Current Screening Strategies Research Articles

Evaluation of the Universal Screening Strategy in Qatar for the Management of Pregnant Women Carrying Group B Streptococci

Group B Streptococcus infection (GBS) has emerged as a serious disease, infecting 18,000 people in the United States annually including life-threatening illness in about 8,000 newly-born infants. To evaluate the efficiency of the current universal screening strategy for the management of GBS carriers a retrospective analysis was made of the records of 1,620 pregnant women in Qatar, 550 of whom were found to be carriers. These latter were then used as a group to be compared with 450 uninfected pregnant women in terms of nationality, parity, age, treatment, and outcome. Young and nullipara pregnant women had a high incidence of GBS but there was no significant effect on birth mortality and morbidity regardless of whether or not they received treatment with antibiotics. It is suggested that the cost of screening for GBS at the 35 th week of gestation cannot be justified.

An Analysis of Falls Occurring in Patients with Stroke on an Acute Rehabilitation Unit

Falls are a common occurrence in stroke patients admitted to a rehabilitation unit. This study evaluates the effect of current fall risk screening and prevention strategies on the number of falls in stroke patients admitted to an acute rehabilitation facility. All stroke patients admitted to a designated acute rehabilitation unit were considered at risk for falls by virtue of their diagnosis. These patients were studied retrospectively during a 24-month period. Wheelchair lap belts and bedrails were provided to all patients admitted to the unit. Further measures consisting of bed and chair alarms, enclosed beds, and placement in rooms close to the nursing station were implemented with high-fall risk patients. One hundred seventeen (15.5%) of the 754 patients in this study fell. The fall index rate was 8.2 falls, based on patient care days during the study period. No injury was observed in 143 of 159 fall cases (90%). In 13 cases (8%) there were only minor injuries, and 3 falls (2%) resulted in serious injuries. Current preventive strategies decrease the number of falls and the severity of fall-related injuries. Patients who do fall are cognitively impaired on admission and have lower ambulation speed.

The cost‐effectiveness of cervical screening in Australia: what is the impact of screening at different intervals or over a different age range?

To estimate the cost-effectiveness of altering the currently recommended interval and age range for cervical screening of Australian women. The cost and effectiveness estimates of alternative screening strategies were generated using an established decision model. This model incorporated a Markov model (of the natural history of cervical cancer and pre-cancerous lesions) and decision trees which: 'mapped' the various pathways to cervical cancer screening; the follow-up of abnormal Pap test results; and the management of confirmed lesions. The model simulated a hypothetical large cohort of Australian women from age 15 to age 85 and calculated the accumulated costs and life-years under each screening strategy. Our model estimated that moving from the current two-yearly screening strategy to annual screening (over the same age range) would cost $379,300 per additional life-year saved. Moving from the current strategy to three-yearly screening would yield $117,100 of savings per life-year lost (costs and effects both discounted at 5% per year), with a relatively modest (<5%) reduction in the total number of life-years saved by the program. Although moving to annual screening would save some additional lives, it is not a cost-effective strategy. Consideration should be given to increasing the recommended interval for cervical screening. However, the net value of any such shift to less effective (e.g. less frequent) and less costly screening strategies will require better evidence about the cost-effectiveness of strategies that encourage non-screeners or irregular screeners to have a Pap test more regularly.

The Overlapping Risk Profile Between Dialysis Patients Listed and Not Listed for Renal Transplantation

The survival advantage of kidney transplantation extends to many high-risk ESRD patients; however, numerous factors ultimately determine which patients are evaluated and listed for the procedure. Broad goals of patient evaluation comprise identifying patients who will benefit from transplantation and excluding patients who might be placed at risk. There is limited data detailing whether current access limitations and screening strategies have achieved the goal of listing the most appropriate patients. The study estimated the life expectancy of adult patients in the United States prior to transplantation with ESRD onset from 1995 to 2003. Factors associated with transplant listing were examined based on patient prognosis after ESRD. Approximately one-third of patients listed for transplantation within 1 year of ESRD had </=5-year life expectancy on dialysis. In contrast, one-third of patients not listed had >5-year life expectancy. The number of patients not listed with 'good' prognosis was significantly higher than those listed with 'poor' prognosis (134 382 vs. 16 807, respectively). Age, race, gender, insurance coverage and body mass index (BMI) were associated with likelihood for listing with 'poor' prognosis and not listing with 'good' prognosis. Over the past decade, many ESRD patients viable for transplantation have not listed for transplantation while higher-risk patients have listed rapidly.

