bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preparation of the first European working standard for phenylalanine determination in dried blood spots
Authors: Dhondt J L , Loeber J G , Elvers L H , Paux E 
Published: May 2013

Objective To develop a standard preparation for measurement of phenylalanine in blood spots in phenylketonuria against which manufacturers of kits for phenylalanine determination could calibrate their own blood spot calibrators. Methods As most of the variation of phenylalanine concentration in dried blood spots is due to the way the blood spot calibrators are prepared, a minimum set of prerequisites for the preparation of blood spot calibrators was established by a group of scientific experts and manufacturers. A “European working standard for phenylalanine in blood spots” (EWS-Phe-01) was prepared and distributed to manufacturers taking part in this project. Results The control of the homogeneity, linearity, and stability of the EWS-Phe-01 batch gave results within expected ranges. The preliminary results of the recalibration of calibrators for phenylalanine against EWS-Phe-01 by the participating manufacturers were promising; the differences between measurements were much decreased. Conclusion Manufacturers have agreed to use EWS-Phe-01, and since November 1996 EWS-Phe calibrators have been routinely available from these companies. This pilot study may act as a model for minimising discrepancies found in other screening tests.
Radiation risk of mammography related to benefit in screening programmes: a favourable balance?
Authors: Beemsterboer P M M , Warmerdam P G , Boer R , de Koning H J 
Published: May 2013

Objectives To estimate the number of breast cancer deaths induced by low dose radiation in breast cancer screening programmes compared with numbers prevented. Methods A computer simulation model on the natural history of breast cancer was combined with a model from BEIR-V on induced breast cancer mortality from low levels of radiation. The improvement in prognosis resulting from screening was based on the results of the Swedish overview of the randomised screening trials for breast cancer and the performance of screening in the Netherlands. Different scenarios (ages and intervals) were used to explore the objectives. Sensitivity analyses were carried out for latency period, dose of mammography, sensitivity of the screening test, early detection by screening of induced breast tumours, and new 1996 risk estimates by Howe and McLaughlin. Results For a screening programme, age group 50–69, two year interval, 2 mGy per view, the balance between the number of deaths induced versus those prevented was favourable: 1:242. When screening is expanded to the age group 40–49 with a one or two year interval the results may be less favourable, that is, 1:66 and 1:97. According to these scenarios and with the Dutch scenario as reference, one breast cancer death from radiation may be expected to occur to save eight extra deaths from breast cancer. If screening was equally effective in young women as in women aged 50–69, the marginal value was 1:±30. Assuming detection of induced cancers by screening could influence the ratios by about 30%, but did not substantially change the conclusions. The new risk estimates by Howe and McLaughlin resulted in five times to eight times favourable ratios breast cancer deaths induced to prevented. Besides age group of screening, dose of mammography is the other determinant of risk. Conclusions For screening under the age of 50, the balance between the number of breast cancer deaths prevented by screening compared with the number induced by radiation seem less favourable. Credibility intervals were however wide, because of many uncertainties of radiation risk at very low doses.
Performance of antenatal HIV screening strategies in the United Kingdom
Authors: Tookey P A , Gibb D M , Ades A E , Duong T , Masters J , Sherr L , Peckham C S , Hudson C N 
Published: May 2013

