Showing papers on "Mass screening published in 1999"

Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin. Irish Hepatology Research Group.

Abstract: Background and Methods In February 1994, batches of anti-D immune globulin used in Ireland during 1977 and 1978 to prevent Rh isoimmunization were found to be contaminated with hepatitis C virus (HCV) from a single infected donor. In March 1994, a national screening program was initiated for all women who had received anti-D immune globulin between 1970 and 1994. Of the 62,667 women who had been screened when this study began, 704 (1.1 percent) had evidence of past or current HCV infection, and 390 of those 704 (55 percent) had positive tests for serum HCV RNA on reverse-transcription–polymerase-chain-reaction analysis. All 390 were offered a referral for clinical assessment and therapy. We evaluated 376 of these 390 women (96 percent); the other 14 were not seen at one of the designated treatment centers. Results The mean (±SD) age of the 376 women was 45±6 years at the time of screening. They had been infected with hepatitis C for about 17 years. A total of 304 women (81 percent) reported symptoms, most...

Decision aids for patients facing health treatment or screening decisions: systematic review

Abstract: Objective: To conduct a systematic review of randomised trials of patient decision aids in improving decision making and outcomes. Design: We included randomised trials of interventions providing structured, detailed, and specific information on treatment or screening options and outcomes to aid decision making. Two reviewers independently screened and extracted data on several evaluation criteria. Results were pooled by using weighted mean differences and relative risks. Results: 17 studies met the inclusion criteria. Compared with the controls, decision aids produced higher knowledge scores (weighted mean difference=19/100, 95% confidence interval 14 to 25); lower decisional conflict scores (weighted mean difference=−0.3/5, −0.4 to −0.1); more active patient participation in decision making (relative risk = 2.27, 95% confidence interval 1.3 to 4); and no differences in anxiety, satisfaction with decisions (weighted mean difference=0.6/100, −3 to 4), or satisfaction with the decision making process (2/100,−3 to 7). Decision aids had a variable effect on decisions. When complex decision aids were compared with simpler versions, they were better at reducing decisional conflict, improved knowledge marginally, but did not affect satisfaction. Conclusions: Decision aids improve knowledge, reduce decisional conflict, and stimulate patients to be more active in decision making without increasing their anxiety. Decision aids have little effect on satisfaction and a variable effect on decisions. The effects on outcomes of decisions (persistence with choice, quality of life) remain uncertain.

Colorectal Cancer Mortality: Effectiveness of Biennial Screening for Fecal Occult Blood

Abstract: Background In 1993, a randomized controlled trial in Minnesota showed, after 13 years of follow-up, that annual fecal occult blood testing was effective in reducing colorectal cancer mortality by at least 33%. Biennial screening (i.e., every 2 years) resulted in only a 6% mortality reduction. Two European trials (in England and in Denmark) subsequently showed statistically significant 15% and 18% mortality reductions with biennial screening. Herein, we provide updated results-through 18 years of follow-up--from the Minnesota trial that address the apparent inconsistent findings among the trials regarding biennial screening. Methods From 1976 through 1977, a total of 46551 study subjects, aged 50-80 years, were recruited and randomly assigned to an annual screen, a biennial screen, or a control group. A screen consisted of six guaiac-impregnated fecal occult blood tests (Hemoccult) prepared in pairs from each of three consecutive fecal samples. Participants with at least one of the six tests that were positive were invited for a diagnostic examination that included colonoscopy. All participants were followed annually to ascertain incident colorectal cancers and deaths. Results The numbers of deaths from all causes were similar among the three study groups. Cumulative 18-year colorectal cancer mortality was 33% lower in the annual group than in the control group (rate ratio, 0.67; 95% confidence interval [CI] = 0.51-0.83). The biennial group had a 21% lower colorectal cancer mortality rate than the control group (rate ratio, 0.79; 95% CI = 0.62-0.97). A marked reduction was also noted in the incidence of Dukes' stage D cancers in both screened groups in comparison with the control group. Conclusion The results from this study, together with the other two published randomized trials of fecal occult blood screening, are consistent in demonstrating a substantial, statistically significant reduction in colorectal cancer mortality from biennial screening.

