Apixaban Reduces Hospitalization In Patients With Venous Thromboembolism: An Analysis Of The AMPLIFY-EXT Trial

Abstract Introduction Venous thromboembolism (VTE) is associated with a considerable risk for morbidity and recurrence and related hospitalizations. In the Apixaban after the Initial Management of Pulmonary Embolism and Deep Vein Thrombosis with First-Line Therapy-Extended Treatment (AMPLIFY-EXT) trial, a double-blind placebo-controlled trial with 12 months of treatment, two doses of apixaban (2.5 mg and 5 mg, twice daily) versus placebo significantly reduced symptomatic recurrent VTE or all-cause death without increasing the rate of major bleeding among 2,482 VTE patients who had completed 6-12 months of anticoagulation therapy. In this study, the effects of apixaban therapy versus placebo on medical hospitalization during AMPLIFY-EXT trial were evaluated. Methods A total of 2,477 patients who received study drugs were included in the analysis. All-cause hospitalizations during the trial were captured by dedicated case report forms. Outcomes of interest were; rate of hospitalizations and time from randomization to the first hospitalization. Patients were censored at either death, loss to follow-up, or end of study, whichever came first. Effects of treatment with apixaban versus placebo on the rates of hospitalization were assessed using Cox proportional hazards regression models. Results During a mean follow-up of 12.3 months, 138 patients were hospitalized at least once, 62 (7.5%/year) in the placebo group (n=826), 42 (4.8%/year) in the apixaban 2.5 mg group (n=840), and 34 (4.0%/year) in the apixaban 5 mg group (n=811). Compared with placebo, apixaban 2.5 mg [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.44–0.96; p=0.030] and 5 mg (HR 0.54, 95%CI 0.36–0.83, p=0.004) were both associated with significant reduction in hospitalization. There was no significant difference in hospitalizations between the 2 doses of apixaban (5 mg vs. 2.5 mg: HR 0.84, 95%CI 0.53–1.32, p=0 .445). The mean time to first hospitalization was 153.7 days in the placebo group, 196.9 days in the apixaban 2.5 mg group, and 202.4 days in the apixaban 5 mg group (Figure). Conclusions Extended anticoagulation with apixaban at either a dose of 5 mg or 2.5 mg significantly reduced the risk of hospitalization, possibly due to the reduction in VTE recurrence. Disclosures: Liu: Pfizer: Employment, Equity Ownership. Thompson:Pfizer: Employment, Equity Ownership. Phatak:BMS: Employment, Equity Ownership. Mardekian:Pfizer: Employment, Equity Ownership. Porcari:Pfizer: Employment, Equity Ownership. Johnson:Pfizer: Employment, Equity Ownership.

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Effects of Fermented Milk Containing Lacticaseibacillus paracasei Strain Shirota on Constipation in Patients with Depression: A Randomized, Double-Blind, Placebo-Controlled Trial

Nutrients ◽

10.3390/nu13072238 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2238

Author(s):

Xiaomei Zhang ◽

Shanbin Chen ◽

Ming Zhang ◽

Fazheng Ren ◽

Yimei Ren ◽

...

Keyword(s):

Mental Illness ◽

Placebo Group ◽

Rating Scale ◽

Controlled Trial ◽

Fermented Milk ◽

Daily Consumption ◽

Double Blind ◽

Tnf Α ◽

Significant Difference ◽

Factor Α

Probiotics have been shown to benefit patients with constipation and depression, but whether they specifically alleviate constipation in patients with depression remains unclear. The aim of this study was to investigate the effect of Lacticaseibacillus paracasei strain Shirota (LcS), formerly Lactobacillus casei strain Shirota, on constipation in patients with depression with specific etiology and gut microbiota and on depressive regimens. Eighty-two patients with constipation were recruited. The subjects consumed 100 mL of a LcS beverage (108 CFU/mL) or placebo every day for 9 weeks. After ingesting beverages for this period, we observed no significant differences in the total patient constipation-symptom (PAC-SYM) scores in the LcS group when compared with the placebo group. However, symptoms/scores in item 7 (rectal tearing or bleeding after a bowel movement) and items 8–12 (stool symptom subscale) were more alleviated in the LcS group than in the placebo group. The Beck Depression Index (BDI) and Hamilton Depression Rating Scale (HAMD) scores were all significantly decreased, and the degree of depression was significantly improved in both the placebo and LcS groups (p < 0.05), but there was no significant difference between the groups. The LcS intervention increased the beneficial Adlercreutzia, Megasphaera and Veillonella levels and decreased the bacterial levels related to mental illness, such as Rikenellaceae_RC9_gut_group, Sutterella and Oscillibacter. Additionally, the interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) levels were significantly decreased in both the placebo and LcS groups (p < 0.05). In particular, the IL-6 levels were significantly lower in the LcS group than the placebo group after the ingestion period (p < 0.05). In conclusion, the daily consumption of LcS for 9 weeks appeared to relieve constipation and improve the potentially depressive symptoms in patients with depression and significantly decrease the IL-6 levels. In addition, the LcS supplementation also appeared to regulate the intestinal microbiota related to mental illness.

