scholarly journals A Systematic Review and Meta- Analysis of Randomized Controlled Trials on Primary Ambulatory Thromboprophylaxis (PATP) in Patients with Gastrointestinal Cancers Receiving Chemotherapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3679-3679
Author(s):  
Kyaw Zin Thein ◽  
Donald P. Quick ◽  
Thein Hlaing Oo
Keyword(s):  
Systematic Review ◽  
High Risk ◽  
Cancer Patients ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Control Group ◽  
Number Needed To Treat ◽  
Solid Cancer ◽  
Gastrointestinal Cancers

Introduction: PATP in solid cancer patients remains uncertain and is not routinely recommended although thrombosis is shown to be the second leading cause of death in cancer patients. Many studies failed to demonstrate in solid cancer outpatients improvement in overall survival despite decreasing venous thromboembolism (VTE) rates by PATP. We conducted a systematic review and meta-analysis of RCTs to determine the benefit and risk of PATP with low-molecular weight heparins (LMWHs) and direct oral anticoagulants (DOACs) in patients with gastrointestinal cancers receiving chemotherapy. Methods: We performed a comprehensive literature search using MEDLINE and EMBASE databases through June 30, 2019. The references of all potential studies were also reviewed for any additional relevant studies. The RCTs with reduction in VTE as a primary or secondary endpoint and the major bleeding (MB) as a safety outcome were incorporated in the analysis. The primary meta- analytic approach was a fixed effects model using the Mantel-Haenszel (MH) method. It was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q- statistic. Results: A total of 1,932 patients with gastric, gastroesophageal junctional (GEJ) and colorectal cancers from a subgroup of three RCTs were included in our meta-analysis. The prophylactic doses of LMWHs and DOAC (rivaroxaban) were used in the studies. The duration of LMWH and DOAC ranged from 3 to 6 months. The randomization ratio was 2 to 1 in PROTECHT study and 1 to 1 in all other studies. The I2 statistic for heterogeneity was 0, suggesting homogeneity among RCTs. The VTE incidence was 13 (1.26%) in PATP group and 23 (2.55%) in control group with a RR of 0.49 (95% CI: 0.25 to 0.96, P = 0.04). The absolute RD in VTE was -0.01 (95% CI: -0.03 to -0.00, P 0.04) with an estimate of the number needed to treat (NNT) of 78 to prevent one VTE event. In a subset of patients with gastric and GEJ cancers (n=587), the VTE incidence was 4 (1.37%) in PATP group and 10 (3.40%) in control group with a RR of 0.40 (95% CI: 0.13 to 1.24, P = 0.11). Conclusions: In our study, the relative risk reduction is 48% with a NNT of 78 to prevent one VTE in ambulatory patients with gastrointestinal cancers. Nevertheless, there is no statistically significant reduction in VTE events in a subset of gastric and GEJ cancers which are considered high risk in Khorana score. Based on the findings, PATP is not recommended in patients with gastrointestinal cancers on chemotherapy at this time. Further studies are necessary to define high risk subsets of gastrointestinal cancer patients receiving chemotherapy who may benefit from PATP. Disclosures Oo: Medical Education Speakers Network: Honoraria; Janssen and Janssen: Other: site co-investigator.

scholarly journals Updated Meta-Analysis of Randomized Controlled Trials on Primary Ambulatory Thromboprophylaxis (PATP) in Patients with Advanced Pancreatic Cancer (APC) Receiving Chemotherapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3469-3469 ◽  
Author(s):  
Kyaw Zin Thein ◽  
Donald P. Quick ◽  
Thein H. Oo
Keyword(s):  
Relative Risk ◽  
High Risk ◽  
Cancer Patients ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Advanced Pancreatic Cancer ◽  
Control Group ◽  
Number Needed To Treat ◽  
Solid Cancer

