Frequency of adverse reactions to first-line anti-tuberculosis chemotherapy in patients with relapse(RTB)and newly diagnosed tuberculosis(NDTB)

2018 ◽  
Author(s):  
Dmytro Butov ◽  
Mykhailo Kuzhko ◽  
Ganna Stepanenko ◽  
Tetiana Butova
Keyword(s):  
Adverse Reactions ◽  
Newly Diagnosed ◽  
First Line ◽  
Tuberculosis Chemotherapy

scholarly journals Effectiveness and Safety of Additive Therapy and Monotherapy of Glaucoma with Prostamides

2019 ◽  
Vol 16 (3) ◽  
pp. 366-370
Author(s):  
I. R. Gazizova ◽  
S. R. Zainullina ◽  
E. B. Martynova
Keyword(s):  
Adverse Reactions ◽  
Initial Level ◽  
Open Angle Glaucoma ◽  
Newly Diagnosed ◽  
First Line ◽  
Main Method ◽  
Group Iii ◽  
Group I ◽  
Additive Component ◽  
First Time

Increased intraocular pressure (IOP) is the main risk factor for the development of primary open-angle glaucoma (POAG). Nowadays medicine that reduce IOP remain the main method of treating for POAG. The first-line drugs for POAG are prostaglandin analogues. In Russia, for the first time, it appeared not in the form of a fixed combination (Bimoptic). In this regard it is very important to evaluate the clinical efficacy and safety of Bimoptic as a monotherapy and additive component in the treatment of patients with POAG. Patients and methods. Patients were divided into 3 groups depending on the treatment. Group I comprised of 34 patients with newly diagnosed glaucoma on monotherapy with bimatoprost 0.03 %. Group II consisted of 30 patients who started taking bimatoprost 0.03 % as a replacement for latanoprost 0.005 % or travoprost 0.004 %. There were 32 patients in group III, who were prescribed bimatoprost 0.03 % as an adjuvant therapy for B-blockers (BB) 0.5 % or carbonic anhydrase inhibitors (ICA) 2 %. Results. According to the results of the clinical study, it was found that instillation of Bimoptik as a monotherapy for newly diagnosed POAG leads to a decrease in IOP level by an average of 32.1 % of the initial level. With the additive tactics of assigning Bimoptik to the BB and / or IKA, the level of IOP goes down by 10.6 % more. If prostaglandin is changed to Bimoptik, the level of IOP decreases by 12.6 % of the prostaglandin-associated values. Also according to acquired data, Bimoptik has a low percentage of adverse reactions, slight hyperemia and discomfort were observed in 5.2 % of cases in all groups. Conclution. Bimoptik effectively reduces the level of IOP in both monotherapy and additive tactics with the least adverse reactions.

Influence of the Acetylation Type on the Incidence of Isoniazid-Induced Hepatotoxicity in Patients with Newly Diagnosed Pulmonary Tuberculosis

2020 ◽  
Vol 65 (7-8) ◽  
pp. 31-36
Author(s):  
N. M. Krasnova ◽  
N. E. Evdokimova ◽  
A. A. Egorova ◽  
O. I. Filippova ◽  
E. A. Alekseeva ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Clinical Laboratory ◽  
Clinical Manifestations ◽  
Normal Activity ◽  
Slow Acetylators ◽  
Nucleotide Polymorphisms ◽  
Newly Diagnosed ◽  
Single Nucleotide ◽  
Tuberculosis Chemotherapy ◽  
Genetically Determined

