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PubMed2004

Colorectal cancer screening with flexible sigmoidoscopy-participants' experiences and technical feasibility.

AIM: To evaluate tolerability and technical feasibility of colorectal cancer screening with flexible sigmoidoscopy. METHODS: One thousand men and women aged 59-61 years, randomly selected from the population register of Uppsala, Sweden, were invited by mail. After random allocation, half of them were called up by a nurse (group 1), while the other half were asked to call themselves (group 2) to book a sigmoidoscopy. After the examination, the participants anonymously answered a questionnaire about their subjective experiences. Endoscopists and their assisting nurse filled out structured forms documenting various technical aspects including an estimation of the subjects' discomfort. RESULTS: Four hundred and sixty-nine subjects participated. Mean intubation depth was 59 cm (range 28-60) and mean duration 5.8 min (range 2-23). On average, participants reported low degrees of discomfort and feeling of exposure, but 19 and 27% rated pain and distension, respectively, on the upper half of a visual analogue scale (VAS). Most subjects found the duration acceptable. Patient discomfort, as appraised by the endoscopists, was lower in men than in women, positively linked to duration of the procedure, but inversely associated with intubation distance. However, the overall differences between strata of participants were small. Among self-reported variables, group 1 and 2 differed significantly only with regard to 'other discomfort'. All but six subjects would accept a repeat examination. Failures, resulting in incomplete examinations, occurred in 14 subjects. CONCLUSIONS: Flexible sigmoidoscopy is generally well tolerated and technically feasible in screening for colorectal cancer. A more personalised invitation did not have any important effects on the subjective experience.

Colorectal Neoplasms↗
PubMed2005

Management of von Hippel-Lindau-associated kidney cancer.

Von Hippel-Lindau disease (VHL) is an autosomal-dominant inherited condition that predisposes patients to develop renal cysts and tumors, most commonly in the second to fourth decades of life. Renal cysts and tumors have historically been a major cause of disease-related morbidity and mortality, so urologists are often called on to manage patients with VHL. Knowledge of the extrarenal manifestations of VHL (hemangioblastomas of the central nervous system and retina, endolymphatic sac tumors, pancreatic cysts, epididymal and broad-ligament cysts, and pheochromocytomas) and integration of nonurologic specialties into management teams for VHL patients will help to achieve successful outcomes. Screening for renal manifestations of VHL, by regular imaging of the abdomen, begins late in the second decade of life. Because renal tumors in VHL can be multifocal and bilateral, management can be complex. Radical nephrectomy removes all tissue at risk for forming renal tumors; however, this necessitates renal replacement therapy. In an effort to control cancer effectively while preserving native renal function and minimizing intervention, some researchers have proposed an observational strategy. Patients are screened until the largest tumor reaches 3 cm in diameter, at which time operative intervention is recommended. Nephron-sparing surgery is undertaken, whenever technically feasible, with the goal of removing all tumors in that renal unit. The role of minimally invasive technologies is currently being evaluated in selected patients with VHL renal masses. Elucidation of molecular pathways associated with VHL renal tumors may facilitate development of effective medical treatments for these lesions in the future.

Humans↗
PubMed1990

Adolescent idiopathic scoliosis.

The effective treatment of adolescent idiopathic scoliosis (AIS) is predicted on timely detection and appropriate intervention. School screening programs have resulted in a reduced incidence of advanced curvature upon referral. Studies of the natural history of AIS demonstrate that a number of factors are of predictive value in assigning risk for progressive curvature and subsequent deformity and/or morbidity. These are age at time of diagnosis, stage of skeletal maturity, and magnitude and pattern of curvature. The options in treating AIS are observation, orthosis, and operation. Spinal orthoses are designed to arrest the progression of curvature during skeletal maturation. Newer brace designs and protocols facilitate compliance with long-term bracing and may reduce the incidence of curves requiring operative intervention. The goal in scoliosis surgery is to reduce curvature and to create a stable framework on which vertebral fusion can occur. Technical advances have yielded a number of instrumentation options for achieving this goal. Basic technical comparisons are made among of prototypes of posterior spinal instrumentation. The newest of these, Cotrel-Dubousset, may supplant Harrington rod instrumentation as the preferred standard in the operative treatment of AIS.

Adolescent↗
PubMed2000

Genomic screening for blood-borne viruses in transfusion settings.

