Individualised variable-interval risk-based screening for sight-threatening diabetic retinopathy: the Liverpool Risk Calculation Engine.

AIMS/HYPOTHESIS: Individualised variable-interval risk-based screening offers better targeting and improved cost-effectiveness in screening for diabetic retinopathy. We developed a generalisable risk calculation engine (RCE) to assign personalised intervals linked to local population characteristics, and explored differences in assignment compared with current practice. METHODS: Data from 5 years of photographic screening and primary care for people with diabetes, screen negative at the first of > 1 episode, were combined in a purpose-built near-real-time warehouse. Covariates were selected from a dataset created using mixed qualitative/quantitative methods. Markov modelling predicted progression to screen-positive (referable diabetic retinopathy) against the local cohort history. Retinopathy grade informed baseline risk and multiple imputation dealt with missing data. Acceptable intervals (6, 12, 24 months) and risk threshold (2.5%) were established with patients and professional end users. RESULTS: Data were from 11,806 people with diabetes (46,525 episodes, 388 screen-positive). Covariates with sufficient predictive value were: duration of known disease, HbA1c, age, systolic BP and total cholesterol. Corrected AUC (95% CIs) were: 6 months 0.88 (0.83, 0.93), 12 months 0.90 (0.87, 0.93) and 24 months 0.91 (0.87, 0.94). Sensitivities/specificities for a 2.5% risk were: 6 months 0.61, 0.93, 12 months 0.67, 0.90 and 24 months 0.82, 0.81. Implementing individualised RCE-based intervals would reduce the proportion of people becoming screen-positive before the allocated screening date by > 50% and the number of episodes by 30%. CONCLUSIONS/INTERPRETATION: The Liverpool RCE shows sufficient performance for a local introduction into practice before wider implementation, subject to external validation. This approach offers potential enhancements of screening in improved local applicability, targeting and cost-effectiveness.

Predictive value of N95 waveforms of pattern electroretinograms (PERGs) in children with optic nerve hypoplasia (ONH).

PURPOSE: As part of a long-term, prospective study of prenatal and clinical risk factors for optic nerve hypoplasia (ONH) at Children's Hospital Los Angeles, pattern ERGs (PERGs) were evaluated for prognostic value using an automated objective and robust analytical method. METHODS: Participants were 33 children with ophthalmoscopically diagnosed ONH [disc diameter-to-disc macula ratio (DD/DM) less than 0.35 in one or both eyes on fundus photographs]. Using cycloplegia and chloral hydrate sedation in one session before 26 months of age, we recorded PERGs to checkerboard reversal using five check sizes. Participants were followed with clinical and psychometric testing until 5 years of age. PERGs were analysed using automated robust statistics based on magnitude-squared coherence and bootstrapping optimized to objectively quantify PERG recovery in the challenging recordings encountered in young patients. PERG measures in the fixating or better-seeing eyes were compared with visual outcome data. RESULTS: PERG recording was complete to at least three check sizes in all eyes and to all five sizes in 79%. Probability of recording a PERG that is significantly different from noise varied with check size from 73% for the largest checks to 30% for the smallest checks (p = 0.002); smaller waveforms were associated with earlier implicit times. The presence of significant PERGs in infancy is associated with better visual outcomes; the strongest association with visual outcome was for the threshold check size with a significant N95 component (ρ = 0.398, p = 0.02). CONCLUSIONS: Automated statistically robust signal-processing techniques reliably and objectively detect PERGs in young children with ONH and show that congenital deficits of retinal ganglion cells are associated with diminished or non-detectable PERGs. The later negativity, N95, was the best indicator of visual prognosis and was most useful to identify those with good visual outcomes (≤0.4 LogMAR). Although PERGs reflect function of the inner layers of the central retina, they lack the specificity required to determine prognosis reliably in individual cases.

Cluster analysis of multiplex ligation-dependent probe amplification data in choroidal melanoma.

