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The Cochrane Database of Systematic... Oct 2014Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication, characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age-matched controls, people with intermittent claudication have a three- to six-fold increase in cardiovascular mortality. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise programme. Antiplatelet treatment is beneficial in patients with intermittent claudication for the reduction of vascular events but has not previously been shown to influence claudication distance. This is an update of a review first published in 2007.
OBJECTIVES
To determine the effect of cilostazol (an antiplatelet treatment) on improving initial and absolute claudication distances, and in reducing mortality and vascular events in patients with stable intermittent claudication.
SEARCH METHODS
For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9).
SELECTION CRITERIA
Double-blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We performed the meta-analysis as a fixed-effect model with weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous data, and odds ratios (ORs) with 95% CIs for dichotomous data.
MAIN RESULTS
We included fifteen double-blind, RCTs comparing cilostazol with placebo, or medications currently known to increase walking distance e.g. pentoxifylline. There were a total of 3718 randomised participants with treatment durations ranging from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Comparisons included cilostazol twice daily, with dosages of 50 mg, 100 mg and 150 mg compared with placebo, and cilostazol 100 mg, twice daily, compared with pentoxifylline 400 mg, three times daily. The methodological quality of the trials was generally low, with the majority being at an unclear risk for selection bias, performance bias, detection bias and other bias. Attrition bias was generally low, but reporting bias was high or unclear in the majority of the studies. For eight studies data were compatible for comparison by meta-analysis, but data for seven studies were too heterogenous to be pooled. For the studies included in the meta-analysis, for initial claudication distance (ICD - the distance walked on a treadmill before the onset of calf pain) there was an improvement in the cilostazol group for the 100 mg and 50 mg twice daily, compared with placebo (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; P < 0.00001) and WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; P = 0.0002), respectively. ICD was improved in the cilostazol group for the comparison of cilostazol 150 mg versus placebo and cilostazol 100 mg versus pentoxifylline, but only single studies were used for these analyses. Absolute claudication distance (ACD - the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg and 50 mg twice daily, compared with placebo (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; P = 0.0007) and WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; P = 0.0004), respectively. As with ICD, ACD was increased in participants taking cilostazol 150 mg versus placebo, but with only one study an association cannot be clearly determined. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise CI (WMD 13.42 metres (95% CI -43.51 to 70.35 metres; P = 0.64). Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; P < 0.00001). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI.There was no association between treatment type and all-cause mortality for any of the treatment comparisons, but there were very few events, and therefore larger, adequately powered studies will be needed to assess if there is a relationship. Only one study evaluated individual cardiovascular events, and from this study there is no clear evidence of a difference between any of the treatment groups and risk of myocardial infarction or stroke. We evaluated adverse side effects, and in general cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations. We only reported quality of life measures descriptively as there was insufficient statistical detail within the studies to combine the results, although there was a possible indication in improvement of quality of life in the cilostazol treatment groups.
AUTHORS' CONCLUSIONS
Cilostazol has been shown to be of benefit in improving walking distance in people with intermittent claudication secondary to PAD. Although there is an increase in adverse side effects, they are generally mild and treatable. There is currently insufficient data on whether taking cilostazol results in a reduction of all-cause mortality and cardiovascular events or an improvement in quality of life. Future research into the effect of cilostazol on intermittent claudication should carefully consider comparability, sample size and homogeneity when designing a study.
Topics: Aged; Cilostazol; Humans; Intermittent Claudication; Middle Aged; Myocardial Infarction; Pentoxifylline; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Tetrazoles; Walking
PubMed: 25358850
DOI: 10.1002/14651858.CD003748.pub4 -
Advances in Medical Sciences Sep 2023Periodontitis is an infectious disease characterized by the inflammatory destruction of the tooth supporting tissues. In multi-rooted teeth, this process leads to... (Review)
Review
Periodontitis is an infectious disease characterized by the inflammatory destruction of the tooth supporting tissues. In multi-rooted teeth, this process leads to periodontal destruction within furcations creating defects demanding in terms of treatment. Regeneration of class II furcation involvement, although possible, is considered an unpredictable procedure, especially in terms of the bone fill. The interest in wound healing improvement by additional use of autologous concentrates of growth factors remains high in many fields of dentistry. Platelet-rich fibrin (PRF) is a second-generation platelet concentrate and biomaterial. PRF forms a solid fibrin matrix, which is slowly remodeled comparable to the natural blood clot. Its utilization is associated with release of growth factors and glycoproteins over a long period of time. PRF activates alkaline phosphates, which show osteoblastic activity and this activation influences the bone formation. The aim of this review of randomized controlled trials (RCTs) was to evaluate the adjunctive use of platelet-rich fibrin in surgical treatment of furcation defects.
