Neonatal screening for cystic fibrosis

Cerebral atrophy often coexists with other brain disorders and by itself may alter the pattern of cerebral perfusion. If unrecognized, it may confound diagnoses based on brain single-photon emission tomography (SPET). In this retrospective study, we describe and evaluate criteria for the diagnosis of cerebral atrophy on technetium-99m hexamethylpropylene amine oxime brain SPET studies. The SPET scans of 11 patients with cerebral atrophy and ten controls were evaluated for the presence of a prominent interhemispheric fissure, presence of prominent cerebral sulci, separation of thalamic nuclei, and pronounced separation of caudate nuclei. The SPET studies were interpreted by two independent observers blind to the findings of magnetic resonance imaging, which provided the final diagnosis of cerebral atrophy. The combination of the four scintigraphic signs was accurate in the diagnosis of cerebral atrophy in 95% of the cases and had a sensitivity of 91% and a specificity of 100%.     

Prenatal screening for cystic fibrosis carriers: an economic evaluation

The cloning of the CFTR gene has made it technically possible to avert the unwanted birth of a child with cystic fibrosis (CF). Several large trials offering prenatal CF carrier screening suggest that such screening is practical and that identified carriers generally use the information obtained. Therefore, a critical question is whether the cost of such screening is justified. Decision analysis was performed that used information about choices that pregnant women were observed to make at each stage in the Rochester prenatal carrier-screening trial. The cost of screening per CF birth voluntarily averted was estimated to be $1,320,000-$1,400,000. However, the lifetime medical cost of the care of a CF child in today's dollars was estimated to be slightly>$1,000,000. Therefore, despite both the high cost of carrier testing and the relative infrequency of CF conceptions in the general population, the averted medical-care cost resulting from choices freely made are estimated to offset approximately 74%-78% of the costs of a screening program. At present, if it is assumed that a pregnancy terminated because of CF is replaced, the marginal cost for prenatal CF carrier screening is estimated to be $8,290 per quality-adjusted life-year. This value compares favorably with that of many accepted medical services. The cost of prenatal CF carrier screening could fall to equal the averted costs of CF patient care if the cost of carrier testing were to fall to $100.     

Heparin-bonded circuits: clinical outcomes and costs

The aim of this study was to use meta-analysis to combine the results of numerous studies and examine the impact of heparin-bonded circuits on clinical outcomes and the resulting costs. Heparin-bonded circuits, both ionically and covalently bonded, are examined separately. The results of the study provide evidence that heparin-bonded circuits result in improved clinical outcomes when compared to the identical nonheparin-bonded circuits. These improved clinical outcomes result in subsequent lower costs per patient with their use. However, differences are apparent in the significance and magnitude of these outcomes between ionically and covalently bonded circuits. Covalently bonded circuits provide a greater magnitude and significance of improvement in clinical outcomes than ionically bonded circuits. Total cost savings can be expected to be three times greater with covalently bonded circuits ($3231 versus $1068). It was concluded that the choice regarding the use of a heparin-bonded circuits and the type of heparin-bonded circuit used has the potential to alter clinical outcomes and subsequent costs. Cost consideration cannot be ignored, but clinical benefits should be the main rationale for the choice of cardiopulmonary bypass circuit. This analysis provides evidence that clinical benefits and cost savings can both be derived from use of the same technology-covalently bonded circuits.     

Neonatal screening for cystic fibrosis: result of a pilot study using both immunoreactive trypsinogen and cystic fibrosis gene mutation analyses

We have evaluated a two-tier neonatal cystic fibrosis (CF) screening of immunoreactive trypsinogen (IRT) followed by CFTR gene mutation analysis using a systematic scanning of exons 7, 10, and 11, and, if necessary, by direct DNA sequencing. Over an 18-month period we screened 32,300 neonates born in the western part of Britanny. The first tier, involving IRT screening at 3 days of age, utilizes a low elevation of the trypsinogen level (600 ng/ml), which is highly sensitive. The second tier, which corresponds to the exhaustive screening for mutations in three exons of the gene, is highly specific for this population (Britanny). The false positive rate is very low, and no false negatives have been reported to date. This strategy has allowed the identification of five novel alleles (V322A, V317A, 1806 del A, R553G, G544S).     

