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The Cochrane Database of Systematic... May 2017Various nerve blocks with local anaesthetic agents have been used to reduce pain after hip fracture and subsequent surgery. This review was published originally in 1999... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Various nerve blocks with local anaesthetic agents have been used to reduce pain after hip fracture and subsequent surgery. This review was published originally in 1999 and was updated in 2001, 2002, 2009 and 2017.
OBJECTIVES
This review focuses on the use of peripheral nerves blocks as preoperative analgesia, as postoperative analgesia or as a supplement to general anaesthesia for hip fracture surgery. We undertook the update to look for new studies and to update the methods to reflect Cochrane standards.
SEARCH METHODS
For the updated review, we searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8), MEDLINE (Ovid SP, 1966 to August week 1 2016), Embase (Ovid SP, 1988 to 2016 August week 1) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO, 1982 to August week 1 2016), as well as trial registers and reference lists of relevant articles.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) involving use of nerve blocks as part of the care provided for adults aged 16 years and older with hip fracture.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed new trials for inclusion, determined trial quality using the Cochrane tool and extracted data. When appropriate, we pooled results of outcome measures. We rated the quality of evidence according to the GRADE Working Group approach.
MAIN RESULTS
We included 31 trials (1760 participants; 897 randomized to peripheral nerve blocks and 863 to no regional blockade). Results of eight trials with 373 participants show that peripheral nerve blocks reduced pain on movement within 30 minutes of block placement (standardized mean difference (SMD) -1.41, 95% confidence interval (CI) -2.14 to -0.67; equivalent to -3.4 on a scale from 0 to 10; I = 90%; high quality of evidence). Effect size was proportionate to the concentration of local anaesthetic used (P < 0.00001). Based on seven trials with 676 participants, we did not find a difference in the risk of acute confusional state (risk ratio (RR) 0.69, 95% CI 0.38 to 1.27; I = 48%; very low quality of evidence). Three trials with 131 participants reported decreased risk for pneumonia (RR 0.41, 95% CI 0.19 to 0.89; I = 3%; number needed to treat for an additional beneficial outcome (NNTB) 7, 95% CI 5 to 72; moderate quality of evidence). We did not find a difference in risk of myocardial ischaemia or death within six months, but the number of participants included was well below the optimal information size for these two outcomes. Two trials with 155 participants reported that peripheral nerve blocks also reduced time to first mobilization after surgery (mean difference -11.25 hours, 95% CI -14.34 to -8.15 hours; I = 52%; moderate quality of evidence). One trial with 75 participants indicated that the cost of analgesic drugs was lower when they were given as a single shot block (SMD -3.48, 95% CI -4.23 to -2.74; moderate quality of evidence).
AUTHORS' CONCLUSIONS
High-quality evidence shows that regional blockade reduces pain on movement within 30 minutes after block placement. Moderate-quality evidence shows reduced risk for pneumonia, decreased time to first mobilization and cost reduction of the analgesic regimen (single shot blocks).
Topics: Aged; Aged, 80 and over; Anesthetics, Local; Confusion; Female; Hip Fractures; Humans; Male; Movement; Myocardial Infarction; Nerve Block; Pain Management; Pain Measurement; Pain, Postoperative; Peripheral Nerves; Pneumonia; Randomized Controlled Trials as Topic; Time Factors
PubMed: 28494088
DOI: 10.1002/14651858.CD001159.pub2 -
Cureus Jan 2017The pulmonary veins (PVs) are the most proximal source of arterial thromboembolism. Pulmonary vein thrombosis (PVT) is a rare but potentially lethal disease; its... (Review)
Review
The pulmonary veins (PVs) are the most proximal source of arterial thromboembolism. Pulmonary vein thrombosis (PVT) is a rare but potentially lethal disease; its incidence is unclear, as most of the literature includes case reports. It most commonly occurs as a complica-tion of malignancy, post lung surgery, or atrial fibrillation and can be idiopathic in some cases. Most patients with PVT are commonly asymptomatic or have nonspecific symptoms such as cough, hemoptysis, and dyspnea from pulmonary edema or infarction. The thrombi are typically detected using a variety of imaging modalities including transesophageal echocardiogram (TEE), computed tomography (CT) scanning, magnetic resonance imaging (MRI), or pulmonary angiog-raphy. Treatment should be determined by the obstructing pathological finding and can include antibiotic therapy, anticoagulation, thrombectomy, and/or pulmonary resection. The delay in diagnosing this medical entity can lead to complications including pulmonary infarction, pulmonary edema, right ventricular failure, allograft failure, and peripheral embolism resulting in limb ischemia, stroke, and renal infarction (RI).