Topics: Humans; Platelet-Rich Fibrin; Furcation Defects; Wound Healing
PubMed: 37757664
DOI: 10.1016/j.advms.2023.09.009 -
BMC Pregnancy and Childbirth Aug 2021Currently, we suffer from an increasing diabetes pandemic and on the other hand from the SARS-CoV-2 pandemic. Already at the beginning of the SARS-CoV-2 pandemic, it was...
BACKGROUND
Currently, we suffer from an increasing diabetes pandemic and on the other hand from the SARS-CoV-2 pandemic. Already at the beginning of the SARS-CoV-2 pandemic, it was quickly assumed that certain groups are at increased risk to suffer from a severe course of COVID-19. There are serious concerns regarding potential adverse effects on maternal, fetal, and neonatal outcomes. Diabetic pregnancies clearly need special care, but clinical implications as well as the complex interplay of diabetes and SARS-CoV-2 are currently unknown. We summarized the evidence on SARS-CoV-2 in diabetic pregnancies, including the identification of novel potential pathophysiological mechanisms and interactions as well as clinical outcomes and features, screening, and management approaches.
METHODS
We carried out a systematic scoping review in MEDLINE (PubMed), EMBASE, CINAHL, Cochrane Library, and Web of Science Core Collection in September 2020.
RESULTS
We found that the prognosis of pregnant women with diabetes mellitus and COVID-19 may be associated with potential underlying mechanisms such as a simplified viral uptake by ACE2, a higher basal value of pro-inflammatory cytokines, being hypoxemic as well as platelet activation, embolism, and preeclampsia. In the context of "trans-generational programming" and COVID-19, life-long consequences may be "programmed" during gestation by pro-inflammation, hypoxia, over- or under-expression of transporters and enzymes, and epigenetic modifications based on changes in the intra-uterine milieu. COVID-19 may cause new onset diabetes mellitus, and that vertical transmission from mother to baby might be possible.
CONCLUSIONS
Given the challenges in clinical management, the complex interplay between COVID-19 and diabetic pregnancies, evidence-based recommendations are urgently needed. Digital medicine is a future-oriented and effective approach in the context of clinical diabetes management. We anticipate our review to be a starting point to understand and analyze mechanisms and epidemiology to most effectively treat women with SARS-COV-2 and diabetes in pregnancy.
Topics: COVID-19; Female; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Maternal Health; Pregnancy; Pregnancy Complications, Infectious; Pregnancy in Diabetics; Prenatal Care; Primary Prevention
PubMed: 34416856
DOI: 10.1186/s12884-021-03975-3 -
European Journal of Vascular and... Jan 2022Adenosine diphosphate (ADP) receptor inhibitors such as clopidogrel are known to be less effective at reducing platelet function for some patients because of a... (Meta-Analysis)
Meta-Analysis
A Systematic Review and Meta-Analysis on the Impact of High On-Treatment Platelet Reactivity on Clinical Outcomes for Patients Taking ADP Receptor Inhibitors Following Lower Limb Arterial Endovascular Intervention.
OBJECTIVE
Adenosine diphosphate (ADP) receptor inhibitors such as clopidogrel are known to be less effective at reducing platelet function for some patients because of a phenomenon called high on-treatment platelet reactivity (HTPR). However, the clinical effect of this for patients undergoing endovascular intervention for peripheral arterial disease is unclear. The aim of this study was to assess the impact of ADP receptor inhibitor HTPR on clinical outcomes following lower limb arterial endovascular intervention for peripheral arterial disease.
METHODS
A systematic review and meta-analysis was performed. Primary outcomes included all cause mortality and major bleeding. Secondary outcomes were major adverse cardiovascular events, major adverse limb events, restenosis, and target lesion revascularisation. Outcome quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool.
RESULTS
There were 10 eligible studies including 1 444 patients included in the meta-analysis. The most commonly tested ADP receptor inhibitor was clopidogrel (seven studies). The pooled rate of ADP receptor inhibitor HTPR was 29% (95% CI 27 - 32). The meta-analysis showed that ADP receptor inhibitor HTPR was associated with a greater risk of major adverse limb events (OR 6.25, 95% CI 2.09 - 18.68, p = .001) and a trend towards a higher all cause mortality (OR 1.71, 95% CI 0.99 - 2.94, p = .050) and more major adverse cardiovascular events (OR 4.23, 95% CI 0.46 - 38.92, p = .20) after endovascular intervention. Overall strength of evidence was very low for all outcomes.
