Systematic literature review and network Meta-analysis of sulodexide and other drugs in chronic venous disease

2021 ◽  
pp. 026835552110150
Author(s):  
Giuseppe Pompilio ◽  
Andrew Nicolaides ◽  
Stavros K Kakkos ◽  
Davide Integlia

Objective To assess the clinical efficacy of sulodexide, including a comparison with venoactive drugs (VAD) (micronized purified flavonoid fraction, MPFF; hydroxy-ethyl-rutosides, HR; calcium dobesilate;Ruscus extract combined with hesperidin methyl chalcone and vitamin C, Ruscus+HMC+VitC; horse chestnut seed extract, HCSE) and pentoxifylline in patients with chronic venous disease. Methods We performed a literature search in MEDLINE, Embase, and Cochrane Library for randomized controlled trials (RCTs) and observational studies. Proportion of patients with complete venous ulcer healing was the primary outcome and lower leg volume, foot volume, ankle circumference and symptoms were the secondary outcomes. Bayesian network meta-analysis (NMA) was perfomed with random effects models using only RCTs. A meta-analysis of observational studies was performed for sulodexide because no RCT could be included in NMA for symptoms or signs. Results Forty-five RCTs and eighteen observational studies were identified. Sulodexide was included only in a single NMA for the proportion of patients with complete ulcer healing and it showed to have the highest probability of being the best treatment (48%) compared with pentoxifylline (37%) and MPFF (16%). MPFF was the most effective treatment in reducing lower leg volume, CIVIQ-20 score and pain VAS scale while calcium dobesilate and Ruscus+HMC+VitC were the most effective in reducing foot volume and ankle circumference respectively. Meta-analyses of observational studies for sulodexide showed that it improves significantly the scoring of pain, feeling of swelling, heaviness and parasthesiae measured by Likert scales. Conclusions Sulodexide is at least as effective as pentoxifylline and more effective than MPFF in improving the rate of ulcer healing in patients with CVD. VADs are effective in improving venous symptoms and signs, as was also shown by sulodexide in the meta-analysis of observational studies. The relative effectiveness of sulodexide and VADs needs to be evaluated by an RCT in order to better inform clinical practice.

2020 ◽  
pp. 1-10
Author(s):  
Hongwei Wu ◽  
Qiang Li ◽  
Lijing Fan ◽  
Dewang Zeng ◽  
Xianggeng Chi ◽  
...  

<b><i>Background:</i></b> Previous studies have reported that serum magnesium (Mg) deficiency is involved in the development of heart failure, particularly in patients with end-stage kidney disease. The association between serum Mg levels and mortality risk in patients receiving hemodialysis is controversial. We aimed to estimate the prognostic value of serum Mg concentration on all-cause mortality and cardiovascular mortality in patients receiving hemodialysis. <b><i>Methods:</i></b> We did a systematic literature search in PubMed, EMBASE, Cochrane Library, and Web of Science to identify eligible studies that reported the prognostic value of serum Mg levels in mortality risk among patients on hemodialysis. We performed a meta-analysis by pooling and analyzing hazard ratios (HRs) and 95% confidence intervals (CIs). <b><i>Results:</i></b> We identified 13 observational studies with an overall sample of 42,967 hemodialysis patients. Higher all-cause mortality (adjusted HR 1.58 [95% CI: 1.31–1.91]) and higher cardiovascular mortality (adjusted HR 3.08 [95% CI: 1.27–7.50]) were found in patients with lower serum Mg levels after multivariable adjustment. There was marked heterogeneity (<i>I</i><sup>2</sup> = 79.6%, <i>p</i> &#x3c; 0.001) that was partly explained by differences in age stratification and study area. In addition, subgroup analysis showed that a serum Mg concentration of ≤1.1 mmol/L might be the vigilant cutoff value. <b><i>Conclusion:</i></b> A lower serum Mg level was associated with higher all-cause mortality and cardiovascular mortality in patients receiving hemodialysis.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yanyan Long ◽  
Yan Liang ◽  
Shujie Li ◽  
Jing Guo ◽  
Ying Wang ◽  
...  

