Background There are no recognized pharmacological treatments for abdominal aortic aneurysms ( AAA ), although statins are suggested to be beneficial. We sought to summarize the literature regarding the effects of statins on human AAA growth, rupture, and 30‐day mortality. Methods and Results We conducted a systematic review and meta‐analysis of randomized and observational studies using the Cochrane CENTRAL database, MEDLINE , and EMBASE up to June 15, 2018. Review, abstraction, and quality assessment were conducted by 2 independent reviewers, and a third author resolved discrepancies. Pooled mean differences and odds ratios with 95% confidence intervals were calculated using random effects models. Heterogeneity was quantified using the I 2 statistic, and publication bias was assessed using funnel plots. Our search yielded 911 articles. One case‐control and 21 cohort studies involving 80 428 patients were included. The risk of bias was low to moderate. Statin use was associated with a mean AAA growth rate reduction of 0.82 mm/y (95% confidence interval 0.33, 1.32, P =0.001, I 2 =86%). Statins were also associated with a lower rupture risk (odds ratio 0.63, 95% confidence interval 0.51, 0.78, P <0.0001, I 2 =27%), and preoperative statin use was associated with a lower 30‐day mortality following elective AAA repair (odds ratio 0.55, 95% confidence interval 0.36, 0.83, P =0.005, I 2 =57%). Conclusions Statin therapy may be associated with reduction in AAA progression, rupture, and lower rates of perioperative mortality following elective AAA repair. These data argue for widespread statin use in AAA patients. Clinical Trial Registration URL : http://www.crd.york.ac.uk . Unique identifier: CRD 42017056480.
Objective Diabetic foot ulcer, which often leads to lower limb amputation, is a devastating complication of diabetes that is a major burden on patients and the healthcare system. The main objective of this study is to determine the economic burden of diabetic foot ulcer-related care. Methods We conducted a multicenter study of all diabetic foot ulcer patients admitted to general internal medicine wards at seven hospitals in the Greater Toronto Area, Canada from 2010 to 2015, using the GEMINI database. We compared the mean costs of care per patient for diabetic foot ulcer-related admissions, admissions for other diabetes-related complications, and admissions for the top five most costly general internal medicine conditions, using the Ontario Case Costing Initiative. Regression models were used to determine adjusted estimates of cost per patient. Propensity-score matched analyses were performed as sensitivity analyses. Results Our study cohort comprised of 557 diabetic foot ulcer patients; 2939 non-diabetic foot ulcer diabetes patients; and 23,656 patients with the top 5 most costly general internal medicine conditions. Diabetic foot ulcer admissions incurred the highest mean cost per patient ($22,754) when compared to admissions with non-diabetic foot ulcer diabetes ($8,350) and the top five most costly conditions ($10,169). Using adjusted linear regression, diabetic foot ulcer admissions demonstrated a 49.6% greater mean cost of care than non-diabetic foot ulcer-related diabetes admissions (95% CI 1.14–1.58), and a 25.6% greater mean cost than the top five most costly conditions (95% CI 1.17–1.34). Propensity-scored matched analyses confirmed these results. Conclusion Diabetic foot ulcer patients incur significantly higher costs of care when compared to admissions with non-diabetic foot ulcer-related diabetes patients, and the top five most costly general internal medicine conditions.
Peripheral artery disease (PAD) is characterized by the atherosclerotic narrowing of lower limb vessels, leading to ischemic muscle pain in older persons. Some patients experience progression to advanced chronic limb-threatening ischemia (CLTI) with poor long-term survivorship. Herein, we performed serum metabolomics to reveal the mechanisms of PAD pathophysiology that may improve its diagnosis and prognosis to CLTI complementary to the ankle–brachial index (ABI) and clinical presentations. Non-targeted metabolite profiling of serum was performed by multisegment injection–capillary electrophoresis–mass spectrometry (MSI–CE–MS) from age and sex-matched, non-diabetic, PAD participants who were recruited and clinically stratified based on the Rutherford classification into CLTI (n = 18) and intermittent claudication (IC, n = 20). Compared to the non-PAD controls (n = 20), PAD patients had lower serum concentrations of creatine, histidine, lysine, oxoproline, monomethylarginine, as well as higher circulating phenylacetylglutamine (p < 0.05). Importantly, CLTI cases exhibited higher serum concentrations of carnitine, creatinine, cystine and trimethylamine-N-oxide along with lower circulating fatty acids relative to well matched IC patients. Most serum metabolites associated with PAD progression were also correlated with ABI (r = ±0.24−0.59, p < 0.05), whereas the ratio of stearic acid to carnitine, and arginine to propionylcarnitine differentiated CLTI from IC with good accuracy (AUC = 0.87, p = 4.0 × 10−5). This work provides new biochemical insights into PAD progression for the early detection and surveillance of high-risk patients who may require peripheral vascular intervention to prevent amputation and premature death.