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Randomised Double-Blind Trial of Combination Antibiotic Therapy in Rheumatoid Arthritis

International Journal of Rheumatology ◽

10.1155/2011/585497 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Angela Smith ◽

Caroline Doré ◽

Peter Charles ◽

Alena Vallance ◽

Tara Potier ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Placebo Group ◽

Active Treatment ◽

Active Rheumatoid Arthritis ◽

Controlled Trial ◽

Primary Outcome Measure ◽

Good Evidence ◽

Double Blind ◽

Acr20 Response ◽

Significant Difference

Objective. A combination of intravenous clindamycin and oral tetracycline has been used for many years as a treatment for active rheumatoid arthritis (RA), despite the absence of good evidence for its efficacy. A single-blind pilot study of this therapy suggested that a double-blind placebo-controlled trial was warranted.Methods. Patients with active RA were randomised in a 2 : 1 ratio to receive active treatment or placebo for 25 weeks. The active treatment consisted of intravenous clindamycin in a reducing regime, and oral tetracycline twice daily three times a week. 50 patients were to be recruited. The primary outcome measure was the proportion of patients achieving an ACR20 response.Results. An interim statistical analysis was performed after 20 patients had completed the study. Two patients in the active group achieved an ACR20 response, with none in the placebo group (NS). There was a better ESR20 response in the placebo group (P=.02). There were no other significant differences between the groups. The results indicated that it was unlikely that a significant difference in ACR20 response would emerge if the remaining 30 patients were recruited. The trial was therefore halted.Conclusion. This antibiotic regime is unlikely to be a valuable therapy for active rheumatoid arthritis.

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Is Adherence to the American College of Chest Physicians Recommended Anticoagulation Treatment Duration Associated with Different Outcomes Among Patients with Venous Thromboembolism?

Blood ◽

10.1182/blood.v126.23.1126.1126 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1126-1126 ◽

Cited By ~ 1

Author(s):

Alex C. Spyropoulos ◽

Ron Preblick ◽

Jackie Kwong ◽

Melissa Lingohr-Smith ◽

Jay Lin

Keyword(s):

