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PubMed2005

Association between mammography timing and measures of screening performance in the United States.

PURPOSE: To evaluate whether there is an association between the number of months since previous mammography (MSPM) and performance measures (sensitivity, specificity, recall rate, cancer detection rate, and positive predictive value) in women who underwent U.S. community-based screening mammography. MATERIALS AND METHODS: Data from seven registries (Breast Cancer Surveillance Consortium) and mammographic data and cancer outcome in regard to 1 213 754 screening mammographic examinations performed in 680 641 women who were 40-89 years old for the years 1996-2000 were used in this study. These data are submitted annually in a standard format to a central statistical coordinating center that is subject to institutional review board approval, quality control, and confidentiality standards. Performance measures were calculated for first and subsequent screening mammography. For subsequent mammography, performance measures were calculated according to categories of MSPM (9-15, 16-20, 21-27, and >/=28 months). Receiver operating characteristic and multivariable logistic regression analyses were conducted to test the association between the number of MSPM and performance measures. RESULTS: With increasing MSPM in each category from 9-15 to 28 months or more and for first mammographic examinations, respectively, there was increased sensitivity (70.9%, 75.7%, 85.4%, 82.5%, and 88.6%), decreased specificity (93.3%, 92.7%, 91.6%, 91.0%, and 85.9%), increased recall rate (7.0%, 7.6%, 8.8%, 9.4%, and 14.7%), and increased cancer detection rates (3.2, 3.5, 4.5, 4.6, and 6.1 per 1000 mammographic examinations). When the category of 9-15 MSPM was compared with that of 21-27 MSPM, there was a slight increase in positive predictive value from 4.6% to 5.1%. Confidence intervals were narrow and did not overlap. Age affected these associations for all performance measures except sensitivity. CONCLUSION: Performance measures increased as MSPM increased, except for specificity, which decreased. Time between mammograms is an important factor to consider when audits are reviewed or screening performance measures are compared.

Adult↗
PubMed2002

Mutations at the galactose-1-p-uridyltransferase gene in infants with a positive galactosemia newborn screening test.

Newborn screening for galactosemia yields a high number of false-positive results. Confirmatory DNA testing for unknown galactosemia mutations on the initial positive sample using novel techniques of mutation detection tenders itself to reduce the recall rate. The potential benefits of confirmatory DNA testing, however, could be offset by the detection of a high percentage of galactosemia carriers, Duarte/galactosemia compound heterozygotes, and infants with benign sequence changes in the galactose-1-phosphate uridyltransferase (GALT) gene among infants with a positive biochemical screening test. Our aim was to determine the frequency and allelic distribution of all sequence changes in the GALT gene in 110 newborns with a positive total galactose screening test among 43,688 Austrian newborns screened consecutively. We found that only 20 of the 110 probands carried at least one known or novel candidate galactosemia mutation (one galactosemia homozygote, 7 Duarte/galactosemia compounds, 12 carriers) as judged by denaturing gradient gel electrophoresis and cleavage fragment length polymorphism analysis. Four novel galactosemia candidate mutations (Q9H, A46fsdelCAGCT, M129T, L342I) were identified. Sixty-seven probands had no detectable sequence changes and 23 carried only the benign Duarte or Los Angeles variant alleles or silent mutations. We conclude that a rapid and automatable confirmation test for unknown GALT mutations, e.g. on a high-density oligonucleotide array basis, has the potential to lower the recall rate of galactosemia screening in our population by about five-fold from 0.25 to 0.046%. Further research, however, will be required before the development of such a test can be advocated.

Austria↗
PubMed1999

Two-year clinical evaluation of tooth whitening using an at-home bleaching system.

PURPOSE: The purpose of this study was to evaluate the 2-year effectiveness of a carbamide peroxide at-home bleaching gel used to provide tooth lightening treatment. MATERIAL AND METHODS: Twenty-nine patients participated in the original study, during which they treated their maxillary teeth with a 10% carbamide peroxide gel nightly for 2 weeks. Shades were determined before and after treatment by comparison with a Vita shade guide. Twenty-four patients (a recall rate of 83%) were recalled for evaluation 2 years after the initial bleaching treatment. The shade of the maxillary incisors was evaluated and compared with shades before, immediately after, and at 6 months and 2 years after initial treatment. Data were analyzed using a repeated-measures analysis of variance. RESULTS: At 2 years after bleaching with a 10% carbamide peroxide gel, the median shade was D2, a six-increment difference from the baseline median of D3. Twenty of 24 patients (83.3%) had a shade change of two or more units, which is the threshold value for bleaching efficacy using American Dental Association guidelines. The lightening result remained statistically significant (p < .0001) at 2 years. CLINICAL SIGNIFICANCE: Although some reversal of the lightening effect occurs over time following the original bleaching treatment, loss of the lighter color appears to be gradual for most patients. Although the longevity of the lightening effect remains to be determined, this clinical trial indicates that the majority of patients have a satisfactory result 2 years after treatment.

