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Population based randomized study of uptake and yield of screening by flexible sigmoidoscopy compared with screening by faecal occult blood testing.

OBJECTIVES: To compare the feasibility of mass screening by flexible sigmoidoscopy with screening by faecal occult blood testing (Haemoccult) and both tests combined. DESIGN: Patients were randomised to screening by flexible sigmoidoscopy, faecal blood testing, or both tests. The flexible sigmoidoscopy examinations were performed by a general practitioner. SETTING: General practice. SUBJECTS: 3744 patients aged 50-75 years. MAIN OUTCOME MEASURES: Uptake, positive results, detection of neoplasia, complications, and recall for diagnostic colonoscopy. RESULTS: Uptake was significantly higher in the flexible sigmoidoscopy group (46.6%) than in the faecal blood test group (31.6%; P<0.001) or than in the group having both tests (30.1%; P<0.001). Telephone reminders increased uptake of sigmoidoscopy to 61.8%. In total, 1116 sigmoidoscopy examinations were performed without major complication. Polyps were found in 19. 3% (95% confidence interval 17.0% to 21.6%) but only 6.8% (5.3% to 8. 3%) had adenomas and 2.4% (1.5% to 3.3%) "high risk" adenomas. Cancer was detected in four subjects. The faecal blood test yielded positive results in 0.8% (0.2% to 1.4%) but missed at least one cancer and 30 cases of adenoma which were found by sigmoidoscopy in the combined group. Use of histological criteria-shown elsewhere to correlate with future risk of colorectal cancer-to select "positive" patients could reduce recall for diagnostic colonoscopy from about 20% to less than 5%. CONCLUSIONS: Some of the predicted obstacles to screening with flexible sigmoidoscopy are surmountable. Clear evidence relating to efficacy will be obtained only from a randomised controlled trial.

Aged↗

Primary screening for high risk HPV by home obtained cervicovaginal lavage is an alternative screening tool for unscreened women.

BACKGROUND/AIMS: Self sampling is considered an adjuvant tool to facilitate the participation of women in cervical cancer screening programmes. This study aimed to evaluate whether cervicovaginal lavage could be an alternative for the cervical smear in cytology and human papillomavirus (HPV) testing and to assess the acceptance of the self sampling device by women. METHODS: Fifty six women with abnormal cervical cytology (very mild dyskaryosis or worse) and 15 women with normal cervical cytology obtained a self collected cervicovaginal lavage at home and filled in a questionnaire on the use of the device. At the colposcopy clinic the gynaecologist performed the same procedure followed by a cervical smear for cytology and HPV DNA testing. RESULTS: The self sampling device was acceptable to 88% of the women. The concordance between the cytology results in the smear and the lavage by the doctor and the patient was 54% and 41%, respectively (kappa = 0.28 and 0.14). The concordance between high risk HPV detection in the smear and the lavage by the doctor and the patient was 93% and 78%, respectively (kappa = 0.82 and 0.53). Ninety one per cent of the women with high grade cervical intraepithelial neoplasia (CIN) had a high risk HPV positive test in the smear, compared with 91% and 81% in the lavages taken by the doctor and the patient, respectively. CONCLUSIONS: HPV DNA testing by home obtained samples is useful as a screening tool for cervical cancer, whereas cervical cytology by self sampling is not. Although the sensitivity for high grade CIN by high risk HPV testing in the lavage by the patient is not significantly lower than that in the cervical smear, self sampling for HPV DNA is a feasible alternative method in women who decline to participate in population based cervical cancer screening programmes. However, participation in the screening programme remains the best option.

Adult↗

Glucose-6-phosphate dehydrogenase deficiency neonatal screening: preliminary evidence that a high percentage of partially deficient female neonates are missed during routine screening.