A screening questionnaire for Asperger syndrome and other high-functioning autism spectrum disorders in school age children.

Abstract: The high-functioning Autism Spectrum Screening Questionnaire (ASSQ) is a 27-item checklist for completion by lay informants when assessing symptoms characteristic of Asperger syndrome and other high-functioning autism spectrum disorders in children and adolescents with normal intelligence or mild mental retardation. Data for parent and teacher ratings in a clinical sample are presented along with various measures of reliability and validity. Optimal cutoff scores were estimated, using Receiver Operating Characteristic analysis. Findings indicate that the ASSQ is a useful brief screening device for the identification of autism spectrum disorders in clinical settings.

Validation Studies for Models Projecting the Risk of Invasive and Total Breast Cancer Incidence

Abstract: Background In 1989, Gail and colleagues developed a model for estimating the risk of breast cancer in women participating in a program of annual mammographic screening (designated herein as model 1). A modification of this model to project the absolute risk of developing only invasive breast cancer is referred to herein as model 2. We assessed the validity of both models by employing data from women enrolled in the Breast Cancer Prevention Trial. Methods We used data from 5969 white women who were at least 35 years of age and without a history of breast cancer. These women were in the placebo arm of the trial and were screened annually. The average follow-up period was 48.4 months. We compared the observed number of breast cancers with the predicted numbers from the models. Results In terms of absolute risk, the ratios of total expected to observed numbers of cancers (95% confidence intervals [CIs]) were 0.84 (0. 73-0.97) for model 1 and 1.03 (0.88-1.21) for model 2, respectively. Within the age groups of 49 years or less, 50-59 years, and 60 years or more, the ratios of expected to observed numbers of breast cancers (95% CIs) for model 1 were 0.91 (0.73-1.14), 0.96 (0.73-1. 28), and 0.66 (0.52-0.86), respectively. Thus, model 1 underestimated breast cancer risk in women more than 59 years of age. For model 2, the risk ratios (95% CIs) were 0.93 (0.72-1.22), 1.13 (0.83-1.55), and 1.05 (0.80-1.41), respectively. Both models exhibited a tendency to overestimate risk for women classified in the higher quintiles of predicted 5-year risk and to underestimate risk for those in the lower quintiles of the same. Conclusion Despite some limitations, these methods provide useful information on breast cancer risk for women who plan to participate in an annual mammographic screening program.

Cancer Surveillance Series: Interpreting Trends in Prostate Cancer—Part I: Evidence of the Effects of Screening in Recent Prostate Cancer Incidence, Mortality, and Survival Rates

Abstract: Background The prostate-specific antigen test was approved by the U.S. Food and Drug Administration in 1986 to monitor the disease status in patients with prostate cancer and, in 1994, to aid in prostate cancer detection. However, after 1986, the test was performed on many men who had not been previously diagnosed with prostate cancer, apparently resulting in the diagnosis of a substantial number of early tumors. Our purpose is to provide insight into the effect of screening on prostate cancer rates. Detailed data are presented for whites because the size of the population allows for calculating statistically reliable rates; however, similar overall trends are seen for African-Americans and other races. Methods Prostate cancer incidence data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program and mortality data from the National Center for Health Statistics were analyzed. Results/conclusions The following findings are consistent with a screening effect: 1) the recent decrease since 1991 in the incidence of distant stage disease, after not having been perturbed by screening; 2) the decline in the incidence of earlier stage disease beginning the following year (i.e., 1992); 3) the recent increases and decreases in prostate cancer incidence and mortality by age that appear to indicate a calendar period effect; and 4) trends in the incidence of distant stage disease by tumor grade and trends in the survival of patients with distant stage disease by calendar year that provide suggestive evidence of the tendency of screening to detect slower growing tumors. Implications The decline in the incidence of distant stage disease holds the promise that testing for prostate-specific antigen may lead to a sustained decline in prostate cancer mortality. However, population data are complex, and it is difficult to confidently attribute relatively small changes in mortality to any one cause.