Adult↗
PubMed2006

Automated recognition of malignancy mentions in biomedical literature.

BACKGROUND: The rapid proliferation of biomedical text makes it increasingly difficult for researchers to identify, synthesize, and utilize developed knowledge in their fields of interest. Automated information extraction procedures can assist in the acquisition and management of this knowledge. Previous efforts in biomedical text mining have focused primarily upon named entity recognition of well-defined molecular objects such as genes, but less work has been performed to identify disease-related objects and concepts. Furthermore, promise has been tempered by an inability to efficiently scale approaches in ways that minimize manual efforts and still perform with high accuracy. Here, we have applied a machine-learning approach previously successful for identifying molecular entities to a disease concept to determine if the underlying probabilistic model effectively generalizes to unrelated concepts with minimal manual intervention for model retraining. RESULTS: We developed a named entity recognizer (MTag), an entity tagger for recognizing clinical descriptions of malignancy presented in text. The application uses the machine-learning technique Conditional Random Fields with additional domain-specific features. MTag was tested with 1,010 training and 432 evaluation documents pertaining to cancer genomics. Overall, our experiments resulted in 0.85 precision, 0.83 recall, and 0.84 F-measure on the evaluation set. Compared with a baseline system using string matching of text with a neoplasm term list, MTag performed with a much higher recall rate (92.1% vs. 42.1% recall) and demonstrated the ability to learn new patterns. Application of MTag to all MEDLINE abstracts yielded the identification of 580,002 unique and 9,153,340 overall mentions of malignancy. Significantly, addition of an extensive lexicon of malignancy mentions as a feature set for extraction had minimal impact in performance. CONCLUSION: Together, these results suggest that the identification of disparate biomedical entity classes in free text may be achievable with high accuracy and only moderate additional effort for each new application domain.

Algorithms↗
PubMed2002

High reliability of neonatal screening for congenital adrenal hyperplasia in Switzerland.

Newborn screening for congenital adrenal hyperplasia (CAH) is justified by the sometimes difficult clinical diagnosis and the risks associated with missed diagnosis, particularly the life-threatening salt-wasting crisis. In Switzerland, nationwide screening for CAH by measuring 17-hydroxyprogesterone levels in dried blood spots was introduced in 1992. At the Zurich University Children's Hospital, 50% of the population of Switzerland is screened. The aim of the study was to evaluate the efficiency of the Zurich screening program. Between January 1, 1993, and May 31, 2001, 333,221 newborns were screened for CAH. Thirty-one newborns had CAH (incidence, 1 in 10,749); 30 were detected through screening (sensitivity, 97%). A recall for suspected CAH was performed in only 60 cases, corresponding to a very low recall rate (0.0018%). In 30 recalls CAH was confirmed (positive predictive value, 50%; specificity, 99.99%). Fifteen of 31 patients profited from screening, as CAH had not been recognized clinically. The timely availability of screening results made therapy possible within the first week of life in most cases and helped in preventing salt-wasting crisis in all patients. With a sensitivity of 97%, a specificity of 99.99%, and a positive predictive value of 50%, the Zurich neonatal screening program for CAH can be considered highly reliable.

17-alpha-Hydroxyprogesterone↗
PubMed2001

The impact of alternative practices on the cost and quality of mammographic screening in the United States.