OBJECTIVES: To provide preliminary evidence that the currently employed semiquantitative method of screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency can only detect infants who are totally deficient for G6PD and misses all cases of partial G6PD deficiency. SETTING: General population: 2150 randomly selected blood samples from the Blood Donation Department, Speliopouleion General Hospital, Athens, Greece. Neonate population: 2000 samples from neonates (50% male; 50% female) in maternity hospitals in the greater Athens area. High risk population: a total of 545 individuals from 133 families in the Athens area, the minimum acceptance criteria being the parents and any brother or sister. METHOD: Blood specimens from neonates or adults were collected and either spotted and dried on special filter paper (Schleicher and Schull 2992, Darmstadt, Germany) or used in tubes after being heparinised. For the quantitative evaluation of G6PD enzyme activity, the Quantase G6PD screening kit (Quantase Limited, Perth, UK) was used. Quantase G6PD controls (Quantase Limited) were used at three levels of G6PD. These controls are rated at 24, 30, and 37 degrees C. Alternatively, we used the Sigma G6PDH controls (Sigma Chemical Company, St Louis, USA) which are rated at 30 and 37 degrees C. The assay was performed according to the instructions included in the kit with the modification for haemoglobin normalisation. RESULTS: General population: 36 females who were classified as having normal enzymatic activity with the semiquantitative test, were classified as partially deficient with the quantitative test. Neonate population: using the quantitative test, the percentage of G6PD deficient neonates in this population was 5.5%, compared with 3.17% reported in routine screening using the semiquantitative method. High risk population: the quantitative method detected 28 cases of total or partial G6PD deficiency in sisters of males with known total deficiency. The semiquantitative CONCLUSIONS: A considerable amount of partially G6PD deficient female neonates (heterozygotes) are undetected and classified as having normal enzymatic activity using the semiquantitative method, which uses a cut off of 2.1 U/g haemoglobin (Hb). The use of a fully quantitative G6PD screening kit is proposed, employing the automated haemoglobin normalisation and a cut off of 6.4 U/g Hb. Any neonate with an activity below this mark should be regarded as G6PD deficient, and all preventive measures should be taken.

Clinical Enzyme Tests↗

Radiological peer review of interval cancers in the East Anglian breast screening programme: what are we missing? East Anglian Breast Screening Programme.

OBJECTIVE: To determine whether association between classification of interval cancers (false negative, minimal sign, true interval, occult) and tumour characteristics can indicate areas for improvement in effectiveness of screening. SETTING: East Anglian regional Breast: Screening Programme. METHOD: The consensus classification of interval cases, obtained through peer review, was compared with tumour characteristics: size; grade; and nodal status, and with radiological signs. A set of 923 cancers with known tumour characteristics, presenting in unscreened women, was available for comparison. RESULT: In total, 385 interval cases were analysed. Prognosis of interval cancers was at least as good as that of cancers in unscreened women, with fewer node positive cases. No significant relation was found between classification of cases and age of patients. True intervals tended to present later after a negative screen, although false negatives commonly presented earlier. Occult cancers were significantly smaller than false negatives. Analysis of histological type yielded little of relevance, and mammographic appearance was similar in all classifications. At diagnosis, cancers in the low risk group were more likely to be seen as spiculate masses, whereas high risk cases more often appeared as opacities. A higher proportion of interval cases had been assessed than in the normal screened population. CONCLUSION: Sensitivity may be improved by reducing false negative and minimal sign cases (21% of interval cancers in East Anglia). These will include tumours in all risk groups, and with all radiological features, thus no particular age group or radiological feature may be targeted for improvement. Misdiagnosis at assessment reduces sensitivity and therefore merits particular study.

Aged↗

Effects of age, breast density, ethnicity, and estrogen replacement therapy on screening mammographic sensitivity and cancer stage at diagnosis: review of 183,134 screening mammograms in Albuquerque, New Mexico.

