Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 62
Filter
1.
Diabetes Res Clin Pract ; 204: 110925, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37774979

ABSTRACT

INTRODUCTION: The aim of this study was to investigate the concept of an 8-week personalised activity plan, using short periods of physical activity to break up sitting time in people with Intermittent Claudication (IC), to improve walking ability, and reduce time spent sitting. METHODS: The study was designed as a single centre, single arm, before and after study and is registered with clinicaltrials.gov (NCT04572737). The co-primary outcomes are time spent sitting and walking ability measured via the walking impairment questionnaire. Normally distributed data was analysed using paired samples T-tests; non-normally distributed data was analysed using related-samples Wilcoxon signed rank tests. RESULTS: There was a significant improvement in both co-primary outcomes: walking ability and time spent sitting, as well as the following secondary outcomes: total bouts and time spent in prolonged sitting, time spent standing and stepping, anxiety, depression, and activity levels reported on the vascular quality of life questionnaire. CONCLUSION: An 8-week personalised activity plan to break up sitting time shows promise as a treatment for people with IC, improving walking ability and reducing time spent sitting. This study supports the use of large randomised controlled trials to further develop this treatment in people with IC.


Subject(s)
Quality of Life , Sitting Position , Humans , Intermittent Claudication/therapy , Walking , Time Factors
2.
Ann Phys Rehabil Med ; 66(6): 101756, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37276748

ABSTRACT

BACKGROUND: Objective physical performance-based outcome measures (PerBOMs) are essential tools for the holistic management of people who have had an amputation due to vascular disease. These people are often non-ambulatory, however it is currently unclear which PerBOMs are high quality and appropriate for those who are either ambulatory or non-ambulatory. RESEARCH QUESTION: Which PerBOMs have appropriate clinimetric properties to be recommended for those who have had amputations due to vascular disease ('vascular amputee')? DATA SOURCES: MEDLINE, CINAHL, EMBASE, EMCARE, the Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL) and Scopus databases were searched for the terms: "physical performance" or "function", "clinimetric properties", "reliability", "validity", "amputee" and "peripheral vascular disease" or "diabetes". REVIEW METHODS: A systematic review of PerBOMs for vascular amputees was performed following COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology and PRISMA guidelines. The quality of studies and individual PerBOMs was assessed using COSMIN risk of bias and good measurement properties. Overall PerBOM quality was evaluated with a modified GRADE rating. Key clinimetric properties evaluated were reliability, validity, predictive validity and responsiveness. RESULTS: A total of 15,259 records were screened. Forty-eight studies (2650 participants) were included: 7 exclusively included vascular amputees only, 35 investigated validity, 20 studied predictive validity, 23 investigated reliability or internal consistency and 7 assessed responsiveness. Meta-analysis was neither possible nor appropriate for this systematic review in accordance with COSMIN guidelines, due to heterogeneity of the data. Thirty-four different PerBOMs were identified of which only 4 are suitable for non-ambulatory vascular amputees. The Amputee Mobility Predictor no Prosthesis (AMPnoPro) and Transfemoral Fitting Predictor (TFP) predict prosthesis use only. PerBOMs available for assessing physical performance are the One-Leg Balance Test (OLBT) and Basic Amputee Mobility Score (BAMS). CONCLUSION: At present, few PerBOMs can be recommended for vascular amputees. Only 4 are available for non-ambulatory individuals: AMPnoPro, TFP, OLBT and BAMS.

3.
Exp Gerontol ; 178: 112207, 2023 07.
Article in English | MEDLINE | ID: mdl-37196824

ABSTRACT

AIM: To quantify differences in device-measured physical activity (PA) behaviours, and physical function (PF), in people with type 2 diabetes mellitus (T2DM) with and without peripheral artery disease (PAD). MATERIALS AND METHODS: Participants from the Chronotype of Patients with T2DM and Effect on Glycaemic Control cross-sectional study wore accelerometers on their non-dominant wrist for up to 8-days to quantify: volume and intensity distribution of PA, time spent inactive, time in light PA, moderate-to-vigorous PA in at least 1-minute bouts (MVPA1min), and the average intensity achieved during the most active continuous 2, 5, 10, 30, and 60-minute periods of the 24-h day. PF was assessed using the short physical performance battery (SPPB), the Duke Activity Status Index (DASI), sit-to-stand repetitions in 60 s (STS-60); hand-grip strength was also assessed. Differences between subjects with and without PAD were estimated using regressions adjusted for possible confounders. RESULTS: 736 participants with T2DM (without diabetic foot ulcers) were included in the analysis, 689 had no PAD. People with T2DM and PAD undertake less PA (MVPA1min: -9.2 min [95 % CI: -15.3 to -3.0; p = 0.004]) (light intensity PA: -18.7 min [-36.4 to -1.0; p = 0.039]), spend more time inactive (49.2 min [12.1 to 86.2; p = 0.009]), and have reduced PF (SPPB score: -1.6 [-2.5 to -0.8; p = 0.001]) (DASI score: -14.8 [-19.8 to -9.8; p = 0.001]) (STS-60 repetitions: -7.1 [-10.5 to -3.8; p = 0.001]) compared to people without; some differences in PA were attenuated by confounders. Reduced intensity of activity for the most active continuous 2-30 min in the 24-h day, and reduced PF, persisted after accounting for confounders. There were no significant differences in hand-grip strength. CONCLUSIONS: Findings from this cross-sectional study suggest that, the presence of PAD in T2DM may have been associated with lower PA levels and PF.


