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1.
Erythromycin prior to endoscopy for acute upper gastrointestinal haemorrhage
Adão, D., Gois, A. F., Pacheco, R. L., Pimentel, C. F., Riera, R.
The Cochrane Database of Systematic Reviews. 2023;2(2):Cd013176
Abstract
BACKGROUND Upper endoscopy is the definitive treatment for upper gastrointestinal haemorrhage (UGIH). However, up to 13% of people who undergo upper endoscopy will have incomplete visualisation of the gastric mucosa at presentation. Erythromycin acts as a motilin receptor agonist in the upper gastrointestinal (GI) tract and increases gastric emptying, which may lead to better quality of visualisation and improved treatment effectiveness. However, there is uncertainty about the benefits and harms of erythromycin in UGIH. OBJECTIVES To evaluate the benefits and harms of erythromycin before endoscopy in adults with acute upper gastrointestinal haemorrhage, compared with any other treatment or no treatment/placebo. SEARCH METHODS We used standard, extensive Cochrane search methods. The latest search date was 15 October 2021. SELECTION CRITERIA We included randomised controlled trials (RCTs) that investigated erythromycin before endoscopy compared to any other treatment or no treatment/placebo before endoscopy in adults with acute UGIH. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were 1. UGIH-related mortality and 2. serious adverse events. Our secondary outcomes were 1. all-cause mortality, 2. visualisation of gastric mucosa, 3. non-serious adverse events, 4. rebleeding, 5. blood transfusion, and 5. rescue invasive intervention. We used GRADE criteria to assess the certainty of the evidence for each outcome. MAIN RESULTS We included 11 RCTs with 878 participants. The mean age ranged from 53.13 years to 64.5 years, and most participants were men (72.3%). One RCT included only non-variceal haemorrhage, one included only variceal haemorrhage, and eight included both aetiologies. We defined short-term outcomes as those occurring within one week of initial endoscopy. Erythromycin versus placebo Three RCTs (255 participants) compared erythromycin with placebo. There were no UGIH-related deaths. The evidence is very uncertain about the short-term effects of erythromycin compared with placebo on serious adverse events (risk difference (RD) -0.01, 95% confidence interval (CI) -0.04 to 0.02; 3 studies, 255 participants; very low certainty), all-cause mortality (RD 0.00, 95% CI -0.03 to 0.03; 3 studies, 255 participants; very low certainty), non-serious adverse events (RD 0.01, 95% CI -0.03 to 0.05; 3 studies, 255 participants; very low certainty), and rebleeding (risk ratio (RR) 0.63, 95% CI 0.13 to 2.90; 2 studies, 195 participants; very low certainty). Erythromycin may improve gastric mucosa visualisation (mean difference (MD) 3.63 points on 16-point ordinal scale, 95% CI 2.20 to 5.05; higher MD means better visualisation; 2 studies, 195 participants; low certainty). Erythromycin may also result in a slight reduction in blood transfusion (MD -0.44 standard units of blood, 95% CI -0.86 to -0.01; 3 studies, 255 participants; low certainty). Erythromycin plus nasogastric tube lavage versus no intervention/placebo plus nasogastric tube lavage Six RCTs (408 participants) compared erythromycin plus nasogastric tube lavage with no intervention/placebo plus nasogastric tube lavage. There were no UGIH-related deaths and no serious adverse events. The evidence is very uncertain about the short-term effects of erythromycin plus nasogastric tube lavage compared with no intervention/placebo plus nasogastric tube lavage on all-cause mortality (RD -0.02, 95% CI -0.08 to 0.03; 3 studies, 238 participants; very low certainty), visualisation of the gastric mucosa (standardised mean difference (SMD) 0.48 points on 10-point ordinal scale, 95% CI 0.10 to 0.85; higher SMD means better visualisation; 3 studies, 170 participants; very low certainty), non-serious adverse events (RD 0.00, 95% CI -0.05 to 0.05; 6 studies, 408 participants; very