[Cystic fibrosis carrier screening: a Health technology assessment.] / Lo screening del portatore di fibrosi cistica: una valutazione di Health technology assessment.

This project of Health technology assessment was aimed at defining the impacts of offering a cystic fibrosis (CF) carrier screening to the general population, compared to the current situation, where the test is offered to individuals at high-risk to give birth to a child with CF. Results revealed: i) a lack of robust and updated data; ii) a return on investment up to six years from the screening's introduction, despite important economic and organizational efforts; iii) a general positive attitude of healthcare professionals, people with CF, families and general population; iv) possible issues related to the social impact.

Effectiveness of preconceptional and prenatal cystic fibrosis carrier screening: a systematic review

BACKGROUND: genetic testing for cystic fibrosis (CF) has been offered to people with higher risk of being carrier. OBJECTIVES: to assess the effectiveness of population-based CF carrier screening for adults of reproductive age and its optimal organizational features. DESIGN: systematic review. SETTING AND PARTICIPANTS: MedLine, Embase, Cochrane Library, CINAHL and LILACS (1990-2022) were searched to retrieve primary and secondary studies on adults (16 years and older), with no clinical indication or genetic risk, eligible for genetic testing for CF carrier status. MAIN OUTCOMES MEASURES: attitude to screening, uptake of screening offered, informed reproductive choices. RESULTS: a total of 3,326 records were screened and 292 potentially eligible full-text publications assessed. The review included 71 publications, corresponding to 3 reviews, 40 cohort studies (11 comparative, 29 single-arm), and 6 model studies, published between 1992 and 2021 (median 1998). Only one study compared screening or no screening. This study suggested an association between carrier screening and a lower incidence of CF. Comparative studies examined different approaches for invitation and testing, i.e., settings, target population (individuals/couples, prenatal/preconceptional), how invitations are organized (primary care/maternal hospitals), and format and content of the pre-test information. However, no firm conclusions can be drawn on the impact of these features on informed reproductive choices, uptake, and attitude, because of the limitations of the evidence collected. CONCLUSIONS: the broad heterogeneity of the studies, methodological weaknesses, and the limited transferability of the results mean there is still uncertainty about the effectiveness of preconceptional and prenatal CF carrier screening in the general population.

CADORmed: a tool for internal dose assessment.

CADORmed is a free bespoke Excel® tool for committed effective dose assessment using latest dose coefficients from ICRP OIR publications. The field of application of CADORmed is special monitoring, and it is not available for the dose assessment of chronic exposure. Calculations are made according to EURADOS guidelines and principles (EURADOS report 2013-1). The Chi-squared test for the goodness of fit is made with a scattering factor for type A and type B errors according to the EURADOS report. The Intake is calculated with the maximum likelihood method. Measurements that are below the detection limit are incorporated by the use of an allocated value equal to one-half or one-quarter of the detection limit. The Identification of rogue data can easily be achieved. Advanced options may also be used: mixed ingestion and inhalation, mixture of default absorption types, correction for DTPA treatment, calculation with a new intake and adjustment when the date of intake are unknown. The validation of the tool has been included in the work plan of EURADOS WG 7. The validation plan has been defined and the validation tests completed. All changes are traced in a Quality Assurance document.

International intercomparison on internal dose assessment (ICIDOSE 2017).

Internal dose assessment intercomparison exercises are useful tools: to verify the performance of an internal dosimetry service; to promote the harmonisation of dose assessments; and to identify weaknesses where further improvements are necessary. However, no such international intercomparisons have been performed for more than ten years. In the period May 2014-May 2016, the 'Technical Recommendations for Monitoring Individuals for Occupational Intakes of Radionuclides' were developed on the initiative of the European Commission, and later published within the EC Radiation Protection series, as RP188. In 2017 the Working Group 'Internal Dosimetry' of the European Radiation Dosimetry Group (EURADOS) organised a new intercomparison action, named ICIDOSE 2017, with the main aim of testing the practical applicability of these technical recommendations (RP188). Four case studies were proposed to participants: an artificially created case of inhalation of 60Co to simulate a simple special monitoring case; a real case of inhalation of 125I, with simple routine monitoring; a real and more complex case of incorporation of 234+235+238U, featuring both confirmatory and special monitoring; and a complex real case of an accidental incorporation of 241Am, including multiple administrations of diethylenetriamine pentaacetic acid (DTPA). Results were received from 66 participants from 26 countries; these were compared to reference or recommended solutions, developed for each case based on the application of RP188. In cases 1, 2 and 4 only a small number of results were identified as outliers, with the spread of all the results, expressed as the geometric standard deviation (GSD) of the values, assessed as 1.07, 1.04 and 1.43, respectively. This observed spread of the submitted results was improved from those obtained from similar cases in previous intercomparison exercises, showing that the availability of RP188 contributes to the harmonisation of the internal dose assessment process. There was a much wider spread of results for the uranium case: this case was characterised by an absence of any prior knowledge of the exposure scenario, and participants assumed a range of different exposure pathways and patterns.

