Biomedical subjects
Publications and source records attributed to R M Greenhalgh.
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OBJECTIVE: To assess whether a pragmatic policy of perioperative beta-blockade, with metoprolol, reduced the 30-day cardiovascular morbidity and mortality and reduced the length of hospital stay in average patients undergoing infrarenal vascular surgery. METHODS: This was a double-blind randomized placebo-controlled trial that occurred in vascular surgical units in four UK hospitals. Participants were 103 patients without previous myocardial infarction who had infrarenal vascular surgery between July 2001 and March 2004. Interventions were oral metoprolol (50 mg twice daily, supplemented by intravenous doses when necessary) or placebo from admission until 7 days after surgery. Holter monitors were kept in place for 72 hours after surgery. RESULTS: Eighty men and 23 women (median age, 73 years) were randomized, 55 to metoprolol and 48 to placebo, and 97 (94%) underwent surgery during the trial. The most common operations were aortic aneurysm repair (38%) and distal bypass (29%). Intraoperative inotropic support was required in 64% and 92% of patients in the placebo and metoprolol groups, respectively. Within 30 days, cardiovascular events occurred in 32 patients, including myocardial infarction (8%), unstable angina (9%), ventricular tachycardia (19%), and stroke (1%). Four (4%) deaths were reported. Cardiovascular events occurred in 15 (34%) and 17 (32%) patients in the placebo and metoprolol groups, respectively (unadjusted relative risk, 0.94; 95% confidence interval, 0.53-1.66; adjusted [for age, sex, statin use, and aortic cross-clamping] relative risk, 0.87; 95% confidence interval, 0.48-1.55). Time from operation to discharge was reduced from a median of 12 days (95% confidence interval, 9-19 days) in the placebo group to 10 days (95% confidence interval, 8-12 days) in the metoprolol group (adjusted hazard ratio, 1.71; 95% confidence interval, 1.09-2.66; P < .02). CONCLUSIONS: Myocardial ischemia was evident in a high proportion (one third) of the patients after surgery. A pragmatic regimen of perioperative beta-blockade with metoprolol did not seem to reduce 30-day cardiovascular events, but it did decrease the time from surgery to discharge.
BACKGROUND: The elastinolytic cysteine proteases, including cathepsins S and K, are overexpressed at sites of arterial elastin damage. Cystatin C, an inhibitor of these enzymes, is expressed in arterial smooth muscle cells; an imbalance in cystatin C has been implicated in the aortic wall degeneration observed in abdominal aortic aneurysms (AAAs). The aim of the study was to investigate the impact of a polymorphism in the signal peptide of the cystatin C gene on the growth of small AAAs. METHODS: Some 424 patients with a small AAA (4.0-5.5 cm) were monitored for AAA growth by ultrasonography and provided a DNA sample for analysis of the + 148 G > A polymorphism in the cystatin C signal peptide and the-82 G > C polymorphism in the gene promoter. The median length of follow-up was 2.8 years and AAA growth rates were calculated by linear regression analysis. RESULTS: For patients of + 148 GG (n = 263), GA (n = 147) and AA (n = 20) genotypes, the mean(s.d.) AAA growth rates were 0.37(0.29), 0.37(0.23) and 0.30(0.26) cm, and initial diameters were 4.58(0.35), 4.58(0.35) and 4.62(0.36) cm, respectively. Patients of + 148 AA genotype had a slower aneurysm growth rate (unadjusted P = 0.058; after adjustment for age, sex, initial AAA diameter and smoking, P = 0.027). There also was a trend for the rare homozygotes of the-82 C allele to have slower AAA growth (adjusted P = 0.055). Smoking history had a stronger association with aneurysm growth (P = 0.003). CONCLUSION: There was a weak association between variation in the cystatin C gene and AAA growth. Medical strategies to limit AAA growth might include the inhibition of cysteine proteases.