PURPOSE: To examine how common patient factors affect screening mammographic sensitivity and cancer stage at diagnosis. MATERIALS AND METHODS: The authors used a population-based database of 183,134 screening mammograms and a statewide tumor registry to identify 807 breast cancers detected at screening mammography. RESULTS: Sensitivity varied significantly with ethnicity, use of estrogen replacement therapy, mammographic breast density, and age. Sensitivity was 54% (13 of 24) in women younger than 40 years, 77% (121 of 157) in women aged 40-49 years, 78% (224 of 286) in women aged 50-64 years, and 81% (277 of 340) in women older than 64 years. Sensitivity was 68% (162 of 237) for dense breasts and 85% (302 of 356) for nondense breasts and 74% (180 of 244) in estrogen replacement therapy users and 81% (417 of 513) in nonusers. Sensitivity was most markedly reduced with the combination of dense breasts and estrogen replacement therapy use; there was little difference when only one factor was present. Median cancer size and the percentage of early cancers showed little change with any factors. CONCLUSION: Age is a minor determinant of mammographic sensitivity in women aged 40 years or older. Sensitivity is substantially decreased with the combination of higher breast density and estrogen replacement therapy use. There was not a notable shift in cancer outcomes in the groups with lower mammographic sensitivity. These data do not support different screening recommendations in women aged 40-49 years or in estrogen replacement therapy users.

Adult↗

Proposed guidelines for screening of metabolic and endocrine diseases of dependent neonates of the U.S. Armed Forces. Derived from a survey of state guidelines for neonatal screening of metabolic diseases.

State regulations for neonatal screening for metabolic diseases do not optimally serve the needs of the dependents of the U.S. Armed Forces. Guidelines are therefore proposed for the neonatal screening for metabolic disease based both on responses received across the United States and on the unique needs of the U.S. Armed Forces. The guidelines agree with the policies outlined by various national medical and scientific organizations. It is suggested that neonates be screened for phenylketonuria (PKU), hypothyroidism, galactosemia, and maple syrup urine disease (MSUD). The screening program is cost-effective and feasible. Prior to implementing the program throughout the U.S. military, a pilot program based at the Armed Forces Institute of Pathology should be started.

Costs and Cost Analysis↗

A comparative study on the efficacy of a mass screening program for colorectal cancer--comparison between cancer cases detected by mass screening and by outpatient clinics.

The present study was carried out to investigate the efficacy of colorectal screening through a comparison of the characteristics of the cancer cases detected by screening programs and by outpatient clinics. A total of 78 cases with colorectal cancer diagnosed by screening programs using fecal occult blood test in Nagano Prefecture, Japan, was collected as the index group and the same cases (one matched cases) diagnosed through outpatient clinics served as the control group for the present study. A comparison of various factors, such as tumor site, Dukes' stage, histological type, and survival rate, was made between the index and control groups. No differences were noted in tumor site and histological type between the two groups examined. The proportion of early cancer and the survival rate, however, were significantly higher in the index group than in the control group (p < 0.01). These results suggest that colorectal screening is an efficient preventive measure.

Ambulatory Care Facilities↗

Neonatal hearing screening: modelling cost and effectiveness of hospital- and community-based screening.

BACKGROUND: Children with congenital hearing impairment benefit from early detection and management of their hearing loss. These and related considerations led to the recommendation of universal newborn hearing screening. In 2001 the first phase of a national Newborn Hearing Screening Programme (NHSP) was implemented in England. Objective of this study was to assess costs and effectiveness for hospital and community-based newborn hearing screening systems in England based on data from this first phase with regard to the effects of alterations to parameter values. METHODS DESIGN: Clinical effectiveness analysis using a Markov Model. OUTCOME MEASURE: quality weighted detected child months (QCM). RESULTS: Both hospital and community programmes yielded 794 QCM at the age of 6 months with total costs of 3,690,000 pound sterling per 100,000 screened children in hospital and 3,340,000 pound sterling in community. Simulated costs would be lower in hospital in 48% of the trials. Any statistically significant difference between hospital and community in prevalence, test sensitivity, test specificity and costs would result in significant differences in cost-effectiveness between hospital and community. CONCLUSION: This modelling exercise informs decision makers by a quantitative projection of available data and the explicit and transparent statements about assumptions and the degree of uncertainty. Further evaluation of the cost-effectiveness should focus on the potential differences in test parameters and prevalence in these two settings.

