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Real-time ultrasonography--an efficient screening method for abdominal and pelvic lymphadenopathy.

Real-time ultrasonography of the abdomen and pelvis was performed in 129 patients with malignant lymphoma and malignant tumors in the course of clinical and pathological staging. The results of real-time ultrasonography were compared with the findings of computed tomography, lymphography and staging laparotomy. Analysis of the data indicated a sensitivity of 72,6% a specificity of 88,8% and an overall accuracy of 78.3%. Real-time ultrasonography, thus, proved to be an efficient screening method for abdominal and pelvic lymphadenopathy. It can reduce the number of lymphographies as well as abdominal CT examinations. Sonographic anatomy of the lymph system and the varying features of lymphomatous involvement in the peritoneal cavity and retroperitoneal space are described, diagnostic pitfalls and the clinical importance of real-time ultrasonography in the diagnostic work-up in patients with adenopathy are detailed.

Abdominal Neoplasms↗

Estimation of sojourn time in chronic disease screening without data on interval cases.

Estimation of the sojourn time on the preclinical detectable period in disease screening or transition rates for the natural history of chronic disease usually rely on interval cases (diagnosed between screens). However, to ascertain such cases might be difficult in developing countries due to incomplete registration systems and difficulties in follow-up. To overcome this problem, we propose three Markov models to estimate parameters without using interval cases. A three-state Markov model, a five-state Markov model related to regional lymph node spread, and a five-state Markov model pertaining to tumor size are applied to data on breast cancer screening in female relatives of breast cancer cases in Taiwan. Results based on a three-state Markov model give mean sojourn time (MST) 1.90 (95% CI: 1.18-4.86) years for this high-risk group. Validation of these models on the basis of data on breast cancer screening in the age groups 50-59 and 60-69 years from the Swedish Two-County Trial shows the estimates from a three-state Markov model that does not use interval cases are very close to those from previous Markov models taking interval cancers into account. For the five-state Markov model, a reparameterized procedure using auxiliary information on clinically detected cancers is performed to estimate relevant parameters. A good fit of internal and external validation demonstrates the feasibility of using these models to estimate parameters that have previously required interval cancers. This method can be applied to other screening data in which there are no data on interval cases.

Aged↗

Influence of direct referrals on time to diagnosis after an abnormal breast screening result.

This study examined the influence of a direct referral process implemented by a population-based provincial breast screening program on the time from screening to first procedure, first procedure to diagnosis, and screening to diagnosis following an abnormal breast screening result. The direct referral process shifted the responsibility for the coordination of diagnostic follow-up procedures from the family physician to the screening program. Three cohorts of women were included: a control cohort (screened prior to the initiation of a direct referral process, n = 1347), a usual care cohort (screened after the initiation of a direct referral process but for whom permission to refer was denied by the family physician, n = 1225), and a direct referral cohort (screened after the initiation of the direct referral process and for whom permission to refer was given by the family physician, n = 1232). The direct referral cohort was subdivided into women referred to a breast health centre (BHC group) (n = 606) and women referred to a diagnostic facility (diagnostic group) (n = 626). The direct referral cohort completed all three time intervals significantly faster than the other two cohorts (P < 0.0001). The diagnostic group experienced a significantly lower time from screening to the first procedure than the other cohorts or the BHC group (P < 0.0001). However, the BHC group had a significantly lower time from first procedure to diagnosis than the other cohorts or the diagnostic group (P < 0.0001). The control and the usual care cohorts were not significantly different from each other (P = 0.6250). The direct referral process significantly reduced the time to diagnosis after an abnormal screening result.

Breast Neoplasms↗

Mammography screening for breast cancer in Copenhagen April 1991-March 1997. Mammography Screening Evaluation Group.

