Accuracy of SIAscopy for pigmented skin lesions encountered in primary care: development and validation of a new diagnostic algorithm.

BACKGROUND: Diagnosing pigmented skin lesions in general practice is challenging. SIAscopy has been shown to increase diagnostic accuracy for melanoma in referred populations. We aimed to develop and validate a scoring system for SIAscopic diagnosis of pigmented lesions in primary care. METHODS: This study was conducted in two consecutive settings in the UK and Australia, and occurred in three stages: 1) Development of the primary care scoring algorithm (PCSA) on a sub-set of lesions from the UK sample; 2) Validation of the PCSA on a different sub-set of lesions from the same UK sample; 3) Validation of the PCSA on a new set of lesions from an Australian primary care population. Patients presenting with a pigmented lesion were recruited from 6 general practices in the UK and 2 primary care skin cancer clinics in Australia. The following data were obtained for each lesion: clinical history; SIAscan; digital photograph; and digital dermoscopy. SIAscans were interpreted by an expert and validated against histopathology where possible, or expert clinical review of all available data for each lesion. RESULTS: A total of 858 patients with 1,211 lesions were recruited. Most lesions were benign naevi (64.8%) or seborrhoeic keratoses (22.1%); 1.2% were melanoma. The original SIAscopic diagnostic algorithm did not perform well because of the higher prevalence of seborrhoeic keratoses and haemangiomas seen in primary care. A primary care scoring algorithm (PCSA) was developed to account for this. In the UK sample the PCSA had the following characteristics for the diagnosis of 'suspicious': sensitivity 0.50 (0.18-0.81); specificity 0.84 (0.78-0.88); PPV 0.09 (0.03-0.22); NPV 0.98 (0.95-0.99). In the Australian sample the PCSA had the following characteristics for the diagnosis of 'suspicious': sensitivity 0.44 (0.32-0.58); specificity 0.95 (0.93-0.97); PPV 0.52 (0.38-0.66); NPV 0.95 (0.92-0.96). In an analysis of lesions for which histological diagnosis was available (n = 111), the PCSA had a significantly greater Area Under the Curve than the 7-point checklist for the diagnosis of melanoma (0.83; 95% CI 0.71-0.95 versus 0.61; 95% CI 0.44-0.78; p = 0.02 for difference). CONCLUSIONS: The PCSA could have a useful role in improving primary care management of pigmented skin lesions. Further work is needed to develop and validate the PCSA in other primary care populations and to evaluate the cost-effectiveness of GP management of pigmented lesions using SIAscopy.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Risk Prediction Models for Colorectal Cancer: A Systematic Review.

Colorectal cancer is the second leading cause of cancer-related death in Europe and the United States. Survival is strongly related to stage at diagnosis and population-based screening reduces colorectal cancer incidence and mortality. Stratifying the population by risk offers the potential to improve the efficiency of screening. In this systematic review we searched Medline, EMBASE, and the Cochrane Library for primary research studies reporting or validating models to predict future risk of primary colorectal cancer for asymptomatic individuals. A total of 12,808 papers were identified from the literature search and nine through citation searching. Fifty-two risk models were included. Where reported (n = 37), half the models had acceptable-to-good discrimination (the area under the receiver operating characteristic curve, AUROC >0.7) in the derivation sample. Calibration was less commonly assessed (n = 21), but overall acceptable. In external validation studies, 10 models showed acceptable discrimination (AUROC 0.71-0.78). These include two with only three variables (age, gender, and BMI; age, gender, and family history of colorectal cancer). A small number of prediction models developed from case-control studies of genetic biomarkers also show some promise but require further external validation using population-based samples. Further research should focus on the feasibility and impact of incorporating such models into stratified screening programmes.J Usher-Smith is funded by a National Institute of Health Research (NIHR) Clinical Lectureship and F Walter by an NIHR Clinician Scientist award. J Emery is funded by an Australian National Health and Medical Research Council (NHMRC) Practitioner Fellowship. A Wong has an NHMRC Early Career Fellowship. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.This is the author accepted manuscript. The final version is available from American Association for Cancer Research via http://dx.doi.org/10.1158/1940-6207.CAPR-15-027

Learning a novel technique to identify possible melanomas: are Australian general practitioners better than their U.K. colleagues?

