Proportion Of Positive Cases Research Articles

Analysis of Molecular Testing for Suspected Myeloproliferative Neoplasm at a Hybrid Community-Academic Health System

Testing for somatic mutations in JAK2, MPL, and CALR genes is a crucial element in the diagnosis of myeloproliferative neoplasms (MPN). This may have inadvertently led to increased requests for testing to “rule out MPN,” including clinical situations with low pre-test probability. This paper examines JAK2, MPL, and CALR testing by next generation sequencing (NGS) with the goal of formulating practical guidelines to make test utilization more efficient and effective. NGS results from 1482 patients tested between 2015 and March 2022 were retrieved, along with corresponding bone marrow biopsies and CBC results performed within 90 days prior to NGS and 245 (16.5%) cases were positive for pathogenic variants in JAK2, MPL, or CALR genes.The findings showed an increase in the proportion of positive cases with patient age, and a statistically significant difference in RBC counts and platelet counts among patients with positive versus negative results. Utilizing these factors, simple algorithms were constructed to predict positive results with a maximum sensitivity of 91%, while potentially eliminating 28% of negative tests. However, these models still failed to identify ∼9% of patients with MPNs. Among these “missed” patients, many had either primary myelofibrosis or MDS/MPN. Considering a simple triage model to help guide MPN testing could represent a more cost effective approach, particularly if “missed” patients could be further reduced.

Estimaci´on simultánea de la sensibilidad y la especificidad utilizando la metodolog´ía GSK en presencia de covariables

Sensitivity and specificity are measures used to evaluate the performance of diagnostic tests, not only in the health sector with areas such as epidemiology, psychology, and genetics, but also in other fields such as the banking and financial sector, as well as agronomy. Sensitivity indicates the proportion of positive cases that are correctly detected by the test, in other words, sensitivity measures the effectiveness of the test when used in positive individuals, while specificity indicates the proportion of negative cases that are correctly detected by the test, i.e., it measures the effectiveness of the test when used in negative individuals. For the estimation of both quantities, various authors have proposed different methods such as the ’Gold standard’ test, Bayesian approximation, maximum likelihood, or through logistic models. However, these tests only provide marginal type estimates. In this article, we develop a procedure for simultaneously estimating sensitivity and specificity using the GSK methodology in the presence of covariates.

Evolution of the COVID-19 Pandemic: An Analysis of the Brunt of the Second and Third Waves on Patients in Western Uttar Pradesh.

Background: The recent second wave and the latest third wave of coronavirus disease 2019 (COVID-19) in India caused havoc on health infrastructure. However, there is a scarcity of studies from India and abroad that compare the second and third waves of the COVID-19 pandemic. We aimed to assess the factors like age, sex, and death comparison among diagnostically proven COVID-19 patients of the Meerut district in both waves.Methodology: A total of 297554 samples during the second wave (1st March 2021 to 30th June 2021) and 240655 during the third wave (1st January 2022 to 30th April 2022) were tested for reverse transcription polymerase chain reaction (RT-PCR) in the Department of Microbiology, Lala Lajpat Rai Medical College, using The Indian Council of Medical Research (ICMR) approved RT-PCR testing kits. The data like age, sex, place, follow-ups, etc. were recorded and data were analyzed statistically.Results: The RT-PCR positivity of 8.24% for COVID-19 in the second wave while 5.66% of patients in the third wave have been reported. The proportion of positive cases in children ≤10 years in the second and third wave were quite similar i.e., 3.59% and 3.40% respectively, whereas the proportion of positive cases in adolescents (10-20 years) was significantly higher (12.96%) in the third wave in contrast to the second wave (10.15%), while age group (41-60 years) is significantly less (26.65%) in proportion during the third wave in comparison to the second wave (29.50%). The proportion of positivity in young males has significantly increased in the third wave as compared to the second wave. The mortality also decreased significantly by 1/3rd of the second wave.Conclusion: The third wave showed low overall positivity (5.66%) as compared to the second wave (8.24%), while the brunt on young children was comparable to the second wave which was assumed to be higher. The mortality and hospitalization also decreased significantly in the second wave. Regular surveillance and analysis should continue to combat this pandemic.

