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

Diagnostics ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 446 ◽  
Author(s):  
Giovanni Taccetti ◽  
Matteo Botti ◽  
Vito Terlizzi ◽  
Maria Chiara Cavicchi ◽  
Anna Silvia Neri ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Dna Analysis ◽  
Screening Program ◽  
Genetic Disorder ◽  
False Negative ◽  
Clinical Manifestations ◽  
Primary Care Providers ◽  
Developed Countries ◽  
Care Providers

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.

scholarly journals The first five-year evaluation of cystic fibrosis neonatal screening program in São Paulo State, Brazil

2020 ◽  
Vol 36 (10) ◽  
Author(s):  
Léa Maria Zanini Maciel ◽  
Patrícia Künzle Ribeiro Magalhães ◽  
Ieda Regina Lopes Del Ciampo ◽  
Maria Luísa Barato de Sousa ◽  
Maria Inez Machado Fernandes ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Screening Program ◽  
False Negative ◽  
Clinical Manifestations ◽  
Sao Paulo ◽  
São Paulo ◽  
Court Order ◽  
Paulo State ◽  
São Paulo State

The Hospital of the Ribeirão Preto Medical School, University of São Paulo is one of the three screening centers in São Paulo State, Brazil, and has included a test for cystic fibrosis (CF) since February 6, 2010, by a court order. We evaluated the first five years of this CF-newborn screening program. The original immunoreactive trypsinogen (IRT)/IRT screening protocol was adopted in Brazil. A total of 173,571 newborns were screened, 1,922 (1.1%) of whom showed IRT1 ≥ 70ng/mL. Of these, 1,795 (93.4%) collected IRT2, with elevated results (IRT2 ≥ 70ng/mL) in 102 of them (5.2%). We identified a total of 26 CF cases during this period, including three CF cases that were not detected by the CF-newborn screening. The incidence of the disease among the screened babies was 1:6,675 newborns screened. Median age at the initial evaluation was 42 days, comparable to that of neonates screened with the IRT/DNA protocol. Almost all infants with CF already exhibited some manifestations of the disease during the neonatal period. The mutation most frequently detected in the CF cases was F508del. These findings suggest the early age at the beginning of treatment at our center was due to the effort of the persons involved in the program regarding an effective active search. Considering the false negative results of CF-newborn screening and the early onset of clinical manifestations of the disease in this study, pediatricians should be aware of the diagnosis of CF even in children with negative test.

Neonatal Screening for Cystic Fibrosis: Position Paper

PEDIATRICS ◽  
1983 ◽  
Vol 72 (5) ◽  
pp. 741-745 ◽  
Author(s):  
◽  
Lynn M. Taussig ◽  
Thomas F. Boat ◽  
Delbert Dayton ◽  
Norman Fost ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Neonatal Screening ◽  
Task Force ◽  
Genetic Disorder ◽  
Clinical Manifestations ◽  
Screening Tests ◽  
Current Status ◽  
Screening Methods ◽  
Asymptomatic Patients

Neonatal screening represents the search for a disorder in a general newborn population. The purpose of screening may be to improve the health of the affected infant, to provide counseling, or for research. Screening tests have been widely accepted for conditions such as phenylketonuria, hypothyroidism, and other metabolic conditions. Cystic fibrosis (CF) is the most common lethal genetic disorder among the white population (with a lower incidence among blacks), and thus there has been interest in screening newborns for CF1 However, proposals emanating from this interest have remained controversial.2-4 The recent development of a relatively simple test—the dried blood immuno-reactive trypsinogen (IRT) assay—has increased this interest.5-12 Besides considering technical reliability and validity of newborn screening methods, it is crucial that all other aspects of screening (including medical, ethical, psychosocial, and economic aspects) be rigorously examined before implementing mass screening.13-15 To address these issues the Cystic Fibrosis Foundation convened a Task Force on Neonatal Screening. Although the Task Force considered the current status of the IRT test, it focused on the generally accepted criteria for newborn screening, summarized in the Table,14 and the relationship of these criteria to the present state of knowledge related to CF. The issues identified by the Task Force, are summarized in this paper, and recommendations are presented at the conclusion. EFFECTIVENESS OF PRESYMPTOMATIC TREATMENT Evidence suggesting that the initiation of treatment before clinical manifestations of CF first appear improves prognosis has been controversial. Whereas some studies have yielded supportive data,16 others have not.4 There are no generally accepted treatment protocols for use in symptomatic or asymptomatic patients.

