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Case-control studies of the efficacy of cancer screening: overcoming bias from nonrandom patterns of screening.

A case-control study of the efficacy of cancer screening, like any other case-control study, must deal with potential confounding. There are 2 categories of confounding variables that pose special problems for studies of screening: (1) age and calendar time resulting from different temporal distributions of screening between cases and controls irrespective of whether the screening test leads to a reduction in mortality; and (2) the administration of other screening tests for the cancer in question when it is not clear whether the result of the other test had a bearing on the decision to order the test under study. We describe circumstances in which confounding from these sources can be dealt with satisfactorily by means of restriction or adjustment, and other circumstances in which it cannot.

Age Factors↗

Improving the NHS cervical screening laboratory performance indicators by making allowance for population age, risk and screening interval.

OBJECTIVE: One of the key performance measures in the monitoring of the NHS cervical screening programme is the targeting of laboratories with very high or low percentages (outside the 10th-90th percentile) of adequate smears that have moderate dyskaryosis or worse. These laboratories are assumed to include those laboratories that may have extremes of sensitivity and specificity. A clear limitation with this methodology is that laboratories do not examine smears from women with the same underlying risk, age distribution or screening interval and adjustment for these factors should considerably improve the method. METHODS: This paper describes a method that allows for these confounding variables and a new age-risk-interval adjusted moderate dyskaryosis or worse rate (ARI-adjusted mod+ rate) can be calculated. The adjusted rate is the rate of moderate or worse dyskaryotic smears that the laboratory would have detected had it been screening women with an English 'average' age-risk-interval. All laboratories can therefore be compared using this method. RESULTS: The methodology is illustrated using data from the NHSCSP South West Region. The particularly low percentage of moderate or worse smears detected by one or two laboratories can be shown to be due to a local screened population with a very low risk because of a high mean age, relatively short screening interval and census variables associated with a low risk, rather than any under-calling by the associated laboratories. CONCLUSIONS: The ARI-adjusted mod+ rate requires to be calculated for all laboratories in England if it is to be used as a primary performance indicator. Alternatively, it can be used to further examine laboratories that are deemed to be outliers using the current methodology.

Adult↗

Screening for allergic respiratory disease in the general population with the ADVIA Centaur Allergy Screen Assay.

BACKGROUND: In patients in whom the clinical indication for immunoglobulin E (IgE)-mediated allergic respiratory disease is weak, a single qualitative multiallergen-screening assay for IgE antibody to multiple allergen specificities may support the absence of IgE-mediated allergic respiratory disease. The aim was to investigate the diagnostic efficacy of a new multiallergen-screening assay in relation to skin prick test (SPT) reactivity and objective diagnoses of allergic respiratory disease in a general population setting. METHODS: A total of 709 participants in a population-based study were examined by questionnaire and SPT. Serum was analysed by using a multiallergen-screening assay: the ADVIA Centaur Allergy Screen (AS) assay. The dichotomized result of the AS assay was compared with SPT reactivity, specific IgE positivity, and a clinical diagnosis of allergic rhinitis or allergic asthma defined by the presence of relevant symptoms and positive SPTs. RESULTS: Sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of the AS against SPT reactivity were 86%, 96%, 94%, and 89%, respectively. A negative AS assay test was able to exclude allergic rhinitis and allergic asthma with a probability of more than 96% and 98% (NPV), respectively. The AS assay was able to identify more than 92% and 92% (sensitivity) of cases of allergic rhinitis and allergic asthma, respectively. CONCLUSIONS: The AS assay proved to be a valid measure of allergic respiratory disease and may be used as a screening tool to rule out allergic respiratory disease, and as an objective measure of allergic respiratory disease in epidemiological studies.

Antibodies, Anti-Idiotypic↗

Screening for congenital hypothyroidism. II. Clinical findings in infants with positive screening tests.

