Rituximab (Ritux) Maintenance Infusions in Immune Thrombocytopenia (ITP) to Prolong Remission Following Relapse after Initial Ritux Induction but Responded to a Second Course

Abstract Introduction: ITP is an autoimmune disease characterized by low platelet counts and variable bleeding. Ritux treatment of ITP patients (pts) receiving 375 mg/m2 once a week for 4 weeks results in 50-60% achieving complete responses (CR). However, most pts will relapse, usually around 1 year from initial treatment. In a previous study, 20 pts were retreated with a second round of 4 infusions of ritux and 16 (80%) had essentially the same response to retreatment with ritux with the second set of 4 infusions (Hasan A, AmJHem, 2009). Maintenance ritux infusions in Non-Hodgkin Lymphoma are now well-demonstrated to increase cure despite variable infusion schedules. This retrospective study explores ritux maintenance in pts with ITP or / and other autoimmune cytopenias who responded to but relapsed after a first induction with Ritux and who then received a 2nd to 4th induction with ritux. Methods: We enrolled 17 pts with ITP, Autoimmune hemolytic anemia (AIHA), Autoimmune Neutropenia (AIN) and/or Evans syndrome, who previously responded to but then relapsed following induction with 4 ritux infusions. Ritux was administered to relapsed pts at standard dose during weeks 1, 2, 3, and 4 of induction. During the maintenance phase, single infusions of ritux were given at 1 dose of 375 mg/m2 every 4 months for a total of 2 years or until relapse or development of unacceptable adverse effects or infections or withdrawal from the study (to become pregnant); 3 pts with shorter remission times following previous ritux were treated at 3 month intervals. 5 pts received 40mg/day of dexamethasone (Dex) with the ritux maintenance infusions: 3 4-day cycles of Dex at 2 weekly intervals (Chapin, AJH, 2016) with induction and single dose dex with each maintenance infusion. The primary endpoint was the duration of response. Secondary endpoints included safety. Statistical analysis was largely descriptive. Comparisons of first and second ritux treatments (without and with maintenance) were made using the Fisher Exact test. Results: Of the 17 pts who received ritux maintenance, 11 had ITP, 2 AIHA, and 4 had Evans syndrome. Three pts had AIN as part of their Evans syndrome. 7 had received more than 1 ritux induction (2-4) in the past. At initiation of maintenance, there were 10 males and 7 females and 13 adults and 4 children. Three had undergone splenectomy prior to starting ritux. The mean duration of response following the first cycle of 4 ritux standard infusions was 19 months, while the mean duration of response with maintenance schedule was 48 months. Fifteen of 17 patients achieved CR with ritux re-induction; of these 7 relapsed. 2 patients achieved PR, 1 relapsed. The mean duration of response with ritux maintenance was 36.8 months in adults and 63.8 months in children; it was 48 months each in males and females; it was 49 months in the 3 patients who had undergone splenectomy and also in those who had not undergone splenectomy. Fisher exact test did not show any statistical difference in clinical parameters including the type of autoimmune cytopenia. Pts with more previous ritux inductions did worse than those receiving their 2nd reinduction. Three patients developed hypogammaglobulinemia and needed IVIG prophylaxis against infections; one patient had bacteremia. One patient developed sepsis secondary to hypogammaglobulinemia requiring ICU admission. JC virus cultures were negative in all tested pts. No pts developed transaminitis or signs of renal failure. Discussion: The expectation for these 17 very difficult to treat pts was that they would have all relapsed in 1 year or less following a "routine" ritux re-induction based on past data and clinical experience. The number of pts reported who achieved lasting remission following a second or third course of ritux is very small. Dex was added to reinduction in 5 of these multiply-induced pts, but curative effects occur only in female pts treated within 1 year of diagnosis, and these were pts with years of disease so this would not explain the results. Being able to achieve lasting remission over many years in half this group appears to be a significant improvement on their expected outcomes. Hypogammaglobulinemia became clinically significant in 1 pt who stopped coming for checkups; it has been reported primarily with the combination of dex-ritux but even then in only 10% of patients. A randomized controlled trial is needed to test these exciting findings. Figure. Figure. Disclosures Bussel: Prophylix: Consultancy, Research Funding; Momenta: Consultancy; Rigel: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Uptodate: Honoraria; Amgen Inc.: Consultancy, Research Funding; Protalex: Consultancy.