In the loop: Primary care providers' role in newborn screening for cystic fibrosis

2014 ◽  
Vol 47 (15) ◽  
pp. 147-148
Author(s):  
Robin Z. Hayeems ◽  
Fiona A. Miller ◽  
Carolyn J. Barg ◽  
Yvonne Bombard ◽  
Peter Durie ◽  
...  
Keyword(s):  
Primary Care ◽  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Primary Care Providers ◽  
Care Providers

scholarly journals Performance of a Three-Tier (IRT-DNA-IRT) Cystic Fibrosis Screening Algorithm in British Columbia

2020 ◽  
Vol 6 (2) ◽  
pp. 46
Author(s):  
Graham Sinclair ◽  
Vanessa McMahon ◽  
Amy Schellenberg ◽  
Tanya N. Nelson ◽  
Mark Chilvers ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
British Columbia ◽  
Newborn Screening ◽  
Screening Program ◽  
False Negative ◽  
Yukon Territory ◽  
Screening Algorithm ◽  
Sweat Testing ◽  
Cftr Mutations ◽  
Cystic Fibrosis Screening

Newborn screening for Cystic Fibrosis has been implemented in most programs worldwide, but the approach used varies, including combinations of immunoreactive trypsinogen (IRT) and CFTR mutation analysis on one or more specimens. The British Columbia (BC) newborn screening program tests ~45,000 infants per year in BC and the Yukon Territory, covering almost 1.5 million km2 in western Canada. CF screening was initiated using an IRT-DNA-IRT approach with a second bloodspot card at 21 days of age for all CFTR mutation heterozygotes and any non-carriers in the top 0.1% for IRT. This second IRT was implemented to avoid sweat testing of infants without persistent hypertrypsinemia, reducing the burden of travel for families. Over nine years (2010–2018), 401,977 infants were screened and CF was confirmed in 76, and a further 28 were deemed CF screen positive inconclusive diagnosis (CFSPID). Day 21 IRT was normal in 880 CFTR mutation carriers who were quoted a very low CF risk and offered optional sweat testing. Only 13% of families opted for sweat testing and a total of 1036 sweat tests were avoided. There were six false negative CF cases (and three CFSPID) due to a low initial IRT or no CFTR mutations. Although one CFSPID case had a normal repeat IRT result, the addition of the day 21 IRT did not contribute to any CF false negatives.

Thirty-years of screening for cystic fibrosis in East Anglia

2012 ◽  
Vol 97 (12) ◽  
pp. 1043-1047 ◽  
Author(s):  
Jacqui Calvin ◽  
Sarah L Hogg ◽  
Donna McShane ◽  
Sharon Anne McAuley ◽  
Richard Iles ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Dna Analysis ◽  
Screening Programme ◽  
Clinical Investigation ◽  
False Negative ◽  
Outcome Data ◽  
Meconium Ileus ◽  
False Negatives ◽  
Second Tier