BACKGROUND: This was a randomized clinical trial to determine the efficacy and safety of a 'blanket' protocol of low molecular weight heparin (LMWH) and the best length of antiembolism stocking, for every patient requiring surgery under general anaesthesia. METHODS: Of 426 patients interviewed, 376 agreed to be randomized to receive one of three types of stocking: thigh-length Medi thrombexin climax (Medi UK, Hereford, UK), knee-length thrombexin climax and thigh-length Kendall T.E.D. (Tyco Healthcare UK, Redruth, UK). All patients received LMWH thromboprophylaxis. Duplex ultrasonography was used to assess the incidence of postoperative deep vein thrombosis (DVT). RESULTS: No postoperative DVT occurred in 85 patients at low or moderate risk. Nineteen DVTs occurred, all in the 291 high-risk patients: two with the Medi thigh-length stockings, 11 with the Medi knee-length stockings (odds ratio 0.18 (95 per cent confidence interval 0.04 to 0.82); P = 0.026) and six with the Kendall T.E.D. thigh-length stockings. No patient developed a pulmonary embolism. Stocking groups were similar for age, sex, thromboembolic risk, type of operation and compliance. One significant bleeding complication occurred. CONCLUSION: A single protocol comprising LMWH and thigh-length stockings abolished DVT in low- and moderate-risk patients, and reduced the rate of DVT to 2 per cent in high-risk patients.
OBJECTIVE: Exercise advice is the main treatment for symptom relief in the UK for patients with mild to moderate Intermittent Claudication (IC). Would a weekly exercise and motivation class for 6 months offer adjuvant benefit over written and verbal exercise advice alone? PATIENTS AND METHODS: Fifty-nine patients attending a regional vascular centre for whom IC was the main factor affecting mobility were randomised to either exercise advice alone (n=30) or exercise advice with a once a week 45 min supervised exercise/motivation class (n=29). The mean age was 68 years. Baseline and 6-month assessment included a Quality of Life Questionnaire--the Short-Form-36, the Charing Cross Symptom Specific Claudication Questionnaire (CCCQ) and treadmill walking distance (3.5 km/h 12%). RESULTS: At 6-month follow-up the supervised exercise group had improved their treadmill walking by 129% compared to 69% in the advice alone group (p=0.001). This significant improvement was maintained at the subsequent 9 and 12-month follow-up assessments. By the 9-month stage the advice only group CCCQ score had improved 16% from baseline, while the supervised exercise group had a significantly better 43% improvement in base line score (p<0.05). Self reported frequency of walks was higher in the exercise class group being significant for improvement in CCCQ score. CONCLUSION: A weekly, supervised exercise and motivation class for a 6-month period provides a significant improvement in patients' symptoms, quality of life, and distance walked compared with advice alone and this improvement continues after attendance at class has ceased.
BACKGROUND: A stress test is required in patients with a resting ankle brachial pressure index (ABPI) of >0.9 in whom peripheral arterial disease (PAD) is suspected. OBJECTIVE: To see if the Stresst'er Ergometer could mimic a standard 1 min treadmill exercise test and successfully diagnose the presence of significant PAD. METHODS: Legs with a resting ABPI >0.9, a positive exercise test and PAD confirmed on Duplex ultrasound, underwent various protocols on the Stresst'er Ergometer. The results were compared to control legs with no PAD (normal stress test). RESULTS: By making various adjustments to the rate and duration of the exercise, the resistance provided by the Stresst'er to the exercise and the timing of the post exercise ABPI measurement it was possible to accurately diagnose significant PAD. CONCLUSION: Using an appropriate protocol it is possible to use the Stresst'er Ergometer to assist in the diagnosis of significant PAD. Being a portable, space saving device, the Stresst'er offers the opportunity of diagnosis outside the vascular laboratory. This would facilitate medical therapy to at risk patients.
OBJECTIVES: The endovascular aneurysm repair (EVAR) trials aim to assess the efficacy of EVAR in the treatment of AAA in terms of mortality, quality of life, durability and cost-effectiveness. DESIGN: Male and female patients aged at least 60 years with an AAA diameter measuring at least 5.5 cm on a computed tomography (CT) scan are assessed for anatomical suitability for EVAR. Suitable patients are offered entry either into EVAR Trial 1 if they are considered fit for conventional open repair or EVAR Trial 2 if they are considered unfit. EVAR 1 randomly allocates patients to EVAR or open repair and EVAR 2 randomly allocates patients to EVAR with best medical treatment or best medical treatment alone. Target recruitment for EVAR Trials 1 and 2 is 900 and 280 patients, respectively. PROGRESS: Recruitment began in September 1999 and there are currently 40 UK centres participating in the trials. Monthly targets are being exceeded in EVAR Trial 1 with 1037 patients randomised by October 2003. EVAR Trial 2 is also meeting monthly targets with a total of 319 patients randomised. When recruitment closes in December 2003 patients will need to be followed for at least 1 year from their operation. Publication of full results for both trials is expected in mid 2005.