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Comparing Two Views Of Video Demonstration For Access Cavity Preparation: A QuasiRandomized Controlled Trial

IIUM Medical Journal Malaysia ◽

10.31436/imjm.v16i2.1063 ◽

2017 ◽

Vol 16 (2) ◽

Author(s):

Amy Liew Kia Cheen ◽

Hazem Dabbour ◽

Dalia Abdullah

Keyword(s):

Controlled Trial ◽

Dental Students ◽

Fisher Exact Test ◽

Test Results ◽

Cavity Preparation ◽

Exact Test ◽

Baseline Group ◽

And Performance ◽

Video Demonstration

Introduction: Demonstration of the access cavity preparation procedures to dental students is challenging due to the limited operating field and detailed nature of the procedures. It is especially difficult to visualize how instruments are functioning inside the pulp space. The aim of this study was to develop and compare two different views of video demonstration in teaching access cavity preparation. Materials and Methods: Two videos of access cavity preparation were filmed, showing occlusal view of a whole tooth (WT) and sagittal view of a sectioned tooth (ST). Using quasirandomization, third year dental students (n=57) were divided into two groups to watch either one of the videos. The perception and performance of both groups were compared using Mann-Whitney U test and Fisher exact test. Results: At baseline, group WT (n=29) and group ST (n=28) were not significantly different in terms of operative scores (p=0.330). After watching the videos, the basic understanding of the theories were similar between both groups. However, ST responded more positively towards the helpfulness of the video in visualizing the inner anatomy of the tooth and in implementing the procedures (p<0.05). ST also completed the exercise within a shorter time (p<0.001). Nevertheless, the quality of the prepared access cavities was not significantly different between groups. Conclusion(s): Using sagittal view of sectioned tooth in video demonstration of access cavity preparation can improve students learning and performance speed. We highly recommend showing the sagittal view of sectioned tooth in video demonstration of access cavity preparation.

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Foodborne Snow Mountain Agent Gastroenteritis in a School Cafeteria

PEDIATRICS ◽

10.1542/peds.79.4.559 ◽

1987 ◽

Vol 79 (4) ◽

pp. 559-563

Author(s):

Charles Guest ◽

Kenneth C. Spitalny ◽

H. Paul Madore ◽

Katherine Pray ◽

Raphael Dolin ◽

...

Keyword(s):

Relative Risk ◽

Strong Association ◽

Case Definition ◽

Enzyme Linked Immunosorbent Assay ◽

Fisher Exact Test ◽

Confidence Limits ◽

Serum Samples ◽

Exact Test ◽

Relative Risks ◽

The Mean

In 1984, an outbreak of gastroenteritis occurred at a school with 1,860 students in Brooklyn, NY. In a single-stage cluster sample of 375 students, 129 (34%) had illnesses that met our case definition of vomiting or diarrhea. The mean incubation period was 26 hours, and the mean illness duration was 24 hours. All case students had eaten in the cafeteria on at least one day between Nov 13 and 16, compared with 174/214 (81%) noncase students (P = 10-8, Fisher exact test). Foods implicated were french fries (relative risk 1.7, 95% confidence limits 1.4, 2.0) and hamburgers (relative risk 1.6, 95%, confidence limits 1.2, 2.1). Two cafeteria employees had served those foods while affected by diarrhea. By a recently developed blocking enzyme-linked immunosorbent assay, six of 11 (55%) case students showed fourfold antibody increases between acute-and convalescent-phase serum samples for Snow Mountain agent, a Norwalk-like virus, compared with one of ten (10%) noncase students (P = .04, Fisher exact test). We strongly suspect, but cannot document conclusively, that the Snow Mountain agent was spread to students on a vector of hot foods contaminated by ill food handlers. Implicated foods conferred low relative risks and could only have accounted for 74% of cases of illness. The strong association between cafeteria exposure and illness, therefore, suggests that additional modes of spread occurred.

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A profile and treatment outcome of seasonal hyper-acute panuveitis

Nepalese Journal of Ophthalmology ◽

10.3126/nepjoph.v2i1.3702 ◽

1970 ◽

Vol 2 (1) ◽

pp. 35-38 ◽

Cited By ~ 4

Author(s):

E Shrestha

Keyword(s):