Background In 1996 only 13.5% of previously undiagnosed HIV infected women were detected in pregnancy. In this study, all 265 maternity units in the United Kingdom were surveyed to determine the relation between screening strategy, uptake of testing, and detection rate. Methods Data on HIV screening strategy and uptake of testing were collected in 1997 by postal questionnaire. The proportion of women with previously undiagnosed HIV infection identified during pregnancy (detection rate) was calculated using data from national obstetric HIV surveillance and unlinked anonymous seroprevalence studies. Results 239 (90%) units responded; 25 of these (10%) had a universal offer strategy, 89 (37%) a selective offer, and 125 (52%) tested only women who requested it. All selective units offered testing to injecting drug users, but only 26% to women who had lived abroad in high prevalence areas. Uptake was over 10% in only eight units, all with a universal strategy, and in 76% of selective units it was below 0.1%. The detection rate was 14.7% in universal units, 7.8% in selective units, and 7.7% in on request units. In universal units, detection increased by 6.3% (95% confidence interval 3.7% to 8.8%) for every 10% increase in uptake of testing. There was evidence of both selective presentation for testing and avoidance of testing among infected women. Conclusions All current antenatal HIV testing strategies fail to identify most infected women. Universal offer strategies achieve a very low uptake and a poor detection rate. Units with selective strategies tend to test only a minority of women at high risk and do not target all the main high risk groups.
Does the frame affect the picture? A study into how attitudes to screening for cancer are affected by the way benefits are expressed
Authors: Sarfati D , Howden-Chapman P , Woodward A , Salmond C 
Published: May 2013

Objective To find out how presenting information about the benefits of screening for cancer in different ways affects an individual's decision to accept or reject screening. Methods A telephone survey of the Wellington region, New Zealand was carried out. Results A response rate of 75.6% was obtained. Respondents were most likely to accept screening when the benefits of screening were presented as a relative risk reduction. They were most likely to reject screening when the benefits were presented as numbers needed to screen to save one life. Conclusions An individual's decision about screening for cancer is affected by the way the benefits are framed. Health professionals must choose between framing the benefits of screening in the most positive light, to enhance participation rates, and presenting information in such a way as to reduce framing effects—for example, by expressing the benefits in a variety of forms. Clearly there may be a tension between these approaches; the former is arguably manipulation, and the latter may enhance informed choice, but may also reduce participation rates in screening programmes.
Efficiency of cancer detection during routine repeat (incident) mammographic screening: two versus one view mammography
Authors: Blanks R G , Given-Wilson R M , Moss S M 
Published: May 2013

Objective To examine the influence of one view versus two view mammography on cancer detection and recall for further investigation of women attending incident (subsequent) screening. Setting All cancers (invasive and in situ) detected as incident cases during the second screening round (January 1994 to January 1997) at the South West London Breast Screening Service were used. This service uses two view mammography and double reading, with arbitration by a third or further readers for all screens. Methods Mammograms of cases were mixed with those of controls in a 1:2 ratio in nine test sets; each set was read independently by three film readers. Fourteen readers, each reading from one to four test sets, took part in the study. Initially, the oblique view only was read, then the craniocaudal view was read in addition. Previous films were available to the readers. Data on abnormalities noted on the films and probability of recall were recorded and analysed. Results 10 of the 14 readers obtained increased sensitivity using two views (p=0.04), for two readers there was no difference, and for two readers sensitivity decreased. The mean sensitivity increase was 6.1% (p=0.01). The overall increase in sensitivity from all readings of invasive cancers was 8.9%, with no increase seen for in situ cancers. 11 of the 14 readers obtained an increase in specificity (p=0.006), two readers showed no increase, and the specificity for one reader was decreased. The mean increase in specificity using two views was 5.7% (p=0.006). Conclusion This study showed an increase of 8.9% in sensitivity for the detection of invasive cancers when two views are used at incident screening, with a ratio of two control mammograms for every case. This is equivalent to a sample from population screening with a cancer detection rate of 333 per 1000. Such a study is considered to be likely to underestimate the benefit of two views in screening under non-test conditions where the cancer detection rate is of the order of five per 1000. The use of two view mammography for the detection of in situ cancers showed no increased benefit. A randomised controlled trial is needed to obtain a reliable estimate of the increase in cancer detection rate for incident screening in normal populations.
General population screening for infection with Helicobacter pylori: a realistic option?
Authors: Stone M A , Barnett D B , Mayberry J F 
Published: May 2013