The decentralized structure of health care in the Unites States hinders population-based analysis of breast cancer screening. Our objectives are to model mammography in the United States as a whole, to identify the variables that most profoundly affect cost and efficacy, and to develop a strategy to improve mammography screening from a population perspective. A spreadsheet model was used to represent the variables of mammography screening in the United States. The population-based national screening program in Sweden provides a framework for comparison. The outcome measures are the aggregate cost and the number of cancers detected by mammography. We used deterministic sensitivity analysis to calculate the impact of variation in practice. Aggregate costs of screening in the United States are in the range of $3-$5 billion dollars. The percentage of women screened, cost per mammogram, cancer to biopsy ratio, recall rate, and cost of recall have the most profound effect on the quality and cost of a national screening program. Variance of these high-impact variables, based on the U.S. population, modifies the aggregate cost of screening by over $2 billion. As mammography screening in the United States increases to include all women over age 40, high-impact variables should be optimized to decrease costs and improve breast cancer detection. Our model establishes which parameters are most important.

Adult↗
PubMed1995

Herault breast screening programme: results after 30 months of a mobile French schedule.

Breast screening in the Herault Department (France) has been carried out since July 1990. As with other French programmes, it is a population-based screen, whose main features are related to its organization in that: (a) it is performed by a specific unit (the 'Institut Montpelliérain d'Imagerie Medico-Biologique'); and (b) the group of women targeted is those aged 40-70 years. The two-view mammography is performed every 2 years in mobile units. This paper presents the results after 30 months: 26,026 participants were screened from a target population of 52,617 women, giving a participation rate of 49%. The recall rate and the biopsy rate observed were 7% and 1.5%, respectively. The predictive positive value was 8.4% for a positive test while it was 35% for the biopsy; the values increased with age. 137 cancers were observed giving a detection rate of 5.3%, of which 82% were in situ. Small (< or = to 10 mm) tumours represented 41.5%, and 71.5% of the cancers were node negative. The surgical treatment was conservative for 66% of them.

Adult↗
PubMed1994

Phenylketonuria screening with a fluorometric microplate assay.

A fluorometric assay in microtitre plates for the screening of phenylketonuria was evaluated and adapted to a neonatal screening programme. Using this assay, it is possible to determine quantitatively the phenylalanine concentration in dried blood spots on filter paper. The test exhibited a linear calibration curve with a good slope as well as sufficient precision and accuracy in the statistical analysis. Interference by other amino acids and antibiotics was not observed. Only elevated concentrations of leucine interfered to a small degree. The phenylalanine concentration in dried blood spots of 13 phenylketonuria patients correlated to that in serum. 7381 dried blood samples of newborn infants were tested simultaneously by both the fluorometric and the Guthrie test. The results did not show significant differences. We screened 29,182 newborns using the fluorometric assay and an online data processing programme. The internal repetition rate was 0.64%, the external recall rate 0.15%. False negative results were not observed. In December 1991 the fluorometric method replaced the Guthrie test in our routine programme for phenylketonuria screening, and was introduced as a follow up test for phenylketonuria patients.

Fluorometry↗
PubMed1996

[Systematic screening for breast cancer in Rhone].

OBJECTIVE: As systematic breast cancer screening is progressively being implemented on a nationwide basis in France, we would like to describe the first population based breast cancer screening programme that started in the Rhône departement in 1987. METHOD: All women aged 50 to 70 living in the Rhône are invited for single-view mammography every three years. Mammograms are done using the existing facilities by one of the 120 radiologists of the department qualified for screening for the program. All screens undergo double reading organized by l'Association des Radiologues du Rhône pour le Dépistage des Maladies du Sein (ARRADEMAS). The result of the test is given to the woman and her primary care doctor or gynaecologist who initiates the assessment of screen detected abnormalities. Evaluation and monitoring of the programme are based on the combined data of the screening information center and the local breast cancer registry. RESULTS: Available data, seven years after the beginning of the programme, already show that its main short term measures are satisfactory: recent data show an acceptance rate of 50% and a recall rate of about 8%. At the prevalent screen, biopsy rate is 1.3% and detection rate 6 per 1000. Moreover, the programme information system has achieved its target in enabling us to collect data on all breast cancer cases occurring not only in women screened but in the whole population invited to screening.

Aged↗
PubMed2001

Effectiveness and cost-effectiveness of double reading of mammograms in breast cancer screening: findings of a systematic review.

