The Italian external quality assessment program for Cystic Fibrosis sweat chloride test: CFTR modulators and the impact of a new sweat test report form.

Background: The advent of CFTR modulators highlighted that the sweat test (ST) for CF can be used also as an outcome measure for the basic defect of CFTR. Despite the technological advances, ST still remains operator-dependent and its execution should be strongly paired with guidelines. In 2022, due to the advent of CFTR modulators, the Italian CF Society introduced a specific ST report. The aim of the present paper is to discuss the impact of this new report in the 2022-23 round of the Italian External Quality Assessment program for ST (I-EQA-SCT). Methods: The scheme of the I-EQA-SCT is prospective, enrolment is voluntary, the payment of a fee is required and results are shared through a web-facility. Assessment covers analysis, interpretation, and reporting of results. In the 2022-23 round, 2 out of the 3 mock clinical information referred to patients who started modulators. Results: Fourteen laboratories completed the 2022-23 I-EQA-SCT round. Three of them failed in the interpretation of results from these two mock cases and/or used a wrong report not consistent with the more recent Italian Sweat Test Recommendations. Conclusions: The overall results obtained from the laboratories involved in the I-EQA-SCT program clearly showed that the laboratories' qualitative and quantitative performance improved significantly. Results emerged from this round highlighted an issue in the report form used for monitoring patients on CFTR modulator therapy thus stressing the importance of these programs in improving both the performance of lab services and ameliorating the sweat test recommendations.

Unmet needs in countries participating in the undiagnosed diseases network international: an international survey considering national health care and economic indicators.

Background: Patients, families, the healthcare system, and society as a whole are all significantly impacted by rare diseases (RDs). According to various classifications, there are currently up to 9,000 different rare diseases that have been recognized, and new diseases are discovered every month. Although very few people are affected by each uncommon disease individually, millions of people are thought to be impacted globally when all these conditions are considered. Therefore, RDs represent an important public health concern. Although crucial for clinical care, early and correct diagnosis is still difficult to achieve in many nations, especially those with low and middle incomes. Consequently, a sizeable amount of the overall burden of RD is attributable to undiagnosed RD (URD). Existing barriers and policy aspects impacting the care of patients with RD and URD remain to be investigated. Methods: To identify unmet needs and opportunities for patients with URD, the Developing Nations Working Group of the Undiagnosed Diseases Network International (DNWG-UDNI) conducted a survey among its members, who were from 20 different nations. The survey used a mix of multiple choice and dedicated open questions covering a variety of topics. To explore reported needs and analyze them in relation to national healthcare economical aspects, publicly available data on (a) World Bank ranking; (b) Current health expenditure per capita; (c) GDP per capita; (d) Domestic general government health expenditure (% of GDP); and (e) Life expectancy at birth, total (years) were incorporated in our study. Results: This study provides an in-depth evaluation of the unmet needs for 20 countries: low-income (3), middle-income (10), and high-income (7). When analyzing reported unmet needs, almost all countries (N = 19) indicated that major barriers still exist when attempting to improve the care of patients with UR and/or URD; most countries report unmet needs related to the availability of specialized care and dedicated facilities. However, while the countries ranked as low income by the World Bank showed the highest prevalence of referred unmet needs across the different domains, no specific trend appeared when comparing the high, upper, and low-middle income nations. No overt trend was observed when separating countries by current health expenditure per capita, GDP per capita, domestic general government health expenditure (% of GDP) and life expectancy at birth, total (years). Conversely, both the GDP and domestic general government health expenditure for each country impacted the presence of ongoing research. Conclusion: We found that policy characteristics varied greatly with the type of health system and country. No overall pattern in terms of referral for unmet needs when separating countries by main economic or health indicators were observed. Our findings highlight the importance of identifying actionable points (e.g., implemented orphan drug acts or registries where not available) in order to improve the care and diagnosis of RDs and URDs on a global scale.

The Italian External Quality Assessment Program for Cystic Fibrosis Sweat Chloride Test: Does Active Participation Improve the Quality?

