Prognostic Impact of TS, MTHFR and XRCC1 Genetic Variants in 113 Patients with Myelodysplastic Syndromes

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1675-1675
Author(s):  
Federica Loscocco ◽  
Giuseppe Visani ◽  
Elisa Giacomini ◽  
Annamaria Ruzzo ◽  
Sara Galimberti ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Genetic Variants ◽  
Rank Test ◽  
P Value ◽  
Prognostic Impact ◽  
Genotype Distribution ◽  
Log Rank Test ◽  
Hazard Risk ◽  
Significant Difference ◽  
Variant Alleles

Abstract Background: Several studies have suggested that genetic variability related with single nucleotide polymorphisms (SNPs) of the BER system, DNA synthesis and folate-metabolizing pathway genes could modulate DNA repair capacity. Moreover, these genes are supposed to be related to cancer risk. However, the prognostic impact of the association of individual and/or combined genetic variants in patients with myelodysplastic syndromes (MDS) remains undetermined. Methods: We genotyped 113 MDS patients, 54 with IPSS low/int-1 receiving only best supportive care (BSC group) and 59 with IPSS int-2/high treated with azacitidine (AZA-group), for the following polymorphisms: XRCC1 194 and 399, APE1 148, XRCC3 241, TS5'-UTR (2R/3R and G/C) and 3'-UTR (6bp+/6bp-), MTHFR 677 and 1298. Genomic DNA was analyzed by High Resolution Melting assay and restriction digests of PCR products. Overall survival (OS) was calculated using the Kaplan-Meier estimate probabilities, and differences between survival curves were analyzed by the log-rank test. Multivariate analyses were performed using the Cox method. Results: For all the target genes, the distribution of genotypes was consistent with the Hardy-Weinberg equilibrium. Among the baseline characteristics analyzed (age, sex, diagnosis according to WHO, hemoglobin) there was no statistically significant difference in the genotype distribution of studied polymorphisms. In the BSC group, the variants XRCC1 399 GG [Hazard ratio (HR)=7.07; p=0.02], -6/-6 of TS3'-UTR (HR=4.65; p=0.05), 2R/3G, 3C/3G, 3G/3G of TS5'-UTR (HR=11.44; p=0.02) and TT of MTHFR 677 (HR=67.12; p<0.001), were associated with a statistically significant adverse clinical outcome compared to variant alleles (Table 1). This is consistent with the enzymatic activity reduction attributed to these genetic variants. Multivariable regression model analysis was also performed in the AZA group for the same genetic variants. We found similar results for the association between XRCC1 399 GG(HR=5.71 p=0.002), TS3'-UTR +6/+6(HR=0.097 p=0.004), MTHFR 677 TT (HR=8.58 p<0.001) and survival, but not for SNPs in TS5'-UTR (Table 2). Finally, we performed an exploratory analysis to investigate the combined effect of the unfavorable genotypes on survival. In the BSC group, the 3-year OS was 33% for those patients with ≥2 variant alleles, as compared to 62.5%, and 100%, respectively, for those with 2 or 0/1 variant alleles. The predictive role of the adverse genotypes combination on survival was confirmed also in the AZA group, suggesting that patients with a higher number of genetic variants had a shorter survival. Interestingly, when we compared survival of patients with adverse genotypes between BSC and AZA groups, we did not find any statistically significant difference between the 2 groups (Kaplan-Meyer and Log-rank test). Therefore, we speculated that azacitidine could give a survival advantage to patients with unfavorable genetic variants, independently from IPSS at diagnosis. Conclusion: Our study reveals, for the first time, an associations between genetic variants in TS, MTHFR and XRCC1 genes, BSC, azacitidine and survival in MDS patients. If confirmed, they could represent new prognostic markers able to provide guidance for clinical management of MDS patients. In particular, the presence of adverse genotypes could represent a biomarker to treat patients with low-risk IPSS with azacitidine, if confirmed on larger series. Further studies with larger population are needed to validate these associations, especially in SNPs with low variant allele frequency. Table 1. Gene Genotype Hazard risk 95,0% CI forHazard Risk Lower 95,0% CI forHazard Risk Upper p value XRCC1 399 [G/G] versus [A/G-A/A] 7,072 1,295 38,619 0,024 TS5'-UTR [3G/3G, 3G/3C, 2R/3G] versus [2R/2R, 2R/3C, 3C/3C] 11,447 1,330 98,544 0,026 TS3'-UTR [Del/Del] versus [Del/Ins, Ins/Ins] 4,653 0,946 22,874 0,058 MTHFR 677 [T/T] versus [C/T-C/C] 67,125 6,409 703,081 <0,001 Table 2. Gene Genotype Hazard risk 95,0% CI forHazard Risk Lower 95,0% CI forHazard Risk Upper p value XRCC1 399 [G/G] versus [A/G-A/A] 5,713 1,904 17,142 0,002 TS3'-UTR [Ins/Ins] versus [Ins6/del6, del6/del6] 0,097 0,019 0,479 0,004 MTHFR 677 [T/T] versus [C/T-C/C] 8,587 2,749 26,828 <0,001 Disclosures Finelli: Celgene: Other: Speaker, Research Funding; Novartis: Other: Speaker; Janssen: Other: Speaker.