low certainty), rebleeding (RR 1.13, 95% CI 0.63 to 2.02; 1 study, 169 participants; very low certainty), and blood transfusion (MD -1.85 standard units of blood, 95% CI -4.34 to 0.64; 3 studies, 180 participants; very low certainty). Erythromycin versus nasogastric tube lavage Four RCTs (287 participants) compared erythromycin with nasogastric tube lavage. There were no UGIH-related deaths and no serious adverse events. The evidence is very uncertain about the short-term effects of erythromycin compared with nasogastric tube lavage on all-cause mortality (RD 0.02, 95% CI -0.05 to 0.08; 3 studies, 213 participants; very low certainty), visualisation of the gastric mucosa (RR 1.19, 95% CI 0.79 to 1.79; 2 studies, 198 participants; very low certainty), non-serious adverse events (RD -0.10, 95% CI -0.34 to 0.13; 3 studies, 213 participants; very low certainty), rebleeding (RR 0.77, 95% CI 0.40 to 1.49; 1 study, 169 participants; very low certainty), and blood transfusion (median 2 standard units of blood, interquartile range 0 to 4 in both groups; 1 study, 169 participants; very low certainty). Erythromycin plus nasogastric tube lavage versus metoclopramide plus nasogastric tube lavage One RCT (30 participants) compared erythromycin plus nasogastric tube lavage with metoclopramide plus nasogastric tube lavage. The evidence is very uncertain about the effects of erythromycin plus nasogastric tube lavage on all the reported outcomes (serious adverse events, visualisation of gastric mucosa, non-serious adverse events, and blood transfusion). AUTHORS' CONCLUSIONS We are unsure if erythromycin before endoscopy in people with UGIH has any clinical benefits or harms. However, erythromycin compared with placebo may improve gastric mucosa visualisation and result in a slight reduction in blood transfusion.
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2.
Continuous vs. intermittent terlipressin infusion for portal hypertension: a systematic review and meta-analysis
Hassan, M., Merza, N., Nawras, Y., Bahbah, E. I., Al-Hillan, A., Ahmed, Z., ElSheref, Sedm, Dahiya, D. S., Dar, S., Al Azzawi, M., et al
Annals of medicine and surgery (2012). 2023;85(10):5001-5010
Abstract
BACKGROUND Portal hypertension, a major complication of chronic liver disease, often leads to life-threatening variceal bleeding, managed effectively with vasoactive drugs like terlipressin. However, the most optimal method of terlipressin administration, continuous versus intermittent infusion, remains a subject of debate, necessitating this systematic review and meta-analysis for evidence-based decision-making in managing this critical condition. METHODS This systematic review and meta-analysis adhered to the PRISMA standards and explored multiple databases until 6 April 2023, such as MEDLINE through PubMed, Scopus, Web of Science, and CENTRAL. Independent reviewers selected randomized controlled trials (RCTs) that met specific inclusion criteria. After assessing study quality and extracting necessary data, statistical analysis was performed using Review Manager (RevMan), with results presented as risk ratios (RR) or mean differences. RESULTS Five RCTs (n=395 patients) were included. The continuous terlipressin group had a significantly lower risk of rebleeding (RR=0.43, P=0.0004) and treatment failure (RR=0.22, P=0.02) and fewer total adverse effects (RR=0.52, P<0.00001) compared to the intermittent group. However, there were no significant differences between the two groups in mean arterial pressure (P=0.26), length of hospital stays (P=0.78), and mortality rates (P=0.65). CONCLUSION This study provides robust evidence suggesting that continuous terlipressin infusion may be superior to intermittent infusions in reducing the risk of rebleeding, treatment failure, and adverse effects in patients with portal hypertension. However, further large-scale, high-quality RCTs are required to confirm these findings and to investigate the potential benefits of continuous terlipressin infusion on mortality and hospital stays.