Deciding on cystic fibrosis carrier screening: three citizens' juries and an online survey.

Background: Health technology assessment and ethical issues have to be dealt with in deciding on national carrier screening for cystic fibrosis (CF)-the most frequent severe autosomal recessive disease in Caucasian populations and several stakeholders need to be involved. A citizens' jury is one way to ask citizens to deliberate on controversial topics in the interests of a society. The aims of this project were to gather opinions about CF carrier screening through citizens' jury deliberations and to match them with the findings of a large online consultation survey open to the general population, people with CF and families and health professionals. Methods: Three citizens' juries and an online survey were asked: 'Should the Health Service organize screening of the population with the aim of identifying healthy people who may have children with CF?' The jurors had no medical background and no personal or family CF history. The survey was open to people with CF, families, and healthcare professionals. Results: Jurors and survey respondents were in favour of CF carrier screening, mainly considering the severity of CF, the value of informed reproductive choices and the equality of the screening. All the citizens' juries felt positively about the health service actively offer CF carrier screening to provide women and couples of reproductive age equal access and standardized information on the pros and cons. Conclusion: Considering the favourable attitude towards CF screening, the feasibility of CF screening, in terms of best setting, target age and healthcare professionals providing it, should be tested in a clinical trial.

Newborn screening for cystic fibrosis.

Since the late 1970s when the potential of the immunoreactive trypsinogen assay for early identification of infants with cystic fibrosis was first recognised, the performance of newborn blood spot screening (NBS) has been continually assessed and its use has gradually expanded. NBS for cystic fibrosis is a cost-effective strategy and, if standards of care are fully implemented and robust management pathways are in place, has a positive effect on clinical outcomes. In the past decade, NBS has undergone rapid expansion and an unprecedented number of infants with cystic fibrosis have access to early diagnosis and care. Cystic fibrosis NBS has now moved on from the development phase and is entering an era of consolidation. In the future, research should focus on the rationalisation and optimisation of existing programmes, with particular attention to bioethical implications such as unwanted detection of carriers and inconclusive diagnoses.

Report of the European Respiratory Society/European Cystic Fibrosis Society task force on the care of adults with cystic fibrosis.

The improved survival in people with cystic fibrosis has led to an increasing number of patients reaching adulthood. This trend is likely to be maintained over the next decades, suggesting a need to increase the number of centres with expertise in the management of adult patients with cystic fibrosis. These centres should be capable of delivering multidisciplinary care addressing the complexity of the disease, in addition to addressing the psychological burden on patients and their families. Further issues that require attention are organ transplantation and end of life management.Lung disease in adults with cystic fibrosis drives most of the clinical care requirements, and major life-threatening complications, such as respiratory infection, respiratory failure, pneumothorax and haemoptysis, and the management of lung transplantation require expertise from trained respiratory physicians. The taskforce therefore strongly reccommends that medical leadership in multidisciplinary adult teams should be attributed to a respiratory physician adequately trained in cystic fibrosis management.The task force suggests the implementation of a core curriculum for trainees in adult respiratory medicine and the selection and accreditation of training centres that deliver postgraduate training to the standards of the HERMES programme.

Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report.

Newborn screening (NBS) for cystic fibrosis (CF) is increasingly being implemented and is soon likely to be in use throughout the United States, because early detection permits access to specialized medical care and improves outcomes. The diagnosis of CF is not always straightforward, however. The sweat chloride test remains the gold standard for CF diagnosis but does not always give a clear answer. Genotype analysis also does not always provide clarity; more than 1500 mutations have been identified in the CF transmembrane conductance regulator (CFTR) gene, not all of which result in CF. Harmful mutations in the gene can present as a spectrum of pathology ranging from sinusitis in adulthood to severe lung, pancreatic, or liver disease in infancy. Thus, CF identified postnatally must remain a clinical diagnosis. To provide guidance for the diagnosis of both infants with positive NBS results and older patients presenting with an indistinct clinical picture, the Cystic Fibrosis Foundation convened a meeting of experts in the field of CF diagnosis. Their recommendations, presented herein, involve a combination of clinical presentation, laboratory testing, and genetics to confirm a diagnosis of CF.