The residual risk of post-transfusion human immunodeficiency virus (HIV) infection is low but slightly higher for hepatitis B virus (HBV) and hepatitis C virus (HCV), the main reason being viraemia during the window period preceding antibody or antigen detection by enzyme immunoassays. Immunosilent-infected individuals and carriers of distant viral variants also play an unquantifiable role. Multiple techniques, e.g. reverse transcription-polymerase chain reaction (RT-PCR), PCR, ligase-chain reaction, nucleic acid sequence-based amplification (NASBA) and transcription-mediated amplification (TMA) have been developed to amplify and detect viral genomes as single or multiplex assays. Equipment providing various degrees of automation has been adapted to these techniques. Applying nucleic acid amplification techniques (NAT) to blood screening, two main approaches have been advocated: plasma pool and single-donation testing. Pool testing presents the advantage of lower cost and readily available equipment although it is prone to false negative and positive reactions. The time required to identify infected donations is incompatible with blood component release, and may lead to product waste. Single-unit testing, although appealing, is not yet fully automated and potentially very costly unless a systematic multiplex approach is taken. Although technically feasible, NAT applied to the blood supply needs to be clinically evaluated and its cost efficiency assessed in the general public health context. However, pool NAT is currently implemented in continental Europe and the USA.

Blood Donors↗
PubMed1999

Selective determination of aromatic sulfonates in landfill leachates and groundwater using microbore liquid chromatography coupled with mass spectrometry.

Aromatic sulfonates (AS) are large-volume chemicals used in many technical processes of, for instance, the textile industry or construction. A LC/MS method for the selective determination of AS in environmental samples, based on a single-quadrupole MS, was developed and validated. The central point of this technique is the use of the compound-specific fragment ion SO3.- as marker for aromatic sulfonates. This negatively charged SO3 radical, together with the fact that AS undergo loss of SO2, allows screening for AS in complex matrixes, even in the presence of sulfate anions. Calibration curves generated from LC/MS data showed good linearity over 3 orders of magnitude, with an absolute limit of detection of approximately 1 ng. The relative standard deviation for mean areas obtained from reconstructed ion chromatograms ranged from 2.9 to 8.6%. Unlike UV detection, this LC/MS method gives similar response for both naphthalene- and benzene-sulfonates. The method presented was successfully applied to landfill leachates and groundwater, downstream of a landfill. Furthermore, this technique allowed identification of an unknown AS found in drain samples.

Chromatography, High Pressure Liquid↗
PubMed1990

Canadian National Breast Screening Study: assessment of technical quality by external review.

Mammograms from the Canadian National Breast Screening Study (NBSS) were reviewed by three external experts to provide an objective evaluation of their technical quality, to establish a model for auditing mammograms in a screening program, and to assess whether NBSS mammograms improved over time. The sample reviewed included 10 randomly chosen mammograms from each of 15 screening centers for each calendar year of their operation between 1980 and 1987. All 830 mammograms were reviewed on two consecutive days in randomized sequence by each reader, and rated 0-3 for each of four criteria including positioning and image quality, with a total possible score of 0-12. Although the mammograms were not in temporal sequence when reviewed, the scores assigned by each reader were significantly higher for mammograms dating from later years. Subjects' ages at entry (40-49 vs 50-59 years) did not affect the score. The largest increase in scores was associated with a 1985 protocol change in which mediolateral oblique positioning replaced straight mediolateral positioning. This study reinforces the importance of monitoring technical quality in screening programs and establishes that the NBSS benefited from technical improvements during its operation. A retrospective review of NBSS mammography by three external reviewers confirmed that technical quality improved from 1980 to 1987. This improvement was associated with improved technology (film, processing, and units) and with the quality assurance programs operating during the NBSS, which identified problems and offered remedies.

Adult↗
PubMed1995

Impact of prenatal screening and diagnosis on the epidemiology of structural congenital anomalies.