Abstract Background Spectrophotometric intracutaneous analysis (SIAscopy™) is a multispectral imaging technique that is used to identify 'suspicious' (i.e. potentially malignant) pigmented skin lesions for further investigation. The MoleMate™ system is a hand-held scanner that captures SIAscopy™ images that are then classified by the clinician using a computerized diagnostic algorithm designed for the primary health care setting. The objectives of this study were to test the effectiveness of a computer program designed to train health care workers to identify the diagnostic features of SIAscopy™ images and compare the results of a group of Australian and a group of English general practitioners (GPs). Methods Thirty GPs recruited from the Perth (Western Australia) metropolitan area completed the training program at a workshop held in March 2008. The accuracy and speed of their pre- and post-test scores were then compared with those of a group of 18 GPs (including 10 GP registrars) who completed a similar program at two workshops held in Cambridge (U.K.) in March and April, 2007. Results The median test score of the Australian GPs improved from 79.5% to 86.5% (median increase 5.5%; p < 0.001) while the median test score of the English GPs improved from 74.5% to 86.5% (median increase 9.5%; p < 0.001). The Australian GPs had significantly higher pre-test scores but there were no significant differences in post-test scores between the Australian and English GPs or between the GPs and GP registrars. There was no significant difference in scores between GPs with previous dermoscopy experience or dermatology training. Conclusion Most of the SIAscopy™ features can be learnt to a reasonable degree of accuracy with this brief computer training program. Although the Australian GPs scored higher in the pre-test, both groups had similar levels of accuracy and speed in interpreting the SIAscopy™ features after completing the program. Scores were not affected by previous dermoscopy experience or dermatology training, which suggests that the MoleMate™ system is relatively easy to learn

The CRISP colorectal cancer risk prediction tool: an exploratory study using simulated consultations in Australian primary care

Abstract Background In Australia, screening for colorectal cancer (CRC) with colonoscopy is meant to be reserved for people at increased risk, however, currently there is a mismatch between individuals’ risk of CRC and the type of CRC screening they receive. This paper describes the development and optimisation of a Colorectal cancer RISk Prediction tool (‘CRISP’) for use in primary care. The aim of the CRISP tool is to increase risk-appropriate CRC screening. Methods CRISP development was informed by previous experience with developing risk tools for use in primary care and a systematic review of the evidence. A CRISP prototype was used in simulated consultations by general practitioners (GPs) with actors as patients. GPs were interviewed to explore their experience of using CRISP, and practice nurses (PNs) and practice managers (PMs) were interviewed after a demonstration of CRISP. Transcribed interviews and video footage of the ‘consultations’ were qualitatively analyzed. Themes arising from the data were mapped onto Normalization Process Theory (NPT). Results Fourteen GPs, nine PNs and six PMs were recruited from 12 clinics. Results were described using the four constructs of NPT: 1) Coherence: Clinicians understood the rationale behind CRISP, particularly since they were familiar with using risk tools for other conditions; 2) Cognitive participation: GPs welcomed the opportunity CRISP provided to discuss healthy and unhealthy behaviors with their patients, but many GPs challenged the screening recommendation generated by CRISP; 3) Collective Action: CRISP disrupted clinician-patient flow if the GP was less comfortable with computers. GP consultation time was a major implementation barrier and overall consensus was that PNs have more capacity and time to use CRISP effectively; 4) Reflexive monitoring: Limited systematic monitoring of new interventions is a potential barrier to the sustainable embedding of CRISP. Conclusions CRISP has the potential to improve risk-appropriate CRC screening in primary care but was considered more likely to be successfully implemented as a nurse-led intervention

Local non-Gaussianity from rapidly varying sound speeds

We study the effect of non-trivial sound speeds on local-type non-Gaussianity during multiple-field inflation. To this end, we consider a model of multiple-field DBI and use the deltaN formalism to track the super-horizon evolution of perturbations. By adopting a sum separable Hubble parameter we derive analytic expressions for the relevant quantities in the two-field case, valid beyond slow variation. We find that non-trivial sound speeds can, in principle, curve the trajectory in such a way that significant local-type non-Gaussianity is produced. Deviations from slow variation, such as rapidly varying sound speeds, enhance this effect. To illustrate our results we consider two-field inflation in the tip regions of two warped throats and find large local-type non-Gaussianity produced towards the end of the inflationary process.Comment: 30 pages, 7 figures; typos corrected, references added, accepted for publication in JCA

Protein Phylogenetic Analysis of Ca2+/cation Antiporters and Insights into their Evolution in Plants

Cation transport is a critical process in all organisms and is essential for mineral nutrition, ion stress tolerance, and signal transduction. Transporters that are members of the Ca2+/cation antiporter (CaCA) superfamily are involved in the transport of Ca2+ and/or other cations using the counter exchange of another ion such as H+ or Na+. The CaCA superfamily has been previously divided into five transporter families: the YRBG, Na+/Ca2+ exchanger (NCX), Na+/Ca2+, K+ exchanger (NCKX), H+/cation exchanger (CAX), and cation/Ca2+ exchanger (CCX) families, which include the well-characterized NCX and CAX transporters. To examine the evolution of CaCA transporters within higher plants and the green plant lineage, CaCA genes were identified from the genomes of sequenced flowering plants, a bryophyte, lycophyte, and freshwater and marine algae, and compared with those from non-plant species. We found evidence of the expansion and increased diversity of flowering plant genes within the CAX and CCX families. Genes related to the NCX family are present in land plant though they encode distinct MHX homologs which probably have an altered transport function. In contrast, the NCX and NCKX genes which are absent in land plants have been retained in many species of algae, especially the marine algae, indicating that these organisms may share “animal-like” characteristics of Ca2+ homeostasis and signaling. A group of genes encoding novel CAX-like proteins containing an EF-hand domain were identified from plants and selected algae but appeared to be lacking in any other species. Lack of functional data for most of the CaCA proteins make it impossible to reliably predict substrate specificity and function for many of the groups or individual proteins. The abundance and diversity of CaCA genes throughout all branches of life indicates the importance of this class of cation transporter, and that many transporters with novel functions are waiting to be discovered

Understanding implementation and usefulness of electronic clinical decision support (eCDS) for melanoma in English primary care: a qualitative investigation.

