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Congenital toxoplasmosis in the United Kingdom: to screen or not to screen?

The United Kingdom National Screening Committee recently reviewed the evidence for prenatal and neonatal screening for toxoplasma infection and concluded that there was insufficient evidence to recommend screening in the United Kingdom. This issue will need to be revisited as new information or treatments become available. In this paper, the extent to which the research evidence on toxoplasma infection meets the criteria that need to be fulfilled for the introduction of screening in the United Kingdom is reviewed.

Female↗

Screen-film mammography versus full-field digital mammography with soft-copy reading: randomized trial in a population-based screening program--the Oslo II Study.

PURPOSE: To prospectively compare cancer detection rates, recall rates, and positive predictive values at screen-film mammography (SFM) with those at full-field digital mammography (FFDM) with soft-copy reading in a population-based screening program in Norway. MATERIALS AND METHODS: Of 43,429 women invited, 25,263 women aged 45-69 years attended the screening program and were randomized, with adjustments for age and area of residence, to undergo SFM or FFDM. Two standard views of each breast were acquired. Independent double reading was performed with use of a five-point rating scale for probability of cancer. Recall rates, positive predictive values, and cancer detection rates were compared for two age groups (45-49 and 50-69 years) by using the chi(2) test. RESULTS: Overall, 73 cancers in 17,911 women were detected at SFM (detection rate, 0.41%), compared with 41 cancers in 6,997 women at FFDM (detection rate, 0.59%; P =.06). In the group aged 50-69 years, 56 cancers in 10,304 women were detected at SFM (detection rate, 0.54%), compared with 33 cancers in 3,985 at FFDM (detection rate, 0.83%); the difference in cancer detection rates approached significance (P =.053). In the group aged 45-49 years, 17 cancers in 7,607 women were detected at SFM (detection rate, 0.22%), compared with eight cancers in 3,012 at FFDM (detection rate, 0.27%). Recall rates in both age groups were significantly higher at FFDM than at SFM (P <.05), but positive predictive value was not significantly different. CONCLUSION: FFDM allowed a higher cancer detection rate than did SFM in the group aged 50-69, although the difference did not reach statistical significance. The detection rate was nearly equal for the two modalities in the group aged 45-49. SFM and FFDM with soft-copy reading are comparable techniques for population-based screening mammography programs.

Aged↗

Newborn screening: toward a uniform screening panel and system--executive summary.

The Maternal and Child Health Bureau commissioned the American College of Medical Genetics to outline a process of standardization of outcomes and guidelines for state newborn screening programs and to define responsibilities for collecting and evaluating outcome data, including a recommended uniform panel of conditions to include in state newborn screening programs. The expert panel identified 29 conditions for which screening should be mandated. An additional 25 conditions were identified because they are part of the differential diagnosis of a condition in the core panel, they are clinically significant and revealed with screening technology but lack an efficacious treatment, or they represent incidental findings for which there is potential clinical significance. The process of identification is described, and recommendations are provided.

Consensus↗

Pathology review of screening negative neuroblastomas: a report from the Quebec Neuroblastoma Screening Project.

