Coeliac disease detected by screening is not silent--simply unrecognized

Coeliac disease (CD) is associated with a wide spectrum of clinical presentation and may be overlooked as a diagnosis. There is some evidence that untreated CD is associated with a doubling of mortality, largely due to an increase in the incidence of malignancy and small intestinal lymphoma, which is decreased by a strict gluten-free diet. We studied the clinical features of screening-detected coeliacs compared to age- and sex-matched controls as a 3-year follow-up to a population screening survey, and followed-up subjects who had had CD-associated serology 11 years previously to determine whether they have CD or an increased mortality rate compared to the general population. Samples of the general population (MONICA 1991 and 1983) were screened for CD-associated serology and followed-up after 3 and 11 years, respectively, and assessed by a clinical questionnaire, screening blood tests and jejunal biopsy. Mortality rates for 'all deaths' and 'cancer deaths' were compared in subjects with positive serology in 1983 with reference to the general population. Thirteen coeliacs were diagnosed by villous atrophy following screening, compared to two patients with clinically detected CD, giving a prevalence of 1:122. Clinical features or laboratory parameters were not indicative of CD compared to controls. Subjects with positive serology followed up after 11 years did not have an excess mortality for either cancer deaths or all causes of death. Screening-detected CD is rarely silent and may be associated with significant symptoms and morbidity. In this limited study with small numbers, there does not appear to be an increased mortality from screening-detected CD, although the follow-up may be too short to detect any difference.

DemTect:a new, sensitive cognitive screening test to support the diagnosis of mild cognitive impairment and early dementia

To design a new, highly sensitive psychometric screening to identify patients with mild cognitive impairment (MCI) and patients with dementia in the early stages of the disease.

Ecotoxicological screening of Kenyan tannery dust using a luminescent-based bacterial biosensor

Ecotoxicological screening of dust sampled throughout a Kenyan tannery was conducted using a luminescence (lux)-based bacterial biosensor for both solid and liquid assays. This was complemented by chemical analysis in an attempt to identify possible causative toxic components. The biosensor results showed a highly significant (p <0.001) difference in both solid and liquid phase toxicity in samples collected from various identified sampling points in the tannery. A positive correlation was observed between results of the solid and liquid phase techniques, for most of the sampling points indicating that the toxic contaminants were bioavailable both in the solid and liquid state. However, the results generally indicated toxicity associated with liquid phase except certain areas in solid phase such as chemical handling, buffing area and weighing. The most toxic tannery area identified was the weighing area (p <0.001), showing the lowest bioluminescence for both the solid (0.38 +/- 2.21) and liquid phases (0.01 +/- 0.001). Chromium was the metal present in the highest concentration indicating levels higher than the stipulated regulatory requirement of 0.5 mg Cr/m3 for total Cr (highest Cr concentration was at chemical handling at 209.24 mg l(-1)) in all dust samples. The weighing area had the highest Ni concentration (1.87 mg l(-1)) and the chemical handling area showed the highest Zn concentration (31.9 mg l(-1)). These results raise environmental health concerns, as occupational exposure to dust samples from this site has been shown to give rise to elevated concentrations (above the stipulated levels) of chromium in blood, urine and some body tissues, with inhalation being the main route. Health and Safety Executive (HSE), UK, and American Conference of Governmental Industrial Hygienist (ACGIH) and National Institute for Occupational Safety and Health (NIOSH), USA stipulates an occupational exposure limit of 0.5 mg Cr/m3 (8 h TWA) for total chromium. However, schedule 1 of Controls of substances hazardous to health (COSHH) regulations developed by HSE, indicate 0.05 mg m3 (8 h TWA reference periods) to be the limit for Cr (VI) exposure. The exposure limit for individual (e.g., Cr, Zn, Ni etc.) contaminants (homogeneity) was not exceeded, but potential impact of heterogeneity (multi-element synergistic effect) on toxicity requires application of the precautionary principle.