Introduction: Thrombosis is the second leading cause of death in cancer patients and patients with APC are categorized as high-risk of developing venous thromboembolism (VTE). Many trials had failed to demonstrate improvement in survival with PATP. Despite decreasing VTE events, PATP in solid cancer patients is not routinely recommended. We conducted an updated meta- analysis of RCTs to determine the benefit and risk of PATP with low-molecular weight heparins (LMWH) and direct oral anticoagulants (DOAC) in patients with APC receiving chemotherapy. Methods: We performed a comprehensive literature search using MEDLINE and EMBASE databases through June 30, 2019. The references of all potential studies were also reviewed for any additional relevant studies. The RCTs with reduction in VTE as a primary or secondary endpoint and the major bleeding (MB) as a safety outcome were incorporated in the analysis. The primary meta- analytic approach was a random effects model using the Mantel-Haenszel (MH) method. It was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q- statistic. Results: A total of 1,013 patients with APC from two RCTs and a subgroup of another three RCTs were included in our meta-analysis. The prophylactic, intermediate and therapeutic doses of LMWH and prophylactic dose of DOAC (rivaroxaban) were used in the studies. The duration of LMWH and DOAC ranged from 3 to 6 months. The randomization ratio was 2 to 1 in PROTECHT study and 1 to 1 in all other studies. The I2statistic for heterogeneity was 60, suggesting some heterogeneity among RCTs. The VTE incidence was 28 (5.43%) in PATP group and 60 (12.07%) in control group with a RR of 0.44 (95% CI: 0.20 to 0.99, P = 0.05) and RD of -0.06 (95% CI: -0.11 to -0.01, P = 0.01). In fixed effects model, the pooled RR was 0.45 (95% CI: 0.29 to 0.70, P = 0.0003) and the absolute RD in VTE was -0.07 (95% CI: -0.10 to -0.03, P = 0.0002) with an estimate of the number needed to treat (NNT) of 15 to prevent one VTE event. MB events were reported in 9 (4.11%) patients in PATP group compared to 7 (3.27%) in control group according to an analysis of 2 RCTs. The pooled relative risk for MB was statistically non-significant at 1.25 (95% CI: 0.47 to 3.31, P = 0.65). Conclusions: In our study, PATP in APC may statistically significantly decrease VTE events, approximately with relative risk reduction of 55% and a NNT of 15, without increasing MB events. Proper selection of patients who are high risk for VTE in outpatient setting is important. More RCTs are required to further define high risk subsets of APC patients receiving chemotherapy who may benefit from PATP. Disclosures Oo: Medical Education Speakers Network: Honoraria; Janssen and Janssen: Other: Research: site co-investigator .

A Systematic Review and Meta-Analysis of Randomized Controlled Trials (RCT) in Ambulatory Thromboprophylaxis (ATP) in Patients with Lung Cancer Receiving Chemotherapy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3825-3825
Author(s):  
Kyaw Zin Thein ◽  
Sai-Ching J Yeung ◽  
Thein H. Oo
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Cancer Patients ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Control Group ◽  
Number Needed To Treat ◽  
Solid Cancer ◽  
Fixed Effects Model ◽  
Bleeding Events

Abstract Introduction: Lung cancer (LC) is the commonest cause of cancer mortality in USA. Thromboembolism (TE) is the second leading cause of death in cancer patients. The ambulatory thromboprophylaxis (ATP) in solid cancer patients remains uncertain. However, LC is at least an intermediate risk for TE according to Khorana scoring system. We conducted a systematic review and meta-analysis of RCTs to determine the benefit and risk of ATP with low-molecular weight heparins (LMWH) in LC patients receiving chemotherapy. Methods: We performed a comprehensive literature search using MEDLINE and EMBASE databases through June 30, 2016. The RCTs with reduction in TE as a primary or secondary endpoint and the major bleeding (MB) as a safety outcome were included in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Fixed effects model was applied. Results: A total of 4315 patients with LC from 4 RCTs and a subgroup of another 2 RCTs were included in our analysis. The prophylactic doses of dalteparin, nadroparin, certoparin, semuloparin and bemiparin were used in the studies. The ATP duration ranged from 3 to 6 months. The randomization ratio was 2 to 1 in PROTECHT study and 1 to 1 in other studies. The TE incidence was 89 (4.007%) in ATP group and 166 (7.927%) in control group with a RR of 0.510 (95% CI: 0.397 to 0.654, P < 0.001). The absolute RD was -0.039 (95% CI: -0.053 to -0.025, P < 0.001) with an estimated number needed to treat (NNT) of 25 to prevent one TE event. MB events were 24 (1.506%) in ATP group compared to 15 (1.019%) in control group according to an analysis of 4 RCTs. The pooled RR for MB was statistically nonsignificant at 1.468 (95% CI: 0.785 to 2.746, P = 0.229). Clinically relevant nonmajor (CRNM) bleeding events were 80 (5.571%) in ATP group and in 24 (1.674%) in control group on an analysis of 4 RCTs. The RR for CRNM bleeding was statistically significant at 3.253 (95% CI: 2.092 to 5.059, P < 0.001). Conclusions: In our study, the relative risk reduction for TE is 49% with a NNT of 25 to prevent one TE without increasing MB. Nevertheless, CRNM bleeding episodes were significant at a ratio of 3.253. Based on the findings, selection of LC patients who are at high TE risk is important. Further studies are necessary to define a subset of LC patients who may benefit from ATP. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Oo: Daiichi Sankyo: Research Funding.