PURPOSE: To determine underlying correlations in multiplex ligation-dependent probe amplification (MLPA) data and their significance regarding survival following treatment of choroidal melanoma (CM). METHODS: MLPA data were available for 31 loci across four chromosomes (1p, 3, 6, and 8) in tumor material obtained from 602 patients with CM treated at the Liverpool Ocular Oncology Center (LOOC) between 1993 and 2012. Data representing chromosomes 3 and 8q were analyzed in depth since their association with CM patient survival is well-known. Unsupervised k-means cluster analysis was performed to detect latent structure in the data set. Principal component analysis (PCA) was also performed to determine the intrinsic dimensionality of the data. Survival analyses of the identified clusters were performed using Kaplan-Meier (KM) and log-rank statistical tests. Correlation with largest basal tumor diameter (LTD) was investigated. RESULTS: Chromosome 3: A two-cluster (bimodal) solution was found in chromosome 3, characterized by centroids at unilaterally normal probe values and unilateral deletion. There was a large, significant difference in the survival characteristics of the two clusters (log-rank, p<0.001; 5-year survival: 80% versus 40%). Both clusters had a broad distribution in LTD, although larger tumors were characteristically in the poorer outcome group (Mann-Whitney, p<0.001). Threshold values of 0.85 for deletion and 1.15 for gain optimized the classification of the clusters. PCA showed that the first principal component (PC1) contained more than 80% of the data set variance and all of the bimodality, with uniform coefficients (0.28±0.03). Chromosome 8q: No clusters were found in chromosome 8q. Using a conventional threshold-based definition of 8q gain, and in conjunction with the chromosome 3 clusters, three prognostic groups were identified: chromosomes 3 and 8q both normal, either chromosome 3 or 8q abnormal, and both chromosomes 3 and 8q abnormal. KM analysis showed 5-year survival figures of approximately 97%, 80%, and 30% for these prognostic groups, respectively (log-rank, p<0.001). All MLPA probes within both chromosomes were significantly correlated with each other (Spearman, p<0.001). CONCLUSIONS: Within chromosome 3, the strong correlation between the MLPA variables and the uniform coefficients from the PCA indicates a lack of evidence for a signature gene that might account for the bimodality we observed. We hypothesize that the two clusters we found correspond to binary underlying states of complete monosomy or disomy 3 and that these states are sampled by the complete ensemble of probes. Consequently, we would expect a similar pattern to emerge in higher-resolution MLPA data sets. LTD may be a significant confounding factor. Considering chromosome 8q, we found that chromosome 3 cluster membership and 8q gain as traditionally defined have an indistinguishable impact on patient outcome.

Comparison of human expert and computer-automated systems using magnitude-squared coherence (MSC) and bootstrap distribution statistics for the interpretation of pattern electroretinograms (PERGs) in infants with optic nerve hypoplasia (ONH).

PURPOSE: Pattern electroretinograms (PERGs) have inherently low signal-to-noise ratios and can be difficult to detect when degraded by pathology or noise. We compare an objective system for automated PERG analysis with expert human interpretation in children with optic nerve hypoplasia (ONH) with PERGs ranging from clear to undetectable. METHODS: PERGs were recorded uniocularly with chloral hydrate sedation in children with ONH (aged 3.5-35 months). Stimuli were reversing checks of four sizes focused using an optical system incorporating the cycloplegic refraction. Forty PERG records were analysed; 20 selected at random and 20 from eyes with good vision (fellow eyes or eyes with mild ONH) from over 300 records. Two experts identified P50 and N95 of the PERGs after manually deleting trials with movement artefact, slow-wave EEG (4-8 Hz) or other noise from raw data for 150 check reversals. The automated system first identified present/not-present responses using a magnitude-squared coherence criterion and then, for responses confirmed as present, estimated the P50 and N95 cardinal positions as the turning points in local third-order polynomials fitted in the -3 dB bandwidth [0.25 … 45] Hz. Confidence limits were estimated from bootstrap re-sampling with replacement. The automated system uses an interactive Internet-available webpage tool (see http://clinengnhs.liv.ac.uk/esp_perg_1.htm). RESULTS: The automated system detected 28 PERG signals above the noise level (p ≤ 0.05 for H0). Good subjective quality ratings were indicative of significant PERGs; however, poor subjective quality did not necessarily predict non-significant signals. P50 and N95 implicit times showed good agreement between the two experts and between experts and the automated system. For the N95 amplitude measured to P50, the experts differed by an average of 13% consistent with differing interpretations of peaks within noise, while the automated amplitude measure was highly correlated with the expert measures but was proportionally larger. Trial-by-trial review of these data required approximately 6.5 h for each human expert, while automated data processing required <4 min, excluding overheads relating to data transfer. CONCLUSIONS: An automated computer system for PERG analysis, using a panel of signal processing and statistical techniques, provides objective present/not-present detection and cursor positioning with explicit confidence intervals. The system achieves, within an efficient and robust statistical framework, estimates of P50 and N95 amplitudes and implicit times similar to those of clinical experts.

