P622 Comparison of midterm outcomes in Pediatric Crohn’s Disease patients treated with either Exclusive Enteral Nutrition or Corticosteroids around disease diagnosis– a population based study

Background Corticosteroids (CS) and exclusive enteral nutrition (EEN) are commonly used as induction therapy in pediatric Crohn’s disease (PCD). Pediatric studies showed that CS treatment is equivalent to EEN for induction of remission, and it is easier to tolerate. However, EEN may be associated with superior long-term outcomes but this remains controversial. We thus aimed in this population-based study to compare CS dependency rate in children receiving EEN vs CS as induction therapy at the time of diagnosis, and to explore additional outcomes after one and two years of follow-up: IBD-related surgery, hospitalizations, and the use of biologics. Methods This study was performed on data from two Israeli Health Maintenance Organizations (HMOs), covering 78% of the population. We included all PCD patients (<18 years) diagnosed between 2005 and 2017 treated with EEN or CS within the first six months of diagnosis, with at least one-year follow-up. We excluded patients who initiated biologics within the same quarter. CS dependency was defined as a systemic steroid course lasting >90 days or four purchases with 12 months. Results A total of 2,730 PCD were identified, of whom 669 (24.5%) received induction therapy with either EEN [n=227 (8.3%)] or CS ([n=442 (16.2%)]. Median age at diagnosis was 13.04 years (3.8). Baseline (BL) characteristics, including age at diagnosis, anthropometrics data and gender, were similar between the groups. Steroid dependency was higher in the CS group compared to the EEN group during the 1st and the 2nd year (10% vs. 7%, p<0.001 and 14% vs. 12%, p<0.001 respectively). Use of biologics was higher in the 1st but not the 2nd year in the EEN group compared to the CS group (28% vs. 19%, p=0.0016 and 40% vs. 33%, p=0.066 respectively). Hospitalization rate was higher in the CS group in both the 1st and 2nd years (42% vs. 22%, p<0.001 and 51% vs. 30%, p<0.001 respectively). There were no differences between the groups in surgeries rate and growth during the 1st and 2nd year follow-ups. Conclusion The use of CS as induction therapy in PCD was associated with a higher corticosteroid dependency rate, as well as more hospitalizations during the first two years of follow-up.

Treatment Outcome for Symptomatic Patients with Clonal Cytopenia of Undetermined Significance: A Single-Institution Retrospective Study

Background Clonal cytopenia of undetermined significance (CCUS) is a newly described entity with a high probability to progress into myeloid disorders upon follow-up (Malcovati et al, Blood 2017). Little data is known on how to effectively treat patients with CCUS. We hereby describe a single institution experience in managing symptomatic CCUS patients. Methods Patients who had CCUS and underwent active treatment were identified after receiving IRB approval. CCUS diagnosis was rendered if patients had non-diagnostic bone marrow biopsy evaluation combined with evidence of pathogenic myeloid somatic mutation using our institution next generation sequencing (NGS) panel (OncoHeme, Mayo Clinic). "Symptomatic patients" is determined by patients who need therapy beyond blood transfusion. Treatment type is based on physicians' choice. Clinical and lab results were collected. Response and progression were graded based on the MDS IWG 2006 criteria. The date of treatment initiation was used for overall survival (OS) and progression (either to myeloid neoplasm or worsening cytopenias) free survival (PFS) calculation. Stata 14.1(StatCorp) was used for data analysis. Results 1) Cohort characteristics: Between 2015 and 2020, 24 patients met inclusion criteria with median age of 72 years (range: 24-87). Twenty (83%) were men. 15 (63%) were white, 1 (4%) African American, 1 (4%) Native American and 7 unknown (33%). Eighty percent had ECOG PS≤1. Four (17%) patients had prior other hematology disorders and 3 (13%) had solid tumor. Two (8%) patients had previous radiation therapy, 2 (8%) received chemotherapy and 1 (4%) received allogeneic stem cell transplantation. At the time of treatment, the median of hemoglobin was 8.9 (range 6.8-13.7) g/dL, white blood cell 2.9 (range 1.4-12.3) *109/L, and platelet 76 (range 8-407) *109/L. Red blood cell (RBC) and platelet transfusion dependency rate were 54% and 29%, respectively. We identified 23 different mutations. Most common mutations occurred in SRSF2 (N=5, 21%), TET2 (N=5, 21%), U2AF1 (N=5, 21%), and TP53 (N=4, 17%). Ten (42%) patients had 1 mutation, and 14 (58%) had ≥2 mutations. Treatment included hypomethylating agents (HMA) (N=10, 42%), growth factors (N=11, 46%), steroid (N=4, 17%), testosterone (N=2, 8%), cyclosporine (N=2, 8%), rituximab (N=1, 4%), immunoglobulin (N=1, 4%), vitamin B12 and iron (N=1, 4%). Seven (29%) patients received ≥2 treatments. Median follow up duration was 17.5 months (range 8.9-26.1). Median time from the diagnosis to treatment was 2.1 months (range 0-26.8). 2) Molecular correlation with response The overall response rate (RR) was 50% (hematological or symptomatic improvement). Most responders (67%) were treated with HMA (p=0.013). HMA treatment effect was not significantly associated with DNA methylation genes (DNMT3A, IDH1, IDH2 and TET2, all p>0.05). The RR was 100% for the three patients with IDH1 mutation (treated with HMA, steroid and erythropoietin stimulating agent (ESA), respectively). The RR was 100% for the 3 patients with ZRSR2 mutation (2 HMA, 1 testosterone). The RR was 0% for 3 patients with SF3B1 mutation (1 testosterone and ESA, 1 vitamin B12 and iron, and 1 HMA). The number of mutations had no impact on RR (p=0.41). Table demonstrates the RR for each treatment. 3) Survival and progression outcome At the last day of follow up, RBC and platelet transfusion dependency rate were 38% and 25%, respectively. The median PFS was 16.9 months (95% CI: 7.5-65.3). Six patients (25%) progressed to myeloid malignancy with 4 myelodysplastic syndrome (MDS) and 2 acute myeloid leukemia (AML). Five patients progressed with worsening cytopenias. Among the 4 MDS patients, they had SF3B1, TET2, and ASXL1 mutations at the diagnosis of CCUS. Within the 2 AML pts, 1 had RUNX1 mutation, 1 had BCOR, DNMT3A, PHF6, RUNX1, SF3B1, STAG2, and TET2 mutations at the diagnosis of CCUS. The median OS was not reached with an estimated 2 year OS 77%. Three (13%) patients progressed with cytopenia and died. Their NGS at CCUS diagnosis showed ASXL1, TP53 and U2AF1 mutations, respectively. Conclusion Patients with CCUS responded to available treatments used for myeloid diseases. HMA were effective in this cohort. Mutation profile may have an impact on treatment response. Studies of larger cohorts are needed to validate our findings. Additionally, development of response and progression criteria would be helpful for such patients for reporting treatment outcomes. Disclosures Shah: Dren Bio: Consultancy.

