ABSTRACT
Previous studies of genome sequencing (GS) in critically ill childrenhave made use of either modified hardware or working procedureswhich would be difficult, if not impossible, to integrate into existingclinical workflows1. Our lab’s transition from exome sequencing (ES) to GS offered an opportunity to implement in-house rapid genomesequencing (rGS) in critically ill children in a manner which couldintegrate with existing clinical workflows. We conducted a feasibilityand implementation pilot by offering rGS to child-parent triosconcurrently undergoing clinical rapid ES (rES) via a reference lab.The purpose of this study was to identify and address operationalbarriers to implementation of a rGS program capable of communicatinga preliminary result within 7 days of consent. We consideredthis time span to be more reflective of clinical realities than lab-quotedturnaround times (TAT) which typically start at sample receipt andthus do not account for challenges in sample acquisition and pre-testcounseling in a critical care setting, nor the impact of shipping times.Here we present data on TAT and lessons learned from the first 27subjects enrolled.Using rapid cycle improvement methodologies, we identified fourdistinct but inter-related workflows requiring optimization:1. Pre-analytic: patient identification through acquisition ofsamples2. Wet-lab: extraction through sequencing3. Bioinformatics: secondary and tertiary analysis as well as rapididentification of causal variants4. Return of resultsFigure 1 summarizes TAT across cases, demonstrating the markedimprovements in TAT with our programmatic approach to improvement.We used our first 9 cases to determine a baseline TAT for theentire process and to delineate the 4 main workflows (above). Atbaseline, excluding cases delayed by COVID-19 restrictions, mean TATwas 17.12 days (3 sequential deviant range: 7.05–27.19 days).Following deployment of our programmatic approach to rGS, meanTAT fell to 6.19 days (3 sequential deviant range: 0.51–11.87 days).Table 1 summarizes the observations and insights, by workflow, whichimpacted upon TAT and/or implementation. The single biggest impacton TAT was optimization of bioinformatics by removing all manualsteps between starting sequencing and producing human interpretable,filtered, annotated output of high-priority variants for interpretation.The second biggest source of improvement was optimization ofthe sequencing itself as well as prioritizing sample processing for andaccess to sequencing runs. While variant ranking is helpful in identifying causal variants, in 9/10 cases with a diagnostic findingthe causal variant(s)were obvious to the study teamwithin minutes ofviewing the annotated variant list, regardless of variant rank. (Figure Presented) As time required for sequencing and analytic workflows fell, therelative contribution of other workflows to overall TAT shifted and itbecame more obvious that early identification and utilization of thisapproach is very important in lowering overall time to diagnosis(Figure 2). In 6/10 cases with a diagnostic finding, the initial approachof the clinical team was NOT rES (and thus patients were not eligiblefor rGS on a research basis). Had rGS been the initial diagnosticmodality chosen, a diagnosis could have been reached in a median 12days sooner (range 2–28 days). There were also several cases wheresequencing was delayed when one or both parents did not present tothe lab to provide a blood sample in a timely manner. Optimization ofsequencing or analytic workflows cannot meaningfully improveoutcomes either of these situations.Our findings suggest some important considerations for institutionsdeveloping or seeking to improve rapid sequencing programs for acuteand critically ill children: (Table Presented) • Optimization of computational resource utilization and phenotypecuration saves more time than improved variant filtering orprioritization.• Obtaining samples from parents is non-trivial.• Even trained geneticists may fail to recognize appropriatecandidates for rGS.
ABSTRACT
Human history is observing a very horrible and strange situation fighting a very small enemy. The Novel COVID-19 corona virus. On 11 feb 2020 world health organization has declared a name for covid disorder and has said covid as a global public health diease and also as a pandemic due to its worldwide spread. It started as an outbreak in december with its birth place in wuhan people of china has came out as a global public health exigency of worldwide trouble. Corona virus are the group of virus with non segmented, single stranded and positive sence RNA genome. In this narrative review article, reference was taken from different article published in various database. Maximum article including the information of pregnancy and covid-19 were reviewed. A review of 11article with world health organization site information it is found that the symptoms of corona virus disease in non-pregnant occurred indistinguishable to that of gravid mother. There is no information regarding perinatal transmission in parturiency. It has been disclosed that corona virus can cause distress in gravid mother, miscarriage and also fetal distress. In general due to lack of relevant information regarding the effect of corona virus disease on gravidity it is obligatory to have more and more studies in this area.
ABSTRACT
“A lesson learned the hard way is a lesson learned for a lifetime.” Every bad situation hurts;however, it sure does teach us something – a lesson. In the same manner of a new lesson for Human lifetime, history is observing ’The Novel COVID-19 coronavirus’, a very horrible and strange situation created due to fighting with a microscopic enemy. WHO on 11 February 2020 has announced a name for new covid disease as covid-19 and has declared covid as a global public health emergency and subsequently as pandemic because of its widespread. This began as an outbreak in December 2019, with its centre in Wuhan, the People Republic of China has emerged as a public health emergency of international concern. Coronavirus is the group of a virus with non-segmented, single-stranded and positive RNA genome. This bad situation of pandemic creates new scenes in the life of people in a different manner, which will be going to be life lessons for them. Such lessons should be kept in mind for the safety of living beings and many more things. In this narrative review article, reference was taken from a different article published in vari-ous databases which include the view of different authors and writers on the ”Lessons to be learnt from Corona”. © 2020, J. K. Welfare and Pharmascope Foundation. All rights reserved.