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Performance characteristics and results of a large-scale screening program for viral hepatitis and risk factors associated with exposure to viral hepatitis B and C: results of the National Hepatitis Screening Survey. National Hepatitis Surveillance Group.

Chronic viral hepatitis frequently goes undetected until cirrhosis develops. Although the effect of interferon on the natural history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection in asymptomatic persons is unknown, treatment may modify the course of the infection, producing cures in some. In September 1992, screening for HBV and HCV was offered in 40 centers throughout the United States. Demographic features, potential risk factors, and symptoms were studied. Blood samples were obtained for the determination of serum alanine aminotransferase levels and for markers of HBV and HCV infection. Thirteen thousand nine hundred ninety seven subjects were screened. The prevalence of infection with HBV or HCV was 24.8% (HBV 17.8%; HCV 7.0%; and both 2.8%). Hepatitis B and C disease was present in 0.7% and 4.4% of the population, respectively. Risk factors for HBV and HCV infection were similar in: blood transfusions, hemodialysis, IV drug use, and sex with an IV drug user. For HBV infection, sex with multiple partners, increasing age, and birth in South East Asia or Africa were additional risk factors. The cost to find a case of HCV infection is less than the costs for finding many other treatable diseases. Screening for HBV, though more costly, is reasonably efficient, and simultaneous screening for HBV and HCV provides greater efficiency. It is practical to consider screening for HBV and HCV in the United States, particularly if any risk factor is present. Improved treatment strategies will make screening even more cost effective.

Adult↗

The effect of changing from one to two views at incident (subsequent) screens in the NHS breast screening programme in England: impact on cancer detection and recall rates.

AIM: To assess the effect on cancer detection and recall rates of changing from one to two views for incident (subsequent) screens. METHODS: Controlled, comparative, observational study of programmes in NHS breast screening programme in England. SUBJECTS: women aged 50-64 years were screened by the NHSBSP between 1 April 2001 and 31 March 2003. RESULTS: The effect of changing to two-view mammography was a 20% increase in overall incident screen cancer detection rate, with the biggest effect seen for small (<15 mm) invasive cancers. This increased detection rate was achieved with an 11% drop-in recall rate. CONCLUSION: The introduction of two-view mammography for incident screens has resulted in considerable improvements in overall NHS breast screening performance.

Aged↗

A novel screening assay for hydroxynitrile lyases suitable for high-throughput screening.

Hydroxynitrile lyases (Hnls) are important biocatalysts for the synthesis of optically pure cyanohydrins, which are used as precursors and building blocks for a wide range of high price fine chemicals. Although two Hnl enzymes, from the tropical rubber tree Hevea brasiliensis and from the almond tree Prunus amygdalus, are already used for large scale industrial applications, the enzymes still need to be improved and adapted to the special demands of industrial processes. In many cases directed evolution has been the method of choice to improve enzymes, which are applied as industrial biocatalysts. The screening procedure is the most crucial point in every directed evolution experiment. Herein, we describe the successful development of a novel screening assay for Hnls and its application in high-throughput screening of Escherichia coli mutant libraries. The new assay allows rapid screening of mutant libraries and facilitates the discovery of improved enzyme variants. Hnls catalyze the cleavage of cyanohydrins to hydrocyanic acid and the corresponding aldehyde or ketone. The enzyme assay is based on the detection of hydrocyanic acid produced, making it an all-purpose screening assay, without restriction to any kind of substrate. The gaseous HCN liberated within the Hnl reaction is detected by a visible colorimetric reaction. The facile, highly sensitive and reproducible screening method was validated by identifying new enzyme variants with novel substrate specificities.

Aldehyde-Lyases↗

Utility of the Pediatric Symptom Checklist as a psychosocial screen to meet the federal Early and Periodic Screening, Diagnosis, and Treatment (EPSDT) standards: a pilot study.