OBJECTIVE: To assess the impact of prenatal screening on the birth prevalence of three categories of structural congenital anomaly: abdominal wall defects (omphalocele and gastroschisis), renal agenesis/dysgenesis, and limb reduction defects. SETTING: Glasgow, Scotland, United Kingdom. METHODS: Data on the selected defects were obtained retrospectively from the population based Glasgow Register of Congenital Anomalies for the period 1980-91 inclusive. The register records all clinical or laboratory diagnoses of congenital anomaly in live births, stillbirths, and induced abortions occurring in women resident within the boundaries of the Greater Glasgow Health Board. The secular trends in the proportions of the defects diagnosed prenatally and terminated after screening, and in their prevalence at birth and during pregnancy, were examined. A total of 154,845 births were surveyed: 309 cases were identified in the selected anomaly categories. RESULTS: 83 cases of omphalocele/gastroschisis (5.4/10,000 births), 92 cases of renal agenesis/dysgenesis (5.9/10,000 births), and 134 cases of limb reduction defects (8.7/10,000 births) were found. Marked increases occurred over the study period in the proportions of cases diagnosed prenatally but not in the proportions terminated. The greatest difference between the prevalence at birth and during pregnancy was found for omphalocele. There were no significant secular trends in the prevalence of the selected defects. CONCLUSIONS: Prenatal screening has made a limited epidemiological impact on the prevalence of these defects. It has been moderately (but inconsistently) effective in the avoidance of births of infants with omphalocele/gastroschisis and renal agenesis/dysgenesis but not of limb reduction defects. Future efforts should be directed towards improving the technical aspects of the ultrasonographic detection of fetal abnormalities and exploring in detail, locally, the reasons for the varying pattern of decision making about termination of pregnancy among prospective parents.

Abortion, Induced↗
PubMed2003

A comparison of single and combined visual, cytologic, and virologic tests as screening strategies in a region at high risk of cervical cancer.

Increased understanding of human papillomavirus (HPV) infection as the central cause of cervical cancer has permitted the development of improved screening techniques. To evaluate their usefulness, we evaluated the performance of multiple screening methods concurrently in a large population-based cohort of >8500 nonvirginal women without hysterectomies, whom we followed prospectively in a high-risk region of Latin America. Using Youden's index as a measure of the trade-off between sensitivity and specificity, we estimated the performances of a visual screening method (cervicography), conventional cytology, liquid-based cytology (ThinPrep), and DNA testing for 13 oncogenic HPV types. The reference standard of disease was neoplasia > or = cervical intraepithelial neoplasia grade 3 (CIN 3), defined as histologically confirmed CIN 3 detected within 2 years of enrollment (n=90) or invasive cancer detected within 7 years (n=20). We analyzed each technique alone and in paired combinations (n=112 possible strategies), and evaluated the significance of differences between strategies using a paired Z test that equally weighted sensitivity and specificity. As a single test, either liquid-based cytology or HPV DNA testing was significantly more accurate than conventional cytology or cervicography. Paired tests incorporating either liquid-based cytology or HPV DNA testing were not substantially more accurate than either of those two test strategies alone. However, a possibly useful synergy was observed between the conventional smear and cervicography. Consideration of age or behavioral risk profiles did not alter any of these conclusions. Overall, we conclude that highly accurate screening for cervical cancer and CIN 3 is now technically feasible. The remaining vital issue is to extend improved cervical cancer prevention programs to resource-poor regions.

Adolescent↗
PubMedDate not supplied

Biochemical applications of mass spectrometry in pharmaceutical drug discovery.

Biochemical applications of mass spectrometry (MS) are important in the pharmaceutical industry. They comprise compositional analyses of biomolecules, especially proteins, and methods that measure molecular functions such as ligand binding. In early drug discovery, MS is used to characterize essential reagents and in structural biology. A number of MS-based methods have been proposed for use in high-throughput screening (HTS), but are unlikely to supplant established radiometric and fluorometric methods for this purpose. These methods, which include pulsed-ultrafiltration MS, frontal affinity chromatography-MS, and size-exclusion chromatography-MS, may ultimately be most successful in the post-screening lead development phase. In full development, MS is used heavily in the search for biomarkers that can be used to gauge disease progression and drug action. This review gives equal attention to the technical aspects of MS-based methods and to selective pressures present in the industrial environment that influence their chances of gaining wide application.

Drug Design↗
PubMed2003

Realtime ultrasound screening by satellite telecommunication.

Realtime ultrasound screening was carried out using a medical examination vehicle equipped with a diagnostic ultrasound scanner and a satellite telecommunication system. Screening was performed on 205 residents in a rural community in Japan and consisted of 57 cardiac, 57 abdominal, 60 thyroid and 31 breast ultrasound scans. The resolution of the realtime ultrasound images sent via communications satellite at 1.5 Mbit/s was almost identical to that of the original images taken by the ultrasound scanner. A disorder was diagnosed in 11 (19%) of the cardiac examinations, 28 (49%) of the abdominal, 19 (32%) of the thyroid and 7 (23%) of the breast examinations. Although some technical problems occurred, ultrasound screening by telemedicine appears to be a promising technique for those who live in rural communities.