PubMed: 28265529
DOI: 10.7759/cureus.993 -
The Journal of Rheumatology Dec 2021The epidemiology and treatment of peripheral neuropathy in systemic sclerosis (SSc) is poorly understood. The objectives of this study were to evaluate the incidence,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The epidemiology and treatment of peripheral neuropathy in systemic sclerosis (SSc) is poorly understood. The objectives of this study were to evaluate the incidence, prevalence, risk factors, and treatments of peripheral neuropathy in SSc.
METHODS
A systematic review of MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases for literature reporting peripheral neuropathy in SSc was performed. Studies evaluating incidence, prevalence, risk factors, and treatments were synthesized. A metaanalysis using a random effects model was used to evaluate the prevalence of peripheral neuropathy.
RESULTS
This systematic review identified 113 studies that reported 949 of 2143 subjects with at least 1 type of peripheral neuropathy. The mean age was 48.5 years. The mean time between SSc onset and detection of peripheral neuropathy was 8.85 years. The pooled prevalence of neuropathy was 27.37% (95% CI 22.35-32.70). Risk factors for peripheral neuropathy in SSc included advanced diffuse disease, anticentromere antibodies, calcinosis cutis, ischemia of the vasa nervorum, iron deficiency anemia, metoclopramide, pembrolizumab, silicosis, and uremia. There were 73 subjects with successful treatments (n = 36 restoring sensation, n = 37 restoring motor or sensorimotor function). Treatments included decompression surgery, prednisone, cyclophosphamide, carbamazepine, transcutaneous electrical nerve stimulation, tricyclic antidepressants, and intravenous Ig.
CONCLUSION
All-cause peripheral neuropathy is not uncommon in SSc. Compression neuropathies can be treated with decompression surgery. Observational data reporting immunosuppressives and anticonvulsants to treat peripheral neuropathy in SSc are limited and conflicting. Randomized controlled trials are needed to evaluate the efficacy of these interventions.
Topics: Humans; Incidence; Iron Deficiencies; Middle Aged; Peripheral Nervous System Diseases; Risk Factors; Scleroderma, Systemic
PubMed: 34210833
DOI: 10.3899/jrheum.201299 -
BMJ (Clinical Research Ed.) Sep 2016To quantify the association between atrial fibrillation and cardiovascular disease, renal disease, and death. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To quantify the association between atrial fibrillation and cardiovascular disease, renal disease, and death.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Medline and Embase.
ELIGIBILITY CRITERIA
Cohort studies examining the association between atrial fibrillation and cardiovascular disease, renal disease, and death. Two reviewers independently extracted study characteristics and the relative risk of outcomes associated with atrial fibrillation: specifically, all cause mortality, cardiovascular mortality, major cardiovascular events, any stroke, ischaemic stroke, haemorrhagic stroke, ischaemic heart disease, sudden cardiac death, congestive heart failure, chronic kidney disease, and peripheral arterial disease. Estimates were pooled with inverse variance weighted random effects meta-analysis.