Low pressure carbon dioxide solubility in lithium-ion batteries based electrolytes as a function of temperature. Measurement and prediction

We present in this study the effect of nature and concentration of lithium salt, such as the lithium hexafluorophosphate, LiPF6; lithium tris(pentafluoroethane)-trifluorurophosphate LiFAP; lithium bis(trifluoromethylsulfonyl)imide, LiTFSI, on the CO2 solubility in four electrolytes for lithium ion batteries based on pure solvent that include ethylene carbonate (EC), dimethyl carbonate (DMC), ethyl methyl carbonate (EMC), diethyl carbonate (DEC), as well as, in the EC:DMC, EC:EMC and EC:DEC (50:50) wt.% binary mixtures as a function of temperature from (283 to 353) K and atmospheric pressure. Based on experimental solubility values, the Henry’s law constant of the carbon dioxide in these solutions with the presence or absence of lithium salt was then deduced and compared with reported values from the literature, as well as with those predicted by using COSMO-RS methodology within COSMOThermX software. From this study, it appears that the addition of 1 mol · dm-3 LiPF6 salt in alkylcarbonate solvents decreases their CO2 capture capacity. By using the same experimental conditions, an opposite CO2 solubility trend was generally observed in the case of the addition of LiFAP or LiTFSI salts in these solutions. Additionally, in all solutions investigated during this work, the CO2 solubility is greater in electrolytes containing the LiFAP salt, followed by those based on the LiTFSI case. The precision and accuracy of the experimental data reported therein, which are close to (1 and 15)%, respectively. From the variation of the Henry’s law constant with temperature, the partial molar thermodynamic functions of dissolution such as the standard Gibbs energy, the enthalpy, and the entropy, as well as the mixing enthalpy of the solvent with CO2 in its hypothetical liquid state were calculated. Finally, a quantitative analysis of the CO2 solubility evolution was carried out in the EC:DMC (50:50) wt.% binary mixture as the function of the LiPF6 or LiTFSI concentration in solution to elucidate how ionic species modify the CO2 solubility in alkylcarbonates-based Li-ion electrolytes by investigating the salting effects at T = 298.15 K and atmospheric pressure.

Comparison of Wavelet Transform and Time-Domain Analysis of Second Trimester Uterine Artery Doppler Waveforms in Screening for Pre-Eclampsia

The aim of this study was to compare time-domain waveform analysis of second-trimester uterine artery Doppler using the resistance index (RI) with waveform analysis using a mathematical tool known as wavelet transform for the prediction of pre-eclampsia (PE). This was a retrospective, nested case-cohort study of 336 women, 37 of whom subsequently developed PE. Uterine artery Doppler waveforms were analysed using both RI and waveform analysis. The utility of these indices in screening for PE was then evaluated using receiver operating characteristic curves. There were significant differences in uterine artery RI between the PE women and those with normal pregnancy outcome. After wavelet analysis, significant difference in the mean amplitude in wavelet frequency band 4 was noted between the 2 groups. The sensitivity for both Doppler RI and frequency band 4 for the detection of PE at a 10% false-positive rate was 45%. This small study demonstrates the application of wavelet transform analysis of uterine artery Doppler waveforms in screening for PE. Further prospective studies are needed in order to clearly define if this analytical approach to waveform analysis may have the potential to improve the detection of PE by uterine artery Doppler screening.

Screening tests for detecting open-angle glaucoma: systematic review and meta-analysis

PURPOSE: To assess the comparative accuracy of potential screening tests for open angle glaucoma (OAG).

METHODS: Medline, Embase, Biosis (to November 2005), Science Citation Index (to December 2005), and The Cochrane Library (Issue 4, 2005) were searched. Studies assessing candidate screening tests for detecting OAG in persons older than 40 years that reported true and false positives and negatives were included. Meta-analysis was undertaken using the hierarchical summary receiver operating characteristic model.

RESULTS: Forty studies enrolling over 48,000 people reported nine tests. Most tests were reported by only a few studies. Frequency-doubling technology (FDT; C-20-1) was significantly more sensitive than ophthalmoscopy (30, 95% credible interval [CrI] 0-62) and Goldmann applanation tonometry (GAT; 45, 95% CrI 17-68), whereas threshold standard automated perimetry (SAP) and Heidelberg Retinal Tomograph (HRT II) were both more sensitive than GAT (41, 95% CrI 14-64 and 39, 95% CrI 3-64, respectively). GAT was more specific than both FDT C-20-5 (19, 95% CrI 0-53) and threshold SAP (14, 95% CrI 1-37). Judging performance by diagnostic odds ratio, FDT, oculokinetic perimetry, and HRT II are promising tests. Ophthalmoscopy, SAP, retinal photography, and GAT had relatively poor performance as single tests. These findings are based on heterogeneous data of limited quality and as such are associated with considerable uncertainty.

CONCLUSIONS: No test or group of tests was clearly superior for glaucoma screening. Further research is needed to evaluate the comparative accuracy of the most promising tests.