Acetylsalicylic acid (ASA), also known as aspirin, appears to be ineffective in inhibiting platelet aggregation in 20–30% of patients. Light transmission aggregometry (LTA) is a gold standard platelet function assay. In this pilot study, we used LTA to personalize ASA therapy ex vivo in atherosclerotic patients. Patients were recruited who were on 81 mg ASA, presenting to ambulatory clinics at St. Michael’s Hospital (n = 64), with evidence of atherosclerotic disease defined as clinical symptoms and diagnostic findings indicative of symptomatic peripheral arterial disease (PAD), with an ankle brachial index (ABI) of <0.9 (n = 52) or had diagnostic features of asymptomatic carotid arterial stenosis (CAS), with >50% stenosis of internal carotid artery on duplex ultrasound (n = 12). ASA compliance was assessed via multisegmented injection-capillary electrophoresis-mass spectrometry based on measuring the predominant urinary ASA metabolite, salicyluric acid. LTA with arachidonic acid was used to test for ASA sensitivity. Escalating ASA dosages of 162 mg and 325 mg were investigated ex vivo for ASA dose personalization. Of the 64 atherosclerotic patients recruited, 8 patients (13%) were non-compliant with ASA. Of ASA compliant patients (n = 56), 9 patients (14%) were non-sensitive to their 81 mg ASA dosage. Personalizing ASA therapy in 81 mg ASA non-sensitive patients with escalating dosages of ASA demonstrated that 6 patients became sensitive to a dosage equivalent to 162 mg ASA and 3 patients became sensitive to a dosage equivalent to 325 mg ASA. We were able to personalize ASA dosage ex vivo in all ASA non-sensitive patients with escalating dosages of ASA within 1 h of testing.
Background Peripheral arterial disease (PAD) affects more than 150 million people worldwide and is associated with high rates of lower extremity amputation, myocardial infarction, stroke and death. Fatty acid binding protein 3 (FABP3) is released into circulation in patients with skeletal muscle injury. In this pilot study, we investigated a possible association between PAD and blood levels of FABP3. Methods Blood samples were collected from patients with clinical symptoms and diagnostic findings indicative of PAD (PAD group; ankle-brachial index [ABI] <0.9; n = 75) and in those without clinical or diagnostic features of PAD (non-PAD group; ABI >0.9; n = 75) presenting to vascular surgery ambulatory clinics at St. Michael's Hospital. Plasma samples were analyzed by protein multiplex to quantify FABP3 levels. Results PAD patients were found to have higher blood levels of FABP3 compared to patients without PAD (mean 3.90 ± 1.69 vs 2.03 ± 0.78; P < .001). A subgroup analysis demonstrated that the FABP3 levels were increased by almost two-fold in patients with PAD, independent of coronary artery disease ( P < .001) or diabetes mellitus status ( P < .001). Moreover, a significant negative correlation between FABP3 and the ABI was observed in PAD and patients without PAD matched groups (r = –0.51; P = .001). Last, immunohistochemistry demonstrated elevated expressions of FABP3 within skeletal muscle obtained from patients with the most severe form of PAD, chronic limb-threatening ischemia, when compared with patients without PAD. Conclusions Patients with PAD have elevated plasma levels of FABP3. An increasing severity of PAD is associated with higher FABP3 levels.