Costs, effects, and savings of screening for cystic fibrosis gene carriers

STUDY OBJECTIVE: Evaluating the costs, effects, and savings of several strategies for cystic fibrosis (CF) gene carrier screening. DESIGN: A general model for evaluating prenatal, preconceptional, school, and neonatal carrier screening was constructed. For prenatal and preconceptional screening, two strategies were evaluated: single entry and double entry two step couple screening. Firstly, the Dutch situation was evaluated prospectively; subsequently the results were generalised to other carrier frequencies. SETTING: Prospective simulation model. MAIN RESULTS: Of all screening strategies, neonatal carrier screening gives most carrier couples an informed choice concerning reproduction. If the parents of carrier newborns would not be tested however, prenatal screening detects most carrier couples. Prenatal and single entry preconceptional screening programmes have a favourable cost-savings balance in the Netherlands under a wide range of assumptions. For double entry preconceptional screening and neonatal screening, high enough values of uptake of screening, prenatal diagnosis, and induced abortion are necessary. School carrier screening does not have a favourable cost-savings balance. CONCLUSIONS: If a CF screening programme is judged to be useful on individual and social grounds, costs considerations are no obstacle for prenatal and single entry preconceptional screening.     

A preliminary trial of couple screening for cystic fibrosis: designing an appropriate information leaflet

An information leaflet, inviting participation in an antenatal screening trial for cystic fibrosis, was sent to 388 couples together with the pregnant woman's first clinic appointment. The leaflet pointed out that couples would be treated as a unit and that further action would be taken only if both partners were found to carry mutant alleles. Participants and non-participants were also asked to fill in a questionnaire eliciting their views on the leaflet. Three hundred and twelve (80%) questionnaires were returned and 253 (65%) couples elected to be screened. More than 90% of respondents found the leaflet easy to understand, although about 10% wanted more information on cystic fibrosis. The main reason for entering the trial was to avoid the birth of an affected child, and the main reason for non-entry was opposition to termination of pregnancy. There was little anxiety about the prospect of being screened. However, more than a third of couples mis-identified their risk of both carrying a CF gene, despite the figure of 1 in 600 being explicitly stated in the leaflet.     

Neonatal screening for the cystic fibrosis main mutation delta F508 in Estonia

When patients exhibit Class II defects requiring restoration, the treatment modality and respective preparation requirements may present challenges to the clinician. Aesthetics, chairside time, and expense become factors for the consideration of both dentist and patient. However, a new sonically driven system for the preparation and restoration of proximal defects was recently introduced (SONICSYS, Ivoclar Vivadent, Amherst, NY). This system, composed of diamond-coated tips and prefabricated ceramic inserts, promises to enable clinicians to efficiently, confidently, and expertly prepare and restore Class II defects in a timely, consistent, and cost-efficient manner. This article describes the components of the system and demonstrates its utilization in a case report.     

New therapies for cystic fibrosis

In the decade since the gene responsible for cystic fibrosis (CF) was identified, our understanding of the pathophysiology of CF pulmonary disease has significantly improved. The current model for CF lung disease suggests several levels at which clinical interventions may be made in an attempt to alter the natural course of disease progression. The first part of this review highlights some of the progress made in novel forms of therapy directed at earlier portions of the pathophysiologic cascade such as gene therapy, protein therapy, and ion-transport regulatory therapy. New developments in well-established modes of therapy such as mucolytic therapy, airway clearance therapy, and antibiotic therapy are discussed next. The review concludes with a look at the use of two forms of therapy that have been adapted to CF care, anti-inflammatory therapy and lung transplantation.     

Community-based care in cystic fibrosis: role of the cystic fibrosis nurse specialist and implications for patients and families

Improved survival for cystic fibrosis has rapidly increased over the past four decades, with patients now living well into adult life. With changes in the structure of the National Health Service and the formation of provider units and general practitioner (GP) fund-holding practices, it is important to strengthen links between the hospital and community teams to ensure that the CF patient receives adequate care. Increasingly, treatment is being carried out at home, and this emphasis on home-based therapy demands that parents/carers and patients must acquire the skills and knowledge of complex therapies in order to optimize health. It is the role of the CF nurse specialist (NS) to educate those who will deliver the care, co-ordinate the provision of services at home, liaise with the CF team and community health-care professionals and to support the patient and their carers.     