scholarly journals Updated Meta-Analysis of Randomized Controlled Trials on Primary Ambulatory Thromboprophylaxis (PATP) in Patients with Locally Advanced or Metastatic Lung Cancer Receiving Chemotherapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2435-2435
Author(s):  
Kyaw Zin Thein ◽  
Lukman Tijani ◽  
Thein H. Oo
Keyword(s):  
Lung Cancer ◽  
Relative Risk ◽  
High Risk ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Locally Advanced ◽  
The United States ◽  
Control Group ◽  
Number Needed To Treat ◽  
Solid Cancer

Introduction: Lung cancer (LC) is the second most common cancer in both sexes and is the leading cause of cancer mortality in the United States. Thrombosis is the second leading cause of death in cancer patients and PATP in solid cancer patients were performed in research trials to decrease venous thromboembolism (VTE) rates with ultimate aim to improve survival. We undertook an updated meta- analysis of RCTs to determine the benefit and risk of PATP with low-molecular weight heparins (LMWHs) and direct oral anticoagulants (DOAC) in patients with locally advanced or metastatic LC receiving chemotherapy. Methods: We performed a comprehensive literature search using MEDLINE and EMBASE databases through June 30, 2019. The references of all potential studies were also reviewed for any additional relevant studies. The RCTs with reduction in VTE as a primary or secondary endpoint and the major bleeding (MB) as a safety outcome were incorporated in the analysis. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q- statistic. Fixed effects model was applied. Results: A total of 5,375 patients with LC from five RCTs and a subgroup of another four RCTs were included in our meta-analysis. The prophylactic doses of bemiparin, certoparin, dalteparin, nadroparin, semuloparin and tinzaparin, intermediate dose of enoxaparin and prophylactic dose of rivaroxaban were used in the studies. The duration of LMWH and DOAC ranged from 3 to 6 months. The randomization ratio was 2 to 1 in PROTECHT study and 1 to 1 in all other studies. The I2statistic for heterogeneity was 0, suggesting homogeneity among RCTs. The VTE incidence was 114 (4.16%) in PATP group and 207 (7.85%) in control group with a RR of 0.53 (95% CI: 0.43 to 0.67, P < 0.001). The absolute RD in VTE was -0.04 (95% CI: -0.05 to -0.02, P < 0.001) with an estimate of the number needed to treat (NNT) of 28 to prevent one VTE event. MB events were reported in 26 (1.37%) patients in PATP group compared to 15 (0.84%) in control group according to an analysis of 6 RCTs. The pooled relative risk for MB was statistically non-significant at 1.57 (95% CI: 0.85 to 2.88, P = 0.15). Conclusions: Our analysis showed that the relative risk reduction is 46% with a NNT of 28 to prevent one VTE without increasing MB events in ambulatory patients with locally advanced or metastatic LC. Selection of appropriate patients who are high risk for VTE is crucial and further studies are required to define high risk subsets of LC patients receiving chemotherapy who may benefit from PATP. Disclosures Oo: Janssen and Janssen: Other: Research: site co-investigator ; Medical Education Speakers Network: Honoraria.

Risk of Bleeding from Primary Thromboprophylaxis (PTP) in Patients with Solid Cancer Receiving Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (RCT)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3820-3820
Author(s):  
Kyaw Zin Thein ◽  
Aung M Tun ◽  
Sai-Ching J Yeung ◽  
Thein H. Oo
Keyword(s):  
Systematic Review ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Bleeding Event ◽  
Bleeding Risk ◽  
Risk Difference ◽  
Control Group ◽  
Solid Cancer ◽  
Bleeding Events ◽  
Risk Of Bleeding