Newborn and Infant Hearing Loss: Detection and Intervention

Abstract: This statement endorses the implementation of universal newborn hearing screening. In addition, the statement reviews the primary objectives, important components, and recommended screening parameters that characterize an effective universal newborn hearing screening program.

Effect of screening on incidence of and mortality from cancer of cervix in England: evaluation based on routinely collected statistics

Abstract: Objective To assess the impact of screening on the incidence of and mortality from cervical cancer. Design Comparison of age specific incidence and mortality before and after the introduction of the national call and recall system in 1988. Setting England. Subjects Women aged over 19 years. Results From the mid-1960s, the number of smears taken rose continuously to 4.5 million at the end of the 1980s. Between 1988 and 1994, coverage of the target group doubled to around 85%. Registrations of in situ disease increased broadly in parallel with the numbers of smears taken. The overall incidence of invasive disease remained stable up to the end of the 1980s, although there were strong cohort effects; from 1990 incidence fell continuously and in 1995 was 35% lower than in the 1980s. The fall in overall mortality since 1950 accelerated at the end of the 1980s; there were strong cohort effects. Mortality in women under 55 was much lower in the 1990s than would have been expected. Conclusions The national call and recall system and incentive payments to general practitioners increased coverage to around 85%. This resulted in falls in incidence of invasive disease in all regions of England and in all age groups from 30 to 74. The falls in mortality in older women were largely unrelated to screening, but without screening there might have been 800 more deaths from cervical cancer in women under 55 in 1997.

Using fetal nuchal translucency to screen for major congenital cardiac defects at 10-14 weeks of gestation: population based cohort study

Abstract: Objectives: To examine the utility of measuring fetal nuchal translucency thickness in screening for major defects of the heart and great arteries at 10-14 weeks of gestation. Design: Population based cohort study. Subjects: 29 154 singleton pregnancies with chromosomally normal fetuses at 10-14 weeks of gestation. Setting: Fetal medicine centre in London. Main outcome measure: Prevalence of major defects of the heart and great arteries. Results: Of 50 cases with major defects of the heart and great arteries (prevalence 1.7 per 1000 pregnancies) 28 (56%, 95% confidence interval 42% to 70%) were in the subgroup of 1822 pregnancies with fetal nuchal translucency thicknesses above the 95th centile of the normal range. The positive and negative predictive values for this cut off point of nuchal translucency thickness were 1.5% and 99.9% respectively. Conclusions: Measurement of fetal nuchal translucency thickness—traditionally used to identify fetuses at high risk of aneuploidy—at 10-14 weeks of gestation can identify a large proportion of fetuses with major defects of the heart and great arteries.

Chlamydia trachomatis: impact on human reproduction

Abstract: Chlamydia trachomatis infections are the most prevalent bacterial sexually transmitted infections (STI) recognized throughout the world. Worldwide, the magnitude of morbidity associated with sexually transmitted chlamydial infections is enormous. C.trachomatis is a common cause of urethritis and cervicitis, and sequelae include pelvic inflammatory disease (PID), ectopic pregnancy, tubal factor infertility, epididymitis, proctitis and reactive arthritis. The sharp worldwide increase in the incidence of PID during the past two decades has led to the secondary epidemics of tubal factor infertility and ectopic pregnancy. Chlamydial PID is the most important preventable cause of infertility and adverse pregnancy outcome. Chlamydial infections, like STI in general, are primarily a woman's health care issue since the manifestations and consequences are more damaging to the reproductive health in women than in men. Based on the available evidence, approximately 20% of women with chlamydial lower genital tract infection will develop PID, approximately 4% develop chronic pelvic pain, 3% infertility, and 2% adverse pregnancy outcome. However, these estimates are based on relatively weak evidence. Research on the link between C.trachomatis and male aspects of infertility has been much more limited. Currently recommended treatment regimens include azithromycin in a single dose or doxycycline for 7 days. These therapies are highly efficacious. Timely management of sex partners is essential for decreasing the risk for re-infection. Immunopathogenesis of C.trachomatis infection is one of the main focal points of current research into Chlamydia. Chlamydial infection fills the general prerequisites for disease prevention by screening, i.e. chlamydial infections are highly prevalent, usually asymptomatic, are associated with significant morbidity, can be reliably diagnosed, and are treatable. Screening programmes for C.trachomatis will be of paramount importance in the prevention of long-term sequelae. The cost of screening is only a fraction of the health care costs incurred due to complications resulting from undiagnosed and untreated chlamydial infections. Current strategies to control C.trachomatis still largely depend on clinic-based screening of symptomatic patients, and have not been successful. The development of highly sensitive and specific nucleic acid amplification tests for the diagnosis of chlamydial infections has been an important advance in the ability to conduct population-based screening programmes to prevent complications. Thus, the case for screening is clearly made, but much detail remains to be worked out.