What role does land consolidation play in the multi-dimensional rural revitalization in China? A research synthesis

With the rural revitalization strategy was proposed in 2017, large-scale land consolidation has been carried out in rural areas of China, which has profoundly impacted rural development and sustainability. To assess the multi-dimensional effects of land consolidation on rural revitalization, an evaluation system was constructed following the proposed "target-indicator-outcome" framework and subsequently applied to 193 cases documented in 92 peer-reviewed articles for a systematic review and meta-analysis. The results indicate that rural land consolidation had played more positive than no/negative roles in facilitating rural revitalization, with cases reporting generally positive outcomes accounting for 74%. Considering four targets of rural revitalization, positive effects were statistically significant in the case of Prosperous Life and Industrial Prosperity, with positive cases accounting for 86% and 79%. However, the positive effects in terms of Ecological Livability and Rural Civilization & Effective Governance is statistically non-significant, with positive cases accounting for 65% and 47%. In terms of 12 indicators, an overview of the positive and no/negative effects brought by land consolidation were summarized. The cases of the indicators related to rural producting and living were largely positive, however, the indicators related to rural ecology, rural civilization and governance reported higher no/negative outcomes. From the perspective of spatial differentiation, the positive effects were significant in eastern, central and western China, and the proportion of positive cases in eastern China (80%) and western China (77%) were higher than those in central China (67%). The opportunities and threats of rural land consolidation in multi-dimension deserve policy attention in rural revitalization strategy.

Analysis of the COVID-19 testing parameters and progression of the pandemic at the district level: findings from the ICMR Hundred Million Test (HMT) database during the first wave in India

BackgroundIndia had the second-highest number of COVID-19 cases globally. We evaluated the progression of the pandemic across the lockdowns and phased reopenings at the district level during the first wave (in India). MethodsFor the analysis in this study, we used more than 100 million COVID-19 test results along with other parameters available in the Indian Council of Medical Research database from March 2020 to October 2020. The districts were stratified as high, moderate, and low caseload districts and data analysis was done for each phase of lockdown. FindingsOf the 110.5 million tests included in the analysis, 54.79 million tests were performed using molecular methods, 53.58 million by rapid antigen tests, and 2.13 million using the indigenous TruNat platform. The proportion of positive cases among symptomatic individuals (22.6%) was significantly higher than asymptomatic individuals (8.6%). The tests conducted and proportions of positivity were significantly higher in high caseload districts; 58% of these tests were conducted using molecular methods as opposed to only one-third in low caseload districts. InterpretationLaboratory parameters, along with other demographic information, can help us better understand the spread of the pandemic in a country. This information can be crucial to formulating and implementing public health policies in future waves of the pandemic.

Screening of group B Streptococcus infection in pregnancy and neonatal outcomes in the province of Trento, Italy.

The study analyzes the trend of group B streptococcal (GBS) infection in pregnancy in the province of Trento, Italy, where a universal screening of GBS infection in pregnancy has been active for some time. Data from pregnant women who gave birth at local maternity units between 2015-2019 were obtained from birth attendance certificates (BAC), the main - and mandatory - source of information for monitoring pregnancies, births and neonatal health in Italy. The BAC used in the province of Trento acquires the results of a vast range of infections in pregnancy. The data collected from the BAC were integrated with those provided by the Hospital Information System (SIO). The occurrence of neonatal GBS infection was investigated on 2019 birth cohort, using the hospital discharge archive as an ancillary information source. Between 2015-2019, 20,905 pregnant women received care at maternity units of the province of Trento, Italy, of whom 25.5% were foreigners. The average coverage of GBS testing in pregnancy was 91.8% (95% CI 91.25-92.35) without significant variations from one year to the next. Test coverage varies in relation to maternity units and some socio-demographic characteristics of mothers. The average proportion of GBS positive cases over the study period was 21.0% (95% CI 20.7-21.3), a value that does not show statistically significant changes from one year to the next. The proportion of positive cases appears uneven among the subgroups of pregnant women considered, even if the differences are not statistically significant. In the 2019 birth cohort, newborns to GBS-positive mothers had an excess of stillbirths, of those born with Apgar at 5 minutes <7 and hospitalized at birth. However, these excesses were not statistically significant. Intravenous Antibiotic Prophylaxis (IAP) was performed in 86.8% of births from GBS positive mothers who had an indication for IAP. IAP was inadequate in 7.4% of the GBS positive mothers. Postnatal evaluation of 783 live births to GBS positive mothers identified 3 cases of early neonatal GBS infection. The incidence of neonatal GBS infection over the whole series of live births is 0.71/1,000 (95% CI 0.56-0.86), 0.68/1000 (CI 95% 0.55-0.79) in Italians and 1.07/1000 (95% CI 0.45-1.65) in foreigners. Data collection on infections in pregnancy through BAC allows area-based assessment. The quality of the data recorded in the BAC can be considered satisfactory but it was necessary to access to other information sources. The local availability of various information sources should allow periodic audits and closer monitoring of neonatal GBS infection.