Introduction. Liver damage can be a dangerous side effect of using isoniazid. Individual susceptibility to isoniazid in humans is dependent on the presence of N-acetyltransferase 2 allelic variants in genome. It was imperative to assess the effect of genetically determined isoniazid acetylation rate in terms of risk of developing isoniazid-induced hepatotoxicity, as well as prevention of potential hepatopathy, and improvement of tuberculosis chemotherapy safety. Aim. To study the effect of acetylation type on the incidence of isoniazid hepatotoxicity in residents of the Sakha Republic (Yakutia) with newly diagnosed pulmonary tuberculosis. Methods. The study included 112 patients with newly diagnosed pulmonary tuberculosis. Genotyping was performed using real-time polymerase chain reaction. The following single nucleotide polymorphisms were studied: rs1801280, rs1799930, rs1799931, rs1799929, rs1208, rs1041983. Hepatotoxicity was determined based on the results of clinical laboratory monitoring and using the criteria developed by the European Association for the Study of the Liver (2019). Results. Hepatotoxic reactions developed more often in slow acetylators (43.2%), compared to fast acetylators (20.7%) and intermediate acetylators (10.9%); p=0.002. Serum alanine aminotransferase activity was 5 or more times above the upper limit of normal activity in 37.8% of slow acetylators, and in 8.7% of intermediate acetylators; p=0.001. Clinical manifestations of isoniazid hepatotoxicity were observed more often in slow acetylators (29.7%), than in fast acetylators (3.4%); p=0.000. Conclusion. Slow acetylation type ought to be considered an important risk factor for developing isoniazid hepatotoxicity in patients with pulmonary tuberculosis.

Incorporation of plasma-based next-generation sequencing to improve guideline-concordant molecular testing in patients with newly diagnosed metastatic nonsquamous non-small cell lung cancer.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 14-14
Author(s):  
Charu Aggarwal ◽  
Melina Elpi Marmarelis ◽  
Wei-Ting Hwang ◽  
Dylan G. Scholes ◽  
Aditi Puri Singh ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Practice Change ◽  
Molecular Testing ◽  
Tier 2 ◽  
Newly Diagnosed ◽  
Next Generation ◽  
First Line ◽  
Tier 1 ◽  
Tier 3 ◽  
The Impact

14 Background: Current NCCN guidelines recommend comprehensive molecular profiling for all newly diagnosed patients with metastatic non-squamous NSCLC to enable the delivery of personalized medicine. We have previously demonstrated that incorporation of plasma based next-generation gene sequencing (NGS) improves detection of clinically actionable mutations in patients with advanced NSCLC (Aggarwal et al, JAMA Oncology, 2018). To increase rates of comprehensive molecular testing at our institution, we adapted our clinical practice to include concurrent use of plasma (P) and tissue (T) based NGS upon initial diagnosis. P NGS testing was performed using a commercial 74 gene assay. We analyzed the impact of this practice change on guideline concordant molecular testing at our institution. Methods: A retrospective cohort study of patients with newly diagnosed metastatic non-squamous NSCLC following the implementation of this practice change in 12/2018 was performed. Tiers of NCCN guideline concordant testing were defined, Tier 1: complete EGFR, ALK, BRAF, ROS1, MET, RET, NTRK testing, Tier 2: included above, but with incomplete NTRK testing, Tier 3: > 2 genes tested, Tier 4: single gene testing, Tier 5: no testing. Proportion of patients with comprehensive molecular testing by modality (T NGS vs. T+P NGS) were compared using one-sided Fisher’s exact test. Results: Between 01/2019, and 12/2019, 170 patients with newly diagnosed metastatic non-Sq NSCLC were treated at our institution. Overall, 98.2% (167/170) patients underwent molecular testing, Tier 1: n = 100 (59%), Tier 2: n = 39 (23%), Tier 3/4: n = 28 (16.5%), Tier 5: n = 3 (2%). Amongst these patients, 43.1% (72/167) were tested with T NGS alone, 8% (15/167) with P NGS alone, and 47.9% (80/167) with T+P NGS. A higher proportion of patients underwent comprehensive molecular testing (Tiers 1+2) using T+P NGS: 95.7% (79/80) compared to T alone: 62.5% (45/72), p < 0.0005. Prior to the initiation of first line treatment, 72.4% (123/170) patients underwent molecular testing, Tier 1: n = 73 (59%), Tier 2: n = 27 (22%) and Tier 3/4: n = 23 (18%). Amongst these, 39% (48/123) were tested with T NGS alone, 7% (9/123) with P NGS alone and 53.6% (66/123) with T+P NGS. A higher proportion of patients underwent comprehensive molecular testing (Tiers 1+2) using T+P NGS, 100% (66/66) compared to 52% (25/48) with T NGS alone (p < 0.0005). Conclusions: Incorporation of concurrent T+P NGS testing in treatment naïve metastatic non-Sq NSCLC significantly increased the proportion of patients undergoing guideline concordant molecular testing, including prior to initiation of first-line therapy at our institution. Concurrent T+P NGS should be adopted into institutional pathways and routine clinical practice.