Visual Acuity ◽

Medical Treatment ◽

Visual Outcome ◽

P Value ◽

Fisher Exact Test ◽

Mean Values ◽

Exact Test ◽

Pediatric Age Group ◽

Significant Difference ◽

The Mean

Introduction: Seasonal hyper-acute panuveitis (SHAPU) is a sight-threatening disease and its management is challenging. Objective: To study the profile and evaluate the visual outcome of the patients of clinicallydiagnosed cases of SHAPU after treatment. Subjects and methods: A retrospective interventional hospital-based study was carried out involving 21 subjects with clinically-diagnosed SHAPU. The data were retrieved from the record section of the hospital and analyzed. The variables studied were demographic pattern, clinical condition, duration of presentation and visual acuity before and after the treatment. Statistics: The data were analyzed using Epi Info version 2000. Percentage prevalence, mean values with standard deviation, relative risk, 95% CI and p value were calculated. P value of < 0.05 was considered to be significant. Results: Among the 21 cases, the numbers of male and female were 11 (52.4 %) and 10 (46.7 %) respectively. A comparative analysis of gender in children and adults did not show any significant difference (RR=0.47, 95% CI = 0.22 - 1.01, Fisher exact test: p = 0.14). The mean for all ages was 7 ± 12.68 years, while the mean age in pediatric cases was 4.5 ± 3.91 years. Thirteen (61.9%) cases occurred in children below fifteen years. Fifteen (71.4 %) cases reported during September and October. Presenting visual acuity of all cases was less than 3/60. All of them received medical treatment. By the end of the 4th week, seven (33.3 %) patients regained vision to 6/18. Conclusion: SHAPU is more prevalent in pediatric age group. It is equally prevalent among males and females. The visual acuity can improve with early medical treatment. Keywords: SHAPU; panuveitis; steroid; phthisis bulbi DOI: 10.3126/nepjoph.v2i1.3702 Nep J Oph 2010;2(1) 35-38

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The Effects of Recombinant Human Granulocyte–Macrophage Colony-Stimulating Factor Gel on Third-Degree Frostbite Wounds in Northeastern China: A Randomized Controlled Trial

Journal of Burn Care & Research ◽

10.1093/jbcr/iraa019 ◽

2020 ◽

Author(s):

Xiu-Hang Zhang ◽

Chang-Lei Cui ◽

Hao-Yue Zhu ◽

Jian Wang ◽

Yan Xue ◽

...

Keyword(s):

Bacterial Culture ◽

Controlled Trial ◽

Healing Time ◽

Control Group ◽

Fisher Exact Test ◽

Chi Square ◽

Exact Test ◽

Positive Effects ◽

Positive Bacterial Culture ◽

Better Than

Abstract The aim of the study was to investigate the effects of the rhGM-CSF gel on third-degree frostbite wounds. Sixty-two patients who had suffered third-degree frostbite on their hand or foot (91 wounds in total) were selected using a convenience sampling method and randomly allocated to two groups: the rhGM-CSF group(31patients,45 frostbite wounds) received the rhGM-CSF gel when wound dressing change daily; however, the control group (31patients, 46 frostbite wounds) received aloe glue. The wound healing time, the score of inflammation about the wound and the positive bacterial culture of wound secretions were used to measure outcomes, respectively. Data were analyzed using SPSS (25.0), Student’s t test or Mann–Whitney U test and chi-square test or Fisher exact test were selected, as appropriate. The healing time of the rhGM-CSF group was (12.2 ± 5.0) days, which was significantly shorter than that of the control group (15.5 ± 4.7) days (P < .0001). The rhGM-CSF group’s wound inflammation scores on the 7th and 14th day of treatment were (0.96 ± 0.21) and (1.88 ± 0.29), respectively, which were better than those of the control group (1.12 ± 0.24) and (1.38 ± 0.15) (both P < .0001). The positive bacterial culture of wound secretions in the rhGM-CSF group was also better than that in the control group on the 3rd, 7th, and 14th day after treatment (P = .027, .004, .030, respectively). According to the results, using rhGM-CSF gel considerably increases the speed of frostbite wounds healing, and have an effect on protecting third-degree frostbite wounds regarding the positive effects. Trial Registration: This trial was registered in the Chinese Clinical Trial Register, ChiCTR1900021299.

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Effect of probiotic on innate inflammatory response and viral shedding in experimental rhinovirus infection – a randomised controlled trial

Beneficial Microbes ◽

10.3920/bm2016.0160 ◽

2017 ◽

Vol 8 (2) ◽

pp. 207-215 ◽

Cited By ~ 19

Author(s):

R.B. Turner ◽

J.A. Woodfolk ◽

L. Borish ◽

J.W. Steinke ◽

J.T. Patrie ◽

...

Keyword(s):

