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

Patient's experience of life after weight loss surgery: Psychological adjustment

Background: Little is known about the psychological impact weight loss surgery has on people’s life.1 A recent systematic review in this area showed some persisting disordered psychosocial wellbeing after the procedure when compared to control groups, especially after longer term follow up typically beyond 4 years.2 This highlighted potential need for psychological support and more research on long term psychological wellbeing after weight loss surgery. Even clearer from the review was the lack of patient perspective on the lived experience of having weight loss surgery which left a gap in knowledge around their needs following the procedure. For that reason, it was felt generating detailed information of the postoperative weight loss surgery experience would be useful to provide health professionals evidence on this patient group’s psychological wellbeing after weight loss surgery, their stance on the need for psychological support, and if relevant, what their ideal psychological support would be. Study aim: To explore people’s long term life experiences after weight loss surgery by discussing their perceived benefits and limitations of having the procedure, and whether their expectations were realised. Methods: Ten individuals who had weight loss surgery between 2 and 6 years ago were recruited within an NHS bariatric surgery service through purposeful sampling and individually interviewed by the researcher. The semi-structured interviews were subsequently transcribed and analysed using thematic analysis

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

Nostalgia as a psychological resource for people with dementia: A systematic review and meta-analysis of evidence of effectiveness from experimental studies

Objective: This review systematically examines evidence relating to the effect of nostalgia on psychological well-being through a meta-analysis of measures of social connectedness, self-esteem, meaning in life, self-continuity, optimism and positive and negative affect. Rationale: If nostalgia is to be used as a clinical intervention to boost well-being in dementia by reducing threat, then it is important to assess its therapeutic potential. Results: Searches carried out in July 2014 and updated in February 2018 identified 47 eligible experimental studies comparing nostalgic reminiscence and non-nostalgic reminiscence to be included in the meta-analysis. Nostalgic reminiscence had moderate effects on positive affect (0.51 (0.37, 0.65), p= 0.001), social connectedness (0.72 (0.57, 0.87), p= 0.001), self-esteem (0.50 (0.30, 0.70), p= 0.001), meaning in life (0.77 (0.47, 1.08), p= 0.001) and optimism (0.38 (0.28, 0.47), p= 0.001) and a large effect on self-continuity (0.81 (0.55, 1.07), p= 0.001). There was, however, no difference between the effect of nostalgic reminiscence and non-nostalgic reminiscence for negative affect (−0.06 (−0.20, 0.09), p= 0.443). Conclusion: This systematic review and meta-analysis provides an overview of the evidence base for nostalgia. This is an important stage in developing nostalgia as a clinical intervention for people with dementia which might be achieved, for instance, by adapting current reminiscence and life review techniques. This meta-analysis will therefore also serve as a valuable reference point for the continued exploration of nostalgia as an intervention

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

PRO development: rigorous qualitative research as the crucial foundation

Recently published articles have described criteria to assess qualitative research in the health field in general, but very few articles have delineated qualitative methods to be used in the development of Patient-Reported Outcomes (PROs). In fact, how PROs are developed with subject input through focus groups and interviews has been given relatively short shrift in the PRO literature when compared to the plethora of quantitative articles on the psychometric properties of PROs. If documented at all, most PRO validation articles give little for the reader to evaluate the content validity of the measures and the credibility and trustworthiness of the methods used to develop them. Increasingly, however, scientists and authorities want to be assured that PRO items and scales have meaning and relevance to subjects. This article was developed by an international, interdisciplinary group of psychologists, psychometricians, regulatory experts, a physician, and a sociologist. It presents rigorous and appropriate qualitative research methods for developing PROs with content validity. The approach described combines an overarching phenomenological theoretical framework with grounded theory data collection and analysis methods to yield PRO items and scales that have content validity