Spatial and Temporal Analysis of COVID-19 in the Elderly Living in Residential Care Homes in Portugal.

Background: The goal of this study is to identify geographic areas for priority actions in order to control COVID-19 among the elderly living in Residential Care Homes (RCH). We also describe the evolution of COVID-19 in RHC throughout the 278 municipalities of continental Portugal between March and December 2020. Methods: A spatial population analysis of positive COVID-19 cases reported by the Portuguese National Health Service (NHS) among the elderly living in RCH. The data are for COVID-19 testing, symptomatic status, comorbidities, and income level by municipalities. COVID-19 measures at the municipality level are the proportion of positive cases of elderly living in RCH, positive cases per elderly living in RCH, symptomatic to asymptomatic ratio, and the share of comorbidities cases. Spatial analysis used the Kernel density estimation (KDE), space-time statistic Scan, and geographic weighted regression (GWR) to detect and analyze clusters of infected elderly. Results: Between 3 March and 31 December 2020, the high-risk primary cluster was located in the regions of Braganca, Guarda, Vila Real, and Viseu, in the Northwest of Portugal (relative risk = 3.67), between 30 September and 13 December 2020. The priority geographic areas for attention and intervention for elderly living in care homes are the regions in the Northeast of Portugal, and around the large cities, Lisbon and Porto, which had high risk clusters. The relative risk of infection was spatially not stationary and generally positively affected by both comorbidities and low-income. Conclusion: The regions with a population with high comorbidities and low income are a priority for action in order to control COVID-19 in the elderly living in RCH. The results suggest improving both income and health levels in the southwest of Portugal, in the environs of large cities, such as Lisbon and Porto, and in the northwest of Portugal to mitigate the spread of COVID-19.

Prehospital characteristics of COVID-19 patients in Helsinki \u2013 experience of the first wave of the pandemic

BackgroundThere is a lack of knowledge how patients with COVID-19 disease differ from patients with similar signs or symptoms (but who will have a diagnosis other than COVID-19) in the prehospital setting. The aim of this study was to compare the characteristics of these two patient groups met by the emergency medical services.MethodsAll prehospital patients after the World Health Organisation (WHO) pandemic declaration 11.3.2020 until 30.6.2020 were recruited for the study. The patients were screened using modified WHO criteria for suspected COVID-19. Data from the electronic prehospital patient reporting system were linked with hospital laboratory results to check the laboratory confirmation for COVID-19. For comparison, we divided the patients into two groups: screening- and laboratory-positive patients with a hospital diagnosis of COVID-19 and screening-positive but laboratory-negative patients who eventually received a different diagnosis in hospital.ResultsA total of 4157 prehospital patients fulfilled the criteria for suspected COVID-19 infection during the study period. Five-hundred-thirty-six (12.9%) of the suspected cases received a laboratory confirmation for COVID-19. The proportion of positive cases in relation to suspected ones peaked during the first 2 weeks after the declaration of the pandemic. In the comparison of laboratory-positive and laboratory-negative cases, there were clinically insignificant differences between the groups in age, tympanic temperature, systolic blood pressure, heart rate, on-scene time, urgency category of the call and mode of transportation. Foreign-language-speakers were overrepresented amongst the positive cases over native language speakers (26,6% vs. 7,4%, p < 0,001). The number of cases in which no signs or symptoms of COVID-19 disease were reported, but patients turned out to have a positive test result was 125 (0,3% of the whole EMS patient population and 11,9% of all verified COVID-19 patients encountered by the EMS).ConclusionsIn a sample of suspected COVID-19 patients, the laboratory-positive and laboratory-negative patients were clinically indistinguishable from each other during the prehospital assessment. Foreign-language-speakers had a high likelihood of having Covid-19. The modified WHO criteria still form the basis of screening of suspected COVID-19 patients in the prehospital setting.

COVID-19 public health measures and respiratory viruses in children in Melbourne.