Venous Thromboembolism ◽

Treatment Duration ◽

Bleeding Risk ◽

Patient Characteristics ◽

Baseline Period ◽

Employment Equity ◽

Minimum Duration ◽

Study Population ◽

Equity Ownership

Abstract Introduction: Venous thromboembolism (VTE) represents a major clinical and economic burden. The American College of Chest Physicians (ACCP) Guideline 9th Edition on the treatment of VTE recommends a minimum duration of anticoagulation (AC) therapy depending on patient risk profiles. The objectives of this study were to evaluate the clinical and economic outcomes associated with adherence to the AC treatment duration recommendation among VTE patients in the real world setting. Methods: Adult patients (≥18 years of age) with at least 1 inpatient diagnosis or 2 outpatient diagnoses on two different dates of deep vein thrombosis (DVT) and/or pulmonary embolism (PE), based on ICD-9-CM codes, were identified from the IMS Pharmetrics Plus database during 1/1/2009 through 3/31/2013. The first VTE diagnosis was defined as the index event. Study patients were required to have continuous insurance coverage during the 12 months before (baseline) and after (follow-up) the index event and no prior VTE diagnosis in the baseline period. They were also required to have received at least one outpatient anticoagulant treatment within 30 days of the initial VTE diagnosis with a minimum medication days of supply of 30 days. ACCP recommend that patients with provoked VTE or unprovoked VTE and high bleeding risks receive AC treatment for at least 3 months and that patients with unprovoked VTE and low or moderate bleeding risks or patients with cancer receive AC treatment for at least 6 months. Patient records in the database including ICD-9-CM codes and RIETE bleeding risk scores were used to group patients into 2 cohorts, one comprised of patients who received AC treatment for a duration as recommended by the ACCP (adherent group, AD) and the other comprised of patients who received AC treatment for a duration less than that recommended by the ACCP (non-adherent group, non-AD). Patient demographics and clinical characteristic were evaluated during the baseline period. Healthcare resource utilization, including hospital admissions, outpatient medical services, and prescription drug usage, were measured during the baseline and follow-up periods. VTE recurrence, defined as hospitalization or ER visit with a VTE diagnosis code, was also measured during the follow-up period. Multivariate regression analysis was utilized to compare clinical and economic outcomes of study cohorts while controlling for key patient characteristics. Results: The study population included 81,827 patients with a mean age (standard deviation) of 55.3 (13.8) years. For the index VTE event, 61% had DVT only, 26% had PE only, and 13% had DVT/PE. Of the study population, the minimum ACCP recommended AC treatment durations were 3 and 6 months for 27% (n=22,157) and 73% (n=59,670) of patients, respectively. Among all patients, 74% (n=60,550) received AC therapy for the ACCP recommended duration. The proportion of patients with VTE risks, including recent hospitalization (17% vs. 9%, p<0.001), recent surgery (9% vs. 6%, p<0.001), index diagnosis of PE only (28% vs. 20%, p<0.001), and index diagnosis of DVT/PE (15% vs. 8%, p<0.001) was greater in the AD cohort than in the non-AD cohort. Furthermore, mean Charlson Comorbidity Index score (1.67 vs. 1.59, p<0.001) and RIETE bleeding risk score (RIETE ≥1: 66% vs. 55%, p<0.001) were higher for the AD cohort compared to the non-AD cohort. The most prevalent anticoagulants used for treatment were warfarin (89% vs. 96%, p<0.001) and low molecular weight heparin (58% vs. 59%, p<0.01). After controlling for key patient characteristics, risks for all-cause hospitalization (Odds ratio (OR): 0.80, confidence interval (CI): 0.77-0.83, p<0.001) and VTE recurrence (OR=0.91, CI: 0.86-0.95, p<0.001) were lower among VTE patients in the AD cohort vs. the non-AD cohort, as were differences in all-cause total healthcare payments (-$3,416, p<0.001) and VTE-related healthcare payments (-$2,139, p<0.001) during the follow-up period. Conclusions: Approximately a quarter of the study population with VTE did not receive treatment with AC therapy for the minimum duration as recommended by the ACCP guideline. Patients who did not receive outpatient AC therapy for the recommended duration had more VTE recurrences, utilized more inpatient services, and had higher healthcare costs than patients who received AC therapy for the ACCP recommended duration. Disclosures Spyropoulos: Daiichi Sankyo, Inc.: Consultancy. Preblick:Daiichi Sankyo, Inc.: Employment, Equity Ownership. Kwong:Daiichi Sankyo, Inc.: Employment, Equity Ownership. Lingohr-Smith:Chimerix, Inc.: Consultancy; Bristol-Myers Squibb: Consultancy; Daiichi Sankyo, Inc: Consultancy; Novosys Health: Employment. Lin:Chimerix, Inc.: Consultancy; Daiichi Sankyo, Inc: Consultancy; Bristol-Myers Squibb: Consultancy; Novosys Health: Employment.

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The addition of omeprazole to ondansetron for treating chemotherapy-induced nausea and vomiting in pediatric cancer patients

Paediatrica Indonesiana ◽

10.14238/pi1.1.2018.42-7 ◽

2018 ◽

Vol 1 (1) ◽

pp. 42

Author(s):

Perjuangan Dapot Hamonangan Simbolon ◽

Selvi Nafianti ◽

Pertin Sianturi ◽

Bidasari Lubis ◽

Aznan Lelo

Keyword(s):

