Supermarket/hypermarket opportunistic screening for atrial fibrillation (SHOPS-AF) using sensors embedded in the handles of supermarket trolleys: A feasibility study.

BACKGROUND: Atrial fibrillation (AF) increases the risk of death, stroke, heart failure, cognitive decline, and healthcare costs but is often asymptomatic and undiagnosed. There is currently no national screening program for AF. The advent of validated hand-held devices allows AF to be detected in non-healthcare settings, enabling screening to be undertaken within the community. METHOD AND RESULTS: In this novel observational study, we embedded a MyDiagnostick single lead ECG sensor into the handles of shopping trolleys in four supermarkets in the Northwest of England: 2155 participants were recruited. Of these, 231 participants either activated the sensor or had an irregular pulse, suggesting AF. Some participants agreed to use the sensor but refused to provide their contact details, or consent to pulse assessment. In addition, some data were missing, resulting in 203 participants being included in the final analyses. Fifty-nine participants (mean age 73.6 years, 43% female) were confirmed or suspected of having AF; 20 were known to have AF and 39 were previously undiagnosed. There was no evidence of AF in 115 participants and the remaining 46 recordings were non-diagnostic, mainly due to artefact. Men and older participants were significantly more likely to have newly diagnosed AF. Due to the number of non-diagnostic ECGs (n = 46), we completed three levels of analyses, excluding all non-diagnostic ECGs, assuming all non-diagnostic ECGs were masking AF, and assuming all non-diagnostic ECGs were not AF. Based on the results of the three analyses, the sensor's sensitivity (95% CI) ranged from 0.70 to 0.93; specificity from 0.15 to 0.97; positive predictive values (PPV) and negative predictive values (NPV) ranged from 0.24 to 0.56 and 0.55 to 1.00, respectively. These values should be interpreted with caution, as the ideal reference standard on 1934 participants was imperfect. CONCLUSION: The study demonstrates that the public will engage with AF screening undertaken as part of their daily routines using hand-held devices. Sensors can play a key role in identifying asymptomatic patients in this way, but the technology must be further developed to reduce the quantity of non-diagnostic ECGs.

Amniotic membrane application in surgical treatment of conjunctival tumors.

The amniotic membrane (AM) has special properties, making it ideal for clinical applications in various surgical fields like ophthalmology. It is used more frequently to cover conjunctival and corneal defects. In our retrospective study we have been combined 68 patients with epibulbar conjunctival tumors they have been surgically treated in the period of 2011-2021. Seven (10.3%) patients have been treated with AM application after surgical removal of the tumor. 54 (79%) cases were malignant, and 14 (21%) were benign. In the analyzed dataset the males had just slightly higher chance of malignancy than females, 80% versus 78.3%. For the significancy calculation the Fisher exact test was used and the result proved no significancy (p = 0.99). Six patients with AM application were malignant. The observed difference in the number of quadrants of the bulbar conjunctiva infiltrated versus significant malignancy with p = 0.050 calculated by Fisher Exact test and with p = 0.023 calculated by Likelihood-ratio test. The results of our study indicate that AM grafts are an effective alternative to cover defects after removal of epibulbar lesions due to their anti-inflammatory properties because the conjunctiva must be preserved, and especially the most important application is in malignant epibulbar conjunctival tumors.

Diffusion kurtosis imaging for characterizing tumor heterogeneity in an intracranial rat glioblastoma model.

The utility of diffusion kurtosis imaging (DKI) for assessing intra-tumor heterogeneity was evaluated in a rat model of glioblastoma multiforme. Longitudinal MRI including T2 -weighted and diffusion-weighted MRI (DWI) was performed on six female Fischer rats 8, 11 and 14 days after intracranial transplantation of F98 cells. T2 -weighted images were used to measure the tumor volumes and DWI images were used to compute diffusion tensor imaging (DTI) and DWI based parametric maps including mean diffusivity (MD), mean kurtosis (MK), axial diffusivity (AD), axial kurtosis, radial diffusivity, radial kurtosis, fractional anisotropy (FA) and kurtosis fractional anisotropy (KFA). Median values from the segmented normal contralateral cortex, tumor and edema from the diffusion parameters were compared at the three imaging time points to assess any changes in tumor heterogeneity over time. ex vivo DKI was also performed in a representative sample and compared with histology. Significant differences were observed between normal cortex, tumor and edema in both the DTI and DKI parameters. Notably, at the earliest time point MK and KFA were significantly different between normal cortex and tumor in comparison with MD or FA. Although a decreasing trend in MD, AD and FA values of the tumor were observed as the tumor grew, no significant changes in any of the DTI or DKI parameters were observed longitudinally. While DKI was equally sensitive to DTI in differentiating tumor from edema and normal brain, it was unable to detect longitudinal increases in intra-tumoral heterogeneity in the F98 model of glioblastoma multiforme.