Genetic screening protocol for familial hypercholesterolemia which includes splicing defects gives an improved mutation detection rate

Familial hypercholesterolemia (FH) is a common single gene disorder, which predisposes to coronary artery disease. In a previous study, we have shown that in patients with definite FH around 20% had no identifiable gene defect after screening the entire exon coding area of the low density lipoprotein receptor (LDLR) and testing for the common Apolipoprotein B (ApoB) R3500Q mutation. In this study, we have extended the screen to additional families and have included the non-coding intron splice regions of the gene. In families with definite FH (tendon xanthoma present, n = 68) the improved genetic screening protocol increased the detection rate of mutations to 87%. This high detection rate greatly enhances the potential value of this test as part of a clinical screening program for FH. In contrast, the use of a limited screen in patients with possible FH (n = 130) resulted in a detection rate of 26%, but this is still of significant benefit in diagnosis of this genetic condition. We have also shown that 14% of LDLR defects are due to splice site mutations and that the most frequent splice mutation in our series (c.1845 + 11 c > g) is expressed at the RNA level. In addition, DNA samples from the patients in whom no LDLR or ApoB gene mutations were found, were sequenced for the NARC-1 gene. No mutations were identified which suggests that the role of NARC-1 in causing FH is minor. In a small proportion of families (

Mutation screening and genotype:phenotype correlation in familial hypercholesterolaemia

The aim of this study was to develop a mutation screening protocol for familial hypercholesterolaemia (FH) patients and to assess genotype/phenotype effects in terms of pre-treatment lipid profiles and presentation of tendon xanthomata (TX). A total of 158 families with clinical definitions of possible (120) or definite (38) FH were studied using a tiered screening protocol. Mutations were identified in 52 families, 44 families showing 23 different LDLR gene defects and eight families showing the common Apo B100 gene defect R3500Q. LDLR defects were detected in various regions of the gene with 56% in the LDL binding domain (exons 2-6) and 37% in the EGF precursor homology domain (exons 7-14). The most common mutations were D461N(7), C210X(5), 932delA(5), and C163Y(4). Frameshift mutations accounted for 20% with nonsense 13%, mis-sense 35%, splice 3%, Apo B 13% and 2% large deletion, 13% of clinically definite FH remained undefined. In conclusion, DNA based diagnosis is possible in 79% (30/38) of clinically definite FH families and of the 120 possible FH families at the start of the screening program, 18% (22/120) now have defined mutations. Overall 60 families from the original 158 meet the clinical and/or genetic criteria for definite FH. Tendon xanthomata were present in only 58% (30/52) of genetically defined FH families, thus limiting its use as a strict diagnostic criteria. Families with low density lipoprotein receptor (LDLR) defects present with higher total and LDL cholesterol levels and a higher incidence of TX than do those with the common Apo B variant, and frameshift mutations appear to have the most severe presentation. Copyright (C) 1999 Elsevier Science Ireland Ltd.

Developing the specifications of an open angle glaucoma screening intervention in the United Kingdom: a Delphi approach.

Abstract
BACKGROUND:
Glaucoma is a leading cause of blindness. Early detection is advocated but there is insufficient evidence from randomized controlled trials (RCTs) to inform health policy on population screening. Primarily, there is no agreed screening intervention. For a screening programme, agreement is required on the screening tests to be used, either individually or in combination, the person to deliver the test and the location where testing should take place. This study aimed to use ophthalmologists (who were experienced glaucoma subspecialists), optometrists, ophthalmic nurses and patients to develop a reduced set of potential screening tests and testing arrangements that could then be explored in depth in a further study of their feasibility for evaluation in a glaucoma screening RCT.
METHODS:
A two-round Delphi survey involving 38 participants was conducted. Materials were developed from a prior evidence synthesis. For round one, after some initial priming questions in four domains, specialists were asked to nominate three screening interventions, the intervention being a combination of the four domains; target population, (age and higher risk groups), site, screening test and test operator (provider). More than 250 screening interventions were identified. For round two, responses were condensed into 72 interventions and each was rated by participants on a 0-10 scale in terms of feasibility.
RESULTS:
Using a cut-off of a median rating of feasibility of =5.5 as evidence of agreement of intervention feasibility, six interventions were identified from round 2. These were initiating screening at age 50, with a combination of two or three screening tests (varying combinations of tonometry/measures of visual function/optic nerve damage) organized in a community setting with an ophthalmic trained technical assistant delivering the tests. An alternative intervention was a 'glaucoma risk score' ascertained by questionnaire. The advisory panel recommended that further exploration of the feasibility of screening higher risk populations and detailed specification of the screening tests was required.
CONCLUSIONS:
With systematic use of expert opinions, a shortlist of potential screening interventions was identified. Views of users, service providers and cost-effectiveness modeling are now required to identify a feasible intervention to evaluate in a future glaucoma screening trial.