BACKGROUND: The Quebec Neuroblastoma Screening (QNS) Project completed a 5-year program for measuring urinary vanillylmandelic acid (VMA)/homovanillic acid (HVA) levels at age 3 weeks and/or 6 months in 89% of 476,603 Quebec-born infants from 1989-1994; 45 screening positive preclinical cases (S-positive cases) and 20 congenital/neonatal (C/N) cases were identified. As of April 1997, an additional 59 cases in the same birth cohort were diagnosed clinically; these neuroblastomas developed after screening verified normal VMA/HVA levels (S-negative cases). METHODS: Pathology specimens from 45 of 59 S-negative cases were reviewed centrally and classified according to the Shimada system. Results were compared with clinical data and also with S-positive and C/N cases. RESULTS: Of 45 S-negative cases, 27 tumors had favorable histology (FH) and 18 had unfavorable histology (UH). Approximately 52% of FH tumors were diagnosed before age 1 year, whereas UH tumors were nearly exclusively (94%) diagnosed after age 1 year (P < 0.01). Approximately 89% of FH tumors were Stage I, II, or IV-S, whereas 72% UH tumors were Stage III or IV (P < 0.001). All children with FH tumors were alive at last follow-up (range of follow-up period: 9-79 months; median, 35 months), whereas 8 children with UH tumors died of disease even after limited follow-up (range of follow-up period: 0-60 months; median, 20 months). By contrast, S-positive and C/N cases were predominantly (97%) FH tumors, often (76%) Stage I, II, or IV-S, with excellent clinical outcome (survival rate of 98%). CONCLUSIONS: The majority of the UH neuroblastomas that developed in the birth cohort of the QNS Project were included in the group of S-negative cases and could not be detected by the screening at age 3 weeks and/or 6 months.

Child↗

Musculoskeletal screening examination (pGALS) for school-age children based on the adult GALS screen.

OBJECTIVE: To develop and validate a musculoskeletal screening examination applicable to school-age children based on the adult Gait, Arms, Legs, Spine (GALS) screen. METHODS: Adult GALS was tested in consecutive school-age children attending pediatric rheumatology clinics and was compared with an examination conducted, on the same day, by a pediatric rheumatologist who classified children as having abnormal or normal joints. Adult GALS was tested for validity compared with the pediatric rheumatologist's assessment and deficiencies in adult GALS were identified. Experts proposed amendments to adult GALS, achieving consensus by modified Delphi techniques. The resultant pediatric screening tool (pGALS) was tested (methodology identical to the testing of adult GALS) in an additional group of children. RESULTS: Adult GALS was tested in 50 children (median age 11 years, range 4-16), of whom 37 (74%) had juvenile idiopathic arthritis. Adult GALS missed important abnormalities in 18% of children, mostly at the ankle, foot, and temporomandibular joints. The pGALS was tested in 65 children (median age 13 years, range 5-17 years) and demonstrated excellent sensitivity (97-100%) and specificity (98-100%) at all joints, with high acceptability scored by child and parent/guardian. The median time to perform pGALS was 2 minutes (range 1.5-3 minutes). CONCLUSION: The pGALS musculoskeletal screening tool has excellent validity, is quick to perform, and is acceptable to school-age children and parents/guardians. We propose that pGALS be incorporated into undergraduate and postgraduate medical training to improve pediatric musculoskeletal clinical skills and facilitate diagnosis and referral to specialists.

Adolescent↗

Prostate cancer mortality reduction by screening: power and time frame with complete enrollment in the European Randomised Screening for Prostate Cancer (ERSPC) trial.

From 1992-2001, 7 countries in Europe gradually recruited men for the European Randomised Screening for Prostate Cancer (ERSPC) trial. Centres recruit different age groups and have different designs for recruiting and countries have different underlying risks for prostate cancer. Recruitment has reached 163,126 men aged 55-69 at entry now. Our purpose was to calculate the power of the trial and at what point in time can statistically significant differences in prostate cancer mortality be expected. Recruitment data were collected from the screening centres. We calculated the expected number of prostate cancer deaths in each follow-up year, based on national statistics and expected rate in trial entrants. The power was calculated using different assumptions on intervention effect and contamination rate and also if the ERSPC trial would cooperate with other trials. With an assumed 25% intervention effect in men actually screened and a 20% contamination rate, the trial will reach a power of 0.86 in 2008. With an assumed intervention effect of 40%, the power reaches 0.90 in 2003-2004. Pooling data with those of the Prostate, Lung, Colorectal and Ovary (PLCO) trial early is expected to improve the power to 79% (20% intervention effect) to 92% (40% intervention effect PLCO). Adding more centres with compliance rates lower than 45% decreases the power of the trial. The ERSPC trial has sufficient power to detect a significant difference in prostate cancer mortality between the 2 arms if the true reduction in mortality by screening is 25% or more or if contamination remains limited to 10% if the true effect is 20% or more. If early detection and treatment turns out to have a stronger effect as may be suggested by observational data, the ERSPC trial is likely to conclusively show that within the next 5 years.