OBJECTIVE: To examine the usefulness of the Pediatric Symptom Checklist (PSC) as the psychosocial screening measure to meet federal Medicaid/Early and Periodic Screening, Diagnosis, and Treatment (EPSDT) standards in a low-income Hispanic community. DESIGN AND SETTING: Three hundred seventy-nine children (aged 6 to 16 years) were screened with the PSC in a 10-month period during well child visits to three clinics in Ventura and San Mateo counties in California. The PSC was available in English and Spanish and was administered both in written (paper-and-pencil) and oral formats. Follow-up services were provided for children identified as needing evaluation. RESULTS: The Cronbach alpha was high (r = 0.91) for the PSC in the whole sample and virtually identical for English, Spanish, oral, and written formats. All the PSC items were significantly associated with total score on the PSC in English, Spanish, oral, and written formats. Overall, the PSC identified 10.6% of the sample as at risk for psychosocial problems. Thirty-six children (9.5% of sample) were referred for mental health follow-up. Public health data from Ventura County showed a statistically significant increase in referrals for psychologic problems during the study period in two locations using the PSC: from 0.5% to 2.9% of the school-aged children seen. CONCLUSION: The PSC provides a feasible, well-accepted method for screening for psychosocial problems during EPSDT examinations of school-aged children. Psychosocial screening using a validated instrument such as the PSC, as well as increased efforts to refer positive screening results, track outcomes, and assess cost benefits should be essential requirements in capitated Medicaid approaches to caring for poor children.

Adolescent↗

Chlamydia in colposcopy clinics: to screen or not to screen?

The objective of the study was to assess the prevalence of Chlamydia trachomatis in our colposcopy clinic. A total of 337 consecutive patients newly referred to the colposcopy clinic between May and November 2003 were screened for chlamydia trachomatis. All our patients were referred by their GPs and none of the patients had had a recent chlamydia test performed. Four patients screened positive, overall giving a prevalence of 1.2% [95% CI 0.04-2.36%]. Three of those with positive results were in the 21 - 30 year age group (139 in the group, which equals 2.2% prevalence [95% CI 0 - 4.6%]). The fourth positive result was in the group over the age of 60. None of those screened in the other age groups was positive (< or =20, 31 - 40, 41 - 50, 51 - 60 years). Numbers screened in each of those groups were: 14, 115, 53 and 12, consecutively. Our study, though small in sample size, supports the view that the prevalence of chlamydia is not high in all colposcopy clinic attenders. Women younger than 30 years old are more likely to be infected than older women; hence opportunistic screening should target this age group. The prevalence rate may be low due to the enzyme linked immunosorbent assay giving a poor detection rate for chlamydia screening.

Adult↗

Characterization of a hERG screen using the IonWorks HT: comparison to a hERG rubidium efflux screen.

The introduction of parallel patch clamp instruments offers the promise of moderate-throughput, high-fidelity voltage clamp for drug screening assays. One such device, the IonWorks HT (Molecular Devices, Sunnyvale, CA), was evaluated and compared to conventional human ethera- go-go-related gene (hERG) patch clamp data and an alternative functional screen based on rubidium flux. Data generated by the IonWorks HT and rubidium assays were compared to determine if either offered superior predictive value compared to conventional patch clamp. Concentration-effect curves for a panel of known hERG blockers were shifted to higher concentrations on the IonWorks HT compared to conventional voltage clamp determinations. The magnitude of the potency shifts was compound-specific and ranged from no shift (e.g., quinidine) to over 200-fold (astemizole). When the extreme value for astemizole was disregarded, the potency shift for 13 other known reference standards was 12-fold or less, with an average shift of fivefold. The same subset of compounds in the rubidium efflux assay exhibited an average potency shift of 12-fold. To provide a simulation of how the IonWorks HT assay might perform in a single concentration screening mode, a panel of test compounds was evaluated. The IonWorks HT screen did not outperform the rubidium efflux screen in predicting conventional voltage clamp measurements. The most likely explanation appears to rest with variable and compound-specific potency shifts in the IonWorks HT assay. The variable potency shifts make it difficult to select a screening concentration that meets the criterion of a high positive predictive value while avoiding false-positives.

Animals↗

Screen-positive rates and agreement among six family history screening protocols for breast/ovarian cancer in a population-based cohort of 21- to 55-year-old women.

PURPOSE: Mutations in the BRCA1 and BRCA2 genes are responsible for approximately 2% of breast cancers by age 70 years. Professional and governmental groups recommend using family history protocols as an initial step in identifying women and families for mutation testing. We assess screen-positive rates and levels of agreement between these protocols. METHODS: We applied six family history screening protocols to a population-based cohort of 321 women, age 21 to 55 years, who reported their personal and family history of breast and ovarian cancer. RESULTS: The proportion of women and families identified as candidates for mutation testing ranged from 4.4% to 7.8%, depending on the protocol. The protocols had low or fair agreement (kappa <0.75 for 14 of 15 comparisons), but all identified six women (1.9%, 95% confidence interval 0.7%-4.0%) as screen positive. When the effect of missing ages of cancer onset was modeled, these rates increased (range 6.5%-11.5%), and nine women (2.8%) were screen positive by all protocols. CONCLUSION: Given limitations of family history as a screening test for hereditary cancer related to BRCA1/2 mutations, 1% to 2% of women in the general population should initially be identified for mutation testing. One way to achieve this would be to require that multiple screening protocols agree.

