Evaluating the Incidence of Leukopenia and Neutropenia with Valproate, Quetiapine, or the Combination in Children and Adolescents

2009 ◽  
Vol 43 (5) ◽  
pp. 822-830 ◽  
Author(s):  
Aminur Rahman ◽  
Lisa M Mican ◽  
Charles Fischer ◽  
Angela H Campbell
Keyword(s):  
Children And Adolescents ◽  
State Hospital ◽  
Laboratory Data ◽  
Child And Adolescent ◽  
Severe Neutropenia ◽  
Combination Group ◽  
Hematologic Toxicity ◽  
Monotherapy Group ◽  
Increased Risk ◽  
Significant Difference

Background At the Austin State Hospital, Austin, TX, a number of cases of neutropenia and leukopenia have been observed in children and adolescents who were treated with the combination of valproate and quetiapine. Use of this combination has raised concerns regarding an increased risk of hematologic toxicity. Objective To evaluate the incidence of leukopenia and neutropenia associated with the use of valproate, quetiapine, or the combination in the child and adolescent population. Methods This study was a retrospective evaluation of patients from the child and adolescent psychiatric service of the Austin State Hospital who were treated with valproate, quetiapine, or the combination. Subjects were selected from patients discharged between August 1, 2004, and August 31, 2007. Laboratory data were evaluated to determine the incidence and severity of leukopenia and neutropenia associated with valproate, quetiapine, and a combination of the 2. Results A total of 131 patients were included in the study. Analysis of the laboratory data revealed a combined incidence of neutropenia and/or leukopenia of 44%, 26%, and 6% in the combination group, valproate monotherapy group, and quetiapine monotherapy group, respectively. Differences in the incidence of neutropenia and/or leukopenia between the quetiapine monotherapy group and valproate monotherapy group, as well as the quetiapine monotherapy group and the combination group reached statistical significance. A significant difference was found among groups based on absolute neutrophil count Common Toxicity Criteria severity (p < 0.001). The combination group differed significantly in incidence of moderate-to-severe neutropenia (14 cases) from both the valproate (5 cases) and quetiapine (0 cases) monotherapy groups, A significantly greater number (44%) of African American patients experienced neutropenia and/or leukopenia than white (not Hispanic or Latino; 29%) or Hispanic or Latino (11%) patients. Conclusions Patients treated with valproate or the combination of valproate and quetiapine should be monitored for the occurrence of leukopenia and neutropenia. Controlled studies are warranted to examine possible pharmacokinetic and pharmacodynamic interactions with the combination of valproate and quetiapine to further evaluate the hematologic findings of this study.

scholarly journals AB0566 NAILFOLD EXTENT OF REDUCED CAPILLARY DENSITY IS ASSOCIATED WITH DIGITAL ULCERS AND WITH AN INCREASED RISK OF DIGITAL ULCERS IN SYSTEMIC SCLEROSIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1580.2-1580
Author(s):  
R. De Angelis ◽  
F. Salaffi
Keyword(s):  
Systemic Sclerosis ◽  
Laboratory Data ◽  
Quantitative Measure ◽  
Capillary Density ◽  
Optical Probe ◽  
Typical Feature ◽  
Slight Reduction ◽  
Digital Ulcers ◽  
Increased Risk ◽  
Significant Difference