scholarly journals Outcome of Adolescents and Young Adults with Acute Myeloid Leukemia (AML) As Compared to Pediatric AML Patients: Real World Data from SEER Registry

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4484-4484
Author(s):  
Smith Giri ◽  
Nunnery Sara ◽  
Syed S. Nasir ◽  
Michael G Martin
Keyword(s):  
Overall Survival ◽  
Pediatric Patients ◽  
Survival Curve ◽  
Population Based ◽  
Early Mortality ◽  
Rank Test ◽  
P Value ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Significant Difference

Abstract Background: Limited data exists regarding the characteristics and outcomes of adolescents and young adults (AYAs) with acute myeloid leukemia (AML) which are largely under-represented in both pediatric and adult trials. We sought to compare the characteristics and outcomes of AYAs with AML using a large population based registry in the United States. Methods: We utilized Surveillance Epidemiology and End Results (SEER)-18 registry to identify all pediatric (0-18 years) and AYA (age 19-30 years) patients diagnosed with AML using appropriate histology codes based on the International Classification of Diseases for Oncology, 3rd version. Patients with acute promyelocytic leukemia (APL) were excluded from all analysis. Survival statistics were computed for each group using actuarial (Kaplan-Meier method) and compared using Z test for comparison of population proportions. Early mortality, defined as mortality within 1 month of diagnosis, was used as a surrogate for treatment related mortality. Kaplan Meier survival curves were plotted and compared using log-rank test. Multivariate analysis was done using logistic regression and Cox proportional hazard regression model. All p values were two sided and the level of significance was chosen at 0.05. Results: A total of 6343 eligible patients were identified, which comprised 2836 (44.7%) AYAs. A total of 52% (n=3346) were males, whereas 76%(n=4825) were whites. Histologically, majority of patients (56%; n=3545) were categorized as AML, not otherwise specified, followed by acute monocytic leukemia (9.9%, n=630). Majority (55%; n-3509) of the patients were diagnosed between 2001-2012. The early mortality rate was lower in the pediatric AML patients (pAML) as compared to AYAs (6.2% vs 9.2%; p<0.01). Similarly the 1 year (70.3% versus 62.1%; p <0.01) and 5 year (48.2% vs 36.4%; p<0.01) was higher in pediatric patients as compared to AYAs. Kaplan Meier plot showed worse overall survival of AYAs compared to pAMLs (Figure 1; p value of log rank <0.01). Multivariate logistic regression showed higher early mortality among AYAs as compared to pAML patients (OR 1.48; 95% CI 1.23-1.79; p<0.01). Similarly Cox regression showed worse overall survival among AYAs as compared to pAML (HR 1.34; 95% CI 1.26-1.44; p <0.01) Conclusions: Our population based analysis shows worse overall survival among AYAs as compared to pAML patients. Future clinical trials specifically focused on this age group are warranted to establish appropriate treatment regimens in this population. Figure 1. Kaplan Meier Survival curve showing cumulative survival among pediatric patients with AML as compared to AYAs. Log rank test showed statistically significant difference between the two curves (p value <0.01) Figure 1. Kaplan Meier Survival curve showing cumulative survival among pediatric patients with AML as compared to AYAs. Log rank test showed statistically significant difference between the two curves (p value <0.01) Disclosures No relevant conflicts of interest to declare.

