Background: Ever since the Coronavirus disease (COVID-19) outbreak emerged in China, there has been several attempts to predict the epidemic across the world with varying degrees of accuracy and reliability. This paper aims to carry out a short-term projection of new cases; forecast the maximum number of active cases for India and selected high-incidence states; and evaluate the impact of three weeks lock down period using different models. Methods: We used Logistic growth curve model for short term prediction; SIR models to forecast the maximum number of active cases and peak time; and Time Interrupted Regression model to evaluate the impact of lockdown and other interventions. Results:The predicted cumulative number of cases for India was 58,912 (95% CI: 57,960, 59,853) by May 08, 2020 and the observed number of cases was 59,695. The model predicts a cumulative number of 1,02,974 (95% CI: 1,01,987, 1,03,904) cases by May 22, 2020. As per SIR model, the maximum number of active cases is projected to be 57,449 on May 18, 2020. The time interrupted regression model indicates a decrease of about 149 daily new cases after the lock down period, which is statistically not significant. Conclusion:The Logistic growth curve model predicts accurately the short-term scenario for India and high incidence states. The prediction through SIR model may be used for planning and prepare the health systems. The study also suggests that there is no evidence to conclude that there is a positive impact of lockdown in terms of reduction in new cases.
Background: Since the onset of the COVID-19 in China, forecasting and projections of the epidemic based on epidemiological models have been in the centre stage. Researchers have used various models to predict the maximum extent of the number of cases and the time of peak. This yielded varying numbers. This paper aims to estimate the effective reproduction number (R) for COVID-19 over time using incident number of cases that are reported by the government. Methods: Exponential Growth method to estimate basic reproduction rate R 0 , and Time dependent method to calculate the effective reproduction number (dynamic) were used. "R0" package in R software was used to estimate these statistics. Results: The basic reproduction number (R 0 ) for India was estimated at 1.
Adolescent and young adult (AYA) patients with acute lymphoblastic leukaemia (ALL) have inferior survival when compared to children. The causes are multiple and include bad biology, differences in treatment approaches, and other complex social, economic and psychological factors that affect therapy adherence. 1 Intensive 'paediatric' regimens improve outcomes, but these come with the cost of higher toxicity, which may even negate these benefit of reduced relapse. 2-5 To understand the real-world data from India, we analysed the outcomes of AYA ALL (aged 15-29 years, treated between 2012 and 2017) from a retrospective database maintained by the Hematology Cancer Consortium (HCC). Baseline data of all patients (including those who were not treated) diagnosed within the period stipulated by a particular centre were captured, including reasons for not availing treatment. Survival outcomes were estimated for treated patients (censored on 31 July 2019). For this analysis, 'high risk' was defined based on white blood cell count (WBC) at diagnosis (B cell >30 9 10 9 /l, T cell >100 9 10 9 /l). Protocols such as Multicentre protocol 841 (MCP-841), Berlin-Frankfurt-M€ unster 95 (BFM-95), BFM-90, and Children's Oncology Group (COG) were considered 'paediatric type', whereas German Multicentre ALL (GMALL), hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), and UKALL were considered 'adult type'. Minimal residual disease (MRD) >0Á01% (when assessed by flow cytometry) was considered positive. Of the 1383 patients registered, 1141(82Á5%) underwent treatment (Supplementary Table S1 and S2, baseline characteristics), and 242 did not start treatment (Fig 1). The inability to afford treatment was the commonest cause for not initiating treatment (105/1383, 7Á6%). There were no Fig 1. Flowchart depicting the outcomes of patients who were included in the registry. Of the 1383 patients, only 1141 started therapy (induction) and 863 (76%) achieved complete remission (CR). At last follow-up, 574 were in CR and on follow-up. A total of 336/1383 (24%) patients either did not start therapy (N = 242), or abandoned therapy after starting induction (N = 94) (A). (B) Comparison of induction outcomes between those treated with 'paediatric' and 'adult' protocols. There were no differences in terms of achievement of CR (76% vs. 73%, P = 0Á509), induction mortality (4Á7% vs. 3Á2%, P = 0Á842), or minimal residual disease (MRD) positivity rate (36% vs. 42%, P = 0Á382). (C) The commonest cause of induction mortality was infection (56%) followed by progressive disease (23%).