Health psychology: mapping biobehavioral contributions to health and illness.

Abstract: ▪ Abstract Our evolving understanding of how psychosocial and behavioral factors affect health and disease processes has been marked by investigation of specific relationships and mechanisms underlying them. Stress and other emotional responses are components of complex interactions of genetic, physiological, behavioral, and environmental factors that affect the body's ability to remain or become healthy or to resist or overcome disease. Regulated by nervous, endocrine, and immune systems, and exerting powerful influence on other bodily systems and key health-relevant behaviors, stress and emotion appear to have important implications for the initiation or progression of cancer, HIV, cardiovascular disease, and other illnesses. Health-enhancing and health-impairing behaviors, including diet, exercise, tobacco use, and protection from the sun, can compromise or benefit health and are directed by a number of influences as well. Finally, health behaviors related to being ill or trying to avoid disease or its...

The London Fibromyalgia Epidemiology Study: the prevalence of fibromyalgia syndrome in London, Ontario.

Abstract: Objective. To estimate the point prevalence of fibromyalgia syndrome (FM) among noninstitutionalized Canadian adults; and to assess the effect of demographic variables on the odds of having FM. Methods. A screening questionnaire was administered via telephone to a random community sample of 3395 noninstitutionalized adults residing in London, Ontario. Individuals screening positive were invited to be examined by a rheumatologist to confirm or exclude FM using the 1990 American College of Rheumatology classification criteria. Results. One hundred confirmed cases of FM were identified, of whom 86 were women. Mean age among FM cases was 49.2 years among women, 39.3 years among men (p < 0.02). FM affects an estimated 4.9% (95% CI 4.7%, 5.1%) of adult women and 1.6% (1.3%, 1.9%) of adult men in London, for a female to male ratio of roughly 3 to one. In women, prevalence rises steadily with age from < 1% in women aged 18-30 to almost 8% in women 55-64. Thereafter, it declines. The peak prevalence in men also appears to be in middle age (2.5%; 1.1%, 5.7%). FM affects 3.3% (3.2%, 3.4%) of noninstitutionalized adults in London. Female sex, middle age, less education, Idwer household income, being divorced, and being disabled are associated with increased odds of having FM. Conclusion. FM is a common musculoskeletal disorder among Canadian adults, especially among women and persons of lower socioeconomic status.

Use of the Pediatric Symptom Checklist to Screen for Psychosocial Problems in Pediatric Primary Care: A National Feasibility Study