Adult↗

Impact of hemochromatosis screening in patients with indeterminate results: the hemochromatosis and iron overload screening study.

PURPOSE: Assess the quality of life impact of receiving indeterminate test results for hemochromatosis, a disorder involving HFE genetic mutations and/or elevated serum transferrin saturation and ferritin. METHODS: The study sample was from the Hemochromatosis and Iron Overload Screening Study, a large observational study of hemochromatosis among primary care patients in the US and Canada using HFE genotype and serum transferrin saturation and ferritin screening. Study subjects included 2,304 patients found with hemochromatosis risk of uncertain clinical significance. Assessed was SF-36 general health and emotional well-being before screening and six weeks after participants received their test results. Health worries were assessed after screening. RESULTS: Of the study subjects, 1,268 participants (51.5%) completed both assessments. Compared to normal controls, those with HFE mutations or elevated serum transferrin saturation and ferritin levels of uncertain significance were more likely to report diminished general health and mental well-being, and more health worries. These effects were associated with participants' belief of having tested positive for hemochromatosis or iron overload. CONCLUSION: Notification of indeterminate results from screening may be associated with mild negative effects on well-being, and might be a potential participant risk in screening programs for disorders with uncertain genotype-phenotype.

Adult↗

Carrier screening for cystic fibrosis in primary care: evaluation of a project in South Wales. The South Wales Cystic Fibrosis Carrier Screening Research Team.

Population carrier screening for cystic fibrosis (CF) was offered to all patients aged 16-45 in one general practice in South Wales, excluding those in couples with a current pregnancy. Out of 1553 patients in this group, 481 subjects were tested, giving an overall uptake rate of more than 30%. The rate of uptake varied with the mode of invitation. Twenty-six carriers were identified, giving a prevalence of identified carriers of 5.4% (1 in 18.5) for those with no family history of CF. A further 18 carriers were identified by cascade testing of these 26. We describe the practical difficulties encountered in setting up this programme in primary care in South Wales. Questionnaires were administered or distributed to all subjects before and after testing. The response rate for the pre-test questionnaire was 95%, and 40-50% for the post-test questionnaires. These showed that, at 3 months post-test, 1 in 4 screen-negative subjects did not appreciate that they had a residual risk of being a carrier. At the same time, 15% of this group thought that there was a 1 in 4 chance of a child being affected if one parent was screen-positive (carried an identified mutation) and the other was screen-negative, and 40% thought there was no risk. Anxiety in relation to testing did not appear to be a major problem, although individual patterns of response to carrier status varied widely and more sensitive indicators of psychosocial impact of genetic tests are required. A pilot study of couple screening showed that this approach is unlikely to be useful in primary care, although we did not assess couple testing during pregnancy. For any programme of CF carrier screening to be established in primary care, it will be necessary to involve the primary care team from the earliest planning stage, so that the opportunity costs, training needs and other costs of the programme can be fully resourced.

Adolescent↗

Nova Scotia Breast Screening Program experience: use of needle core biopsy in the diagnosis of screening-detected abnormalities.

PURPOSE: To evaluate a mammography screening program that uses a multidisciplinary team approach and needle core biopsy. MATERIALS AND METHODS: A total of 10,000 asymptomatic women (aged 40-74 years) underwent screening in the Nova Scotia Breast Screening Program between June 1991 and April 1994. Women aged 50-69 years were the target group. All mammograms were read by one of four radiologists. Patients with abnormal screening findings underwent work-up, which included needle core biopsy, at one of two diagnostic centers. RESULTS: Of 10,000 women, 2,794 were aged 40-49 years; 4,097, 50-59 years; 2,941, 60-69 years; and 168, 70-74 years, with 3.9, 6.4, 12.2, and 23.8 cancers detected per 1,000 patients, respectively. The overall rate was 7.7 cancers detected per 1,000 patients. Abnormalities were detected at screening in 838 patients (8.4%), 181 of whom underwent open surgery, with malignancy diagnosed in 77 (42%). Sixty-one (79%) of 77 patients had stage 0 or I cancer. In 43 (72%) of 60 patients in whom node status was assessed, findings were negative. CONCLUSION: A screening program with needle core biopsy and a multidisciplinary team approach to diagnosis is effective.