A biennial mammography screening programme started for all women aged 50-69 in the municipality of Copenhagen, Denmark, on 1 April 1991. We report here on the outcome of the first three invitation rounds. Copenhagen has approximately 40,000 female residents aged 50-69. The Copenhagen Municipality IT Service runs the data files and issues the invitations based on the daily updated population register. Screening takes place at a special clinic at Bispebjerg Hospital, and since 1 September 1996 all assessment and surgery take place at Rigs-hospitalet. The first invitation round covered the period April 1991 to April 1993, the second invitation round the period May 1993 to May 1995, and the third invitation round the period June 1995 to March 1997. By now in total 120,772 invitations have been issued, 84,036 screening tests have been performed, 4110 women have been assessed with additional tests, 1057 women have undergone surgery, and 697 cases of invasive breast cancer cases or carcinoma in situ have been detected. The number of women screened during each of the three invitation rounds as a percentage of the target population aged 50-69 was 71%, 65% and 63%, respectively. It is possible for a woman to notify the programme if she does not want to be invited, and this caused the coverage to decline. The participation rate among the invited women was 71%, 69% and 70%, respectively. Ninety percent of those screened the first and second times and invited the third time participated. The number of screen detected invasive breast cancers of carcinoma in situ cases per 1000 participants during each invitation round was 11.9; 6.3; and 6.1, respectively. When compared with the incidence of invasive breast cancer in Copenhagen before screening, the ratios were 4-7 for all first time screened and 2 for all second or third time screened. Among the 697 screen detected cases, 84% were invasive breast cancers and 11% carcinoma in situ in women not previously known with breast cancer, and 5% were second primary breast cancers. Fifty two invasive interval cancers were found when women who tested negative during the first invitation round were followed up for two years in the Danish Cancer Register and the files of invasive breast cancers of the Danish Breast Cancer Cooperative Group. Compared with the incidence of invasive breast cancer in Copenhagen before screening this gave a proportionate interval cancer rate of 0.34 (95% confidence interval 0.26-0.45). Eight percent of the women who ever participated in the programme had experienced at least one false positive screening test, and 10% of the women who participated all three times in the programme had experienced at least one false positive test. The assessment was an efficient procedure for the sorting out of the false positive screening tests. During the third invitation round, three quarters of those who underwent surgery had either invasive breast cancer or carcinoma in situ. The participation rate in the present programme is relatively low as are the participation rates in other large cities. However, the programme is well accepted among those who participate, as a high proportion of these women come back. The detection rates compared with the previous incidence of invasive breast cancer indicate a good performance of the programme, and so does the proportionate interval cancer rate following the first invitation round. The programme is thus functioning well. The relatively low coverage and the flow in the target population limit the reduction in breast cancer mortality to be expected from the screening programme in the Copenhagen municipality.

Aged↗

[Automated infant auditory screening using the Natus-ALGO 2e in the NICU].

Natus-ALGO 2e, an automated ABR screener(Natus Medical, Foster City, CA, USA), compares the V wave of ABR evoked by 35-dB-nHL click stimuli by using a template-matching detection algorithm that provides only a pass-refer outcome. The aim of this study was to compare Natus-ALGO 2e with conventional ABR, and to evaluate its usefulness. The Natus-ALGO 2e screener was used to screen 202 ears of 101 neonates in our neonatal intensive care unit. The mean conceptional age at the time of screening was 40.4 +/- 3.0 weeks. 60 ears of 30 infants at high-risk of hearing impairment, including "refer" infants, were tested by the Natus-ALGO 2e and conventional ABR methods, and the results were compared. All neonates were tested with the Natus-ALGO 2e screener in a state of natural sleep, and screening time averaged 2 minutes 58 seconds. There were 97 cases in which both ears were passed, 3 cases in which both ears were referred, and one case in which one ear was referred. In comparison with conventional ABR, 53 of the 60 ears of 30 high-risk infants passed by the Natus-ALGO 2e method, whereas 14 of the 53 ears initially failed the conventional ABR screening. Of these 14 ears disagreements (the results of the Natus-ALGO 2e method passed, but the results of the conventional ABR failed), the results of the ABR screening changed to normal in 11 ears, and ABR showed improved threshold and latency in the other 3 ears after 5 weeks to 12 months. Among those that passed the Natus-ALGO 2e screening, the number of sweeps that failed the ABR screen was significantly greater than with normal ABR. Of the 7 ears of 4 patients that were referred on the basis of the Natus-ALGO 2e screening and failed by the conventional ABR method, 3 ears screened by the ABR method were normal when retested, and one ear passed by the Natus-ALGO 2e screening 12 weeks to 11 months later. In conclusion, Natus-ALGO 2e is useful for screening infant hearing because it can be performed quickly while the patient is sleeping naturally. In infants at high-risk for hearing impairment, the results of Natus-ALGO 2e and conventional ABR screening conflicted in numerous sweeps. Therefore, when there are many sweeps in high-risk infants, a retest should be performed that includes conventional ABR, even if they passed with Natus-ALGO 2e.

