Balancing high accrual and ethical recruitment in paediatric oncology: a qualitative study of the 'look and feel' of clinical trial discussions

Background  

High accrual to clinical trials enables new treatment strategies to be tested rapidly, accurately and with generalisability. Ethical standards also must be high so that participation is voluntary and informed. However, this can be difficult to achieve in trials with complex designs and in those which are closely embedded in clinical practice. Optimal recruitment requires a balance of both ethical and accrual considerations. In the context of a trial of stratified treatments for children with acute lymphoblastic leukaemia (UKALL2003) we examined how recruitment looked to an observer and how it felt to the parents, to identify how doctors' communication could promote or inhibit optimal recruitment.     

Moderate acute exercise (70% VO2 peak) induces TGF‐β, α‐amylase and IgA in saliva during recovery

Strenuous exercise promotes changes in salivary IgA and can be associated with a high incidence of upper respiratory tract Infections. However, moderate exercise enhances immune function. The effect of exercise on salivary IgA has been well studied, but its effect on other immunological parameters is poorly studied. Thus, this study determined the effect of moderate acute exercise on immunological salivary parameters, such as the levels of cytokines (TGF‐β and IL‐5), IgA, α‐amylase and total protein, over 24 h. Ten male adult subjects exercised for 60 min at an intensity of 70% VO₂ peak. Saliva samples were collected before (‘basal’) and 0, 12 and 24 h after an exercise session. The total salivary protein was lower after 12 and 24 h than immediately after exercise, whereas α‐amylase increased at 12 and 24 h after exercise compared with basal levels. The IgA concentration was increased at 24 h after exercise relative to immediately after exercise, and there was no difference in the IL‐5 while TGF‐β concentration increased in recovery. In conclusion, 70% VO₂ peak exercise does not induce changes immediately after exercise, but after 24 h, it produces an increase in salivary TGF‐β without changing IL‐5.     

Intracranial circulation: pulse-sequence considerations in three- dimensional (volume) MR angiography

The technique and feasibility of magnetic resonance (MR) angiography of intracranial vessels were studied in 35 healthy volunteers. Variations in image orientation, repetition time (TR), and flip angle were evaluated to determine their effects on flow-related enhancement. Gradient modifications--including echo time (TE), motion compensation, bandwidth, and field of view--were also studied in an effort to reduce motion-induced phase shifts. Results indicated that a FISP (fast imaging with steady precession) sequence with a TR of 50 msec, TE of 15 msec, velocity compensation in the read and section-select directions, acceleration compensation in the read direction, anisotropic volume, and a 1.25-mm partition thickness produced three-dimensional angiographic MR images that were accurate and reproducible in the depiction of the major intracranial vessels. Difficulties with field of view, persistent signal void secondary to higher-order motion, and spatial resolution remain major problems requiring additional study.     

Chondromalacia patellae: assessment with MR imaging

Magnetic resonance (MR) images of the posterior patellar hyaline articular cartilage were obtained in 23 subjects to determine if MR imaging could accurately demonstrate the patellar cartilage. Arthroscopy was used as the standard of reference. Three subjects were asymptomatic volunteers. In the remaining 20 who had patellofemoral pain, arthroscopy was performed before MR imaging in seven and afterward in 12; one did not undergo arthroscopy. MR imaging showed focal areas of swelling of the patellar cartilage, focal hypointensity, surface irregularity, areas of thinning, and areas of cartilage loss with exposure of subchondral bone. The surgical findings agreed with those from MR images in all seven patients who underwent arthroscopy before MR imaging and in ten of the 12 who underwent surgery afterward. MR imaging is an accurate means of examining the posterior patellar cartilage and should be considered as an alternative to diagnostic arthroscopy when chondromalacia patellae is suspected.     

Acute experimental cerebral ischemia: MR enhancement using Gd-DTPA

The effects of a paramagnetic contrast agent, gadolinium-DTPA (Gd-DTPA), on magnetic resonance (MR) imaging of acute cerebral ischemia was investigated in a feline model of middle cerebral artery occlusion. Imaging was performed both before and after administration of an intravenous dose of 0.2 mmol/kg of Gd-DTPA. The animals were then sacrificed for pathologic correlation. No changes in intensity or relaxation times were noted before or after Gd-DTPA administration in two animals with 2 hours of occlusion. Infarcts were noted before and after contrast enhancement in all six cats with ischemia of greater than 16-hours duration. Gd-DTPA caused significant increase in intensity of infarct but not in that of normal cerebral tissue. Rapid enhancement was visible in infarcts of 16-24 hours, but such enhancement was slower in infarcts of 72-168 hours, presumably owing to slowed inflow caused by increased vasogenic edema in the latter group. Contrast enhancement of acute cerebral ischemic lesions with Gd-DTPA offers no improvement in sensitivity of MR imaging, although the conspicuity of the lesion may be improved. Additionally, contrast media may provide potential temporal and pathophysiological data for better characterization of cerebral ischemia.     

The efficacy of prophylactic intravenous antibiotics in elective foot and ankle surgery

A retrospective chart review of 555 patients who received elective foot and ankle surgeries between 1995 and 2001 at 1 outpatient podiatric hospital clinic was performed to evaluate the efficacy of preoperative intravenous antibiotic use. Only those patients who were having elective foot or ankle surgery for the first time, were being followed up at the hospital's outpatient clinic, and had a nontraumatic cause for their surgery were included in this study. A wound was considered infected when purulent material from the wound sites was noted and an organism(s) was cultured. A wound complication was defined as a superficial dehiscence, edema, erythema, or stitch abscess. Three hundred six (55.1%) patients received a preoperative antibiotic and 249 (44.9%) patients did not. Of the 306 patients who received a preoperative antibiotic, 9 (1.6%) acquired a postoperative wound infection, whereas 8 (1.4%) of the 249 patients who did not receive preoperative antibiotics acquired a postoperative infection. A logistic regression model and chi square tests of association were used to determine if preoperative antibiotic use, age, gender, type of surgical procedure, operative time, tourniquet use, past medical history, and internal fixation were predictive of or associated with postoperative wound infection or complication. None of the study factors was predictive of postoperative wound infection or complication (P >.01). Preoperative antibiotic use was associated with surgical category and internal fixation use (P <.001) but not postoperative wound infection or complication (P >.01). The results suggest that prophylactic intravenous antibiotic use in routine elective foot and ankle surgery is not warranted.     

Morphometric data to FIGO stage and histological type and grade for prognosis of ovarian tumours.

The prognostic value of using histological typing, grading, and morphology, in addition to clinical staging, was assessed in 98 cases of invasive ovarian cancer of the common epithelial types (serous, mucinous, and endometrial). All of these cases had at least five years of follow up. When regression analysis was used, the International Federation of Gynaecology and Obstetrics' (FIGO) staging system was the best indicator for prognosis. Analysis of a combination of morphometric features was the second best indicator, being especially useful for the those patients with stage I disease. Variables that indicated a relatively poor prognostic outcome were mitotic index above 30; volume percentage epithelium above 65%; shortest nuclear axis above a mean of 1 X 1 micrometers. Histological typing of ovarian tumours was of limited value; mucinous tumours have a somewhat better prognosis than serous tumours, but the prognostic value of typing alone was found to be limited. Qualitative histological grading was useful, but the prognostic value of morphometric grading was better. Measurement of morphological features with an interactive computer program is simple and can be done by a pathologist or a technician: in future it is likely that such automated systems of measurement will improve the objectivity of tissue analysis.