RESULTS
104 eligible cohort studies involving 9 686 513 participants (587 867 with atrial fibrillation) were identified. Atrial fibrillation was associated with an increased risk of all cause mortality (relative risk 1.46, 95% confidence interval 1.39 to 1.54), cardiovascular mortality (2.03, 1.79 to 2.30), major cardiovascular events (1.96, 1.53 to 2.51), stroke (2.42, 2.17 to 2.71), ischaemic stroke (2.33, 1.84 to 2.94), ischaemic heart disease (1.61, 1.38 to 1.87), sudden cardiac death (1.88, 1.36 to 2.60), heart failure (4.99, 3.04 to 8.22), chronic kidney disease (1.64, 1.41 to 1.91), and peripheral arterial disease (1.31, 1.19 to 1.45) but not haemorrhagic stroke (2.00, 0.67 to 5.96). Among the outcomes examined, the highest absolute risk increase was for heart failure. Associations between atrial fibrillation and included outcomes were broadly consistent across subgroups and in sensitivity analyses.
CONCLUSIONS
Atrial fibrillation is associated with an increased risk of death and an increased risk of cardiovascular and renal disease. Interventions aimed at reducing outcomes beyond stroke are warranted in patients with atrial fibrillation.
Topics: Adult; Age Distribution; Aged; Atrial Fibrillation; Death, Sudden, Cardiac; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Prevalence; Renal Insufficiency, Chronic; Risk Factors; Sex Distribution; Stroke
PubMed: 27599725
DOI: 10.1136/bmj.i4482 -
Journal of Vascular Surgery Aug 2022Studies have investigated the effects of gender on vascular surgery care. However, to the best of our knowledge, no comprehensive synthesis of the literature has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Studies have investigated the effects of gender on vascular surgery care. However, to the best of our knowledge, no comprehensive synthesis of the literature has been performed on the presentation severity and postoperative outcomes for abdominal aortic aneurysms (AAAs), carotid artery stenosis (CAS), peripheral artery disease (PAD), and type B aortic dissection (TBAD). We conducted a systematic review and meta-analysis of the sex and gender differences in the presentation severity and outcomes for patients who had undergone major vascular surgery.
METHODS
The MEDLINE, Embase, and Cochrane CENTRAL databases were searched from their inception to December 2020. All observational studies and randomized controlled trials that had evaluated the gender differences in presentation severity or outcomes for patients who had undergone open or endovascular AAA or TBAD repair, carotid endarterectomy or stenting, or lower extremity bypass or angioplasty were included. The presentation severity was defined as follows: AAA (symptomatic or ruptured vs asymptomatic), carotid artery disease (symptomatic vs asymptomatic), PAD (chronic limb-threatening ischemia [CLTI] vs claudication), and TBAD (complicated vs uncomplicated). The postoperative outcomes included long-term mortality, stroke, amputation, revascularization, and graft and/or stent thrombosis. A random effects model was used to derive the odds ratios (ORs), risk ratios (RRs), and 95% confidence intervals (CIs).
RESULTS
A total of 236 studies met the inclusion criteria for our systematic review. Of the 236 studies, 86 (n = 2,099,534 patients), 62 (n = 2,300,888 patients), 28 (n = 2,394,143 patients), and 4 (n = 4525 patients) had evaluated the effects of gender on the outcomes for patients with AAA, CAS, PAD, and TBAD, respectively. The female patients were more likely to have presented with a ruptured AAA (OR, 1.18; 95% CI, 1.09-1.28) and CLTI (OR, 1.10; 95% CI, 1.02-1.19) than were the male patients. The all-cause mortality for those with an AAA (RR, 1.35; 95% CI, 1.20-1.52) and those with PAD (RR, 1.14; 95% CI, 1.05-1.23) was higher for the women. However, the female patients with CAS had had lower all-cause mortality (RR, 0.85; 95% CI, 0.76-0.94). No sex differences were found in the TBAD outcomes.