Subject(s)
Diabetes Mellitus, Type 2 , Peripheral Arterial Disease , Humans , Cross-Sectional Studies , Exercise , Sedentary Behavior , Peripheral Arterial Disease/complications
4.
Ann Vasc Surg ; 93: 157-165, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37023916

ABSTRACT

BACKGROUND: Vascular Emergency Clinics (VEC) improve patient outcomes in chronic limb-threatening ischemia (CLTI). They provide a "1 stop" open access policy, whereby "suspicion of CLTI" by a healthcare professional or patient leads to a direct review. We assessed the resilience of the outpatient VEC model to the first year of the coronavirus disease (COVID-19) pandemic. METHODS: A retrospective review of a prospectively maintained database of all patients assessed in our VEC for lower limb pathologies between March 2020 and April 2021 was performed. This was cross-referenced to national and loco-regional Governmental COVID-19 data. Individuals with CLTI were further analysed to determine Peripheral Arterial Disease-Quality Improvement Framework compliance. RESULTS: Seven hundred and ninety one patients attended for 1,084 assessments (Male n = 484, 61%; Age 72.5 ± standard deviation 12.2 years; White British n = 645, 81.7%). In total, 322 patients were diagnosed with CLTI (40.7%). A total of 188 individuals (58.6%) underwent a first revascularization strategy (Endovascular n = 128, 39.8%; Hybrid n = 41, 12.7%; Open surgery n = 19, 5.9%; Conservative n = 134, 41.6%). Major lower limb amputation rate was 10.9% (n = 35) and mortality rate was 25.8% (n = 83) at 12 months of follow-up. Median referral to assessment time was 3 days (interquartile range: 1-5). For the nonadmitted patient with CLTI, the median assessment to intervention was 8 days (interquartile range: 6-15) and median referral to intervention time of 11 days (11-18). CONCLUSIONS: The VEC model has demonstrated strong resilience to the COVID-19 pandemic with rapid treatment timelines maintained for patients with CLTI.


Subject(s)
COVID-19 , Coronavirus Infections , Coronavirus , Endovascular Procedures , Peripheral Arterial Disease , Humans , Male , Aged , Female , Pandemics , Risk Factors , Endovascular Procedures/adverse effects , Ischemia , Treatment Outcome , Limb Salvage , Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/epidemiology , Peripheral Arterial Disease/surgery , Chronic Limb-Threatening Ischemia , Retrospective Studies , Chronic Disease
5.
Prim Health Care Res Dev ; 23: e77, 2022 11 28.
Article in English | MEDLINE | ID: mdl-36440656

ABSTRACT

AIMS: Major lower extremity amputations (MLEAs) are understood to be well recorded in secondary care in England in the Hospital Episode Statistics (HES) database. It is unclear how well MLEAs are recorded in primary care databases. BACKGROUND: This study compared MLEA event case ascertainment in Clinical Practice Research Datalink (CPRD) to that in HES. METHODS: MLEA events were ascertained in CPRD and in HES linkage between 1 January 2010 and 31 December 2019. The number of MLEA events and the number of patients with at least one MLEA in each database were recorded and compared. Individual events were matched between the databases using varying date-matching windows. Reasons for differences in case ascertainment were explored. FINDINGS: In total 23 262 patients had at least one MLEA record, 8716 (37.5%) had an MLEA record in HES only, 5393 (23.2%) in CPRD only and 9153 (39.4%) in both. Out of a total of 75 221 events, 13 071 (62.4%) were recorded in HES only and 44 151 (81.3%) in CPRD only. 7874 (37.6%) of HES events were recorded in CPRD and 10 125 (18.6%) of CPRD events were recorded in HES when using the maximum date matching window of 28 days plus the time between admission and procedure. The main reasons for differences in case ascertainment included, re-recordings and miscoding in CPRD.Compared to HES, MLEAs are poorly recorded in CPRD predominantly due to re-recordings of events and miscoding procedures. CPRD data cannot solely be relied upon to ascertain cases of MLEA; however, HES linkage to CPRD may be useful to obtain medical history of diagnoses, medication and diagnostic tests.


Subject(s)
Amputation, Surgical , Electronic Health Records , Humans , England , Primary Health Care , Lower Extremity
6.
Br J Surg ; 109(8): 686-694, 2022 07 15.
Article in English | MEDLINE | ID: mdl-35552376

ABSTRACT

BACKGROUND: The aim was to determine the comparative benefits of structured high-pain exercise, structured low-pain exercise, and usual-care control, to identify which has the largest effect on walking ability in people with intermittent claudication (IC). METHODS: A network meta-analysis was undertaken to assess two outcomes: pain-free walking ability (PFWA) and maximal walking ability (MWA). Nine electronic databases were searched. Trials were included if they were: RCTS; involved adults with IC; had at least two of the following arms-structured low-pain exercise, structured high--pain exercise or usual-care control; and a maximal or pain-free treadmill walking outcome. RESULTS: Some 14 trials were included; results were pooled using the standardized mean difference (MD). Structured low-pain exercise had a significant large positive effect on MWA (MD 2.23, 95 percent c.i. 1.11 to 3.35) and PFWA (MD 2.26, 1.26 to 3.26) compared with usual-care control. Structured high-pain exercise had a significant large positive effect on MWA (MD 0.95, 0.20 to 1.70) and a moderate positive effect on PFWA (0.77, 0.01 to 1.53) compared with usual-care control. In an analysis of structured low- versus high pain exercise, there was a large positive effect in favour of low-pain exercise on MWA (MD 1.28, -0.07 to 2.62) and PFWA (1.50, 0.24 to 2.75); however, this was significant only for PFWA. CONCLUSION: There is strong evidence in support of use of structured high-pain exercise, and some evidence in support of structured low-pain exercise, to improve walking ability in people with IC compared with usual-care control (unstructured exercise advice).