Improving time to molecular testing results in patients with newly diagnosed, metastatic non-small cell lung cancer (NSCLC).

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 244-244
Author(s):  
Stephanie Ossowski ◽  
Elad Neeman ◽  
Charles Borden ◽  
Amy Ying Ju Lin ◽  
Raymond Liu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Turnaround Time ◽  
Small Cell ◽  
Pathological Diagnosis ◽  
Genomic Testing ◽  
Newly Diagnosed ◽  
Small Cell Lung ◽  
First Line ◽  
Metastatic Nsclc

244 Background: Next generation sequencing (NGS) is a crucial component of evaluation of newly diagnosed patients with metastatic non-small cell lung cancer (NSCLC) to determine appropriate first line treatment. Delays in NGS can lead to psychologic distress for patients and can affect choices in first line therapy, especially for patients with underlying targetable mutations. While more data is needed to benchmark turnaround time for NGS results, guidelines and expert consensus suggest time from diagnosis to treatment should be 15 days and turnaround time for genomic testing 10-14 days. This study was aimed at reducing time to NGS results in a large integrated health care system. Methods: Through the ASCO Quality Training Program, we reviewed electronic medical records of 25 patients with newly diagnosed, untreated metastatic NSCLC from 12/2018 to 9/2020 and determined number of days from pathological diagnosis to NGS results. We reviewed process maps for oncology, pathology, the internal data management division, and a genomic testing company to determine factors leading to significant preventable delays. Since 11/2020, we created an automated weekly report using CoPath to identify new pathological diagnoses of potential metastatic NSCLC. The oncology department reviewed these cases weekly and NGS orders were placed for patients with metastatic NSCLC. Eleven additional patients with newly diagnosed metastatic NSCLC were included in the prospective cohort. Results: Demographic characteristics are noted in Table. Our intervention reduced median time from pathological diagnosis to NGS results from 24 to 19 days. Median time from biopsy results to NGS order was reduced from 7 to 1 day. Time from specimen being sent from pathology to NGS vendor was a median of 6 days in both cohorts. Total time from pathological diagnosis to appropriate treatment was reduced from a median of 33 to 25 days. Conclusions: Delays in time to NGS results can be reduced by improved communication between departments and simple, automated interventions to ensure results are efficiently released to an oncologist. Additional Plan-Do-Study-Act cycles are currently being developed to further reduce time from biopsy results to NGS results. [Table: see text]

scholarly journals Decitabine as a First-Line Treatment for Older Adults Newly Diagnosed with Acute Myeloid Leukemia

2017 ◽  
Vol 58 (1) ◽  
pp. 35 ◽  
Author(s):  
Hyunsung Park ◽  
Haerim Chung ◽  
Jungyeon Lee ◽  
Jieun Jang ◽  
Yundeok Kim ◽  
...  
Keyword(s):  
Older Adults ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Line Treatment ◽  
Newly Diagnosed ◽  
First Line ◽  
First Line Treatment ◽  
Acute Myeloid

scholarly journals Short-term outcomes associated with temozolomide vs. PCV chemotherapy for 1p/19q-codeleted WHO grade III anaplastic oligodendrogliomas: a national evaluation