Community Health Services↗

Choice of screening modality in a colorectal cancer education and screening program for the uninsured.

BACKGROUND: Starting in 2001, the state of Maryland established a carefully planned and executed multicomponent intervention to reduce mortality and disparities in colorectal cancer. METHODS: In the most populous county, uninsured participants received education and a choice of free screening by fecal occult blood testing (FOBT) or colonoscopy or both. RESULTS: Over 2 years, a group of 1,672 uninsured individuals, of whom 90% were minorities, registered with the program. Overall, screening uptake was 41% with colonoscopy, 10% with FOBT, and 10% with both FOBT and colonoscopy. CONCLUSION: The choices of colorectal cancer screening modalities by a diverse uninsured population demonstrates the importance of maintaining screening options.

Adenomatous Polyps↗

Screening for dementia with the memory impairment screen.

OBJECTIVES: To validate a sensitive and specific screening test for AD and other dementias, assess its reliability and discriminative validity, and present normative data for its use in various applied settings. BACKGROUND: To improve discrimination in screening for AD and dementia, we developed the Memory Impairment Screen (MIS), a 4-minute, four-item, delayed free- and cued-recall test of memory impairment. The MIS uses controlled learning to ensure attention, induce specific semantic processing, and optimize encoding specificity to improve detection of dementia. METHODS: Equivalent forms of the MIS were given at the beginning and end of the testing session to assess alternate forms reliability. Discriminative validity was assessed in a criterion sample of 483 aged individuals, 50 of whom had dementia according to Diagnostic and Statistical Manual of Mental Disorders (3rd ed., revised) criteria. RESULTS: The MIS had good alternate forms reliability, high construct validity for memory impairment, and good discriminative validity in terms of sensitivity, specificity, and positive predictive value. We present normative data for use in settings with different base rates (prevalences) of AD and dementia. CONCLUSION: The MIS provides efficient, reliable, and valid screening for AD and other dementias.

Aged↗

Mass screening in low-income populations: the challenges of securing diagnostic and treatment services in a national cancer screening program.

Funding for many mass screening programs for low-income and uninsured populations provides resources for screening tests, yet only rarely does it provide coverage for necessary follow-up diagnostic and treatment services. The National Breast and Cervical Cancer Early Detection Program (NBCCEDP), a federally funded initiative that provides cancer screening to low-income uninsured and underinsured women, covers some diagnostic follow-up tests and no treatment services. We conducted in-depth case studies of seven state programs participating in the NBCCEDP to investigate the strategies and approaches being used to secure diagnostic and treatment services. The results suggest that the program relies on a patchwork of resources--at state and local levels--to provide diagnostic and treatment services. This includes a number of components of local safety nets, all of which are unstable and have uncertain futures. Public health disease-screening initiatives need to reconsider the feasibility of continued reliance on case-by-case appeals to the local safety net for diagnostic follow-up and treatment services.

Breast Neoplasms↗

Will men attribute fault to their GP for adverse effects arising from controversial screening tests? An Australian study using scenarios about PSA screening.

OBJECTIVE: To determine men's attribution of fault for adverse consequences of prostate-specific antigen (PSA) screening. SETTING: Representative, population-based sample recruited from Sydney, Australia (n=405). METHODS: Telephone interview to assess reactions to two scenarios: Scenario 1, depicting a GP who dismisses an opportunity to order a PSA test (missed diagnosis); and Scenario 2, depicting a GP who recommends PSA screening to a patient who then experiences adverse outcomes from treatment of his prostate cancer (iatrogenic consequences). RESULTS: Two-thirds of participants (66.9%) ascribed fault to the GP in Scenario 1. Men in fair or poor health (adjusted odds ratio [AOR] 1.81; 95% confidence interval [CI] 1.04-3.12; p=0.03) and those with better knowledge about PSA screening (AOR 0.98; 95% CI 0.97-0.99; p=0.002) were significantly and independently more likely to ascribe fault in Scenario 1. By contrast, only 15.8% of participants ascribed responsibility to the GP in Scenario 2. Older men (AOR 1.05; 95% CI 1.00-1.10; p=0.04) and those with higher levels of decisional conflict (AOR 1.19; 95% CI 1.04-1.37; p=0.01) were significantly and independently more likely to ascribe responsibility. CONCLUSION: Public education could better target men's tendency to ascribe fault to GPs when they miss an opportunity to diagnose prostate cancer early through PSA screening, even though the corollary of potential iatrogenic consequences is perceived as less blameworthy. As decisional conflict and knowledge were found to predict attribution of fault, evidence-based information may reduce the medicolegal volatility of this controversy.