Impact of allergic rhinitis and its treatment on the pharmacokinetics of nasally administered fentanyl.

OBJECTIVES: Fentanyl pectin nasal spray (FPNS, Lazanda® in the US and PecFent® in Europe and Australia) is a novel analgesic approved for the management of breakthrough pain in cancer patients. Given that the fentanyl is nasally administered, it is important to understand whether concomitant allergic rhinitis, or its treatment with a vasoconstrictor, would affect its absorption and, potentially, its efficacy or safety. METHODS AND SUBJECTS: Subjects with a history of allergic rhinitis were screened to identify subjects who developed at least moderate rhinitis symptoms on exposure to pollen allergen (either ragweed or tree) in an environmental exposure chamber (EEC). These were entered into a randomized, three-way crossover study in which each subject received 100 µg of FPNS under three exposure conditions; Control (no rhinitis), Rhinitis (symptomatic without decongestant), Treated (symptomatic with concomitant oxymetazoline). Blood samples for fentanyl were collected over a 24-hour period. RESULTS: A total of 132 subjects was screened to identify 54 for inclusion in the study; 31 were evaluable for pharmacokinetics. Measures of fentanyl absorption (mean or median) were similar between Control and Rhinitis conditions: Cmax 453.0 vs. 467.8 pg/ml; AUCt 1,292.3 vs. 1,325.4 pg×h/ml, AUC0-∞ 1,430.6 vs. 1,387 pg×h/ml and tmax 20 vs. 17 minutes. When oxymetazoline was co-administered, overall fentanyl absorption was slightly reduced (AUC0-∞ 1,362.4 pg×h/ml); but, more clinically relevant were the delayed rate of absorption (tmax 53 minutes) and reduced Cmax (235.3 pg/ml). CONCLUSIONS: Patients treated with FPNS will be unaffected by the development of allergic rhinitis; but, if oxymetazoline is prescribed, the patient would benefit from added supervision when oxymetazoline is started and stopped.

Investigation of the temporal properties of the retina using the m-sequence.

The mfERG provides a topographic map of function of the retina and has been used in numerous studies to identify macular, paramacular and peripheral retinal dysfunction. This study investigates the changes in response due to the presentation rate of the stimulus. Twenty subjects gave informed consent to take part in the study, which had local regional ethical committee approval. Only a single hexagon of 8° diameter was presented to reduce ambiguity when identifying the higher-order kernels (HOK). Six rates were tested using a 60-Hz CRT monitor by introducing blank (black ~0 cd/m2) filler frames (FF). The rates tested were 0FF; 1FF; 2FF; 4FF; 7FF; and 14FF. The first-order kernel had largest responses to the slower stimuli (4FF and above). HOK had largest amplitudes at faster rates with the second-order kernel peaking at 1FF. At rates with 4FF and slower, the higher-order kernels were indiscernible above the noise.

Use of Continuous Glucose Monitoring in People with Type 1 Diabetes: Perspectives of Two People with Diabetes and Physician Perspective.

This article details perspectives from two individuals with type 1 diabetes (T1DM) who use continuous glucose monitoring (CGM) devices to improve their quality of life and self-management of diabetes. It provides a unique perspective of how CGM can make living with T1DM safer and easier, while improving the time spent in the target glucose range (time in range). The perspectives of these two individuals highlight both the immediate need for improved access and support for CGM as well as the need for an understanding of the benefits of using non-medically approved technologies.

Artificial neural networks estimating survival probability after treatment of choroidal melanoma.