(1) Background: Diagnostic testing for cystic fibrosis (CF) is based on a sweat chloride test (SCT) considering the appropriate signs and symptoms of the disease and results of a gene mutation analysis. In 2014, the Istituto Superiore di Sanità (ISS) established a pilot Italian external quality assessment program for CF SCT (Italian EQA-SCT), which is now a third party service carried out by the ISS. (2) Methods: The ongoing scheme is prospective, enrollment is voluntary, and the payment of a fee is required. Results are shared through a dedicated web-facility. Assessment covers the analysis, interpretation, and reporting of results. (3) Results: Thirteen, fifteen, sixteen, and fifteen different laboratories, respectively, participated from 2015 to 2016 and from 2018 to 2019 in the Italian EQA-SCT scheme. Eleven different laboratories participated each year in all four rounds of the Italian EQA-SCT. (4) Conclusions: The overall results obtained from the laboratories participating constantly clearly show that their qualitative and quantitative performance improved significantly. This is due to the opportunity-after receiving the EQA results-to constantly review their performance and address any inconsistencies. We firmly believe that participation in the EQA program will improve the quality of participating laboratories and that EQA participation should become mandatory as a fundamental requirement for laboratory accreditation.

Italian external quality assessment program for cystic fibrosis sweat chloride test: a 2015 and 2016 results comparison.

BACKGROUND: Diagnostic testing in cystic fibrosis (CF) is based on the sweat chloride test (SCT) in the context of appropriate signs and symptoms of disease and results of the gene mutation analysis. In 2014 the Istituto Superiore di Sanità (ISS) established a pilot Italian external quality assessment program for CF sweat chloride test (Italian EQA-SCT). In 2015 this activity was recognized as a third party service carried out by the ISS. The aim of the paper is to compare 2015 and 2016 results and experiences. METHODS: The scheme is prospective; enrollment is voluntary and the payment of a fee is required. Participants are registered and identified by a specific Identification Number (ID) through a dedicated web-facility. Assessment covers analysis, interpretation and reporting of results. RESULTS: Thirteen and fifteen laboratories, participated in the 2015 and 2016 round respectively. Seven laboratories participated constantly from 2014, eleven participated both in 2015 and 2016 and four participated in 2016 for the first time. Variability in scores of chloride titration and heterogeneity in interpretation/reporting results were detected in both rounds. A total of 18 critical errors in chloride titration were made by eight different participants. Four laboratories made errors in chloride titration in 2015 but drastically improved their performance in 2016. In 2016 poor performance criteria were established and adopted. CONCLUSIONS: Even though results show variability in performance of laboratories, constant and mandatory participation may contribute to the improvement of performance and quality reached by laboratory.

The Italian pilot external quality assessment program for cystic fibrosis sweat test.

OBJECTIVES: Sweat chloride test is the gold standard test for cystic fibrosis (CF) diagnosis. In 2014 the Istituto Superiore di Sanità established the Italian pilot external quality assessment program for CF sweat test (IEQA-ST). DESIGN AND METHODS: Ten laboratories, included among the 33 Italian CF Referral Centers, were selected and enrolled on the basis of their attitude to perform sweat test (ST) analysis by using methods recommended by the Italian Guidelines. They received three different sweat-like samples (normal, borderline and pathologic chloride concentration), with mock clinical indications, for analysis according to routine procedures. Assessment, performed by a panel of experts, covered analytical performance, interpretation and reporting of results; categories of "poor" and "satisfactory" performance were not defined. All data were managed through a web utility. RESULTS: The program identified important areas of interest and, in some case, of concern. It is important to underline that results are referred to a small proportion, i.e. about 30%, of Italian laboratories performing CF ST in the context of the Referral Centers. CONCLUSIONS: Data collected highlight the importance of participation in EQA programs as it may improve laboratory/clinical performance; our study represents a model for the setting up of a large-scale EQA scheme for ST.