Aged↗

CIN 2/3 and cervical cancer in an organised screening programme after an unsatisfactory or a normal Pap smear: a seven-year prospective study of the Norwegian population-based screening programme.

OBJECTIVES: To estimate the risk of cervical intraepithelial neoplasia (CIN) 2/3 and invasive cervical cancer (ICC) in an organised screening programme after an unsatisfactory or a normal Pap smear. SETTING: A seven-year prospective cohort study of the Norwegian population-based co-ordinated screening programme based on the actual diagnostic and screening procedures performed. Observations of 526,661 women with a normal index Pap smear and 21,405 women with an unsatisfactory index Pap smear were made during 3.26 million women-years. METHODS: The risk of being diagnosed with CIN 2/3 or ICC was calculated by logistic regression for the first two years of follow-up. The hazard of being diagnosed with CIN 2/3 or ICC for the women who were not diagnosed during the two first years was estimated by non-parametrical survival regression. RESULTS: After two years of follow-up, 0.2% of the women were diagnosed with CIN 2/3 and 0.01% with ICC after a normal Pap smear. An unsatisfactory Pap smear indicated a 1.6-4.0 times higher risk of harbouring a CIN 2/3 or ICC compared to women with a normal Pap smear. No increased risk of ICC was found during long-term follow-up for the 70% of the women with an unsatisfactory Pap smear who were returned to ordinary screening. Prior series of low-grade Pap smears followed by a normal Pap were associated with an increased risk of CIN 2/3 and ICC. CONCLUSIONS: An unsatisfactory Pap smear indicates a risk of harbouring CIN II/III or ICC. Repeated Pap smears are adequate as a follow-up of an unsatisfactory Pap smear. Women with repeated series of equivocal/LSIL Pap smears followed by a normal Pap should be considered at high risk.

Cohort Studies↗

Cascade screening for familial hypercholesterolaemia: implications of a pilot study for national screening programmes.

OBJECTIVES: To determine what proportion of cases of heterozygous familial hypercholesterolaemia would be identified by cascade screening conducted by a specialist hospital clinic, and by how much this would increase the prevalence of diagnosed cases. SETTING: Hospital clinic serving a population of 605,900 in Oxfordshire, UK. METHODS: A specialist nurse obtained details of living first-degree relatives from 227 adult patients with heterozygous familial hypercholesterolaemia currently or previously attending Oxford lipid clinic after excluding 79 adults without relatives living in Oxfordshire and 48 children. Index cases were asked to invite relatives resident in Oxfordshire for testing. RESULTS: A total of 227 index cases had 1075 first-degree relatives, including 442 adults and 117 children aged < 18 years resident in Oxfordshire. We excluded 171 previously screened adults and 46 for other reasons. Among 225 eligible adult relatives, 28 responders (12%) planned to consult their general practitioner and 52 (23%) attended the clinic for testing. Parents of 113 children (97%) wanted them tested. The positive diagnostic rate was 29% (15/52) in adults and 32% (36/113) in children. Screening increased prevalence by 14.4%, from 0.58/1000 (95% confidence intervals [CI] 0.52-0.65) to 0.67/1000 (95% CI 0.60-0.73), representing 33.5% of predicted cases. CONCLUSIONS: Cascade screening conducted by a specialist hospital clinic within its population catchment area did not substantially increase the prevalence of diagnosed familial hypercholesterolaemia. To maximize response rates, clinic staff need to approach relatives directly. Validated age, sex and country-specific diagnostic criteria should be defined, possibly with access to DNA-based tests, to help resolve diagnostic uncertainty.

