Planning the development of cystic fibrosis gene carrier screening

OBJECTIVES: It is now possible to test individuals to assess their cystic fibrosis gene carrier status and a range of strategies for screening the population have been piloted. The objective of this research was to develop a planning framework which health care planners and purchasers can use to assess the overall quantifiable outcomes and direct costs resulting from a year of alternative screening strategies and the ways costs and outcomes evolve over time. Beyond broader ethical and clinical considerations the information provided by such a framework is needed to support decisions surrounding the development of screening programmes. DESIGN: Operational Research modelling techniques were used to develop the planning framework. To help illustrate the framework it was then used to assess the quantifiable outcomes and direct costs of three of the main alternative screening strategies: from antenatal clinics, '2-step' screening where females are tested first followed by a screening invitation to the partners of female carriers, and 'couple' screening where both partners must agree to be tested at the outset; and from primary practice clinics 'active' contact of attenders. Quantifiable outcomes are defined as the number of individuals informed of their carrier status and the number of carriers, carrier couples, and affected fetuses detected. Direct costs are those associated with the recruitment and testing of individuals and the subsequent counselling of any gene carriers or carrier couples identified. Results are based on services for a resident population of 250,000 at two time points, year one and a year at 'steady state'. RESULTS: The resultant framework estimates the number of individuals tested using data on the size of the target population, the proportion of that population alerted to the screening service, and the proportion who agree to be tested when approached. Given service users, prevalence data are used to assess service outcomes. Given the number of individuals approached and the subsequent demands for services, service costs can be estimated. Preliminary results indicate that in the short-term health care purchasers and planners who favour screening are likely to opt for antenatal strategies. Although the high coverage of the primary practice strategy leads to high outcomes in year one, relative to the antenatal strategies, it also leads to very high costs. At 'steady state', cost and outcome differences between the strategies are less marked. CONCLUSION: This paper provides a framework which can be used to provide information to support decision-making surrounding the development of screening services. The methodology fills an important void in the literature and complements research elsewhere by health economists and by geneticists and their research colleagues. Preliminary findings based upon use of the approach demonstrate the need for continued research to further refine and improve the methodology.     

Menstrual dysfunction in cystic fibrosis

Several factors potentially involved in the menstrual dysfunction of some females with cystic fibrosis were analyzed by a retrospective chart review. The mean age of menarche for the cystic fibrosis patients was 14.4 years, compared to 12.9 years for American females (p less than 0.001). At last evaluation, comparison of the mean figures for amenorrheic patients and for menarchal cystic fibrosis patients reveals statistically significant differences in the age of diagnosis, weight-height index, weight, height, percent of body fat, weight percentile, and height percentile. The highest correlative was weight (r = 0.59). Of our cystic fibrosis patients who were menarchal, 95% had a weight greater than 82 pounds, whereas 75% of those who were amenorrheic weighed less than 82 pounds. Menstrual irregularities, sexual activity, and contraceptive use among these patients also is discussed.     

Endocrine complications of cystic fibrosis

Patients with cystic fibrosis (CF) are now living longer, with a median survival of 32 years in 2000. With longer life expectancy and improved treatments for pulmonary disease, other complications of CF are becoming more apparent. The primary endocrine complications affecting adolescents with CF include (1) poor growth and pubertal development, (2) CF-related diabetes, and (3) poor bone mineralization. This chapter discusses pathophysiology, screening, and treatment of endocrine complications of CF.     

Newborn screening for cystic fibrosis in the Netherlands

- Dutch newborns have been screened for cystic fibrosis (CF) in the neonatal heel-prick screening programme since May of 2011.- Neonatal screening is beneficial to health because early treatment of patients with CF results in growth and nutritional statuses being almost equivalent to those of healthy children. These patients retain a good lung function longer, need fewer invasive treatments and have a better survival rate. Screening also offers parents the option of family planning. In addition, screening for CF is cost-effective.- There are also disadvantages, however: an abnormal test result can lead to anxiety and uncertainty; also, current screening methods result in many false-positive test results and in identification of healthy carriers and children with atypical CF.- The Dutch screening programme consists of two biochemical measurements of immunoreactive trypsinogen (IRT) and pancreatitis-associated protein (PAP). If both concentrations are elevated, DNA mutation analysis is performed and, if necessary, sequencing of the entire cystic fibrosis transmembrane conductance regulator (CFTR) gene.- This four-step approach has a very high specificity and positive predictive value; therefore, the benefits outweigh the disadvantages. Children with CF and with meconium ileus may nevertheless be missed, because they may have normal IRT and PAP levels.