Subject(s)
Exercise Therapy , Intermittent Claudication , Adult , Exercise , Exercise Test , Exercise Therapy/methods , Humans , Intermittent Claudication/therapy , Pain , Walking
7.
BMJ Open ; 11(10): e053599, 2021 10 06.
Article in English | MEDLINE | ID: mdl-34615685

ABSTRACT

OBJECTIVE: Estimate the prevalence/incidence/number of major lower extremity amputations (MLEAs) in the UK; identify sources of routinely collected electronic health data used; assess time trends and regional variation; and identify reasons for variation in reported incidence/prevalence of MLEA. DESIGN: Systematic review and narrative synthesis. DATA SOURCES: Medline, Embase, EMcare, CINAHL, The Cochrane Library, AMED, Scopus and grey literature sources searched from 1 January 2009 to 1 August 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Reports that provided population-based statistics, used routinely collected electronic health data, gave a measure of MLEA in adults in the general population or those with diabetes in the UK or constituent countries were included. DATA EXTRACTION AND SYNTHESIS: Data extraction and quality assessment using the Joanna Briggs Institute Critical Appraisal Instruments were performed by two reviewers independently. Due to considerable differences in study populations and methodology, data pooling was not possible; data were tabulated and narratively synthesised, and study differences were discussed. RESULTS: Twenty-seven reports were included. Incidence proportion for the general population ranged from 8.2 to 51.1 per 100 000 and from 70 to 291 per 100 000 for the population with diabetes. Evidence for trends over time was mixed, but there was no evidence of increasing incidence. Reports consistently found regional variation in England with incidence higher in the north. No studies reported prevalence. Differences in database use, MLEA definition, calculation methods and multiple procedure inclusion which, together with identified inaccuracies, may account for the variation in incidence. CONCLUSIONS: UK incidence and trends in MLEA remain unclear; estimates vary widely due to differences in methodology and inaccuracies. Reasons for regional variation also remain unexplained and prevalence uninvestigated. International consensus on the definition of MLEA and medical code list is needed. Future research should recommend standards for the reporting of such outcomes and investigate further the potential to use primary care data in MLEA epidemiology. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020165592.


Subject(s)
Amputation, Surgical , Lower Extremity , Adult , Humans , Incidence , Lower Extremity/surgery , Prevalence , United Kingdom/epidemiology
8.
Eur J Vasc Endovasc Surg ; 60(6): 829-835, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32912760

ABSTRACT

OBJECTIVE: Left renal vein (LRV) ligation is performed during open abdominal aortic aneurysm (AAA) repair to facilitate proximal anastomosis. Its impact on short, medium, and long term renal function has not been investigated in detail using appropriately validated endpoints. METHODS: This was a nested case control study using data from a prospectively maintained AAA institutional dataset (tertiary centre). A total of 76 patients who underwent elective open AAA repair and had LRV ligation (1 January 2012 to 1 January 2018) were individually case matched based on age (within two years), sex, estimated glomerular filtration rate (eGFR), American Society of Anesthesiologist (ASA) score, chronic kidney disease (CKD) stage, and history of diabetes with 76 patients who had open AAA repair without LRV ligation. Renal outcomes were compared between groups, including proportion of patients developing acute kidney injury (AKI) using the Kidney Disease Improving Global Outcomes (KDIGO) criteria, proportion developing major adverse kidney events (MAKE90) at 90 days (comprising mortality and/or decrease in eGFR >25%), and absolute decrease in eGFR at latest follow up. RESULTS: A higher proportion of patients developed AKI and MAKE90 in the LRV ligation group (AKI: 11 patients [14.8%] vs. 2 [2.6%], p = .009; MAKE90: 6 [7.9%] vs. 1 [1.3%] p = .053, in the LRV ligation and the non-LRV ligation groups, respectively) - even though the difference in the MAKE90 endpoint was not statistically significant. Changes in eGFR were not statistically different in the LRV ligation group at 90 days (4.0 ± 1.1 mL/min/1.73 m2vs. 4.4 ± 2.1, p = .64) or by the time of latest follow up (median: 28 months; 3.7 ± 1.6 vs. 2.6 ± 2.0, p = .55). CONCLUSION: Ligation of the LRV is associated with increased levels of AKI and renal deterioration in the early post-operative phase using validated reporting criteria; however, long term renal function does not seem to be affected.


