scholarly journals 30 year experience of index case identification and outcomes of cascade testing in high-risk breast and colorectal cancer predisposition genes

Author(s):  
Emma R. Woodward ◽  
Kate Green ◽  
George J. Burghel ◽  
Michael Bulman ◽  
Tara Clancy ◽  
...  

AbstractIt is 30 years since the first diagnostic cancer predisposition gene (CPG) test in the Manchester Centre for Genomic Medicine (MCGM), providing opportunities for cancer prevention, early detection and targeted treatments in index cases and at-risk family members. Here, we present time trends (1990–2020) of identification of index cases with a germline CPG variant and numbers of subsequent cascade tests, for 15 high-risk breast and gastro-intestinal tract cancer-associated CPGs: BRCA1, BRCA2, PALB2, PTEN, TP53, APC, BMPR1a, CDH1, MLH1, MSH2, MSH6, PMS2, SMAD4, STK11 and MUTYH. We recorded 2082 positive index case diagnostic screening tests, generating 3216 positive and 3140 negative family cascade (non-index) tests. This is equivalent to an average of 3.05 subsequent cascade tests per positive diagnostic index test, with 1.54 positive and 1.51 negative non-index tests per family. The CPGs with the highest numbers of non-index positive cases identified on cascade testing were BRCA1/2 (n = 1999) and the mismatch repair CPGs associated with Lynch Syndrome (n = 731). These data are important for service provision and health economic assessment of CPG diagnostic testing, in terms of cancer prevention and early detection strategies, and identifying those likely to benefit from targeted treatment strategies.

Author(s):  
Anja Schoeps ◽  
Dietmar Hoffmann ◽  
Claudia Tamm ◽  
Bianca Vollmer ◽  
Sabine Haag ◽  
...  

AbstractBackgroundThe lack of precise estimates on transmission risk hampers rational decisions on closure of educational institutions during the COVID-19 pandemic.MethodsSecondary attack rates (SARs) for schools and day-care centres were calculated using data from state-wide mandatory notification of SARS-CoV-2 index cases in educational institutions and information on routine contact tracing and PCR-testing.FindingsFrom August to December 2020, every sixth of overall 784 independent index cases caused a transmission in educational institutions (risk 0·17, 95% CI 0·14–0·19). In a subgroup, monitoring of 14,594 institutional high-risk contacts (89% PCR-tested) of 441 index cases revealed 196 secondary cases (SAR 1·34%, 1·16–1·54). Transmission was more likely from teachers than from students/children (incidence risk ratio [IRR] 3·17, 1·79–5·59), and from index cases in day-care centres (IRR 3·23, 1·76–5·91) than from those in secondary schools. In 748 index cases, teachers caused four times more secondary cases than children (1·08 vs. 0·25 secondary cases per index, IRR 4·39, 2·67–7·21). This difference was mainly due to a large number of teacher-to-teacher transmissions in day-care centres (mean number of secondary cases 0.66) and a very low number of student/child-to-teacher transmissions in schools (mean number of secondary cases 0.004).InterpretationIn educational institutions, the risk of infection for contacts to a confirmed COVID-19 case is one percent, but varies depending on type of institution and index case. Hygiene measures and vaccination targeting the day-care setting and teacher-to-teacher transmission are priorities in reducing the burden of infection and may promote educational justice during the pandemic.FundingNo particular funding was received for this study.Research in contextEvidence before this studyWe searched PubMed on Jan 27, 2021, without any language restrictions for all articles in which the title or abstract contained the search terms “COVID 19” or “corona”, and “school”, “education*”, or “daycare”, and “transmission”, and “risk”, “attack rate”, or “SAR”, and screened 175 results for original research or reviews on COVID-19 transmission risk in the educational setting. Following a similar strategy, we also searched Google Scholar, SSRN, medRxiv, and the reference lists of identified literature. We found five cohort studies on transmission risk looking at overall 171 index cases and their 6,910 contact persons in Australian, Italian, Irish, Singaporean, and German schools and reporting attack rates between 0% and 3% percent. These five studies were conducted before October 2020 and thus looked at COVID-19 transmission risk in schools before the second wave in Europe.A number of modelling studies from the first wave of COVID-19 provide inconclusive guidance to policy makers. While two publications, one from several countries and one from Switzerland, concluded that school closures contributed markedly to the reduction of SARS-CoV-2 transmission and individual mobility, two other studies, one using cross-country data and one from Japan rated school closures among the least effective measures to reduce COVID-19 incidence rates.Added value of this studyBased on a large data set that emerged from the current public health practice in Germany, which incorporates routine PCR-testing during active follow-up of asymptomatic high-risk contacts to index cases, this study provides a precise estimate of the true underlying SARS-CoV-2 transmission risk in schools and day-care centres. Its analysis also allows for a meaningful examination of differences in the risk of transmission with respect to the characteristics of the index case. We found that the individual risk of acquiring SARS-CoV-2 among high-risk contacts in the educational setting is 1.3%, but that this risk rises to 3.2% when the index case is a teacher and to 2.5% when the index case occurs in a day-care centre. Furthermore, we could show that, on average, teacher index cases produced about four times as many secondary cases as student/child index cases. Despite the relatively small proportion of teachers among index cases (20%), our study of transmission pathways revealed that the majority of all secondary cases (54%), and the overwhelming majority of secondary cases in teachers (78%) were caused by teacher index cases. Of note, most cases of teacher-to-teacher transmission (85%) occurred in day-care centres.Implications of all the available evidenceIn this setting, where preventative measures are in place and COVID-19 incidence rates were rising sharply in the population, we found a low and stable transmission risk in educational institutions over time, which provides evidence for the effectiveness of current preventative measures to control the spread of COVID-19 in schools. The identification of a substantial teacher-to-teacher transmission risk in day-care, but a clearly mitigated child/student–to-teacher transmission risk in schools, indicates the need to shift the focus to hygiene among day-care teachers, including infection prevention during staff-meetings and in break rooms. These findings also strongly support the re-prioritization of vaccination against SARS-CoV-2 to educational staff in day-care.