Placebo Group ◽

Cancer Patients ◽

Pediatric Cancer ◽

Controlled Trial ◽

Complete Response ◽

Nausea And Vomiting ◽

Chi Square ◽

Double Blind ◽

Significant Difference ◽

Pediatric Cancer Patients

Background Chemotherapy-induced nausea and vomiting are some of the most disturbing side effects in pediatric cancer patients. The standard recommendation is the use of 5-hydroxytryptamine 3 receptor antagonist, such as ondansetron, to treat these symptoms. Despite this treatment, more than 50% of patients still experience nausea and vomiting.Objective To evaluate the effect of the addition of omeprazole to ondansetron in the treatment of chemotherapy-induced nausea and vomiting.Methods A double-blind, randomized, controlled trial was conducted at Haji Adam Malik Hospital, Medan, North Sumatera, from March to May 2016. Subjects were children aged 1 to 18 years, diagnosed with cancer, and who received intravenous chemotherapy. Patients were randomized to receive either a single dose of ondansetron (0.5 mg/kg) plus placebo or ondansetron (0.5 mg/kg) plus omeprazole (0.5 mg/kg). The severity of nausea and vomiting were measured using the Rhodes index of nausea, vomiting, and retching during the 24 hours after initiation of emetogenic chemotherapy. The primary outcome of efficacy was the proportion of patients who achieved complete response (lack of nausea/vomiting). Statistical analysis was performed by Chi-square and Fischer’s exact tests.Results Seventy eligible pediatric patients were randomized into two groups: 32 subjects in the ondansetron + placebo group and 38 others in the ondansetron + omeprazole group. The therapy failed in 50% (16/32) of the ondansetron + placebo group and 18.4% (7/38) of the ondansetron + omeprazole group. There was a significant difference in the clinical response between groups (P=0.01).Conclusion The addition of omeprazole to ondansetron for the treatment of chemotherapy-induced nausea and vomiting is more effective than administration of ondansetron alone.

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Efficacy and Safety of Lenalidomide (LEN) Versus Placebo (PBO) in RBC-Transfusion Dependent (TD) Patients (Pts) with IPSS Low/Intermediate (Int-1)-Risk Myelodysplastic Syndromes (MDS) without Del(5q) and Unresponsive or Refractory to Erythropoiesis-Stimulating Agents (ESAs): Results from a Randomized Phase 3 Study (CC-5013-MDS-005)

Blood ◽

10.1182/blood.v124.21.409.409 ◽

2014 ◽

Vol 124 (21) ◽

pp. 409-409 ◽

Cited By ~ 8

Author(s):

Valeria Santini ◽

Antonio Almeida ◽

Aristoteles Giagounidis ◽

Stephanie Gröpper ◽

Anna Jonasova ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Efficacy And Safety ◽