Prognostic Impact of VH Gene Mutational Status and CD38 Expression in Japanese CLL Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4783-4783
Author(s):  
Hiromi Koiso ◽  
Masamitsu Karasawa ◽  
Arito Yamane ◽  
Takeki Mitsui ◽  
Takafumi Matsushima ◽  
...  
Keyword(s):  
Overall Survival ◽  
Peripheral Blood ◽  
Germ Line ◽  
Rank Test ◽  
Prognostic Impact ◽  
Cd38 Expression ◽  
Log Rank Test ◽  
Mutational Status ◽  
Significant Difference ◽  
Vh Gene

Abstract In the western countries, it has been well established that both immunoglobulin VH gene mutational status and CD38 expression are useful prognostic markers in chronic lymphocytic leukemia (CLL). However, it is not clear whether it is also true in other regions, especially such as Japan where CLL incidence is not so frequent as other countries. Therefore, we investigated the prognostic impact of VH gene mutational status and CD38 expression in Japanese B-CLL. The subjects of this study were 44 patients (29 males and 15 females) referred to our institutions between March 1999 and March 2004. The median age at the time of diagnosis was 68 years (37–92 years). The diagnosis was based on immunophenotypic analysis and cell morphology analyzed on Wright’s–stained peripheral blood and bone marrow smears. Median follow-up period of these patients was 4.0 years (0.5–34.2 years). cDNA mainly prepared from peripheral blood samples of the CLL patients was amplified using VH family-specific framework region primers or leader primers, and CH primers. PCR products were sequenced directly or after TA-cloning using the BigDye Terminator Cycle Sequencing FS Ready Reaction kit on a 310 Genetic Analyzer. Nucleotide sequences were compared to the nearest germ line VH genes in databases: IMGT, V-QUEST or IgBLAST. Of 44 B-CLL patients, IgH variable region genes could be sequenced from their cDNA in 43 patients; no amplified band was obtained in 1 patient. The usage of the seven VH gene families in the 43 B-CLL patients were as following: VH 1, 4/43 (9.3%); VH 2, 2/43 (4.6%); VH 3, 23/43 (53.5%); VH 4, 12/43 (27.9%); VH 5, 1/43 (2.3%); VH 6, 1/43 (2.3%); VH 7, 0/43 (0%). Eighteen cases (41.9%) displayed unmutated V H genes, defined as the sequences having more than or equal to 98% homology with nearest germ line gene, and 25 cases (58.1%) showed somatically mutated, defined as less than 98% homology. The proportion of unmutated cases in this study was almost comparable to previous reports, which showed a range of 30% to 50%. It have been uniformly reported that prognostic difference is apparent between unmutated (bad) and mutated (good) groups. Also in this study, the overall survival, defined as the time from diagnosis to death from any cause or to last contact, was significantly shorter for unmutated cases compared to mutated cases estimated by the Kaplan-Meier method as previous reports: predicted 50% survival rate for the unmutated cases was 9.1 years, but that for mutated cases did not reach the median survival. The difference was significant (p=0.029, log-rank test). Cell surface CD38 expression, which has been reported to correlate with a poor prognosis, was analyzed by flow cytometry in all patients. With the cut off level of 30% in CD19+CD5+ lymphocytes, 13 patients (29.5%) were estimated to be CD38 positive and 31 patients (70.5 %) to be negative. There was no significant difference in overall survival between those 2 groups (p=0.519, log-rank test). In conclusion, VH gene mutational status is a strong prognostic indicator whereas CD38 expression is not in our B-CLL cohort.

Influence of the fusion gene ETV6-RUNX1 in the prognosis of the Pediatric B- Precursor Acute Lymphoblastic Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2515-2515
Author(s):  
Alejandro Contento-Gonzalo ◽  
Antonio Jimenez-Velazco ◽  
Alcala-Peña Magdalena ◽  
Manuel Barrios ◽  
Katie Hurst ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Rank Test ◽  
Prognostic Impact ◽  
Excellent Outcome ◽  
Log Rank Test ◽  
Significant Difference