In a pilot screening programme for congenital hypothyroidism, PKU filter paper blood samples from 20 000 infants born in Stockholm were analysed for TSH and T4 to identify optimal conditions for routine nationwide screening. Among 160 infants with positive screening tests, 7 infants (group I) had true-positive results, 6 had primary and one secondary hypothyroidism. The 153 infants with false-positive tests were divided into group II:74 infants with an isolated increased TSH level; group III: 71 infants with an isolated decreased T4 concentration; and group IV: 8 infants with increased TSH and decreased T4 levels. In group I the clinical signs and symptoms of hypothyroidism varied when the diagnosis was made at 3 weeks of age. The median hypothyroid index score was 8 (range 0--18). In groups II-IV most infants showed very few signs of hypothyroidism. The median hypothyroid index scores were 1, 1, and 0, respectively. Clinical findings were of little value in the individual case for distinguishing true from false positive screening tests. We suggest that nation-wide screening should be based on TSH analyses of PKU blood samples, with a cut-off level corresponding to 50 mU/l of plasma. Recall frequency will be less than 0.1%.

Congenital Hypothyroidism↗

Developmental screenings in rural settings: a comparison of the child development review and the Denver II Developmental Screening Test.

Screening results for the Child Development Review (CDR) and the Denver II Developmental Screening Test (Denver II) were compared in two locations: the Cheyenne River Reservation in South Dakota and Sioux Falls, S.D. Seventy-three white, Native American and other minority children, half originating from the reservation and half from Sioux Falls, were randomly assigned to take one developmental screening test. A chi-square analysis indicated a significant difference in results across tests. Specifically, more CDR than Denver II subjects passed the screening and more Denver II than CDR subjects failed the screening. This pattern held for subjects living on, but not off, the reservation. Thus, for Native American, white and other minority children living on the Cheyenne River Reservation, the CDR may be undersensitive and/or the Denver II oversensitive to suspect presentations. Medical practitioners are advised to use these instruments with caution in rural settings.

Chi-Square Distribution↗

The risks of screening: data from the Nottingham randomised controlled trial of faecal occult blood screening for colorectal cancer.

AIMS: To determine the harm that ensues from faecal occult blood (FOB) screening for colorectal cancer. METHODS: 150 251 people were randomly allocated either to receive biennial Haemoccult FOB tests (n =75 253) or not to be contacted (n=74 998). Study group patients returning positive tests were offered colonic investigation; 1774 underwent complete investigation of the colon. RESULTS: There was no significant difference in the stage at presentation of interval versus control group cancers. Survival in the interval cancer group was significantly prolonged compared with the control group. Sensitivity for colonoscopy or flexible sigmoidoscopy and double contrast barium enema (DCBE) was 96.7%. There were no complications of DCBE but seven (0.5%) complications of colonoscopy, of which six required surgical intervention. There were no colonoscopy related deaths. No patients without colorectal cancer died within 30 days of colonic investigation. Five patients died within 30 days of surgery for screen detected colorectal neoplasia and a further two died without having surgery. Six patients died after 30 days but within two years of surgery for screen detected benign adenomas or stage A cancers; in all cases the cause of death was not related to colorectal cancer. CONCLUSIONS: There was investigation related morbidity but no mortality and little to support overdiagnosis bias. The group returning falsely negative tests had a better outcome compared with the whole control group. There is a negative side to any screening programme but mortality reduction in this and other trials suggests that a national programme of colorectal cancer screening should be given consideration.

Aged↗

Oral cancer screening as an integral part of general health screening in Tokoname City, Japan.

