Development of a core outcome set for venous leg ulceration (CoreVen) research evaluations (protocol)

BackgroundA venous leg ulcer is a chronic leg wound caused by poor venous blood circulation in the lower limbs. It is a recurring condition causing pain, malodour, reduced mobility, and depression. Randomised controlled trials evaluating treatments for venous leg ulcers provide important evidence to inform clinical decision-making. However, for findings to be useful, outcomes need to be clinically meaningful, consistently reported across trials, and fully reported. Research has identified the large number of outcomes reported in venous leg ulcer trials, impacting both synthesis of results, and clinical decision-making. To address this, a core outcome set will be developed. A core outcome set is an agreed standardised set of outcomes which should be, as a minimum, measured and reported in all trials which evaluate treatment effectiveness for a given indication. A core outcome set has the potential to reduce research waste, improve the utility of RCTs, reduce reporting bias, facilitate treatment comparisons across different sources of evidence and expedite the production of systematic reviews, meta-analyses and evidence-based clinical guidelines.AimThe aim of this project is to develop a core outcome set for research evaluating the effectiveness of interventions for treating venous leg ulceration.MethodsThrough a scoping review of the literature on venous leg ulceration, we will firstly identify a list of candidate outcome domains (broad categories in relation to what is being measured) from randomised controlled trials and qualitative research, and outcomes (specific methods in relation to what is being measured). In two further stages, we will use the resulting lists of outcome domains and outcomes to design two online surveys. A range of stakeholders will be invited to participate in the surveys and they will be asked to indicate which outcome domains and outcomes are most important and should be considered as core in future research reports.     

Phase I and pharmacokinetic study of gefitinib in children with refractory solid tumors: a Children's Oncology Group Study.

PURPOSE: Epidermal growth factor receptor is expressed in pediatric malignant solid tumors. We conducted a phase I trial of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in children with refractory solid tumors. PATIENTS AND METHODS: Gefitinib (150, 300, 400, or 500 mg/m2) was administered orally to cohorts of three to six patients once daily continuously until disease progression or significant toxicity. Pharmacokinetic studies were performed during course one (day 1 through 28). RESULTS: Of the 25 enrolled patients, 19 (median age, 15 years) were fully evaluable for toxicity and received 54 courses. Dose-limiting toxicity was rash in two patients treated with 500 mg/m2 and elevated ALT and AST in one patient treated with 400 mg/m2. The maximum-tolerated dose was 400 mg/m2/d. The most frequent non-dose-limiting toxicities were grade 1 or 2 dry skin, anemia, diarrhea, nausea, and vomiting. One patient with Ewing's sarcoma had a partial response. Disease stabilized for 8 to > or = 60 weeks in two patients with Wilms' tumor and two with brainstem glioma (one exophytic). At 400 mg/m2, the median peak gefitinib plasma concentration was 2.2 microg/mL (range, 1.2 to 3.6 microg/mL) and occurred at a median of 2.3 hours (range, 2.0 to 8.3 hours) after drug administration. The median apparent clearance and median half-life were 14.8 L/h/m2 (range, 3.8 to 24.8 L/h/m2) and 11.7 hours (range, 5.6 to 22.8 hours), respectively. Gefitinib systemic exposures were comparable with those associated with antitumor activity in adults. CONCLUSION: Oral gefitinib is well tolerated in children. Development of the drug in combination with cytotoxic chemotherapy will be pursued.     

Interactions of angiotensin IV and oxytocin on behaviour in mice.

INTRODUCTION: Angiotensin (Ang) IV enhances learning and memory in rats but there are strain differences in its effects in mice. Oxytocin (OT) also influences learning and memory in rats and mice and, in the light of the proposed effects of Ang IV on oxytocinase, the hypothesis that the effects of Ang IV on cognition in mice involve OT was tested. MATERIALS AND METHODS: The effects of Ang IV and OT, alone and combined, were determined in rat isolated uterine smooth muscle and in object recognition and forced swim tests in BKW mice. RESULTS: Ang potentiated the contractile effects of OT in the uterus. Neither peptide had any effect on object recognition nor locomotor activity. Ang IV had no effect in the forced swim test but abolished the effects of OT. CONCLUSIONS: Ang IV influences the actions of OT in vitro and in vivo, possibly by inhibition of oxytocinase, but the lack of effect of Ang IV on object recognition in BKW mice is unlikely to be a consequence of a deficiency endogenous OT. Unlike OT, Ang IV alone has no effect on learned helplessness in the forced swim test, an effect often used to predict potential antidepressant efficacy in humans.     