Abstract Abstract 2515 INTRODUCTION AND OBJECTIVES: The ETV6-RUNX1 (TEL-AML1) rearrangement comes from the translocation of two chromosomes t(12;21)(p12;q22), and represents one of the most frequently detected anomalies (15–30%) in the B-precursor Acute Lymphoblastic Leukemia (B-ALL). It must be identified by polymerase chain reaction (PCR) or fluorescent in situ hybridization (FISH) methods, since this translocation is not detected by conventional cytogenetic techniques. The prognostic value of ETV6-RUNX1 is still a matter of controversy. Recently, the group of the St Jude Children's Hospital reported an excellent outcome in patients carrying the translocation, whereas the BMF group did not find any significant difference in the survival of ETV6-RUNX1 positive patients when compared to ETV6-RUNX1 negative. The aim of our study has been to determine the prognostic impact of the ETV6-RUNX1 rearrangement in patients diagnosed of B-ALL in our Hospital, after a long period of follow-up and with the same Spanish treatment protocols (from PETHEMA and SHOP groups). PATIENTS AND METHODS: All patients with B-ALL diagnosis from January 1997 to May 2011 were included in the study: in total, 114 patients with a mean of age of 6 ys (0.3–14). The type of leukemia was ALL common (83 patients), pro-B (17 patients), pre-B (13 patients) and mature (1 patient). All the children over 1 yr received treatment according to PETHEMA group protocols, adjusted to the risk. Children under 1 yr were treated following SHOP group protocols. Seventeen patients received an allogeneic transplantation. The main clinical features of the positive and negative patients for ETV6-RUNX1 are detailed in table 1. ETV6-RUNX1 assay was performed in our laboratory by RT-PCR, according to the European BIOMED project methodology. RESULTS: ETV6-RUNX1 was found in 31 of the 114 patients (27.2%). These patients showed a significantly higher frequency of myeloid antigens (p<0.001), and were always positive for CD10 (p=0.006). All cases of positive ETV6-RUNX1 were over 2 years old. No significant differences between positive and negative ETV6-RUNX1 were obtained when complete remissions (100 vs 80%), relapse (16 vs 20%) or deaths (10 vs 13%) were analyzed. Furthermore, estimation of disease free survival (DSF) at 14 ys for both groups were similar: 80 ± 8% for positive vs 66 ± 7% for negative (p=0.21, log-rank test). And the same happened for overall survival (OS): 87 ± 7% for positive vs 83 ± 5% for negative (p=0.4, log-rank test). DISCUSSION: In our series, including patients with B-ALL treated with similar protocols with long periods of follow-up, we could not find differences between positive and negative ETV6-RUNX1 patients. It is well known that the intensity of the chemotherapy regimen and the age of inclusion in different protocols may influence the prognosis. Therefore, at present, it is still a matter of discussion if previous reported differences in the B-ALL ETV6-RUNX1 positive group could be explained by a different stratification in risk groups or by different chemotherapy regimens. This work has been funded by a grant from AECC, Carmen Lavigne Prize 2010 Disclosures: No relevant conflicts of interest to declare.

P4698Survival outcomes in patients with Eisenmenger syndrome after heart-lung or bilateral sequential lung transplantation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Kearney ◽  
N Bart ◽  
K Khush ◽  
D Hayes ◽  
A Keogh
Keyword(s):  
Lung Transplantation ◽  
Septal Defect ◽  
Cardiac Repair ◽  
Rank Test ◽  
P Value ◽  
Eisenmenger Syndrome ◽  
Post Transplant ◽  
Log Rank Test ◽  
Significant Difference

Abstract Background Eisenmenger syndrome (ES) is defined as pulmonary hypertension secondary to a right to left intracardiac shunt, commonly an atrial septal defect (ASD) or ventricular septal defect (VSD). Heart-lung (HLTx) or bilateral sequential lung transplantation (BSLT) are both treatment options for some candidates. The choice between these two procedures has varied historically and according to transplant centre preference and donor availability. We completed a retrospective study to determine if BSLT with cardiac repair was associated with better outcomes compared to HLTx. Aim This study compared post-transplant survival in patients with ES undergoing HLTx or BSLT. Method Using the International Society Heart and Lung Transplantation Registry data, we identified all patients with ES between October 1, 1987 and March 31, 2018. Results A total of 177 patients underwent HLTx for ES ASD and 101 who underwent BSLT with cardiac repair. Median follow up was 890 days (range 0–9888 days) for the entire post-transplant cohort. 126 HLTx and 66 BSLT patients died in the follow up period. A total of 173 ES VSD patients underwent HLTx in the database, and 52 underwent BSLT with cardiac repair. Median follow up was 460 days (range 0–8406 days) for the entire post-transplant cohort. 116 HLTx and 36 BSLT patients died during the follow up period. Figure 1 demonstratres the comparative Kaplan-Meier survival curves following BSLT or HLTx for Eisenmenger's ASD and VSD patients. No statistically significant difference in Eisenmenger survival between combined heart-lung transplantation or bilateral sequential lung transplantation group (ASD log rank test p value = 0.99, VSD log rank test p value = 0.1 performed for the first 6 year). Figure 1 Conclusions Our analysis determined that patients with ES and either VSD or ASD had similar long-term survival comparing HLTx with BSLT and cardiac repair.