Humans↗
PubMed2005

Meta-analysis: computed tomographic colonography.

BACKGROUND: Computed tomographic (CT) colonography, also called virtual colonoscopy, is an evolving technology under evaluation as a new method of screening for colorectal cancer. However, its performance as a test has varied widely across studies, and the reasons for these discrepancies are poorly defined. PURPOSE: To systematically review the test performance of CT colonography compared to colonoscopy or surgery and to assess variables that may affect test performance. DATA SOURCES: The PubMed, MEDLINE, and EMBASE databases and the Cochrane Controlled Trials Register were searched for English-language articles published between January 1975 and February 2005. STUDY SELECTION: Prospective studies of adults undergoing CT colonography after full bowel preparation, with colonoscopy or surgery as the gold standard, were selected. Studies had to have used state-of-the-art technology, including at least a single-detector CT scanner with supine and prone positioning, insufflation of the colon with air or carbon dioxide, collimation smaller than 5 mm, and both 2-dimensional and 3-dimensional views during scan interpretation. The evaluators of the colonogram had to be unaware of the findings from use of the gold standard test. Data on sensitivity and specificity overall and for detection of polyps less than 6 mm, 6 to 9 mm, and greater than 9 mm in size were abstracted. Sensitivities and specificities weighted by sample size were calculated, and heterogeneity was explored by using stratified analyses and meta-regression. DATA SYNTHESIS: 33 studies provided data on 6393 patients. The sensitivity of CT colonography was heterogeneous but improved as polyp size increased (48% [95% CI, 25% to 70%] for detection of polyps <6 mm, 70% [CI, 55% to 84%] for polyps 6 to 9 mm, and 85% [CI, 79% to 91%] for polyps >9 mm). Characteristics of the CT colonography scanner, including width of collimation, type of detector, and mode of imaging, explained some of this heterogeneity. In contrast, specificity was homogenous (92% [CI, 89% to 96%] for detection of polyps <6 mm, 93% [CI, 91% to 95%] for polyps 6 to 9 mm, and 97% [CI, 96% to 97%] for polyps >9 mm). LIMITATIONS: The studies differed widely, and the extractable variables explained only a small amount of the heterogeneity. In addition, only a few studies examined the newest CT colonography technology. CONCLUSIONS: Computed tomographic colonography is highly specific, but the range of reported sensitivities is wide. Patient or scanner characteristics do not fully account for this variability, but collimation, type of scanner, and mode of imaging explain some of the discrepancy. This heterogeneity raises concerns about consistency of performance and about technical variability. These issues must be resolved before CT colonography can be advocated for generalized screening for colorectal cancer.

Aged↗
PubMedDate not supplied

PAPNET. The human and other dimensions.

OBJECTIVE: To study the effect of specimen preparation and observer variation on the accuracy of interpretation of PAPNET images. STUDY DESIGN: The PAPNET scanner makes use of conventional Papanicolaou-stained smears and presents the cytologist with pictures of selected "abnormal" cells. This minitrial was designed to investigate the human variability in different grades of personnel and to consider any problems caused by the use of conventional smears. RESULTS: The personnel involved consisted of a consultant cytopathologist, a senior chief medical laboratory scientific officer and two senior cytotechnologists, one from another laboratory. Experience with the system ranged from six months to a few years. The best interobserver agreement was found between the senior chief and the senior technologist, who worked in the same laboratory. Majority agreement with the "gold standard" (at least three out of four) was highest for the extremes of "negative" and "high grade" smears. Three high grade smears were "missed" due to the quality of the smears and scantiness of "abnormal" cells. CONCLUSION: Although fatigue in screening is reduced by the interactive mode, it does not overcome the subjectivity of human examination both in review of the dat tape and in microscopic examination of selected cells on the slides. Experience with the method is important, and different background experiences will have an effect. The technical quality of the smear is important since the automated scanner cannot be expected to select abnormal cells if they are absent or obscured for any reason. A monolayer may be the solution, although at greater cost.

Diagnosis, Computer-Assisted↗
PubMed1992

[Neonatal diagnosis of hemoglobinopathies].

The technical problem of neonatal diagnosis of haemoglobinopathies has definitely been solved. There is no longer a methodological obstacle to a formal distinction between heterozygous and homozygous subjects with sickle cell disease, despite the presence at birth of strong haemoglobin F and F-acetylated concentrations. In France as in the USA and Great Britain mass screening for sickle cell disease in the newborn is necessary because this disease is frequent- as a monogenic hereditary disease it ranks second to cystic fibrosis on average and first in the Paris region-detection is useful for an early diagnosis and the new method is inexpensive.