Abstract Background and purpose Stereotactic body radiotherapy (SBRT) is a promising ablative modality for hepatocellular carcinoma (HCC) especially for those with small-sized or early-stage tumors. This study aimed to synthesize available data to evaluate efficacy and explore related predictors of SBRT for small liver-confined HCC (≤ 3 lesions with longest diameter ≤ 6 cm). Materials and methods A systematic search were performed of the PubMed and Cochrane Library databases. Primary endpoints were overall survival (OS) and local control (LC) of small HCC treated with SBRT, meanwhile, to evaluate clinical parameters associated with treatment outcome by two methods including subgroup comparisons and pooled HR meta-analysis. The secondary endpoint was treatment toxicity. Results After a comprehensive database review, 14 observational studies with 1238 HCC patients received SBRT were included. Pooled 1-year and 3-year OS rates were 93.0% (95% confidence interval [CI] 88.0–96.0%) and 72.0% (95% CI 62.0–79.0%), respectively. Pooled 1-year and 3-year LC rates were 96.0% (95% CI 91.0–98.0%) and 91.0% (95% CI 85.0–95.0%), respectively. Subgroup comparisons regarding Child–Pugh class (stratified by CP-A percentage 100%, 75–100%, 50–75%) showed there were statistically significant differences for both 1-year and 3-year OS rate (p < 0.01), while that regarding number of lesions, pretreatment situation, age (median/mean age of 65), macrovascular invasion, tumor size, and radiation dose (median BED10 of 100 Gy), there were no differences. In subgroup comparisons for LC rate, it showed number of lesions (1 lesion vs. 2–3 lesions) was significantly associated with 1-year LC rate (p = 0.04), though not associated with 3-year LC rate (p = 0.72). In subgroup comparisons categorized by other factors including pretreatment situation, age, CP-A percentage, macrovascular invasion, tumor size, and radiation dose, there were no significant differences for 1- or 3-year LC rate. To further explore the association between CP class and OS, the second method was applied by combining HR and 95% CIs. Results indicated CP-A was predictive of better OS (p = 0.001) with pooled HR 0.31 (95% CIs 0.11–0.88), which was consistent with subgroup comparison results. Concerning adverse effect of SBRT, pooled rates of grade ≥ 3 hepatic complications and RILD were 4.0% (95% CI 2.0–8.0%) and 14.7% (95% CI 7.4–24.7%), respectively. Conclusion The study showed that SBRT was a potent local treatment for small liver-confined HCC conferring excellent OS and LC persisting up to 3 years, even though parts of included patients were pretreated or with macrovascular invasion. CP-A class was a significant predictor of optimal OS, while number of lesions might affect short term tumor control (1-year LC). Tumor size and radiation dose were not vital factors impacting treatment outcome for such small-sized HCC patients. Because of the low quality of observational studies and heterogeneous groups of patients treated with SBRT, further clinical trials should be prospectively investigated in large sample sizes.


Author(s):  
Yu-Lin Hsieh ◽  
Meng-Che Wu ◽  
Jon Wolfshohl ◽  
James d’Etienne ◽  
Chien-Hua Huang ◽  
...  

Abstract Introduction This study is aimed to investigate the association of intraosseous (IO) versus intravenous (IV) route during cardiopulmonary resuscitation (CPR) with outcomes after out-of-hospital cardiac arrest (OHCA). Methods We systematically searched PubMed, Embase, Cochrane Library and Web of Science from the database inception through April 2020. Our search strings included designed keywords for two concepts, i.e. vascular access and cardiac arrest. There were no limitations implemented in the search strategy. We selected studies comparing IO versus IV access in neurological or survival outcomes after OHCA. Favourable neurological outcome at hospital discharge was pre-specified as the primary outcome. We pooled the effect estimates in random-effects models and quantified the heterogeneity by the I2 statistics. Time to intervention, defined as time interval from call for emergency medical services to establishing vascular access or administering medications, was hypothesized to be a potential outcome moderator and examined in subgroup analysis with meta-regression. Results Nine retrospective observational studies involving 111,746 adult OHCA patients were included. Most studies were rated as high quality according to Newcastle-Ottawa Scale. The pooled results demonstrated no significant association between types of vascular access and the primary outcome (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.27–1.33; I2, 95%). In subgroup analysis, time to intervention was noted to be positively associated with the pooled OR of achieving the primary outcome (OR: 3.95, 95% CI, 1.42–11.02, p: 0.02). That is, when the studies not accounting for the variable of “time to intervention” in the statistical analysis were pooled together, the meta-analytic results between IO access and favourable outcomes would be biased toward inverse association. No obvious publication bias was detected by the funnel plot. Conclusions The meta-analysis revealed no significant association between types of vascular access and neurological outcomes at hospital discharge among OHCA patients. Time to intervention was identified to be an important outcome moderator in this meta-analysis of observation studies. These results call for the need for future clinical trials to investigate the unbiased effect of IO use on OHCA CPR.


Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Uday M Jadhav ◽  
Tiny Nair ◽  
SANDEEP BANSAL ◽  
Saumitra Ray

Introduction: Selective beta-1 blockers (s-BBs) are used in the management of hypertension (HT) in specific subsets. Studies comparing the potency of blood pressure (BP) lowering with different s-BBs are sparse. The objective of this meta-analysis was to evaluate the efficacy of bisoprolol compared to other s-BBs (Atenolol, Betaxolol, Esmolol, Acebutolol, Metoprolol, Nebivolol) in HT patients by examining their effect on BP, heart rate (HR) and metabolic derangements, by examining the evidences reported in observational studies. Methods: Electronic databases like PubMed, EMBASE, Cochrane Library, Clinicaltrials.gov, Surveillance, Epidemiology and End Results Program and 12 PV databases were systematically searched from inception to October 2019. Observational studies that compared bisoprolol with other s-BBs in patients with HT were evaluated in accordance with the PRISMA guidelines. Pooled data were calculated using random-effects model for meta-analysis in terms of mean difference (MD) and 95% confidence interval (95% CI) for each outcome. Outcomes of interest were BP, HR and lipid profile. Results: Four observational studies which compared bisoprolol with other s-BBs (nebivolol and atenolol) were included in this meta-analysis. Significant reduction was observed in office diastolic BP [MD: -1.70; 95% CI: -2.68,-0.72; P <0.01] among arterial HT patients treated with bisoprolol for 26 weeks (w) compared to those treated with other s-BBs. HT patients treated with bisoprolol for 26 w showed significant reduction in HR [MD: -2.20; 95% CI: -3.57,-0.65; P <0.01] and office HR [MD: -2.55; 95% CI: -3.57,-1.53; P <0.01] than other s-BBs. HDL cholesterol levels increased significantly in essential HT patients treated with bisoprolol at 26 w [MD: 7.17; 95% CI: 1.90,12.45; P <0.01], 78 w [MD: 11.70; 95% CI: 4.49,18.91; P <0.01] and 104 w [MD: 10.20, 95% CI: 4.49,18.91; P <0.01] compared to other s-BBs. Conclusion: Our results suggests that bisoprolol is superior to other s-BBs in reducing BP and HR. Bisoprolol also had a favourable effect on lipid profile shown by increase in HDL cholesterol. This meta-analysis emphasizes the efficacy of bisoprolol over other s-BBs, which aids clinical decision making in treatment of patients with HT.


2021 ◽  
Author(s):  
Oyungerel Byambasuren ◽  
Elaine Beller ◽  
Justin Clark ◽  
Peter Collignon ◽  
Paul Glasziou

Background: The effect of eye protection to prevent SARS-CoV-2 infection in the real-world remains uncertain. We aimed to synthesize all available research on the potential impact of eye protection on transmission of SARS-CoV-2. Methods: We searched PROSPERO, PubMed, Embase, The Cochrane Library for clinical trials and comparative observational studies in CENTRAL, and Europe PMC for pre-prints. We included studies that reported sufficient data to estimate the effect of any form of eye protection including face shields and variants, goggles, and glasses, on subsequent confirmed infection with SARS-CoV-2. Findings: We screened 898 articles and included 6 reports of 5 observational studies from 4 countries (USA, India, Columbia, and United Kingdom) that tested face shields, googles and wraparound eyewear on 7567 healthcare workers. The three before-and-after and one retrospective cohort studies showed statistically significant and substantial reductions in SARS-CoV-2 infections favouring eye protection with odds ratios ranging from 0.04 to 0.6, corresponding to relative risk reductions of 96% to 40%. These reductions were not explained by changes in the community rates. However, the one case-control study reported odds ratio favouring no eye protection (OR 1.7, 95% CI 0.99, 3.0). The high heterogeneity between studies precluded any meaningful meta-analysis. None of the studies adjusted for potential confounders such as other protective behaviours, thus increasing the risk of bias, and decreasing the certainty of evidence to very low. Interpretation: Current studies suggest that eye protection may play a role in prevention of SARS-CoV-2 infection in healthcare workers. However, robust comparative trials are needed to clearly determine effectiveness of eye protections and wearability issues in both healthcare and general populations.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10683
Author(s):  
Jun Chen ◽  
Lingchun Lyu ◽  
Jiayi Shen ◽  
Chunlai Zeng ◽  
Cheng Chen ◽  
...  