Objective Peripheral artery disease patients have been shown to be more susceptible to thrombotic events compared to non-peripheral artery disease patients. Therefore, the aim of this study was to investigate the coagulation profile in peripheral artery disease patients with chronic limb threatening ischemia, moderate peripheral artery disease patients with claudication, and non-peripheral artery disease controls. Methods Chronic limb threatening ischemia patients were matched to peripheral artery disease patients with claudication and non-peripheral artery disease controls in a 1:1:1 ratio. Each patient had their cytokines, markers of thrombin generation, coagulation factors, natural anti-coagulants, fibrinolysis, and endothelial injury markers assessed. Results Markers of thrombin activation, thrombin Fragments F1 + 2 (Frag 1 + 2), and thrombin–anti-thrombin complex were found to be significantly elevated in all peripheral artery disease and chronic limb threatening ischemia patients relative to non-peripheral artery disease controls. Similarly, relative to non-peripheral artery disease controls, inflammatory markers including C-reactive protein, soluble platelet factor 4, and neutrophil gelatinase-associated lipocalin were also found to be significantly upregulated in chronic limb threatening ischemia patients, but not in peripheral artery disease patients with claudication. Furthermore, our data demonstrated significant increases in markers of endothelial injury in chronic limb threatening ischemia patients relative to non-peripheral artery disease controls. Finally, decreases in natural anti-coagulants (protein C and protein S) and coagulation factors FIX, FXI, and FXII were also observed in chronic limb threatening ischemia patients when compared with non-peripheral artery disease controls. Conclusions Our data suggest that in relation to non-peripheral artery disease controls, chronic limb threatening ischemia patients are more hypercoagulable. However, peripheral artery disease patients with claudication appear to have similar levels of circulating procoagulant markers as non-peripheral artery disease patients. This may explain the increased risk of thrombotic events observed in chronic limb threatening ischemia patients.
Plasma levels of fatty acid binding protein 3 (pFABP3) are elevated in patients with peripheral artery disease (PAD). Since the kidney filters FABP3 from circulation, we investigated whether urinary fatty acid binding protein 3 (uFABP3) is associated with PAD, and also explored its potential as a diagnostic biomarker for this disease state. A total of 130 patients were recruited from outpatient clinics at St. Michael’s Hospital, comprising of 65 patients with PAD and 65 patients without PAD (non-PAD). Levels of uFABP3 normalized for urine creatinine (uFABP3/uCr) were 1.7-folds higher in patients with PAD [median (IQR) 4.41 (2.79–8.08)] compared with non-PAD controls [median (IQR) 2.49 (1.78–3.12), p-value = 0.001]. Subgroup analysis demonstrated no significant effect of cardiovascular risk factors (age, sex, hypertension, hypercholesteremia, diabetes and smoking) on uFABP3/uCr in both PAD and non-PAD patients. Spearmen correlation studies demonstrated a significant negative correlation between uFABP3/uCr and ABI (ρ = − 0.436; p-value = 0.001). Regression analysis demonstrated that uFABP3/Cr levels were associated with PAD independently of age, sex, hypercholesterolemia, smoking, prior history of coronary arterial disease and Estimated Glomerular Filtration rate (eGFR) [odds ratio: 2.34 (95% confidence interval: 1.47–3.75) p-value < 0.001]. Lastly, receiver operator curve (ROC) analysis demonstrated unadjusted area under the curve (AUC) for uFABP3/Cr of 0.79, which improved to 0.86 after adjusting for eGFR, age, hypercholesteremia, smoking and diabetes. In conclusion, our results demonstrate a strong association between uFABP3/Cr and PAD and suggest the potential of uFABP3/Cr in identifying patients with PAD.
Study Design. Qualitative study. Objective. The objective of this study was to compare the perceptions of patients and surgeons regarding the risks and benefits of lumbar decompressive surgery for sciatica following a consultation meeting. Summary of Background Data. Evidence regarding pain improvement in patients following lumbar decompressive surgery for sciatica is inconsistent. Given this inconsistency, patients choosing to undergo lumbar decompressive surgery must accept the risks associated with the surgery despite uncertainty regarding benefits. This raises questions as to the nature of informed decision-making for patients choosing to undergo surgery for sciatica. Methods. We undertook a qualitative descriptive study with 12 adult lumbar decompressive surgery candidates and six of their spine surgeons and analyzed data using inductive content analysis. Results. Our analysis revealed that most patients were satisfied with the consultation despite limited understanding of lumbar decompressive surgery. We found discrepancies between patients’ preoperative expectations and understanding of information provided by surgeons and what surgeons believed they had conveyed. Surgeons and patients disagreed on how much information is needed about postsurgical activity modifications and long-term outcomes to make a decision about whether or not to undergo surgery, with patients desiring more information. As a result, for most patients, the decision-making process extended beyond the information provided by surgeons and incorporated information from family members, friends, family doctors, and the internet. Conclusion. Our results highlight misunderstandings between patients and surgeons, particularly in regard to prognosis and activity modifications. Since this information is important for patients choosing whether to undergo a surgical intervention, our study provides guidance to improve informed decisions about sciatica and, potentially, other elective surgeries. Level of Evidence: 4
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