MORTALITY OF PATIENTS WITH UVEAL MELANOMA DETECTED BY DIABETIC RETINOPATHY SCREENING.

PURPOSE: To investigate whether early detection and treatment of uveal melanoma by screening was associated with a lower mortality rate. METHODS: Retrospective assessment of prospectively collected data comparing 132 patients with uveal melanoma referred by the National Diabetic Screening Service with 608 control patients referred through other means. RESULTS: Mean tumor diameter was smaller in the diabetic screening group (11.1 mm vs. 12.5 mm) as was tumor thickness (3.4 mm vs. 5.4 mm). The prevalence of high-risk monosomy 3 was also lower (17/40, 43% vs. 62/110, 56%). Despite a higher rate of systemic comorbidities in the patients diagnosed through screening and despite older age at diagnosis, the 5-year all-cause mortality was similar in both groups (17% vs. 20%); however, the metastatic mortality was lower in the diabetic screening group (11/132, 8% vs. 95/608, 16%). CONCLUSION: Despite higher rates of comorbidities, the patients detected at diabetic screening had a lower 5-year mortality rate. The diabetic screening programme enabled detection and treatment of posterior uveal melanomas at an earlier stage. However, the confounding factors of lead and length time bias are not to be ignored.

Application of SPF moisturisers is inferior to sunscreens in coverage of facial and eyelid regions.

Many moisturisers contain sun protection factors (SPF) equivalent to those found in sunscreens. However, there is a lack of research into how SPF moisturiser application compares to sunscreens in terms of coverage achieved and protection afforded. Previously we demonstrated that users incompletely covered their eyelid regions during routine sunscreen application. Here, we aimed to determine if SPF moisturiser users also displayed these tendencies. A study population of 84 participants (22 males, 62 females, age 18-57) were exposed to UV radiation and photographed using a tripod mounted UV sensitive DSLR camera on two separate visits. At visit one, images were acquired before and after applying either SPF30 sunscreen or moisturiser, then at visit two the study was repeated with the other formulation. Images were processed for facial landmark identification followed by segmentation mapping of hue saturation values to identify areas of the face that were/were not covered. Analyses revealed that application of moisturiser was significantly worse than sunscreen in terms area of the whole face missed (11.1% missed with sunscreen compared to 16.6% for SPF moisturiser p<0.001 paired t-test). This difference was primarily due to decreased coverage of the eyelid regions (14.0% missed with sunscreen, 20.9% moisturiser, p<0.001). Analysis of a post-study questionnaire revealed participants to be unaware of their incomplete coverage. Secondary analyses revealed improved coverage in males (p = 0.05), and, with moisturiser only, in participants with darker skin tones (p = 0.02). Together these data indicate that, despite potential advantages in terms of increased frequency of application of moisturiser, the areas of the face that are at higher cancer risk are likely not being protected, and that participants are unaware that they are at risk. As such, alternative sun-protection strategies should be promoted.

A systematic review and meta-analysis of the prevalence of small fiber pathology in fibromyalgia: Implications for a new paradigm in fibromyalgia etiopathogenesis.