Aged↗

Randomized controlled trial of human papillomavirus testing versus Pap cytology in the primary screening for cervical cancer precursors: design, methods and preliminary accrual results of the Canadian cervical cancer screening trial (CCCaST).

Since infection with oncogenic human papillomavirus (HPV) has been considered a necessary cause of cervical cancer, tests for oncogenic HPV types have been proposed as adjuncts or replacements to Pap cytology. We designed the Canadian Cervical Cancer Screening Trial (CCCaST) to compare the relative efficacy of HPV DNA testing and Pap cytology in primary screening for cervical cancer and its high-grade precursors. CCCaST randomized women aged 30-69 years in Montreal (Quebec) and in St. John's (Newfoundland) to 1 of 2 screening groups: focus on Pap (conventional) or focus on HPV testing (Hybrid Capture 2). Women in both arms received both tests, but were randomized as to their order, the first test being the index test. Women with an abnormal Pap test or a positive HPV test underwent colposcopy and biopsy, as did a random sample of women with a negative index test. CCCaST enrolled 9,667 women between October 2002 and October 2004. At enrolment, 2.8% had an abnormal Pap test, 6.1% had a positive HPV test and 1.1% were abnormal in both tests. ASC-US was the most frequent cytological abnormality, representing 64% of abnormal Pap results. The frequency of abnormal Pap and HPV results decreased with increasing age and the proportion of HPV-positive results increased with the severity of Pap abnormality. Efficacy analysis will determine if the extra referrals with HPV DNA testing will translate into a relevant increase in high-grade cervical cancer precursor detection. Because of its design, CCCaST will provide sound evidence for formulating cervical cancer screening strategies.

Adult↗

Current status of newborn screening: decision-making about the conditions to include in screening programs.

Newborn screening is considered a highly successful public health program that has resulted in the reduction of mortality, mental retardation, and other serious disabilities in thousands of children since the introduction of screening for phenylketonuria (PKU) in the 1960s. Programs are based in state public health departments such that each state independently reaches decisions as to which conditions should be mandated for inclusion in programs, leading to considerable variability among the states as to what is being screened. New technologies and knowledge of the genetics of many conditions have greatly expanded the number of conditions with potential for inclusion in newborn screening.

Decision Making, Organizational↗

Lesions predictive for prostate cancer in a screened population: first and second screening round findings.

BACKGROUND: We evaluated the incidence of prostate cancer, high-grade prostatic intraepithelial neoplasia (PIN) and lesions suspicious for prostate cancer (LSPC) in sextant biopsies in two subsequent screening rounds at a 4-year interval and their predictive value for subsequent prostate cancer detection. METHODS: In the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC), 4,117 men underwent sextant biopsy in the 1st screening round. The 2nd round was performed at a 4-year interval and biopsies were taken in 1,840 men. RESULTS: The incidences of prostate cancer, LSPC and PIN in the 1st, respectively 2nd round were 24.6, resp. 19.9% (P = 0.001), 2.7, resp. 2.8% and 0.8, resp. 2.5% (P < 0.0001). Prostate cancer incidence after repeat biopsy for LSPC in the 1st, respectively 2nd round was 36.7 and 17.0%, and after repeat biopsy for PIN 13.3% in both rounds, respectively. Men with a benign biopsy in the 1st round had a significantly lower prostate cancer incidence in the 2nd round compared to men who did not undergo biopsy in the 1st round (10.7 vs. 22.7%, P < 0.0001). CONCLUSIONS: The decrease of prostate cancer detection in the 2nd round was associated with an increase in the incidence of PIN. Strikingly, LSPC diagnosed during the 1st round, but not during the 2nd round were predictive for prostate cancer, while isolated PIN was never predictive for prostate cancer. PIN should not be an indication for repeat biopsy in a screening population. Importantly a 1st round benign biopsy outcome proved to be a negative predictor of subsequent prostate cancer detection.