Objective Our study aimed to assess the risk of all fractures and hip fractures in patients with atrial fibrillation (AF) who took non-vitamin K antagonist oral anticoagulants (NOACs) compared to warfarin. Methods We searched PubMed, Embase, and Cochrane Library and Clinical Trials.gov Website. Reviewed related researches up to January 31, 2020, to identify studies with more than 12 months of follow-up data. The protocol for this systematic review and meta-analysis has been registered in the International Prospective Register of Systematic Reviews (PROSPERO Number: CRD42020156893). Results We included five RCT studies, and five observational studies that contained a total of 326,846 patients in our meta-analysis. Our meta-analysis showed that patients taken NOACs had no significant all fracture risk (RR = 0.91, 95% CI [0.81–1.01]) and hip fracture risk (RR = 0.92, 95% CI [0.82–1.03]) compared with those taken warfarin. Subanalysis showed that the risk of all fractures and hip fractures treated by NOACs were significant lower compared with warfarin in observational studies compared with RCT studies. Also, a subanalysis across the duration of anticoagulation showed the NOACs users have lower all fracture risk than warfarin users when the duration of anticoagulation ≤2 years (RR = 0.89, 95% CI [0.80–0.99]). Further analysis, significant lower all fracture risk in the rivaroxaban therapy (RR = 0.81; 95% CI [0.76–0.86]) compared with warfarin but no statistical significance in hip fracture. There were no significant difference of all fracture risk and hip fracture risk in dabigatran, apixaban, and edoxaban therapy compared with warfarin. Conclusion The meta-analysis demonstrated that NOACs associated with a significantly lower all fracture risk compared with warfarin when the duration of anticoagulation more than 2 years. Rivaroxaban users had lower risk of all fracture than warfarin users in AF patients. But there was no evidence to verify apixaban, edoxaban, and dabigatranin could decrease all fracture and hip fracture risk compared with warfarin.


2021 ◽  
Vol 8 ◽  
Author(s):  
Xiao-Ce Dai ◽  
Zhuo-Yu An ◽  
Zi-Yang Wang ◽  
Zi-Zhen Wang ◽  
Yi-Ren Wang

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share a target receptor with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The use of ACEIs/ARBs may cause angiotensin-converting enzyme 2 receptor upregulation, facilitating the entry of SARS-CoV-2 into host cells. There is concern that the use of ACEIs/ARBs could increase the risks of severe COVID-19 and mortality. The impact of discontinuing these drugs in patients with COVID-19 remains uncertain. We aimed to assess the association between the use of ACEIs/ARBs and the risks of mortality and severe disease in patients with COVID-19. A systematic search was performed in PubMed, EMBASE, Cochrane Library, and MedRxiv.org from December 1, 2019, to June 20, 2020. We also identified additional citations by manually searching the reference lists of eligible articles. Forty-two observational studies including 63,893 participants were included. We found that the use of ACEIs/ARBs was not significantly associated with a reduction in the relative risk of all-cause mortality [odds ratio (OR) = 0.87, 95% confidence interval (95% CI) = 0.75–1.00; I2 = 57%, p = 0.05]. We found no significant reduction in the risk of severe disease in the ACEI subgroup (OR = 0.95, 95% CI = 0.88–1.02, I2 = 50%, p = 0.18), the ARB subgroup (OR = 1.03, 95% CI = 0.94–1.13, I2 = 62%, p = 0.48), or the ACEI/ARB subgroup (OR = 0.83, 95% CI = 0.65–1.08, I2 = 67%, p = 0.16). Moreover, seven studies showed no significant difference in the duration of hospitalization between the two groups (mean difference = 0.33, 95% CI = −1.75 to 2.40, p = 0.76). In conclusion, the use of ACEIs/ARBs appears to not have a significant effect on mortality, disease severity, or duration of hospitalization in COVID-19 patients. On the basis of the findings of this meta-analysis, there is no support for the cessation of treatment with ACEIs or ARBs in patients with COVID-19.