Background:A growing evidence supports the role of microvasculopathy as a primary pathogenic event in systemic sclerosis (SSc). The most commonly used imaging technique to identify microangiopathy in SSc is high magnification videocapillaroscopy (NVC), and reduced capillary density and/or capillary loss, which is a typical feature of “scleroderma microangiopathy”, easily identified by NVC, has been associated with digital ulcers (DUs). Different approaches have been proposed to measure capillary density or capillary loss. Some of these were qualitative methods, others semi-quantitative, others only concerned a limited nailfold area, without ever evaluating the overall density, which is more suitable for quantitative estimate.Objectives:To assess the association between the extent of different values of nailfold capillary density and the presence of DUs and to identify the risk of developing DUs, based on quantitative parameters.Methods:The study involved 54 SSc selected patients (47 women and 7 men, mean age 59.5 years, 50 with limited and 4 with diffuse). The study population came from an ongoing database, that includes clinical and laboratory data of patients with definite SSc. A videocapillaroscope (VideoCap® 3.0, DS Medica, Milan, Italy) with a 200x optical probe was used. During examination, eight fingers (fingers 2–5 of each hand), 4 fields per finger, according to the standard literature were assessed. For each patient, a total of 32 images were collected, then classified as having either “normal”, “non-specific” or the “scleroderma pattern” (SP). Capillary density was defined as the number of capillaries/mm in the distal row, regardless of its shape and morphology. Avascular areas were defined by the absence of loops within a width/area extending over more than 500 microns. For each patient, the SP images were further graded with no/slight reduction of the capillary density (7-9 loops/mm) (NOR), with a well-defined reduction of capillary density (6-4 loops/mm) (RED) and with loss of capillaries (<4) plus avascular areas (AA). Then, the overall percentages were calculated (the number with SP, the number with NOR, with RED and with AA, respect to 32), thus obtaining the quantitative measures. All data were analysed using the MedCalc® version 18.6; 64-bit (MedCalc Software, Mariakerke, Belgium).Results:A total of 1728 images were analyzed. Patients with DUs were 16/54 (29.6%). All patients had a SP, but only five patients showed a SP along the entire nailfold. A comparison between patients with or without DUs showed a significant difference both for the overall extent of AA (p=0.032), and particularly for the overall extent of RED (p<0.001). No significant difference was found regarding the overall extent of the SP (p=0.085). Factor significantly associated with DUs in multivariate analysis was the overall extent of RED (p=0.0286). The ROC curve was very effective at discriminating the capillary feature able to distinguish patients with DUs from patients without DUs. The discriminatory power of the overall extent of RED was very good, with an AUC of 0.948 (95 % CI 0.852 ± 0.990). Then, we calculated the cut-off values of the overall extent of RED for presence/absence of DUs with the highest combination of sensitivity and specificity. The resulting cut-off value (Yourden index of 0.825) was >68.7 (sensitivity 92.31 %; specificity 90.24 %) with a LR+ of 9.46.Conclusion:Our data strongly support that the capillary density between 4 and 6 loops/mm is the best capillaroscopic quantitative measure associated with DUs and able to discriminate the probability of having DUs. If all SSc-specific antibodies and/or other laboratory/clinical parameters are not yet available, the overall capillary density can allow physicians to assess SSc patients easily, regarding DUs and risk for developing DUs.Disclosure of Interests:None declared

scholarly journals The Comparison of Hypomethylating Agents (HMA) Monotherapy with HMA Combined with Intensive Chemotherapy for Intermediate / High-Risk MDS or AML

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3903-3903
Author(s):  
Jiang Ji ◽  
Zhao Wang ◽  
Bing Han
Keyword(s):  
High Risk ◽  
Combination Therapy ◽  
Death Rate ◽  
Therapy Group ◽  
Meta Analysis ◽  
Combination Group ◽  
Combination Therapy Group ◽  
Hypomethylating Agents ◽  
Monotherapy Group ◽  
Significant Difference