Objectives To consider the effectiveness of a community programme of Helicobacter pylori (H pylori) screening and eradication run in collaboration with general practitioners. Specifically, to assess numbers successfully eradicating H pylori and consequently reducing the prevalence of infection, and to identify and consider areas of poor compliance. Setting A large general practice in Market Harborough, Leicestershire, UK. Methods A general population sample of 4015 subjects aged 21–55 was offered a serological screening test for H pylori through their general practitioners. Those testing positive were offered a prescription for eradication treatment and an information pack designed to encourage good compliance. Successful eradication was assessed by a urea breath test. Results The screening test was accepted by 1566 (39%) of those invited, with men and younger people least likely to attend. Of the 235 (15%) subjects who tested positive, 186 (79%) were treated and eradication was confirmed in 170 (95%) of the 179 subjects who had a urea breath test. Overall, eradication was confirmed in 4% (170/4015) of those offered screening. Assuming a 15% overall prevalence of H pylori infection, it is estimated that H pylori was eradicated in 29% of those infected in the target group. Conclusions When an intervention was used to encourage good compliance, the eradication rate was high. Effectiveness was limited most strongly by the acceptance rate for the screening test, but also by the rate of uptake of eradication treatment. If benefits of population screening can be shown, appropriate interventions to improve compliance in these areas would need consideration.
Analysis of 31 CFTR mutations by polymerase chain reaction/oligonucleotide ligation assay in a pilot screening of 4476 newborns for cystic fibrosis
Authors: Gasparini P. , Arbustini E. , Restagno G. , Zelante L. , Stanziale P. , Gatta L. , Sbaiz L. , Sedita A.M. , Banchieri N. , Sapone L. , Fiorucci G.C. , Brinson E. , Shulse E. , Rappaport E. , Fortina P. 
Published: May 2013

Objectives Molecular biological testing for genetic diseases has grown rapidly, but speed, accuracy, specificity, sensitivity, throughput, and cost become more important as large scale screening is considered. This is a pilot study of an assay for the simultaneous detection of up to 31 cystic fibrosis mutations in a multicentre population based screening of 4476 Italian newborns. Methods The assay is a polymerase chain reaction, followed by an oligonucleotide ligation assay (PCR/OLA) and finally a sequence coded separation. It allows the detection of up to 31 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Guthrie spots were used as a source of template DNA. Results 144 carriers were detected during the analysis of 4476 samples, which translates into a carrier frequency of 1/31.1. Forty two carriers were detected from 1341 samples in Pavia (1/31.9), 53 from 1574 in Turin (1/29.7), and 49 from 1561 in San Giovanni Rotondo (1/31.8). Fifteen different mutations were detected, the most common being ΔF508 (0.625). Other common mutations included G542X (16 of 144), which was particularly common in southern Italy (14 of 49), N1303K (8 of 144), and R117H (8 of 144), detected only in the northern centres. Conclusions PCR/OLA is a robust, accurate, user friendly method for cystic fibrosis screening of newborns using blood spots in a semiautomated way at a low cost per mutation (0.8 Euro).
Neonatal screening for congenital hypothyroidism in Mexico: experience, obstacles, and strategies
Authors: Vela M. , Gamboa S. , Loera-Luna A. , Aguirre B.E. , Pérez-Palacios G. , Velázquez A. 
Published: May 2013

Objective To report the experience, obstacles, and strategies of screening for congenital hypothyroidism. Setting Newborns in Mexico. Methods Thyroid stimulating hormone (TSH) was measured by enzyme immunoassay using commercial kits in 1 140 364 newborns. Results There were 464 positive cases, of whom 299 (64.4%) were girls. 236 (50.9% showed ectopic nodules, 202 (43.5%) thyroid agenesis, 21 (4.5%) dyshormonogenesis, and 5 (1.1%) an unclassified goitre. The false positive rate was 0.024% and there were 11 false negative results. Currently, 600 000 (26%) of the 2 300 000 newborns are screened. This percentage has been increased in recent years by taking samples from cord blood and will be increased further by starting congenital hypothyroidism screening at social security units and by midwives screening infants born at home. Conclusions Mental retardation in infants in developing countries can be reduced by neonatal screening, and carefully planned strategies can steadily extend the benefits of screening.
Psychosocial predictors of first attendance for organised mammography screening
Authors: Aro A.R. , de Koning H.J. , Absetz P. , Schreck M. 
Published: May 2013