Audiometry, Evoked Response↗

[Applicability of activated partial thromboplastin time (APTT) as a screening test of milk to medium deficiencies of coagulation factors in cats].

The present investigation examined if the aPTT shows sufficient sensitivity for single factor activities also in cats when measured with the test optimized for humans using a commercial reagent. Comparative measurements were done with different modifications of the aPTT (sample predilution, addition of fibrinogen). Measurements of the aPTT using different methods and the activity of the coagulation factors II, V, X, VIII, IX, XI, and XII were performed in 42 healthy cats in order to determine the reference ranges. The same measurements were done on 21 cat plasmas where at least one of the coagulation factors was diminished in relation to the corresponding reference range. The conventional aPTT reflected the decrease in coagulation factor activity in each of the 21 plasmas by prolongation above the reference range (14.6-24.4 s). The test thus possesses high sensitivity and is a suitable screening test also for the cat. In contrast, in tests with sample predilution the sensitivity was lower (3-4 false negative results). This was probably caused by the distinct increase of the range of the reference values.

Animals↗

Non-parametric estimation of the post-lead-time survival distribution of screen-detected cancer cases.

The goal of screening programmes for cancer is early detection and treatment with a consequent reduction in mortality from the disease. Screening programmes need to assess the true benefit of screening, that is, the length of time of extension of survival beyond the time of advancement of diagnosis (lead-time). This paper presents a non-parametric method to estimate the survival function of the post-lead-time survival (or extra survival time) of screen-detected cancer cases based on the observed total life time, namely, the sum of the lead-time and the extra survival time. We apply the method to the well-known data set of the HIP (Health Insurance Plan of Greater New York) breast cancer screening study. We make comparisons with the survival of other groups of cancer cases not detected by screening such as interval cases, cases among individuals who refused screening, and randomized control cases. As compared with Walter and Stitt's model, in which they made parametric assumptions for the extra survival time, our non-parametric method provides a better fit to HIP data in the sense that our estimator for the total survival time has a smaller sum of squares of residuals.

Breast Neoplasms↗

Predictive value of photoscreening and traditional screening of preschool children.

PURPOSE: To compare the usefulness of traditional vision screening and photoscreening of 3- and 4-year-old children in the pediatrician's office. METHODS: Following training of pediatricians and office staff, six pediatric clinics used both the MTI PhotoScreener (Medical Technology Industries, LLC, Riviera Beach, FL) and traditional acuity and stereopsis screening materials (HOTV charts/Random Dot E tests as recommended by established AAP-MCHB-PUPVS guidelines) during well-child exams. Clinics used one testing method for a 6-month period and switched to the other for the following 6 months, in a randomized manner. Referred children received a complete eye examination with cycloplegic refraction by local ophthalmologists or optometrists who forwarded the results to Vanderbilt Ophthalmology Outreach Center. Amblyogenic factors were defined using standardized published criteria. RESULTS: Six hundred five children were screened with the photoscreener and 447 were screened with traditional techniques. Mean time for screening was less with the photoscreener: 2.5 versus 5.9 minutes ( P < 0.01). Untestable rates were similar (18% vs 10%, respectively P = NS), but higher with the photoscreener due to one clinic's 70% unreadable rate. Referral rates were also similar: 3.8% versus 4.5%. The positive predictive value (PPV) rate differed greatly. With follow-up results obtained from 56% of referred children, 73% of photoscreening referred children (8/11 examined) had amblyogenic factors confirmed on formal eye exams, whereas all children referred using traditional screening methods (10/10 examined) were normal. CONCLUSION: Photoscreening is more time efficient than traditional screening and has a significantly higher PPV in 3- and 4-year-old children. This study was unable to validate traditional screening techniques in this preschool age group. If these results can be replicated, support for traditional vision screening must undergo intense scrutiny, and attention should be turned toward making photoscreening feasible for widespread implementation.

Amblyopia↗

Silica clotting time (SCT) as a screening and confirmatory test for detection of the lupus anticoagulants.