Introduction: Hypomethylating agents (HMA) azacitidine and decitabine were the first-line therapy for intermediate/ higher-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients unsuitable for hematopoietic cell transplantation (HSCT). HMA combined with chemotherapy was recently used to achieve for a better outcome. However, few studies were carried out to compare the HMA monotherapy to the HMA and chemotherapy combination therapy. This meta-analysis aimed to compare the efficacy, survival benefit and safety of HMA monotherapy and combination therapy (with chemotherapy) in patients with intermediate/high-risk MDS or AML. Methods: Related articles published between January 2009 and April 2019 were selected and patients were separated as monotherapy group and combination group for meta-analysis. To further eliminate the potential influence of differences in patients' baseline characteristic between the two groups, subgroups with similar patients' baseline characteristics were selected for further analysis. Complete response (CR) rate, overall response (ORR) rate, 1-year overall survival (OS) rate, 1-month death rate and the proportion of adverse event (AE) were pooled and compared. Results: 13 RCT or cohort studies with 997 patients (790 in monotherapy group, 207 in HMA combination group) were selected for meta-analysis. For the pooled data, there was no significant difference in sex and cytogenetic risk between the 2 groups, but the age of combination therapy group was significantly younger than that of the monotherapy group (61.3±13.2 year-old vs 67.7±10.2 year-old, p=0.000). The CR and ORR rate were significantly higher in combination therapy group (53% vs 17%, p=0.000 for CR and 67% vs 44%, p=0.000 for ORR). However, the 1-year OS (56% for combination therapy vs 51% for HMA monotherapy group, p=0.282) and 1-month death rate (5% for combination therapy vs 4% for HMA monotherapy group, p=0.965) were similar between the two groups. The incidence of CTCAE grade 3-4 infection and bleeding were significantly higher (infection: 50% for combination therapy vs 25.7% for monotherapy group, p=0.003; bleeding: 27.5%% for combination therapy vs 7.8% for monotherapy group, p=0.004) in combination group. In subgroup analysis, 117 and 179 patients were included in combination group and HMA monotherapy group, respectively. There was no significant difference in age (69.5±4.6 vs 69.0±6.8 years old, p=0.451) and proportion of favorable/intermediate cytogenetic risk (62% vs 71%, p=0.114) between the two groups, but a significantly lower proportion of male was found in combination therapy group (57% vs 74%, p=0.003). Although combination group had a higher CR rate (49% vs 17%, p=0.000), it had similar ORR rate (58% vs 49%, p=0.140) to monotherapy group. Meanwhile, combination therapy came with higher 1-month death rate (12% vs 3%, p=0.008) and lower 1-year OS (54% vs 68%, p=0.013) compared with monotherapy group. Conclusions: HMA combined with chemotherapy could increase CR rate in all patients and ORR rate in younger patients, but could not improve OS. For patients with similar older age, combination therapy could result in higher 1-month death rate and less 1-year OS. Disclosures No relevant conflicts of interest to declare.

Risk Versus Benefit of Combined Aspirin and Warfarin Therapy in Patients With Atrial Fibrillation

2020 ◽  
pp. 089719002091663
Author(s):  
Tara A Nagaraj ◽  
Melissa J. Snider ◽  
Erica Davidson ◽  
Raul Weiss ◽  
Junan Li ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Combination Therapy ◽  
Major Bleeding ◽  
Therapy Group ◽  
Stable Coronary Artery Disease ◽  
Group Versus ◽  
Bleeding Risk ◽  
Combination Group ◽  
Monotherapy Group ◽  
Significant Difference

Purpose: Guidelines have differing recommendations for aspirin use in patients with an indication for anticoagulation. The purpose of this study was to evaluate the incidence of major bleeding and thromboembolic events (TEs) in patients with atrial fibrillation (AF) receiving warfarin alone (monotherapy group) versus warfarin plus aspirin (combination therapy group). Methods: This was a retrospective, cohort study including patients from a pharmacist-run anticoagulation clinic. Inclusion criteria were patients with AF receiving anticoagulation between January 2013 and January 2014 observed over 5 years. Results: One hundred forty-two patients were included in the combination group versus 89 in monotherapy group. In the combination group, 60 (42.3%) patients were on aspirin for no apparent indication, 19 (13.4%) had stable coronary artery disease and diabetes, and 26 (18.3%) had diabetes alone. Major bleeding occurred in 21 (14.9%) patients in the combination group versus 7 (7.9%) patients in the monotherapy group (odds ratio [OR] = 2.02, 95% confidence interval [CI]: 0.78-5.91; P = .17). TE occurred in 10 (7%) patients in the combination group versus 4 (4.5%) in the monotherapy group (OR = 1.61, 95% CI: 0.44-7.24; P = .57). There was no significant difference in bleeding ( P = .85) or TE ( P = .37) rates between aspirin indications in the combination group. Conclusion: Combination therapy versus monotherapy may increase bleeding risk with little benefit in decreasing AF-related stroke or cardiovascular events.