Adult↗

Routine PHQ-9 depression screening in home health care: depression, prevalence, clinical and treatment characteristics and screening implementation.

This study aimed to examine: the prevalence and correlates of depression among adults age 65 and over on admission to diverse home health care programs; nurse compliance with routine screening using the PHQ-9; and concordance between the number of depressed individuals identified by the PHQ-9 and Medicare-mandated nursing assessment following targeted nurse training in identifying depression among the elderly using a standard diagnostic screen. Data are drawn from routine screening of 9,178 patients (a 77% screening compliance rate). Of all patients screened, 782 (8.5%) met criteria for probable major depression and 148 (1.6%) for mild depression. Concordance between nurse identified depression via PHQ-9 and OASIS depression assessment improved over that reported in previous studies. Findings suggest that the use of a routine screening tool for depression can be implemented with minimal in-house training and improves detection of depression among older adults with significant physical and functional impairment.

Aged↗

Type and screen completion for scheduled surgical procedures. A College of American Pathologists Q-Probes study of 8941 type and screen tests in 108 institutions.

CONTEXT: Market-driven changes in the timing of elective surgeries and admissions have introduced barriers to completing pretransfusion testing in a timely manner. Consequently, blood bank personnel may not have adequate time to identify appropriate blood products for scheduled surgeries. Incomplete pretransfusion testing can delay surgery and significantly compromise patient safety. OBJECTIVES: To identify the incidence of avoidable problems associated with obtaining timely samples for adequate pretransfusion type and screen (T&S) testing, to identify the practices and characteristics associated with improved rates of pretransfusion testing completed prior to surgery, and to determine the likelihood of antibody identification problems that affect the availability of blood. DESIGN: Participants in the College of American Pathologists (CAP) Q-Probes laboratory quality improvement program were asked to collect data on when a T&S was collected in anticipation of elective scheduled surgery, when the T&S was completed, when the surgery started, and the results of those T&S tests. Participants also completed questionnaires describing their facilities, procedures, and practices. SETTING AND PARTICIPANTS: One hundred eight public and private institutions participated in this Q-Probes Study, 97% of which were located in the United States. MAIN OUTCOMES MEASURES: Type and screen collection and completion relative to the start of surgery, and the results of those tests. RESULTS: Of the 8941 T&Ss, 64.6% were collected prior to the day of surgery. The median laboratory completed approximately 69% of their T&S testing for scheduled surgeries at least 1 day prior to the surgery. Of those T&S tests that were collected on the day of surgery, the median laboratory completed almost 23% after the start of surgery. For 10% of participants, more than 75% of all T&Ss collected on the same day as surgery were not complete until after the start of surgery. When red blood cell-directed antibodies were identified, 78.7% were considered clinically significant, and 95.2% were alloantibodies. Positive antibody screens were significantly associated with delayed surgery and special efforts needed to obtain blood. Of those institutions with a specific protocol in place to collect T&S samples prior to hospital admission, the median laboratory completed the T&S at least 1 day prior to surgery 74% of the time. When the institution coupled the T&S collection protocol with T&S collection earlier than 3 days prior to surgery, the median laboratory completed the T&S at least 1 day prior to surgery almost 87% of the time. Type and screen collection less than 3 days prior to surgery resulted in special efforts needed to obtain blood more than 1% of the time. Type and screen collected on the same day as surgery directly resulted in a surgery delay 0.8% of the time. CONCLUSIONS: Patients are unnecessarily being placed at risk by inadequate mechanisms to ensure available blood for surgery. All T&Ss were collected for scheduled surgeries with adequate opportunity for a T&S to be completed in advance of the surgery. Specific protocols helped improve the performance in terms of completing the T&S prior to surgery, as did mechanisms that permitted T&S collections in advance of the admission. Type and screen collection time relative to surgery was significantly associated with the incidence of surgery delay due to unavailable blood; the less time between collection and surgery, the less likely blood was available.

Accreditation↗

A critical review of periodic health screening using specific screening criteria. Part 4: selected miscellaneous diseases.

Despite the increasing interest in recent years in prevention and early recognition of asymptomatic disease, an objectively based program for periodic health screening of asymptomatic adults has yet to be proposed for the primary care physician. This is the last in a series of four articles which have critically examined the feasibility of screening procedures for 36 selected diseases. Six basic criteria are adopted as necessary to justify periodic screening. Specific screening recommendations are made for each disease, and a longitudinal screening program for asymptomatic adults is proposed. Cost and patient education are two important factors in any viable screening program.

Adult↗