PURPOSE: To describe neural networks predicting survival from choroidal melanoma (i.e., any uveal melanoma involving choroid) and to demonstrate the value of entering age, sex, clinical stage, cytogenetic type, and histologic grade into the predictive model. DESIGN: Nonrandomized case series. PARTICIPANTS: Patients resident in mainland Britain treated by the first author for choroidal melanoma between 1984 and 2006. METHODS: A conditional hazard estimating neural network (CHENN) was trained according to the Bayesian formalism with a training set of 1780 patients and evaluated with a test set of another 874 patients. Conditional hazard estimating neural network-generated survival curves were compared with those obtained with Kaplan-Meier analyses. A second model was created with information on chromosome 3 loss, using training and test sets of 211 and 140 patients, respectively. MAIN OUTCOME MEASURES: Comparison of CHENN survival curves with Kaplan-Meier analyses. Representative results showing all-cause survival and inferred melanoma-specific mortality, according to age, sex, clinical stage, cytogenetic type, and histologic grade. RESULTS: The predictive model plotted a survival curve with 95% credibility intervals for patients with melanoma according to relevant risk factors: age, sex, largest basal tumor diameter, ciliary body involvement, extraocular extension, tumor cell type, closed loops, mitotic rate, and chromosome 3 loss (i.e., monosomy 3). A survival curve for the age-matched general population of the same sex allowed estimation of the melanoma-related mortality. All-cause survival curves generated by the CHENN matched those produced with Kaplan-Meier analysis (Kolmogorov-Smirnov, P<0.05). In older patients, however, the estimated melanoma-related mortality was lower with the CHENN, which accounted for competing risks, unlike Kaplan-Meier analysis. Largest basal tumor diameter was most predictive of mortality in tumors showing histologic and cytogenetic features of high-grade malignancy. Ciliary body involvement and extraocular extension lost significance when cytogenetic and histologic data were included in the model. Patients with a monosomy 3 melanoma of a particular size were predicted to have shorter survival if their tumor showed epithelioid cells and closed loops. CONCLUSIONS: Estimation of survival prognosis in patients with choroidal melanoma requires multivariate assessment of age, sex, clinical tumor stage, cytogenetic melanoma type, and histologic grade of malignancy.

Heat treatment of arthroscopic knots and its effect on knot security.

PURPOSE: The purpose of this study was to investigate heat application to arthroscopic knots as a method of improving knot security. METHODS: Heat treatment was assessed on 4 suture materials--Ethibond (Ethicon, Somerville, NJ), PDS (Ethicon), Orthocord (DePuy Mitek, Raynham, MA), and FiberWire (Arthrex, Naples, FL)--tied by use of the Duncan loop, compared with untreated controls. A hand-tied surgeon's knot with Ethibond was included as the gold standard. Knots were tied around a plastic rod immersed in a saline solution-filled water bath at 37 degrees C, with heat treatment performed by use of the Mitek VAPR 3 electrosurgical unit and VAPR S(90) electrode (DePuy Mitek), applied directly to the knot body. Loops were subjected to a 5-N preload, followed by loading to clinical failure (>3 mm of displacement) and ultimate (breaking) failure by use of a tensile tester. RESULTS: Load to ultimate failure was significantly higher in the FiberWire 1-second heat treatment arm (26.0% increase, 234.25 +/- 62.34 N, P < .03), Orthocord 1-second heat treatment arm (55.6% increase, 204.72 +/- 78.47 N, P < .03), and Orthocord 5-second heat treatment arm (69.2% increase, 222.58 +/- 56.57 N, P < .001) than in controls. Load to clinical failure was significantly higher in the Orthocord 10-second heat treatment arm (34.7% increase, 78.58 +/- 13.88 N, P < .0001) when compared with controls. The FiberWire 5- and 10-second heat treatment arms showed lower load to clinical and ultimate failure (P < .001). Ethibond, Orthocord, and FiberWire showed higher load to clinical failure than PDS (P < .0001). Ethibond and Orthocord knots were more likely to fail through knot slippage after heat treatment compared with controls (P < .01). CONCLUSIONS: Heat treatment resulted in greater knot security when combined with Orthocord and FiberWire suture materials. Heat-treated Ethibond and Orthocord knots were more likely to fail through suture breakage than knot slippage. CLINICAL RELEVANCE: This study presents a simple and novel technique of improving knot security in the arthroscopic repair. The effects of heat were extremely well tolerated in the Orthocord and FiberWire groups, making this technique particularly suitable for clinical use.

