Diagnostic accuracy and clinical management by realtime teledermatology. Results from the Northern Ireland arms of the UK Multicentre Teledermatology Trial

Diagnostic accuracy and management recommendations of realtime teledermatology consultations using low-cost telemedicine equipment were evaluated. Patients were seen by a dermatologist over a video-link and a diagnosis and treatment plan were recorded. This was followed by a face-to-face consultation on the same day to confirm the earlier diagnosis and management plan. A total of 351 patients with 427 diagnoses participated. Sixty-seven per cent of the diagnoses made over the video-link agreed with the face-to-face diagnosis. Clinical management plans were recorded for 214 patients with 252 diagnoses. For this cohort, 44% of the patients were seen by the same dermatologist at both consultations, while 56% were seen by a different dermatologist. In 64% of cases the same management plan was recommended at both consultations; a sub-optimum treatment plan was recommended in 8% of cases; and in 9% of cases the video-link management plans were judged to be inappropriate. In 20% of cases the dermatologist was unable to recommend a suitable management plan by video-link. There were significant differences in the ability to recommend an optimum management plan by video-link when a different dermatologist made the reference management plan. The results indicate that a high proportion of dermatological conditions can be successfully managed by realtime teledermatology.

Collectives of diagnostic biomarkers identify high-risk subpopulations of hematuria patients: exploiting heterogeneity in large-scale biomarker data

Background: Ineffective risk stratification can delay diagnosis of serious disease in patients with hematuria. We applied a systems biology approach to analyze clinical, demographic and biomarker measurements (n = 29) collected from 157 hematuric patients: 80 urothelial cancer (UC) and 77 controls with confounding pathologies.

Methods: On the basis of biomarkers, we conducted agglomerative hierarchical clustering to identify patient and biomarker clusters. We then explored the relationship between the patient clusters and clinical characteristics using Chi-square analyses. We determined classification errors and areas under the receiver operating curve of Random Forest Classifiers (RFC) for patient subpopulations using the biomarker clusters to reduce the dimensionality of the data.

Results: Agglomerative clustering identified five patient clusters and seven biomarker clusters. Final diagnoses categories were non-randomly distributed across the five patient clusters. In addition, two of the patient clusters were enriched with patients with ‘low cancer-risk’ characteristics. The biomarkers which contributed to the diagnostic classifiers for these two patient clusters were similar. In contrast, three of the patient clusters were significantly enriched with patients harboring ‘high cancer-risk” characteristics including proteinuria, aggressive pathological stage and grade, and malignant cytology. Patients in these three clusters included controls, that is, patients with other serious disease and patients with cancers other than UC. Biomarkers which contributed to the diagnostic classifiers for the largest ‘high cancer- risk’ cluster were different than those contributing to the classifiers for the ‘low cancer-risk’ clusters. Biomarkers which contributed to subpopulations that were split according to smoking status, gender and medication were different.

Conclusions: The systems biology approach applied in this study allowed the hematuric patients to cluster naturally on the basis of the heterogeneity within their biomarker data, into five distinct risk subpopulations. Our findings highlight an approach with the promise to unlock the potential of biomarkers. This will be especially valuable in the field of diagnostic bladder cancer where biomarkers are urgently required. Clinicians could interpret risk classification scores in the context of clinical parameters at the time of triage. This could reduce cystoscopies and enable priority diagnosis of aggressive diseases, leading to improved patient outcomes at reduced costs. © 2013 Emmert-Streib et al; licensee BioMed Central Ltd.

Standardization of diagnostic biomarker concentrations in urine; the hematuria caveat

Sensitive and specific urinary biomarkers can improve patient outcomes in many diseases through informing early diagnosis. Unfortunately, to date, the accuracy and translation of diagnostic urinary biomarkers into clinical practice has been disappointing. We believe this may be due to inappropriate standardization of diagnostic urinary biomarkers. Our objective was therefore to characterize the effects of standardizing urinary levels of IL-6, IL-8, and VEGF using the commonly applied standards namely urinary creatinine, osmolarity and protein. First, we report results based on the biomarker levels measured in 120 hematuric patients, 80 with pathologically confirmed bladder cancer, 27 with confounding pathologies and 13 in whom no underlying cause for their hematuria was identified, designated “no diagnosis”. Protein levels were related to final diagnostic categories (p = 0.022, ANOVA). Osmolarity (mean = 529 mOsm; median = 528 mOsm) was normally distributed, while creatinine (mean = 10163 µmol/l, median = 9350 µmol/l) and protein (0.3297, 0.1155 mg/ml) distributions were not. When we compared AUROCs for IL-6, IL-8 and VEGF levels, we found that protein standardized levels consistently resulted in the lowest AUROCs. The latter suggests that protein standardization attenuates the “true” differences in biomarker levels across controls and bladder cancer samples. Second, in 72 hematuric patients; 48 bladder cancer and 24 controls, in whom urine samples had been collected on recruitment and at follow-up (median = 11 (1 to 20 months)), we demonstrate that protein levels were approximately 24% lower at follow-up (Bland Altman plots). There was an association between differences in individual biomarkers and differences in protein levels over time, particularly in control patients.