CONCLUSION
ADP receptor inhibitor HTPR was associated with worse clinical outcomes after lower limb endovascular intervention for peripheral arterial disease. Prospective studies are required to determine the impact of modifying the antithrombotic regimen on clinical outcomes.
Topics: Cause of Death; Clopidogrel; Endovascular Procedures; Humans; Lower Extremity; Peripheral Arterial Disease; Platelet Activation; Platelet Function Tests; Postoperative Complications; Postoperative Hemorrhage; Purinergic P2 Receptor Antagonists; Treatment Outcome
PubMed: 34844834
DOI: 10.1016/j.ejvs.2021.09.026 -
Basic and Clinical Neuroscience 2021The change of stroke incidence during the COVID-19 pandemic period and the proposed mechanisms of the relationship between SARS-CoV-2 and stroke is reviewed. (Review)
Review
INTRODUCTION
The change of stroke incidence during the COVID-19 pandemic period and the proposed mechanisms of the relationship between SARS-CoV-2 and stroke is reviewed.
METHODS
Web of Science, PMC/Medline, and Scopus databases were searched until July 2020 without time and language limitations. After quality assessment, 22 articles were included in this study.
RESULTS
Based on the results, it is impossible to conclude any definite relationship between the rising or decreasing stroke frequency or the shift in the ischemic and hemorrhagic ratio and SARS-CoV-2 infection. However, it appears that SARS-CoV-2 infection has some correlation with stroke. The supposed mechanisms for the SARS-CoV-2-related hemorrhagic stroke include 1) SARS-CoV-2-related vasculopathy with the endothelial damage of small vessels, 2) viral infection-induced platelet dysfunction or thrombocytopenia, and 3) activation of the proinflammatory cascade leading to coagulopathy. The helpful strategies are receiving therapeutic anticoagulation for high D-dimer or a known thrombus due to SARS-CoV-2 infection, as well as using extracorporeal membrane oxygenation (ECMO) in some patients. Furthermore, the possible mechanisms for the SARS-CoV-2-related ischemic stroke include 1) dysregulation of angiotensin-converting enzyme 2 (a key host cellular receptor for SARSCoV-2)-related physiologic functions, 2) endothelial cell damages, 3) thrombo-inflammation, and 4) coagulopathy and coagulation abnormalities related to SARS-CoV-2 infection.
CONCLUSION
A better understanding of the SARS-CoV-2 pathogenesis and its relation to neurologic abnormalities such as stroke can help to design new therapeutic approaches.
PubMed: 35173912
DOI: 10.32598/bcn.2021.3277.1 -
Polymers Aug 2022Fibrin, derived from proteins involved in blood clotting (fibrinogen and thrombin), is a biopolymer with different applications in the health area since it has... (Review)
Review
Fibrin, derived from proteins involved in blood clotting (fibrinogen and thrombin), is a biopolymer with different applications in the health area since it has hemostasis, biocompatible and three-dimensional physical structure properties, and can be used as scaffolds in tissue regeneration or drug delivery system for cells and/or growth factors. Fibrin alone or together with other biomaterials, has been indicated for use as a biological support to promote the regeneration of stem cells, bone, peripheral nerves, and other injured tissues. In its diversity of forms of application and constitution, there are platelet-rich fibrin (PRF), Leukocyte- and platelet-rich fibrin (L-PRF), fibrin glue or fibrin sealant, and hydrogels. In order to increase fibrin properties, adjuvant therapies can be combined to favor tissue repair, such as photobiomodulation (PBM), by low-level laser therapy (LLLT) or LEDs (Light Emitting Diode). Therefore, this systematic review aimed to evaluate the relationship between PBM and the use of fibrin compounds, referring to the results of previous studies published in PubMed/MEDLINE, Scopus and Web of Science databases. The descriptors "fibrin AND low-level laser therapy" and "fibrin AND photobiomodulation" were used, without restriction on publication time. The bibliographic search found 44 articles in PubMed/MEDLINE, of which 26 were excluded due to duplicity or being outside the eligibility criteria. We also found 40 articles in Web of Science and selected 1 article, 152 articles in Scopus and no article selected, totaling 19 articles for qualitative analysis. The fibrin type most used in combination with PBM was fibrin sealant, mainly heterologous, followed by PRF or L-PRF. In PBM, the gallium-aluminum-arsenide (GaAlAs) laser prevailed, with a wavelength of 830 nm, followed by 810 nm. Among the preclinical studies, the most researched association of fibrin and PBM was the use of fibrin sealants in bone or nerve injuries; in clinical studies, the association of PBM with medication-related treatments osteonecrosis of the jaw (MRONJ). Therefore, there is scientific evidence of the contribution of PBM on fibrin composites, constituting a supporting therapy that acts by stimulating cell activity, angiogenesis, osteoblast activation, axonal growth, anti-inflammatory and anti-edema action, increased collagen synthesis and its maturation, as well as biomolecules.