Women's knowledge, practises, and intentions regarding correct pelvic floor exercises.

AIM: Although research has demonstrated the efficacy of pelvic floor exercises (PFXs) for the prevention and treatment of female urinary incontinence (FUI), adherence to PFX regimens is commonly poor. There is some evidence that this finding is in part due to a lack of knowledge about how to perform PFXs correctly and misconceptions about the required frequency and duration of PFX regimens. METHODS: By using a sample of 720 postpartum women, this study investigates women's PFX regimens both before and during pregnancy and postpartum. RESULTS: Findings demonstrated that most women were aware of the required frequency for PFXs (at least every second day): just over half had done them this often during pregnancy and 91% intended to do so postpartum. However, few had done them at this level before pregnancy and less than half knew that PFXs should be carried out indefinitely throughout the lifetime. Moreover, only two thirds were confident that they were doing PFXs correctly. CONCLUSION: The findings suggest that, despite good knowledge of the required frequency of PFXs, few women practise them regularly over their lifetime, many apparently perceiving PFXs as relevant only to the childbirth years. Implications for health professionals in addressing these gaps in women's knowledge and practises are discussed.     

An Evaluation of Technetium-99m Tin Colloid--Its Value in the Diagnosis of Renal Transplant Rejection

The value of the Technetium-99m tin colloid (TTC) scan in thediagnosis of renal transplant rejection occurring more than1 month following transplantation was assessed. To our knowledge,use of this agent has not previously been reported. Gamma cameraimaging was performed on 15 occasions in 14 patients in whomplasma creatinine was rising and in three patients in whom renalfunction was stable. Both a qualitative and a quantitative assessmentof images was made. The radioactivity recorded over the graft at 12–16 mmpost injection was expressed as a percentage of that recordedat 0–4 min. In the nine patients in whom graft perfusionwas adequate to allow interpretation of the TTC scan and inwhom rejection was diagnosed by biopsy (six cases) or on clinicalgrounds (three cases), the index ranged from 45 to 153%. Intwo patients the graft was poorly perfused and the accumulationof TTC was predictably low despite the presence of rejection.In the seven patients with either a stable creatinine or withrising creatinine not due to rejection, the index ranged from5 to 43%. Previously reported studies have shown that sulphur colloidsmay be of value in diagnosing graft rejection. This study suggeststhat Tc99m tin colloid may be regarded as a suitable alternativescanning agent and that some simplification of data collectionand analysis can be achieved.     

Nasal polyposis: prevalence of positive food and inhalant skin tests.

OBJECTIVES: To investigate the etiology of nasal polyps and its relationship to allergy. The prevalence of positive food and inhalant skin tests in patients with nasal polyps and nonatopic controls was compared. STUDY DESIGN AND SETTING: Prospective controlled study in tertiary referral rhinology clinic. RESULTS: Seventy percent (70%) of the patients with nasal polyps had positive skin tests to an average of four foodstuffs, compared to 34 percent of controls (P = 0.006). Only 35 percent of the nasal polyp patients also had positive inhalant skin tests. Overall, the prevalence of positive inhalant skin tests was similar in the nasal polyp patients and controls. CONCLUSIONS: These findings suggest that the positive skin tests to foods are not merely a reflection of the general atopic status of patients with nasal polyps. It may be that non-IgE-mediated hypersensitivities, such as to ingested foods, play a role on the basis of a significant number of patients with positive intradermal skin tests to foods. SIGNIFICANCE: Evaluation of the allergic status of patients with polyposis is important. Dietary manipulation may be indicated, though its role needs further investigation.