2017 ◽  
Vol 26 (12) ◽  
pp. 1931-1939 ◽  
Author(s):  
Ye Zhang ◽  
Hong Deng ◽  
Zhouping Tang

Diabetes mellitus is a widely spread chronic disease with growing incidence worldwide, and diabetic foot ulcer is one of the most serious complications of diabetes. Cellular therapy has shown promise in the management of diabetic foot ulcer in many preclinical experiments and clinical researches. Here, we performed a meta-analysis to evaluate the efficacy and safety of cellular therapy in the management of diabetic foot ulcer. We systematically searched PubMed, MEDLINE, EMBASE, and Cochrane Library databases from inception to May 2017 for randomized controlled trials assessing the efficacy of cellular therapy in diabetic foot ulcer, and a meta-analysis was conducted. A total of 6 randomized controlled clinical trials involving 241 individuals were included in this meta-analysis. The results suggested that cellular therapy could help accelerating the healing of diabetic foot ulcer, presented as higher ankle-brachial index (mean difference = 0.17, 95% confidence interval [CI] = 0.11 to 0.23), higher transcutaneous oxygen pressure (standardized mean difference [SMD] = 1.43; 95% CI, 1.09– to 1.78), higher ulcer healing rate (relative risk [RR] = 1.78; 95% CI, 1.41 to 2.25), higher amputation-free survival (RR = 1.25; 95% CI, 1.11 to 1.40), and lower scale of pain (SMD = −1.69; 95% CI, −2.05 to −1.33). Furthermore, cellular therapy seemed to be safe, with no serious complications and low risk of short-term slight complications. Cellular therapy could accelerate the rate of diabetic foot ulcer healing and may be more efficient than standard therapy for diabetic foot treatment.


2018 ◽  
Vol 100-B (2) ◽  
pp. 134-142 ◽  
Author(s):  
A. T. Hexter ◽  
S. M. Hislop ◽  
G. W. Blunn ◽  
A. D. Liddle

Aims Periprosthetic joint infection (PJI) is a serious complication of total hip arthroplasty (THA). Different bearing surface materials have different surface properties and it has been suggested that the choice of bearing surface may influence the risk of PJI after THA. The objective of this meta-analysis was to compare the rate of PJI between metal-on-polyethylene (MoP), ceramic-on-polyethylene (CoP), and ceramic-on-ceramic (CoC) bearings. Patients and Methods Electronic databases (Medline, Embase, Cochrane library, Web of Science, and Cumulative Index of Nursing and Allied Health Literature) were searched for comparative randomized and observational studies that reported the incidence of PJI for different bearing surfaces. Two investigators independently reviewed studies for eligibility, evaluated risk of bias, and performed data extraction. Meta-analysis was performed using the Mantel–Haenzel method and random-effects model in accordance with methods of the Cochrane group. Results Our search strategy revealed 2272 studies, of which 17 met the inclusion criteria and were analyzed. These comprised 11 randomized controlled trials and six observational studies. The overall quality of included studies was high but the observational studies were at high risk of bias due to inadequate adjustment for confounding factors. The overall cumulative incidence of PJI across all studies was 0.78% (1514/193 378). For each bearing combination, the overall incidence was as follows: MoP 0.85% (1353/158 430); CoP 0.38% (67/17 489); and CoC 0.53% (94/17 459). The meta-analysis showed no significant difference between the three bearing combinations in terms of risk of PJI. Conclusion On the basis of the clinical studies available, there is no evidence that bearing choice influences the risk of PJI. Future research, including basic science studies and large, adequately controlled registry studies, may be helpful in determining whether implant materials play a role in determining the risk of PJI following arthroplasty surgery. Cite this article: Bone Joint J 2018;100-B:134–42.


2019 ◽  
Vol 35 (2) ◽  
pp. 73-83 ◽  
Author(s):  
A Kürşat Bozkurt ◽  
Martin Lawaetz ◽  
Gudmundur Danielsson ◽  
Andreas M Lazaris ◽  
Milos Pavlovic ◽  
...  

Background The purpose of the guideline was to achieve consensus in the care and treatment of patients with chronic venous disease, based on current evidence. Method A systematic literature search was performed in PubMed, Embase, Cinahl, and the Cochrane library up until 1 February 2019. Additional relevant literature were added through checking of references. Level of evidence was graded through the GRADE scale and recommendations were concluded. Results For the treatment of great and small saphenous vein reflux, endovenous ablation with laser or radiofrequency was recommended in preference to surgery or foam sclerotherapy. If tributaries are to be treated it should be done in the same procedure. Treatment with mecanicochemical ablation and glue can be used but we still need long term follow up results. Conclusion For the treatment of truncal varicosities, endovenous ablation with laser or radiofrequency combined with phlebectomies is recommended before surgery or foam.


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