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.     

The diagnostic utility of immunohistochemistry and electron microscopy in distinguishing between peritoneal mesotheliomas and serous carcinomas: a comparative study.

The histologic distinction between peritoneal epithelioid mesotheliomas and serous carcinomas diffusely involving the peritoneum may be difficult, but it can be facilitated by the use of immunohistochemistry and electron microscopy. D2-40 and podoplanin are two recently recognized lymphatic endothelial markers that can be expressed in normal mesothelial cells and mesotheliomas. The purpose of this study is to compare the value of these new mesothelial markers with those that are commonly used for discriminating between mesotheliomas and serous carcinomas, and also to determine the current role of electron microscopy in distinguishing between these malignancies. A total of 40 peritoneal epithelioid mesotheliomas and 45 serous carcinomas of the ovary (15 primary, 30 metastatic to the peritoneum) were investigated for the expression of the following markers: D2-40, podoplanin, calretinin, keratin 5/6, thrombomodulin, MOC-31, Ber-EP4, B72.3 (TAG-72), BG-8 (Lewis(Y)), CA19-9, and leu-M1 (CD15). All 40 (100%) of the mesotheliomas reacted for calretinin, 93% for D2-40, 93% for podoplanin, 93% for keratin 5/6, 73% for thrombomodulin, 13% for Ber-EP4, 5% for MOC-31, 3% for BG-8, and none for B72.3, CA19-9, or leu-M1. All 45 (100%) serous carcinomas were positive for Ber-EP4, 98% for MOC-31, 73% for B72.3, 73% for BG-8, 67% for CA19-9, 58% for leu-M1, 31% for keratin 5/6, 31% for calretinin, 13% for D2-40, 13% for podoplanin, and 4% for thrombomodulin. After analyzing the results, it is concluded that Ber-EP4 and MOC-31 are the best negative mesothelioma markers for differentiating between epithelioid mesotheliomas and serous carcinomas. The best discriminators among the positive markers for mesotheliomas are D2-40, podoplanin, and calretinin. From a practical point of view, Ber-EP4 and MOC-31, in combination with calretinin, and/or D2-40 or podoplanin allow the differential diagnosis to be established between mesothelioma and serous carcinoma in nearly all instances. As a clear distinction could be made between these two malignancies in all of the cases in which electron microscopy was performed, this technique can be very useful in establishing the correct diagnosis when the immunohistochemical results are equivocal or further support of a diagnosis of either mesothelioma or serous carcinoma is needed.     

Segregation analysis of leprosy in families of northern Thailand

Sixty-three families with multiple instances of leprosy were identified through a major leprosy treatment center in northern Thailand. Complex segregation analyses for single major genes or polygenic inheritance were performed using the maximum-likelihood routine POINTER to determine the most likely etiologic model of genetic susceptibility. Liability differences between men and women were considered in these models. When individuals were considered to be affected because they had any form of leprosy, a generalized major gene model with nearly dominant parameters on the liability scale, but additive penetrances, was found to be the most likely. When only those individuals who had tuberculoid forms of leprosy were considered to be affected, a recessive model was found to be the most likely; however, the discrimination between various models was poor. Further analyses are necessary to delineate genetic mechanisms to explain these apparently divergent results. In particular, methods of testing two locus models should be considered.     

Paracetamol absorption from a feeding jejunostomy.

Disposition of paracetamol oral elixir was determined in two male patients after administration via feeding jejunostomy and compared with four male controls who received the same dose by mouth. Area under the plasma concentration-time curve, elimination half-life, and time to maximum concentration were similar in both groups after 650 mg paracetamol elixir. The absolute amounts and ratio of paracetamol glucuronide to sulphate, the major urinary metabolites after therapeutic paracetamol doses, were similar after jejunal administration as compared to oral administration. Paracetamol is absorbed and biotransformed in a similar manner after either jejunal or oral administration. Therefore, it may be administered effectively via jejunostomy tube in patients who require this route of administration.