A Multicentre, Double-Blind, Randomized, Phase 2 Trial Comparing Pegfilgrastim with Filgrastim as an Adjunct to Chemotherapy for Acute Myeloid Leukaemia (AML).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 866-866 ◽  
Author(s):  
Alberto Bosi ◽  
Jeffrey Szer ◽  
Jeannine Kassis ◽  
Jorge Sierra ◽  
Claire Desborough ◽  
...  
Keyword(s):  
Median Time ◽  
Induction Chemotherapy ◽  
De Novo ◽  
Severe Neutropenia ◽  
Single Administration ◽  
Serious Adverse Events ◽  
Treatment Groups ◽  
Risk Of Death ◽  
Increased Risk ◽  
Significant Difference

Abstract BACKGROUND: Heil et al (Blood ‘97) demonstrated that the duration of neutropenia and its clinical consequences following induction chemotherapy for AML were significantly reduced by the addition of filgrastim, with no increased risk of death, second malignancy or relapse (ASH ‘99). A single injection of pegfilgrastim has been shown to be comparable to daily injections of filgrastim in the management of chemotherapy-induced neutropenia. The primary aim of this trial was to estimate the difference in time to recovery from severe neutropenia (SN, ANC < 0.5 x109/L) in the first induction chemotherapy cycle (Induction 1) in AML subjects treated with pegfilgrastim or filgrastim. METHODS: Subjects with de novo AML received 1 or 2 courses of induction chemotherapy (idarubicin 12mg/m2 IV days 1–3, cytarabine 100mg/m2 IV 12 hourly days 1–7 [IA 3+7]) then, if in remission, consolidation chemotherapy (cytarabine 2 [subjects < 55 years] or 3g/m2 [subjects ≥ 55 years] IV 12 hourly days 1, 3, 5). Subjects received either single administration 6μg pegfilgrastim or daily 5μg/kg filgrastim starting 24 hours after completion of chemotherapy until neutrophil recovery. Time to recovery from SN was defined as the number of days from the first day of chemotherapy until the first of two ANC consecutive values after the nadir that were ≥ 0.5 x 109/L whereas duration of SN was defined as the total number of days during the cycle with an ANC < 0.5 x 109/L. RESULTS: Of 84 subjects randomised into the study, 83 received study drug (42 pegfilgrastim, 41 filgrastim). The treatment groups were generally well balanced for demographics and baseline characteristics. The median time to recovery from SN (ANC < 0.5 x109/L) in Induction 1 was 22 days in both treatment groups (95% CI for treatment difference: −1.9, 1.9). There was also no statistically significant difference in the median duration of SN between the 2 groups (21 days pegfilgrastim, 20 days filgrastim). Subjects in the filgrastim group required a median of 16 daily injections compared to a single administration of pegfilgrastim in the second group. Median serum concentration of pegfilgrastim in Induction 1 remained above clinically relevant concentrations until 21 days after the start of chemotherapy, results that are consistent with the neutrophil-mediated clearance of pegfilgrastim. The incidence of serious adverse events was comparable between the 2 groups except for infectious complications, which were higher in the filgrastim group (5 subjects [12%] pegfilgrastim versus 9 subjects [22%] filgrastim). CONCLUSION: In the setting of the first cycle of IA 3+7 induction chemotherapy in AML patients, once per cycle administration of 6 mg pegfilgrastim or daily administration of 5mg/kg filgrastim result in similar median time to recovery to ANC ≥ 0.5 x109/L. Pegfilgrastim is safe and well tolerated in this subject population.

Vinblastine in Children and Adolescents With High-Risk Anaplastic Large-Cell Lymphoma: Results of the Randomized ALCL99-Vinblastine Trial

2010 ◽  
Vol 28 (25) ◽  
pp. 3987-3993 ◽  
Author(s):  
Marie-Cécile Le Deley ◽  
Angelo Rosolen ◽  
Denise M. Williams ◽  
Keizo Horibe ◽  
Grazyna Wrobel ◽  
...  
Keyword(s):  
High Risk ◽  
Children And Adolescents ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Hematologic Toxicity ◽  
Increased Risk ◽  
Large Cell Lymphoma ◽  
The Impact ◽  
To Receive