CONCLUSIONS
We found that female patients who had undergone vascular surgery were associated with more severe disease at presentation, with a greater proportion of ruptured AAAs and CLTI. This potentially contributes to the higher mortality rates for female patients with AAAs and PAD compared with male patients. Future studies are needed to evaluate the reasons for these disparities, and greater efforts are required to support women in receiving more timely vascular surgical care.
Topics: Aortic Aneurysm, Abdominal; Aortic Rupture; Carotid Stenosis; Endovascular Procedures; Female; Humans; Male; Peripheral Arterial Disease; Risk Factors; Sex Factors; Treatment Outcome
PubMed: 35257798
DOI: 10.1016/j.jvs.2022.02.030 -
A systematic review and meta-analysis of outcomes after acute limb ischemia in patients with cancer.Journal of Vascular Surgery Sep 2021Cancer results in a hypercoagulable state that is associated with both venous and arterial thromboses. However, little is known about the effects of acute limb ischemia... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cancer results in a hypercoagulable state that is associated with both venous and arterial thromboses. However, little is known about the effects of acute limb ischemia (ALI) in this cohort of patients. In the present systematic review and meta-analysis, we analyzed the available clinical data on cancer and its association with ALI and evaluated the outcomes in these patients after a diagnosis of ALI.
METHODS
Three databases, including PubMed, EMBASE, and the Cochrane Library, were queried. Studies that met the inclusion criteria were included regardless of the publication year, language, sample size, or follow-up length. All the steps of the meta-analysis were conducted in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) and MOOSE (meta-analysis of observational studies in epidemiology) guidelines.
RESULTS
Seven studies from 6222 references with a total of 2899 patients were included. Of the 2899 patients, 1195 (41%) had had a diagnosis of ALI before their cancer diagnosis, and 1704 (59%) had presented with ALI after a cancer diagnosis. Nearly three quarters of ALI events were among patients with cancer of the skin and soft tissue (19%), genitourinary (18%), lung (17%), and gastrointestinal (16%) systems. ALI recurrence was similar between the two groups, and major amputation was more likely in patients with a diagnosis of ALI after a cancer diagnosis (7.4% vs 4.6%; P < .01). The incidence of mortality at 1 year was significantly greater for patients with established cancer who had presented with ALI compared with the patients who had presented with ALI before a cancer diagnosis (50.6% vs 29.9%; P < .01). After adjusting for study variability using the random effects model, the mortality at 1 year for all patients was 52.3% (95% confidence interval, 37.7%-66.5%). No significant heterogeneity (P = .73) was found between the two groups of patients, which varied by the timing of the ALI diagnosis in relation to the cancer diagnosis.
CONCLUSIONS
The 1-year mortality after the development of ALI in patients with cancer was >50%. For patients presenting with ALI of unclear etiology, the presence of an underlying cancer should be considered.
Topics: Acute Disease; Aged; Amputation, Surgical; Female; Humans; Ischemia; Limb Salvage; Male; Neoplasms; Peripheral Arterial Disease; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 33905869
DOI: 10.1016/j.jvs.2021.03.058 -
British Journal of Clinical Pharmacology Jul 2016Drug-induced Raynaud's phenomenon (RP) has long been associated with the use of different drugs, including cancer chemotherapy or β-adrenoceptor blockers. However,... (Review)
Review
AIM
Drug-induced Raynaud's phenomenon (RP) has long been associated with the use of different drugs, including cancer chemotherapy or β-adrenoceptor blockers. However, sources report extremely variable prevalence and the level of evidence for each class is heterogeneous. Moreover, new signals are emerging from case reports and small series. Our objective was therefore to review available evidence about this adverse drug effect and to propose a mechanistic approach of drug-induced RP.
METHODS
A systematic review of English and French language articles was performed through Medline (1946-2015) and Embase (1974-2015). Further relevant papers were identified from the reference lists of retrieved articles.