BackgroundNewborn screening for cystic fibrosis (CF) relies on the measurement of immunoreactive trypsinogen (IRT) originating from the pancreas. The Norfolk, Suffolk and Cambridgeshire screening programme initially exploited the persistent increase in IRT seen in CF (IRT-IRT protocol) and later changed to include mutation analysis as a second tier test (IRT-DNA-IRT protocol).ResultsDuring a 30 year period 582 966 babies have been screened by IRT-IRT and 147 764 by IRT-DNA-IRT (total 730730), resulting in 296 screen positive cases of CF and 29 false negatives (including 10 false negatives with meconium ileus). Ten missed CF cases were pancreatic insufficient, however all were diagnosed before their first birthday, suggesting that a false negative result did not forestall appropriate clinical investigation. The IRT-DNA-IRT protocol had a much improved positive predictive value (PPV) of 85.9% compared to 67.3% for IRT-IRT, excluding CF babies with meconium ileus. The PPVs increased to 82.2% and 98.2% respectively if only well, term babies were considered. The main factor to account for this improvement in PPV has probably been the incorporation of DNA analysis in the second tier testing.ConclusionsThe diagnosis of screen-positive babies proved difficult in a minority of cases with the classification of some patients changing with evolving phenotype. Our results illustrate the importance of collecting outcome data over a long time period for accurate assessment of the screening programme. This study provides evidence that newborn screening for CF is a valid undertaking that detects 95% of unsuspected CF cases presenting before 3 years of age.

scholarly journals Primary Care Providers’ Experiences Notifying Parents of Cystic Fibrosis Newborn Screening Results

2014 ◽  
Vol 54 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Caitlin Finan ◽  
Samya Z. Nasr ◽  
Erin Rothwell ◽  
Beth A. Tarini
Keyword(s):  
Primary Care ◽  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Primary Care Providers ◽  
Care Providers

COVID-19 may present with an itchy erythematous papular rash: a case report

2020 ◽  
Author(s):  
Alice Serafini ◽  
Peter K. Kurotschka ◽  
Mariabeatrice Bertolani ◽  
Silvia Riccomi
Keyword(s):  
Case Report ◽  
Skin Rash ◽  
Clinical Manifestations ◽  
Primary Care Providers ◽  
Small Scale ◽  
Correct Identification ◽  
Case Detection ◽  
Care Providers ◽  
Early Presentation ◽  
Skin Manifestations

Abstract Background: the most commonly reported clinical manifestations of Coronavirus Disease (COVID- 19) are: fever, fatigue, dry cough, anorexia, myalgias, dyspnoea and sputum production. Other, rarer, manifestations include headache, sore throat, rhinorrhoea, nausea, diarrhoea and olfactory or taste disorders. Two recent small-scale studies suggest the possibility of a skin rash being a clinical presentation of the disease. The purpose of our case report is to bring attention to an atypical presentation of the disease (skin rash) and reflect on the importance of the correct identification of COVID-19 suspicious symptoms as part of the crucial activity of case-finding in primary care.Case presentation: the patient is an Italian 32 years old female nurse who has had several close contacts to COVID-19 cases during her working shifts. On the 13 th March 2020 she developed an itchy erythematous papular rash sparing only her sparing only her face, scalp and abdomen. One week later she developed fever and diarrhoea. During the first week of remote assessment carried out by her General Practitioner (GP), she gradually developed a dry cough, intermittent fever and diarrhoea. At the time of article submission (31 days after the symptoms onset), she has not completely recovered and is still suffering of a dry cough, headache, fatigue and, occasionally, diarrhoea.Conclusions: this study suggest that skin manifestations could be an early presentation of COVID-19 and, during outbreaks, they should be taken into proper account by primary care providers as possibly caused by Sars-Cov-2. Early identification of COVID-19 patients is a crucial part of the strategy of case detection and case isolation, which has shown to be crucial in the reduction of incidence and COVID-19-related mortality. Further research is needed to establish frequency, symptoms, signs, pathogenesis and role in case detection of skin manifestations in COVID-19 patients.

P016 First results from national newborn screening program for cystic fibrosis in the Republic of North Macedonia

2020 ◽  
Vol 19 ◽  
pp. S59
Author(s):  
S. Fustikj ◽  
V. Anastasovska ◽  
D. Plaseska Karanfilska ◽  
L. Spirevska ◽  
M. Pesevska ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Screening Program ◽  
Newborn Screening Program ◽  
First Results ◽  
The Republic
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