We have developed a Silica Clotting Time (SCT) test suitable to screen patients with lupus anticoagulants (LA) and compatible with photo-optical instruments. The SCT results were considered to be positive for LA whenever the clotting times were longer than the upper normal limit at low phospholipid concentration and to be confirmed when the prolonged clotting times were corrected to normal by high phospholipid concentration. We studied plasmas from healthy subjects, patients with known diagnoses of LA, patients with acquired deficiencies of blood coagulation and hemophiliacs with anti-factor VIII antibodies. The test was positive for all LA patients, and negative for all non-LA patients except 7 hemophiliacs with anti-factor VIII antibodies. Our data indicate that the SCT is a sensitive test, suitable for screening patients suspected of having LA. Its compatibility with photo-optical instruments makes it a suitable candidate to replace the kaolin clotting time. The contemporaneous performance of SCT at low and high phospholipid concentrations provides screening and confirmation in a single procedure.

Anticoagulants↗

Histopathology and growth rate of interval breast carcinoma. Characterization of different subgroups.

BACKGROUND: Interval breast cancers are defined as carcinomas occurring within 2 years after a negative screening Distinction has to made between cancers existent at the time of screening but missed for some reason, and fast-growing incident cancers. This is important because the natural history and the implications for the treatment of the patient might differ. METHODS: Radiologic and histopathologic characteristics were assembled for 104 interval cancers diagnosed within the DOM project, the Utrecht program for the early detection of breast cancer. At a mammographic review for 27 cases, signs of malignant or benign tumor were found (missed cases). For 77 cases no radiologic signs were present on review. Twenty of these cases had a mitotic rate of > 3 and a high tumor growth rate (mean doubling time: 51 days). This combination seemed implausible, therefore, it was thought hypothesized that these tumors were most likely present, although radiologically invisible (masked), at the time of screening. The remaining cases (n = 57) were classified as true interval cancers and further divided into 14 fast-growing cases (mitotic rate > or = 3/high-power field [HPF]) and 43 cases with an intermediate growth rate (mitotic rate < 3/HPF). RESULTS: Factors associated with the masking of tumors were the histologic tumor type, absence of microscopic calcifications, and presence of dense breast tissue. Fast-growing tumors were characterized by a young patient age, absence of microscopic calcifications, and a high percentage of regional lymph node positive tumors. The 5-year survival probability was 100% for missed cases, 70% for masked cases, 80% for cases with an intermediate growth rate, and 54% for fast-growing cases. CONCLUSIONS: It is possible to separate interval breast cancers in true interval cases and cases (most likely) existent at the time of screening. Part of this last group is invisible by mammography (masked).

Adult↗

Screening sensitivity and sojourn time from breast cancer early detection clinical trials: mammograms and physical examinations.

PURPOSE: To estimate sensitivities of breast cancer screening modalities and preclinical duration of the disease from eight breast cancer screening clinical trials. PATIENTS AND METHODS: Screening programs invariably lead to diagnosis of disease before signs or symptoms are present. Two key quantities of screening programs are the sensitivity of the disease detection modality and the mean sojourn time (MST). The observed screening histories in a periodically screened cohort make it possible to estimate these quantities of interest. We applied recently developed statistical methods to data from eight randomized breast cancer screening trials to estimate the sensitivities of early detection modalities and MST. Moreover, when a screening trial involved two screening modalities, our methods enabled the estimation of the individual sensitivity of each screening modality. RESULTS: We analyzed breast cancer data from several screening trials and have relatively complete data from the Health Insurance Plan (HIP), Edinburgh, and two Canadian studies. The screening sensitivity for mammography, physical examination, and MST were, respectively, HIP: 0.39, 0.47, and 2.5 years; Edinburgh: 0.63, 0.40, and 4.3 years; Canadian (age 40 to 49 at entry): 0.61, 0.59, and 1.9 years; Canadian (age 50 to 59 at entry): 0.66, 0.39, and 3.1 years. CONCLUSION: The public debate on early breast cancer detection is mainly centered on mammograms. However, the current study indicates that a physical examination is of comparable importance. Cautious interpretation of trial differences is required as a result of various experimental designs and the age dependency of screening sensitivity and MST.

Adult↗

Comparing the information experience of women invited for cervical screening for the first time in 1994 with 2001.