Controlled Trial ◽

Treated Group ◽

Subjective Symptom ◽

Nasal Lavage ◽

Host Responses ◽

Controlled Study ◽

Fisher Exact Test ◽

Exact Test ◽

Virus Challenge ◽

Rhinovirus Infection

Ingestion of probiotics appears to have modest effects on the incidence of viral respiratory infection. The mechanism of these effects is not clear; however, there is evidence from animal models that the probiotic may have an effect on innate immune responses to pathogens. The purpose of this randomised, placebo-controlled study was to determine the effect of administration of Bifidobacterium animalis subspecies lactis Bl-04 on innate and adaptive host responses to experimental rhinovirus challenge. The effect on the response of chemokine (C-X-C motif) ligand 8 (CXCL8) to rhinovirus infection was defined as the primary endpoint for the study. 152 seronegative volunteers who had been supplemented for 28 days, 73 with probiotic and 79 with placebo, were challenged with RV-A39. Supplement or placebo administration was then continued for five days during collection of specimens for assessment of host response, infection, and symptoms. 58 probiotic and 57 placebo-supplemented volunteers met protocol-defined criteria for analysis. Probiotic resulted in higher nasal lavage CXCL8 on day 0 prior to virus challenge (90 vs 58 pg/ml, respectively, P=0.04, ANCOVA). The CXCL8 response to rhinovirus infection in nasal lavage was significantly reduced in the probiotic treated group (P=0.03, ANCOVA). Probiotic was also associated with a reduction in nasal lavage virus titre and the proportion of subjects shedding virus in nasal secretions (76% in the probiotic group, 91% in the placebo group, P=0.04, Fisher Exact test). The administration of probiotic did not influence lower respiratory inflammation (assessed by exhaled nitric oxide), subjective symptom scores, or infection rate. This study demonstrates that ingestion of Bl-04 may have an effect on the baseline state of innate immunity in the nose and on the subsequent response of the human host to rhinovirus infection. Clinicaltrials.gov registry number: NCT01669603.

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Erythropoietic Agents and Venous Thromboembolic Events in Multiple Myeloma Patients Treated with Anthracycline Based Chemotherapy and Immunomodulators.

Blood ◽

10.1182/blood.v108.11.5119.5119 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5119-5119

Author(s):

Rachid Baz ◽

Steven M. Fruchtman ◽

Jerome B. Zeldis ◽

Esteban Walker ◽

Mohamad A. Hussein

Keyword(s):

Multiple Myeloma ◽

Pegylated Liposomal Doxorubicin ◽

Causative Factor ◽

Fisher Exact Test ◽

Thromboembolic Events ◽

Exact Test ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic ◽

The Mean ◽

Aspirin Prophylaxis

Abstract Background: Erythropoietic agents (EPO) have recently been implicated with higher rates of thromboembolic events (VTE) in multiple myeloma (MM) patients receiving lenalidomide (R) and dexamethasone (Knight et al. NEJM 2006). Uncontrolled erythrocytosis, a recognized risk factor for VTE, may complicate therapy with EPO, but was not evaluated as a causative factor for VTE in the above report. We sought to evaluate the putative interactions between erythrocytosis, immunomodulator therapy, EPO and VTE. Patients and Methods: We retrospectively reviewed patients’ records from 2 studies of anthracycline-based chemotherapy with immunomodulators: pegylated liposomal doxorubicin, vincristine, dexamethasone and thalidomide (T) (study A) or lenalidomide (study B) in MM. Demographic variables, aspirin therapy, EPO therapy, immunomodulator therapy (T vs R), as well as laboratory variables (which included all hemoglobin values while on study) were reviewed. Results: From August 2001 to December 2005, 184 multiple myeloma patients with active disease were treated on study A (105) and B (79). The median age for patients was 63 and 62 years on study A and B respectively. Aspirin prophylaxis (81mg daily) was administered for all patients on study B and for all but 19 patients on study A. Among all patients, 113 patients (61%) received EPO. Twenty-six patients on study A and 7 patients on study B developed a VTE. Treatment with EPO was not associated with a higher rate of VTE compared to no treatment with EPO (19% versus 22%, Fisher exact test, p=0.8). The mean peak hemoglobin for patients with a VTE was not statistically different from patients without a VTE (14.2 vs. 13.8 g/dL, p=0.3). Similarly, the mean on study hemoglobin was not different among patients with a VTE and those without a VTE (11.7 vs. 11.6 g/dL, p=0.8). The mean hemoglobin at the time of the VTE was 12.0 g/dL (S.D. 1.5g/dL). Conclusion: Our results do not indicate an association between EPO and VTE in MM patients receiving anthracycline-based chemotherapy with an immunomodulator and aspirin prophylaxis. Uncontrolled erythrocytosis does not appear to be associated with VTE in this patient population. Of note, target hemoglobins were not commonly exceeded. Low dose Aspirin (81mg) is an effective prophylaxis for VTE in multiple myeloma patients receiving anthracycline based therapy with thalidomide or lenalidomide in conjunction with the use of erythropoietin therapy.

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A Randomized Study to Determine the Optimal Dose of Darbepoetin Alfa in Patients with Low- or Intermediate-1 Risk Myelodysplastic Syndromes

Blood ◽

10.1182/blood.v124.21.4642.4642 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4642-4642

Author(s):

Hironori Harada ◽

Hirohiko Shibayama ◽

Jun Ho Jang ◽

Ryutaro Shimazaki ◽

Kinuko Mitani ◽

...