Subject(s)
Acute Kidney Injury/etiology , Acute Kidney Injury/physiopathology , Aortic Aneurysm, Abdominal/surgery , Ligation/adverse effects , Renal Veins/surgery , Aged , Aged, 80 and over , Case-Control Studies , Female , Glomerular Filtration Rate , Humans , Male , Middle Aged , Postoperative Complications/etiology , Postoperative Complications/physiopathology , Postoperative Period , Recovery of Function , Retrospective Studies , Severity of Illness Index , Time Factors
9.
PLoS One ; 15(6): e0233961, 2020.
Article in English | MEDLINE | ID: mdl-32479512

ABSTRACT

Hundreds of target specific peptides are routinely discovered by peptide display platforms. However, due to the high cost of peptide synthesis only a limited number of peptides are chemically made for further analysis. Here we describe an accurate and cost effective method to bin peptides on-phage based on binding region(s), without any requirement for peptide or protein synthesis. This approach, which integrates phage and yeast display platforms, requires display of target and its alanine variants on yeast. Flow cytometry was used to detect binding of peptides on-phage to the target on yeast. Once hits were identified, they were synthesized to confirm their binding region(s) by HDX (Hydrogen deuterium exchange) and crystallography. Moreover, we have successfully shown that this approach can be implemented as part of a panning process to deplete non-functional peptides. This technique can be applied to any target that can be successfully displayed on yeast; it narrows down the number of peptides requiring synthesis; and its utilization during selection results in enrichment of peptide population against defined binding regions on the target.


Subject(s)
Cell Surface Display Techniques/methods , Peptide Library , Alanine/genetics , Alanine/metabolism , Bacteriophages/genetics , Bacteriophages/metabolism , Cell Surface Display Techniques/economics , Cost-Benefit Analysis , Flow Cytometry/economics , Flow Cytometry/methods , Interleukin-12 Subunit p40/genetics , Interleukin-12 Subunit p40/metabolism , Mutation , Protein Binding/genetics , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Reproducibility of Results , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism
10.
BMJ Open ; 10(6): e037053, 2020 06 11.
Article in English | MEDLINE | ID: mdl-32532778

ABSTRACT

INTRODUCTION: It is estimated that peripheral arterial disease occurs in one in five people aged over 60 years in the UK. Major lower limb amputation is a debilitating and life-changing potential outcome of peripheral arterial disease. A number of risk factors are involved in the development of the disease including smoking and diabetes. There is debate over the prevalence of major lower limb amputation in the UK with regional variations unexplained. The choice of data source can affect the epidemiological calculations and sources can also differ in the ability to explain variation. This study will aim to estimate the prevalence/incidence/number of major lower limb amputation in the UK. It will also identify sources of routinely collected electronic health data which report the epidemiology of major lower limb amputation in the UK. METHODS AND ANALYSIS: A systematic search of peer-reviewed journals will be conducted in Medline, Excerpta Medica database, Cumulative Index of Nursing and Allied Health Literature, Allied and Complementary Medicine Database, The Cochrane Library and Scopus. A grey literature search for government and parliament publications, conference abstracts, theses and unpublished articles will be performed. Articles will be screened against the inclusion/exclusion criteria and data extracted using a pretested extraction form by two independent reviewers. Prevalence, incidence or number of cases (depending on data reported) will be extracted. Disagreements will be resolved by discussion. Data synthesis will be performed either as a narrative summary or by meta-analysis. Heterogeneity will be assessed using the I2 statistic. If heterogeneity is low-moderate, pooled estimates will be calculated using random-effects models. If possible, meta-regression for time trends in the incidence of major lower limb amputation will be performed along with subgroup analysis, primarily in regional variation. ETHICS AND DISSEMINATION: Ethics approval is not required for this study as study data are anonymised and available in the public domain. Dissemination will be by publication in a peer reviewed journal and by appropriate conference presentation.PROSPERO registration numberCRD42020165592.


Subject(s)
Amputation, Surgical , Electronic Health Records , Lower Extremity/surgery , Peripheral Vascular Diseases/epidemiology , Peripheral Vascular Diseases/surgery , Aged , Humans , Incidence , Middle Aged , Prevalence , Research Design , Systematic Reviews as Topic , United Kingdom/epidemiology
11.
Eur J Vasc Endovasc Surg ; 58(3): 328-333, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31327538

ABSTRACT

INTRODUCTION: Over the short term endovascular aneurysm repair (EVAR) is associated with superior outcomes compared with open repair; however, the progression of renal function after EVAR remains unknown because of the use of inconsistent reporting measures. The aim was to define long term renal decline following elective EVAR using estimated glomerular filtration rate (eGFR). METHODS: The prospectively maintained in house database was used to identify consecutive patients having elective EVAR who had been followed up for more than five years. Overall, 275 patients (23 females, 8%; mean age, 75 years) who were not previously on renal replacement therapy (RRT) were included (January 2000 to July 2010). Pre-operative, post-operative, and most recent eGFR values were evaluated using the chronic kidney disease epidemiology collaboration equation. The primary outcome was change in eGFR at latest follow up. RESULTS: Patients were followed up over a median of 9 years (range 5-17 years). Their mean eGFR dropped from a pre-operative value of 67 mL/min/1.73 m2 (standard deviation [SD]: 9.4) to 52 mL/min/1.73 m2 (SD 7.7), which amounts to a yearly loss of 1.7 units; six patients (2%) required RRT (dialysis) during late follow up. Patients requiring RRT and those with an eGFR loss exceeding 20% at latest follow up compared with baseline were more likely to die during late follow up (odds ratio 2.4 and 3.3 respectively, p < .001). CONCLUSION: This analysis, with some of the longest available follow up to date, suggests that patients undergoing EVAR may experience a significant long term decrease in renal function. This needs to be taken into account when offering EVAR in younger patients; renal follow up and preservation should be optimised in this patient group.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Endovascular Procedures/adverse effects , Forecasting , Glomerular Filtration Rate/physiology , Kidney/physiopathology , Renal Insufficiency, Chronic/physiopathology , Aged , Aged, 80 and over , Aortic Aneurysm, Abdominal/diagnosis , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Prospective Studies , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/etiology , United Kingdom/epidemiology
12.
Diab Vasc Dis Res ; 15(5): 367-374, 2018 09.
Article in English | MEDLINE | ID: mdl-29874945