AimTo describe the epidemiology of respiratory viruses in children before and during the 2020 SARS‐CoV‐2 pandemic and the relationship to public health measures instituted by the Victorian government.MethodsRetrospective audit of respiratory viruses at a tertiary paediatric hospital in Melbourne from January 2015 up to week 47, 2020 in children under 18 years of age. The proportion of positive cases in weeks 1–47 in 2015–2019 (period 1) were compared to weeks 1–47, 2020 (period 2), and reviewed in the context of public health restrictions in Victoria.ResultsAn annual average of 4636 tests were performed in period 1 compared to 3659 tests in period 2. Proportions of positive influenza A virus, influenza B virus, respiratory syncytial virus (RSV) and human parainfluenza virus were significantly reduced in period 2 compared to period 1: 77.3, 89.4, 68.6 and 66.9% reductions, respectively (all P < 0.001). From week 12–47, 2020, 28 893 SARS‐CoV‐2 tests were performed with a 0.64% positivity rate. Influenza viruses were not detected after week 17, RSV was not detected after week 35.ConclusionsStrict public health measures and border closures were successful in eliminating community transmission of SARS‐CoV‐2 in Melbourne. This was associated with a significant reduction in other respiratory virus infections in children. Identifying sustainable and effective ongoing public health interventions to reduce transmission of RSV and influenza could result in reduced morbidity and mortality in children and requires further research.

Asymptomatic carriage of canine infectious respiratory disease complex pathogens among healthy dogs.

The objectives of this study were to determine the prevalence of canine infectious respiratory disease pathogens among asymptomatic client-owned dogs, and to compare the risks of asymptomatic pathogen carriage between client-owned dogs and dogs in an animal shelter. Pooled tonsillar, conjunctival and nasal cavity swabs from asymptomatic client-owned dogs (n=133) were tested using a real-time polymerase chain reaction canine respiratory panel. Identical samples from asymptomatic dogs in an animal shelter (n=295) were similarly tested for selected pathogens. Risk differences were calculated between client-owned dogs and shelter dogs for each of the respiratory pathogens included in the analyses. A total of 15 of 133 (11.3%) asymptomatic client-owned dogs were positive for at least one pathogen in the complex. Seven dogs (6.1%) were positive for M. cynos, six (5.2%) were positive for B. bronchiseptica, two (1.7%) were positive for canine herpesvirus type 1 and two (1.7%) were positive for canine respiratory coronavirus. For all eight pathogens tested in both groups, the proportion of positive cases was higher among shelter dogs than among client-owned dogs. Shelter dogs had a higher risk for M. cynos (0.18, 95% confidence interval: 0.12 to 0.25), canine respiratory coronavirus (0.15, 95% confidence interval: 0.10 to 0.19), canine distemper virus (0.06, 95% confidence interval: 0.03 to 0.09), and canine pneumovirus (0.05, 95% confidence interval: 0.03 to 0.08) than client-owned dogs. Odds ratios for M. cynos (0.31, 95% confidence interval: 0.08 to 0.92) and canine respiratory coronavirus (0.05, 95% confidence interval: 0.01 to 0.18) were significantly different between client-owned and shelter dogs. In all cases except for canine herpesvirus type 1, dogs within the shelter population were observed to be at higher risk of exhibiting asymptomatic carriage of a respiratory pathogen as compared to client-owned dogs. The strength of this association was strongest for M. cynos and canine respiratory coronavirus. The risk of canine infectious respiratory disease pathogen exposure posed by asymptomatic client-owned dogs is poorly defined. This study also corroborates previous reports of high canine infectious respiratory disease prevalence among clinically healthy shelter dogs, and further determined that the overall prevalence of canine infectious respiratory disease pathogen carriage among clinically healthy client-owned dogs is low but is highest for the traditional pathogen B. bronchiseptica and the emerging pathogen M. cynos.

Human telomerase RNA component (hTERC) gene expression and chromosome 7 ploidy correlate positively with histological grade of cervical intraepithelial neoplasia.

Cervical cancer screening by primary human papilloma virus detection and cytology is fraught with low specificity and variable sensitivity, respectively. Cytology-histology correlation remains modest. Biomarkers associated with early genetic events in cervical squamous carcinogenesis and detectable in cytology material are likely to be relevant. Human telomerase RNA component (hTERC) gene overexpression and aneuploidy are promising candidates in view of their reported early and consistent association with cervical squamous oncogenesis. We analysed hTERC gene expression and chromosome 7 ploidy by fluorescent in-situ hybridisation (FISH) in 50 women with cytological precursor squamous intraepithelial lesions and available histology outcomes. Results were expressed as percentages of cells showing ≥3 signals, mean signals/nucleus, and maximum amplitude across various cytology and histology categories. Proportions of positive cases were calculated from threshold values derived from 6 controls. Distribution of above indices with respect to ≥cervical intraepithelial neoplasia 2 (CIN2) was explored. For both genetic aberrations, there was significant positive correlation (for all indices) between the proportion of positive cases and worsening cytological and histological outcomes (P<.05), with significant intergroup differences (P<.05). High-grade lesions (≥CIN2) had significantly higher results compared to <CIN2 lesions (P≤.001). In five discordant cases with ≥CIN2 under- or overdiagnosed on cytology, FISH supported the histological diagnosis. HTERC gene amplification and chromosome 7 ploidy showed positive association with cervical squamous carcinogenesis and could be relevant in settings of discrepant cytology-histology correlation.