Keyword(s):

Initial Dose ◽

Research Funding ◽

Controlled Trial ◽

Randomized Study ◽

Optimal Dose ◽

Dose Evaluation ◽

Erythroid Response ◽

Evaluation Phase ◽

The Mean ◽

Rbc Transfusion

Abstract [Background] Erythropoiesis stimulating agents (ESAs) are used as standard treatment for anemia in patients with myelodysplastic syndromes (MDS) of low- or intermediate-1 (Int-1) risk according to the International Prognostic Scoring System (IPSS). However, no randomized study has been conducted to determine the optimal dose of ESAs. We conducted a randomized controlled trial of darbepoetin alfa (DA), a long-acting ESA, to find the optimal dose and evaluate efficacy and safety. [Methods] This multicenter randomized controlled trial was conducted in 41 sites in Japan and South Korea. Main inclusion criteria were red blood cell (RBC) transfusion-dependent, IPSS low/Int-1-risk MDS patients with hemoglobin (Hb) ≤ 9.0 g/dL and serum erythropoietin (EPO) ≤ 500 mIU/mL. Eligible patients were randomized to receive weekly subcutaneous doses of DA at a fixed dose of 60, 120 or 240 μg for 16 weeks (initial dose evaluation phase). DA was administered for up to 48 weeks, with dose adjustment allowed from week 17 onward. Dosing frequency was allowed either once every week (QW) or once every 2 weeks (Q2W), with the maximum single dose of 240 µg (extended treatment evaluation phase). The primary endpoint was modified IWG 2000 erythroid response defined as the proportion of patients who achieved an erythroid response [major erythroid response (MaR; RBC transfusion-free with an increase in Hb ≥ 1.0 g/dL above baseline) or a minor erythroid response (MiR; a ≥ 50% reduction in RBC transfusion as compared to baseline)] in the initial dose evaluation phase. Mortality and progression to AML were evaluated for one year. Changes in serum drug concentration and pharmacokinetic parameters were also evaluated. [Results] A total of 52 subjects were randomized. The subjects’ baseline demographics (mean±SD) included Hb of 7.9±0.9 g/dL, serum EPO concentration of 221.1±134.2 mIU/mL, and total amount of RBC transfusion given within 56 days prior to the first DA treatment of 1459±707.2 mL. Among 50 subjects evaluable for efficacy, the proportion of those who achieved an erythroid response during the initial dose evaluation phase in the 60, 120 and 240 μg group was: 64.7% (11/17 subjects) including 17.6% with MaR; 44.4% (8/18 subjects) including 16.7% with MaR; and 66.7% (10/15 subjects) including 33.3% with MaR, respectively. The proportion of subjects achieving erythroid response was similar across the three groups, but the highest proportion of MaR was noted in the 240 μg group. The mean baseline Hb was similar among the groups (7.7, 8.0, 8.0 g/dL in the 60, 120, 240 μg group, respectively). During the initial dose evaluation phase, the mean Hb level continued to rise over the first 2 weeks of DA treatment and remained between 8.6-9.1 g/dL thereafter in the 240 μg group, whereas the mean Hb was slightly lower in the 60 μg group (7.6-8.1 g/dL) and 120 μg group (8.1-8.4 g/dL). During the extended treatment evaluation phase (week 17-48), an increase in DA dose resulted in an improved response from "no response" to MiR and eventually to MaR in 1 subject in the 60 μg group, and from MiR to MaR in 2 subjects each in the 60 and 120 μg groups. There was no major difference among the groups with respect to time to erythroid response. No clinically significant safety concerns were identified. After 1 year of starting the treatment with DA, the survival rate and the proportion of subjects free from AML estimated by Kaplan-Meier method were 84.5% and 96.0%, respectively. The low baseline serum EPO concentration and low RBC transfusion needs were identified as strong predictors of efficacy. [Conclusion] These results demonstrated that treatment with DA is effective and safe in reducing or eliminating transfusion requirements in transfusion-dependent, IPSS low/Int-1-risk MDS patients. Given the highest proportion of subjects achieving MaR in the 240 μg group and the absence of dose-dependent adverse events, the optimal dose was determined to be 240 μg QW. No adverse effects were observed in terms of mortality and proportion of progression to AML. Table. Erythroid Response during the Initial-Dose Evaluation Phase Overall 60 ug 120 ug 240 ug N 50 17 18 15 Major or Minor Response n(%) 29(58.0%) 11(64.7%) 8(44.4%) 10(66.7%) Major Response n(%) 11(22.0%) 3(17.6%) 3(16.7%) 5(33.3%) Disclosures Harada: Kyowa Hakko Kirin Co., Ltd.: Research Funding. Shibayama:Kyowa Hakko Kirin Co., Ltd.: Research Funding. Jang:Kyowa Hakko Kirin Co., Ltd.: Research Funding. Shimazaki:Kyowa Hakko Kirin Co., Ltd.: Employment, Equity Ownership. Mitani:Kyowa Hakko Kirin Co., Ltd.: Consultancy, Research Funding. Sawada:Kyowa Hakko Kirin Co., Ltd.: Consultancy. Kim:Kyowa Hakko Kirin Co., Ltd.: Consultancy.