BACKGROUND: Two clinical trials, one British and one American, have shown that early, prophylactic elective surgery does not improve five-year survival among patients with small abdominal aortic aneurysms. We report long-term outcomes in the United Kingdom Small Aneurysm Trial. METHODS: We randomly assigned 1090 patients, 60 to 76 years of age, with small abdominal aortic aneurysms (diameter, 4.0 to 5.5 cm) to one of two groups: 563 were assigned to undergo early elective surgery, and 527 were assigned to undergo surveillance by ultrasonography. Patients were followed in the trial until June 1998 and thereafter until August 2001; the mean duration of follow-up was 8 years (range, 6 to 10). RESULTS: The mean duration of survival was 6.5 years among patients in the surveillance group, as compared with 6.7 years among patients in the early-surgery group (P=0.29). The adjusted hazard ratio for death from any cause in the early-surgery group as compared with the surveillance group was 0.83 (95 percent confidence interval, 0.69 to 1.00; P=0.05). The 30-day operative mortality in the early-surgery group (5.5 percent) led to an early disadvantage in terms of survival. The survival curves crossed at three years, and at eight years, mortality in the early-surgery group was 7.2 percentage points lower than that in the surveillance group (P=0.03). There was no evidence that age, sex, or the initial size of the aneurysm modified the hazard ratio or that delayed surgery in the surveillance group increased 30-day postoperative mortality. Death was attributable to a ruptured aneurysm in 19 of the 411 men who died (5 percent) and in 12 of the 85 women who died (14 percent) (P=0.001). The rate of early cessation of smoking was higher in the early-surgery group than in the surveillance group. CONCLUSIONS: Among patients with a small abdominal aortic aneurysm, we found no long-term difference in mean survival between the early-surgery and surveillance groups, although after eight years, total mortality was lower in the early-surgery group. This difference may be attributed in part to beneficial changes in lifestyle adopted by members of the early-surgery group.
OBJECTIVE: the ability of colour duplex to accurately locate incompetent venous sites has been widely published; its value in pre-operative marking in simple primary varicose vein surgery is evaluated in this study. DESIGN OF STUDY: prospective randomised controlled trial. SETTING: regional vascular service, hospital patients. SUBJECTS: consecutive patients (149) undergoing primary varicose vein surgery where the only difference was one group of patients received duplex marking prior to surgery. Six weeks and 12 months post-operatively all patients had a colour duplex scan to determine the accuracy of surgery and the presence of residual/recurrent varicose veins and completed the Aberdeen, SF-36, and EuroQol quality of life questionnaires. INTERVENTIONS: varicose vein surgery. MAIN OUTCOME MEASURES: Duplex evidence of venous incompetence, quality of life measures using the SF-36 and Aberdeen Varicose Veins Questionnaire. RESULTS: pre-operative marking of primary varicose veins by skilled duplex ultrasonography does not improve the accuracy or recurrence rate following surgery. Quality of life improved significantly following surgery in both groups, however there was no difference in this improvement between the groups. CONCLUSION: the trial has not demonstrated any additional benefit of pre-operative colour duplex marking over that of clinical and hand held Doppler marking in terms of satisfactory varicose vein surgery performance at 6 weeks or 12 months in patients with primary varicose veins of the long saphenous system. It role in the short saphenous system is less clear.
BACKGROUND: Abdominal aortic aneurysm is a multifactorial disorder in which inflammation is an important pathophysiological feature. In explant culture, aneurysm biopsies secrete large amounts of interleukin-6 (IL-6), and among aneurysm patients, the circulating concentration of IL-6 appears to be increased. METHODS AND RESULTS: We investigated, in 19 patients, whether aneurysm wall was an important source of circulating IL-6. We also tested the hypotheses, in 466 patients with a small aneurysm, that (1) high concentrations of circulating IL-6 signaled rapid aneurysm growth and (2) the -174 G-->C polymorphism in the IL-6 promoter predicted survival. For 19 patients with large or inflammatory aneurysms, the concentration of IL-6 was higher in the iliac arteries than the brachial arteries (median difference 26.5 pg/mL, this difference increasing with aneurysm diameter, P=0.01). In 466 patients with small aneurysms, the frequency of the -174 C allele (0.40) was similar to that in a normal healthy population. Patients of GG genotype had lower plasma concentrations of IL-6 than patients of GC and CC genotypes (medians 1.9, 4.8, and 15.6 pg/mL, respectively, Kruskal-Wallis P=0.047). Cardiovascular and all-cause mortalities were lower for patients of GG genotype than for patients of GC and CC genotype: hazard ratios 0.32 (95% CI 0.12 to 0.93), P=0.036, and 0.51 (95% CI 0.25 to 1.00), P=0.05, respectively. There was no association between plasma IL-6 or IL-6 genotype and aneurysm growth. CONCLUSIONS: Aortic aneurysms appear to be an important source of circulating IL-6, the concentration being influenced by genotype. For patients with small aneurysms, the -174 G-->C IL-6 genotype predicts future cardiovascular mortality.