Purpose The impact of adding vinblastine to a 4-month chemotherapy regimen, based on the Non-Hodgkin's Lymphoma Berlin-Frankfurt-Münster 90 protocol, in childhood high-risk anaplastic large-cell lymphoma (ALCL) was assessed. Patients and Methods Children and adolescents with high-risk ALCL, defined by mediastinal, lung, liver, spleen, or skin involvement, were eligible for the trial. After a prephase and one chemotherapy course, patients were randomly assigned to receive either five further chemotherapy courses without vinblastine or the same regimen with one vinblastine injection (6 mg/m2) during each course followed by weekly vinblastine to complete a total of 1 year of treatment. The primary end point was event-free survival (EFS), analyzed on the intent-to-treat population. Results Between November 1999 and June 2006, 110 patients were randomly assigned to receive vinblastine, and 107 were randomly assigned not to receive vinblastine. Median follow-up was 4.8 years. Patients in the vinblastine arm had a significantly reduced risk of events during the first year (hazard ratio [HR] = 0.31; 95% CI, 0.15 to 0.67; P = .002) followed by an increased risk thereafter (HR = 4.98; 95% CI, 1.65 to 15.0; P = .003). Consequently, EFS at 1 year differed significantly (91% in the vinblastine group v 74% in the no-vinblastine group), with no difference at 2 years (73% and 70%, respectively). Overall EFS curves did not differ significantly (HR = 0.91; 95% CI, 0.55 to 1.5; P = .71). Thirty-one percent of weekly doses of vinblastine were reduced as a result of hematologic toxicity, although vinblastine was discontinued for toxicity in only three patients. Conclusion Adding vinblastine during induction and as maintenance for a total treatment duration of 1 year significantly delayed the occurrence of relapses but did not reduce the risk of failure.

scholarly journals Association between single nucleotide polymorphisms rs72525532, rs45596738, rs148759216, rs188133936, and rs114627122 of APOA5 gene in children and adolescents with metabolic syndrome

2019 ◽  
Vol 21 (4) ◽  
pp. 175-180
Author(s):  
Samaneh Salehi ◽  
Modjtaba Emadi-Baygi ◽  
Parvaneh Nikpour ◽  
Roya Kelishadi
Keyword(s):  
Metabolic Syndrome ◽  
Single Nucleotide Polymorphisms ◽  
Children And Adolescents ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Normal Children ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Significant Difference ◽  
Apoa5 Gene

Background and aims: The APOA5 gene is one of the genes involved in metabolic syndrome (MetS), as a constellation of several cardiovascular disease (CVD) risk factors. The present study evaluated the possible associations between five single nucleotide polymorphisms (SNPs) in the microRNA target site (miR-TS-SNPs) of the APOA5 gene with MetS. Methods: This case-control study included 57 MetS cases, along with 59 normal children and adolescents aged 9-18 years. All miR-TSSNPs rs188133936, rs72525532, rs45596738, rs148759216, and rs114627122 were genotyped by polymerase chain reaction-sequencing. Independent t-test, as well as the chi-square test and logistic regression analysis was used to determine the association of SNPs with MetS risk and its clinical components. Results: The mean (SD) age of MetS participants and controls was 12.35 (0.25) and 13.39 (0.38) years, respectively. Although no nucleotide changes were present in rs188133936, rs45596738, rs148759216, and rs114627122, a greater frequency of A insertion was detected in rs72525532 in MetS cases compared with the control group (P=0.012). This variant showed a significant difference in triglycerides (TG) and high-density lipoprotein cholesterol (HDL) levels between different genotype groups (P<0.0001 and P=0.05, respectively) in controls. Furthermore, AA insertion genotype was correlated with an increased risk of MetS (Odds ratio [95% CI] = 8.12 [0.966-68.27], P=0.05). Conclusion: This study was the first to investigate the association between rs188133936, rs45596738, rs148759216, rs76463524, and rs72525532 variants of the APOA5 gene and MetS. Our findings reveal that rs72525532 might have an impact on TG, HDL levels, and the risk of MetS

Breed related odds ratio and anatomic distribution of canine mast cell tumours in Austria

2014 ◽  
Vol 42 (06) ◽  
pp. 367-373 ◽  
Author(s):  
K. Freeman ◽  
G. Kirtz ◽  
E. H. Hooijberg ◽  
K. Sick ◽  
E. F. Leidinger
Keyword(s):  
Mast Cell ◽  
Disease Risk ◽  
Laboratory Data ◽  
Age Distribution ◽  
Odds Ratios ◽  
Skin Tumours ◽  
Increased Risk ◽  
Mixed Breed ◽  
Significant Difference ◽  
Anatomic Distribution