Employment Equity ◽

Phase 3 ◽

Advisory Committees ◽

Double Blind ◽

Equity Ownership ◽

Grade 3

Abstract Background: Treatment options for RBC-TD pts with lower-risk MDS without del(5q) who are unresponsive or refractory to ESAs are very limited. In a previous phase 2 study, MDS-002 (CC-5013-MDS-002), LEN was associated with achievement of RBC-transfusion independence (TI) ≥ 56 days in 26% of pts with IPSS Low/Int-1-risk MDS without del(5q) (Raza et al. Blood 2008;111:86-93). This international phase 3 study (CC-5013-MDS-005) compared the efficacy and safety of LEN versus PBO in RBC-TD pts with IPSS Low/Int-1-risk MDS without del(5q) unresponsive or refractory to ESAs. Methods: This multicenter, randomized, double-blind, parallel-group phase 3 study included RBC-TD pts (≥ 2 units packed RBCs [pRBCs]/28 days in the 112 days immediately prior to randomization) with IPSS Low/Int-1-risk MDS without del(5q), who were unresponsive or refractory to ESAs (RBC-TD despite ESA treatment with adequate dose and duration, or serum erythropoietin [EPO] > 500 mU/mL). Pts were randomized 2:1 to oral LEN 10 mg once daily (5 mg for pts with creatinine clearance 40–60 mL/min) or PBO. Pts with RBC-TI ≥ 56 days or erythroid response by Day 168 continued double-blind treatment until erythroid relapse, disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was RBC-TI ≥ 56 days (defined as absence of any RBC transfusions during any 56 consecutive days). Secondary endpoints included time to RBC-TI, duration of RBC-TI, RBC-TI ≥ 168 days, progression to acute myeloid leukemia (AML; WHO criteria), overall survival (OS), and safety. Baseline bone marrow gene expression profiles were evaluated according to the Ebert signature (PloS Med 2008;5:e35) identified as predictive of LEN response. Clinical trial identifier: CT01029262. Results: The intent-to-treat population comprises 239 pts (LEN, n = 160; PBO, n = 79). Baseline characteristics were comparable across treatment groups; median age 71 years (range 43–87), 67.8% male, and median time from diagnosis 2.6 years (range 0.1–29.6). Pts received a median of 3.0 pRBC units/28 days (range 1.5–9.8) and 83.7% received prior therapy, including ESAs (78.7%). Significantly more LEN pts achieved RBC-TI ≥ 56 days versus PBO (26.9% vs 2.5%; P < 0.001; Table). The majority (90%) of pts with RBC-TI ≥ 56 days responded within 16 weeks of treatment. Median duration of RBC-TI ≥ 56 days was 8.2 months (range 5.2–17.8). Baseline factors significantly associated with achievement of RBC-TI ≥ 56 days with LEN were: prior ESAs (vs no ESAs; P = 0.005), serum EPO ≤ 500 mU/mL (vs > 500 mU/mL; P = 0.015), < 4 pRBC units/28 days (vs ≥ 4 pRBC units/28 days; P = 0.036), and female sex (vs male; P = 0.035). RBC-TI ≥ 168 days was achieved in 17.5% and 0% of pts in the LEN and PBO groups, respectively. The incidence of AML progression (per 100 person-years) was 1.91 (95% CI 0.80–4.59) and 2.46 (95% CI 0.79–7.64) for LEN and PBO pts, respectively, with median follow-up 1.6 and 1.3 years. Death on treatment occurred in 2.5% of pts on either LEN or PBO. The follow-up period was insufficient to permit OS comparison between the 2 groups. Myelosuppression was the main adverse event (AE); in the LEN versus PBO groups, respectively, grade 3–4 neutropenia occurred in 61.9% versus 11.4% of pts, and grade 3–4 thrombocytopenia in 35.6% versus 3.8% of pts. Discontinuations due to AEs were reported in 31.9% LEN and 11.4% PBO pts; among the 51 LEN pts who discontinued due to AEs, 14 discontinuations were due to thrombocytopenia and 8 due to neutropenia. In the subset of pts evaluated for the Ebert signature (n = 203), the predictive power of the signature was not confirmed. Conclusions: LEN therapy was associated with a significant achievement of RBC-TI ≥ 56 days in 26.9% of pts with a median duration of RBC-TI of 8.2 months; 90% of pts responded within 16 weeks of treatment. These data were consistent with response rates seen in the MDS-002 trial. The overall safety profile was consistent with the known safety profile of LEN and these data suggest LEN can be safely and effectively used in this patient population. Figure 1 Figure 1. Disclosures Santini: Celgene Corporation: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Glaxo Smith Kline: Honoraria. Off Label Use: Trial of Lenalidomide in non-del5q MDS. Almeida:Celgene Corporation: Consultancy, Speakers Bureau. Giagounidis:Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Vey:Celgene: Honoraria. Mufti:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Buckstein:Celgene: Research Funding. Mittelman:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Platzbecker:Celgene: Research Funding. Shpilberg:Celgene Corporation: Consultancy, Honoraria. del Canizo:Celgene Corporation: Consultancy, Research Funding. Gattermann:Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Ozawa:Celgene: Consultancy, not specified Other. Zhong:Celgene: Employment, Equity Ownership. Séguy:Celgene: Employment, Equity Ownership. Hoenekopp:Celgene: Employment, Equity Ownership. Beach:Celgene: Employment, Equity Ownership. Fenaux:Novartis: Research Funding; Janssen: Research Funding; Celgene: Research Funding.

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Does hydroxyapatite coating enhance ingrowth and improve longevity of a Zweymuller type stem? A double-blinded randomised RSA trial

Hip International ◽

10.5301/hipint.5000549 ◽

2017 ◽

Vol 28 (2) ◽

pp. 115-121 ◽

Cited By ~ 4

Author(s):

Daniel Hoornenborg ◽

Inger N. Sierevelt ◽

Joost A. Spuijbroek ◽

John Cheung ◽

Harm M. van der Vis ◽

...