Abstract Introduction: Thrombosis is the second leading cause of death in cancer patients. Hypothetically, prognosis might be improved by preventing thrombotic events by PTP. PTP has to be outweighed with the bleeding risk from PTP benefit. Moreover, PTP in ambulatory cancer patients remains uncertain. We performed a systematic review and meta-analysis of RCTs to determine the risk of major bleeding (MB) and clinically relevant non-major (CRNM) bleeding from PTP with low-molecular weight heparins (LMWH) in solid cancer patients receiving chemotherapy. Methods: We systematically conducted a comprehensive literature search using MEDLINE and EMBASE databases through May 31, 2016. The RCTs with MB and CRNM bleeding as safety outcomes were included in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Random effects model was applied. Results: 12 RCTs with a total of 8643 patients were eligible for analysis. Dalteparin, nadroparin, certoparin, semuloparin and bemiparin were used in the studies. 9 studies utilized prophylactic doses, while one used intermediate doses and 2 employed therapeutic dose. The PTP duration was from 6 weeks to 6 months. MB events were reported in 67 (1.486%) patients on PTP compared to 46 (1.112%) in control group. The pooled RR for MB was statistically nonsignificant at 1.341 (95% CI: 0.917 to 1.960, P = 0.130). CRNM bleeding events were noted in 209 (4.637%) in PTP group and 106 (2.563%) in control group. The RR for CRNM bleeding was statistically significant at 1.729 (95% CI: 1.017 to 2.938, P = 0.043). The absolute RD in CRNM bleeding was 0.020 (95% CI: 0.004 to 0.035, P = 0.012) with an estimated number needed to harm (NNH) of 48 to cause one CRNM bleeding event. Conclusions: Approximately 60 patients are needed to be treated with PTP to prevent one symptomatic venous thrombosis among all ambulatory unselected cancer patients on chemotherapy in a previous meta-analysis. Our meta-analysis revealed that PTP contributed an increase in CRNM bleeding events with NNH of 48. The risk of bleeding should not be underestimated and more RCTs are required before making any recommendations. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Oo: Daiichi Sankyo: Research Funding.

scholarly journals Nervous and Muscular Adverse Events after COVID-19 Vaccination: A Systematic Review and Meta-Analysis of Clinical Trials

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 939
Author(s):  
Jiaxin Chen ◽  
Yuangui Cai ◽  
Yicong Chen ◽  
Anthony P. Williams ◽  
Yifang Gao ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Events ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Phase 1 ◽  
Cochrane Library ◽  
Categorical Variables ◽  
Control Group ◽  
Open Label

Background: Nervous and muscular adverse events (NMAEs) have garnered considerable attention after the vaccination against coronavirus disease (COVID-19). However, the incidences of NMAEs remain unclear. We aimed to calculate the pooled event rate of NMAEs after COVID-19 vaccination. Methods: A systematic review and meta-analysis of clinical trials on the incidences of NMAEs after COVID-19 vaccination was conducted. The PubMed, Medline, Embase, Cochrane Library, and Chinese National Knowledge Infrastructure databases were searched from inception to 2 June 2021. Two independent reviewers selected the study and extracted the data. Categorical variables were analyzed using Pearson’s chi-square test. The pooled odds ratio (OR) with the corresponding 95% confidence intervals (CIs) were estimated and generated with random or fixed effects models. The protocol of the present study was registered on PROSPERO (CRD42021240450). Results: In 15 phase 1/2 trials, NMAEs occurred in 29.2% vs. 21.6% (p < 0.001) vaccinated participants and controls. Headache and myalgia accounted for 98.2% and 97.7%, and their incidences were 16.4% vs. 13.9% (OR = 1.97, 95% CI = 1.28–3.06, p = 0.002) and 16.0% vs. 7.9% (OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) in the vaccine and control groups, respectively. Headache and myalgia were more frequent in the newly licensed vaccines (OR = 1.97, 95% CI = 1.28–3.06, p = 0.02 and OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) and younger adults (OR = 1.40, 95% CI = 1.12–1.75, p = 0.003 and OR = 1.54, 95% CI = 1.20–1.96, p < 0.001). In four open-label trials, the incidences of headache, myalgia, and unsolicited NMAEs were 38.7%, 27.4%, and 1.5%. Following vaccination in phase 3 trials, headache and myalgia were still common with a rate of 29.5% and 19.2%, although the unsolicited NMAEs with incidence rates of ≤ 0.7% were not different from the control group in each study. Conclusions: Following the vaccination, NMAEs are common of which headache and myalgia comprised a considerable measure, although life-threatening unsolicited events are rare. NMAEs should be continuously monitored during the ongoing global COVID-19 vaccination program.

scholarly journals Wilms' tumor 1 (WT1) expression and prognosis in solid cancer patients: a systematic review and meta-analysis