OBJECTIVES: To measure the attendance and compliance rates in oral mucosal screening (OMS) offered as part of a general health screen (GHS) undertaken as an organised programme in Japan. METHODS: In 1996, all adults over the age of 40 years resident in Tokoname City were invited by letter to attend a free GHS annually, conducted by the municipal cooperation and the medical and dental societies of Tokoname City. In the later years only those who attended in 1996 were reinvited. Females aged less than 39 years were also allowed to attend if they wished to participate in the GHS. The GHS consisted of completion of a self administered questionnaire to identify past and current illnesses and any medications used by the screened population coupled with a routine physical check, chest x ray, ECG, and blood and urine examination. The GHS was programmed annually during the years 1996 to 1998. All those attending the GHS were invited to participate in an OMS conducted under the same roof by a visiting dentist (n=37). A referral pathway was established for screen positives requiring follow up. RESULTS: A total of 19 305 subjects (5955 males, 13350 females; mean age 59.2 years; 7033 in 1996, 6289 in 1997, and 5983 in 1998) attended the GHS. Of those who attended the GHS, 19 056 (98.7%) attended the OMS (1.3% refused). This rate was fairly constant over the three years. Excluding repeat examinations, new cases recruited for OMS over the three years were 8723. Of those participating in OMS, 4269 (60.7%) attended all three years. In the cohorts examined, screening dentists recorded oral mucosal lesions in 5.4% in 1996, in 4.0% in 1997, and in 2.6% in 1998. Overall, this amounted to a positive detection rate of 4.1%, or 4.9% excluding repeat examinations. A higher prevalence of oral pre-cancer was recorded among male smokers. CONCLUSIONS: The overall results suggest that although compliance with attending a free GHS was low (26.2%) among Japanese subjects over 40 years of age, of those who complied 74-76% reattended annually. Hence a satisfactory participation rate can be obtained in Japan for OMS when this is coupled to a GHS conducted at the same visit.

Adult↗

Breast cancer screening with mammography: a population-based, randomized trial with mammography as the only screening mode.

A population-based, randomized breast cancer screening project was undertaken using mammography alone. Of 17,447 invited women aged 50-69, 12,765 (73%) attended the screening. On the basis of the screening films, malignancy was suspected in 405 women (3.2%) who were recalled for complete mammography. Additional films showed that the suspicion of malignancy was false in 194 women. The remaining 211 women (1.7%) were referred for clinical and cytological examination. Of these, 159 had surgery. Breast cancer was proved in 97 women, corresponding to a prevalence rate of 7.6/1000. Fifty-three (55%) of the carcinomas were either in situ or invasive with a diameter of less than or equal to 1 cm. Axillary metastases were found in 19 patients (19.6%). Cancers detected at screening were significantly less advanced than those in the control group. There was a remarkably high frequency of tubular carcinoma among cancers detected at screening.

Aged↗

Improvement of x-ray intensifying screen efficiency by special design of the screen.

An investigation of light diffusion in x-ray intensifying screens and the prospects for improvement by confining light spread with a special structure are reported. Light diffusion in CaWO4 screens was studied theoretically using computer simulation. The proportion and spatial distribution of light emerging from different depths in the screen were calculated. The introduction of narrow gaps in the screens made it possible to improve these proportions and distributions. The gaps improved the line spread functions, the screen efficiencies, and the average contribution of the absorbed quanta to the light output.

Light↗

Clinical comparison of high-speed rare-earth screen and par-speed screen for diagnostic efficacy and radiation dosage.

One hundred patients underwent excretory urography and a comparison was made of ten-minute, well-collimated images that were obtained with both par-speed and rare-earth screens, the latter being 6.5 times faster than the par-speed calcium tungstate screens. Radiation dose was greatly reduced with the rare-earth screens. There were fewer inferior examinations, even though fine detail was imaged poorly, and there was a slightly increased quantum mottle, which was only a minor problem at this low 65 kVp. Since quantum mottle increases with kVp, however, our results are not applicable to higher kVp examinations. Despite reduced detail and increased mottle, the overall image quality obtained with the rare-earth screen was superior to the image quality obtained with the par-speed screen.

Body Burden↗

To screen or not to screen for pre-type 1 diabetes?