Keyword(s):

Controlled Trial ◽

Femoral Stem ◽

Hydroxyapatite Coating ◽

Harris Hip Score ◽

Double Blind ◽

Long Term Outcome ◽

Total Hip ◽

Early Migration ◽

Significant Difference

Introduction: An ongoing discussion is whether using a hydroxyapatite coating enhances the ingrowth and longevity of a femoral stem in total hip arthroplasty. The best way to predict speed of ingrowth and long-term outcome is by evaluating micromotion by radiostereometric analysis. To study the effect of hydroxyapatite (HA) coating on the migration of the SL-PLUS hip stem, we performed a prospective double blind randomised controlled trial comparing the early migration of the hydroxyapatite (HA)-coated SL-PLUS stem compared to the Standard (non-coated) SL-PLUS stem. Patients and methods: 51 patients were randomly assigned to receive either an uncoated or a HA-coated femoral component during total hip replacement. RSA images were obtained direct postoperatively and at 6 weeks, 12 weeks, 6 months, 12 months and 24 months. HOOS scores were obtained preoperative and at final follow-up. Results: RSA evaluation demonstrated significant migration up to 3 months postoperatively in both groups. After initial setting no significant migration was observed. There was no significant difference in migration between the HA-coated group and the uncoated group. Both Harris Hip Score (HHS) and HOOS domain scores (pain and ADL) significantly improved compared to baseline at 24 months after surgery in both treatment groups (p<0.001 for all comparisons). Improvement did not differ significantly between the 2 groups. Conclusions: At 2 years follow-up, the HA-coated and uncoated Zweymuller type, distal fitting stem do not show different migration patterns.

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Effect of vitamin D supplementation on selected inflammatory biomarkers in older adults: a secondary analysis of data from a randomised, placebo-controlled trial

British Journal Of Nutrition ◽

10.1017/s0007114515002366 ◽

2015 ◽

Vol 114 (5) ◽

pp. 693-699 ◽

Cited By ~ 23

Author(s):

Mary Waterhouse ◽

Bich Tran ◽

Peter R. Ebeling ◽

Dallas R. English ◽

Robyn M. Lucas ◽

...

Keyword(s):

Vitamin D ◽

Placebo Group ◽

Inflammatory Markers ◽

Controlled Trial ◽

Intervention Group ◽

Vitamin D Supplementation ◽

Post Intervention ◽

Double Blind ◽

Specific Patient ◽

Significant Difference

AbstractObservational studies have suggested that 25-hydroxyvitamin D (25(OH)D) levels are associated with inflammatory markers. Most trials reporting significant associations between vitamin D intake and inflammatory markers used specific patient groups. Thus, we aimed to determine the effect of supplementary vitamin D using secondary data from a population-based, randomised, placebo-controlled, double-blind trial (Pilot D-Health trial 2010/0423). Participants were 60- to 84-year-old residents of one of the four eastern states of Australia. They were randomly selected from the electoral roll and were randomised to one of three trial arms: placebo (n 214), 750 μg (n 215) or 1500 μg (n 215) vitamin D3, each taken once per month for 12 months. Post-intervention blood samples for the analysis of C-reactive protein (CRP), IL-6, IL-10, leptin and adiponectin levels were available for 613 participants. Associations between intervention group and biomarker levels were evaluated using quantile regression. There were no statistically significant differences in distributions of CRP, leptin, adiponectin, leptin:adiponectin ratio or IL-10 levels between the placebo group and either supplemented group. The 75th percentile IL-6 level was 2·8 pg/ml higher (95 % CI 0·4, 5·8 pg/ml) in the 1500 μg group than in the placebo group (75th percentiles:11·0 v. 8·2 pg/ml), with a somewhat smaller, non-significant difference in 75th percentiles between the 750 μg and placebo groups. Despite large differences in serum 25(OH)D levels between the three groups after 12 months of supplementation, we found little evidence of an effect of vitamin D supplementation on cytokine or adipokine levels, with the possible exception of IL-6.

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Double-blind placebo-controlled trial of etanercept in the prevention of work disability in ankylosing spondylitis: Table 1

Annals of the Rheumatic Diseases ◽

10.1136/ard.2009.121327 ◽

2010 ◽

Vol 69 (11) ◽

pp. 1926-1928 ◽

Cited By ~ 46

Author(s):

Nick Barkham ◽

Laura C Coates ◽

Helen Keen ◽

Elizabeth Hensor ◽

Alexander Fraser ◽

...