Abstract: Background Routine use of a brief psychosocial screening instrument has been proposed as a means of improving recognition, management, and referral of children's psychosocial morbidity in primary care. Objective To assess the feasibility of routine psychosocial screening using the Pediatric Symptom Checklist (PSC) in pediatrics by using a brief version of the checklist in a large sample representative of the full range of pediatric practice settings in the United States and Canada. We evaluated large-scale screening and the performance of the PSC in detecting psychosocial problems by (1) determining whether the prevalence of psychosocial dysfunction identified by the PSC was consistent with findings in previous, smaller samples; (2) assessing whether the prevalence of positive PSC screening scores varied by population subgroups; and (3) determining whether the PSC was completed by a significant proportion of parents from all subgroups and settings. Patients and Methods Twenty-one thousand sixty-five children between the ages of 4 and 15 years were seen in 2 large primary care networks: the Ambulatory Sentinel Practice Network and the Pediatric Research in Office Settings network, involving 395 pediatric and family practice clinicians in 44 states, Puerto Rico, and 4 Canadian provinces. Parents were asked to complete a brief questionnaire that included demographic information, history of mental health services, the 35-item PSC, and the number of pediatric visits within the past 6 months. Results The overall prevalence rates of psychosocial dysfunction as measured by the PSC in school-aged and preschool-aged pediatric outpatients (13% and 10%, respectively) were nearly identical to the rates that had been reported in several smaller samples (12%-14% among school-aged children and 7%-14% among preschoolers). Consistent with previous findings, children from low-income families were twice as likely to be scored as dysfunctional on the PSC than were children from higher-income families. Similarly, children from single-parent as opposed to those from 2-parent families and children with a past history of mental health services showed an elevated risk of psychosocial impairment. The current study was the first to demonstrate a 50% increase in risk of impairment for male children. The overall rate of completed forms was 97%, well within an acceptable range, and at least 94% of the parents in each sociodemographic subgroup completed the PSC form. Conclusions Use of the PSC offers an approach to the recognition of psychosocial dysfunction that is sufficiently consistent across groups and locales to become part of comprehensive pediatric care in virtually all outpatient settings. In addition to its clinical utility, the consistency and widespread acceptability of the PSC make it well suited for the next generation of pediatric mental health services research, which can address whether earlier recognition of and intervention for psychosocial problems in pediatrics will lead to cost-effective outcomes.

Are sex and educational level independent predictors of dementia and Alzheimer’s disease? Incidence data from the PAQUID project

Abstract: OBJECTIVES To examine the age specific risk of Alzheimer’s disease according to sex, and to explore the role of education in a cohort of elderly community residents aged 65 years and older. METHODS A community based cohort of elderly people was studied longitudinally for 5 years for the development of dementia. Dementia diagnoses were made according to the DSM III R criteria and Alzheimer’s disease was assessed using the NINCDS-ADRDA criteria. Among the 3675 non-demented subjects initially included in the cohort, 2881 participated in the follow up. Hazard ratios of dementia were estimated using a Cox model with delayed entry in which the time scale is the age of the subjects. RESULTS During the 5 year follow up, 190 incident cases of dementia, including 140 cases of Alzheimer’s disease were identified. The incidence rates of Alzheimer’s disease were 0.8/100 person-years in men and 1.4/100 person-years in women. However, the incidence was higher in men than in women before the age of 80 and higher in women than in men after this age. A significant interaction between sex and age was found. The hazard ratio of Alzheimer’s disease in women compared with men was estimated to be 0.8 at 75 years and 1.7 at 85 years. The risks of dementia and Alzheimer’s disease were associated with a lower educational attainment (hazard ratio=1.8, p CONCLUSION Women have a higher risk of developing dementia after the age of 80 than men. Low educational attainment is associated with a higher risk of Alzheimer’s disease. However, the increased risk in women is not explained by a lower educational level.

Second manifestations of ARTerial disease (SMART) study: rationale and design.

Abstract: The Second Manifestations of ARTerial disease (SMART) study is a single-centre prospective cohort study among patients, newly referred to the hospital with (1) clinically manifest atherosclerotic vessel disease, or (2) marked risk factors for atherosclerosis. The first objectives of the SMART study are to determine the prevalence of concomitant arterial disease at other sites, and risk factors in patients presenting with a manifestation of arterial disease or vascular risk factor and to study the incidence of future cardiovascular events and its predictors in these high-risk patients. At least 1000 patients, aged 18 to 80 years, will undergo baseline examinations, including a questionnaire on cardiovascular disease, height, weight and blood pressure measurements, blood tests for glucose, lipids, creatinine and homocysteine, urinary tests for microproteinuria, resting twelve-lead electrocardiogram, ultrasound scanning of the abdominal aorta, kidneys and the carotid arteries, measurements of common carotid intima-media thickness and arterial stiffness, and a treadmill test to assess atherosclerosis of the leg arteries. Abnormal findings are reported to the treating specialist and general practitioner with a treatment suggestion according to current practice guidelines. Recruitment and baseline examinations began in September 1996. All cohort members will be followed for clinical cardiovascular events for a minimum of three years. In the scope of secondary prevention, the study is expected to support the design of solid based screening and treatment programmes and evidence-based cardiovascular medicine to reduce morbidity and mortality, and improve quality of life, in high-risk patients.

