles. By confining Cas9 catalytic activity to strict temporal windows, RESTRICT-seq mitigates undesired fitness penalties that routinely accumulate throughout pooled screens. When benchmarked against conventional pooled screens and standard inducible protocols, RESTRICT-seq revealed significantly fewer divergent cell clones and increased signal-to-noise ratio, overcoming a key limitation of traditional methods. Leveraging RESTRICT-seq, we conducted a comprehensive functional survey of the druggable mammalian epigenome, uncovering several elusive epigenetic drivers of treatment resistance in cutaneous squamous cell carcinoma (cSCC). This revealed PAK1 as a previously unrecognized mediator of cSCC resistance in human and mouse SCC, offering new insights into a prognostic marker and therapeutic target of high clinical significance. Our findings establish RESTRICT-seq as a powerful tool for extending the applicability of pooled CRISPR screens to dynamic and previously intractable biological contexts.

Allosterically-regulated Cas9 (arCas9)↗