ABSTRACT

INTRODUCTION: Diabetes mellitus appears to be negatively associated with abdominal aortic aneurysm; however, the mechanisms underlying this relationship remain poorly understood. The aim of this article is to provide a comprehensive review of the currently understood biological pathways underlying this relationship. METHODS: A review of the literature ('diabetes' OR 'hyperglycaemia' AND 'aneurysm') was performed and relevant studies grouped into biological pathways. RESULTS: This review identified a number of biological pathways through which diabetes mellitus may limit the presence, growth and rupture of abdominal aortic aneurysms. These include those influencing extracellular matrix volume, extracellular matrix glycation, the formation of advanced glycation end-products, inflammation, oxidative stress and intraluminal thrombus biology. In addition, there is an increasing evidence to suggest that the medications used to treat diabetes can also limit the development and progression of abdominal aortic aneurysms. CONCLUSION: The negative association between diabetes and abdominal aortic aneurysm is robust. Future studies should attempt to target the pathways identified in this review to develop novel therapeutic agents aimed at slowing or even halting aneurysm progression.


Subject(s)
Aorta, Abdominal/pathology , Aortic Aneurysm, Abdominal/etiology , Diabetes Mellitus , Vascular Remodeling , Animals , Aorta, Abdominal/drug effects , Aorta, Abdominal/metabolism , Aortic Aneurysm, Abdominal/blood , Aortic Aneurysm, Abdominal/diagnosis , Aortic Aneurysm, Abdominal/prevention & control , Biomarkers/blood , Blood Glucose/metabolism , Diabetes Mellitus/blood , Diabetes Mellitus/diagnosis , Diabetes Mellitus/drug therapy , Dilatation, Pathologic , Disease Progression , Extracellular Matrix/metabolism , Glycation End Products, Advanced/blood , Humans , Hypoglycemic Agents/therapeutic use , Inflammation Mediators/metabolism , Oxidative Stress , Risk Factors , Vascular Remodeling/drug effects
13.
JAMA Cardiol ; 3(1): 26-33, 2018 01 01.
Article in English | MEDLINE | ID: mdl-29188294

ABSTRACT

Importance: Risk factors for abdominal aortic aneurysm (AAA) are largely unknown, which has hampered the development of nonsurgical treatments to alter the natural history of disease. Objective: To investigate the association between lipid-associated single-nucleotide polymorphisms (SNPs) and AAA risk. Design, Setting, and Participants: Genetic risk scores, composed of lipid trait-associated SNPs, were constructed and tested for their association with AAA using conventional (inverse-variance weighted) mendelian randomization (MR) and data from international AAA genome-wide association studies. Sensitivity analyses to account for potential genetic pleiotropy included MR-Egger and weighted median MR, and multivariable MR method was used to test the independent association of lipids with AAA risk. The association between AAA and SNPs in loci that can act as proxies for drug targets was also assessed. Data collection took place between January 9, 2015, and January 4, 2016. Data analysis was conducted between January 4, 2015, and December 31, 2016. Exposures: Genetic elevation of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Main Outcomes and Measures: The association between genetic risk scores of lipid-associated SNPs and AAA risk, as well as the association between SNPs in lipid drug targets (HMGCR, CETP, and PCSK9) and AAA risk. Results: Up to 4914 cases and 48 002 controls were included in our analysis. A 1-SD genetic elevation of LDL-C was associated with increased AAA risk (odds ratio [OR], 1.66; 95% CI, 1.41-1.96; P = 1.1 × 10-9). For HDL-C, a 1-SD increase was associated with reduced AAA risk (OR, 0.67; 95% CI, 0.55-0.82; P = 8.3 × 10-5), whereas a 1-SD increase in triglycerides was associated with increased AAA risk (OR, 1.69; 95% CI, 1.38-2.07; P = 5.2 × 10-7). In multivariable MR analysis and both MR-Egger and weighted median MR methods, the association of each lipid fraction with AAA risk remained largely unchanged. The LDL-C-reducing allele of rs12916 in HMGCR was associated with AAA risk (OR, 0.93; 95% CI, 0.89-0.98; P = .009). The HDL-C-raising allele of rs3764261 in CETP was associated with lower AAA risk (OR, 0.89; 95% CI, 0.85-0.94; P = 3.7 × 10-7). Finally, the LDL-C-lowering allele of rs11206510 in PCSK9 was weakly associated with a lower AAA risk (OR, 0.94; 95% CI, 0.88-1.00; P = .04), but a second independent LDL-C-lowering variant in PCSK9 (rs2479409) was not associated with AAA risk (OR, 0.97; 95% CI, 0.92-1.02; P = .28). Conclusions and Relevance: The MR analyses in this study lend support to the hypothesis that lipids play an important role in the etiology of AAA. Analyses of individual genetic variants used as proxies for drug targets support LDL-C lowering as a potential effective treatment strategy for preventing and managing AAA.