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Deferoxamine in intracerebral hemorrhage: Systematic review and meta-analysis
Sun T, Zhao YY, Xiao QX, Wu M, Luo MY
Clinical neurology and neurosurgery. 2023;227:107634
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Editor's Choice
Abstract
BACKGROUND Intracerebral hemorrhage (ICH) is a stroke with a high morbidity and mortality rate. Deferoxamine (DFX) is thought to be effective in treating Intracerebral Hemorrhage. In our study, we performed a meta-analysis to evaluate the treatment effects of DFX. METHODS We systematically searched PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and Chinese Biomedical Literature Database in Jan 2022 for studies on DFX for ICH patients. Outcome measures included relative hematoma volume, relative edema volume, good neurological functional outcome and adverse events. Odds risk (OR) and weighted mean difference (WMD) were used to evaluate clinical outcomes. RESULTS After searching 636 articles, 4 RCTs, 2 NRCTs, and 1cohort study were included. We found that DFX was effective in hematoma absorption on day 7 after onset, but the difference was not significant on day 14. DFX could suppress edema expansion on days 3, 7, and 14 after onset. DFX did not contribute to better outcomes after 3 and 6 months when used the modified Rankin Scale and the Glasgow Outcome Scale to evaluate neurological prognosis. The pooled results showed no statistically significant difference in Serious adverse events between the experimental and control groups. CONCLUSIONS DFX could limit edema expansion on days 3, 7, and 14 after commencement and facilitate hematoma absorption at week 1 without significantly increasing the risk of adverse events, but it did not improve neurological prognosis.
PICO Summary
Population
Patients with intracerebral haemorrhage (n= 7 studies).
Intervention
Deferoxamine (DFX).
Comparison
Placebo.
Outcome
Outcome measures included relative haematoma volume, relative oedema volume, good neurological functional outcome and adverse events. DFX was effective in haematoma absorption on day 7 after onset, but the difference was not significant on day 14. DFX could suppress oedema expansion on days 3, 7, and 14 after onset. DFX did not contribute to better outcomes after 3 and 6 months when used the modified Rankin Scale and the Glasgow Outcome Scale to evaluate neurological prognosis. The pooled results showed no statistically significant difference in serious adverse events between the experimental and control groups.
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Efficacy of desferrioxamine mesylate in intracerebral hematoma: a systemic review and meta-analysis
Zhao K, Li J, Zhang Q, Yang M
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2022;:1-12
Abstract
BACKGROUND Previous meta-analysis had concluded that desferrioxamine mesylate (DFO) could effectively treat intracerebral hematoma (ICH) in animal models. We hope to confirm that DFO could treat ICH patients effectively through the systemic review and meta-analysis of clinical researches. METHOD Data extraction included hematoma volume (HV), reduction of National Institute of Health Stroke Scale (NIHSS) scores, and relative perihematomal edema (RPHE). The standard mean difference (SMD) and 95% confidence interval (95%CI) were calculated by fixed effects model. I-square (I(2)) statistic was used to test the heterogeneity. All p values were two-side with a significant level at 0.05. RESULTS Five randomized controlled trials were included in the meta-analysis, which included 239 patients. At 7 days after onset, there was significant difference of RPHE development (- 1.87 (- 2.22, - 1.51) (I(2) = 0, p = 0.639)) and significant difference of HV absorption (- 0.71 (- 1.06, 0.36) (I(2) = 17.5%, p = 0.271)) between DFO and control groups. There was significant difference of reduction of NHISS scores (0.25 (0.05, 0.46) (I(2) = 0, p = 0.992)) between DFO and control groups at 30 days after onset. CONCLUSION DFO reduced HV and perihematomal edema in ICH patients at 7 days after onset and improve neurological function at 30 days after onset efficiently and safely. DFO might be a new route of improving treatment of ICH.