Initial results from a multi-center population-based cluster randomized trial of esophageal and gastric cancer screening in China

BackgroundWe initiated the first multi-center cluster randomized trial of endoscopic screening for esophageal cancer and gastric cancer in China. The objective of the study was to report the baseline screening findings in this trial.MethodsWe recruited a total of 345 eligible clusters from seven screening centers. In the intervention group, participants from high-risk areas were screened by endoscopy; in non-high-risk areas, high-risk individuals were identified using a questionnaire and advised for endoscopy. Lugol’s iodine staining in esophagus and indigo carmine dye in stomach were performed to aid in the diagnosis of suspicious lesions. The primary outcomes of this study were the detection rate (proportion of positive cases among individuals who underwent endoscopic screening) and early detection rate (the proportion of positive cases with stage 0/I among all positive cases).ResultsA total of 149,956 eligible subjects were included. The detection rate was 0.7% in esophagus and 0.8% in stomach, respectively. Compared with non-high-risk areas, the detection rates in high-risk areas were higher, both in esophagus (0.9% vs. 0.1%) and in stomach (0.9% vs. 0.3%). The same difference was found for early-detection rate (esophagus: 92.9% vs. 53.3%; stomach: 81.5% vs. 33.3%).ConclusionsThe diagnostic yield of both esophagus and stomach were higher in high-risk areas than in non-high-risk areas, even though in non-high-risk areas, only high-risk individuals were screened. Our study may provide important clues for evaluating and improving the effectiveness of upper-endoscopic screening in China.Trial registration: Protocol Registration System in Chinese Clinical Trial Registry, ChiCTR-EOR-16008577. Registered 01 June 2016-Retrospectively registered, http://www.chictr.org.cn/showprojen.aspx?proj=14372

Effectiveness of not quarantining passengers after having a negative COVID-19 PCR test at arrival to dubai airports

Since March 11th 2020 as the World Health Organization (WHO) has proclaimed Coronavirus Disease 2019 a pandemic, governments have had to implement regulations and policies to prevent the spread of a deadly disease such as hand hygiene practices, wearing masks in public areas, maintaining social distance as well as quarantine or isolation. Current evidence on the 14-days quarantine which is obtained post-travelling is very limited, and this raises some critical questions about the effectiveness of its implementation in the rising COVID-19 infection trend. This study aims to assess the current non-quarantine practice in Dubai for passengers returning from travel, which is expected to enhance tourism in the emirate of Dubai and boost the economy while maintaining community safety and preventing imported transmission of COVID-19. The study adopts a quantitative method using a survey design to accomplish its objectives. A questionnaire is performed as the main quantitative instrument to collect data from passengers who arrived at Dubai airports with negative Polymerase Chain Reaction (PCR) test at arrival (day 0) and repeated the PCR test on day 5- day 10 from arrival. In this study, all relevant data were accessed using the Dubai airport database, a sample of 574 passengers have been surveyed using a systematic random sampling method. The study findings indicated that the proportion of positive cases on day 5 - day10 from arrival was significantly less than 1% (0.00017) with a p-value of 0.0234. Therefore, it can be concluded that the objectives of implementing a 14-day quarantine post-travel were not met when passengers tested negative for COVID-19 PCR upon arrival at Dubai airports. This study contributes to the literature concerning the effectiveness of implementing a 14-day quarantine strategy on passengers who arrive at airports with a negative PCR test result. Accordingly, it progresses on building theory relating to infectious diseases in the healthcare setting. Furthermore, the study assured what are the best preventive measures to be implemented for travelers coming to Dubai airports.

Gestational diabetes mellitus testing in the COVID-19 pandemic: The problems with simplifying the diagnostic process.