The effect of an instantaneous dependency rate on the social equitability of hybrid PAYG public pension schemes

The defined convex combination (DCC) pay-as-you-go public pension systems recently introduced in the literature are a form of hybridization between defined benefit (DB) and defined contribution (DC) designed to maintain intergenerational social equitability by reacting to demographic shocks in an optimal way. In this paper, we augment DCC schemes with the assumption that the dependency ratio between pensioners and workers is driven by an exogenously modelled instantaneous stochastic rate of change. This assumption enjoys support from the empirical data and allows explicit solutions for the contribution and replacement rate processes which make transparent the nature of the dynamic evolution of a DCC system, as well as the role of the variables involved. The analysis of intergenerational social equitability measures under the assumption of an instantaneous dependency rate confirms the view expressed in previous literature that neither DB nor DC achieves social fairness, and that DCC plans have the potential to improve on both. We perform a calibration test, and our findings seem to indicate that in ageing economies the DC system might indeed be superior to the DB one in terms of intergenerational fairness.

Socio-Economic and Demographic Factors of Poverty Alleviation in Pakistan: A Case Study of Southern Punjab

This study aims to explore the socio-economic and demographic determinants of poverty in Southern Punjab by using the cross sectional data consisting of 785 household heads. Binary logistic regression and ordinary least square method are used for estimation. The findings exhibit that the variables like family system, household size, presence of disease and status of employment of household head are positively and significantly related to poverty whereas household head age, rural-to-urban migration, years of schooling, number of earners, women status of work, remittances, the physical assets value and ownership of house significantly and negatively influence the likelihood of poverty and positively influence the per capita income of the households in Southern Punjab. The study also provides the comparison of regional and division level. It is concluded that DG Khan division is the poorest among all the divisions of the southern Punjab. In DG Khan Division, the households have less education, high dependency ratio. In rural areas of southern Punjab, there is more poverty as compare to urban areas. The rural poverty is due to many factors like high dependency rate, lower level of education, adoption of profession, lower per capita income, dissaving. It is suggested that education should be promoted, employment opportunity should be provided so that dependency rate may be reduced, rural areas should be restructured by provision of basic necessities of life.

Google and Segmentation of the Islamic Finance Body of Knowledge

The study sets out to make evident the existences of segmentation of the Islamic finance body of knowledge (BOK). The segmentation results from the combination of dependency of Islamic finance researchers on google and using Islamic finance terms (IFTs) as search keywords. The study defines Islamic finance terminology as the Arabic/Islamic terms unique to Islamic finance literature written in English, e.g. Shariah. A distinctive feature of Islamic finance terms is that a single term can have many spelling variations. Firstly, to validate the presence of BOK segmentation, we investigated spelling variation among IFTs through a variation analysis among a sample of chosen terms. Secondly, we established the dependency of producers and users of Islamic finance literature on online resources and especially Google and Google Scholar using a survey. Lastly, we observed segmentation in the BOK by examining the absence of search results that overlap for IFTs and their variations. The spelling variations among our samples ranged from zero to eight with an average of (4.8) spelling variations per IFT. The dependency rate on online resources among our respondents was (99%) on Google, while Google Scholar scored (98%). The search results’ analysis yielded zero overlaps between the search results confirming the actuality of segmentation.