2020 ◽  
Author(s):  
Nayan Lamba ◽  
Malia McAvoy ◽  
Vasileios K. Kavouridis ◽  
Timothy R. Smith ◽  
Mehdi Touat ◽  
...  
Keyword(s):  
Cox Regression ◽  
Long Term Results ◽  
National Database ◽  
Newly Diagnosed ◽  
First Line ◽  
Short Term ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Pcv Chemotherapy ◽  
Grade Iii

AbstractPURPOSEThe optimal chemotherapy regimen between temozolomide (TMZ) and procarbazine, lomustine, and vincristine (PCV) remains uncertain for newly-diagnosed anaplastic oligodendroglioma (AO). We therefore addressed this question using a national database.METHODSPatients newly-diagnosed with 1p/19q-codeleted W.H.O. grade III AO between 2010-2016 were identified from the National Cancer Database. Predictors of receiving first-line single-agent TMZ vs. multi-agent PCV were assessed by multivariable logistic regression. Overall survival (OS) was estimated by Kaplan-Meier techniques and evaluated by multivariable Cox regression.RESULTS1,360 AO patients were identified: 74.5% (n=1,013) treated with TMZ, 9.6% (n=131) with PCV, and 15.9% (n=216) with no chemotherapy in the first-line setting. In multivariable logistic analysis, PCV utilization increased from 2010 to 2016 (OR=1.38/year, 95%CI: 1.22-1.56, p<0.001) and was less commonly utilized in privately insured patients (OR=0.38 vs. uninsured, 95%CI: 0.15-0.97, p=0.04). In survival analyses (33.1% reached endpoint), there was no difference in unadjusted OS between TMZ (5yr-OS 60.1%, 95%CI: 55.9-64.1) and PCV (5yr-OS 61.1%, 95%CI: 45.6-73.5; p=0.42). There remained no OS difference between TMZ and PCV in the 75.9% (n=1,032) of AO patients that also received radiotherapy (p=0.51), in the Cox regression analysis adjusted by age, extent of resection, and radiotherapy (TMZ vs. PCV HR=1.31, 95%CI: 0.83-2.08, p=0.24), and in subgroup analyses that incorporate KPS or MGMT status.CONCLUSIONSIn a national database of AOs managed in the ‘real-world’ setting, there is no difference in the short-term mortality between first-line TMZ and PCV chemotherapy. These findings provide preliminary data while we await the long-term results from the CODEL trial.

scholarly journals Prevalence of primary drug resistant tuberculosis in a tertiary care hospital, Nepal

2015 ◽  
Vol 4 (4) ◽  
pp. 36-38
Author(s):  
R Khunjeli ◽  
U R Mohsin ◽  
S K Shrestha ◽  
S Adhikari ◽  
B Srivastava ◽  
...  
Keyword(s):  
Armed Forces ◽  
Care Hospital ◽  
Drug Resistant ◽  
Newly Diagnosed ◽  
First Line ◽  
Sensitivity Testing ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Resistant Strains ◽  
Primary Drug

 Background & objectives: Tuberculosis is a transmissible disease mainly due to inhalation of infected droplet nuclei. The burden of drug resistant tuberculosis is very high in our neighboring countries India and China. Prevalence of primary drug resistant disease is difficult to estimate in our country because culture and sensitivity is not done routinely. This study was an attempt to find out the prevalence of drug resistant in newly diagnosed tuberculosis patients serving in the Nepalese Armed Forces. Methodology: Medical records of patients serving in the Nepalese Armed Forces who had the provisional diagnosis of pulmonary tuberculosis for the first time from July 2012 to June 2014 were analyzed. They had their sputum subjected for both smear and culture with sensitivity testing. Out of 134 patients, 62 had culture positive for Mycobacterium tuberculosis and drug sensitivity was done for the first line 4 antitubercular drugs. Results: Drug resistant strains were found in 5 cases (8.1%) of which 2 (3.2%) were resistant to 4 first line drugs - rifampicin, isoniazid, ethambutol and streptomycin. Prevalence of isoniazid resistance was the highest, found in 3 cases (4.8%). Conclusion: Primary drug resistant tuberculosis in newly diagnosed cases was high even in young healthy adults, and isoniazid resistant strains were the commonest.DOI: http://dx.doi.org/10.3126/jcmc.v4i4.11970