SummaryObjective: An increased risk of mast cell tumours (MCT) in certain breeds has been described repeatedly in the literature. The incidence of MCTs for registered breeds in Austria, an estimate of the risk by means of the odds ratios based on breed as well as the anatomic localisation of MCTs were examined. Material and methods: In the first part of the study, the ranking of breeds in Austria based on 147,802 dogs with known breed (including mixed breed) was determined, based on those dogs included in the laboratory data base from 2000 to 2010. In the second part of the study, 476 dogs were identified with MCTs and analysed by age, sex, Patnaik grade of MCT and breed distribution. The odds ratios with confidence intervals were calculated for all breeds with skin tumours. Results: The age distribution showed a peak in the age group from 6.1 to 8.0 years; 70% of MCTs were localised to the head and trunk. No significant difference was found based on gender. The evaluation of the odds ratios showed that only four of the 20 of the most popular in Austria breeds (Boxer, Bernese Mountain Dog, Golden Retriever, Spaniel) had an increased risk; on the other hand, some breeds which have not been previously identified in the literature were indicated to have a significantly increased risk for MCT (e.g., Dogo Argentino, Tibetan Spaniel, Pyrenean Mountain Dog, Beauceron, and Austrian Smooth-haired Hound). Conclusion and clinical relevance: Because disease risk may influence the popularity of some currently rare breeds, consultation with breeders and owners regarding the identification of the breeds newly identified in this study as an increased risk for development of mast cell tumours is indicated.

Concerns and Side Effects of Azathioprine During Adalimumab Induction and Maintenance Therapy for Japanese Patients With Crohn’s Disease: A Subanalysis of a Prospective Randomised Clinical Trial [DIAMOND Study]

2019 ◽  
Vol 13 (9) ◽  
pp. 1097-1104 ◽  
Author(s):  
Tadakazu Hisamatsu ◽  
Takayuki Matsumoto ◽  
Kenji Watanabe ◽  
Hiroshi Nakase ◽  
Satoshi Motoya ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Side Effects ◽  
Crohn's Disease ◽  
Adverse Effects ◽  
Multivariable Analysis ◽  
Dropout Rate ◽  
Rank Test ◽  
Combination Group ◽  
Monotherapy Group ◽  
Significant Difference

Abstract Background Combining a thiopurine with the human anti-tumour necrosis factor-α monoclonal antibody adalimumab for Crohn’s disease [CD] treatment is controversial with regard to efficacy and safety. By conducting a subanalysis of a multicentre, randomised, prospective, open-label trial [the DIAMOND study, UMIN registration number 000005146], we studied the risk of discontinuation of thiopurine in combination with adalimumab. Methods In the preceding DIAMOND study, we analysed the: [i] timing and reasons for dropout in the monotherapy group and combination group; [ii] risk factors for dropout in the combination group. Results There was no significant difference in the dropout rate up to Week 52 between the monotherapy group and combination group [p = 0.325]. The main reason for study dropout was active CD in the monotherapy group, whereas it was adverse effects in the combination group [Fisher’s exact test, p <0.001]. Kaplan–Meier analyses revealed significantly earlier dropout in the combination group [log-rank test, p = 0.001]. Multivariable analysis revealed low body weight to be a risk for dropout due to adverse effects in the combination group. Conclusions Combination of azathioprine with adalimumab resulted in dropout in the early stage of the study due to side effects of azathioprine, in comparison with late dropout due to active CD in the adalimumab monotherapy group.

Cigarette Smoking and Irinotecan Treatment: Pharmacokinetic Interaction and Effects on Neutropenia

2007 ◽  
Vol 25 (19) ◽  
pp. 2719-2726 ◽  
Author(s):  
Jessica M. van der Bol ◽  
Ron H.J. Mathijssen ◽  
Walter J. Loos ◽  
Lena E. Friberg ◽  
Ron H.N. van Schaik ◽  
...  
Keyword(s):  
Cigarette Smoking ◽  
Treatment Failure ◽  
Pharmacokinetic Interaction ◽  
Underlying Mechanism ◽  
Fixed Dose ◽  
Hematologic Toxicity ◽  
Uridine Diphosphate ◽  
Time Curve ◽  
Increased Risk ◽  
Significant Difference