2021 ◽  
Vol 149 ◽  
Author(s):  
Anja Schoeps ◽  
Dietmar Hoffmann ◽  
Claudia Tamm ◽  
Bianca Vollmer ◽  
Sabine Haag ◽  
...  

Abstract This study aims at providing estimates on the transmission risk of SARS-CoV-2 in schools and day-care centres. We calculated secondary attack rates (SARs) using individual-level data from state-wide mandatory notification of index cases in educational institutions, followed by contact tracing and PCR-testing of high-risk contacts. From August to December 2020, every sixth of overall 784 independent index cases was associated with secondary cases in educational institutions. Monitoring of 14 594 institutional high-risk contacts (89% PCR-tested) of 441 index cases during quarantine revealed 196 secondary cases (SAR 1.34%, 0.99–1.78). SARS-CoV-2 infection among high-risk contacts was more likely around teacher-indexes compared to student-/child-indexes (incidence rate ratio (IRR) 3.17, 1.79–5.59), and in day-care centres compared to secondary schools (IRR 3.23, 1.76–5.91), mainly due to clusters around teacher-indexes in day-care containing a higher mean number of secondary cases per index case (142/113 = 1.26) than clusters around student-indexes in schools (82/474 = 0.17). In 2020, SARS-CoV-2 transmission risk in educational settings was low overall, but varied strongly between setting and role of the index case, indicating the chance for targeted intervention. Surveillance of SARS-CoV-2 transmission in educational institutions can powerfully inform public health policy and improve educational justice during the pandemic.


Endoscopy ◽  
2006 ◽  
Vol 38 (11) ◽  
Author(s):  
A Qasim ◽  
T Tajjudin ◽  
B Zaman ◽  
D Maguire ◽  
J Geoghegan ◽  
...  

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