Validation of the Chinese-Cantonese version of the hospital anxiety and depression scale and comparison with the Hamilton Rating Scale of Depression.

Abstract: Objective The aim of this study was to validate the Chinese-Cantonese version of the Hospital Anxiety and Depression Scale (HADS) and to compare it with the Hamilton Rating Scale of Depression (HRSD) as a screening tool for depressive disorders in general hospital in-patients. Method The Chinese-Cantonese version of the HADS was administered to general hospital in-patients seen on a consultation basis, and psychiatric diagnoses were made according to DSM-111-R. The subjects were further rated independently with the HRSD. Results The Chinese-Cantonese version of the HADS was found to have good internal consistency and external validity, with favourable sensitivity and specificity for screening for psychiatric disorders. However, its performance was marginally inferior to that of the HRSD. The scale also performed poorly in identifying major depression. Conclusion The HADS has limitations with regard to identification of depressive disorders. However, despite its shortcomings, it remains one of the best paper-and-pencil tests for screening psychiatric disorders in the medically ill.

Coeliac disease in primary care: case finding study

Abstract: Objectives: To provide evidence of underdiagnosis of coeliac disease and to describe the main presenting symptoms of coeliac disease in primary care. Design: Case finding in a primary care setting by testing for coeliac disease by using the endomysial antibody test. Setting: Nine surgeries in and around a market town in central England, serving a population of 70 000. Participants: First 1000 patients screened from October 1996 to October 1997. Outcome measures: Determination of endomysial antibody titre of patients fulfilling the study criteria, followed by small intestine biopsy of those with positive results. Results: The 30 patients (out of 1000 samples) with positive results on the endomysial antibody test all had histological confirmation on small intestine biopsy. The commonest mode of presentation (15/30) was anaemia of varying severity. Most patients (25/30) presented with non-gastrointestinal symptoms. Specificity of the endomysial antibody test was 30/30. Conclusions: Underdiagnosis and misdiagnosis of coeliac disease are common in general practice and often result in protracted and unnecessary morbidity. Serological screening in primary care will uncover a large proportion of patients with this condition and should be made widely available and publicised. Coeliac disease should be considered in patients who have anaemia or are tired all the time, especially when there is a family history of the disease.

When can a risk factor be used as a worthwhile screening test

Abstract: One of the most important areas of medical inquiry is the identification of risk factors for specific disorders. Such research is usually aimed at discovering new causes of a disease, but risk factors can also be used as screening tests. The fact that a risk factor must be very strongly associated with a disorder if it is to be a worthwhile screening test is not widely recognised. If this were better understood, fewer risk factors would be proposed unnecessarily as screening tests. Serum cholesterol measurement, for example, would probably never have been considered seriously as a screening test for ischaemic heart disease. Although a high cholesterol concentration is a strong risk factor for ischaemic heart disease in aetiological terms, the association is not sufficiently strong for it to be used as a screening test—in practice, its screening performance is poor.1 In this article we specify the quantitative relation between risk factors and screening tests and show how strongly a risk factor needs to be associated with a disease before it is likely to be a useful screening test. For simplicity, we consider only risk factors with a Gaussian distribution, though the general principles we present can be applied to all frequency distributions. #### Summary points To be a worthwhile screening test, a risk factor must be strongly associated with a disorder The strength of association between a risk factor and a disorder can be quantified by the relative risk or relative odds (odds ratio) A risk factor can also be considered as a screening test, and its association with the disorder can be quantified as the detection rate for a specified false positive rate There is a direct numerical equivalence between the relative odds and the detection rate for specified false positive rate that does not depend on the incidence or prevalence …

ADHD in a school sample of Brazilian adolescents: a study of prevalence, comorbid conditions, and impairments.