BackgroundMultiple professional bodies have temporarily revised recommendations for gestational diabetes mellitus (GDM) testing during the COVID‐19 pandemic to reduce person‐to‐person contact. The current Australian temporary criteria advise that if the fasting glucose is ≤4.6 mmol/L, then no glucose tolerance test (GTT) is required.AimsThe aim of this study is to examine the extent of underdiagnosis of GDM using a fasting glucose ≤4.6 mmol/L as a cut‐off to determine that a GTT is not necessary.Materials and MethodsDe‐identified data from pregnant women having a GTT test in the Illawarra area during a six‐year period was used to determine the number of women with GDM and the proportion of positive cases that would be missed for different fasting glucose values.ResultsThere were 16 522 results identified and GDM was diagnosed in 12.2%. The majority of women were more than 30 years of age (85.2%) and diagnosed at ≥20 weeks gestation (81.1%). Of those diagnosed with GDM, 29% had a fasting glucose of ≤4.6 mmol/L and would have been missed.ConclusionsOur results show that using a fasting glucose of 4.6 mmol/L or less would miss nearly a third of women who would otherwise be diagnosed with GDM.

Cytomegalovirus Infection in Postrenal Transplant Recipients: 18 Years’ Experience From a Tertiary Referral Center

BackgroundCytomegalovirus (CMV) reactivation or infection is one of the most important infectious complications in transplant recipient leading to significant morbidity and mortality. Its early detection and prompt treatment is imperative to improve transplant outcome. The present study estimated the frequency of CMV in renal transplant recipients (RTR). Various aspects of pp65Ag assay and quantitative real-time polymerase chain reaction (qRT-PCR) were evaluated in relation to the recent guidelines for CMV detection and treatment. MethodsRetrospectively, data of clinically suspected cases of CMV (1610 out of total 2681 renal transplants) were analyzed along with a comparison of pp65Ag assay and qRT-PCR. ResultsThe overall incidence of CMV syndrome was 14.25%; however, the incidence of CMV viremia in the clinically suspected group was 23.73%. The proportion of positive cases with pp65Ag assay and qRT-PCR were 13.6% (95% CI; 7.9-22.3) and 19.3% (95% CI; 12.4-28.8) with a substantial agreement (Cohen’s kappa = 0.632) between the 2 techniques. CMV positive recipients were treated with ganciclovir until their viral count was negative or up to 3 weeks, followed by 3 months of prophylaxis with valganciclovir. No graft failure or mortality was reported secondary to CMV infection until 3 to 5 years of follow-up. ResultsCMV infection is quite prevalent in RTR, and early detection and immediate treatment or prophylaxis is of utmost importance. qRT-PCR is the gold standard and preferred over other methods; however pp65Ag assay still holds its importance in low-economic countries and populations where CMV infection is more prevalent and financial constraints are a major limitation.

Abstract PD5-01: Prospective multi-institutional evaluation of pathologist assessment of PD-L1 assays in triple negative breast cancer

Abstract Background: The IMpassion130 study demonstrated prolonged overall survival when atezolizumab, a PD-L1 inhibitor, was added to nab-paclitaxel in PD-L1 positive patients with advanced triple negative breast cancer (TNBC). Approximately 40% of tumors were PD-L1 positive, utilizing a cutoff of ≥ 1% immune cell (IC) staining with the Ventana SP142 immunohistochemical (IHC) assay. The Food and Drug Administration (FDA) approved this assay as a companion test to determine patient eligibility for atezolizumab therapy. However, literature in lung cancer shows that pathologists have a high discordance in assessing PD-L1 on IC. The FDA companion test documentation for SP142 shows high inter-laboratory reproducibility with nearly 95% overall percent agreement (OPA) between 2 readers for 2 category scoring of IC (positive versus negative) in TNBC in a central laboratory. PD-L1 testing for breast cancer is now becoming widespread in pathology laboratories. The goal of this study was to assess concordance in PD-L1 scoring between 19 pathologists from 14 institutions examining the same 86 TNBC tissues stained with the SP142 and SP263 antibodies. We also present a new method to determine the minimum number for evaluators needed to estimate concordance between large numbers of readers as occurs in real life setting. Methods: Full tissue sections were stained exactly as prescribed on the label on the Ventana Benchmark with the SP142 and SP263 PD-L1 assays. Sixty-eight and 76 cases were evaluable respectively. Stained slides were scanned and digital files distributed to pathologists who independently scored cases as either negative (&amp;lt; 1% IC staining) or positive (≥ 1% IC staining) and estimated the % of IC staining for positive cases. We applied a method that we call Observers Needed to Evaluate Subjective Tests (ONEST). For any combination of pathologists, we can quantify the degree of overall agreement using the proportion of tissue samples upon which all selected pathologists agreed, which can lead to a plot of non-increasing trajectory of agreement as the number of pathologists increases. We computed and plotted the empirical estimate of the overall agreement with the 95% confidence interval (CI) from 1000 randomly selected permutations of the pathologists. Results: PD-L1 was interpreted as positive with SP263 in an average of 78% of cases compared to 58% with the SP142 assay (p&amp;lt;.0001). IC positive continuous scores ranged from 1-95% (mean=20%) and 1-90% (mean=10%) for SP263 and SP142. Complete 2 category (positive vs negative) scoring concordance across all observers was achieved in 38 cases (50%) with SP263 and 26 cases (38%) with SP142. The intraclass correlation coefficient (ICC) for 2 category scoring of SP263 and SP142 was 0.513 and 0.560 respectively. ONEST plots made for each assay for 19 pathologists showed a decrease in OPA as number of observers increased, reaching a low plateau of approximately 0.46 at 10 observers for SP263 and 0.42 at 8 observers for SP142. Conclusions: Utilizing the FDA approved SP142 assay, we found a higher prevalence of PD-L1 positive tumors than published in the IMpassion130 trial but lower prevalence than seen with the SP263 assay. The different proportion of positive cases seen with two different assays highlights the need to establish cutoffs for each assay to correspond with clinical benefit. The ICC of scoring immune cells with both PD-L1 assays showed poor reproducibility across multiple pathologists. The ONEST analysis finds a plateau with 10 pathologists, only reaching an OPA of 0.4 for immune cell assessment. This suggests that more than half of the pathologists in real world situations may mis-assign patient IC scores. This could lead to a high percentage of patients either receiving atezolizumab, when they are unlikely to benefit or not receiving atezolizumab when they may benefit. Citation Format: Emily Suzanne Reisenbichler, Gang Han, Vasiliki Pelekanou, Vesal Yaghoobi, Fahad S Ahmed, Andrew Bellizzi, Veerle Bossuyt, Jane Brock, Kimberly Cole, Oluwole Fadare, Omar Hameed, Krisztina Hanley, Beth T Harrison, M G Kuba, Amy Ly, Dylan Miller, Mirna Podoll, Anja C Roden, Mary A Sanders, Kamaljeet Singh, Shi Wei, Hannah Wen, Lajos Pusztai, David L Rimm. Prospective multi-institutional evaluation of pathologist assessment of PD-L1 assays in triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD5-01.

