Microbiology of cystic fibrosis persons not chronically infected with P. aeruginosa: A quasi-experimental study on two different upper airways' sampling methods.

Background: The upper airways of cystic fibrosis (CF) persons are an evolutionary niche where genetically adapted bacterial strains are selected for lung infection. The microbiological studies conducted up to now on the upper airways are not easily comparable. Methods: Using classical culture methods, we simultaneously studied the microbiological status of upper and lower airways in persons not chronically infected with P. aeruginosa. Each person had a single upper airways sampling and a concomitant lower airways sampling. Lower airways sampling was performed by oropharyngeal swab or sputum collection. Using a quasi-experimental design of study, we evaluated the performance of 2 different upper airways' sampling methods, nasal lavage according to method described by Mainz or nasal lavage with a rhino-set. Pain was measured with appropriate scales. Results: A total of 194 persons were enrolled in this study. Pathogenic flora was found in 128 (6.6%) of 194 upper airways samples and in 164 (84.6%) lower airways samples. A statistically significant difference between the upper airways and the lower airways was found in the isolation of S. aureus and non-fermenter gram negatives. Nasal lavage according to Mainz resulted in the isolation of more non-fermenter gramnegatives than the rhino-set (p < 0.05). No differences were found in the pain caused bythe two methods. Conclusions: In our study population, cultures of the upper airway and lower airway differ in CF persons. In people sampled with nasal lavage according to Mainz more non-fermenter gram negatives were detected than with rhino-set. The two sampling methods were comparable with regard to the caused pain, nasal lavage according to Mainz method being quicker to perform.

Can percussive intrapulmonary ventilation improve the efficacy of physiotherapy in children with cystic fibrosis?

Lung disease in cystic fibrosis (CF) is characterized by reduced mucociliary clearance, airway plugging, recurrent infections, and chronic pulmonary inflammation. Patients who are affected undergo daily respiratory physiotherapy to improve airway clearance. Intrapulmonary percussive ventilation (IPV) is a technique used in clinical practice, but it is not commonly used in CF patients. Evidence for various respiratory pathologies, particularly in children, is still lacking. We present the case of an 11-year-old boy with cystic fibrosis who did not respond to traditional respiratory physiotherapy techniques. We proposed and tested the use of IPV during hospitalization. In this case, the use of IPV in physiotherapy treatment reduced the need for intravenous antibiotics, hospitalization, and improved radiologic features. IPV can be used successfully in CF patients who are resistant to traditional physiotherapy techniques.

Nutritional Status and Circulating Levels of Fat-Soluble Vitamins in Cystic Fibrosis Patients: A Cohort Study and Evaluation of the Effect of CFTR Modulators.

BACKGROUND: Improved therapy in CF has led to an overall improvement in nutritional status. The objectives of our study are: to cross-sectionally assess nutritional status and serum levels of fat-soluble vitamins; to retrospectively evaluate the efficacy of modulators on nutritional status and fat-soluble vitamin levels. METHODS: In patients younger than 2 years of age, we evaluated growth, in patients aged 2-18 years, we assessed BMI z-scores, and in adults, we assessed absolute BMI values. Levels of 25(OH)D, vitamins A, and E were measured. RESULTS: A cross-sectional analysis was conducted on 318 patients, 109 (34.3%) with pancreatic sufficiency. Only three patients were under 2 years old. In 135 patients aged 2-18 years, the median BMI z-score was 0.11, and 5 (3.7%) patients had malnutrition (z-score ≤ 2SD). In 180 adults, the median BMI was 21.8 kg/m2. Overall, 15 (13.7%) males (M) and 18 (25.3%) females (F) were underweight (18 < BMI > 20); 3 (2.7%) M and 5 (7.0%) F had a BMI < 18. Suboptimal 25(OH)D levels were found in patients with pancreatic insufficiency. The prevalence of deficiency of vitamins A and E is low. After one year of treatment with modulators, the increase in BMI was more consistent (M: 1.58 ± 1.25 kg/m2 F: 1.77 ± 1.21 kg/m2) in elexacaftor/tezacaftor/ivacaftor (ETI)-treated patients compared with other modulators, with a significant increase in levels of all fat-soluble vitamins. CONCLUSIONS: Malnutrition is present in a limited number of subjects. The prevalence of subjects with suboptimal 25(OH)D levels is high. ETI showed a beneficial effect on nutritional status and circulating levels of fat-soluble vitamins.

Early Effects of Elexacaftor-Tezacaftor-Ivacaftor Therapy on Magnetic Resonance Imaging in Patients with Cystic Fibrosis and Advanced Lung Disease.

This is a prospective, observational study involving three Cystic Fibrosis (CF) adult patients, evaluating the changes in chest magnetic resonance imaging (MRI) three months after the start of elexacaftor/tezacaftor and ivacaftor therapy. MRI showed a drastic reduction in mucus plugging and bronchial wall thickening, with an improvement in the diffusion-weighted MRI score. Similarly, a marked improvement in spirometric parameters, nutritional status, and sweat chloride was observed. Our preliminary data confirm that chest MRI could be a useful tool to assess disease progression in CF patients on modulatory drug therapy.