OBJECTIVES: Fibromyalgia is a condition which exhibits chronic widespread pain with neuropathic pain features and has a major impact on health-related quality of life. The pathophysiology remains unclear, however, there is increasing evidence for involvement of the peripheral nervous system with a high prevalence of small fiber pathology (SFP). The aim of this systematic literature review is to establish the prevalence of SFP in fibromyalgia. METHODS: An electronic literature search was performed using MEDLINE, EMBASE, PubMed, Web of Science, CINAHL and the Cochrane Library databases. Published full-text, English language articles that provide SFP prevalence data in studies of fibromyalgia of patients over 18years old were included. All articles were screened by two independent reviewers using a priori criteria. Methodological quality and risk of bias were evaluated using the critical appraisal tool by Munn et al. Overall and subgroup pooled prevalence were calculated by random-effects meta-analysis with 95% CI. RESULTS: Database searches found 935 studies; 45 articles were screened of which 8 full text articles satisfied the inclusion criteria, providing data from 222 participants. The meta-analysis demonstrated the pooled prevalence of SFP in fibromyalgia is 49% (95% CI: 38-60%) with a moderate degree of heterogeneity, (I2 = 68%). The prevalence estimate attained by a skin biopsy was 45% (95% CI: 32-59%, I2 = 70%) and for corneal confocal microscopy it was 59% (95% CI: 40-78%, I2 = 51%). CONCLUSION: There is a high prevalence of SFP in fibromyalgia. This study provides compelling evidence of a distinct phenotype involving SFP in fibromyalgia. Identifying SFP will aid in determining its relationship to pain and potentially facilitate the development of future interventions and pharmacotherapy.

UV imaging reveals facial areas that are prone to skin cancer are disproportionately missed during sunscreen application.

Application of sunscreen is a widely used mechanism for protecting skin from the harmful effects of UV light. However, protection can only be achieved through effective application, and areas that are routinely missed are likely at increased risk of UV damage. Here we sought to determine if specific areas of the face are missed during routine sunscreen application, and whether provision of public health information is sufficient to improve coverage. To investigate this, 57 participants were imaged with a UV sensitive camera before and after sunscreen application: first visit; minimal pre-instruction, second visit; provided with a public health information statement. Images were scored using a custom automated image analysis process designed to identify areas of high UV reflectance, i.e. missed during sunscreen application, and analysed for 5% significance. Analyses revealed eyelid and periorbital regions to be disproportionately missed during routine sunscreen application (median 14% missed in eyelid region vs 7% in rest of face, p<0.01). Provision of health information caused a significant improvement in coverage to eyelid areas in general however, the medial canthal area was still frequently missed. These data reveal that a public health announcement-type intervention could be effective at improving coverage of high risk areas of the face, however high risk areas are likely to remain unprotected therefore other mechanisms of sun protection should be widely promoted such as UV blocking sunglasses.

Novel Retinal Lesion in Ebola Survivors, Sierra Leone, 2016.

We conducted a case-control study in Freetown, Sierra Leone, to investigate ocular signs in Ebola virus disease (EVD) survivors. A total of 82 EVD survivors with ocular symptoms and 105 controls from asymptomatic civilian and military personnel and symptomatic eye clinic attendees underwent ophthalmic examination, including widefield retinal imaging. Snellen visual acuity was <6/7.5 in 75.6% (97.5% CI 63%-85.7%) of EVD survivors and 75.5% (97.5% CI 59.1%-87.9%) of controls. Unilateral white cataracts were present in 7.4% (97.5% CI 2.4%-16.7%) of EVD survivors and no controls. Aqueous humor from 2 EVD survivors with cataract but no anterior chamber inflammation were PCR-negative for Zaire Ebola virus, permitting cataract surgery. A novel retinal lesion following the anatomic distribution of the optic nerve axons occurred in 14.6% (97.5% CI 7.1%-25.6%) of EVD survivors and no controls, suggesting neuronal transmission as a route of ocular entry.

In vitro experiment to elucidate the mechanism of the 'soft shell technique' for preventing subretinal migration of perfluoro-octane.