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Efficacy and safety of traditional Chinese medicine for intracranial hemorrhage by promoting blood circulation and removing blood stasis: A systematic review and meta-analysis of randomized controlled trials
Lin W, Hou J, Han T, Zheng L, Liang H, Zhou X
Frontiers in pharmacology. 2022;13:942657
Abstract
Background: Although blood-activating Chinese medicine (BACM) has been reported as adjuvant therapy for intracranial hemorrhage (ICH) in China, high-quality evidence is still lacking. Our study aimed to collect the latest high-quality randomized controlled trials (RCTs) and to evaluate the efficacy and safety of BACM for ICH. Methods: RCTs published between January 2015 and March 2022 were searched in databases, including China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Sino-Med, Wanfang, PubMed, Web of Science, Cochrane Library, and Embase without language restrictions. Eligible RCTs were included and both primary (clinical efficacy evidenced by decreased neurological deficit scores) and secondary outcomes (increased Barthel index, decreased NIHSS, hematoma volume, the volume of cerebral edema, the incidence of side effects, and mortality) were analyzed. The quality of included RCTs was assessed using the Cochrane risk of bias tool. In the meta-analysis, the pooled results were analyzed using Review Manager 5.3 and STATA14.0. Finally, The GRADEpro GDT software (Guideline Development Tool) was used to summarize the results. Sensitivity and subgroup analyses were conducted based on the follow-up time. Results: Fifteen RCTs, involving 1,579 participants, were included for analysis in our study. The pooled outcomes indicated that BACM combined with western medicine treatment (WMT) was superior to WMT alone for patients with ICH, demonstrated by the improvements in efficacy (RR = 1.22 (95% CI, [1.13 to 1.32], p < 0.001), neurological functions (MD(NIHSS) = -2.75, 95% CI [-3.74 to -1.76], p < 0.001), and activities of daily living (MD(Barthel index) = 5.95, 95% CI [3.92 to 7.98], p < 0.001), as well as decreased cerebral hematoma, cerebral edema (MD cerebral hematoma = -2.94, 95% CI [-3.50 to -2.37, p < 0.001 and MD(cerebral edema) = -2.66, 95% CI [-2.95 to -2.37], p < 0.001), side effects and mortality (RR = 0.84 (95% CI [0.60 to 1.19], p = 0.330 and RR = 0.51 (95% CI, [0.16 to 1.65], p = 0.260). In addition, Conioselinum anthriscoides "Chuanxiong" [Apiaceae], Camellia reticulata Lindl. [Theaceae], and Bupleurum sibiricum var. jeholense (Nakai) C.D.Chu [Apiaceae]) were the most frequently used herbs in the treatment of ICH. Recently, there was a trend toward the extensive use of another two herbs, including Rheum palmatum L. [Polygonaceae], Astragalus mongholicus Bunge [Fabaceae]) for ICH. Conclusion: BACM combined with WMT seems to be superior to WMT alone for patients with ICH. Further high-quality RCTs are warranted to confirm the efficacy and safety of BACM.
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Cilostazol Administration for Subarachnoid Hemorrhage: A Meta-analysis of Randomized Controlled Trials
Chen, H., Luo, W., Cai, X., Cai, J.
Clinical Neuropharmacology. 2022;45(5):111-116
Abstract
INTRODUCTION The efficacy of cilostazol administration to treat subarachnoid hemorrhage remains controversial. We conduct a systematic review and meta-analysis to explore the influence of cilostazol administration on treatment efficacy for subarachnoid hemorrhage. METHODS We have searched PubMed, Embase, Web of science, EBSCO, and Cochrane Library databases through July 2020 for randomized controlled trials assessing the effect of cilostazol administration in patients with subarachnoid hemorrhage. This meta-analysis is performed using the random-effect model. RESULTS Four randomized controlled trials involving 405 patients were included in the meta-analysis. Overall, compared with control group for subarachnoid hemorrhage, cilostazol intervention can significantly reduce symptomatic vasospasm (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.21-0.60; P = 0.0001) and cerebral infarction (OR, 0.40; 95% CI, 0.22-0.73; P = 0.003) and improve no or mild angiographic vasospasm (OR, 2.01; 95% CI, 1.19-3.42; P = 0.01) and an mRS score of 2 or less (OR, 2.70; 95% CI, 1.09-6.71; P = 0.03), but revealed no obvious influence on severe angiographic vasospasm (OR, 0.53; 95% CI, 0.27-1.02; P = 0.06). There were no increase in adverse events (OR, 1.17; 95% CI, 0.54-2.52; P = 0.69), hemorrhagic events (OR, 0.62; 95% CI, 0.06-6.27; P = 0.69), and cardiac events (OR, 2.14; 95% CI, 0.44-10.27; P = 0.34) after the cilostazol intervention than control intervention. CONCLUSIONS Cilostazol treatment may be effective to treat subarachnoid hemorrhage in the terms of symptomatic vasospasm, cerebral infarction, no or mild angiographic vasospasm, and an mRS score of 2 or less.