BACKGROUND AND PURPOSE: the ankle/brachial pressure index (ABPI) has been shown to be a reliable marker of cardiovascular risk in population studies. We investigated whether the ABPI was a useful prognostic index for patients with abdominal aortic aneurysm. METHODS: patients entered into the U.K. Small Aneurysm Trial and Study had their ABPI measured in both legs at baseline (mean ABPI reported) and were followed up until 30 June 1998, with information about cause of death being obtained from the Office of National Statistics. This study focussed on cardiovascular and all-cause mortality. RESULTS: a total of 1827 men and 478 women, mean age 69 years, median aneurysm diameter 4.4 cm, were followed up for a median of 5.7 years. A total of 829 deaths were reported (rate 8.1 per 100 person-years), 546 (66%) from cardiovascular causes. The all-cause mortality risk increased as the ABPI decreased, hazard ratio 1.25 per 0.2 unit decrease in ABPI (95% CI 1.17 to 1.34, p<0.001). For patients in the lowest tertile group (ABPI <0.87) there were 11.6 deaths per 100 person-years. This increased risk persisted after adjustment for age, sex, evidence of ischaemia on resting ECG and initial aneurysm diameter, adjusted hazard ratio 1.17 per 0.2 unit decrease in ABPI (95% CI 1.07 to 1.28, p<0.001). CONCLUSION: the ankle/brachial pressure index is an important prognostic indicator for patients with abdominal aortic aneurysm. Patients with an ABPI below 0.87 (limit of lowest tertile) have the highest mortality risk and best clinical practice demands that attention is focussed on active treatment to minimise their cardiovascular risk factors.
PURPOSE: Earlier studies have highlighted risk factors for perioperative stroke after carotid endarterectomy, such as female sex, preoperative symptoms, and cerebral infarction. In this study, we investigated the relationship between these factors and perioperative microembolization. METHODS: A total of 235 patients were entered in the study at two centers. Transcranial Doppler ultrasound scanning was possible in 190 patients (81%) and was performed for 1 hour preoperatively and continuously intraoperatively as a means of detecting microemboli and monitoring mean middle cerebral artery velocity. The findings of transcranial Doppler ultrasound scanning were related to perioperative risk factors by means of univariate analysis. RESULTS: Microemboli were detected in 28 (15%), 79 (42%), and 98 (52%) patients preoperatively, during carotid artery dissection, and after closure of the artery, respectively. Having 10 or more emboli after carotid artery closure was more common in women (P = .04) and in patients with symptomatic carotid artery disease (P = .04) and was demonstrated in three of the six patients who had a perioperative stroke. These three patients also had preoperative evidence of cerebral infarction and an intraoperative middle cerebral artery velocity less than 40 cm/s. CONCLUSION: In this study, perioperative microembolization was more common in women and patients with symptomatic carotid artery disease. These findings may explain the increased risk of carotid surgery in these patients.
BACKGROUND AND PURPOSE: The aim of this study was to establish the difference in burden of cerebrovascular disease across the different health regions of the United Kingdom and to determine whether the initial management of new cases of stroke and transient ischemic attack (TIA) was uniform across the United Kingdom: METHODS: The General Practice Research Database (GPRD) is a national database used for epidemiological studies. This was a cohort study identifying incident cases of stroke and TIA over a 5-year study period between 1992 and 1996. The population studied was patients registered with general practitioners contributing to the GPRD across the different health regions of the United Kingdom: Outcome measures were new diagnoses of stroke and TIA, new prescriptions for antiplatelet and anticoagulant agents, and referrals made for specialist opinion. RESULTS: The age-adjusted annual incidence rate across all regions was 151 per 100 000 for stroke and 190 per 100 000 for TIA. There was almost a 2-fold difference in the incidence of cerebrovascular disease between the regions. The management of stroke and TIA in terms of antiplatelet prescription and of referral onward for further opinion to hospital specialists varied significantly between regions. CONCLUSIONS: Reported stroke and TIA incidence on the GPRD was comparable to that of other European studies. There were striking regional differences in the incidence of disease. The primary care management, both in prescription and referral rates, varied significantly between the different regions. There was a marked underuse of antiplatelet and anticoagulant agents, and referral rates for specialists' opinions were low.