Concordance of Programmed Death-Ligand 1 Expression between SP142 and 22C3/SP263 Assays in Triple-Negative Breast Cancer.

PurposeTriple-negative breast cancer (TNBC) represents a major clinical challenge due to its aggressive and metastatic behavior and the lack of available targeted therapies. Therefore, therapeutic strategies are needed to improve TNBC patient management. Recently, atezolizumab and nab-paclitaxel chemotherapy has been approved by the Food and Drug Administration for the first-line treatment of patients with locally advanced and metastatic TNBC. The programmed death-ligand 1 (PD-L1) immunohistochemical SP142 assay was also approved as a companion diagnostic device for selecting TNBC patients for atezolizumab treatment. This study aimed to evaluate and compare the analytical performance of the PD-L1 22C3/SP263 assays in comparison with the SP142 assay for ≥ 1% immune cells (ICs).MethodsImmunohistochemical expression for the PD-L1 22C3/SP263 assays, in comparison with the SP142 assay, was analyzed for the ≥ 1% ICs in 95 TNBCs.ResultsAt the 1% cut-off value, the proportions of positive cases were 52.6% for the SP142 assay in infiltrating ICs and 50.5% and 52.6% for the 22C3 and SP263 assays in tumor cells, respectively. The PD-L1 SP263 assay had the highest while the PD-L1 22C3 assay had the lowest total positive expression rate at all cut-off values. The concordance rate between the assays was highest at a 1% cut-off value and decreased when the cut-off value increased. The concordance rate between the SP142 and SP263 assays at 1% cut-off was high, while in comparison, the concordance rate between the SP142 and 22C3 assays at 1% cut-off was relatively lower.ConclusionThis study demonstrates that although the 22C3 assay at a 1% cut-off value compared with the PD-L1 SP142 assay at the clinically relevant cut-off shows comparable but not interchangeable analytical performance, the analytical performance of the SP263 assay at a 1% cut-off value shows interchangeable performance with the PD-L1 SP142 assay at the clinically relevant cut-off.

Laboratory surveillance for SARS-CoV-2 in India: Performance of testing & descriptive epidemiology of detected COVID-19, January 22 - April 30, 2020.