Background: Characterization of reticulo-endothelial activation in COVID-19 may guide treatment. Objectives: To assess reticulo-endothelial activation and its correlation with disease severity and death in patients across the entire spectrum of COVID-19 severity. Methods: Consecutive hospitalized COVID-19 patients were studied, with similar number of patients in each disease severity category. Baseline serum ferritin, sCD163 (macrophage activation markers) and plasma von Willebrand factor (VWF) antigen (endothelial activation marker) levels were studied. Clinical parameters and plasma D-dimer levels were also studied. The study parameters were correlated with COVID-19 severity and survival. Results: The 143 patients (104 males [80%], age 54 [42 – 65] years, median [inter-quartile range]) presented 4 (3—7) days after symptom onset. Thirty-four patients had mild disease, 36 had moderate disease, 36 had severe disease and 37 had critical disease at baseline. With increasing COVID-19 severity, ferritin, sCD163, VWF and D-dimer levels significantly increased at baseline, however, 139 patients had normal sCD163 levels. Of the reticulo-endothelial markers, VWF level independently correlated with COVID-19 severity and with survival. VWF level > 332.6 units/dl correlated with COVID-19 severity (odds ratio [OR]: 2.77 [95% confidence interval (C.I): 1.1 – 6.99], p value: 0.031) and in-hospital death (OR [95% CI]: 29.28 [5.2 – 165], p value < 0.001). Conclusions: Reticulo-endothelial activation markers increased incrementally with worsening COVID-19 severity. Baseline endothelial activation marker (VWF), and not macrophage activation markers, independently correlated with COVID-19 severity and death.
Introduction Acute lymphoblastic leukemia (ALL) diagnosed in adolescent and young adults (AYA) poses unique challenges. Despite using more intensive "pediatric-type" protocols, outcomes are generally inferior to those seen in children. The reasons are wide ranging, but when compared to pediatric ALL, AYA ALL has higher-risk biology, poorer tolerance to intensive treatments, and worse compliance with treatment regimens. India has one of the largest AYA populations in the world and AYA-ALL form a significant proportion of leukemias. The Indian acute leukemia research database [INwARD] was established in 2018 and had reported outcomes of ALLs from various centers of all age groups (Korula A, et al. Blood 2018 132:1374). Here, we present data focused on AYA-ALL from this database. Methods Retrospective data of AYA (15-29 years) patients with ALL (diagnosed between January 2012 to December 2017) from 9 centers were entered into an independent centralized online data capture system and analyzed for presenting characteristics, treatment and survival outcomes. Protocol choice was based on individual-center preference. For the purpose of this analysis, patients with WBC ≥30000 (B cell) and ≥100,000 (T-cell and other subtypes) were considered as high risk. Intensive protocols (MCP-841, BFM-95, COG), predominantly meant for children were labeled as "pediatric-type" and less intense protocols (GMALL, Hyper CVAD, UKALL) were considered as "adult-type". Results In the 6-year period, 1454 patients were registered [Males: 1114(76%), Median age: 20 years (15-29), Fig. 1.B; Subtype: B -ALL: 916(63%), T-ALL: 396 (27%); Fig. 1.C; High risk disease: 406 (28%)]. Of these,1100 (75%) underwent treatment. Poor financial support was the major reason for not taking treatment (Fig. 1.A). "Pediatric-type" protocols were used in 881 (81%) patients. After induction, 72% achieved complete remission (CR), 11% were refractory, 4% died during induction and 14% were not evaluable. Minimal residual disease was assessed in 581 and was present in 356 (61%). Attainment of CR, induction mortality, or MRD achievement was not affected by the type of regimen. Among these 1100 patients, 138 (12%) were lost to follow up and did not complete treatment. BCR ABL was tested in 636 and was positive in 112 (17%) [19% among patients with B-ALL (107/557)]and 106 of these were treated with additional tyrosine kinase inhibitors [imatinib (N=83) and dasatinib (N=23)]. Survival analysis: After a median follow up of 21 months, 270 patients relapsed [median time to relapse: 24 months (73% medullary, 17% CNS or testis, and 10% had a combined relapse) and 259 had died. The estimated 2-year event-free (EFS), relapse-free (RFS) and overall survival (OS) were 64%, 75% and 75% respectively. On univariate analysis the factors associated with inferior survival were as follows: EFS: WBC count ≥30,000/cmm, and ECOG PS 2-4; RFS: WBC count ≥30,000/cmm and ECOG PS 2-4; OS: use of "adult-type" protocols, ECOG PS 2-4, and BCR-ABL positive disease. On multivariate cox regression analysis, the only factors associated with inferior OS were: use of "adult" protocols (HR: 1.6), and BCR -ABL positive status (HR1.56) (Fig. 1.D). High WBC count at presentation predicted for inferior RFS while no factor could predict EFS on multivariate analysis. Conclusions In a multicenter analysis of AYA-ALL from different parts of India, we found that a quarter of newly diagnosed patients do not start treatment and another 12% are lost from follow up before treatment completion. Majority (80%) of the centers used "pediatric-type" protocols to treat AYA-ALL. Though superior survival was achieved with "pediatric-type" protocols, results must be interpreted with caution as these regimens were likely to be used more often in in younger patients. Variations in treatment protocols used between centers and the retrospective nature of the data are other caveats. Despite these limitations, this is one of the largest reports of AYA ALL from any part of the world and serves as a benchmark for planning prospective studies. Disclosures No relevant conflicts of interest to declare.
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