Exaggeration of the bleeding risk and thrombotic risk with antiangiogenic therapies in open-label trials compared to double-blind trials in cancer patients: A systematic review and meta-analysis

Thrombotic and embolic events contribute to the morbidity and mortality associated to Chronic Heart Failure (HF). Differently from patients with atrial fibrillation (AF) and HF, in which the benefit of anticoagulation is well documented, the use of these drugs in those with HF in sinus rhythm (without AF history) is controversial. In this systematic review from the Cochrane Collaboration, the authors evaluated the benefits and risks associated with oral anticoagulation (versus placebo) in this population. Only 2 randomized controlled trials were published (one with open-label design) enrolling a total of 324 patients. The results of the meta-analysis based on the best available evidence do not support the systematic use of oral anticoagulants in patients with HF and sinus rhythm for preventing death (overall or cardiovascular) or non-fatal cardiovascular events. Furthermore the major bleeding risk was significantly increased. Keywords: Anticoagulation; Heart Failure; Sinus Rhythm; Systematic Review.

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Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia: Systematic review, meta-analysis, and rationale

Molecular Psychiatry ◽

10.1038/s41380-021-01386-6 ◽

2021 ◽

Author(s):

James S. W. Hong ◽

Lauren Z. Atkinson ◽

Noura Al-Juffali ◽

Amine Awad ◽

John R. Geddes ◽

...

Keyword(s):

Systematic Review ◽

Bipolar Disorder ◽

Calcium Channels ◽

Meta Analysis ◽

Good Evidence ◽

Open Label ◽

Double Blind ◽

Voltage Gated ◽

Anxiety States ◽

Voltage Gated Calcium Channels

AbstractThe gabapentinoids, gabapentin, and pregabalin, target the α2δ subunits of voltage-gated calcium channels. Initially licensed for pain and seizures, they have become widely prescribed drugs. Many of these uses are off-label for psychiatric indications, and there is increasing concern about their safety, so it is particularly important to have good evidence to justify this usage. We conducted a systematic review and meta-analysis of the evidence for three of their common psychiatric uses: bipolar disorder, anxiety, and insomnia. Fifty-five double-blind randomised controlled trials (RCTs) and 15 open-label studies were identified. For bipolar disorder, four double-blind RCTs investigating gabapentin, and no double-blind RCTs investigating pregabalin, were identified. A quantitative synthesis could not be performed due to heterogeneity in the study population, design and outcome measures. Across the anxiety spectrum, a consistent but not universal effect in favour of gabapentinoids compared to placebo was seen (standardised mean difference [SMD] ranging between -2.25 and -0.25). Notably, pregabalin (SMD -0.55, 95% CI -0.92 to -0.18) and gabapentin (SMD -0.92, 95% CI -1.32 to -0.52) were more effective than placebo in reducing preoperative anxiety. In insomnia, results were inconclusive. We conclude that there is moderate evidence of the efficacy of gabapentinoids in anxiety states, but minimal evidence in bipolar disorder and insomnia and they should be used for these disorders only with strong justification. This recommendation applies despite the attractive pharmacological and genetic rationale for targeting voltage-gated calcium channels.

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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 ◽

10.1182/blood.v128.22.3820.3820 ◽

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.

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Antipsychotic combinations in schizophrenia

Epidemiology and Psychiatric Sciences ◽

10.1017/s2045796017000245 ◽

2017 ◽

Vol 26 (5) ◽

pp. 462-465 ◽

Cited By ~ 1

Author(s):

C. Gastaldon ◽

D. Papola ◽

G. Ostuzzi

Keyword(s):

Systematic Review ◽

Randomised Controlled Trials ◽

Negative Symptoms ◽

Partial Agonist ◽

Meta Analysis ◽

Open Label ◽

Double Blind ◽

D2 Antagonist ◽

Randomised Controlled ◽

Meta Analyses

In the treatment of resistant schizophrenia, a number of meta-analyses attempted to quantify the efficacy and tolerability of antipsychotic (AP) polypharmacy v. monotherapy with contradictory results. Recently, a systematic review and meta-analysis of randomised controlled trials investigated the efficacy and tolerability of AP combination v. monotherapy in schizophrenia. It included 31 studies: 21 double-blind (considered high-quality studies) and 10 open-label (considered low-quality studies). The meta-analysis showed that, overall, the combination of two APs was more effective than monotherapy in terms of symptom reduction (standardised mean difference (SMD) = −0.53, 95% confidence interval (CI) −0.87 to −0.19); however, this result was confirmed only in the subgroup of low-quality studies. Negative symptoms improved when combining a D2 antagonist with a D2 partial agonist (SMD = −0.41, 95% CI −0.79 to −0.03) both in double-blind and open-label studies. In the present commentary, the results of this systematic review are critically discussed in terms of their clinical and research implications.