RESULTS
We identified 12 classes of drugs responsible for RP, with a variety of underlying mechanisms such as increased sympathetic activation, endothelial dysfunction, neurotoxicity or decreased red blood cell deformability. Cisplatin and bleomycin were associated with the highest risk, followed by β-adrenoceptor blockers. Recent data suggest a possible involvement of tyrosine kinase inhibitors (TKI), through an unknown mechanism.
CONCLUSION
Drug-induced RP is a probably underestimated adverse drug event, with limited available evidence regarding its prevalence. Although rare, serious complications like critical digital ischaemia have been reported. When these treatments are started in patients with a history of RP, careful monitoring must be made and, if possible, alternative therapies that do not alter peripheral blood flow should be considered.
Topics: Adrenergic beta-Antagonists; Animals; Drug-Related Side Effects and Adverse Reactions; Humans; Prevalence; Raynaud Disease
PubMed: 26949933
DOI: 10.1111/bcp.12912 -
Saudi Pharmaceutical Journal : SPJ :... Jul 2021Arterial catheterization is frequently performed in neonatal intensive care units with an inherent risk of peripheral ischemic injury, especially in preterm infants. The... (Review)
Review
BACKGROUND
Arterial catheterization is frequently performed in neonatal intensive care units with an inherent risk of peripheral ischemic injury, especially in preterm infants. The treatment options following vascular damage involve invasive and non-invasive modalities. The primary objective of this systematic review was to evaluate the evidence of the use of topical nitroglycerine (TNG) either alone or as adjunctive therapy. The secondary aim was to develop an approach to the treatment of catheter induced ischemia in infants based on the available evidence.
METHODS
A comprehensive search was conducted of available databases for relevant articles that involved the treatment of peripheral tissue ischemia in neonates with the use of TNG. Citations were restricted to human subjects.
RESULTS
Six hundred and eighty-nine articles were identified, and twenty-seven case reports and case series were compatible with the inclusion and exclusion criteria. Sixty-eight infants out of the 76 published cases (89%) experienced a favorable outcome and 79% (n = 60) demonstrated complete recovery with the topical application of TNG to the ischemic site.
CONCLUSION
The available evidence demonstrates that TNG is effective for the treatment of peripheral ischemia in neonates after standard conservative measures have failed. However, due to the absence of robust evidence for this therapeutic modality, there are no uniform guidelines regarding the frequency, duration, and safety of TNG use. Planning the management of peripheral ischemia in neonates with TNG should be a multidisciplinary decision that includes close surveillance of blood pressure, methemoglobin levels, and follow up cranial ultrasound.
PubMed: 34400871
DOI: 10.1016/j.jsps.2021.05.008 -
The Cochrane Database of Systematic... Oct 2018Peripheral arterial disease (PAD), caused by narrowing of the arteries in the limbs, is increasing in incidence and prevalence as our population is ageing and as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral arterial disease (PAD), caused by narrowing of the arteries in the limbs, is increasing in incidence and prevalence as our population is ageing and as diabetes is becoming more prevalent. PAD can cause pain in the limbs while walking, known as intermittent claudication, or can be more severe and cause pain while at rest, ulceration, and ultimately gangrene and limb loss. This more severe stage of PAD is known as 'critical limb ischaemia'. Treatments for PAD include medications that help to reduce the increased risk of cardiovascular events and help improve blood flow, as well as endovascular or surgical repair or bypass of the blocked arteries. However, many people are unresponsive to medications and are not suited to surgical or endovascular treatment, leaving amputation as the last option. Gene therapy is a novel approach in which genetic material encoding for proteins that may help increase revascularisation is injected into the affected limbs of patients. This type of treatment has been shown to be safe, but its efficacy, especially regarding ulcer healing, effects on quality of life, and other symptomatic outcomes remain unknown.