State-of-the-art review of lung imaging in cystic fibrosis with recommendations for pulmonologists and radiologists from the "iMAging managEment of cySTic fibROsis" (MAESTRO) consortium.

OBJECTIVE: Imaging represents an important noninvasive means to assess cystic fibrosis (CF) lung disease, which remains the main cause of morbidity and mortality in CF patients. While the development of new imaging techniques has revolutionised clinical practice, advances have posed diagnostic and monitoring challenges. The authors aim to summarise these challenges and make evidence-based recommendations regarding imaging assessment for both clinicians and radiologists. STUDY DESIGN: A committee of 21 experts in CF from the 10 largest specialist centres in Italy was convened, including a radiologist and a pulmonologist from each centre, with the overall aim of developing clear and actionable recommendations for lung imaging in CF. An a priori threshold of at least 80% of the votes was required for acceptance of each statement of recommendation. RESULTS: After a systematic review of the relevant literature, the committee convened to evaluate 167 articles. Following five RAND conferences, consensus statements were developed by an executive subcommittee. The entire consensus committee voted and approved 28 main statements. CONCLUSIONS: There is a need for international guidelines regarding the appropriate timing and selection of imaging modality for patients with CF lung disease; timing and selection depends upon the clinical scenario, the patient's age, lung function and type of treatment. Despite its ubiquity, the use of the chest radiograph remains controversial. Both computed tomography and magnetic resonance imaging should be routinely used to monitor CF lung disease. Future studies should focus on imaging protocol harmonisation both for computed tomography and for magnetic resonance imaging. The introduction of artificial intelligence imaging analysis may further revolutionise clinical practice by providing fast and reliable quantitative outcomes to assess disease status. To date, there is no evidence supporting the use of lung ultrasound to monitor CF lung disease.

Cystic fibrosis in Tuscany: evolution of newborn screening strategies over time to the present.

BACKGROUND: Cystic fibrosis (CF) is a life-threatening disease affecting about 1:3000 newborns in Caucasian populations. The introduction of newborn screening for cystic fibrosis (CF NBS) has improved the clinical outcomes of individuals with CF through early diagnosis and early treatment. NBS strategies have been implemented over time. CF NBS was introduced extensively in 1984 in Tuscany, a region with 3.7 million people, characterized by a high allelic heterogeneity of CFTR gene. AIM AND METHODS: The aim of the study is to present the results from 34 years (1984-2018) of CF NBS, retrospectively evaluating the sensitivity, specificity and predictive values of the tests. In particular, we studied the impact of the introduction of DNA molecular analysis in NBS in a region with high allelic heterogeneity, such as Tuscany. RESULTS: Over these 34 years, 919,520 neonates were screened, using four different NBS strategies. From 1984 to 1991, CF NBS was performed by the determination of albumin on dried meconium (sensitivity 68.75%; specificity 99.82%). Subsequently, the analysis of immunoreactive trypsinogen on a blood spot was adopted as CF NBS protocol (sensitivity 83.33%; specificity 99.77%). From 1992 to 2010, this strategy was associated with lactase meconium dosage: IRT1/IRT2 + LACT protocol (sensitivity 87.50%; specificity 99.82%). From 2011, when the existing algorithm was integrated by analysis of CF causing variants of the CFTR gene (IRT1/IRT2 + LACT + IRT1/DNA protocol), a substantial improvement in sensitivity was seen (senisitivity 96.15%; specificity 99.75%). Other improved parameters with DNA analysis in the NBS programme, compared with the previous method, were the diagnosis time (52 days vs. 38 days) and the recall rate (0.58 to 0.38%). CONCLUSION: The inclusion of DNA analysis in the NBS was a fundamental step in improving sensitivity, even in a region with high allelic variability.

Clinical and Genotypical Features of False-Negative Patients in 26 Years of Cystic Fibrosis Neonatal Screening in Tuscany, Italy.

Cystic fibrosis (CF) is a life-threatening and common genetic disorder. Cystic fibrosis newborn screening (CF NBS) has been implemented in many countries over the last 30 years, becoming a widely accepted public health strategy in economically developed countries. False-negative (FN) cases can occur after CF NBS, with the number depending on the method. We evaluated the delayed diagnosis of CF, identifying the patients who had false-negative CF NBS results over 26 years (1992-2018) in Tuscany, Italy. The introduction of DNA analysis to the newborn screening protocol improved the sensitivity of the test and reduced the FNs. Our experience showed that, overall, at least 8.7% of cases of CF received FNs (18 cases) and were diagnosed later, with an average age of 6.6 years (range: 4 months to 22 years). Respiratory symptoms and salt-loss syndrome (metabolic hypochloremic alkalosis) are suggestive symptoms of CF and were commons events in FN patients. In Tuscany, a region with a high CFTR allelic heterogeneity, the salt-loss syndrome was a common event in FNs. Therefore, we provided evidence to support the claim that the FN patients had CFTR mutations rarer compared with the true-positive cases. We underline the importance of vigilance toward clinical manifestations suggestive of CF on the part of the primary care providers and hospital physicians in a region with an efficient newborn screening program.