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Clinical Efficacy of Phytodolor under special consideration of double-blind trials and their meta-analysis

Planta Medica ◽

10.1055/s-2007-986749 ◽

2007 ◽

Vol 73 (09) ◽

Cited By ~ 1

Author(s):

KJ Gundermann

Keyword(s):

Clinical Efficacy ◽

Meta Analysis ◽

Special Consideration ◽

Double Blind ◽

Blind Trials

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Faculty Opinions recommendation of Axillary recurrence after a tumour-negative sentinel node biopsy in breast cancer patients: A systematic review and meta-analysis of the literature.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718493916.793497385 ◽

2014 ◽

Author(s):

Larry Norton

Keyword(s):

Breast Cancer ◽

Systematic Review ◽

Sentinel Node ◽

Cancer Patients ◽

Sentinel Node Biopsy ◽

Meta Analysis ◽

Axillary Recurrence ◽

Breast Cancer Patients ◽

Node Biopsy ◽

Negative Sentinel Node Biopsy

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Coronavirus Disease (COVID-19) in Cancer Patients: A Systematic Review and Meta-Analysis to Evaluate Severity and Fatal Outcomes

SSRN Electronic Journal ◽

10.2139/ssrn.3590492 ◽

2020 ◽

Author(s):

Abhijeet Ashok Salunke ◽

Kunal Nandy ◽

Subodh Kumar Pathak ◽

Ketul Puj ◽

Vikas Warikoo ◽

...

Keyword(s):

Systematic Review ◽

Cancer Patients ◽

Meta Analysis

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Is there Sex-related Outcome Difference According to oral P2Y12 Inhibitors in Patients with Acute Coronary Syndromes? A Systematic Review and Meta-Analysis of 107,126 Patients

Current Vascular Pharmacology ◽

10.2174/1570161116666180123092054 ◽

2019 ◽

Vol 17 (2) ◽

pp. 191-203

Author(s):

Oliver Brown ◽

Jennifer Rossington ◽

Gill Louise Buchanan ◽

Giuseppe Patti ◽

Angela Hoye

Keyword(s):

Systematic Review ◽

Acute Coronary Syndromes ◽

Meta Analysis ◽

Indirect Comparison ◽

Bleeding Risk ◽

Cardiovascular Death ◽

P2y12 Inhibitors ◽

Significant Difference ◽

Coronary Syndromes ◽

Randomised Controlled

Background and Objectives: The majority of patients included in trials of anti-platelet therapy are male. This systematic review and meta-analysis aimed to determine whether, in addition to aspirin, P2Y12 blockade is beneficial in both women and men with acute coronary syndromes. Methods: Electronic databases were searched and nine eligible randomised controlled studies were identified that had sex-specific clinical outcomes (n=107,126 patients). Risk Ratios (RR) and 95% Confidence Intervals (CI) were calculated for a composite of cardiovascular death, myocardial infarction or stroke (MACE), and a safety endpoint of major bleeding for each sex. Indirect comparison analysis was performed to statistically compare ticagrelor against prasugrel. Results: Compared to aspirin alone, clopidogrel reduced MACE in men (RR, 0.79; 95% CI, 0.68 to 0.92; p=0.003), but was not statistically significant in women (RR, 0.88; 95% CI, 0.75 to 1.02, p=0.08). Clopidogrel therapy significantly increased bleeding in women but not men. Compared to clopidogrel, prasugrel was beneficial in men (RR, 0.84; 95% CI, 0.73 to 0.97; p=0.02) but not statistically significant in women (RR, 0.94; 95% CI, 0.83 to 1.06; p=0.30); ticagrelor reduced MACE in both men (RR, 0.85; 95% CI, 0.77 to 0.94; p=0.001) and women (RR, 0.84; 95% CI, 0.73 to 0.97; p=0.02). Indirect comparison demonstrated no significant difference between ticagrelor and prasugrel in either sex. Compared to clopidogrel, ticagrelor and prasugrel increased bleeding risk in both women and men. Conclusion: In summary, in comparison to monotherapy with aspirin, P2Y12 inhibitors reduce MACE in women and men. Ticagrelor was shown to be superior to clopidogrel in both sexes. Prasugrel showed a statistically significant benefit only in men; however indirect comparison did not demonstrate superiority of ticagrelor over prasugrel in women.

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Complications of Outpatient and Inpatient Renal Biopsy: A Systematic Review and Meta-Analysis

Diagnostics ◽

10.3390/diagnostics11040651 ◽

2021 ◽

Vol 11 (4) ◽

pp. 651

Author(s):

Shih-Yi Lin ◽

Cherry Yin-Yi Chang ◽

Cheng-Chieh Lin ◽

Wu-Huei Hsu ◽

I.-Wen Liu ◽

...

Keyword(s):

Systematic Review ◽

Renal Biopsy ◽

Meta Analysis ◽

Random Effect ◽

Bleeding Risk ◽

Complication Rates ◽

Bleeding Events ◽

Cochrane Database ◽

Renal Biopsies ◽

Inpatient Settings

Background: The evidence indicates that the optimal observation period following renal biopsy ranges between 6 and 8 h. This systematic review and meta-analysis explored whether differences exist in the complication rates of renal biopsies performed in outpatient and inpatient settings. Methods: We searched the MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from 1985 to February 2020. Two reviewers independently selected studies evaluating the bleeding risk from renal biopsies performed in outpatient and inpatient settings and reviewed their full texts. The primary and secondary outcomes were risks of bleeding and major events (including mortality) following the procedure, respectively. Subgroup analysis was conducted according to the original study design (i.e., prospective or retrospective). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effect meta-analysis. Heterogeneity was assessed using the I2 test. Results: Data from all 10 eligible studies, which included a total of 1801 patients and 203 bleeding events, were included for analysis. Renal biopsies in outpatient settings were not associated with a higher bleeding risk than those in inpatient settings (OR = 0.81; 95% CI, 0.59–1.11; I2 = 0%). The risk of major events was also comparable across both groups (OR = 0.45; 95% CI, 0.16–1.29; I2 = 4%). Conclusions: Similar rates of bleeding and major events following renal biopsy in outpatient and inpatient settings were observed.

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