Objective To study psychosocial predictors of attendance at an organised breast cancer screening programme. Setting Finnish screening programme based on personal first round invitations in 1992–94, and with 90% attendance rate. Methods Attenders (n=946) belonged to a 10% random sample (n=1680 women, age 50, response rate 64%) of the target population (n=16 886), non-attenders (n=641, 38%) came from the whole target population. Predictors were measured one month before the screening invitation. Measures included items for social and behavioural factors, Breast Cancer Susceptibility Scale, Illness Attitude Scale, Health Locus of Control Scale, Anxiety Inventory, and Depression Inventory. Univariate and multivariate logistic regression analyses were used to predict attendance. Results Those most likely to attend were working, middle income, and averagely educated women, who had not had a mass mammogram recently, but who regularly visited gynaecologists, attended for Pap smear screening, practised breast self examination, and who did not smoke. Low confidence in their own capabilities in breast cancer prevention, overoptimism about the sensitivity of mammography, and perception of breast cancer risk as moderate were also predictive of attendance. Expectation of pain at mammography was predictive of non-attendance. Conclusion Mammography screening organised as a public health service was well accepted. A recent mammogram, high reliance on self control of breast cancer, and an expectation of pain at mammography deterred attendance at screening. Further information about these factors and health information on screening are needed.
Hormone replacement therapy and screening mammography: analysis of the results in the Bouches du Rhône programme
Authors: Séradour B. , Estève J. , Heid P. , Jacquemier J. 
Published: May 2013

Objective To evaluate the effectiveness of a mass screening programme for breast cancer in a French population where hormone replacement therapy (HRT) is common and where mammography is prescribed outside the programme for asymptomatic women. Methods From 1993 to 1996 inclusive, 41 062 women underwent a first test and 48 275 a second or third test in the Bouches du Rhône programme. Their HRT status was ascertained at the time of the test. False positive and false negative tests were identified at one year follow up. The incidence of interval cancers was estimated up to three years after the screening test. Results The odds of being detected at screening rather than as an interval cancer within one year of the test was five times greater among non-users of HRT than among users (odds ratio (OR) 5.14 (confidence interval 2.5 to 11.8)). This high reduction in sensitivity among users (71% v 92%) was associated with a very small reduction in specificity at the incident screen only. The incidence of interval cancers among HRT users was 3.5 times that of non-users within the first year after the test and 1.7 times during the following two years. Conclusions When the early results of a programme have been used to measure its effectiveness they should be reassessed in populations where HRT is in widespread use. As interval cancers had better prognostic factors in HRT users than in non-users, the efficacy of a screening programme in such populations should be the subject of further studies.
Estimating time and travel costs incurred in clinic based screening: flexible sigmoidoscopy screening for colorectal cancer
Authors: Frew E. , Wolstenholme J.L. , Atkin W. , Whynes D.K. 
Published: May 2013

Objectives To identify the characteristics of mode of travel to screening clinics; to estimate the time and travel costs incurred in attending; to investigate whether such costs are likely to bias screening compliance. Setting Twelve centres in the trial of flexible sigmoidoscopy screening for colorectal cancer, drawn from across Great Britain. Method Analysis of 3525 questionnaires completed by screening subjects while attending clinics. Information supplied included sociodemographic characteristics, modes of travel, expenses, activities forgone owing to attendance, and details of companions. Results More than 80% of subjects arrived at the clinics by car, and about two thirds were accompanied. On average, the clinic visit involved a 14.4 mile (22.8 km) round trip, requiring 130 minutes. Mean travel costs amounted to £6.10 per subject. The mean gross direct non-medical and indirect cost per subject amounted to £16.90, and the mean overall gross cost per attendance was £22.40. Compared with the Great Britain population as a whole, non-manual classes were more strongly represented, and the self employed less strongly represented, among the attendees. Conclusions In relation to direct medical costs, the time and travel costs of clinic based screening can be substantial, may influence the overall cost effectiveness of a screening programme, and may deter potential subjects from attending.
Interventions to increase breast screening uptake: do they make any difference?
Authors: Sin J.P. , St Leger A.S. 
Published: May 2013