Adult↗

Neonatal screening for congenital hypothyroidism in Hessen, Germany: efficiency of the screening program and school achievement of 129 children at an age of 8-12 years.

Status and school achievement of 129 children born in Hessen between 1988 and 1992 and notified by a repeatedly elevated concentration of TSH in neonatal screening were evaluated. Interviews of mothers, teachers and pediatricians were used to score the development and educational achievements, respectively. A total of 298,175 newborns were screened and the incidence of permanent congenital hypothyroidism (PCH) was 1: 3,313 (n = 90). The female/male ratio was 1.37:1. In the 69 PCH cases with complete data, athyreosis (52%), hypoplasia (32%), dyshormogenesis (9%) and ectopia (7%) were identified as etiologies. The mean age at start of therapy decreases from day 15 in 1988 to day 9 in 1992; however, 27% of PCH children showed reduced psychomotor development as scored by their pediatrician and 11% attended a special school for educationally subnormal children. Approximately 25% of the children had lower educational achievements irrespective of the school type. Our finding of a relatively high percentage of PCH children with subnormal development points to a failure in disease management. A follow-up program including repeated serum TSH monitoring and yearly examinations by pediatric endocrinologists and supervision by the regional screening center is necessary to ensure the long-term efficacy of neonatal screening for congenital hypothyroidism.

Child↗

Craniofacial screening profile: quick screening for congenital malformations.

The correct identification of syndromes and other congenital malformations at an early age is critical for the child, family and care providers. Most specialists who conduct large screenings of young children are not adequately trained to recognize signs and symptoms that should lead to appropriate referral to the clinical geneticist and/or diagnostic team. A systematic approach for recognizing important signs is presented here; a Craniofacial Screening Profile. Following a brief training program, the Profile was validated by 39 speech-language pathologists in screening 3,539 kindergarten and first grade children. The results were excellent (specificity was 99.6%), demonstrating that with limited training, specialists can effectively screen for important signs and symptoms of a major group of syndromes and other congenital malformations.

Child↗

Prostate cancer: to screen or not to screen.

Screening for early detection of prostate cancer seems both necessary and possible but it remains to be proven that it can lower mortality from the disease. Until properly evaluated, the risks of screening at present do not justify either the cost or the potential benefit that could result. An increased awareness of the problems encountered by screening could lead to greater impetus around the world to design and implement the proper studies. The recent information about the outcome following conservative management means that the value of treatment must also be assessed since it is possible that the only tumors cured by radiation therapy or surgery are those that are not life threatening, whereas the most lethal tumors are not identified sufficiently early by the available screening tests to be cured. The increased incidence and mortality from prostate cancer should lead to increased pressure to answer the important questions as soon as possible.

Humans↗

Emerging technologies in screening for colorectal cancer: CT colonography, immunochemical fecal occult blood tests, and stool screening using molecular markers.

The American Cancer Society's (ACS) Colorectal Cancer Advisory Group held a workshop on new technologies for the early detection of colorectal cancer and adenomatous polyps as part of a regular review of ACS guidelines for colorectal cancer screening. The Advisory Group formally reviewed CT colonography, immunochemical fecal occult blood tests (FOBT), and stool screening using molecular markers, and also addressed other technologies including capsule video endoscopy. With the exception of immunochemical stool testing, the ACS has determined that at this time there is insufficient evidence to recommend these technologies for routine colorectal cancer screening. Based on recommendations of the Advisory Group, only a minor modification has been made to the ACS's Recommendations for Screening and Surveillance of the Early Detection of Adenomatous Polyps and Colorectal Cancer.

Adenomatous Polyps↗