We compared the information experience of women invited to attend cervical screening for the first time in 1994 and 2001 using postal questionnaires. Compared to 1994, women in 2001: found the invitation letter less easy to understand; were not aware of alternative venues for the test; and waited >4 weeks before receiving their results. Negative information experiences may influence attendance.

Adult↗

Randomised controlled trial of faecal-occult-blood screening for colorectal cancer.

BACKGROUND: There is growing evidence that faecal-occult-blood (FOB) screening may reduce colorectal cancer (CRC) mortality, but this reduction in CRC mortality has not been shown in an unselected population-based randomised controlled trial. The aim of this study was to assess the effect of FOB screening on CRC mortality in such a setting. METHODS: Between February, 1981, and January, 1991, 152,850 people aged 45-74 years who lived in the Nottingham area of the UK were recruited to our study. Participants were randomly allocated FOB screening (76,466) or no screening (controls; 76,384). Controls were not told about the study and received no intervention. Screening-group participants were sent a Haemoccult FOB test kit with instructions from their family doctor. FOB tests were not rehydrated and dietary restrictions were imposed only for retesting borderline results. Individuals with negative FOB tests at the first screening, together with those who tested positive but in whom no neoplasia was found on colonoscopy, were invited to take part in further screening every 2 years. Screening was stopped in February, 1995, by which time screening-group participants had been offered FOB tests between three and six times. Screening-group participants who had a positive test were offered full colonoscopy. All participants were followed up until June, 1995. The primary outcome measure was CRC mortality. FINDINGS: Of the 152,850 individuals recruited to the study, 2599 could not be traced or had emigrated and were excluded from the analysis. Thus, there were 75,253 participants in the screening group and 74,998 controls. 44,838 (59.6%) screening-group participants completed at least one screening. 28,720 (38.2%) of these individuals completed all the FOB tests they were offered and 16,118 (21.4%) completed at least one screening but not all the tests they were offered. 30,415 (40.4%) did not complete any test. Of 893 cancers (20% stage A) diagnosed in screening-group participants (CRC incidence of 1.49 per 1000 person-years), 236 (26.4%) were detected by FOB screening, 249 (27.9%) presented after a negative FOB test or investigation, and 400 (44.8%) presented in non-responders. The incidence of cancer in the control group (856 cases, 11% stage A) was 1.44 per 1000 person-years. Median follow-up was 7.8 years (range 4.5-14.5). 360 people died from CRC in the screening group compared with 420 in the control group-a 15% reduction in cumulative CRC mortality in the screening group (odds ratio=0.85 [95%; CI 0.74-0.98], p = 0.026). INTERPRETATION: Our findings together with evidence from other trials suggest that consideration should be given to a national programme of FOB screening to reduce CRC mortality in the general population.

Adenoma↗

Does breast cancer grade worsen with time? Evidence from breast screening.

It has been suggested that alteration of the distribution of histological grades, that has been found in screening programmes, is evidence for progression in histological grade with increasing size. A predictive model, that was based upon estimated growth data from an unselected series of 98 new primary breast cancers, is used to estimate the proportions of tumors that would be diagnosed according to limiting screen diagnostic and clinical diagnostic sizes after particular screening intervals; windows of opportunity are created. The results show that the limitations imposed by time and size criteria alter the distribution of growth rates of tumours that may appear in the windows. Small screen diagnostic sizes and short screening intervals allow only the most rapidly growing tumours to reach large sizes. This produces an apparent association of grade 3 tumours with large size. Interval cancers are also likely to be more rapidly growing while the more slowly growing tumours will be diagnosed at the subsequent screen to produce a spurious association of slowly growing grade 1 tumours with small size. We conclude that the evidence from screening does not support the thesis of progression of histological grade with the ageing of the tumour, since the changes that have been observed are predictable from a simple model based upon patterns of tumour growth rates and the relationships between growth rate and histology.

Breast Neoplasms↗

Decreasing test time in newborn hearing screening.