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Safety and efficacy of intravenous thrombolysis in acute ischemic stroke patients with a history of intracranial hemorrhage: A systematic review and meta-analysis
Gajurel BP, Nepal G, Kharel S, Yadav JK, Yadav SK, Shing YK, Goeschl S, Thapaliya S
Clinical neurology and neurosurgery. 2022;215:107205
Abstract
Acute ischemic stroke (AIS) is a fatal and debilitating condition killing 2.7 million people each year worldwide. The most commonly used treatment modality for AIS is intravenous thrombolysis (IVT) with alteplase which is indicated for those presenting within 4.5 h of onset. Due to a lack of reliable evidence on harm or benefit, the 2019 American Heart Association/American Stroke Association (AHA/ASA) guidelines consider a history of previous intracranial hemorrhage (ICH) as potentially harmful and no longer an absolute contraindication for IVT in patients with AIS, and the U.S. Food and Drug Administration (FDA) removed chronic ICH as a specific contraindication for IVT from the label in 2015. Despite a shift in guidelines, physicians frequently face the dilemmatic choice whether to administer IVT in this subset of patients due to the risk of symptomatic intracranial hemorrhage (SICH). The benefit of IVT in such patients has not been thoroughly investigated, and there are only a few studies on the subject in the literature to date. We conducted the present meta-analysis in an aim to provide solid evidence on the efficacy and safety of IVT for treating AIS in patients with a history of remote ICH. Our meta-analysis found that IVT improves functional outcomes in AIS patients with prior remote ICH without increasing SICH or all-cause mortality. These findings may contribute to the decision-making process for IVT administration in AIS patients.
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Safety of Vitamin K in mechanical heart valve patients with supratherapeutic INR: A systematic review and meta-analysis
Sapapsap B, Srisawat C, Suthumpoung P, Luengrungkiat O, Leelakanok N, Saokaew S, Kanchanasurakit S
Medicine. 2022;101(36):e30388
Abstract
BACKGROUND Patients who had mechanical heart valves and an international normalized ratio (INR) of >5.0 should be managed by temporary cessation of vitamin K antagonist. This study aimed to investigate the safety of low-dose vitamin K1 in patients with mechanical heart valves who have supratherapeutic INR. METHODS CINAHL, Cochran Library, Clinical trial.gov, OpenGrey, PubMed, ScienceDirect, and Scopus were systematically searched from the inception up to October 2021 without language restriction. Studies comparing the safety of low-dose vitamin K1 treatment in patients with placebo or other anticoagulant reversal agents were included. We used a random-effect model for the meta-analysis. Publication bias was determined by a funnel plot with subsequent Begg's test and Egger's test. RESULTS From 7529 retrieved studies, 3 randomized control trials were included in the meta-analysis. Pooled data demonstrated that low-dose vitamin K was not associated with thromboembolism rate (risk ratio [RR] = 0.94; 95% CI: 0.19-4.55) major bleeding rate (RR = 0.58; 95% CI: 0.07-4.82), and minor bleeding rate (RR = 0.60; 95% CI: 0.07-5.09). Subgroup and sensitivity analysis demonstrated the nonsignificant effect of low-dose vitamin K on the risk of thromboembolism. Publication bias was not apparent, according to Begg's test and Egger's test (P = .090 and 0.134, respectively). CONCLUSION The current evidence does not support the role of low-dose vitamin K as a trigger of thromboembolism in supratherapeutic INR patients with mechanical heart valves. Nevertheless, more well-designed studies with larger sample sizes are required to justify this research question.