Keyword(s):

Placebo Group ◽

Ankylosing Spondylitis ◽

Clinical Outcomes ◽

Job Loss ◽

Controlled Trial ◽

Controlled Study ◽

Double Blind ◽

Treatment Groups ◽

Gait Parameters ◽

Significant Difference

ObjectivesEtanercept has been shown to be rapidly effective in suppressing disease activity in ankylosing spondylitis (AS). The aim of this study was to determine whether etanercept improves work instability as measured by the Ankylosing Spondylitis Work Instability Scale (AS-WIS).MethodForty patients with active AS who were in work but were work unstable were recruited. Patients were randomised to receive 25 mg etanercept or placebo twice weekly for 12 weeks. The primary outcome was change in AS-WIS at week 12. The AS-WIS is a patient-derived outcome measure which allows stratification of the risk of job loss. Secondary outcomes included clinical outcomes and gait parameters.ResultsThe mean improvement in AS-WIS score at week 12 was 2.75 in the etanercept group and 0.68 in the placebo group (p=0.125). The risk of job loss decreased for 11 (55%) of the etanercept group compared with 7 (35%) in the placebo group. Conversely, the risk of job loss increased in 3 (15%) of the placebo group compared with 1 (5%) in the etanercept group. There was no statistically significant difference between treatment groups in change in WIS categories (Mann–Whitney U test=0.153, p=0.160). Significant improvement with etanercept was seen at week 12 in clinical outcomes and gait parameters. Etanercept was well tolerated, with no dropouts due to adverse events.ConclusionThis small study confirms the efficacy of etanercept on clinical outcome measures in patients with AS and suggests an effect on work instability which needs to be replicated in a larger controlled study.

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Decrease in the Severity of Painful Sickle Cell Crises with Oral Pglg

Blood ◽

10.1182/blood.v126.23.2175.2175 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2175-2175 ◽

Cited By ~ 3

Author(s):

Yutaka Niihara ◽

Lan Tran ◽

Rafael Razon ◽

Charles Stark ◽

Henry Macan

Keyword(s):

Sickle Cell ◽

Controlled Trial ◽

The United States ◽

Third Party ◽

Employment Equity ◽

Phase 3 ◽

Double Blind ◽

Equity Ownership ◽

The Difference ◽

Sickle Cell Crises

Abstract Background: Our earlier work suggested an enhancement of nicotinamide adenine dinucleotide (NAD) in sickled Red Blood Cells (sRBC) by administering a precursor of NAD, L-glutamine. We hypothesized that L-glutamine would decrease the incidence of painful sickle cell crises (PSCC). Small proof of concept studies led to the development of a multi-center Phase 2 placebo-controlled trial where oral pharmaceutical grade L-glutamine (PGLG) suggested benefit when measuring PSCC incidence at 24 weeks. A large multi-center Phase 3 trial further demonstrated that there was a reduction in the incidence of PSCC by administering PGLG compared to placebo. Additional analyses on the data from this trial were conducted and we are reporting our evaluation on the severity of crises between treatment arms. Methods: A randomized (2:1), double-blind, placebo-controlled, parallel-group Phase 3 study was conducted at 31 sites in the United States. Subjects were stratified by hydroxyurea usage. This study included subjects 5 years of age and older that had at least 2 PSCC during the year prior to enrollment. The primary endpoint for the Phase 3 trial was the number of PSCC between treatment arms. Since PSCC events were adjudicated by a blinded third party committee and data were collected as an adverse event ranked as "None"(0), "Mild" (1), "Moderate" (2) and "Severe" (3), the difference in "Severity" of PSCC between treatment arms using Cochran Mantel Haenszel (CMH) Ranked Scores statistics was evaluated post-hoc. Each patient was counted only once at the highest level of severity. Results; A total of 230 patients were enrolled; ages 5-58; 53.9 % female; 152 were assigned to PGLG and 78 to placebo; and the groups were well balanced for baseline clinical characteristics. The comparison of Severity for PGLG vs. Placebo indicated that at (0) was 24% vs. 10% respectively; at (1) was 6% vs. 8%; at (2) was 36% vs. 35%; and at (3) was 34% vs. 47%. Summary statistics for the cohort taken as a whole indicated a treatment difference benefit for the PGLG treatment (p = 0.0167). Other adverse events in the PGLG arm were similar to those observed in the placebo arm. Conclusion: PGLG therapy may be providing clinical benefit over placebo in adult and pediatric patients with a history of two or more crises per year by reducing the "Severity" of painful crises. Difference appeared to be driven by (0) or "None" PSCC events and by a decrease in (3) "Severe" PSCC events. PGLG was administered without difficulty and did not require special monitoring. Disclosures Niihara: Emmaus Medical, Inc: Employment, Equity Ownership. Tran:Emmaus Medical, Inc: Employment, Equity Ownership. Razon:Emmaus Medical, Inc: Employment. Stark:Emmaus Medical, Inc: Employment, Equity Ownership. Macan:Emmaus Medical, Inc: Employment.