OBJECTIVES
To assess the effects of gene therapy for symptomatic peripheral arterial disease.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched Cochrane CENTRAL, the Cochrane Vascular Specialised Register, MEDLINE Ovid, Embase Ovid, CINAHL, and AMED, along with trials registries (all searched 27 November 2017). We also checked reference lists of included studies and systematic reviews for further studies.
SELECTION CRITERIA
We included randomised and quasi-randomised studies that evaluated gene therapy versus no gene therapy in people with PAD. We excluded studies that evaluated direct growth hormone treatment or cell-based treatments.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, performed quality assessment, and extracted data from the included studies. We collected pertinent information on each study, as well as data for the outcomes of amputation-free survival, ulcer healing, quality of life, amputation, all-cause mortality, ankle brachial index, symptom scores, and claudication distance.
MAIN RESULTS
We included in this review a total of 17 studies with 1988 participants (evidence current until November 2017). Three studies limited their inclusion to people with intermittent claudication, 12 limited inclusion to people with varying levels of critical limb ischaemia, and two included people with either condition. Study investigators evaluated many different types of gene therapies, using different protocols. Most studies evaluated growth factor-encoding gene therapy, with six studies using vascular endothelial growth factor (VEGF)-encoding genes, four using hepatocyte growth factor (HGF)-encoding genes, and three using fibroblast growth factor (FGF)-encoded genes. Two studies evaluated hypoxia-inducible factor 1-alpha (HIF-1α) gene therapy, one study used a developmental endothelial locus-1 gene therapy, and the final study evaluated a stromal cell-derived factor-1 (SDF-1) gene therapy. Most studies reported outcomes after 12 months of follow-up, but follow-up ranged from three months to two years.Overall risk of bias varied between studies, with many studies not providing sufficient detail for adequate determination of low risk of bias for many domains. Two studies did not utilise a placebo control, leading to risk of performance bias. Several studies reported in previous protocols or in their Methods sections that they would report on certain outcomes for which no data were then reported, increasing risk of reporting bias. All included studies reported sponsorships from corporate entities that led to unclear risk of other bias. The overall quality of evidence ranged from moderate to very low, generally as the result of heterogeneity and imprecision, with few or no studies reporting on outcomes.Evidence suggests no clear differences for the outcomes of amputation-free survival, major amputation, and all-cause mortality between those treated with gene therapy and those not receiving this treatment (all moderate-quality evidence). Low-quality evidence suggests improvement in complete ulcer healing with gene therapy (odds ratio (OR) 2.16, 95% confidence interval (CI) 1.02 to 4.59; P = 0.04). We could not combine data on quality of life and can draw no conclusions at this time regarding this outcome (very low-quality evidence). We included one study in the meta-analysis for ankle brachial index, which showed no clear differences between treatments, but we can draw no overall association (low-quality evidence). We combined in a meta-analysis pain symptom scores as assessed by visual analogue scales from two studies and found no clear differences between treatment groups (very low-quality evidence). We carried out extensive subgroup analyses by PAD classification, dosage schedule, vector type, and gene used but identified no substantial differences.
AUTHORS' CONCLUSIONS
Moderate-quality evidence shows no clear differences in amputation-free survival, major amputation, and all-cause mortality between those treated with gene therapy and those not receiving gene therapy. Some evidence suggests that gene therapy may lead to improved complete ulcer healing, but this outcome needs to be explored with improved reporting of the measure, such as decreased ulcer area in cm², and better description of ulcer types and healing. Further standardised data that are amenable to meta-analysis are needed to evaluate other outcomes such as quality of life, ankle brachial index, symptom scores, and claudication distance.