Background Breast screening has an important role in improving survival from breast cancer through early detection and treatment. Increasing uptake of screening in areas of low uptake is important in improving the effectiveness of the national screening programme. This review looks at which initiatives to boost uptake have been successful. Objective To evaluate the effectiveness of the different interventions to increase breast screening uptake. Method A systematic review of interventions to promote breast screening uptake was undertaken. Studies were included if uptake was used as an outcome measure of the intervention and if relevant to the UK screening programme. Results Twenty eight studies were found among 25 citations. Interventions were grouped into “person directed”, “system directed”, “social network directed”, and “multistrategy” categories. Most were person directed. These interventions were more likely to be effective in boosting uptake, be simple in design, and to have been evaluated by a randomised trial design. Evidence of effectiveness in the other groups is limited both by the number of studies and the study designs. A summary of the interventions reviewed is presented. Conclusions Simple, brief, and effective interventions exist to boost breast screening uptake. More complicated approaches are not necessarily any more effective. These findings also have implications for other population based screening programmes of the future. In inner city areas the best approach to raising uptake rates is likely to be multistrategy.
TR3 Modulates Platinum Resistance in Ovarian Cancer
Authors: Wilson Andrew J. , Liu Annie Y. , Roland Joseph , Adebayo Oluwafunmilayo B. , Fletcher Sarah A. , Slaughter James C. , Saskowski Jeanette , Crispens Marta A. , Jones Howard W. , James Samuel , Fadare Oluwole , Khabele Dineo 
Published: May 2013

Abstract
In metastatic ovarian cancer, resistance to platinum chemotherapy is common. Although the orphan nuclear receptor TR3 (nur77/NR4A1) is implicated in mediating chemotherapy-induced apoptosis in cancer cells, its role in ovarian cancer has not been determined. In an ovarian cancer tissue microarray, TR3 protein expression was elevated in stage I tumors, but downregulated in a significant subset of metastatic tumors. Moreover, TR3 expression was significantly lower in platinum-resistant tumors in patients with metastatic disease, and low TR3 staining was associated with poorer overall and progression-free survival. We have identified a direct role for TR3 in cisplatin-induced apoptosis in ovarian cancer cells. Nucleus-to-cytoplasm translocation of TR3 was observed in cisplatin-sensitive (OVCAR8, OVCAR3, and A2780PAR) but not cisplatin-resistant (NCI/ADR-RES and A2780CP20) ovarian cancer cells. Immunofluorescent analyses showed clear overlap between TR3 and mitochondrial Hsp60 in cisplatin-treated cells, which was associated with cytochrome c release. Ovarian cancer cells with stable shRNA- or transient siRNA-mediated TR3 downregulation displayed substantial reduction in cisplatin effects on apoptotic markers and cell growth in vitro and in vivo. Mechanistic studies showed that the cisplatin-induced cytoplasmic TR3 translocation required for apoptosis induction was regulated by JNK activation and inhibition of Akt. Finally, cisplatin resistance was partially overcome by ectopic TR3 overexpression and by treatment with the JNK activator anisomycin and Akt pathway inhibitor, wortmannin. Our results suggest that disruption of TR3 activity, via downregulation or nuclear sequestration, likely contributes to platinum resistance in ovarian cancer. Moreover, we have described a treatment strategy aimed at overcoming platinum resistance by targeting TR3. Cancer Res; 73(15); 4758–69. ©2013 AACR.