Allogeneic Stem Cell Transplantation for Patients with Chemo-Refractory or Progressive Aggressive Non-Hodgkin’s Lymphomas.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3265-3265
Author(s):  
Mehdi Hamadani ◽  
Kristie A. Blum ◽  
Patrick Elder ◽  
Thomas S Lin ◽  
Pierluigi Porcu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Rank Test ◽  
P Value ◽  
Log Rank Test ◽  
Significant Difference ◽  
Hodgkin's Lymphomas

Abstract Background: Patients (pts) with chemo-refractory (Cref) and/or progressive aggressive non-Hodgkin’s lymphomas (A-NHL) generally have a poor clinical outcome. Autologous stem cell transplantation (SCT) has limited efficacy in this setting. Studies reporting outcomes of allogeneic (Allo) SCT in pts with Cref A-NHL are limited. Methods: 108 pts with A-NHL underwent Allo-SCT between 1988 and 2007 at our institution. 46 A-NHL pts with Cref (i.e pts with <50% reduction in tumor size and/or persistent bone marrow involvement following chemotherapy) or progressive disease (PD) by CT-criteria were eligible for this analysis. Positron emission tomography (PET) or PET/CT scans were not performed to assess response. Results: The median age was 46 years (range 22–63 yrs). 39 pts received matched sibling allografts, while 7 underwent unrelated donor SCT. All except 3 pts received myeloablative conditioning. 38 pts received BU/CY-based conditioning, while BEAM (n=5) or Flu/Bu (n=3) was employed in the remaining pts. Diagnosis included diffuse large B-cell lymphoma (n=18), Burkitt’s lymphoma (n=3), transformed lymphoma (n=5), mantle cell lymphoma (n=11) and T-cell lymphomas (n=9). The median number of prior therapies was 3 (range 1–8). 32 pts had Cref disease, while 14 had PD. 41 pts had stage III/IV disease, 23 had elevated LDH, while 36 had extranodal involvement. Median follow-up of surviving pts following Allo-SCT is 5-yrs. The 5-yr overall survival (OS), progression free survival (PFS), and relapse rate for the whole cohort (n=46) was 38%, 34%, and 35% respectively. Rate of grade II-IV acute graft-versus-host disease (GVHD) was 43% (n=20). Among the 33 evaluable pts rate of chronic GVHD was 75%. Overall non-relapse mortality rate was 37%. No significant difference in the baseline characteristics of pts with Cref and PD was present. The 5-yr OS and PFS rates for pts with Cref and PD were 46% vs. 21% (p-value=0.01; log-rank test), and 46% vs. 7% (p-value=0.0002; log-rank test) respectively. On multivariate analysis only PD at the time of SCT predicted for worse OS and PFS. Conclusion: Our study shows encouraging efficacy of Allo-SCT in a group of A-NHL pts with Cref disease by CT scan-criteria who often fail following Auto-SCT. However outcomes of pts with PD remain dismal despite Allo-SCT, and our data question the practice to perform allografting in A-NHL pts with PD. We hypothesize that PET scans may help better define patients with aggressive NHL appearing not to have responded to salvage chemotherapy by standard CT criteria that still may derive significant benefit from allografting.