Topics: Amputation, Surgical; Chemokine CXCL12; Extremities; Fibroblast Growth Factors; Genetic Therapy; Hepatocyte Growth Factor; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Intermittent Claudication; Ischemia; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Vascular Endothelial Growth Factor A
PubMed: 30380135
DOI: 10.1002/14651858.CD012058.pub2 -
The Cochrane Database of Systematic... Jan 2018Peripheral arterial occlusive disease (PAOD) is a common cause of morbidity and mortality due to cardiovascular disease in the general population. Although numerous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral arterial occlusive disease (PAOD) is a common cause of morbidity and mortality due to cardiovascular disease in the general population. Although numerous treatments have been adopted for patients at different disease stages, no option other than amputation is available for patients presenting with critical limb ischaemia (CLI) unsuitable for rescue or reconstructive intervention. In this regard, prostanoids have been proposed as a therapeutic alternative, with the aim of increasing blood supply to the limb with occluded arteries through their vasodilatory, antithrombotic, and anti-inflammatory effects. This is an update of a review first published in 2010.
OBJECTIVES
To determine the effectiveness and safety of prostanoids in patients with CLI unsuitable for rescue or reconstructive intervention.
SEARCH METHODS
For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (January 2017) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1). In addition, we searched trials registries (January 2017) and contacted pharmaceutical manufacturers, in our efforts to identify unpublished data and ongoing trials.
SELECTION CRITERIA
Randomised controlled trials describing the efficacy and safety of prostanoids compared with placebo or other pharmacological control treatments for patients presenting with CLI without chance of rescue or reconstructive intervention.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. We resolved disagreements by consensus or by consultation with a third review author.
MAIN RESULTS
For this update, 15 additional studies fulfilled selection criteria. We included in this review 33 randomised controlled trials with 4477 participants; 21 compared different prostanoids versus placebo, seven compared prostanoids versus other agents, and five conducted head-to-head comparisons using two different prostanoids.We found low-quality evidence that suggests no clear difference in the incidence of cardiovascular mortality between patients receiving prostanoids and those given placebo (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.41 to 1.58). We found high-quality evidence showing that prostanoids have no effect on the incidence of total amputations when compared with placebo (RR 0.97, 95% CI 0.86 to 1.09). Adverse events were more frequent with prostanoids than with placebo (RR 2.11, 95% CI 1.79 to 2.50; moderate-quality evidence). The most commonly reported adverse events were headache, nausea, vomiting, diarrhoea, flushing, and hypotension. We found moderate-quality evidence showing that prostanoids reduced rest-pain (RR 1.30, 95% CI 1.06 to 1.59) and promoted ulcer healing (RR 1.24, 95% CI 1.04 to 1.48) when compared with placebo, although these small beneficial effects were diluted when we performed a sensitivity analysis that excluded studies at high risk of bias. Additionally, we found evidence of low to very low quality suggesting the effects of prostanoids versus other active agents or versus other prostanoids because studies conducting these comparisons were few and we judged them to be at high risk of bias. None of the included studies assessed quality of life.
AUTHORS' CONCLUSIONS
We found high-quality evidence showing that prostanoids have no effect on the incidence of total amputations when compared against placebo. Moderate-quality evidence showed small beneficial effects of prostanoids for rest-pain relief and ulcer healing when compared with placebo. Additionally, moderate-quality evidence showed a greater incidence of adverse effects with the use of prostanoids, and low-quality evidence suggests that prostanoids have no effect on cardiovascular mortality when compared with placebo. None of the included studies reported quality of life measurements. The balance between benefits and harms associated with use of prostanoids in patients with critical limb ischaemia with no chance of reconstructive intervention is uncertain; therefore careful assessment of therapeutic alternatives should be considered. Main reasons for downgrading the quality of evidence were high risk of attrition bias and imprecision of effect estimates.
Topics: Alprostadil; Amputation, Surgical; Epoprostenol; Humans; Iloprost; Ischemia; Leg; Leg Ulcer; Nafronyl; Nicotinic Acids; Pentoxifylline; Peripheral Vascular Diseases; Prostaglandins; Randomized Controlled Trials as Topic; Vasodilator Agents
PubMed: 29318581
DOI: 10.1002/14651858.CD006544.pub3