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Cost-Effectiveness Comparison between Ibrutinib, Chemotherapy, and Chemoimmunotherapy in Front-Line Treatment of Chronic Lymphocytic Leukemia (CLL)

Blood ◽

10.1182/blood-2018-99-118640 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4757-4757 ◽

Cited By ~ 2

Author(s):

Chadi Nabhan ◽

Damion Nero ◽

Choo Hyung Lee ◽

Jonathan K. Kish ◽

Anthony R. Mato

Keyword(s):

Research Funding ◽

Treatment Initiation ◽

Cost Of Care ◽

Fisher Exact Test ◽

Office Visits ◽

Front Line ◽

First Line ◽

Exact Test ◽

Outpatient Visits ◽

Wilcoxon Rank Sum Test

Abstract INTRODUCTION: CLL pts requiring first-line therapy are usually treated with either ibrutinib, chemotherapy alone including monoclonal antibodies (CT), or chemoimmunotherapy (CIT). In the absence of prospective efficacy data comparing CIT with ibrutinib, treatment selection depends on risk stratification, comorbidities, age, goals of therapy, pt preference, and physician familiarity with regimens. When all factors are equal, costs and economics might influence treatment choice especially in a value-based care environment. We performed a cost-comparative analysis between ibrutinib, CT, and CIT-treated CLL pts in the first line aiming to provide additional guidance for clinicians when deciding on initial therapy. PATIENTS and METHODS: This is a retrospective, observational study of CLL pts treated in the first line with ibrutinib, CT, or CIT. Primary end-point was to compare healthcare resource utilization (HRU) between pts in each cohort. Secondary objective was to quantify the incidence of cardiovascular (CV) adverse events between pts who did not have any CV disease prior to treatment initiation. Pts were extracted from Symphony Health's Integrated Dataverse (IDV) between 1/1/2014-12/31/2017. The database is representative of the U.S. population across age, sex, geography, and insurance type. Pts were ≥18 years at diagnosis and initiated therapy after 1/1/2014 and before 11/30/2017 to allow for at least 3 months of follow up. Pts were required to have no CV events during the 12-month period before study entry. CV events included hypertension (HTN), myocardial infarction (MI), atrial fibrillation (Afib), peripheral vascular disease (PVD) and coronary artery disease (CAD). HRU was evaluated using admission codes for hospitalization, emergency room (ER), office visits, and other outpatient visits. Direct medical costs were calculated based on standardized costs and were estimated in US dollars as per patient per month. Comparisons of HRU and costs and the proportion of pts with a CV event were performed using the chi square or Fisher exact test for proportions and the t-test or Wilcoxon rank sum test for continuous data. Fisher exact test and the Wilcoxon rank-sum test were used in cases where the data did not have a normal distribution. The Kruskal-Wallis test was used in cases where multiple groups were being compared. RESULTS: The final cohorts included 4,368 pts receiving ibrutinib, 1,464 receiving CT, and 2,176 treated with CIT (1,523 BR, 634 FCR, and 19 chlorambucil combinations). Mean age at diagnosis and treatment initiation for ibrutinib was 66 and 68 respectively, which was younger than CT (68 and 70 respectively), but older than CIT (62 and 63 respectively). Other characteristics were similar in the three cohorts. Median time from diagnosis to treatment was longer in ibrutinib-treated pts versus CT and CIT (17.4 vs. 10.9 vs. 7.8 months; p<0.0001). CT and CIT pts had significantly higher costs and HRU compared with ibrutinib pts for office and outpatient visits (p<0.0001). ER visits were significantly higher for both CT and CIT pts (p<0.05) while ER costs were slightly higher for ibrutinib pts but not statistically significant. Inpt visits, costs and length of stay were significantly different in CIT pts compared to ibrutinib, but not in CT pts. More pts on ibrutinib developed AFib compared with CIT-treated pts (4.42% vs. 2.67%; p=0.0005). More CIT-treated pts developed HTN compared with the ibrutinib cohort, though the difference was not significant (11.1% vs. 9.8%; p=0.0871). A total of 567 pts (13%) taking ibrutinib went on to have a CV event while 3,801 patients continued therapy without an event. We found significantly higher HRU for ibrutinib pts with and without CV events for outpatient visits (3.86 vs 3.46, p-value <0.0001), office visits (1.04 vs 0.91, p <0.0048), ER visits (p=0.006), ER costs (p<0.0001), and length of inpt stay (3.18 vs. 2.56; p<0.0001). Lastly, we found a significant difference between Medicare/Medicaid and commercial payers in the number of outpt visits (3.581 vs. 3.378 p=0.0002) and the cost of oupt visits (1,507.36 vs 1,126.84, p<0.0001) (Table). CONCLUSIONS: When used as front-line, ibrutinib has lower HRU and ER visits than CT/CIT pts. More ibrutinib-treated patients developed AFib than CT/CIT pts. CV events in ibrutinib-treated pts were observed in 13% of cases and had substantial impact on cost of care. Disclosures Nabhan: Cardinal Health: Employment, Equity Ownership. Nero:Cardinal Health: Employment. Lee:Cardinal Health: Employment. Kish:Cardinal Health: Employment. Mato:Pharmacyclics, an AbbVie Company: Consultancy, Research Funding; AstraZeneca: Consultancy; Celgene: Consultancy; Regeneron: Research Funding; AbbVie: Consultancy, Research Funding; Medscape: Honoraria; Acerta: Research Funding; Portola: Research Funding; TG Therapeutics: Consultancy, Research Funding; Prime Oncology: Honoraria; Johnson & Johnson: Consultancy.