AIM: Perfluorocarbon liquid (PFCL) can migrate into subretinal space in detached and stiffened retina with open holes during vitreoretinal surgery. An innovative 'soft shell' technique was introduced to reduce the complication using hyaluronate (HA) to 'cover' the retinal hole. This study aims to study the effectiveness of this technique in vitro. METHODS: Ex vivo porcine retina was mounted on a transwell insert. Beneath the retina was an aqueous solution. Two retinal holes were made using needle punctures. One of the two retinal holes was covered with HA. Perfluoro-n-octane (PFO) was added above the retina incrementally using a syringe pump. The height of PFO required to cause the migration of PFO through the retinal holes was measured. The 'pendant drop' method was carried out to measure the interfacial tensions between the PFO and aqueous, and between PFO and four different concentrations of HA solution. RESULTS: A statistically higher PFO level was required to cause the migration of PFO through the retinal hole with HA coating than without HA coating (Tobit regression with p<0.05). The use of HA was associated with 2.39-fold increase in hydrostatic pressure before the collapse of the PFO interface at the retinal holes. The interfacial tension between PFO and HA solution with concentrations of 0.05%, 0.25%, 0.5% and 1% were 54.2±0.6, 55.3±0.6, 59.5±1.5 and 68.3±1.3 mN/m, respectively (mean±SD). The interfacial tension between PFO and aqueous with 1% HA coating (68.3±1.3 mN/m) was significantly higher than that without (37.4±3.4 mN/m) (p<0.05). CONCLUSIONS: The interfacial tension between HA and PFO is higher than that between aqueous and PFO. This is a plausible physical explanation of how the 'soft shell' technique might work to prevent subretinal migration of PFCL.

Porous Versus Nonporous Orbital Implants After Enucleation for Uveal Melanoma: A Randomized Study.

PURPOSE: To compare hydroxyapatite with acrylic implants after enucleation for uveal melanoma with respect to eyelid position, ocular motility, implant complications, and patient satisfaction. METHODS: Patients undergoing primary enucleation for uveal melanoma between May 2005 and November 2012 at the Liverpool Ocular Oncology Centre, United Kingdom, were randomized between hydroxyapatite and acrylic implants. Questionnaires were sent to patients and ocularists to comment on the main outcomes. RESULTS: A total of 416 patients were recruited in the study, of whom 281 were included, with 49.5% (139/281) and 50.5% (142/281) receiving a hydroxyapatite (HA) or acrylic (AC) implant. Mailed questionnaires completed at ≥18 months by patients showed no significant differences between the groups in eyelid position, prosthetic motility, socket complications, and patient satisfaction. Complications included implant extrusion (1% vs 4%), enophthalmos (26% vs 26%), and superior sulcus deformity (24% vs 24%) with HA and AC implants, respectively, (Fisher exact test p > 0.0125 in all, Bonferroni correction). Questionnaires completed by ocularists indicated no significant differences in eyelid opening, prosthetic motility, and other complications at 6 months (Fisher exact test, p > 0.05 in all); there was a higher prevalence of ptosis with AC than HA implants (46% vs 25%, p = 0.03) and a greater need for ocularists' treatment with HA than AC (50% vs 28%, p = 0.03). CONCLUSIONS: Patient-reported outcomes after enucleation for uveal melanoma indicate no major differences between hydroxyapatite and acrylic implants in surgical outcomes and patient satisfaction. There was a higher prevalence of ptosis with AC and a greater need of ocularists' visits with HA at around 6 months observed by ocularists.

Towards better characterization and quantification of emulsification of silicone oil in vitro.

PURPOSE: Emulsification is related to complications arising from silicone oil (SO) tamponade. Currently, there is no widely accepted method for testing the propensity of SO to emulsify that are physiologically realistic and quantitative. METHODS: We compared different ways of inducing emulsification namely vortex mixing, sonication and homogenization. Silicone oil (SO) emulsification was quantitatively assessed using the Coulter counter and laser light scattering. The in vitro results are compared with the droplet size distribution profile of vitreous clinical washout. Conventional SO was compared with two novel SO blends with high-molecular-weight (HMW) additives (SOHMW2000 and SOHMW5000 ). RESULTS: Of the three methods for inducing emulsification, homogenization generated the most consistent emulsion samples with the smallest variance. The results from the Coulter counter measurement correlated strongly with the laser light scattering measurement within the range of 1 to 30 µm. The droplet size distribution profiles from human eyes were similar to that of emulsions generated in vitro by homogenization. The human size distribution profile was within the range of values obtained by the in vitro experiment. Compared to the conventional SO, the emulsion droplet counts for the new SO blends were significantly lower (SOHMW2000 and SOHMW5000 were 79% (±17%) and 49% (±18%) of the SO2000 and SO5000 , respectively; p = 0.03 and p = 0.002). CONCLUSION: Emulsion generated in vitro by homogenization has similar droplet size profile as human eyes filled with SO. Using this method to induce emulsion, SO blends with HMW additives demonstrated less propensity to emulsification with lower droplet counts compared to conventional SO with similar shear viscosity.