Aged↗

Comparison of pathologic characteristics of T1c and non-T1c cancers detected in a population-based screening study, the European Randomized Study of Screening for Prostate Cancer.

In recent years the introduction of serum prostate-specific antigen (PSA) determination as a screening tool for early detection of prostate cancer in asymptomatic men has led to a markedly increased detection of prostate cancers that are neither palpable nor visible with transrectal ultrasonography (stage T1c). In this preliminary study we assessed pathologic features and aspects that are indicative of clinical significance in T1c tumors and tumors with palpable or visible lesions (non-T1c tumors). Between June 1994 and December 1995, 51 consecutive radical prostatectomies were performed on screened participants in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC). After determination of pathologic stage and Gleason score, morphometric analysis was performed to determine tumor volume. Radical prostatectomy specimens were divided into three mutually exclusive subsets: T1c tumors, non-T1c tumors with preoperative PSA levels below 4 ng/ml, and non-T1c tumors with PSA levels equal to or greater than 4 ng/ml. These subsets were compared for differences in the distribution of tumor volume, pathologic stage, and Gleason score. An arbitrarily constructed categorization model was used to assess clinical significance. In all, 17 (33%) of the patients had clinical stage T1c disease. In our categorization mode, 88% of the T1c tumors fit the criteria for clinically significant tumors. T1c tumors, however, were significantly smaller (P < 0.01) and were more likely to be organ-confined (P = 0.01) as compared with non-T1c tumors in patients with an elevated preoperative serum PSA level. In contrast, tumors detected at preoperative PSA levels of < 4 ng/ml had comparably the lowest pathologic stages and tumor volumes in our series. In our categorization model, 42% of these tumors fit the criteria for minimal tumor. This group of radical prostatectomies was therefore most likely to harbor clinically insignificant cancer, a finding that was consistent in two other categorization models derived from earlier reports. T1c tumors comprise a large fraction of the tumors found in population-based screening. As judged by their pathologic characteristics. T1c tumors are clinically significant tumors. The overall low pathologic stage and Gleason score of these tumors make these patients excellent candidates for curative treatment by radical prostatectomy or radiotherapy. In contrast, some concern should be raised on the detection of tumors at low serum PSA levels by means of digital rectal examination and transrectal ultrasound alone, since a substantial proportion of these tumors could be considered clinically insignificant. Long-term follow-up, however, is necessary to substantiate this view.

Aged↗

Image quality assurance in the prostate, lung, colorectal, and ovarian cancer screening trial network of the National Lung Screening Trial.

The National Lung Screening Trial is evaluating the effectiveness of low-dose spiral CT and conventional chest X-ray as screening tests for persons who are at high risk for developing lung cancer. This multicenter trial requires quality assurance (QA) for the image quality and technical parameters of the scans. The electronic system described here helps manage the QA process. The system includes a workstation at each screening center that de-identifies the data, a DICOM storage service at the QA Coordinating Center, and Web-based systems for presenting images and QA evaluation forms to the QA radiologists. Quality assurance data are collated and analyzed by an independent statistical organization. We describe the design and implementation of this electronic QA system, emphasizing issues relating to data security and privacy, the various obstacles encountered in the installation of a common system at different participating screening centers, and the functional success of the system deployed.

CD-ROM↗

Screening for autistic spectrum in children aged 14 to 15 months. I: the development of the Early Screening of Autistic Traits Questionnaire (ESAT).