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Assessment of Safety and Efficacy of a New Intravenous Immunoglobulin (IGIV3I 10% Grifols) In Subjects with Chronic Immune Thrombocytopenia

Blood ◽

10.1182/blood.v116.21.4669.4669 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4669-4669

Author(s):

Ali Khojasteh ◽

Giraldo Kato ◽

Nehal Parikh ◽

Tammuella Singleton ◽

Cameron K Tebbi ◽

...

Keyword(s):

Platelet Count ◽

Research Funding ◽

Clinical Laboratory ◽

Vital Signs ◽

Study Drug ◽

Threshold Value ◽

Bleeding Diathesis ◽

Haemorrhagic Diathesis ◽

Duration Of Response ◽

The Mean

Abstract Abstract 4669 Two similarly designed prospective, uncontrolled, open-label clinical trials were planned to assess the safety and efficacy of a new intravenous immunoglobulin (IVIG), IGIV3I 10% Grifols, in subjects with chronic immune thrombocytopenia (ITP) in the USA, Canada and Europe (Spain, Russia and the United Kingdom). Subjects were candidates to be enrolled if they had a diagnosis of chronic ITP and a baseline platelet count ≤ 20 × 109/l. Eligible subjects received treatment with IGIV3I 10% Grifols 1g/kg for 2 consecutive days or 0.4 g/kg for 5 consecutive days. The primary efficacy endpoint was the response rate, defined as the proportion of subjects reaching or exceeding the threshold value of 50 × 109/l on or before day 8 (American study) or on day 30 (European study) where day 1 is the day of the first infusion. Secondary efficacy endpoints were the time to response, defined as the number of days elapsed from day 1 to achievement of the threshold value; duration of response, defined as the number of consecutive days with a platelet count known to be ≥50 × 109/l; the maximum (peak) platelet count and regression of haemorrhagic diathesis for those subjects presenting with bleeding signs at baseline. Safety endpoints included adverse events (AEs), physical examinations, vital signs and clinical laboratory parameters monitoring. A total of 27 subjects (18 adults and 9 pediatrics) have been enrolled, i.e. administered with at least one infusion of the product at any dose, in the study. Twenty-four (24) subjects (89%) were considered responders. This proportion was higher in pediatric subjects (9/9, 100%) than in adult subjects (15/18, 83%). The mean time to response was 1.6 days (Standard Deviation (SD) 0.9); the mean duration of response was 14.0 days (SD 12.1) and the mean maximum platelet count was 263 × 109/l (SD 195.6). Twenty-three (23) subjects (all the pediatric subjects 9/9 and 14/18 adults) presented with some sign of bleeding at baseline. All subjects (23/23, 100%) experienced an improvement in the haemorrhagic diathesis, regardless of some of them being considered non-responders according to the platelet count criterion. A total of 92 AEs potentially related to study drug were reported. The most common of these were headache (25 events), nausea (8 events), pyrexia (7 events) and chills (6 events). Only 1 AE was reported as definitely related to study drug, an event of palmar erythema. Two serious AEs (SAE) potentially related to the study drug were reported in 2 subjects. One of them was an unexpected laboratory alteration which consisted in leukopenia and decreased hemoglobin and advised to maintain the subject hospitalized for further observation during the weekend. The reaction was transient, without complications or other clinical symptoms and total recovery of the normal laboratory values. The second SAE was an event of thrombosis in the right humeral vein, in a patient with a number of predisposing medical conditions. At the time of discharge the patient's overall condition was satisfactory. Analysis of AEs, clinical laboratory values, physical assessments and vital signs did not indicate any safety concerns for subjects receiving the study drug and are in line with those expected for the ITP population treated with IVIG. Both primary and secondary efficacy endpoints show a good response to the product in terms of rapid elevation of platelet counts to an hemostatic level in line with what is expected for an IVIG product. Moreover, the improvement of the baseline bleeding diathesis even in patients considered as non-responders according to the platelet count criterion is highly suggestive of the clinical efficacy of the product. Overall, these results indicate that treatment with the new IGIV3I 10% Grifols is safe and efficacious for rapidly increasing platelet counts in chronic ITP subjects and improving their bleeding diathesis. Disclosures: Khojasteh: Grifols S.A.: Research Funding. Kato:Grifols S.A.: Research Funding. Parikh:Grifols S.A.: Research Funding. Singleton:Grifols S.A.: Research Funding. Tebbi:Grifols S.A.: Research Funding. Cromwell:Grifols S.A.: Research Funding. Fu:Grifols S.A.: Research Funding. Kessler:Grifols S.A.: Research Funding. Letzer:Grifols S.A.: Research Funding. Ritchie:Grifols S.A.: Research Funding. Sexauer:Grifols S.A.: Research Funding. Saxena:Grifols S.A.: Research Funding. Sirpal:Grifols S.A.: Research Funding. Torres:Grifols S.A.: Research Funding. Loriya:Grifols S.A.: Research Funding. Kovaleva:Grifols S.A.: Research Funding. Sandoval:Grifols S.A.: Research Funding. Sanz:Grifols S.A.: Research Funding. Julià:Grifols S.A.: Research Funding. Montañés:Grifols S.A.: Employment. Navarro:Grifols S.A.: Employment.

