Recruitment and retention of participants in UK surgical trials: survey of key issues reported by trial staff.

BACKGROUND: Recruitment and retention of participants in surgical trials is challenging. Knowledge of the most common and problematic issues will aid future trial design. This study aimed to identify trial staff perspectives on the main issues affecting participant recruitment and retention in UK surgical trials. METHODS: An online survey of UK surgical trial staff was performed. Respondents were asked whether or not they had experienced a range of recruitment and retention issues, and, if yes, how relatively problematic these were (no, mild, moderate or serious problem). RESULTS: The survey was completed by 155 respondents including 60 trial managers, 53 research nurses, 20 trial methodologists and 19 chief investigators. The three most common recruitment issues were: patients preferring one treatment over another (81·5 per cent of respondents); clinicians' time constraints (78·1 per cent); and clinicians preferring one treatment over another (76·8 per cent). Seven recruitment issues were rated moderate or serious problems by a majority of respondents, the most problematic being a lack of eligible patients (60·3 per cent). The three most common retention issues were: participants forgetting to return questionnaires (81·4 per cent); participants found to be ineligible for the trial (74·3 per cent); and long follow-up period (70·7 per cent). The most problematic retention issues, rated moderate or serious by the majority of respondents, were participants forgetting to return questionnaires (56·4 per cent) and insufficient research nurse time/funding (53·6 per cent). CONCLUSION: The survey identified a variety of common recruitment and retention issues, several of which were rated moderate or serious problems by the majority of participating UK surgical trial staff. Mitigation of these problems may help boost recruitment and retention in surgical trials.

ANTECEDENTES: El reclutamiento y la retención de participantes en los ensayos quirúrgicos es un desafío. Conocer los problemas más habituales y conflictivos ayudará al diseño de futuros ensayos. Este estudio tuvo como objetivo identificar la percepción de los participantes sobre cuáles son los principales problemas que afectan el reclutamiento y la retención de participantes en los ensayos quirúrgicos del Reino Unido. MÉTODOS: Encuesta electrónica a profesionales de la salud que habían participado en ensayos quirúrgicos del Reino Unido. Se preguntó a los encuestados si habían experimentado o no algún problema en temas de reclutamiento o retención y, en caso afirmativo, qué tan conflictivos fueron (ningún problema/problema leve/moderado/grave). RESULTADOS: Completaron la encuesta 155 participantes, de los que 60 eran directores del ensayo, 53 enfermeras de investigación, 20 metodólogos de ensayos y 19 investigadores principales. Los tres problemas más comunes en el reclutamiento fueron: pacientes que prefieren un tratamiento sobre otro (81,5% de los encuestados), escaso tiempo de dedicación de los médicos (78,1%) y médicos que prefieren un tratamiento sobre otro (76,8%). La mayoría de los encuestados calificaron siete problemas de reclutamiento como "moderados" o "graves", siendo el más conflictivo la falta de pacientes elegibles (60,3%). Los tres problemas de retención más habituales fueron: participantes que olvidaron devolver los cuestionarios (81,4%), participantes que no fueron elegibles para el ensayo (74,3%) y el largo período de seguimiento (70,7%). Los problemas de retención más conflictivos, calificados como "moderados" o "graves" por la mayoría de los encuestados, fueron el olvido de los participantes para devolver los cuestionarios (56,4%) y el escaso tiempo/financiación para la enfermera investigadora (53,6%). CONCLUSIÓN: La encuesta identificó una serie de problemas habituales en el reclutamiento y la retención de los pacientes, muchos ellos calificados como "moderados" o "graves" por la mayoría del personal involucrado en los ensayos quirúrgicos del Reino Unido. Mitigar estos problemas puede ayudar a impulsar el reclutamiento y la retención en los ensayos quirúrgicos.

NKT cells at the maternal-fetal interface.

Establishment of the maternal-fetal interface is characterized by the influx of maternal NK cells, macrophages, and T cells into the decidua. Although a great deal has been learned about the function of NK cells in the decidua, comparatively little is known of decidual T cell function. NKT cells are an unusual T cell subset capable of producing both Th1-like and Th2-like cytokines. Unlike conventional alphabeta T cells that recognize peptides in the context of MHC molecules, NKT cells recognize glycolipids presented by the MHC class I-like molecule, CD1d. Recent reports have demonstrated that NKT cells and CD1d are present at the maternal-fetal interface. Moreover, activation of NKT cells can have dramatic effects on pregnancy. In this article, we will review basic aspects of NKT cell biology and summarize the recent literature on NKT cells at the maternal-fetal interface.