Subject(s)
Aortic Aneurysm, Abdominal/genetics , Hypolipidemic Agents/therapeutic use , Lipid Metabolism/genetics , Polymorphism, Single Nucleotide/genetics , Triglycerides/metabolism , Cholesterol, HDL/genetics , Cholesterol, HDL/metabolism , Cholesterol, LDL/genetics , Cholesterol, LDL/metabolism , Genome-Wide Association Study , Humans , Mendelian Randomization Analysis , Risk Factors , Triglycerides/genetics
14.
Eur J Vasc Endovasc Surg ; 54(5): 564-572, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28919267

ABSTRACT

OBJECTIVE/BACKGROUND: The first paper in this series observed that pre-operative baroreceptor dysfunction and poorly controlled hypertension were independently predictive for identifying patients who went on to require treatment for post-endarterectomy hypertension (PEH). The second paper examines the influence of intra-operative patient, transcranial Doppler (TCD) ultrasound, and anaesthetic variables on the incidence of PEH. METHODS: In total, 106 patients underwent carotid endarterectomy (CEA) under general anaesthesia. Systolic blood pressure (SBP) changes, anaesthetic and vasoactive agents, analgesia, and post-operative pain scores, as well as TCD derived changes in middle cerebral artery (MCA) velocity during surgery were recorded. Patients who met pre-existing unit criteria for treating PEH after CEA (SBP > 170 mmHg without symptoms or SBP > 160 mmHg with headache/seizure/neurological deficit) were treated according to an established and validated protocol. RESULTS: In total, 40/106 patients (38%) required treatment for PEH following CEA (26 in theatre recovery [25%], 27 back on the vascular surgery ward [25%]), whereas seven (7%) had SBP surges > 200 mmHg on the ward. Patients requiring treatment for PEH had significantly higher pre-induction SBP (174 ± 21 mmHg vs. 153 ± 21 mmHg; p < .001), the greatest decreases in SBP after induction of anaesthesia (median decrease 100 ± 32 mmHg vs. 83 ± 24 mmHg; p = .01) and were significantly more likely to experience moderate/severe pain scores post-operatively (p = .003). Logistic regression analysis of the pre- and intra-operative data revealed that higher pre-induction mean SBP and lower pre-operative (impaired) BRS were the only independent predictors of PEH. CONCLUSION: This analysis of intra-operative variables has demonstrated that patients with poorly controlled and/or labile hypertension at induction of general anaesthesia were those at greatest risk of requiring treatment for PEH in the post-operative period after CEA. No other variables, including use of vasopressors, treatment of hypotension, anaesthetic agents, or changes in MCA velocity after clamp release and restoration of flow were able to predict who might go on to require treatment for PEH. Identification of at-risk individuals and aggressive blood pressure control in the post-operative period remains the mainstay of treatment.


Subject(s)
Anesthesia, General , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/surgery , Endarterectomy, Carotid/adverse effects , Hypertension/epidemiology , Postoperative Complications/epidemiology , Aged , Aged, 80 and over , Baroreflex , Blood Flow Velocity , Carotid Stenosis/physiopathology , Cerebrovascular Circulation , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged , Risk Factors , Ultrasonography, Doppler, Transcranial
15.
Eur Heart J ; 37(46): 3452-3460, 2016 Dec 07.
Article in English | MEDLINE | ID: mdl-27520304

ABSTRACT

AIMS: To quantify the difference in long-term survival and cardiovascular morbidity between women and men undergoing elective abdominal aortic aneurysm (AAA) repair at National Health Service hospitals in England. METHODS AND RESULTS: Patients having elective repair of AAA were reviewed using the Hospital Episode Statistics and Office for National Statistics (ONS) datasets. The primary outcome measure was 30-day mortality and the secondary outcomes were 1-year, 5-year, and aortic-related mortality and post-operative complication rates. We used logistic regression and survival models to assess risk factors on the primary and secondary outcomes. Between 1 April 2002 and 31 March 2013, a total of 31 090 patients (4795 women and 26 295 men) underwent open AAA repair. Between 1 January 2006 and 31 March 2013, a total of 16 777 patients (2036 women and 14 741 men) underwent endovascular aneurysm repair (EVAR). All-cause and aortic-related mortalities at 30 days, 1 year, and 5 years were all higher in women, despite a lower prevalence of pre-operative cardiovascular risk factors. Female sex was a significant independent risk factor for 30-day mortality in both open repair [odds ratio (OR) 1.39; 95% confidence interval (CI) 1.25-1.56; P < 0.001] and EVAR (OR 1.57; 95% CI 1.23-2.00; P < 0.001) groups. Based on an all-cause long-term survival model, conditional on 30-day survival, the estimated hazard for women in the open repair group was significantly (P = 0.006) higher than men, but the sex difference was not significant in the EVAR group (P = 0.356). In the open repair group, women had significantly (P < 0.001) higher cumulative incidence probabilities for both aortic-related mortality and other-cause mortality. In the EVAR group, women had significantly (P < 0.001) higher mean cumulative incidence probabilities for the aortic-related mortality compared with men, but not for the other-cause mortality (P = 0.235). CONCLUSION: Women undergoing elective AAA repair at National Health Service hospitals in England had increased short- and long-term mortality and post-operative morbidity compared with men. These findings can be used to improve pre-operative counselling for women undergoing AAA repair, and highlight the need for female-specific pre-, peri-, and post-operative management strategies.