Narrow band imaging in Barrett’s esophagus

Barrett’s esophagus is a well-recognized premalignant condition for the development of esophageal adenocarcinoma, the most rapidly rising cancer in the USA and Western Europe. Detection of intestinal metaplasia and neoplasia arising in Barrett’s esophagus patients continues to be a challenge. Limitations of conventional endoscopy with random biopsies provide the necessary impetus for the development of new approaches aimed at improving current screening and surveillance strategies. Narrow band imaging is a novel endoscopic technique that uses a higher intensity of blue light with narrow band filters, which allows a detailed inspection of mucosal and vascular surface patterns with high-level resolution and contrast. Preliminary studies have provided encouraging results for Narrow band imaging alone or in combination with other advanced endoscopic techniques in the screening and surveillance of Barrett’s esophagus patients.

How to understand the dichotomy of antioxidants

One of the most bewildering aspects of antioxidants is that their excellent in vitro activity cannot necessarily be translated into in vivo effect. Through summarizing the recent progresses made in free radical chemistry and biology, this dichotomy is tentatively explained in terms of the heterogeneity of biological systems and the interactions between antioxidants and surrounding molecules in vivo, which also has important implications for updating the current strategies for screening and designing antioxidant drugs.

Risk Assessment for Ectasia after Corneal Refractive Surgery

To analyze the epidemiologic features of ectasia after excimer laser corneal refractive surgery, to identify risk factors for its development, and to devise a screening strategy to minimize its occurrence. Retrospective comparative and case-control study. All cases of ectasia after excimer laser corneal refractive surgery published in the English language with adequate information available through December 2005, unpublished cases seeking treatment at the authors' institution from 1998 through 2005, and a contemporaneous control group who underwent uneventful LASIK and experienced a normal postoperative course. Evaluation of preoperative characteristics, including patient age, gender, spherical equivalent refraction, pachymetry, and topographic patterns; perioperative characteristics, including type of surgery performed, flap thickness, ablation depth, and residual stromal bed (RSB) thickness; and postoperative characteristics including time to onset of ectasia. Development of postoperative corneal ectasia. There were 171 ectasia cases, including 158 published cases and 13 unpublished cases evaluated at the authors' institution. Ectasia occurred after LASIK in 164 cases (95.9%) and after photorefractive keratectomy (PRK) in 7 cases (4.1%). Compared with controls, more ectasia cases had abnormal preoperative topographies (35.7% vs. 0%; P<1.0x10(-15)), were significantly younger (34.4 vs. 40.0 years; P<1.0x10(-7)), were more myopic (-8.53 vs. -5.09 diopters; P<1.0x10(-7)), had thinner corneas before surgery (521.0 vs. 546.5 microm; P<1.0x10(-7)), and had less RSB thickness (256.3 vs. 317.3 microm; P<1.0x10(-10)). Based on subgroup logistic regression analysis, abnormal topography was the most significant factor that discriminated cases from controls, followed by RSB thickness, age, and preoperative corneal thickness, in that order. A risk factor stratification scale was created, taking all recognized risk factors into account in a weighted fashion. This model had a specificity of 91% and a sensitivity of 96% in this series. A quantitative method can be used to identify eyes at risk for developing ectasia after LASIK that, if validated, represents a significant improvement over current screening strategies.

Non-Ketotic Hyperglycinemia is usually not detectable by tandem mass spectrometry newborn screening

Diagnosis of Non-Ketotic Hyperglycinemia by MSMS newborn screening might benefit patients with post-neonatal presentation. We screened 733,527 babies over eight years, and nine babies were subsequently diagnosed with NKHG. Two had newborn glycine levels above our cut-off and presented within 72h. The remaining patients could not have been diagnosed by newborn screening without an unacceptably high recall rate. We conclude that babies with NKHG are not usually identifiable by current newborn screening strategies.