This article describes the development of a screening instrument for young children. Screening items were tested first in a non-selected population of children aged 8-20 months (n = 478). Then, parents of children with clinically diagnosed ASD (n = 153, average age 87 months) or ADHD (n = 76, average age 112 months) were asked to score the items retrospectively for when their child was 14 months old. A 14-item screening instrument, Early Screening of Autistic Traits (ESAT) which had maximal sensitivity and specificity for ASD was developed. The sensitivity of the ESAT was checked in an independent sample of 34 children aged 16-48 months clinically diagnosed with ASD. A 4-item version appears to be a promising prescreening instrument.

Asperger Syndrome↗

Screening for secretory otitis media: evaluation of some impedance screening programs for long-lasting secretory otitis media in 7-year-old children.

In an unselected cohort of 387 seven-year-old children 90% had all 9 planned impedance audiometries during their first year at school. The results from these 348 children were analyzed in different impedance screening programs, as 3 consecutive screening series, each comprising two or 3 tests at an interval of 4-8 weeks. The specificity of the ASHA and Nashville programs was too low in finding long-lasting secretory otitis media, namely about 70%, so that there were too many false positive cases. Therefore, a new impedance screening program was designed. It had about the same sensitivity (80%) but a far better specificity (95%) than the ASHA and Nashville programs. The predictive value of a positive test was 15% in the ASHA and Nashville programs, but 3 times better (48%) in the designed Hirtshals program. The Hirtshals program had a referral rate of 9% compared with the 32-36% in the ASHA and Nashville programs. The frequencies of retesting were 31% in the ASHA program, 52% in the Nashville Program and 45% in the Hirtshals program. Before general screening for long-lasting secretory otitis media can be recommended, additional information is needed.

Acoustic Impedance Tests↗

Results and efficacy of public screening for hypercholesterolemia: the Bavarian Cholesterol Screening Project.

Hypercholesterolemia is a risk factor for the development of coronary disease. It does not present with symptoms and can be diagnosed by laboratory examination only. Screening is the only means to detect subjects at risk at a time when preventive measures can effectively be applied. We therefore initiated the Bavarian Cholesterol Screening Project (BCSP). Occasional screening was performed in 150,089 subjects (81,286 women, 68,803 men) in 214 campaigns. The mean cholesterol value was 243 +/- 52 mg/dl for women and 231 +/- 53 mg/dl for men; 37.3% of women and 38.1% of men had values of 201-250 mg/dl, 42.2% of women and 33.7% of men values > 250 mg/dl. Also, the following risk factors were recorded: smoking in 11.3% of women and in 20.2% of men, hypertension in 19.8% of women and 17.4% of men, diabetes mellitus in 4.2% of women and 4.1% of men, obesity in 16.8% of women and 20.9% of men, and a family history of myocardial infarction in 34.8% of women and 26.0% of men. Of the 27,084 men who had their cholesterol checked for the first time, 35.6% had levels between 201 and 250 mg/dl, and 22.9% had levels above 250 mg/dl. Of the 27,870 women whose cholesterol level had not been checked before, 38.8% had levels between 201 and 250 mg/dl, and 27.1% had levels above 250 mg/dl. More than 70% of the subjects with levels between 200 and 250 mg/dl had at least one additional risk factor. We conclude, on the basis of this study, that the risk factor hypercholesterolemia is unknown in as much as 20% of the population of Bavaria. These newly detected subjects were offered the opportunity to recognize this risk and take subsequent measures of prevention. Screening projects for hypercholesterolemia therefore can be an effective means of improving public health.

Adolescent↗

Cost-effectiveness analysis of screening for abdominal aortic aneurysms based on five year results from a randomised hospital based mass screening trial.