Perforin expression in eyelid sebaceous carcinomas: a useful and specific immunomarker for the differential diagnosis of eyelid carcinomas.

PURPOSE: Eyelid sebaceous carcinoma (SC) remains a common diagnostic pitfall for both the clinician and histopathologist. The aim of this study was to describe perforin as a new marker in the immunohistochemistry panel for SC. METHODS: A total of 29 cases were retrieved from the Pathology archives, including 11 sebaceous neoplasms (nine SC; two sebaceomas), 10 squamous cell carcinomas (SCC) and eight basal cell carcinomas (BCC). These were stained using the monoclonal antibody for perforin, epithelial membrane antigen (EMA), Ber-EP4 and adipophilin (ADP). Sensitivity and specificity of perforin as an immunohistologic marker for sebaceous tumours were compared to EMA, ADP and Ber-EP4. RESULTS: Perforin stained strongly 9/11 (81%) of the sebaceous neoplasms (SN), 7/9 SC and 2/2 of sebaceomas (2/2), similar to ADP. Epithelial membrane antigen (EMA) stained 8/9 SC and was negative (1/2) or only very weakly expressed (1/2) in sebaceomas. The specificity of perforin in identifying SN versus SCC and BCC was 100% (95% CI 69-100), while EMA specificity in identifying SN varied according the comparison group (SCC: 50%, 95% CI 18-81, 100% (95% CI 63-100). Perforin better highlighted the intraepithelial spread of SC than EMA. Ber-EP4 was strongly expressed in six of nine SC, but was consistently negative in sebaceomas. CONCLUSIONS: The expression pattern of perforin in sebaceous neoplasms enables us to recommend the use of perforin as a new immunohistochemical marker for sebaceous neoplasms.

A practical divergence measure for survival distributions that can be estimated from Kaplan-Meier curves.

This paper introduces a new simple divergence measure between two survival distributions. For two groups of patients, the divergence measure between their associated survival distributions is based on the integral of the absolute difference in probabilities that a patient from one group dies at time t and a patient from the other group survives beyond time t and vice versa. In the case of non-crossing hazard functions, the divergence measure is closely linked to the Harrell concordance index, C, the Mann-Whitney test statistic and the area under a receiver operating characteristic curve. The measure can be used in a dynamic way where the divergence between two survival distributions from time zero up to time t is calculated enabling real-time monitoring of treatment differences. The divergence can be found for theoretical survival distributions or can be estimated non-parametrically from survival data using Kaplan-Meier estimates of the survivor functions. The estimator of the divergence is shown to be generally unbiased and approximately normally distributed. For the case of proportional hazards, the constituent parts of the divergence measure can be used to assess the proportional hazards assumption. The use of the divergence measure is illustrated on the survival of pancreatic cancer patients. Copyright © 2016 John Wiley & Sons, Ltd.

Assessing the quality of ophthalmic anesthesia.

STUDY OBJECTIVE: The study objective is to evaluate a scoring system to assess the quality of anesthesia used in ophthalmic surgery. DESIGN: This is an observational prospective study. SETTING: The setting is at an operating theater. PATIENTS: Patients are all patients undergoing ophthalmic surgery, October 2012. INTERVENTIONS: Quality of ophthalmic anesthesia was measured using an interval scale by the operating surgeon. Parameters were graded depending on the type and route of anesthetic: central eye position, anesthesia, akinesia of the eye and or body, soft tissue or orbital hemorrhage, and absence of vitreous bulge. MEASUREMENTS: The measurements are quality score and proportion of optimal and suboptimal cases of anesthesia and number of surgical complications. MAIN RESULTS: Data were collected on 349 consecutive cases including cataract (55%), retinal (14%), corneal transplant (6%), and strabismus surgery (6%). Sub-Tenon was the most commonly performed (31%) followed by peribulbar (PB) (26%), general anesthesia (GA) (20%), topical (17%), and retrobulbar (RB) (6%) anesthesia. There were 11 surgical complications: posterior capsule rupture (7), dislocated lens (2), and orbital hemorrhage (2). Sub-Tenon had lower quality scores than PB (P = .006), RB (P = .028), and GA (P <.001); and PB and RB had lower scores than GA (P < .01). There was a significant association between suboptimal anesthesia and surgical complications (P < .001), odds ratio = 3.94 (95% confidence interval, 1.03-15.12; P = .046). CONCLUSIONS: The quality of ophthalmic anesthesia is an important component of the surgical procedure and should be considered in any risk stratification. Suboptimal anesthesia is associated with an increased rate of surgical complications.