Cellular responses to nanoparticles: Target structures and mechanisms

Nanotechnology makes use of the special surface properties of extremely small particles. In this rapidly growing field, many different materials are produced for a multitude of diverse applications. Possible adverse health effects of these materials however are so far scarcely investigated and are therefore a special task of toxicology. Although strategies for risk assessment have been suggested, the authors of the current review emphasize the fact that on the cellular, subcellular and molecular levels, interactions between nanoparticles (NP) and target cells relevant for the induction of possible adverse health effects are poorly understood. On the basis of existing literature, the potentially most relevant cellular target sites of NP as well as the so far known major molecular events specifically induced by these xenobiotics are reviewed. Starting with NP uptake across the cell membrane, mechanisms of generation of reactive oxygen species and the activation of redox-sensitive signalling cascades are described. Besides the cell membrane, mitochondria and cell nucleus are considered as major cell compartments relevant for possible NP-induced toxicity. Finally, an integrated research protocol is proposed to identify fundamental cellular responses to NP in order to complement current toxicological screening strategies with a mechanism-based approach.

Breast Cancer in Young Women after Treatment with Irradiation for Hodgkin's Lymphoma.

BACKGROUND: Women who are survivors of Hodgkin's Lymphoma (HL) are at increased risk of developing breast cancer (BCa) as a long-term complication due to the use of extended field (mantle) irradiation (RT) of disease above the diaphragm. Many young women are at significantly increased risk of BCa prior to the age at which routine screening mammography is recommended for the general population. The sensitivity of mammography is lower in these women, in part due to increased breast tissue density characteristic of young pre-menopausal women. Currently, there is a paucity of information on the optimal screening modality and surveillance frequency for these women.METHODS: We reviewed the current BCa screening strategies used for this high risk group at our centre and described the incidence, method of detection, and characteristics of secondary BCas in a cohort of 115 women who received supradiaphragmatic RT for HL before age 30 between 1965 and 2000 at Princess Margaret Hospital (PMH) and who subsequently accepted long-term follow-up in a high-risk screening clinic.RESULTS: Median age at treatment was 22 (range 9–30). Radiation fields were mantle in 106 women, modified mantle in 6, and involved field in 3 (median dose delivered: 35 Gy, range 15–60). RT alone was used for 44 patients while 71 received combined modality therapy, of which 45 (65%) received MOPP. Treatment induced amenorrhea occurred in 15 women (median age 38); hormone replacement therapy was subsequently used by 9. Of the 107 women who participated in annual radiographic BCa screening, 95 were screened with mammogram alone, 1 with breast MRI alone, 8 with mammogram and MRI, and 3 with mammogram and ultrasound. Median age at first mammogram was 36; however, median age decreased with more recent year of HL diagnosis (age 40 for women diagnosed before 1985 compared to age 33 for women diagnosed after 1985, p<0.0001). Women with high breast density received MRI screening more often (p=0.02); however, breast density was not significantly associated with previous breast radiation dose or age at last follow-up. Twelve women were diagnosed with BCa in this cohort, following active breast surveillance for a median of 5 years (representing 584 person-years). The 20-year cumulative incidence of breast cancer was 10.9% (95% CI 5.3–18.8%) in this group of women. This was comparable to the 20-year cumulative incidence of breast cancer of 12% (95% CI 8–17%) in all 448 women with HL treated with supradiaphragmatic radiation before age 30 at PMH during the same time period. BCa occurred after a median of 17 years after treatment for HL (range 13–28). Median age at BCa diagnosis was 40 (range 31–51). Seven cancers were detected by physical exam (6 node-positive invasive BCas, 1 in-situ BCa) and 5 were detected on annual mammograms (1 node-positive invasive BCa, 4 in-situ BCas).CONCLUSIONS: Although women in the more recent treatment cohort are receiving their first mammogram at a younger age, the majority of BCas were still detected clinically, and these BCas had less favorable pathological characteristics. More frequent breast imaging should be considered in women who have had supradiaphragmatic RT for HL. Prospective evaluation of breast MRI as a screening strategy for HL survivors has been initiated at PMH in an effort to detect BCa at an earlier stage.