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Xiao-wei Qi ◽  
Fan Zhang ◽  
Hong Wu ◽  
Jun-lan Liu ◽  
Bei-ge Zong ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cancer Patients ◽  
Wilms Tumor ◽  
Meta Analysis ◽  
Solid Cancer ◽  
Wilms Tumor 1

scholarly journals Effectiveness of diluted povidone-iodine lavage for preventing periprosthetic joint infection: an updated systematic review and meta-analysis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Naomi Kobayashi ◽  
Emi Kamono ◽  
Kento Maeda ◽  
Toshihiro Misumi ◽  
Yohei Yukizawa ◽  
...  
Keyword(s):  
Systematic Review ◽  
Periprosthetic Joint Infection ◽  
Fixed Effects ◽  
Povidone Iodine ◽  
Meta Analysis ◽  
Joint Infection ◽  
Assessment Process ◽  
Cochrane Library ◽  
Saline Control ◽  
Control Group

Abstract Background Of the several methods used to prevent surgical site infection (SSI), diluted povidone-iodine (PI) lavage is used widely. However, the clinical utility of PI for preventing periprosthetic joint infection (PJI) remains controversial. The aim of this study was to perform a systematic review and meta-analysis of the utility of dilute PI lavage for preventing PJI in primary and revision surgery. Methods This study was conducted in accordance with the PRISMA checklist for systematic reviews and meta-analyses. A comprehensive literature search of PubMed, CINAHL, ClinicalTrials.gov, and Cochrane Library databases was performed. The results are summarized qualitatively and as a meta-analysis of pooled odds ratios with 95% confidence intervals (95% CIs). Heterogeneity of treatment effects among studies was classified as low, moderate, or high, corresponding to I2 values of < 25%, 25–50%, and > 50%. A random effects model was applied in cases of high heterogeneity; otherwise, the fixed effects model was applied. Subgroup analyses were conducted to identify potential sources of heterogeneity. Results After the screening and eligibility assessment process, eight studies were finally extracted for analysis. Overall, the results showed that PI had no significant effect on PJI with ununified control group. However, subgroup analysis of studies with a saline control group revealed an odds ratio of 0.33 (95% CI, 0.16–0.71) for the PI group, suggesting a significant effect for preventing PJI. Conclusion The systematic review and meta-analysis of the current literature demonstrates that diluted PI lavage is significantly better than saline solution lavage for preventing PJI. Level of evidence Level I, Systematic review and meta-analysis.

Hemorrhagic and thrombotic events in oncology patients treated with antiangiogenic therapy: Impact of study design on the results assessed by meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14058-e14058
Author(s):  
Jane-Chloe Trone ◽  
Céline Chapelle ◽  
Edouard Ollier ◽  
Laurent Bertoletti ◽  
Michel Cucherat ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Patients ◽  
Study Design ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Antiangiogenic Therapy ◽  
Solid Cancer ◽  
Increasing Risk ◽  
Meta Analyses ◽  
The Impact

e14058 Background: Antiangiogenic (AA) therapies emerge as a new cornerstone for cancer treatment, but carry their own particular risk profile. Several previous meta-analyses have showed increasing risk of bleeding and paradoxically thrombosis in cancer patients receiving antiangiogenic. The aim of the meta-analysis is to investigate the impact of studies design (open or double blind (DB)), on the incidence and the occurrence of bleeding, venous thrombotic events (VTE) and arterial thrombotic events (ATE) in cancer patients treated by AA therapies. Methods: We searched Medline, Cochrane, ClinicalTrial databases, meeting abstracts of the American Society of Clinical Oncology and the European Society of Medical Oncology for relevant clinical trials. We included prospective phase II and III clinical trials that randomly assigned patients with solid cancer to AA therapy or control. Statistical analyses were conducted to calculate the summary incidence, ORs, and 95% CIs, using random-effects or fixed-effects models based on the heterogeneity of included studies. Results: A total of 166 trials (72,024 patients) were included. For bleeding events, comparison on AA treatment versus control yielded an OR of 2.41 (95% CI 2.07 to 2.71; p < 0.001) with an exaggeration of treatment effects by 68% (95% CI, 33 to 113) in open-label studies compared with DB trials. Concerning VTE, an OR of 1.18 (95% CI 1.04 to 1.35; p = 0.0115) was noted, with a significant enhancement of 53% (95% CI, 19 to 96) of treatment side effects with open trials compared with DB trials. AA don’t increase significantly the frequency of VTE when considering only DB trials. For ATE, an OR of 1.59 (95% CI 1.30 to 1.94; p < 0.001) was observed, associated with a significant exaggeration of 65% (95% CI, 13 to 143) with open trials compared with DB trials. Conclusions: The present meta-analysis showed a significant interaction of study design for the tolerance assessment in the AA therapies in cancers. The increasing risk of hemorrhagic events, VTE and ATE appear to have been overestimated in the previous meta-analyses. In the future, meta-analyses should be restricted to DB trials for analysis of toxicity profile.

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