Development of antigen-specific ELISA for circulating autoantibodies to extracellular matrix protein 1 in lichen sclerosus

Lichen sclerosus is a common, acquired chronic inflammatory skin disease of unknown etiology, although circulating autoantibodies to the glycoprotein extracellular matrix protein 1 (ECM1) have been detected in most patients’ sera. We have examined the nature of ECM1 epitopes in lichen sclerosus sera, developed an ELISA system for serologic diagnosis, and assessed clinicopathological correlation between ELISA titer and disease. Epitope-mapping studies revealed that lichen sclerosus sera most frequently recognized the distal second tandem repeat domain and carboxyl-terminus of ECM1. We analyzed serum autoantibody reactivity against this immunodominant epitope in 413 individuals (95 subjects with lichen sclerosus, 161 normal control subjects, and 157 subjects with other autoimmune basement membrane or sclerosing diseases). The ELISA assay was highly sensitive; 76 of 95 lichen sclerosus patients (80.0%) exhibited IgG reactivity. It was also highly specific (93.7%) in discriminating between lichen sclerosus and other disease/control sera. Higher anti-ECM1 titers also correlated with more longstanding and refractory disease and cases complicated by squamous cell carcinoma. Furthermore, passive transfer of affinity-purified patient IgG reproduced some histologic and immunopathologic features of lichen sclerosus skin. This new ELISA is valuable for the accurate detection and quantification of anti-ECM1 autoantibodies. Moreover, the values may have clinical significance in patients with lichen sclerosus

Developing standards for reporting implementation studies of complex interventions (StaRI): a systematic review and e-Delphi

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited

A Delphi study and ranking exercise to support commissioning services:Future delivery of Thrombectomy services in England

Background: Intra-arterial thrombectomy is the gold standard treatment for large artery occlusive stroke. However, the evidence of its benefits is almost entirely based on trials delivered by experienced neurointerventionists working in established teams in neuroscience centres. Those responsible for the design and prospective reconfiguration of services need access to a comprehensive and complementary array of information on which to base their decisions. This will help to ensure the demonstrated effects from trials may be realised in practice and account for regional/local variations in resources and skill-sets. One approach to elucidate the implementation preferences and considerations of key experts is a Delphi survey. In order to support commissioning decisions, we aimed to using an electronic Delphi survey to establish consensus on the options for future organisation of thrombectomy services among physicians with clinical experience in managing large artery occlusive stroke. Methods: A Delphi survey was developed with 12 options for future organisation of thrombectomy services in England. A purposive sampling strategy established an expert panel of stroke physicians from the British Association of Stroke Physicians (BASP) Clinical Standards and/or Executive Membership that deliver 24/7 intravenous thrombolysis. Options with aggregate scores falling within the lowest quartile were removed from the subsequent Delphi round. Options reaching consensus following the two Delphi rounds were then ranked in a final exercise by both the wider BASP membership and the British Society of Neuroradiologists (BSNR). Results: Eleven stroke physicians from BASP completed the initial two Delphi rounds. Three options achieved consensus, with subsequently wider BASP (97%, n=43) and BSNR members (86%, n=21) assigning the highest approval rankings in the final exercise for transferring large artery occlusive stroke patients to nearest neuroscience centre for thrombectomy based on local CT/CT Angiography. Conclusions: The initial Delphi rounds ensured optimal reduction of options by an expert panel of stroke physicians, while subsequent ranking exercises allowed remaining options to be ranked by a wider group of experts within stroke to reach consensus. The preferred implementation option for thrombectomy is conveying suspected stroke patients for CT/CT Angiography and secondary transfer of large artery occlusive stroke patients to the nearest neuroscience centre

A comparison of echocardiography to invasive measurement in the evaluation of pulmonary arterial hypertension in a rat model

Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by progressive elevation in pulmonary artery pressure (PAP) and total pulmonary vascular resistance (TPVR). Recent advances in imaging techniques have allowed the development of new echocardiographic parameters to evaluate disease progression. However, there are no reports comparing the diagnostic performance of these non-invasive parameters to each other and to invasive measurements. Therefore, we investigated the diagnostic yield of echocardiographically derived TPVR and Doppler parameters of PAP in screening and measuring the severity of PAH in a rat model. Serial echocardiographic and invasive measurements were performed at baseline, 21 and 35 days after monocrotaline-induction of PAH. The most challenging echocardiographic derived TPVR measurement had good correlation with the invasive measurement (r = 0.92, P < 0.001) but also more simple and novel parameters of TPVR were found to be useful although the non-invasive TPVR measurement was feasible in only 29% of the studies due to lack of sufficient tricuspid valve regurgitation. However, echocardiographic measures of PAP, pulmonary artery flow acceleration time (PAAT) and deceleration (PAD), were measurable in all animals, and correlated with invasive PAP (r = −0.74 and r = 0.75, P < 0.001 for both). Right ventricular thickness and area correlated with invasive PAP (r = 0.59 and r = 0.64, P < 0.001 for both). Observer variability of the invasive and non-invasive parameters was low except in tissue-Doppler derived isovolumetric relaxation time. These non-invasive parameters may be used to replace invasive measurements in detecting successful disease induction and to complement invasive data in the evaluation of PAH severity in a rat model

Developing agreement on never events in primary care dentistry:an international eDelphi study

Introduction: Never events (NEs) are a subset of serious patient safety incidents that should not occur if appropriate preventive measures are implemented. Although there is a consensus in medicine, there is no agreement on NEs in dentistry. Aim: To identify NEs in primary care dentistry. Method: We undertook an electronic Delphi exercise to develop an international agreement on NEs for primary care dentistry. Results: We initially identified candidate NEs through a scoping review of the literature and then analysed dentistry-related reports in a national incident reporting system. Next, we invited an international panel of 41 experts to complete two rounds of questionnaires; 32 agreed to participate (78%) and completed the first round and 29/41 (71%) members completed the second round. We provided anonymised controlled feedback between rounds and used a cut-off of 80% agreement to define consensus. Consensus was achieved for 23 out of 42 candidate NEs. These related to routine assessment, and pre-operative, intra-operative and post-operative stages of dental procedures. Discussion and conclusion: To our knowledge, this is the first international expert consensus-based approach that has identified NEs for primary care dentistry. We suggest that dental regulators consider these to support quality assessment and governance activities

Learning as an outcome of involvement in research : what are the implications for practice, reporting and evaluation?

Abstract Public involvement in research has evolved over the last two decades in a culture dominated by the principles of evidence-based medicine. It is therefore unsurprising that some researchers have applied the same thinking to involvement, particularly to involvement in research projects. This may explain why they tend to conceptualise involvement as an intervention, seek to evaluate its impact in the same way that treatments are tested, highlight the need for an evidence-base for involvement, and use the language of research to describe its practice and report its outcomes. In this article we explore why this thinking may be unhelpful. We suggest an alternative approach that conceptualises involvement as ‘conversations that support two-way learning’. With this framing, there is no ‘method’ for involvement, but a wide range of approaches that need to be tailored to the context and the needs of the individuals involved. The quality of the interaction between researchers and the public becomes more important than the process. All parties need to be better prepared to offer and receive constructive criticism and to engage in constructive conflict that leads to the best ideas and decisions. The immediate outcomes of involvement in terms of what researchers learn are subjective (specific to the researcher) and unpredictable (because researchers don’t know what they don’t know at the start). This makes it challenging to quantify such outcomes, and to carry out comparisons of different approaches. On this basis, we believe obtaining ‘robust evidence’ of the outcomes of involvement in ways that are consistent with the values of evidence-based medicine, may not be possible or appropriate. We argue that researchers’ subjective accounts of what they learnt through involvement represent an equally valid way of knowing whether involvement has made a difference. Different approaches to evaluating and reporting involvement need to be adopted, which describe the details of what was said and learnt by whom (short term outcomes), what changes were made as a result (medium term outcomes), and the long-term, wider impacts on the research culture and agenda. Sharing researchers’ personal accounts may support wider learning about how involvement works, for whom and when