An update on antenatal screening for Down’s syndrome and specific implications for assisted reproduction pregnancies

Since the introduction of antenatal serum screening for Down's syndrome (DS) more than two decades ago, several screening approaches have been utilized in routine clinical practice. The current DS screening strategies involve mid-trimester serum biochemistry tests, first trimester tests combining sonographic markers and serum biochemistry and integration of first and second trimester markers. In this review, we evaluate the performance of DS screening strategies according to the Serum, Urine and Ultrasound Screening Study (SURUSS), the First and Second Trimester Evaluation of Risks (FASTER) Trial and the Serum Biochemistry and Fetal Nuchal Translucency Screening (BUN) Study. We also evaluate the performance of first trimester screening in studies and meta-analyses by other groups. Specific issues related to assisted reproduction technology (ART) pregnancies are also addressed in this review.

Father-to-daughter transmission of Cornelia de Lange syndrome caused by a mutation in the 5′ untranslated region of theNIPBL Gene

Cornelia de Lange syndrome (CdLS; also called Brachmann de Lange syndrome) is a developmental disorder characterized by typical facial dysmorphism, growth and mental retardation, microcephaly, and various malformations. Mutations in the NIPBL gene have been identified in approximately 40% of reported cases, suggesting either genetic heterogeneity or that some NIPBL mutations are not detected by current screening strategies. We screened a cohort of 21 patients with no previously identified NIPBL anomaly for mutations in the 5' untranslated region (5'UTR) and the proximal promoter of the NIPBL gene. We identified a heterozygous deletion-insertion mutation in exon 1, 321 nucleotides upstream of the translation initiation codon (c.-321_-320delCCinsA) in one affected girl and her mildly affected father. This mutation altered highly conserved nucleotides, was not found in 400 control alleles, arose de novo in the father, and cosegregated with the disease in the family. Using real-time quantitative PCR, we showed that NIPBL mRNA expression was lowered in patients' lymphocytes compared to control samples. Finally, we showed that, when subcloned into a luciferase reporter vector, the mutation leads to a significant reduction of reporter gene activity. Our results demonstrate that mutations in the 5' noncoding region of the NIPBL gene can be involved in the pathogenesis of CdLS. Mutations affecting this region of the gene might be associated with a milder phenotype.

The Role of Proteomics in the Diagnosis and Treatment of Ovarian Cancer

Ovarian cancer is the leading cause of gynecologic cancer death in the Western world and more than 70% of patients are diagnosed with advanced stage disease. The high mortality rate is due to the difficulty in the early detection of ovarian cancer. Current screening strategies lack the necessary sensitivity and specificity to reliably and accurately diagnose affected women, prompting investigators to seek alternative means of analysis found in protein pathways and networks. Proteomics seeks to advance the understanding of how proteins interact in cancer and may provide a mechanism for early stage diagnosis. The proteomic techniques of laser capture microdissection, mass spectrometry and tissue lysate arrays have led to the discovery of new biomarkers and the identification, development and approval of a number of targeted therapeutic agents. Following validation through clinical trials, the application of these techniques will contribute to the changing paradigm of cancer detection and treatment toward personalized medicine.