Prognostic Factors in the UK LRF CLL4 Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 299-299 ◽  
Author(s):  
David Graham Oscier ◽  
Rachel Wade ◽  
Jenny Orchard ◽  
Zadie Davis ◽  
Giles Best ◽  
...  
Keyword(s):  
Risk Group ◽  
Univariate Analysis ◽  
Treatment Modalities ◽  
Rank Test ◽  
P Value ◽  
Cox Regression Analysis ◽  
Log Rank Test ◽  
Significant Difference ◽  
Trisomy 12 ◽  
Vh Genes

Abstract The LRF CLL4 trial randomised 777 previously untreated patients with Binet stage progressive A, B or C disease between January 1999 and October 2004 to receive either Chlorambucil, Fludarabine or Fludarabine and Cyclophosphamide. Interphase FISH for deletions of chromosome 6q, 11q, 13q, 17p and trisomy 12, IgVH gene mutational status (98% cut off), CD38 (7% cut off) and ZAP70 (10% cut off) expression were measured at randomisation on 579, 523, 535 and 478 patients respectively. Leukemic cells from 39 patients utilised the VH3-21 gene of whom 33 had homologous CDR3’s. Among the biological markers, log rank analysis showed that >20% p53 loss, del 11q, unmutated VH genes, high CD38 and high ZAP 70 correlated with disease progression or death (Table 1) but not deletion of chromosome 6q, 13q and trisomy 12 (p=0.7, 0.3 and 0.2 respectively). There was no difference in PFS or response duration between the 52 patients with 5–20% p53 loss and the 494 patients with no p53 loss. Multivariate Cox regression analysis showed that >20% p53 loss (p<0.0001), unmutated IgVH genes (p=0.0001), deletion of 11q (p=0.02) and male gender (p=0.03) were independent risk factors for short PFS. The effects of stage and age were overridden by FISH abnormalities. High ZAP70 expression was only significant when VH gene mutation status was not included in the model. CD38 expression was only significant in univariate analysis. Table 1 Variable Progression or Death/N Univariate p-value(log rank test) Gender Male 384/573 0.002 Female 111/204 17q(p53) No 131/546 <0.00005 Yes 21/33 IgVH Unmutated 105/203 <0.00005 Mutated 225/320 del 11q No 288/463 <0.00005 Yes 87/116 ZAP70 Negative 140/242 0.003 Positive 158/236 CD38 Negative 110/201 0.0001 Positive 227/334 Among the 320 unmutated cases there was no significant difference in PFS between those with 100% homology (227 cases) and those with 99% or 98% homology to the germline sequence (93 cases). Mutated VH3-21 cases were more likely to express ZAP70 than other mutated cases, p=0.004. Excluding patients with >20% p53 loss, patients using the VH3-21 gene had similar progression free survival (PFS) to those remaining patients with unmutated VH genes and an inferior PFS to those with mutated VH genes (2p=0.0001). The adverse prognostic significance of 11q deletions was not clearly evident in an interim analysis presented at ASH ‘05. Patients can now be divided into 3 risk groups (Table 2). This risk stratification provides the basis of evaluating differing treatment modalities for each risk group in subsequent clinical trials. Table 2 Risk Group Definition Progression or Death/N Univariate p-value (log-rank test) 3 yr PFS Poor >20%p53 loss 28/33 0% Standard Unmutated VH or 11q deletion or VH3-21 208/292 <0.00001 24.7% Good Mutated VH(excl VH3–21) 79/161 55.0%

scholarly journals Reducing the Dosing Frequency of Selective Digestive Tract Decontamination to Three Times Daily Provides Effective Decontamination of Potentially Pathogenic Micro-Organisms

2021 ◽  
Author(s):  
Jara Rebekka de la Court ◽  
Kim C.E. Sigaloff ◽  
Thomas Groot ◽  
Johan I. van der Spoel ◽  
Rogier P. Schade
Keyword(s):  
Digestive Tract ◽  
Rank Test ◽  
P Value ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Log Rank Test ◽  
Significant Difference ◽  
Selective Digestive Tract Decontamination ◽  
Before And After ◽  
Micro Organisms