Self-management of cystic fibrosis: short-term outcomes of the Cystic Fibrosis Family Education Program

This study tested the efficacy of the Cystic Fibrosis Family Education Program, a cystic fibrosis self-management program, on improving participants' knowledge, self-efficacy, self-management behavior, health, and quality of life. A quasi-experimental pretest-posttest nonequivalent comparison group design was employed. Participants made up 104 patient-primary caregiver dyads from the intervention site cystic fibrosis center and 95 from the usual care comparison center. The intervention, a self-paced print curriculum based on social cognitive theory, targeted behavioral capability, self-efficacy, and outcome expectations and was implemented as an integral part of medical care. Parents, early childhood, middle childhood, and adolescents received separate materials on respiratory, nutrition and malabsorption, communication, and coping issues. Significant intervention effects were found on the knowledge scores for caregivers, adolescents, and children; caregiver and adolescent total self-management scores; Child Behavior Checklist total score; one parent coping scale score; the modified NIH score; NIH pulmonary factor 1; and the Brasfield total score. Significant interaction effects were evident in the self-efficacy scores for caregivers and children.     

Lung transplantation for cystic fibrosis

This reprint of an article that first appeared in Nucleonics in 1966 provides a unique perspective of the introduction of the cyclotron into clinical medicine and medical research. The cyclotron offers a potentially powerful tool to biomedical centers. With this accelerator one can produce a variety of short-lived nuclides that are unavailable from other sources.     

Gene therapy for cystic fibrosis: perspectives for the otolaryngologist

Morbidly obese patients are prone to many clinical conditions that can effect anaesthesia. Of major concern to the anaesthetist are difficulties with airway management and abnormalities of cardiorespiratory function. Safe anaesthesia requires an appreciation of potential problems and a thorough understanding of the pathophysiological changes that accompany morbid obesity.     

Mammography screening: prospects and opportunity costs

Health care costs in the United States now consume nearly 15% of the gross domestic product. Continued expansion of health expenditures may have serious economic consequences, including reduction in the standard of living. Health care reform must include cost control without consequent detrimental effects on health status. As a case example, we consider the controversy surrounding mammography screening for premenopausal women. Several literature reviews of published studies suggest that screening of women less than 50 years of age does not statistically significantly reduce mortality from breast cancer. These results are not explained by screening interval, recentness of study, or patient compliance to screening. We conclude that screening is effective in decreasing mortality from breast cancer for women older than 50 years. For women less than 50, mammography screening programs displace resources that could have a greater benefit in women's health status if used for other purposes.     

Pediatric and adult lung transplantation for cystic fibrosis

OBJECTIVE: This paper was undertaken to review the experience at our institution with bilateral sequential lung transplantation for cystic fibrosis. METHODS: Since 1989, 103 bilateral sequential lung transplants for cystic fibrosis have been performed (46 pediatric, 48 adult, 9 redo); the mean age was 21 +/- 10 years. Cardiopulmonary bypass was used in all but one pediatric (age <18) transplant, and in 15% of adults. RESULTS: Hospital mortality was 4.9%, with 80% of early deaths related to infection. Bronchial anastomotic complications occurred with equal frequency in the pediatric and the adult populations (7.3%). One- and 3-year actuarial survival are 84% and 61%, respectively (no significant difference between pediatric and adult age groups; average follow-up 2.1 +/- 1.6 years). Mean forced expiratory volume in 1 second increased from 25% +/- 9% before transplantation to 79% +/- 35% 1 year after transplantation. Acute rejection occurred 1.7 times per patient-year, with most episodes taking place within the first 6 months after transplantation. The need for treatment of lower respiratory tract infections occurred 1.2 times per patient in the first year after transplantation. Actuarial freedom from bronchiolitis obliterans was 63% at 2 years and 43% at 3 years. Redo transplantation was performed only in the pediatric population and was associated with an early mortality of 33%. Eight living donor transplants (four primary transplants, four redo transplants) were performed with an early survival of 87.5%. CONCLUSION: Patients with end-stage cystic fibrosis can undergo bilateral lung transplantation with morbidity and mortality comparable to that seen in pulmonary transplantation for other disease entities.