The unrecognized prevalence of chronic kidney disease in diabetes

Diabetes mellitus and chronic kidney disease (CKD) are common and exhibit synergistic associations with premature mortality. Current diabetes guidelines in the UK recommend annual urinary albumin and serum creatinine determinations to screen for diabetic kidney disease. The aim of this study was to estimate the burden of CKD in patients with diabetes and examine the ability of serum creatinine and albuminuria to detect clinically meaningful CKD compared with estimated glomerular filtration rate (eGFR). All adults known to have diabetes in primary and secondary care in Salford, UK, alive with independent renal function on 1 January 2004 were included in this observational study (n=7596). Demographic and laboratory parameters were obtained from the Electronic Patient Record. eGFR was determined using the 4-variable modification of diet in renal disease (MDRD) formula. Clinically meaningful CKD was defined as an eGFR <60 ml/min/1.73 m(2). Creatinine and albuminuria were measured in the preceding 2 years in 82.3 and 55.2% of subjects, respectively. In patients with CKD, normoalbuminuria was present in 48.8%, and serum creatinine was normal (<or=120 micromol/l) in 54.7%. An abnormal serum creatinine (>or=120 micromol/l) had a sensitivity and specificity of 45.3 and 100%, respectively, to identify CKD. The combination of abnormal creatinine and albuminuria had an improved performance but still failed to detect a large number with CKD (sensitivity 82.4%, specificity 75.4%). Serum creatinine failed to identify CKD more often in females (OR 8.22, CI 6.56-10.29). Undiagnosed CKD is common in diabetes. Current screening strategies, based on creatinine or albuminuria, fail to identify a considerable number of subjects with CKD. Incorporating eGFR into screening for CKD would identify individuals earlier in the natural history of the disease and enable early effective treatment to delay progression of CKD.

Bronchoscopy in the diagnosis and surveillance of respiratory infections in lung and heart-lung transplant recipients

Fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) and transbronchial biopsies (TBB) is a widely used method to detect respiratory infections and to differentiate them from other postoperative complications in lung transplant (LTX) recipients, but the usefulness of surveillance FOBs is not yet established. The aim of this study was to evaluate the usefulness of FOB in the diagnosis and surveillance of infections in LTX recipients. We reviewed all the consecutive 609 FOBs performed on 40 lung or heart-LTX recipients between February 1994 and November 2002. The overall diagnostic yield was 115/190 (61%) and 43/282 (15%) for clinically indicated and surveillance FOBs respectively (P < 0.001). Infection was established by bronchoscopic samples in 96/190 (50.5.%) of the clinically indicated FOBs and 34/282 (12.1%) of the surveillance FOBs (P < 0.001). The diagnostic yield of the clinically indicated FOBs was highest (72%) from 1 to 6 months post-transplant (P = 0.04). Pneumocystis carinii was detected in 23 (4.9%) of the bronchoscopic specimens and 15 (65%) of the P. carinii infections were detected during adequate chemoprophylaxis. To conclude, in LTX recipients clinically indicated FOB has a good diagnostic yield in detecting infections and other postoperative complications, whereas the information received from surveillance FOB has remained less significant. With current prophylaxis and screening strategies FOB is still required to detect P. carinii infections.

Diabetes and its prevention: pragmatic solutions for people with schizophrenia.

Patients with schizophrenia have an increased risk of developing diabetes. However, no pragmatic pathway of care has ever been proposed in order to identify individuals at risk and manage that risk effectively. To develop practical recommendations for the screening and management of diabetes in schizophrenia. Staged review of evidence for the under recognition of diabetes in people with schizophrenia and of the applicability of current screening strategies to this population. Recommendations for pragmatic pathways of care were developed. All patients with schizophrenia should be screened and managed as a high-risk group for the development of diabetes. Psychiatrists should be responsible for screening and diabetes risk management; primary care physicians and/or diabetologists should be responsible for managing diabetes. Choice of antipsychotics should be based on achieving good control of schizophrenia, which may improve compliance with diabetes risk reduction strategies. Effective multidisciplinary team working should reduce the burden of diabetes in schizophrenia.

Large deletions of the MECP2 gene detected by gene dosage analysis in patients with Rett syndrome.

MECP2 mutations are responsible for Rett syndrome (RTT). Approximately a quarter of classic RTT cases, however, do not have an identifiable mutation of the MECP2 gene. We hypothesized that larger deletions arising from a deletion prone region (DPR) occur commonly and are not being routinely detected by the current PCR-mediated screening strategies. We developed and applied a quantitative PCR strategy (qPCR) to samples referred for diagnostic assessment from 140 patients among whom RTT was strongly suspected and from a second selected group of 31 girls with classical RTT. Earlier MECP2 mutation screening in both groups of patients had yielded a wild-type result. We identified 10 large deletions (7.1%) within the first group and five deletions in the second group (16.1%). Sequencing of the breakpoints in 11 cases revealed that eight cases had one breakpoint within the DPR. Among seven cases, the breakpoint distant to the DPR involved one of several Alu repeats. Sequence analysis of the junction sequences revealed that eight cases had complex rearrangements. Examination of the MECP2 genomic sequence reveals that it is highly enriched for repeat elements, with the content of Alu repeats rising to 27.8% in intron 2, in which there was an abundance of breakpoints among our patients. Furthermore, a perfect chi sequence, known to be recombinogenic in E. coli, is located in the DPR. We propose that the chi sequence and Alu repeats are potent factors contributing to genomic rearrangement. We suggest that routine mutation screening in MECP2 should include quantitative analysis of the genomic sequences flanking the DPR.