scholarly journals The Clinical Utility of Pharmacogenomics Testing in Assessing Tyrosine Kinase Inhibitor Therapy, Intolerance and Responses in Patients with Chronic Myelogenous Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5440-5440
Author(s):  
Darci Zblewski ◽  
Naseema Gangat ◽  
Michelle A. Elliott ◽  
Aref Al-Kali ◽  
Mark R. Litzow ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Chronic Myelogenous Leukemia ◽  
Metabolic Pathways ◽  
Research Funding ◽  
Small Sample ◽  
Poor Metabolizers ◽  
Myelogenous Leukemia ◽  
Second Line ◽  
Newly Diagnosed ◽  
First Line

Abstract Background: Chronic myelogenous leukemia (CML) is a BCR-ABL1 driven myeloid neoplasm, with excellent response rates to tyrosine kinase inhibitors (TKI). TKI such as imatinib (IM), dasatinib (DAS), nilotinib (NIL), bosutinib (BOS), and ponatinib (PON) currently US FDA approved, have dramatically changed survival outcomes. That being said, two main challenges exist; suboptimal responses and TKI intolerance. The reason why some patients tolerate/respond to TKI better than others is unknown, but is potentially explainable based on drug metabolism. The field of pharmacogenomics (PGX) is rapidly evolving, with commercial panel's rapidly assessing metabolic pathways such as cytochrome P450 (CYP), UGTA1A, p-glycoprotein/ABCB1. We carried out this study using a 22 gene-PGX panel to assess potential causes of TKI related intolerance and suboptimal responses in compliant patients. Methods: Twenty-nine Mayo Clinic patients with CML were prospectively recruited after informed consent. Buccal swabs were utilized for PGX testing to assess variations/polymorphisms involving CYP3A4/5, 1A2, 2C9, UGT1A1, amongst others (www.Oneome.com). Three groups of patients were recruited, those with i) TKI intolerance, ii) suboptimal responses by ELN criteria, iii) and newly diagnosed cases, to assess if PGX testing could explain TKI intolerance or resistance, or alter choice of therapy in newly diagnosed cases. A pharmacology review was obtained to interpret reports in all cases. Results: 29 patients with CML were prospectively enrolled, median age 64 years, 15 (52%) male. At last follow up (median 21 months), 3 (10%) deaths and no disease progressions were documented. 82% received first line IM, whereas 18% received first line DAS. Major metabolic pathways assessed for IM included, CYP3A4 and 5, while minor pathways included 2C19, 2C9 and 2D6. Majority (83%) of IM patients had normal major pathways with 17% being intermediate-normal. With regards to the minor pathways, 25% were rapid metabolizers for 2C19, whereas 29% were intermediate and 4% poor metabolizers for 2C9 and 50% and 16% were intermediate and poor metabolizers for 2D6. In all IM treated patients PGX testing did not completely explain intolerance or resistance and did not change clinical decision making. Front line DAS was used in 18% and the major pathway assessed was CYP 3A4, with 80% being normal and 20% being intermediate metabolizers. Once again PGX testing did not completely explain intolerance/resistance and no therapeutic changes were based on PGX analysis. Seventeen (59%) patients received second line TKI therapy (50% each for intolerance and resistance), with DAS (58%) and NIL (29%), being the two most common. Once again for DAS, 90% had normal 3A4 metabolism while 10% were intermediate and for NIL 80% were normal and 20% intermediate. Only one of 2 NIL treated patients with UGTA1A polymorphisms developed indirect hyperbilirubinemia (grade 1). In the second line setting, PGX testing did not completely explain or alter treatment decisions. BOS was used as a third line agent in 3 (>10%) patients, 2 who remained refractory and one with intolerance, and all three were normal CYP3A4 metabolizers. None of these patients developed diarrhea a common side effect of BOS. PON was used in one patient with intermediate CYP3A4 metabolism as a 5th line agent and the patient continues to have refractory disease with no thrombotic events. In all cases, no changes were made to concomitant medications based on PGX testing. Conclusion: In conclusion, while PGX testing has rapidly evolved and become commercially available, in the context of TKI therapy for CML, while it offers useful insights on minor metabolic derangements and side effects like NIL induced hyperbilirubinemia, in our study, currently limited by a small sample size, it did not completely explain TKI intolerance or resistance. Recruitment of additional patients (n=100) and correlations with plasma drug levels are currently ongoing. Table. Table. Disclosures Al-Kali: Novartis: Research Funding. Stewart:Amgen Inc., Celgene, Roche, Seattle Genetics: Research Funding; Amgen Inc., BMS, Celgene, Takeda, Roche, Seattle Genetics, Janssen, Ono: Consultancy.