Defining research priorities in cystic fibrosis. Can existing knowledge and training in biomedical research affect the choice?

The aim of this report is to assess whether the research issues priorities are perceived differently according to the Stakeholders (SH)'s individual knowledge of research topics and degree of training in biomedical research. Four groups of SH were enrolled in this study: 1. Skilled SH, specifically trained in biomedicine; 2. Unskilled untrained SH who responded to a written questionnaire in 2015; 3. SH who were trained for one year in a course delivered by professionals; 4. Untrained SH who responded to an online questionnaire in 2017. The large ranking order variability observed among groups addresses the question that the choices are markedly influenced by the SH's backgrounds. Such results emphasize the need to consider the education level and the delivery of ad hoc training activities by professionals to broaden the base of SH who may be considered qualified to transfer the Patient Centered Outcome Research principles into practice.

A 1-m distance is not safe for children with cystic fibrosis at risk for cross-infection with Pseudomonas aeruginosa.

Although maintaining a distance of 1 m between persons with cystic fibrosis (CF) is a universal recommendation to prevent respiratory cross-infections such as Pseudomonas aeruginosa, evidence supporting this preventive measure is scarce. Examining 336 samples from 42 patients with CF collected experimentally from sterile surfaces after speaking and coughing, we found that transmission of P aeruginosa beyond 1 m is possible during both talking and coughing, although the probability is low (1.7%).

Use of non-conventional nurses' attire in a paediatric hospital: a quasi-experimental study.

AIMS: To test the impact of a multi-coloured non-conventional attire on a population of children admitted to a paediatric hospital. DESIGN: Quasi-experimental before-after controlled study. BACKGROUND: It has been suggested that non-conventional nurses' uniforms in paediatric settings may contribute to lowering children's distrust towards healthcare providers and reduce fear. Little formal research has investigated on the impact of nursing attire in a paediatric setting. No study has so far analysed the effects in actual use of a non-conventional, other than the traditional type of uniform, on a paediatric hospitalised population. Design: A quasi-experimental study. METHODS: We introduced multi-coloured nurses' attire in two wards of a paediatric hospital. Using open questions and semantic differential scales (SDS), we evaluated the effects of this non-conventional attire on a group of hospitalised children, compared to sex-and-age-matched controls interviewed before the introduction. Parents were also interviewed. RESULTS: One hundred and twelve hospitalised children and their parents (n = 112) were studied. The percentage of positive words used by children to define their nurse was higher in children interviewed after the introduction of non-conventional uniforms (96.2% vs. 81.8%, p = 0.01). Children's perception of nurses was significantly improved by the use of multi-coloured attire ('bad'-'good' SDS: p = 0.01; 'disagreeable'-'nice' SDS: p = 0.001). Children's perceptions regarding hospital environment did not change. Parents' perception of nurses' uniform adequacy to the role and capability to reassure resulted improved (p < 0.0001, p = 0.0003). CONCLUSIONS: Multi-coloured non-conventional attire were preferred by hospitalised children and their parents. Their introduction improved the perception children have of their nurses. Moreover, the coloured uniforms improve the parents perception about the reliability of the nurse. RELEVANCE TO CLINICAL PRACTICE: The use of non-conventional nurses' attire can contribute to improve the child-nurse relation, which has the potential to ease the discomfort experienced by children due to hospitalisation.

[Voluntary incident reporting by nurses in a pediatric hospital: a pilot study]. / La segnalazione volontaria di eventi awersi da parte di infermieri in un ospedale pediatrico: studio pilota.

UNLABELLED: In recent years Voluntary Incident Reporting (VIR) has spread as a tool to monitor and prevent adverse events in healthcare (AE). In Italy, experiences of VIR are limited. AIM: The goals of this pilot study were to test the feasibility of a VIR system in a population of nurses of a Pediatric Hospital and to make a preliminary survey of situations of risk for patients' safety, to plan corrective actions. METHODS: Nurses of 3 wards were asked to report AEs with or without harm for patient, near misses and unsafe behaviours or situations at risk for generating AEs. Results were cumulatively reported to participating nurses during ward's meetings and possible corrective interventions were discussed. RESULTS: The study was carried out from April to August 2006. Eighty-seven nurses participated. Forty-eight reports were made (one third signed, two thirds anonymous). Twenty reports (41.6%) regarded unsafe behaviours or situations at risk for AEs, 11 near misses, 15 AEs without patient harm and 2 AEs with harm. Twenty-three reports involved patients. Reports regarded mainly therapy (62.5%), care delivery (14.5%), equipment (8.3%), clinical documentation (6.3%). 40% of all AEs and near misses were reported to happen during the first or the last hour of the shift. AEs most frequently reported were: missing administration of treatments, administration of a wrong drug or of a wrong dose. "Look-alike" drugs and incomplete or illegible prescriptions. CONCLUSIONS: Our pilot study confirms that nurses are generally willing to get involved in VIR systems. It also suggests that to succeed VIR systems have to ensure that reporters remain anonymous and non-prosecutable.