BACKGROUND: The aim of this study was to estimate the cost effectiveness of screening for abdominal aortic aneurysm (AAA). MATERIAL AND METHODS: All 12,639 men born in the years 1921-1933 (aged 64-73) living in Viborg County, Denmark, were randomly allocated either to receive an invitation to abdominal ultrasound scanning for AAA or to be controls. Costs for screening and surveillance were assessed prospectively. Diagnosis Related Group (DRG) costs from 1999 were used concerning admissions with uncomplicated and complicated operations. Admissions for AAA surgery were retrospectively classified according to complications in patient records. RESULTS: Mean follow-up time was 52 months. 76.6% of invited men attended screening, and 191 (4.0%) had an AAA. As previously reported, the cumulative 5-year AAA-specific mortality in the invited group was significantly reduced by 67% compared to the control group (P = 0.003). The costs were estimated to be Euro 11.23 per scan. The costs per life-year saved were Euro 9057 (Euro 5872-20,063) after 5 years, and were expected to decrease to Euro 2708 (Euro 1758-6031) after 10 years and to Euro 1825 (Euro 1185-4063) after 15 years. CONCLUSION: Screening of 64-73 years old males in Denmark seems cost effective.

Aged↗

Current capacity for endoscopic colorectal cancer screening in the United States: data from the National Cancer Institute Survey of Colorectal Cancer Screening Practices.

PURPOSE: There is a national goal in the United States to increase the level of colorectal cancer screening, but there is currently little information on resources for the delivery of endoscopic screening and follow-up diagnostic and surveillance procedures. The purpose of this study was to provide nationally representative data on endoscopic resources at the provider level. METHODS: A nationally representative survey of primary care physicians, general surgeons, and gastroenterologists that was conducted during 1999 to 2000 provided data from survey responses by 1235 primary care physicians, 349 gastroenterologists, and 316 general surgeons. RESULTS: We estimated that 65% of all sigmoidoscopy procedures were performed by primary care physicians, 25% by gastroenterologists, and 10% by general surgeons. Only 30% of all primary care physicians performed any procedures, and average volume among those who did was relatively low (seven per month). Gastroenterologists performed two thirds of all colonoscopy procedures, with most of the remainder performed by general surgeons. CONCLUSION: There is potential to increase the capacity to perform screening sigmoidoscopy procedures through primary care delivery. However, without careful consideration of organizational factors, this could result in increased cost and quality control problems. Increasing the capacity for screening colonoscopy is feasible, but will require attention to other problems, such as avoiding overfrequent (e.g., annual or biennial) procedures in low-risk patients.

Academies and Institutes↗

Effectiveness of a targeted screening program in identifying infants with positive urine toxicology screening results in a regular neonatal nursery.

We compared the effectiveness in identifying infants with positive results on urine screening for drugs of abuse of a universal screening program and a targeted screening program on the basis of clinical suspicion. A carefully run targeted screening program identified 24.3% of the admissions for toxicology testing and would have found all but two of the infants with positive results.

Chicago↗

Screening for congenital hypothyroidism: results of screening one million North American infants.

Pilot programs for screening of newborn infants for congenital hypothyroidism began in North America in 1972. To date, the five oldest programs (Quebec, Pittsburgh, Toronto, Oregon Regional, and New England Regional) have screened 1,046,362 infants. A total of 277 infants with congenital hypothyroidism have been detected and seven have been missed, resulting in a total of 284 affected infants in the screened population and an overall incidence of one in 3,684 live births. Of the affected infants, 246 were determined to have primary hypothyroidism, an incidence of one in 4,254 births. Ten infants with secondary-tertiary hypothyroidism were detected in Quebec, Oregon, and Toronto, an incidence of one in 68,200 births. Of all the infants with primary hypothyroidism who were adequately studied, 63% were determined to have aplastic or hypoplastic glands, 14% normal or enlarged glands, and 23% ectopic thyroid tissue. The estimated minimum incidence of infants with TBG deficiency is one in 8,913 births. Only 8 of the 277 detected infants were suspected clinically to have congenital hypothyroidism prior to the time of confirmation of the diagnosis at 4 to 8 weeks of age. The cost of screening varied from $0.70 to $1.60 per infant, depending on which costs were included in the estimate. Preliminary evidence from Quebec suggests that infants treated in the program have normal developmental testing scores at 18 months of age.

Alpha-Globulins↗