Abstract PurposeThis study evaluated the effectiveness of selective digestive tract decontamination (SDD) application three times daily (t.i.d.) compared to the standard four times daily (q.i.d.).MethodsRetrospective equivalence study with a before-and-after design on a tertiary ICU in which the SDD frequency was reduced from q.i.d. to t.i.d. All patients with ICU admissions ≥72h, and with ≥2 surveillance cultures collected on different dates were included in this study. We compared successful decontamination of Gram-negative bacteria (GNB). Furthermore, time to decontamination, ICU-acquired GNB bacteraemia and 28-day mortality were compared between the two groups. ResultsIn total 1958 ICU admissions (1236 q.i.d., 722 t.i.d). Decontamination was achieved during the first week of admission in 77% and 76% of patients receiving SDD q.i.d and t.i.d., respectively. Successful decontamination within 14 days (without consecutive acquisition of Gram-negative bacteria) was achieved in 69.3.% of the admissions with q.i.d. versus 66.8% in t.i.d. SDD (p-value = 0.2519). The proportions of successful decontamination of GNB were equivalent in both groups (-0.025, 98% CI: -0.087; 0.037). There was no significant difference in time to decontamination between the two regimens (log-rank test p-value = 0.55). Incidence (episodes/1000 days) of ICU-acquired GNB bacteraemia was 0.9 in both groups and OR for death at day 28 in the t.i.d. group compared to the q.i.d. group was 0.99 (95% confidence interval, 0.80-1.21). ConclusionsThis study shows that a t.i.d. application regimen provides equally effective SDD compared to the standard q.i.d. regime, for both microbiological and clinical outcome measures.

scholarly journals COVID-19 in Hospitalized Ethiopian Children: Characteristics and Outcome Profile

2020 ◽  
Author(s):  
Tigist W. Leulseged ◽  
Ishmael S. Hassen ◽  
Endalkachew H. Maru ◽  
Wuletaw C. Zewde ◽  
Negat W. Chamiso ◽  
...  
Keyword(s):  
Clinical Improvement ◽  
Disease Severity ◽  
Rank Test ◽  
P Value ◽  
Rt Pcr ◽  
Chi Square ◽  
Survival Distribution ◽  
Exact Test ◽  
Log Rank Test ◽  
Significant Difference

ABSTRACTBackgroundConsidering the number of people affected and the burden to the health care system due to the Coronavirus pandemic, there is still a gap in understanding the disease better leaving a space for new evidence to be filled by researchers. This scarcity of evidence is observed especially among children with the virus. Understanding the disease pattern and its effect among children is vital in providing timely and targeted intervention.AimTo assess the characteristics and outcome profile of 115 RT-PCR confirmed children with COVID-19, and to determine the presence of significant difference in disease severity and survival distribution between groups among children admitted to Millennium COVID-19 Care Center in Ethiopia.MethodsA prospective cohort study was conducted among 90 consecutively admitted eligible RT-PCR confirmed COVID-19 children from end of June to mid September, 2020. Frequency tables, KM plots, median survival times and Log-rank test were used to describe the data and compare survival distribution between groups. A chi-square test/ Fischer’s exact test were used to determine the presence of a significant difference between the independent variables and disease severity. A statistically significant difference was detected for variables with a P-value of ≤ 0.05. Survival experience of different groups was compared using KM survival curves. Log-rank test was used to assess the presence of significant difference among survival distributions of groups for equality where a statistically significant difference in survival distribution between groups was detected for variables with a P-value of ≤ 0.05.ResultsFrom the 90 children, 67 (74.4%) achieved clinical improvement and 23 (25.6%) were censored. There was no death. The median time to clinical improvement was 14 days. The median age of the participants was 15 years and 63.3% of the participants were females. The commonest reported route of disease transmission was through close contact with a diagnosed person (45.6%). Only three (3.3%) had a history of pre-existing comorbid illness. More than a quarter (26.7%) had one or more symptoms at admission, the commonest being cough (22.2%). Seventy three (81.1%) of the patients had mild COVID-19 at admission and the rest (18.9%) had moderate disease. On the chi-square and Fischer’s exact test, children with one or more symptom at presentation (73.3% Vs 36.7%, p-value= 0.0001), fever (40.0 % Vs 60.0%, p-value=0.045), cough (20.0 % Vs 80.0%, p-value=0.0001), sore throat (44.4 % Vs 55.6%, p-value=0.011), and headache (44.4 % Vs 55.6%, p-value=0.011) were more likely to develop moderate COVID-19. On the log rank test, a significant difference in survival between groups was observed only for sex. A significantly longer time was needed for female patients to achieve clinical improvement compared to male patients (15 days Vs 14 days, p-value= 0.042).ConclusionsThe average duration of time to clinical improvement was 14 days and 74.4% achieved clinical improvement. There was no death during the observation period. The pediatric patients seemed to have a milder disease presentation and a favorable outcome compared to other countries report and also the adult pattern observed in our country. Having particular symptom groups is associated with the development of moderate COVID-19. Being female seemed to delay the time to clinical improvement. Further multicenter study with a large sample size is recommended to reach at a better conclusion.