Hemoglobinopathies↗
PubMed1996

Variability in the interpretation of screening mammograms by US radiologists. Findings from a national sample.

OBJECTIVE: To evaluate the effectiveness of screening mammography by estimating the variability in radiologists' ability to detect breast cancer within the US population of radiologists at mammography centers accredited by the American College of Radiology. METHODS: A two-way sample survey design was used as follows. Fifty mammography centers having an American College of Radiology-accredited unit were randomly sampled from across the United States. One hundred eight radiologists from these centers gave blinded interpretation to the same set of 79 randomly selected screening mammograms. The mammograms were from women who had been screened at a large screening center. Before their sampling, these women had been stratified by their breast disease status, established either by biopsy or by 2-year follow-up. Rates of biopsy recommendations were summarized by the mean, median, minimum, maximum, and range of sensitivity and specificity. Overall cancer detection ability was summarized by similar statistics for receiver operating characteristic curve areas. Ninety-five percent lower confidence bounds on the ranges in accuracy measures were established by boo-strapping. RESULTS: There is a range of at least 40% among US radiologists in their screening sensitivity. There is a range of at least 45% in the rates at which women without breast cancer are recommended for biopsy. As indicated by receiver operating characteristic curve areas, the ability of radiologists to detect cancer mammograms varies by as much as 11%. CONCLUSIONS: Our findings indicate that there is wide variability in the accuracy of mammogram interpretation in the population of US radiologists. Current accreditation programs that certify the technical quality of radiographic equipment and images but not the accuracy of the interpretation given to mammograms may not be sufficient to help mammography fully realize its potential to reduce breast cancer mortality.

Breast Diseases↗
PubMedDate not supplied

Current and future trends in colorectal cancer screening.

Current modalities for colorectal cancer screening include fecal occult-blood testing, flexible sigmoidoscopy, colonoscopy, and double-contrast barium enema. Among these, colonoscopy is becoming the dominant modality, in light of its efficacy and continuing technical refinements. Emerging technologies, such as stool DNA tests and virtual colonoscopy, hold promise for the future but cannot be recommended for screening at present.

Barium Sulfate↗
PubMed2007

Creation of a CT Image Library for the Lung Screening Study of the National Lung Screening Trial.

The CT Image Library (CTIL) of the Lung Screening Study (LSS) network of the National Lung Screening Trial (NLST) consists of up to three annual screens using CT imaging from each of 17,308 participants with a significant history of smoking but no evidence of cancer at trial enrollment (Fall 2002-Spring 2004). Screens performed at numerous medical centers associated with 10 LSS-NLST screening centers are deidentified of protected health information and delivered to the CTIL via DVD, external hard disk, or Internet/Virtual Private Network transmission. The collection will be completed in late 2006. The CTIL is of potential interest to clinical researchers and software developers of nodule detection algorithms. Its attractiveness lies in its very specific, well-defined patient population, scanned via a common CT protocol, and in its collection of evenly spaced serial screens. In this work, we describe the technical details of the CTIL collection process from screening center retrieval through library storage.

Clinical Protocols↗
PubMed1997

Pure tone audiometry and impedance screening of school entrant children by nurses: evaluation in a practical setting.

BACKGROUND: Screening for hearing loss in English children at entry to school (age 5-6 years) is usually by pure tone audiometry sweep undertaken by school nurses. This study aimed to compare the validity and screening rates of pure tone audiometry with impedance screening in these children. METHODS: Two stage pure tone audiometry and impedance methods of screening were compared in 610 school entry children from 19 infant schools in north east England. Both procedures were completed by school nurses. The results of screening were validated against subsequent clinical assessment, including otological examination and actions taken by an independent assessor. RESULTS: Both methods produced broadly similar validation indices after two stages of screening: sensitivity was 74.4% for both methods; specificity was 92.1% and 90.0%; and predicted values of a positive test 43.2% and 37.6% respectively for pure tone audiometry and impedance methods. Single stage screening in both methods produced higher sensitivity but lower specificity and predictive values of a positive test than two stage screening. Screening rates were appreciably higher with impedance methods than with pure tone audiometry. CONCLUSIONS: In choosing the method to be used, it must be borne in mind that the impedance method is technically more efficient but takes longer than pure tone audiometry screening. However, the latter method allows opportunity for other health inquiries in these children.

Audiometry, Pure-Tone↗