BACKGROUND: Timely diagnosis of the serious skin cancer melanoma can improve patient outcomes. Clinical guidelines suggest that GPs use checklists, such as the 7-point checklist (7PCL), to assess pigmented lesions. In 2016, the 7PCL was disseminated by EMIS as an electronic clinical decision support (eCDS) tool. AIM: To understand GP and patient perspectives on the implementation and usefulness of the eCDS. DESIGN & SETTING: Semi-structured interviews with GPs and patients were undertaken. The interviews took place in four general practices in the south east of England following consultations using the eCDS for suspicious pigmented lesions. METHOD: Data were collected from semi-structured face-to-face interviews with GPs and from telephone interviews with patients. They were recorded and transcribed verbatim. The Consolidated Framework for Implementation Research (CFIR) underpinned the analysis using thematic approaches. RESULTS: A total of 14 interviews with GPs and 14 interviews with patients were undertaken. Most GPs reported that, as the eCDS was embedded in the medical record, it was useful, easy to use, time-efficient, and could facilitate patient-GP communication. They were less clear that it could meet policy or patient needs to improve early diagnosis, and some felt that it could lead to unnecessary referrals. Few felt that it had been sufficiently implemented at practice level. More felt confident with their own management of moles, and that the eCDS could be most useful for borderline decision-making. No patients were aware that the eCDS had been used during their consultation. CONCLUSION: Successful implementation of a new tool, such as eCDS for melanoma, requires GPs to perceive its value and understand how it can best be integrated into clinical practice. Disseminating a tool without such explanations is unlikely to promote its adoption into routine practice.NIH

Surgical versus nonsurgical treatment for lumbar degenerative spondylolisthesis.

BACKGROUND: Management of degenerative spondylolisthesis with spinal stenosis is controversial. Surgery is widely used, but its effectiveness in comparison with that of nonsurgical treatment has not been demonstrated in controlled trials. METHODS: Surgical candidates from 13 centers in 11 U.S. states who had at least 12 weeks of symptoms and image-confirmed degenerative spondylolisthesis were offered enrollment in a randomized cohort or an observational cohort. Treatment was standard decompressive laminectomy (with or without fusion) or usual nonsurgical care. The primary outcome measures were the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36) bodily pain and physical function scores (100-point scales, with higher scores indicating less severe symptoms) and the modified Oswestry Disability Index (100-point scale, with lower scores indicating less severe symptoms) at 6 weeks, 3 months, 6 months, 1 year, and 2 years. RESULTS: We enrolled 304 patients in the randomized cohort and 303 in the observational cohort. The baseline characteristics of the two cohorts were similar. The one-year crossover rates were high in the randomized cohort (approximately 40% in each direction) but moderate in the observational cohort (17% crossover to surgery and 3% crossover to nonsurgical care). The intention-to-treat analysis for the randomized cohort showed no statistically significant effects for the primary outcomes. The as-treated analysis for both cohorts combined showed a significant advantage for surgery at 3 months that increased at 1 year and diminished only slightly at 2 years. The treatment effects at 2 years were 18.1 for bodily pain (95% confidence interval [CI], 14.5 to 21.7), 18.3 for physical function (95% CI, 14.6 to 21.9), and -16.7 for the Oswestry Disability Index (95% CI, -19.5 to -13.9). There was little evidence of harm from either treatment. CONCLUSIONS: In nonrandomized as-treated comparisons with careful control for potentially confounding baseline factors, patients with degenerative spondylolisthesis and spinal stenosis treated surgically showed substantially greater improvement in pain and function during a period of 2 years than patients treated nonsurgically. (ClinicalTrials.gov number, NCT00000409 [ClinicalTrials.gov].)

The effect of phase fluctuations on the single-particle properties of the underdoped cuprates

We study the effect of order parameter phase fluctuations on the single-particle properties of fermions in the underdoped cuprate superconductors using a phenomenological low-energy theory. We identify the fermion-phase field coupling as the Doppler-shift of the quasiparticle spectrum induced by the fluctuating superfluid velocity and we calculate the effect of these fluctuations on the fermion self-energy. We show that the vortex pair unbinding near the superconducting transition causes a significant broadening in the fermion spectral function, producing a pseudogap-like feature. We also discuss the specific heat and show that the phase fluctuation effect is visible due to the short coherence length.Comment: RevTex 11 pages; 11 epsf figures included. Added and updated reference