The incidence of type 1 diabetes is increasing worldwide and the disease is an onerous burden both to the individual and to society. There are thus important reasons to screen for the disease before it becomes manifest: (1) to improve understanding of the natural history of the prediabetic period; (2) to gain further insights into the immunopathogenesis of the disease; (3) to identify individuals for prevention trials; (4) to make an earlier diagnosis in order to reduce morbidity and mortality. Great strides have been made, yet there is still a great deal to be learned. Opponents of screening argue that screening tests for the disease have a low positive predictive value and that predicting the disease without a primary prevention capability raises ethical considerations because of induced stress, lifestyle changes, cost and potential effects on insurability. The greatest single barrier against large-scale population screening and prevention of the disease remains the lack of an effective intervention. However, screening in the context of well-designed research studies must continue - ultimately the benefit to the individual and to society will be immense.

Diabetes Mellitus, Type 1↗

Universal screening for hemoglobinopathies using high-performance liquid chromatography: clinical results of 2.2 million screens.

In screening for hemoglobinopathies, high-performance liquid chromatography (HPLC) achieves excellent sensitivity and specificity, while adding the very important quantitative element to the analysis. Due to the development of a rapid, automated HPLC system, California began screening 600,000 births per year in 1990 using this method. Based on confirmatory testing for 97% of the initial positive results resulting from 2.2 million screens, HPLC has proven to be clinically accurate. In conjunction with the availability of quantitative data, HPLC provides a complete screening system, eliminating the need for a second screening test, and accurately discriminating beta thalassemia compound conditions. The large degree of ethnic diversity and high birth rate in California have produced detailed and reliable birth prevalence rates for most conditions and ethnicities.

Blood↗

Raising awareness and providing free screening improves cervical cancer screening among economically disadvantaged Lebanese/Armenian women.

Women need to practice cervical screening regularly to reduce morbidity and mortality. The purpose of this study was to examine the impact of an intervention program on knowledge, attitude, and practice of cervical screening in the population of Lebanese/Armenian women. The design was a cross-sectional, quasi-experimental posttest survey following a year long intervention program. The sample included 176 women, who were members of the Armenian Relief Cross in Lebanon. Interventions consisted of educational classes, media messages, and free screening. The instrument was a self-administered questionnaire. Knowledge of women with intervention was higher (p > .05) and practice rate increased between intervention and comparison groups. No difference in attitude was noted. The study was successful in raising awareness and increasing screening in the sample. It is recommended to continue helping women to overcome barriers for cervical screening.

Adolescent↗

Colonoscopic screening for colorectal cancer improves quality of life measures: a population-based screening study.

BACKGROUND: Screening asymptomatic individuals for neoplasia can have adverse consequences on quality of life. Colon cancer screening is widespread but the quality of life (QOL) consequences are unknown. This study determined the impact of screening colonoscopy on QOL measures in asymptomatic average-risk participants. METHODS: Asymptomatic male and female participants aged 55-74 years were randomly selected from the Australian Electoral Roll or six primary care physicians' databases. Participants completed the Short-Form (SF-36) Quality of Life Assessment at baseline and at a mean of 39 days after colonoscopy. Outcome measures were (i) significant changes in raw scores in any of the eight SF-36 domains assessed following colonoscopic screening and (ii) improvements or declines in previously validated categories, representing clinically significant changes, within any of the eight SF-36 domains. RESULTS: Baseline QOL measures were similar to those of a matched general population sample. Role Limitations due to Emotions, Mental Health and Vitality raw scores significantly improved following colonoscopy (P < 0.05, 2-tailed t-test). Health ratings according to Category were similar (same clinical status) in the majority of participants. However, 30% participants recorded clinically significant improvement in the Mental Health and Vitality domains (P < 0.05, Wilcoxon Signed-Ranks test). This improvement was not offset by declines in other domains or in other participants. Improvement in QOL was not related to colonoscopy results. CONCLUSION: Average-risk persons benefit significantly from colon cancer screening with colonoscopy, improving in Mental Health and Vitality domains of Quality of Life. This improvement is not offset by declines in other domains.