Human Conjunctival Stem Cells are Predominantly Located in the Medial Canthal and Inferior Forniceal Areas.

PURPOSE: The conjunctiva plays a key role in ocular surface defence and maintenance of the tear film. Ex vivo expansion of conjunctival epithelial cells offers potential to reconstruct the ocular surface in cases of severe cicatrising disease, but requires initial biopsies rich in stem cells to ensure long-term success. The distribution of human conjunctival stem cells, however, has not been clearly elucidated. METHODS: Whole human cadaveric conjunctiva was retrieved and divided into specific areas for comparison. From each donor, all areas from one specimen were cultured for colony-forming efficiency assays and immunocytochemical studies; all areas from the other specimen were fixed and paraffin embedded for immunohistochemical studies. Expression of CK19, p63, and stem cell markers ABCG2, ΔNp63, and Hsp70 were analyzed. Results were correlated to donor age and postmortem retrieval time. RESULTS: Conjunctiva was retrieved from 13 donors (26 specimens). Colony-forming efficiency and expression of stem cell markers ABCG2, ΔNp63, and Hsp70 in cultures and ABCG2 in fixed tissue were all consistently demonstrated throughout the tissue but with highest levels in the medial canthal and inferior forniceal areas (P < 0.01 for each). Both increasing donor age and longer postmortem retrieval times were associated with significantly lower colony-forming efficiency, stem cell marker expression in cell cultures and ABCG2 expression in fixed tissue. CONCLUSIONS: Biopsies from the medial canthus and inferior forniceal areas, from younger donors, and with short postmortem retrieval times offer the greatest potential to developing conjunctival stem cell-rich epithelial constructs for transplantation.

Menopausal hormone therapy and risk of gastrointestinal cancer: nested case-control study within a prospective cohort, and meta-analysis.

Use of menopausal hormone therapy (HT) has been associated with reduced risk of colorectal cancer; evidence for its effect on other gastrointestinal cancers is limited. We conducted a nested case-control study within a UK cohort, and meta-analyses combining our results with those from published studies. Our study included women aged 50+ in the UK General Practice Research Database (GPRD): 1,054 with oesophageal, 750 with gastric and 4,708 with colorectal cancer, and 5 age- and practice-matched controls per case. Relative risks (RRs) and 95% confidence intervals (CIs) for cancer in relation to prospectively-recorded HT prescriptions were estimated by conditional logistic regression. Women prescribed HT had a reduced risk of oesophageal cancer (adjusted RR for 1+ vs. no HT prescriptions, 0.68, 95% CI 0.53-0.88; p = 0.004), gastric cancer (0.75, 0.54-1.05; p = 0.1) and colorectal cancer (0.81, 0.73-0.90; p < 0.001). There were no significant differences in cancer risk by HT type, estimated duration of HT use or between past and current users. In meta-analyses, risks for ever vs. never use of HT were significantly reduced for all three cancers (summary RR for oesophageal cancer, 0.68, 0.55-0.84, p < 0.001; for gastric cancer, 0.78, 0.65-0.94, p = 0.008; for colorectal cancer, 0.84, 0.81-0.88, p < 0.001). In high-income countries, estimated incidence over 5 years of these three cancers combined in women aged 50-64 was 2.9/1,000 in HT users and 3.6/1,000 in never users. The absolute reduction in risk of these cancers in HT users is small compared to the HT-associated increased risk of breast cancer.