scholarly journals Clinical evaluation of the failure rate of metallic brackets bonded with orthodontic composites

2012 ◽  
Vol 23 (4) ◽  
pp. 399-402 ◽  
Author(s):  
Fábio Lourenço Romano ◽  
Rodrigo Alexandre Valério ◽  
Jaciara Miranda Gomes-Silva ◽  
José Tarcísio Lima Ferreira ◽  
Gisele Faria ◽  
...  
Keyword(s):  
Failure Rate ◽  
Orthodontic Treatment ◽  
Color Change ◽  
Rank Test ◽  
Initial Alignment ◽  
Bond Failure ◽  
Log Rank Test ◽  
Significant Difference ◽  
Mandibular Teeth

The purpose of the present study was to evaluate in vivo the failure rate of metallic brackets bonded with two orthodontic composites. Nineteen patients with ages ranging from 10.5 to 38.7 years needing corrective orthodontic treatment were selected for study. The enamel surfaces from second premolars to second premolars were treated with Transbond Plus-Self Etching Primer (3M Unitek). Next, 380 orthodontic brackets were bonded on maxillary and mandibular teeth, as follows: 190 with Transbond XT composite (3M Unitek) (control) and 190 with Transbond Plus Color Change (3M Unitek) (experimental) in contralateral quadrants. The bonded brackets were light cured for 40 s, and initial alignment archwires were inserted. Bond failure rates were recorded over a six-month period. At the end of the evaluation, six bond failures occurred, three for each composite. Kaplan-Meyer method and log-rank test (Mantel-Cox) was used for statistical analysis, and no statistically significant difference was found between the materials (p=0.999). Both Transbond XT and Transbond Plus Color Change composites had low debonding rates over the study period.

Effectiveness of the Bactiseal Universal Shunt for reducing shunt infection in a sub-Saharan African context: a retrospective cohort study in 160 Ugandan children

2014 ◽  
Vol 13 (2) ◽  
pp. 140-144 ◽  
Author(s):  
Jordan D. Lane ◽  
John Mugamba ◽  
Peter Ssenyonga ◽  
Benjamin C. Warf
Keyword(s):  
Cohort Study ◽  
Low Income ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Shunt Infection ◽  
Low Income Countries ◽  
Rank Test ◽  
Log Rank Test ◽  
Significant Difference ◽  
Chi Square Analysis

Object Antibiotic-impregnated shunts have yet to find widespread use in the developing world, largely due to cost. Given potential differences in the microbial spectrum, their effectiveness in preventing shunt infection for populations in low-income countries may differ and has not been demonstrated. This study is the first to compare the efficacy of a Bactiseal shunt system with a non–antibiotic-impregnated system in a developing country. Methods The Bactiseal Universal Shunt (BUS) was placed in 80 consecutive Ugandan children who required a shunt. In this retrospective cohort study, the outcome for that group was compared with the outcome for the immediately preceding 80 consecutive children in whom a Chhabra shunt had been placed. The primary end points were shunt failure, shunt infection, and death. Shunt survival was analyzed using the Kaplan-Meier method. Significance of differences between groups was tested using the log-rank test, chi-square analysis, Fisher's exact test, and t-test. Results There was no difference between groups in regard to age, sex, or etiology of hydrocephalus. Mean follow-up for cases of nonfailure was 7.6 months (median 7.8 months, interquartile range 6.5–9.5 months). There was no significant difference between groups for any end point. The BUS group had fewer infections (4 vs 11), but the difference was not significant (p = 0.086, log-rank test). Gram-positive cocci were the most common culturable pathogens in the Chhabra group, while the only positive culture in the BUS group was a gram-negative rod. Conclusions These results provide equipoise for a randomized controlled trial in the same population and this has been initiated. It is possible that the observed trends may become significant in a larger study. The more complex task will involve determining not only the efficacy, but also the cost-effectiveness of using antibiotic-impregnated shunt components in limited-resource settings.

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