Adenomatous Polyps↗

Opportunistic chlamydia screening; should positive patients be screened for co-infections?

This study examines the requirement for testing patients for other sexually transmitted infections (STIs) and bacterial vaginosis (BV) when diagnosed with genital chlamydia during opportunistic screening. Data were collected on all patients participating in the Department of Health chlamydia screening pilot study in Portsmouth. One thousand two hundred and forty-five women and 490 men with genital chlamydia were seen in Portsmouth genitourinary medicine (GUM) department. Of the women screened in GUM, 28% had coexisting STIs and 21% had BV. The corresponding figures for those initially screened in the community were 4% and 17%. An increased number of female sexual partners of male patients (76%) and male partners of female patients (55%) of the GUM group had co-infections; 58% of male partners from the community group had another STI. The increased morbidity associated with these infections warrants screening of all patients with chlamydia for other STIs and BV.

Adolescent↗

False-negative primary neonatal thyroid screening: the need for clinical vigilance and secondary screening.

The screening of newborn babies for congenital hypothyroidism has changed the natural history of this abnormality. We describe here a case of a female patient with congenital hypothyroidism that was missed by primary neonatal thyroid screening (using thyroid-stimulating hormone) at two days of age; it was detected only after the development and persistence of jaundice during the first three weeks of life. A normal neonatal screening result does not preclude the development of hypothyroidism later in infancy. Clinical vigilance must be maintained by practitioners. A second screening between two and six weeks of age may be useful in order to detect the few cases missed at first screening.

False Negative Reactions↗

Current concepts in screening for noncommunicable disease: World Health Organization Consultation Group Report on methodology of noncommunicable disease screening.

Screening people for serious diseases is receiving increasing attention as studies demonstrates the potential benefits of early detection and early intervention in preventing morbidity and mortality. Screening tests are available for some of the most important noncommunicable diseases, including cardiovascular disease, type 2 diabetes and several site-specific cancers. However, screening guidelines for cardiovascular disease, cancers and diabetes vary within and between countries because many national and international organizations are developing their own guidelines. There is a need to address the issue of screening for disease, with an emphasis on providing accurate and practical information relevant to all countries. This report arose from a Consultation Group meeting held at WHO headquarters in Geneva. It presents an examination of the principles of screening with an emphasis on noncommunicable disease prevention and control policy.

Humans↗

Second reading of screening mammograms increases cancer detection and recall rates. Results in the Florence screening programme.

OBJECTIVE: To assess double reading effectiveness in mammography screening. DESIGN: Retrospective study of 177,631 consecutive mammograms double read during 1998-2003. SETTING: The Florence screening programme, involving 11 trained radiologists. Abnormalities reported by at least one reader prompted assessment. RESULTS: The referral rate was 2.89% for the first reader, 3.15% for the second reader, and 3.59% for either reader. Of 713 total cancers detected, 43 were suspected only by the second reader (6.4% relative, 0.024% increase in absolute detection rate) and had a lower stage compared to the first reader (pTis-pT1b = 65.7 versus 52.0%): 41 were reviewed and classified (error type) as "minimal sign" in six, and "screening error" in 35 cases, or as BI-RADS 3 in one, 4a in 20, 4b in 13, and 4c in three cases. The second reading cost was 2.70 per woman examined, or 11,168 per additional cancer detected (versus 11,585 at a single reading). DISCUSSION: Second reading is effective in detecting a limited number of additional cancer cases. Tumour stage (one-third over 1 cm in diameter) and review findings (high rate of "screening errors" and BI-RADS R4b-c categories) suggest that second reading detects small "difficult cases" as well as larger cancers missed due to fatigue or loss of attention. Second reading reduces screening specificity to a minor extent, and since cancer detection at second reading seems cost-effective the procedure is recommendable in routine practice.

Aged↗