PubMed: 35956667
DOI: 10.3390/polym14153150 -
Turkish Journal of Anaesthesiology and... Oct 2022Thromboelastography and rotational thromboelastometry are the viscoelastic point of care devices that use whole blood samples to assess coagulation and fibrinolysis....
Role of Thromboelastography and Thromboelastometry in Predicting Risk of Hypercoagulability and Thrombosis in Critically Ill COVID-19 Patients: A Qualitative Systematic Review.
Thromboelastography and rotational thromboelastometry are the viscoelastic point of care devices that use whole blood samples to assess coagulation and fibrinolysis. These devices give information from initiation of the coagulation cascade, activation of clotting factors to fibrin cross-linking, and contribution of fibrinogen and platelet to clot strength and clot lysis. Viscoelastic point of care tests are well established in hypocoaguable states like trauma, cardiac surgery, liver transplantation, and their use in critical care settings with coronavirus disease 2019 (COVID-19) is not so well-known. We performed a systematic review of studies on thromboelastography and rotational thromboelastometry and their modifications to assess their role in critically ill patients with COVID-19. Inclusion criteria were any kind of studies using thromboelastography or rotational thromboelastometry during coronavirus disease critical illness published in English. Ninety-three articles, from December 1, 2019, to August 31, 2020, were identified in the initial search, out of which 12 articles (a total of 380 patients) satisfied the inclusion and exclusion criteria. Thromboelastography and rotational thromboelastometry were observed to detect the hypercoagulable changes and fibrinolysis shutdown associated with COVID-19. Hypercoagulability is associated with an increased risk of venous thrombosis and micro-thrombosis. This review identifies the role of thromboelastography and rotational thromboelastometry in studying the mechanisms contributing to coagulopathy and incidence of thrombosis in COVID-19.
PubMed: 36301281
DOI: 10.5152/TJAR.2021.21118 -
Hepatology International Jan 2019While the association between platelet activation and hepatic fibrosis has been previously demonstrated in animal studies; the utility of anti-platelet agents in... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
While the association between platelet activation and hepatic fibrosis has been previously demonstrated in animal studies; the utility of anti-platelet agents in reversing the progression of hepatic fibrosis requires further review. Utilizing systematic review methods, we provide to our knowledge the first meta-analysis combining evidence from all studies aimed to establish the effect of anti-platelet agents in the prevention of hepatic fibrosis.
METHODS
We searched Medline, EMBASE and PubMed databases from inception to October 2018 to identify all studies aimed at evaluating the role of anti-platelet agents in the prevention of hepatic fibrosis. The primary outcome was hepatic fibrosis. The initial title, abstract, and full-text screening were performed in duplicate. Risk of bias was evaluated using the Newcastle-Ottawa Scale. A fixed-effect generic inverse variance method was used to create a pooled estimate of the odds of hepatic fibrosis in patients with anti-platelet agents versus without anti-platelet agents.
RESULTS
Among the 2310 unique articles identified during the title screening, 4 studies with a combined population of 3141 patients were deemed eligible for inclusion into the meta-analysis establishing the effect of anti-platelet agents on hepatic fibrosis. One study failed to report their findings in the entire cohort, electing to instead summarize the effects of anti-platelets within subgroups categorized by fibrotic risk factors. Use of anti-platelets was associated with 32% decreased odds of hepatic fibrosis, (adjusted pooled OR 0.68; CI 0.56-0.82, p ≤ 0.0001). The statistical heterogeneity among the studies was insignificant.
CONCLUSION
Use of anti-platelet agents is associated with the decreased odds of hepatic fibrosis. Due to limited evidence, future high-quality randomized controlled trials with larger comparative samples are required to further delineate the potential beneficial effects of these drugs in preventing hepatic fibrosis.