scholarly journals Remission in Patients with Acute Promyelocytic Leukemia Treated with Arsenic Trioxide (varitrinox) As the First Line in Colombia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 3-3
Author(s):  
Gustavo Milone ◽  
Samuel Sarmiento Doncel ◽  
Carol Agudelo Rico ◽  
Fabiola Vizcarra Reyes ◽  
Gina Alejandra Diaz Mosquera ◽  
...  
Keyword(s):  
High Risk ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Conflicts Of Interest ◽  
Promyelocytic Leukemia ◽  
Remission Induction ◽  
Intermediate Risk ◽  
Newly Diagnosed ◽  
First Line ◽  
Risk Patients

Acute promyelocytic leukemia (APL) is a subtype of Acute Myeloid Leukemia (AML) in which a chromosomal translocation t (15; 17) (q22; q12) is generated by fusing produces a hybrid PML / RARα gene, generating an altered signal . The combination of transretinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of newly diagnosed standard risk patients with acute promyelocytic leukemia (APL) in several countries. The objective of the present study is to describe the frequency of remission in patients with acute promyelocytic leukemia who were administered as a first line Arsenic Trioxide (varitrinox) during the period from November 2017 to June 2020 in Colombian patients. Methods: Retrospective observational and descriptive study of 12 patients diagnosed with acute promyelocytic leukemia treated with ATO Arsenic trioxide (Varitrinox) as first line, the source of information was provided by the treating hematologists (medical records) by filling out the technical concept format. Active pharmacovigilance scientist in Colombia, this format keeps the identification information of the patient anonymized and the confidentiality of the data is guaranteed as well as compliance with the rules of good clinical practice. Results: Twelve patients with age range between 22 and 69 years with a median age of 34.0 were analyzed. It was found in the analysis that 100% had induction hematologic remission with a median of 45 days. 75% of patients received ATO + ATRA and were at low and intermediate risk, the remaining 25% received ATRA + ATO + Chemotherapy and were at high risk, and intermediate risk. 91.7% of molecular remission in consolidation was obtained and it was measured in cycle 3 by means of PCR (undetectable), 8.3% (n = 1) was positive 3% and is finishing consolidation. Regarding the most frequent adverse events, intravascular coagulation (n = 9), neutropenia (n = 6) and thrombocytopenia (n = 6) were observed. 75% of patients are disease-free, 16.7% are on maintenance (they received ATO + ATRA + Induction chemotherapy) and 8.3% are on consolidation. So far, none of the patients under study have died. Conclusions: Our results support the use of ATO (Varitrinox) in newly diagnosed APL patients (as first line), as a care strategy for low, intermediate and high risk patients. The role of ATRA-ATO is guaranteed in other studies where they manage patients of different risks. Key words: Arsenic trioxide, leukemia promyelocytic acute, leukemia myeloid acute, remission induction, tretinoin. Disclosures No relevant conflicts of interest to declare.

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