Background & objectives:India has been reporting the cases of coronavirus disease 2019 (COVID-19) since January 30, 2020. The Indian Council of Medical Research (ICMR) formulated and established laboratory surveillance for COVID-19. In this study, an analysis of the surveillance data was done to describe the testing performance and descriptive epidemiology of COVID-19 cases by time, place and person.Methods:The data were extracted from January 22 to April 30, 2020. The frequencies of testing performance were described over time and by place. We described cases by time (epidemic curve by date of specimen collection; seven-day moving average), place (area map) and person (attack rate by age, sex and contact status), and trends were represented along with public health measures and events.Results:Between January 22 and April 30, 2020, a total of 1,021,518 individuals were tested for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Testing increased from about 250 individuals per day in the beginning of March to 50,000 specimens per day by the end of April 2020. Overall, 40,184 (3.9%) tests were reported positive. The proportion of positive cases was highest among symptomatic and asymptomatic contacts, 2-3-fold higher than among those with severe acute respiratory infection, or those with an international travel history or healthcare workers. The attack rate (per million) by age was highest among those aged 50-69 yr (63.3) and was lowest among those under 10 yr (6.1). The attack rate was higher among males (41.6) than females (24.3). The secondary attack rate was 6.0 per cent. Overall, 99.0 per cent of 736 districts reported testing and 71.1 per cent reported COVID-19 cases.Interpretation & conclusions:The coverage and frequency of ICMR's laboratory surveillance for SARS-CoV-2 improved over time. COVID-19 was reported from most parts of India, and the attack rate was more among men and the elderly and common among close contacts. Analysis of the data indicates that for further insight, additional surveillance tools and strategies at the national and sub-national levels are needed.

Immunostaining for galactose-deficient immunoglobulin A is not specific for primary immunoglobulin A nephropathy.

Primary immunoglobulin A nephropathy (IgAN) is characterized by IgA1-dominant or codominant glomerular deposits, postulated to be galactose deficient (Gd). However, glomerular IgA deposition can also occur in nonrenal diseases such as liver cirrhosis, psoriasis and inflammatory bowel disease ('secondary IgAN') or be an incidental finding in biopsies with other pathologies. A glomerulonephritis resembling IgAN can develop in patients with bacterial, mainly staphylococcal infections [staphylococcal infection-associated glomerulonephritis (SAGN)]. There are no specific histological features to distinguish between these, but differentiation is critical for appropriate management. The aim of this study was to investigate whether a recently described antibody to Gd-IgA1 (KM-55) could aid in differentiating primary IgAN from other conditions with glomerular IgA deposition, especially SAGN. We performed a retrospective cohort study of patients who underwent kidney biopsy for clinical indications and were found to have glomerular IgA deposits. We evaluated 100 biopsies, including primary IgAN (n = 44), secondary IgAN (n = 27), SAGN (n = 13), incidental IgA deposition (n = 8) and lupus nephritis (n = 8). There was no difference in Gd-IgA staining intensity or the proportion of positive cases between primary and secondary IgAN. SAGN and cases with incidental IgA deposits had significantly lower Gd-IgA staining intensity than primary IgAN, but up to 69% of SAGN cases were positive (albeit weaker). Gd-IgA staining is present not only in primary IgAN, but also in biopsies with secondary IgAN, SAGN and incidental IgA. Weak or negative staining may favor SAGN, especially in the setting of infection, or incidental IgA in the absence of nephritic symptoms or in the presence of other unrelated glomerular pathologies. However, positive staining for Gd-IgA alone is not specific enough for a diagnosis of primary IgAN.

Impact of electronic reminder systems on hepatitis C screening in primary care.

Screening for hepatitis C virus (HCV) was recommended in 2012 by the Centers for Disease Control (CDC) for the population born between 1946 and 1965. Reminder systems are effective at promoting HCV screening, but the yield of positive tests among various population subgroups and the linkage to specialty HCV treatment is not well understood. We sought to determine: (i) the effect of the CDC recommendation alone, and the effect of an electronic medical record (EMR) reminder on the proportion of the population screened; (ii) the yield of positive HCV tests as screening strategies have evolved, and according to a patient's history of serum aminotransferase testing; (iii) the proportion of positive cases followed up for HCV treatment. This retrospective cohort study included 60000 primary care patients at a northeast US academic medical centre serving an urban and rural population in which an EMR reminder was instituted in 2014. Results demonstrated an increase in proportion tested for HCV from 12% prior to the CDC recommendation to 37% after the reminder system. The yield of positive HCV antibody (HCV Ab) tests decreased from 7% in the "case-finding" era to 1.6% after the EMR reminder prompted screening of a lower risk population (P<.001). Patients with a history of abnormal aminotransferase tests had a fivefold higher rate of positive HCV Ab testing (6.7% vs 1.5%, P<.001). Ninety per cent of patients with confirmed HCV infection were seen in specialty care.