The biomechanics of leg ulceration.

Research performed in the late 1960s, using 24Na, suggested that the perfusion of skin and subcutaneous tissues is critically dependent on the relationship between capillary (Pc) and tissue pressures (Pt). Perfusion changes differed significantly between controls and patients with venous disease and the differences could be interpreted as evidence that Pt remained high in venous diseased patients. From this starting point, a biomechanical theory for the aetiology of venous ulceration was developed and tested by measuring skin elasticity, limb cross-sectional area and laser Doppler flux. The results confirm that, modelled as a two-compartment system (vascular and interstitial fluid), forces can be demonstrated sufficient to cause intermittent capillary closure and subsequent reperfusion injury. These forces are maximal in the gaiter area, the site of most leg ulcers.

An epidemiological needs assessment of carotid endarterectomy in an English health region. Is the need being met?

OBJECTIVE: To compare the level of provision of carotid endarterectomy (an intervention of proved efficacy for prevention of stroke in patients with symptomatic high grade carotid artery stenosis) with estimates of need. DESIGN: Comparison of regional, district, and age-sex specific operation rates derived from hospital episode statistics with estimates of need based on demographic and epidemiological data; interviews with regional vascular surgeons and a joint provider-purchaser workshop to discuss implications. SETTING: Former Wessex Regional Health Authority, 1991-2 to 1995-6. SUBJECTS: All residents covered by Wessex region treated for carotid artery reconstruction. MAIN OUTCOME MEASURES: Regional, district, and age-sex operation rates as three year average 1993-6 (use) compared with respective estimates of need for carotid endarterectomy among those who presented with symptomatic carotid disease-transient ischaemic attack or minor stroke. RESULTS: The operation rate more than doubled between 1991-2 and 1995-6, from 35 to 89 per million population, compared with an estimated level of need in the region's general population of 153 per million population (transient ischaemic attack 77, minor stroke 76). The ratio of use to need was 0.47 (95% confidence interval 0.4 to 0.54); district ratios were 0.28 (0.19-0.38) to 0.81 (0.62 to 1.06). The annual use:need ratio rose over the three years 1993-6 from 0.38 to 0.59. Use:need ratios were lower in elderly and female patients. Providers were keen to develop guidelines for referral and to increase access to diagnostic facilities; purchasers were more reluctant, given the limited impact of this intervention on the incidence of stroke and the relatively high cost of the operation. CONCLUSION: Although treatment rates increased in Wessex there is still unmet need. Further research is needed to determine the referral pathways of patients with symptomatic carotid disease for diagnosis and operation and to evaluate strategies to improve access to diagnostic facilities.

Early effect of carotid endarterectomy on arterial blood pressure measured with an ambulatory monitor.

BACKGROUND: Carotid artery disease and hypertension are associated, and carotid endarterectomy is often followed by acute changes in blood pressure. As the carotid sinus is responsible for short-term blood pressure control, occlusive carotid disease may contribute to the mechanism of preoperative hypertension. METHODS: Ten patients undergoing carotid endarterectomy and eight having a peripheral bypass procedure were studied 2 weeks before and 2 weeks after operation, using home ambulatory blood pressure measurement. RESULTS: A significant fall in both mean systolic (-14.4 mmHg) and mean diastolic (-12.7 mmHg) pressure was observed after carotid endarterectomy (P < 0.006), whereas no change was seen in controls. CONCLUSION: These results suggest that there is an increase in carotid sinus activity in patients following carotid endarterectomy and supports the hypothesis that carotid sinus dysfunction contributes to hypertension in patients with carotid artery disease.

Prospective randomized placebo-controlled trial of aprotinin for elective aortic reconstruction.