PurposeSeveral constituents of cigarette smoke are known to interact with drug metabolizing enzymes and potentially affect treatment outcome with substrate drugs. The purpose of this study was to determine the effects of cigarette smoking on the pharmacokinetics and adverse effects of irinotecan.Patients and MethodsA total of 190 patients (49 smokers, 141 nonsmokers) treated with irinotecan (90-minute intravenous administration on a 3-week schedule) were evaluated for pharmacokinetics. Complete toxicity data were available in a subset of 134 patients receiving 350 mg/m2or 600 mg flat-fixed dose irinotecan.ResultsIn smokers, the dose-normalized area under the plasma concentration-time curve of irinotecan was significantly lower (median, 28.7 v 33.9 ng · h/mL/mg; P = .001) compared with nonsmokers. In addition, smokers showed an almost 40% lower exposure to SN-38 (median, 0.54 v 0.87 ng · h/mL/mg; P < .001) and a higher relative extent of glucuronidation of SN-38 into SN-38G (median, 6.6 v 4.5; P = .006). Smokers experienced considerably less hematologic toxicity. In particular, the incidence of grade 3 to 4 neutropenia was 6% in smokers versus 38% in nonsmokers (odds ratio [OR], 0.10; 95% CI, 0.02 to 0.43; P < .001). There was no significant difference in incidence of delayed-onset diarrhea (6% v 15%; OR, 0.34; 95% CI, 0.07 to 1.57; P = .149).ConclusionThis study indicates that smoking significantly lowers both the exposure to irinotecan and treatment-induced neutropenia, indicating a potential risk of treatment failure. Although the underlying mechanism is not entirely clear, modulation of CYP3A and uridine diphosphate glucuronosyltransferase isoform 1A1 may be part of the explanation. The data suggest that additional investigation is warranted to determine whether smokers are at increased risk for treatment failure.

scholarly journals Clinical Characteristics of COVID-19 Patients with Gastrointestinal Symptoms

2021 ◽  
Vol 24 (2) ◽  
pp. 131-138
Author(s):  
Mahnaz Montazeri ◽  
Nastaran Maghbouli ◽  
Raika Jamali ◽  
Alireza Sharifi ◽  
Marzieh Pazoki ◽  
...  
Keyword(s):  
Disease Severity ◽  
Clinical Characteristics ◽  
Laboratory Data ◽  
Gastrointestinal Symptoms ◽  
Chi Square ◽  
Increased Risk ◽  
Gi Symptoms ◽  
Significant Difference ◽  
Treatment Data ◽  
Risk Of Disease

Background: We aimed to assess the gastrointestinal (GI) manifestations of patients with severe acute respiratory syndrome coronavirus 2 infection and determine factors predicting disease prognosis and severity among patients with GI symptoms. Methods: In this retrospective study, we evaluated laboratory confirmed (by real-time polymerase chain reaction) inpatient cases of coronavirus-associated disease 2019 (COVID-19), referred to Sina hospital, a tertiary educational hospital of Tehran University of Medical Sciences, from March 10 to May 20, 2020. Demographic and clinical characteristics, laboratory data, outcomes and treatment data were extracted and analyzed using SPSS version 20. Results: A total of 611 patients (234 women and 377 men) were included with 155 patients having GI symptoms. The most prevalent reported GI symptom was nausea/vomiting in 115 (18.8%) of patients. A total of 20 patients (3.2%) only had GI symptoms (without respiratory symptoms). There was no statistically significant difference in the clinical outcomes, disease severity, intensive care unit (ICU) admission and mortality between patients with and without GI symptoms. Aspartate Aminotransferase level was associated with 446% increased risk of disease severity (adjusted odds ratio: 5.46, 95% CI: 2.01 to 14.81) (P=0.040) among patients with GI symptoms. Additionally, we found that treatment with antibiotics in addition to mechanical ventilation was associated with increased survival among patients with GI symptoms (Pearson Chi square: 6.22; P value: 0.013). Conclusion: More attention should be paid to patients with only GI symptoms for early patient detection and isolation. Moreover, patients with GI manifestations are not exposed to higher rates of disease severity or mortality.

Sign in / Sign up

Export Citation Format

Share Document