Subject(s)
Aortic Aneurysm, Abdominal , Elective Surgical Procedures , Endovascular Procedures , England , Female , Humans , Male , National Health Programs , Retrospective Studies , Risk Assessment , Risk Factors , Sex Characteristics , Treatment Outcome
16.
Interact Cardiovasc Thorac Surg ; 23(3): 477-85, 2016 09.
Article in English | MEDLINE | ID: mdl-27222002

ABSTRACT

Previous research suggests an association between hospital volume and outcomes in high-risk surgical pathologies. The association between hospital volume and outcomes in patients with isolated descending thoracic aortic aneurysms (DTAAs) and type-B thoracic aortic dissections (TBADs) is conflicting. We aimed to investigate this in a literature review and meta-analysis. A systematic review of the literature was performed to identify studies reporting mortality and morbidity following repair (elective or emergency) of DTAA and/or TBAD using the Medline and Embase Databases (2000-2015). Hospital volume was assessed based on the number of patients treated per institution: low volume (1-5 cases per year), medium volume (6-10) and high volume (>10). The primary outcome of interest was all-cause mortality during inpatient stay and at 30 days. Eighty-four series of non-dissecting DTAA or TBAD were included in data synthesis (4219 patients; mean age: 62 years; males: 73.5%). For all patients (emergency and elective) undergoing DTAA repair, in-hospital mortality was 8% [95% confidence interval (CI): 6-8%]. Results were not superior in high-volume centres (8 vs 6 vs 11% for high-, medium- and low-volume, respectively). Sub-analyses for emergency and elective repairs showed no significant differences. For TBAD repairs, in the combined population (emergency and elective), results reached borderline significance (P = 0.0475), favouring high-volume centres (6 vs 11 vs 14%), but this association disappeared when emergency and elective repairs were analysed separately. Nine series reported outcomes at 1 year and 5 series followed DTAA and 18 TBAD treatment. No meaningful long-term comparisons were possible due to the lack of data. No significant associations were detected between hospital volume and subsequent mortality following DTAA or TBAD treatment. Data were heterogeneous and long-term results were scarcely reported. A well-designed longitudinal study of sufficient size is required to inform future strategies in this area.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Aortic Aneurysm, Thoracic/surgery , Aortic Dissection/surgery , Blood Vessel Prosthesis Implantation , Hospitals, High-Volume , Hospitals, Low-Volume , Aortic Aneurysm, Abdominal/mortality , Aortic Aneurysm, Thoracic/mortality , Cause of Death/trends , Global Health , Hospital Mortality/trends , Humans , Survival Rate/trends , Treatment Outcome
17.
Vasc Health Risk Manag ; 12: 53-63, 2016.
Article in English | MEDLINE | ID: mdl-27042087

ABSTRACT

Type II endoleaks are the most common endovascular complications of endovascular abdominal aortic aneurysm repair (EVAR); however, there has been a divided opinion regarding their significance in EVAR. Some advocate a conservative approach unless there is clear evidence of sac expansion, while others maintain early intervention is best to prevent adverse late outcomes such as rupture. There is a lack of level-one evidence in this challenging group of patients, and due to a low event rate of complications, large numbers of patients would be required in well-designed trials to fully understand the natural history of type II endoleak. This review will discuss the imaging, management, and outcome of patients with isolated type II endoleaks following infra-renal EVAR.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Blood Vessel Prosthesis Implantation/adverse effects , Embolization, Therapeutic , Endoleak/therapy , Endovascular Procedures/adverse effects , Aortic Aneurysm, Abdominal/diagnosis , Aortography/methods , Embolization, Therapeutic/adverse effects , Endoleak/diagnosis , Endoleak/etiology , Humans , Reoperation , Risk Assessment , Risk Factors , Tomography, X-Ray Computed , Treatment Outcome , Ultrasonography, Doppler, Color
18.
Ann Vasc Surg ; 31: 52-9, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26658089

ABSTRACT

BACKGROUND: Postoperative acute kidney injury (AKI) may occur in up to 18% of elective endovascular abdominal aortic aneurysm repair (EVAR) and has been associated with poor outcome; however, it is not clear which patients are at highest risk, to target renoprotection effectively. We sought to determine the predictive factors of AKI after elective EVAR. METHODS: Overall, 947 patients undergoing elective EVAR between January 2004 and December 2014 were analyzed, using prospectively collected data. Postoperative AKI was defined by serum creatinine change within 48 hr, as per the Kidney Disease Improving Global Outcomes guidelines. Cardiovascular and kidney-disease risk factors were entered in univariate and multivariate analyses to assess influence on AKI development. RESULTS: Overall, 167 (17.6%) patients developed AKI but only 2 patients required dialysis perioperatively. At multivariate analysis, adjusted for established AKI-risk factors and parameters that differed between groups at baseline, preoperative estimated glomerular filtration rate (eGFR; as per the chronic kidney disease epidemiology [CKD] formula); odds ratio (OR): 1.02 (per unit decrease); 95% confidence interval (CI): 1.003-1.041; P = 0.025; and chronic kidney disease (CKD) stage > 2 (OR: 1.28; 95% CI: 1.249-2.531, P = 0.001) were associated with development of AKI. CONCLUSIONS: AKI was common after elective infrarenal EVAR and preoperative renal function appears to be the main factor associated with AKI. Patients with a low eGFR need to be targeted with more aggressive renal protection.