Abstract: Objective To evaluate the prevalence, comorbid conditions, and impairments of attention-deficit/hyperactivity disorder (ADHD) among young adolescents in Porto Alegre, Brazil Method 1,013 students aged 12 to 14 years were evaluated at 64 state schools, using a screening instrument based on the 18 DSM-IV ADHD symptoms All positive screened students ( n = 99) and a random subset of negative screened subjects ( n = 92) had a psychiatric evaluation carried out within a hospital setting or at home Results The prevalence of ADHD was estimated to be 58% (95% confidence interval=32–106), and the comorbidity with other disruptive behavior disorders was high (478%) Youths with ADHD ( n = 23) had significantly higher rates of school repetitions, suspensions, and expulsions ( p n = 168) No association was identified between ADHD and alcohol, marijuana, and inhalant use Conclusion The results extend to adolescents well-documented findings in children, indicating that ADHD is quite prevalent in early adolescence and affected youths are at high risk for impairment and dysfunction in multiple domains

Plasma very long chain fatty acids in 3,000 peroxisome disease patients and 29,000 controls

Abstract: The assay of plasma very long chain fatty acids (VLCFAs), developed in our laboratory in 1981, has become the most widely used procedure for the diagnosis of X-linked adrenoleukodystrophy (X-ALD) and other peroxisomal disorders. We present here our 17 years' experience with this assay. Three VLCFA parameters, the level of hexacosanoic acid (C26:0), the ratio of C26:0 to tetracosanoic acid (C24:0), and of C26:0 to docosanoic acid (C22:0), were measured in 1,097 males (hemizygotes) with X-ALD, 1,282 women heterozygous for this disorder, including 379 obligate heterozygotes, 797 patients with other peroxisomal disorders, and 29,600 control subjects. All X-ALD hemizygotes who had not previously received Lorenzo's oil or a diet with a high erucic acid content had increased VLCFA levels, but the application of a discriminant function based on all three measurements is required to avoid the serious consequences of a false-negative result. VLCFA levels are increased at day of birth, thus providing the potential for neonatal mass screening, are identical in the childhood and adult forms, and do not change with age. Eighty-five percent of obligate heterozygotes had abnormally high VLCFA levels, but a normal result does not exclude carrier status. VLCFA levels were increased in all patients homozygous for Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum's disease, and in patients with deficiencies of peroxisomal acyl-coenzyme A oxidase, bifunctional enzyme, and 3-oxoacyl-coenzyme A thiolase. In these patients the degree of VLCFA excess correlated with clinical severity.

HPV testing in primary screening of older women.

Abstract: Certain types of the human papilloma virus (HPV) are well established as the primary cause of cervical cancer. Several studies have shown that HPV testing can improve the detection rate of high-grade cervical intraepithelial neoplasia (CIN), but these have been carried out primarily in younger women. In this study we evaluated the role of HPV testing as an adjunct to cytology in women aged 35 or over. An additional aim was to evaluate commercially available kits for HPV testing. A total of 2988 eligible women aged 34 or more attending for a routine smear in 40 general practitioner practices received HPV testing in addition to routine cytology, after having given written informed consent. Samples were assayed by polymerase chain reaction (PCR) and two versions of the Hybrid Capture test for HPV, and women were invited for colposcopy if there was any cytological abnormality (including borderline smears) or the PCR test was positive. Any apparent abnormality was biopsied and loop-excision was performed as necessary. CIN was judged by histology; 42 women had high-grade CIN, of which six were cytology negative (86% sensitivity for borderline or worse) and three had a borderline smear (79% sensitivity for mild dyskaryosis or worse). The positive predictive value of a borderline smear was only 3.1%. Eleven high-grade lesions were negative by the PCR HPV test (sensitivity 74%). The first generation Hybrid Capture II test had a similar sensitivity but an unacceptably high false positive rate (18.3%), while the newer Hybrid Capture II microtitre kit had a 95% sensitivity and a 2.3% positivity rate in normal women when used at a 2 pg ml−1 cut-off (positive predictive value 27%). Cytology performed very well in this older cohort of women. The newer Hybrid Capture II microtitre test may be a useful adjunct, especially if the results reported here are reproducible in other studies. A combined screening test offers the possibility of greater protection and/or longer screening intervals, which could reduce the overall cost of the screening programme. © 1999 Cancer Research Campaign

Breast tumor characteristics as predictors of mammographic detection: comparison of interval- and screen-detected cancers.