This study examined the effect of reducing the number of accepted responses in transiently evoked otoacoustic emissions based on the results of a universal neonatal hearing screening program. Our intention was to decrease the test time of newborns. A total of 464 ears were examined by using a universal newborn hearing-screening program implemented in a private maternity hospital. ILO88 Otodynamics Analyzer Quickscreen program was used for all testing and a two-stage procedure was adopted. In the first stage, the results were continuously evaluated for the 'pass' criteria, during the test, after at least 20 low-noise sweeps had been presented. As soon as the criteria were met, the test was interrupted and the results were recorded. In the second stage of the procedure, the test was continued and finally terminated after 260 quiet samples had been recorded. The results of each stage of this procedure were compared and evaluated. A total of 402 ears had normal otoacoustic emissions and only 62 ears had absent emissions. It was concluded that after a minimum of 20 averaged quiet responses, which we consider necessary in order to record reliable emissions and as soon as the 'pass' criteria were fulfilled the test could be terminated without affecting the 'pass-fail' rates which were similar in both stages. However, we believe that for diagnostic and clinical purposes, all 260 quiet samples must be used, because the results after the second stage indicated statistically better scores in response and reproducibility measures.

Audiometry, Evoked Response↗

[Real-time fluorescent PCR for screening AZFc/DAZ microdeletions on the Y chromosome in male infertility patients].

OBJECTIVE: To develop a real-time fluorescent PCR protocol suitable for the routine screening of AZFc/DAZ microdeletions on the Y chromosome in azoospermic and oligozoospermic male infertility patients. METHODS: A set of real-time fluorescent PCR was established. Eighty-seven azoospermic and ligozoospermic patients undergoing ICSI in the IVF center and 30 azoospermic men undergoing testicular biopsy in the clinic of urology surgery were screened for AZFc/DAZ microdeletions of Y chromosome. RESULTS: Eleven cases (9.4%) of AZFc/DAZ microdeletions were found in 117 cases of azoospermic and oligozoospermic patients by screening of realtime fluorescent PCR. Four cases (6.6%) were found in 61 oligozoospermic patients, and 7 cases (12.5%) were found in 56 azoospermic patients. CONCLUSION: The real-time fluorescent PCR protocol presented in this study is an easy and reliable method for detection of AZFc/DAZ microdeletions on the Y chromosome, which yields identical results to those of the multiplex PCR.

Chromosome Deletion↗

Estimating lead time and sensitivity in a screening program without estimating the incidence in the screened group.

Early indicators of the effectiveness of a screening test for chronic diseases such as breast cancer are the length of time the diagnosis is advanced by screening, the lead time, and the sensitivity of the screening test. This paper describes a model for simultaneously estimating the mean lead time and the sensitivity when only the number of cancers detected at the successive screenings and the number of cancers occurring in the time interval between the screening examinations are known. This model is particularly useful in assessing the effect of screening when the underlying cancer incidence in the screened group is unknown. The model is fitted to the data of 235 screen-detected breast cancer cases and 146 interval cancers diagnosed across 6 screening rounds of the program in Nijmegen. The maximum likelihood estimate for the mean lead time ranges from 1.3 years in the under age 50 group to 2.2 years in the age 50-65 group, both estimates having large confidence intervals. The corresponding sensitivity estimates are 0.92 and 1.00.

Adult↗

Time-dependent gestational diabetes screening values.

OBJECTIVE: This study was undertaken to determine use of different cut-off values with regard to the time of the patient's last meal in screening for gestational diabetes mellitus which could result in better results and change patient management. METHODS: Two hundred and seventy-four non-diabetic women undergoing routine screening for glucose intolerance between 26 to 28 weeks' gestation were classified with regard to the time of previous meal. A glucose challenge test and an oral glucose challenge test were conducted for each patient in the study. Results were evaluated with both a standard cut-off value of 140 mg/dl without regard to the time of the last meal and suggested cut-off values of 148 mg/dl, 142 mg/dl, and 150 mg/dl if the patient ate < 2 h, 2-3 h, and > 3 h before the screening test, respectively. RESULTS: Two hundred and seventy-four women completed the study. With these suggested cut-off values, the number of patients with a positive glucose challenge test dropped from 15.7% to 11.3%. With these cut-off values, positive predictive value increased from 27.3% to 32.3%. CONCLUSIONS: The time since previous meal affects 50 g glucose challenge test results. These new cut-off values would lead to improved efficiency of the screening test and decreased frequency with which patients require the 3-h oral glucose tolerance test.

Adolescent↗