Subject(s)
Acute Kidney Injury/etiology , Aortic Aneurysm, Abdominal/surgery , Blood Vessel Prosthesis Implantation/adverse effects , Endovascular Procedures/adverse effects , Kidney/physiopathology , Renal Insufficiency, Chronic/physiopathology , Acute Kidney Injury/diagnosis , Acute Kidney Injury/physiopathology , Aged , Aortic Aneurysm, Abdominal/complications , Aortic Aneurysm, Abdominal/diagnosis , Biomarkers/blood , Chi-Square Distribution , Creatinine/blood , Elective Surgical Procedures , Female , Glomerular Filtration Rate , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Predictive Value of Tests , Registries , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/diagnosis , Retrospective Studies , Risk Factors , Severity of Illness Index , Treatment Outcome
19.
Am J Nephrol ; 42(4): 285-94, 2015.
Article in English | MEDLINE | ID: mdl-26495853

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) has been associated with all-cause short- and long-term mortality. However, its association with cardiovascular (CV) events remains unclear. We sought to investigate this in patients undergoing open (OAR) or endovascular (EVAR) abdominal aortic aneurysm repair, as they are likely to develop both AKI and CV morbidity. A meta-analysis was subsequently performed to confirm this in other CV-interventions. METHODS: AKI-incidence was assessed in a multicentre-cohort of 1,068 patients undergoing EVAR (947 individuals) or OAR electively using the 'Acute Kidney Injury Network' criteria. A composite-endpoint was used, consisting of non-fatal myocardial infarction (MI), stroke, vascular event, hospitalisation due to heart failure and CV death. A systematic literature review identified studies reporting AKI-incidence and CV events. Risk ratios (RRs) at 1 and 5 years were combined using meta-analysis. RESULTS: During a median follow-up of 62 months (range 11-121), AKI was associated with CV events on adjusted (for CV risk-factors) analyses (Incidence 36% of EVAR, 32% of OAR patients; hazard ratio 1.73, 95% CI 1.06-3.39, p=0.03) for the overall population. In the meta-analysis, 7 studies reported incidence of MI on 23,936 patients 1-year after coronary intervention (PCI) with a pooled RR of 1.76 (95% CI 1.45-2.83, p<0.001); at 2 years, 3 studies reported MI incidence on 17,773 patients after PCI with a pooled RR of 1.34 (95% CI 1.10-1.63, p=0.003). MI-incidence was reported 5 years after cardiac surgery by 3 studies (33,701 patients) with a pooled RR of 1.60 (95% CI 1.43-1.81). CONCLUSION: AKI is associated with long-term CV events after surgery or endovascular intervention.


Subject(s)
Acute Kidney Injury/epidemiology , Aortic Aneurysm, Abdominal/surgery , Cardiovascular Diseases/mortality , Endovascular Procedures , Heart Failure/epidemiology , Hospitalization/statistics & numerical data , Myocardial Infarction/epidemiology , Postoperative Complications/epidemiology , Stroke/epidemiology , Aged , Aged, 80 and over , Cardiovascular Diseases/epidemiology , Cohort Studies , Female , Humans , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Percutaneous Coronary Intervention , Prognosis , Proportional Hazards Models , Risk Factors , Vascular Surgical Procedures
20.
Clin J Am Soc Nephrol ; 10(11): 1930-6, 2015 Nov 06.
Article in English | MEDLINE | ID: mdl-26487770

ABSTRACT

BACKGROUND AND OBJECTIVES: Endovascular repair (EVAR) is a common treatment for abdominal aortic aneurysm (AAA). However, its long-term effects on renal function remain unclear. We aimed to assess long-term renal dysfunction after EVAR using a contemporary estimate of GFR and to compare long-term renal outcomes in patients after EVAR with open aneurysm repair (OAR) and in patients without an AAA. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: We performed a nested case-matched analysis of 726 patients (using a prospectively maintained database for repairs that took place between January 2000 and May 2010 in a tertiary center): 121 patients undergoing OAR (with data at baseline and 5 years postrepair) were case matched (age, sex, smoking, diabetes, baseline eGFR) to patients undergoing suprarenal and infrarenal fixation EVAR (242 in each group) and to 121 patients undergoing carotid endarterectomy (CEA) without AAA. Changes in eGFR were compared (1 and 5 years). RESULTS: The OAR patients lost an average of 7.4 ml/min per 1.73 m2 at 5 years (95% confidence interval [95% CI], 4.8 to 10.6), compared with 8.2 ml/min per 1.73 m2 (95% CI, 6.5 to 10.8; P<0.001) for infrarenal-fixation EVAR, 16.9 ml/min per 1.73 m2 (95% CI, 13.0 to 21.9, P<0.001) for suprarenal-fixation EVAR, and 5.4 ml/min per 1.73 m2 (95% CI, 1.7 to 7.5; P<0.001) for CEA. The decrease in eGFR was steeper during the first postoperative year, with each group losing -2.2 ml/min per 1.73 m2 (infrarenal-fixation EVAR), -10.7 ml/min per 1.73 m2 (suprarenal-fixation EVAR), and -4.6 ml/min per 1.73 m2 (OAR), compared with -1.9 ml/min per 1.73 m2 for CEA. CONCLUSIONS: Elective EVAR is associated with a significant decline in eGFR after 5 years, which is steeper in the first postoperative year and more pronounced compared with a similar population with atherosclerotic disease.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Endovascular Procedures , Kidney/physiology , Humans , Time Factors , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL
...