Significant changes have occurred in the treatment of renal artery disease over the past few years. Although excellent clinical results can be obtained with surgery, percutaneous transluminal renal angioplasty has proved similarly efficacious and is now the treatment of choice for nonostial atherosclerotic stenoses and fibromuscular dysplasia. The introduction of stents has become a valuable adjunctive therapy for postangioplasty restenosis and dissection.
BACKGROUND: In regional and population studies, the mortality rate within 30 days of elective surgical repair of abdominal aortic aneurysm is approximately 8 per cent. Identification of preoperative factors associated with this mortality risk is important for informing surgical policy and may suggest suitable preoperative interventions. METHODS: In the UK Small Aneurysm Trial, 820 patients aged 60-80 years underwent elective open surgical repair of an abdominal aortic aneurysm. The relationship between 30-day mortality rate and 13 prespecified potential prognostic factors was investigated. The value of a published clinical prediction rule was also evaluated. RESULTS: The postoperative mortality rate was 5.6 per cent overall (46 deaths in 820 patients). Postoperative mortality risk was significantly associated with older age (P = 0. 03), higher serum creatinine level (P = 0.002) and lower forced expiratory volume in 1 s (FEV1) (P = 0.003) in univariate analyses. Evidence of a relationship between age and postoperative death was weakened (P = 0.08) after adjustment for creatinine level and FEV1. The predicted postoperative mortality risk ranged from 2.7 per cent in younger patients with below average creatinine levels and above average FEV1, to 7.8 per cent in older patients with above average creatinine levels and below average FEV1. The published clinical prediction rule did not validate well on these data; observed risk did not correlate with predicted risk except for a small group of high-risk patients. CONCLUSION: Poor preoperative lung and renal function was strongly associated with postoperative death. Age was less important once these two important prognostic factors had been taken into account. The potential for preoperative improvement in lung and renal function to reduce postoperative mortality rates should be addressed in future studies.
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OBJECTIVES: To compare the outcome of exercise therapy or angioplasty for the treatment of patients with intermittent claudication. DESIGN: A summation analysis. METHODS: A search using MEDLINE and PUBMED between 1966 and April 1999 followed by a review of the manuscripts yielded 54 studies involving angioplasty and 27 studies involving exercise therapy for intermittent claudication. Studies were only included (12 angioplasty and nine exercise series) when results were available for patients with intermittent claudication alone, and when outcome was assessed in terms of symptoms at a minimum of 6 months. RESULTS: The total number of claudicants undergoing exercise therapy was 294 patients, with a mean symptomatic success rate of 38. 4% and a mean improvement in maximum walking distance of 189.7% at 6 months. The total number of claudicants undergoing angioplasty was 2071, with a mean overall symptomatic success rate of 76.6%. The mean overall complication rate was 9% and mean major complication rate was 2.7% for the angioplasty studies. CONCLUSION: Although the result demonstrates an advantage of angioplasty over exercise therapy at 6 months, there is a small risk of major complications. However, comparison of studies was impaired due to disparity in patient numbers, limited follow-up time and lack of uniformity in outcome assessment. In order to achieve a valid comparison of these therapies in a future randomised study, a validated disease-specific instrument for the assessment of symptomatic outcome for claudicants is required.
PURPOSE: This prospective study aimed to validate a newly designed specific measure of quality of life for patients with venous ulcers. METHODS: The study was set in a London teaching hospital and surrounding community clinics. Items for the questionnaire were selected by means of patient interviews, a literature review, and expert opinion. The questionnaire and the Short Form 36-item (SF-36) Health Survey were given to a prospective consecutive cohort of 98 patients with proven venous ulcers that were diagnosed by means of clinical and color duplex examination. Fifty-eight of the patients were women (60%), and the median age of patients was 76 years. The questionnaire was assessed for reliability, validity, and responsiveness. RESULTS: The ulcer-specific questionnaire showed good reliability, as assessed by means of the internal consistency (Cronbach alpha = 0.93) and test-retest analysis (r = 0.84). Factor analysis identified four important health factors: social function, domestic activities, cosmesis, and emotional status. Validity was demonstrated by means of a high correlation with all eight domains of the SF-36 general health measure (r > 0.55, P <.001). Responsiveness was demonstrated by means of a significant reduction in the score on the ulcer questionnaire as ulcers healed at 6 and 11 weeks (P <.05). CONCLUSION: Good evidence exists that a clinically derived measure for patients with venous ulcers has validity to measure the quality of life.