Spin-Based Diagnostic of Nanostructure in Copper Phthalocyanine-C-60 Solar Cell Blends

Nanostructure and molecular orientation play a crucial role in determining the functionality of organic thin films. In practical devices, such as organic solar cells consisting of donor-acceptor mixtures, crystallinity is poor and these qualities cannot be readily determined by conventional diffraction techniques, while common microscopy only reveals surface morphology. Using a simple nondestructive technique, namely, continuous-wave electron paramagnetic resonance spectroscopy, which exploits the well-understood angular dependence of the g-factor and hyperfine tensors, we show that in the solar cell blend of C-60 and copper phthalocyanine (CuPc)-for which X-ray diffraction gives no information-the CuPc, and by implication the C-60, molecules form nanoclusters, with the planes of the CuPc molecules oriented perpendicular to the film surface. This information demonstrates that the current nanostructure in CuPc:C-60 solar cells is far from optimal and suggests that their efficiency could be considerably increased by alternative film growth algorithms.

Neonatal facial and cry responses to invasive and non-invasive procedures

Evaluation of pain in neonates is difficult due to their limited means of communication. The aim was to determine whether behavioural reactions of cry and facial activity provoked by an invasive procedure could be discriminated from responses to non-invasive tactile events. Thirty-six healthy full-term infants (mean age 2.2 h) received 3 procedures in counterbalanced order: intramuscular injection, application of triple dye to the umbilical stub, and rubbing thigh with alcohol. Significant effects of procedure were found for total face activity and latency to face movement. A cluster of facial actions comprised of brow bulging, eyes squeezed shut, deepening of the naso-labial furrow and open mouth was associated most frequently with the invasive procedure. Comparisons between the 2 non-invasive procedures showed more facial activity to thigh swabbing and least to application of triple dye to the umbilical cord. Acoustic analysis of cry showed statistically significant differences across procedures only for latency to cry and cry duration for the group as a whole. However, babies who cried to two procedures showed higher pitch and greater intensity to the injection. There were no significant differences in melody, dysphonation, or jitter. Methodological difficulties for investigators in this area were examined, including criteria for the selection of cries for analysis, and the logical and statistical challenges of contrasting cries induced by different conditions when some babies do not always cry. It was concluded that facial expression, in combination with short latency to onset of cry and long duration of first cry cycle typifies reaction to acute invasive procedures.

Demarcation laser therapy in the management of macular-sparing persistent subretinal fluid after scleral buckling procedures

Background: Persistent or recurrent macular-sparing subretinal fluid (SRF) can sometimes occur following scleral buckling procedures. Observation and reoperation have been used in the management of such cases. Demarcation laser therapy (DLT) has been used to treat macular-sparing retinal detachments in the context of cytomegalovirus retinitis and as primary treatment for selected rhegmatogenous retinal detachments. There are, however, scarce data in the literature regarding its use following primary scleral buckling procedures. The current study explores the use of DLT under the latter circumstances. Methods: The medical records of all consecutive patients with persistent SRF sparing the macula following primary rhegmatogenous retinal detachment repair using a scleral buckling procedure were retrospectively reviewed. Only those patients in whom the breaks were localised to the area of indentation and, thus, seemed to be well supported by the buckle were included. Demographics, clinical characteristics of the retinal detachment prior to scleral buckling, extension of the residual SRF observed postoperatively, details of the laser procedure, anatomical and functional outcomes and complications were evaluated. Results: Seven patients, all females, with a mean age of 47.9 years (range: 20-81) were included in the study. The retinal detachments were superior (n=3), inferior (n=3) and subtotal, affecting both superior and inferior retina (n=1). Scleral buckling procedures were used to treat the retinal detachments in all cases. Following demarcation laser therapy, the area of SRF remained stable in two patients, and flattened in four. In one patient, extension of SRF occurred requiring further surgery. Conclusions: Demarcation laser therapy appears to be a reasonable option in the management of patients with persistent or recurrent SRF sparing the macula following scleral buckling surgery. © Springer-Verlag 2006.

Indications for penetrating keratoplasty and associated procedures, 1989-1995

Purpose. To identify changing trends in indications for penetrating keratoplasty and associated surgical procedures. Methods. Review of charts from all patients who underwent penetrating keratoplasty at Wills Eye Hospital from January 1, 1989 through December 31, 1995. Results. A total of 2,442 corneal transplants were performed in 2,186 patients. The leading indication for penetrating keratoplasty was pseudophakic corneal edema, accounting for 634 cases (26.0%); 54.7% of them were associated with anterior chamber intraocular lenses, 36.4% with posterior chamber intraocular lenses, and 3.1% with iris-fixated intraocular lenses. Regraft (17.8%), Fuchs' dystrophy (15.7%), and keratoconus (13.2%) followed pseudophakic corneal edema in frequency. Cataract extraction, with or without intraocular lens implantation, was combined with penetrating keratoplasty in 439 cases of 1,264 phakic eyes (34.7%). Intraocular lens exchange was performed in 285 of the 634 cases of pseudophakic cornea edema (44.9%). Conclusion. Pseudophakic corneal edema was the leading indication for penetrating keratoplasty, with an increasing number of cases associated with posterior chamber intraocular lenses during the study period (p = 0.001). The number of regrafts steadily increased between 1989 and 1995 (p = 0.001), being the second most common indication for corneal transplantation since 1992.