There is a lack of direct evidence on the effectiveness of double reading of breast screening mammograms within the context of national screening programmes even though about half of the countries that use mammography screening have implemented double reading. A systematic review was conducted to compare double reading with single reading of mammograms for screening accuracy, patient outcomes and costs. We searched an extensive range of electronic databases, bibliographies of studies were scanned and experts were contacted. Data extraction and quality assessment was undertaken independently by two reviewers. Estimates of the diagnostic accuracy were calculated for those studies with follow-up to identify interval cancers. Only 10 cohort studies met the inclusion criteria with reported extractable data on the effectiveness of double compared to single reading. The mix of methodologies meant that few conclusions could be drawn about the effect of double reading independent of number of views, or effects on size and type of tumours detected. Overall, double reading increases the cancer detection rate by 3-11 per 10,000 women screened and has a double impact on recall rates depending on the recall policy used. The benefit could be mainly in the detection of small cancers, and could be greatest where two readers have different strengths and weaknesses, or where readers are less experienced. Double reading can improve accuracy as compared with single reading. In particular, double reading by consensus or arbitration achieves an increase in cancer detection rate together with a reduction in the rate of women recalled for assessment. Further research should quantify the relative benefit from double reading according to recall policy and number of mammographic views, and estimate the impact on patient outcome.

Journal Article↗
PubMed2005

Computer-aided detection (CAD) of cancers detected on double reading by one reader only.

We evaluated the role of computer-aided detection (CAD) in cancers undergoing double reading and detected by one reader only. A series of 33 cancers, originally missed by the first reader and detected by the second reader, and 75 negative controls were processed to assess CAD sensitivity, and was read by the six radiologists who originally missed the cancers with the help of CAD printouts. CAD case-based sensitivity, specificity and positive predictive value were 51.5%, 18.6% and 21.7%, respectively. Average sensitivity of all radiologists in all cancers in the series was 74.7%, being higher for CAD+ (86.2%) than for CAD- (62.5%) cancers (P<0.01). When reading cancer cases that they had originally missed, radiologists had a sensitivity of 75.8%, which was higher for CAD+ (100.0%) than for CAD- (58.3%) cancers. The average recall rate was 14.2%, the majority of recalls (45 out of 64) occurring for lesions marked by CAD. CAD may help in detecting at most half of cancers missed at a single reading but detected by a second reader.

Breast Neoplasms↗
PubMed1998

Output loss or rehearsal loop? Output-time versus pronunciation-time limits in immediate recall for forgetting-matched materials.

Forgetting during recall may be one limit on memory span. Output time and accuracy of immediate serial recall using spoken and keypress responses were measured for digit, letter, and word sets approximately matched in phonemic discriminability and in immediate recognition memory. Nonetheless, the materials differed from one another in recall span, in output time during recall, and in pronunciation time (speech rate). Recall output times accounted precisely and completely for the measured memory span for these matched materials. Pronunciation times are correlated with recall output times, but output time gives a slightly better account of recall accuracy. The output time equivalent to the rule that short-term memory span corresponds to the number of items that can be said in about 1.5-2 s is that span corresponds to the number of items that can be recalled in about 4-6 s. Additional variations in span reflect differential item interference.

Attention↗
PubMed1990

Referral policy and positive predictive value of call for surgical biopsy in the Florence Breast Cancer Screening Program.

The authors evaluate the referral rates and the predictive value (PV) of call for diagnostic work up or biopsy in a population based breast cancer screening program in the 1979-1986 period. The presence of mammographic abnormalities either benign or suspicious proved to be the only reliable referral criterion (recall rate = 7.9%, recall PV = 3.8%, biopsy call PV = 39%). When mammography was normal the presence of breast complaints other than pain or of a radiologically dense breast were aspecific referral criteria, and since the latter was abandoned, (a) referral rates dropped especially in younger women, (b) referral or biopsy PV improved, whereas (c) cancer detection rate was almost unaffected. Younger age was associated with higher referral rates and with lower PV of both referral or biopsy. Whenever comparison with previous examination was possible, mammography accuracy was higher; this explains the decrease in referral rates and the increased predictivity observed at further rounds with respect to first screening round.

Adult↗
PubMed2006

Prospective assessment of computer-aided detection in interpretation of screening mammography.