Topics: Adult; Aged; Chronic Disease; End Stage Liver Disease; Female; Humans; Liver Cirrhosis; Male; Middle Aged; Platelet Aggregation Inhibitors; Risk Factors; Treatment Outcome
PubMed: 30539518
DOI: 10.1007/s12072-018-9918-2 -
Platelet Function During Extracorporeal Membrane Oxygenation in Adult Patients: A Systematic Review.Frontiers in Cardiovascular Medicine 2018Hemorrhagic and thromboembolic complications are common during treatment with extracorporeal membrane oxygenation (ECMO), resulting in considerable morbidity and...
Hemorrhagic and thromboembolic complications are common during treatment with extracorporeal membrane oxygenation (ECMO), resulting in considerable morbidity and mortality. This emphasizes the clinical relevance of understanding hemostatic changes occurring during ECMO treatment. As platelets are key players in hemostasis, detailed knowledge on how ECMO treatment affects platelet function is of great importance. We therefore aimed to systematically summarize and discuss existing knowledge on platelet function during ECMO treatment in adult patients. Systematic review complying with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Objectives and methods were specified in a PROSPERO protocol (ID no CRD42018084059). The MEDLINE/PubMed, EMBASE, and Web of Science databases were systematically searched on September 10, 2018. A standardized quality assessment tool was used to assess the risk of bias in included studies. Primary outcome was platelet function during ECMO treatment, measured as platelet adhesion, activation or aggregation. Secondary outcomes were thrombosis, bleeding, and mortality during ECMO treatment. A total of 591 studies were identified, of which seven were eligible for inclusion in the qualitative synthesis. Of these, one study investigated expression of platelet adhesion receptors and found them to be reduced during ECMO treatment; two studies reported a decrease in platelet activation markers during ECMO treatment; and five studies demonstrated reduced platelet aggregation during ECMO treatment. Three studies reported on thrombosis, mortality and/or bleeding during ECMO treatment; no thromboembolic events were reported; all three studies reported frequent bleeding episodes defined on basis of transfusion requirements. An in-hospital mortality of 35-40% and a 30-day mortality of roughly 30% were reported in three different studies. The present systematic review reveals a substantial knowledge gap regarding platelet function during ECMO treatment in adult patients and underscores the demand for more and well-designed studies on this topic. There is suggested evidence of reduced platelet adhesion, decreased platelet activation, and reduced platelet aggregation in adult patients during ECMO treatment. Importantly, platelet aggregation results need to be interpreted in the light of low platelet counts. The associations of platelet function and bleeding and/or thromboembolic complications during ECMO treatment remain to be fully elucidated.
PubMed: 30474031
DOI: 10.3389/fcvm.2018.00157 -
Frontiers in Cardiovascular Medicine 2022Humans have been ascending to high altitudes for centuries, with a growing number of professional- and leisure-related sojourns occurring in this millennium. A multitude...
Humans have been ascending to high altitudes for centuries, with a growing number of professional- and leisure-related sojourns occurring in this millennium. A multitude of scientific reports on hemostatic disorders at high altitude suggest that hypoxia is an independent risk factor. However, no systematic analysis of the influence of environmental hypoxia on coagulation, fibrinolysis and platelet function has been performed. To fill this gap, we performed a systematic literature review, including only the data of healthy persons obtained during altitude exposure (<60 days). The results were stratified by the degree of hypoxia and sub-categorized into active and passive ascents and sojourns. Twenty-one studies including 501 participants were included in the final analysis. Since only one study provided relevant data, no conclusions regarding moderate altitudes (1,500-2,500 m) could be drawn. At high altitude (2,500-5,400 m), only small pathophysiological changes were seen, with a possible impact of increasing exercise loads. Elevated thrombin generation seems to be balanced by decreased platelet activation. Viscoelastic methods do not support increased thrombogenicity, with fibrinolysis being unaffected by high altitude. At extreme altitude (5,400-8,850 m), the limited data showed activation of coagulation in parallel with stimulation of fibrinolysis. Furthermore, multiple confounding variables at altitude, like training status, exercise load, fluid status and mental stress, prevent definitive conclusions being drawn on the impact of hypoxia on hemostasis. Thus, we cannot support the hypothesis that hypoxia triggers hypercoagulability and increases the risk of thromboembolic disorders, at least in healthy sojourners.
PubMed: 35252392
DOI: 10.3389/fcvm.2022.813550