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Transition of Care for Pediatric and Adult Patients with Venous Thromboembolism in the American Thrombosis Hemostasis Network

Blood ◽

10.1182/blood-2018-99-117533 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4711-4711

Author(s):

Madhvi Rajpurkar ◽

Maura Malone ◽

Jim Munn ◽

Julie Jaffray ◽

Crystal Watson ◽

...

Keyword(s):

Quality Improvement ◽

Venous Thromboembolism ◽

Research Funding ◽

Pediatric Patients ◽

Anticoagulation Therapy ◽

Adult Patients ◽

First Episode ◽

Transition Of Care ◽

Significant Difference

Abstract Background Venous thromboembolism (VTE) is the third leading cause of cardiovascular morbidity and mortality worldwide in adults and is increasingly seen in children. Optimal transition of care (TOC) from the inpatient to the outpatient setting may lead to improved outcomes for patients with VTE. Although several examples of TOC for patients with VTE exist, this project (ATHN 4: Transition of Care for Patients with VTE) is the first to create a uniform TOC model in the U.S that includes both pediatric and adult patients. The aim of this study was to improve the transition of care of adult and pediatric patients discharged on an anticoagulant after a first episode of VTE and evaluate patient/parent understanding and adherence to anticoagulation therapy-related instructions at seven and 30 days after hospital discharge. Methods Pediatric and adult hospitalized patients with a first episode of VTE requiring anticoagulation therapy were eligible to participate in ATHN 4, a multi-center quality improvement (QI) project conducted by the American Thrombosis and Hemostasis Network (ATHN). The project has two phases: a pre-intervention (PI) phase with no change in standard TOC practice, and a QI intervention phase consisting of enhanced education with standardized Comprehensive Discharge Instruction Modules (CDIM) for each anticoagulant. Demographics, disease, treatment characteristics, and outcomes were collected. Knowledge and feedback questionnaires were administered at 30 days post-discharge. Adult and pediatric data from the PI phase are presented. Results Complete data were submitted for 188 (91%) patients who were enrolled in the PI phase between May 2016 and March 2017 (Table 3). Results show that 73 (39%) were under 18 years of age, 90 (48%) were female, and 156 (83%) were non-Hispanic. A significant difference (p<0.001) in the location of the first VTE was noted among the pediatric and adult patients (Table 4). Approximately 66% (n=48) of the pediatric patients had a DVT, compared to 30% (n=34) of the adult patients. There were more adults with PE as compared to pediatric patients(43% vs. 3%). Adult and pediatric patients differ substantially (p <0.001) with respect to anticoagulant prescriptions. Pediatric patients were more likely to be prescribed Enoxaparin at discharge compared to adults (86% vs. 21%). Additionally, a significantly larger proportion of adult compared to pediatric patients was prescribed Warfarin (17% vs. 3%). Direct oral anticoagulants (DOACs) were mainly prescribed in the adult patients: Apixaban (24% vs. 0%) and Rivaroxaban (18% vs. 3%) compared to the pediatric patients. Based on the responses provided by the patients or guardians (for pediatric patients) during the Day 30 follow-up, there was almost an equal distribution among pediatric and adult patients who by clinical assessment were determined to have correctly taken the prescribed anticoagulant between the time of discharge and follow-up (98.6% of pediatrics and 97.4% of adults). Conclusions Our quality improvement study shows that the majority of pediatric and adult patients correctly took the anticoagulation medication prescribed to them at discharge for at least a month. Majority of pediatric patients presented with a DVT while PE was the most common presentation in adult patients. Enoxaparin and Apixaban were the most commonly prescribed anticoagulants to pediatric and adult patients, respectively. Factors affecting anticoagulation adherence and outcomes in these patients are currently being analyzed. Disclosures Rajpurkar: Bristol Myers Squibb: Research Funding; Shire: Honoraria; HEMA biologics: Honoraria; Pfizer: Honoraria, Research Funding; Novonordisk: Honoraria. Jaffray:Octapharma: Consultancy; CSL Behring: Consultancy, Research Funding; Bayer: Consultancy.

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