BACKGROUND: The serine protease antagonist, aprotinin, reduces perioperative blood loss in cardiac surgery and orthotopic liver transplantation. A pilot study suggested that the drug may also reduce bleeding during infrarenal aortic replacement; the aim was to confirm or refute this observation with a prospective, randomized, double-blind, placebo-controlled trial. METHODS: Some 136 patients were randomized to receive either aprotinin, given as a loading dose of 2 x 10(6) kallikrein inactivator (KI) units followed by 0.5 x 10(6) KI units/h or equal volumes of 0.9 per cent saline. After 80 patients had been randomized the infusion dose was doubled to ensure that plasma levels were similar to those seen in successful cardiac studies. Blood loss, coagulation and haematological parameters were recorded throughout surgery and for 7 days afterwards. Blood was transfused to maintain the haemoglobin level at 100 g/l. RESULTS: Four patients were withdrawn after randomization when found at laparotomy to be unsuitable for the planned reconstruction. The 30-day mortality rate was 4.5 per cent, with no excess complications in either group. Blood loss collected on swabs was reduced from 480 ml in placebo-treated patients to 379 ml with aprotinin (P = 0.014). Blood loss into suction drains in the first 24 h after operation was reduced from 295 to 205 ml in aprotinin-treated patients (P = 0.002). However, no significant reduction was found in intraoperative or total blood loss, or transfusion requirement. CONCLUSION: The small reduction in blood loss in patients treated with aprotinin demonstrated in this study does not support its use in routine elective aortic surgery.

Effect of flow on the resistance of modelled femoral artery stenoses.

An accurate model of the pressure-flow relationship of a stenosis is necessary for the correct interpretation of haemodynamic measurements. Modelled femoral artery stenoses were tested in vitro and the pressure drop: flow ratio (resistance) was most accurately represented by a fixed component (Rf) combined with a variable component (Rv) that increased linearly with flow (Q) such that Rv = SvQ. For stenoses of 68-94 per cent area, Rf increased from 3.2 to 77.7 milliperipheral resistance units (mPRU), while Sv increased from 0.009 to 0.578 mPRU ml-1 min and Rv was dominant for physiological flow rates. It was concluded that the approximation of a significant stenosis to a fixed resistance is incorrect.

Intraoperative heparinisation, blood loss and myocardial infarction during aortic aneurysm surgery: a Joint Vascular Research Group study.

OBJECTIVES: The primary aim of this prospective multi-centre study involving patients undergoing elective abdominal aortic aneurysm (AAA) surgery was to investigate the relationship between intraoperative intravenous heparinisation, blood loss during surgery and thrombotic complications. METHODS: Two hundred and eighty-four patients were randomised to receive intravenous heparin (n = 145) or no heparin (n = 139). Groups were evenly matched for age, sex, weight, aneurysm size, haemoglobin concentration, platelet counts and distal occlusive disease measured by ankle/brachial systolic pressure. RESULTS: There were no statistically significant differences in blood loss (median 1400 ml vs. 1500 ml; z = 0.02, p = 0.98, 95% C.I. = -200 to 200), blood transfused (4.0 units vs. 4.0 units; z = 1.09, p = 0.28, 95% C.I. = -1 to 0) or distal thrombosis between the two groups. However, analysis of the clinical outcome revealed that 5.7% of the non-heparin group but only 1.4% of the heparinised patients suffered a fatal perioperative myocardial infarction (MI); p < 0.05. All MI, including non fatal events, affected 8.5% and 2% respectively (p = 0.02). CONCLUSIONS: Heparin does not increase blood loss or the need for blood transfusion during surgery. Heparin is not necessary to prevent distal thrombosis when the aorta is cross clamped. The results of the study are consistent with the known mechanisms leading to intraoperative MI and strategies for its prevention. Intravenous heparin, given before aortic cross clamping, is an important prophylaxic against perioperative MI in relation to AAA surgery.

Randomized controlled trial of patch angioplasty for carotid endarterectomy. The Joint Vascular Research Group.

A randomized controlled trial was performed to evaluate patch angioplasty for patients undergoing carotid endarterectomy. There were 213 patient episodes affecting 148 men and 65 women, with 109 allocated to patch angioplasty. Following surgery six patients suffered transient ischaemic attacks but these did not delay discharge from hospital. Six individuals (four patched operations, two not patched) required re-exploration for postoperative haemorrhage and eight (two patched procedures, six not) had potentially serious neurological problems after operation. Of these eight patients, four (none receiving patch angioplasty) underwent re-exploration and in each case a clot was removed and a patch inserted; three of the four made a good long-term recovery. The other four patients suffered completed strokes from which one died. Two further patients (one patched procedure, one not) died after operation from myocardial events, giving an overall 30-day stroke or mortality rate of 2.8 per cent. Objective follow-up assessment with duplex scanning at 1 year was completed by 94.8 per cent of patients; significantly more vessel restenoses and occlusions were observed in those not receiving patches (P < 0.01). Patch angioplasty reduces the number of immediate postoperative complications, and significantly lowers vessel restenosis and occlusion rates at 1 year after operation.