OBJECTIVE: The purpose of this study was to prospectively assess the usefulness of computer-aided detection (CAD) in the interpretation of screening mammography and to provide the true sensitivity and specificity of this technique in a clinical setting. SUBJECTS AND METHODS: Over a 26-month period, 5,016 screening mammograms were interpreted without, and subsequently with, the assistance of the iCAD MammoReader detection system. Data collected for actionable findings included dominant feature (calcification, mass, asymmetry, architectural distortion), detection method (radiologist only, CAD only, or both radiologist and CAD), BI-RADS assessment code, associated histopathology for those undergoing biopsy, and tumor stage for malignant lesions. The study population was cross-checked against an independent reference standard to identify false-negative cases. RESULTS: Of the 5,016 cases, the recall rate increased from 12% to 14% with the addition of CAD. Of the 107 (2%) patients who underwent biopsy, 101 (94%) were prompted by the radiologist and six (6%) were prompted by CAD. Of the 124 biopsies performed on actionable findings in the 107 patients, findings in 79 (64%) were benign and in 45 (36%) were in situ or invasive carcinoma. Three study participants who were not recalled by the radiologist with the assistance of CAD developed cancer within 1 year of the screening mammogram and were considered to be false-negative cases. The radiologist detected 43 (90%) of the 48 total malignancies and 45 (94%) of the 48 malignancies with the assistance of CAD. CAD missed eight cancers that were detected by the radiologist, which presented as architectural distortions (n = 3), irregular masses (n = 4), and a circumscribed mass (n = 1). CAD detected two in situ cancers as a faint cluster of calcifications that had not been perceived by the radiologist and one mass that was dismissed by the radiologist, accounting for at least a 4.7% increase in cancer detection rate. Sensitivity of screening mammography with the use of CAD (94%) represented an absolute and relative 4% increase over the sensitivity of the radiologist alone (90%). Specificity of screening mammography with and without the use of CAD was 99%. CONCLUSION: Routine use of CAD while interpreting screening mammograms significantly increases recall rates, has no significant effect on positive predictive value for biopsy, and can increase cancer detection rate by at least 4.7% and sensitivity by at least 4%. This study provides "true" values for sensitivity and specificity for use of CAD in interpretation of screening mammography as measured prospectively in the context of a working clinical setting.

Adult↗
PubMed2003

Can the NHS Breast Screening Programme afford not to double read screening mammograms?

AIM: Rapid expansion of the National Health Service (UK) Breast Screening Programme (NHSBSP) to routinely invite women aged 50-70 years will result in many new readers undertaking screen reading. A timely method for assessing performance and preferably one that facilitates a steep learning curve will be required. MATERIALS AND METHODS: This unit screens a population of 88000 women aged 50-64 years and double reads >90% films. A record is kept of proven screen-detected cancers not recalled for assessment by either the first or second reader but correctly recalled following third-reader arbitration. Individual readers' workload and recall rates are obtained by running an annual co-writer report. The results of this 7 year prospective audit are presented. RESULTS: In total 177167 women were screened between 1/4/95 and 31/3/02 resulting in the detection of 1072 cancers. Eighty-seven cancers (8.1%) were detected after arbitration. Individual readers recall to assessment rates and percentage of cases incorrectly returned to routine recall varied. Prompt feedback of missed/misinterpreted cases allowed both experienced and inexperienced readers to modify their recall thresholds for particular mammographic abnormalities. CONCLUSION: It is recommended this audit method is adopted by all units in the NHSBSP and that the Advisory Committee for Breast Cancer Screening review the policy of single versus double reading.

Breast Neoplasms↗
PubMed2004

Extracting phenotypic information from the literature via natural language processing.

In recent years, the amount of biomedical knowledge has been increasing exponentially. Several Natural Language Processing (NLP) systems have been developed to help researchers extract, encode and organize new information automatically from textual literature or narrative reports. Some of these systems focus on extracting biological entities or molecular interactions while others retrieve and encode clinical information. To exploit gene functions in the post-genome era, it is necessary to extract phenotypic information automatically from the literature as well. However, few NLP projects have focused on this. We present the development of a system called BioMedLEE that extracts a broad variety of phenotypic information from the biomedical literature. The system was developed by adapting MedLEE, an existing clinical information extraction NLP engine. A feasibility evaluation study of BioMedLEE was performed using 300 randomly chosen journal titles. Results showed that experts achieved an average precision rate of 65.4%, (95%CI: [58.0%, 72.8%]) and a recall rate of 73.0%, (95%CI: [66.2%, 80.0%]). BioMedLEE had 64.0% precision and 77.1% recall respectively, according to expert agreements.

Databases as Topic↗