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A Comparison Between Enteral and Intravenous Nimodipine in Subarachnoid Hemorrhage: A Systematic Review and Network Meta-Analysis
Geraldini F, De Cassai A, Diana P, Correale C, Boscolo A, Zampirollo S, Disarò L, Carere A, Cacco N, Navalesi P, et al
Neurocritical care. 2022
Abstract
Our objective was to compare the effectiveness of intravenous and enteral nimodipine in preventing poor outcome from delayed cerebral ischemia in patients with subarachnoid hemorrhage. We performed a systematic search and a network meta-analysis using the following databases: PubMed, Scopus, the Cochrane Central Register of Controlled Trials, and Google Scholar. Risk of Bias 2 tool was used to assess risk of bias of included studies. A ranking among methods was performed on the basis of the frequentist analog of the surface under the cumulative ranking curve. Published studies that met the following population, intervention, comparison, outcomes and study (PICOS) criteria were included: patients with subarachnoid hemorrhage aged 15 years or older (P); nimodipine, intravenous and oral formulation (I); placebo or no intervention (C); poor outcome measured at 3 months (defined as death, vegetative state, or severe disability), case fatality at 3 months, delayed cerebral ischemia, delayed ischaemic neurologic deficit, and vasospasm measured with transcranial Doppler or digital subtraction angiography (O); and randomized controlled trials (S). No language or publication date restrictions were applied. Ten studies were finally included, with a total of 1527 randomly assigned patients. Oral and intravenous nimodipine were both effective in preventing poor outcome, delayed cerebral ischemia, and delayed ischaemic neurological deficit. Neither treatment was effective in improving case fatality. Evolving clinical protocols over a 30-year period and the risk of bias of the included studies may limit the strength of our results. Enteral and intravenous nimodipine may have a similar effectiveness in terms of preventing poor outcome, delayed cerebral ischemia, and delayed ischaemic neurological deficit. More research may be needed to fully establish the role of intravenous nimodipine in current clinical practice.
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10.
Infliximab as a Second-Line Therapy for Children with Refractory Kawasaki Disease; A Systematic Review and Meta-analysis of Randomized Controlled Trials
Kabbaha S, Milano A, Aldeyab MA, Thorlund K
British journal of clinical pharmacology. 2022
Abstract
AIM: Infliximab is a tumor necrosis factor-alpha inhibitor that is being used to treat children with refractory Kawasaki disease. Our purpose was to evaluate the safety and the impact of infliximab versus intravenous immunoglobulins on the incidence of coronary artery aneurysms (CAAs) and treatment resistance in children with refractory Kawasaki disease (KD). METHODS The Medline/PubMed, Embase, CINAHL, Cochrane Central Register of Controlled Trials and clinical trials registries were searched to December 2021. Randomized controlled trials (RCTs) comparing infliximab as second-line therapy to a second dose of intravenous immunoglobulin (IVIG) in children with refractory KD, reported in abstract or full text were included. Studies were selected and assessed for risk of bias by two reviewers. Data were extracted and pooled using conventional random-effects meta-analysis. The certainty of evidence was assessed using the GRADE system. RESULTS A total of 199 participants from 4 RCTs were included. Pooled risk ratio (RR) for the incidence of treatment resistance in patients treated with infliximab was RR=0.40 (95% CI 0.25-0.64). For incidence of CAAs RR was 1.20 (95% CI 0.54-2.63), the incidence of adverse effect 'infusion reactions' RR=0.48, (95% CI 0.12-1.92), and 'infections' RR=0.55 (95% CI 0.27-1.12). Overall, the GRADE strength of evidence for the primary outcomes was low. Evidence on the duration of fever and inflammatory biomarkers was sparse, heterogeneous, and inconclusive. CONCLUSION Moderate-certainty evidence indicates that infliximab may reduce the incidence of treatment resistance in children with refractory KD. However, the limited strength of evidence warrants further research.