Abstract: Background Although mammographic screening is useful for detecting early breast cancer, some tumors are detected in the interval between screening examinations. This study attempted to characterize fully the tumors detected in the two different manners. Methods Our study utilized a case-control design and involved a cohort of women undergoing mammographic screening within the defined population of a health maintenance organization (the Group Health Cooperative of Puget Sound). Women were classified as having "interval" or "interval-detected" cancers (n = 150) if their diagnosis was made within 24 months after a negative-screening mammogram or one that indicated a benign condition. Cancers were classified as "screen detected" (n = 279) if the diagnosis occurred after a positive assessment by screening mammography. Tumors from women in each group were evaluated for clinical presentation, histology, proliferative characteristics, and expression of hormone receptors, p53 tumor suppressor protein, and c-erbB-2 protein. Results Interval-detected cancers occurred more in younger women and were of larger tumor size than screen-detected cancers. In unconditional logistic regression models adjusted for age and tumor size, tumors with lobular (odds ratio [OR] = 1.9; 95% confidence interval [CI] = 0.9-4.2) or mucinous (OR = 5.5; 95% CI = 1.5-19.4) histology, high proliferation (by either mitotic count [OR = 2.9; 95% CI = 1.5-5.7] or Ki-67 antigen expression [OR = 2.3; 95% CI = 1.3-4.1]), high histologic grade (OR = 2.1; 95% CI = 1.2-4.0), high nuclear grade (OR = 2.0; 95% CI = 1.0-3.7), or negative estrogen receptor status (OR = 1.8; 95% CI = 1.0-3.1) were more likely to surface in the interval between screening examinations. Tumors with tubular histology (OR = 0.2; 95% CI = 0.0-0.8) or with a high percentage of in situ components (50%) (OR = 0.5; 95% CI = 0.2-1.2) were associated with an increased likelihood of screen detection. Conclusions Our data from a large group of women in a defined population indicate that screening mammography may miss tumors of lobular or mucinous histology and some rapidly proliferating, high-grade tumors.

A Screening Procedure for Oropharyngeal Dysphagia

Abstract: The present study was designed to examine the sensitivity and specificity of a 28-item screening test in identifying patients who aspirate, have an oral stage disorder, a pharyngeal delay, or a pharyngeal stage disorder. The screening test includes 28 items divided into 5 categories: (1) 4 medical history variables; (2) 6 behavioral variables; (3) 2 gross motor variables; (4) 9 observations from oromotor testing; and (5) 7 observations during trial swallows. Results identified variables that were able to classify patients correctly as having or not having aspiration 71% of the time, an oral stage disorder 69% of the time, a pharyngeal delay 72% of the time, and a pharyngeal stage swallowing problem 70% of the time. Sensitivity and specificity for each of these judgments and all 28 items on the test are also provided. Results are discussed relative to statistical, clinical, and third-party perspectives on the goals of screening, data from other screening tests, and the role of screening versus diagnostic testing in care of dysphagic patients.

The Southern Cone Initiative against Chagas Disease

Abstract: Chagas disease (also known as American trypanosomiasis) is now ranked as the most serious parasitic disease of the Americas, with an economic impact far outranking the combined effects of other parasitic diseases such as malaria, schistosomiasis and leishmaniasis. Although the chronic infection remains virtually incurable, transmission can be halted by eliminating the domestic insect vectors and screening blood donors to avoid transfusional transmission. In line with this strategy, governments of the six Southern Cone countries (Argentina, Bolivia, Brazil, Chile, Paraguay and Uruguay) launched in 1991 an ambitious initiative to control Chagas disease through elimination of the main vector, Triatoma infestans, and large-scale screening of blood donors. Now at its mid-point, the programme has achieved remarkable success, with transmission halted over vast areas of the previously endemic regions. Well over 2 million rural houses have been sprayed to eliminate T. infestans, and the programme has already shown significant economic rates of return in addition to the medical and social benefits.