Cervical Cytology Screening and Management of Abnormal Cytology in Adolescent Girls

Human papillomavirus (HPV) infection is highly prevalent in sexually active adolescent and young adult women. Although infection frequently is asymptomatic, it may be associated with the development of condylomata and cervical carcinoma. Recent information about the natural history of HPV infection and abnormal cytology in adolescent and young adult women, as well as the availability of HPV DNA testing and new techniques for cytologic screening, have led to a comprehensive reassessment of current screening and management strategies in young women. In this review we will summarize new data on the natural history of HPV infection and cytology in young women, review the limitations of cervical cytology and resulting new technologies for cytologic screening and HPV DNA testing, and present strategies for cytologic screening and management of abnormal cytology in adolescent and young adult women.

Barrett's esophagus

Barrett's esophagus is an acquired condition resulting from severe esophageal mucosal injury. It still remains unclear why some patients with gastroesophageal reflux disease develop Barrett's esophagus whereas others do not. The diagnosis of Barrett's esophagus is established if the squamocolumnar junction is displaced proximal to the gastroesophageal junction and if intestinal metaplasia is detected by biopsy. Despite this seemingly simple definition, diagnostic inconsistencies remain a problem, especially in distinguishing short segment Barrett's esophagus from intestinal metaplasia of the gastric cardia. Barrett's esophagus would be of little importance were it not for its well-recognized association with adenocarcinoma of the esophagus. The incidence of esophageal adenocarcinoma continues to increase and the 5-year survival rate for this cancer remains dismal. However, cancer risk for a given patient with Barrett's esophagus is lower than previously estimated. Current strategies for improved survival in patients with esophageal adenocarcinoma focus on cancer detection at an early and potentially curable stage. This can be accomplished either by screening more patients for Barrett's esophagus or with endoscopic surveillance of patients with known Barrett's esophagus. Current screening and surveillance strategies are inherently expensive and inefficient. New techniques to improve the efficiency of cancer surveillance are evolving rapidly and hold the promise to change clinical practice in the future. Treatment options include aggressive acid suppression, antireflux surgery, chemoprevention, and ablation therapy, but there is still no clear consensus on the optimal treatment for these patients.

Micromachined nanocalorimetric sensor for ultra-low-volume cell-based assays.

Current strategies for cell-based screening generally focus on the development of highly specific assays, which require an understanding of the nature of the signaling molecules and cellular pathways involved. In contrast, changes in temperature of cells provides a measure of altered cellular metabolism that is not stimulus specific and hence could have widespread applications in cell-based screening of receptor agonists and antagonists, as well as in the assessment of toxicity of new lead compounds. Consequently, we have developed a micromachined nanocalorimetric biological sensor using a small number of isolated living cells integrated within a subnanoliter format, which is capable of detecting 13 nW of generated power from the cells, upon exposure to a chemical or pharmaceutical stimulus. The sensor comprises a 10-junction gold and nickel thermopile, integrated on a silicon chip which was back-etched to span a 800-nm-thick membrane of silicon nitride. The thin-film membrane, which supported the sensing junctions of the thermoelectric transducer, gave the system a temperature resolution of 0.125 mK, a low heat capacity of 1.2 nJ mK(-1), and a rapid (unfiltered) response time of 12 ms. The application of the system in ultra-low-volume cell-based assays could provide a rapid endogenous screen. It offers important additional advantages over existing methods in that it is generic in nature, it does not require the use of recombinant cell lines or of detailed assay development, and finally, it can enable the use of primary cell lines or tissue biopsies.