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Comparison of Functional and MRI Outcomes of Microfracture with and without BioCartilage for Osteochondral Lesions of the Talus

Foot & Ankle Orthopaedics ◽

10.1177/2473011419s00389 ◽

2019 ◽

Vol 4 (4) ◽

pp. 2473011419S0038

Author(s):

Yoshiharu Shimozono ◽

Hao Huang ◽

Timothy Deyer ◽

John G Kennedy

Keyword(s):

Treatment Strategy ◽

Cartilage Regeneration ◽

Cartilage Tissue ◽

Categorical Variables ◽

Osteochondral Lesions ◽

Fisher Exact Test ◽

Continuous Variables ◽

Exact Test ◽

The Mean

Category: Ankle, Arthroscopy, Sports Introduction/Purpose: Microfracture (MF) remains a dominant treatment strategy for symptomatic osteochondral lesions of the talus (OLT). Micronized cartilage allograft (BioCartilage) is a biologic scaffold and is utilized for MF augmentation to improve the quality for cartilage regeneration. However, there is still lack of evidence on efficacy of BioCartilage as an adjunct to MF, as no comparative studies have been reported to date. The purpose of this study is to clarify the effectiveness of BioCartilage as an adjuvant to MF compared to MF alone in the treatment of OLT. Methods: A retrospective cohort study comparing patients treated with MF with BioCartilage and MF alone between 2014 and 2017 was undertaken. Patients with a minimum follow-up time of 12 months were included. All patients received concentrated bone marrow aspirate injection at the time of surgery. Clinical outcome was evaluated with the Foot and Ankle Outcome Score (FAOS) pre- and postoperatively. Postoperative MRIs were evaluated using a modified Magnetic Resonance Observation of Cartilage Tissue (MOCART) score. Comparisons between groups were made with the Man-Whitney U test for continuous variables and the Chi-squared test or Fisher exact test for categorical variables. Results: Twenty-four patients underwent MF with BioCartilage (MF-BC group) and 24 patients underwent MF alone (MF group). The mean age was 40.8 years in MF-BC group and 47.8 years in MF group (p=0.068). The mean follow-up time was 19.2 months in MF-BC group and 24.5 months in MF group (p=0.042). Both groups showed significant improvements in all FAOS subscales. No significant differences between groups were found in postoperative FAOS subscales including symptoms, pain, daily activities, sports activities and quality of life (MF-BC; 72.8, 77.8, 87.4, 60.8, 56.6, MF; 73.3, 79.3, 86.0, 60.9, 60.6, respectively, p>0.05). The mean MOCART score in MF-BC group was higher (73.2vs64.1), but not statistically significant (p=0.315). When assessing each MOCART parameter individually, MF-BC group had significant better infill in the defect (p=0.028). Conclusion: MF with BioCartilage is an effective treatment strategy for the treatment of OLT and results in similar functional outcomes compared with MF alone in the short-term. However, MF with BioCartilage provides better cartilage infill in the defect on MRI. This finding suggests that the repair seen in a cartilage defect treated with BioCartilage augmentation may be superior to treatment with MF alone. Further long-term follow-up studies are warranted.

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