A web-based tool for the assessment of discrimination and calibration properties of prognostic models.

Prognostic models are developed to assist clinicians in making decisions regarding treatment and follow-up management. The accuracy of these models is often assessed either in terms of their discrimination performance or calibration but rarely both. In this paper, we describe the development of an online tool for discrimination using Harrell C index and calibration using a Hosmer-Lemeshow type analysis (http://clinengnhs.liv.ac.uk/AADP/AADP_Welcome.htm). We show examples of using the tool on real data. We highlight situations where the model performed well in terms of either discrimination or calibration but not both depending on the sample size of the test set. We conclude that prognostic models should be assessed both in terms of discrimination and calibration and that calibration analysis should be carried out numerically and graphically.

The behaviour of knots and sutures during the first 12 hours following a Bankart repair.

It has been reported that the effectiveness of arthroscopic procedures in terms of preventing recurrent dislocation has not matched that from open techniques. Also little is known about how these knots behave when exposed to physiological loading following repair. This study presents the development of a practical tool to allow surgeons to test the quality of their arthroscopic knots and allow them to make choices with regard to knot configuration and suture material. This study uses an apparatus to model the repair of a Bankart lesion. Ten examples of the Duncan loop and SMC knots were tied using PDS, Ethibond, Panacryl and Fibrewire. An arthroscopic knotting technique was used. Reverse slippage occurring during the tying process was recorded. Each knot was then left for 12 hours under loads equivalent to a Bankart repair and the subsequent reverse slippage was recorded. After initial passing of the Duncan loop and after passing of locking hitches the sutures were ranked inversely to size of suture loop (resistance to slippage). Only Fibrewire showed a significant difference (5.7 +/- 1.03 mm to 5.66 +/- 0.5 mm; p <0.05). After 12 hrs, some evidence of reverse slippage was noted, especially with Fibrewire (5.66 +/- 0.5 mm--significant p <0.05). The SMC knot showed generally inferior results. In this study using arthroscopic techniques, Fibrewire performed less well than other materials.

Pain, functional disability, and psychologic status in tennis elbow.

OBJECTIVES: First to compare pain and functional disability in tennis elbow (TE) patients with healthy controls. Second, to evaluate the relationship between the 2 major psychologic factors (anxiety and depression) and TE. METHODS: Sixteen TE patients were recruited from 46 consecutive attendees at an upper limb clinic: inclusion criteria were lateral epicondyle tenderness, pain with resisted wrist and middle finger extension and at least 3 months localized lateral elbow pain. Sixteen healthy controls with no upper limb problem were recruited from students and staff. Participants were given 4 questionnaires, together with instructions for completion: Disabilities of the Arm, Shoulder, and Hand, Patient-Rated Forearm Evaluation Questionnaire, Patient-Rated Wrist Evaluation Questionnaire, and Hospital Anxiety and Depression Scale. The independent t test was used to compare the total and subscale scores between the groups. RESULTS: Significantly higher scores were found in TE for pain and function subscales and also total score for Disabilities of the Arm, Shoulder, and Hand, Patient-Rated Forearm Evaluation Questionnaire, and Patient-Rated Wrist Evaluation Questionnaire. For Hospital Anxiety and Depression Scale, both anxiety and depression subscales (P<0.001) and the total score (P<0.01) were significantly higher in TE. According to the anxiety and depression subscales, 55% and 36% of patients, respectively, were classified as probable cases (score >11). DISCUSSION: TE patients showed markedly increased pain and functional disability. Significantly elevated levels of depression and anxiety pointed out the importance of psychologic assessment in TE patients. In the development of supportive and treatment strategies, we suggest the combination of "upper limb" and "psychologic" assessment tools.

The differential diagnosis of vertical strabismus from prism cover test data using an artificially intelligent expert system.

An expert system is described for the differential diagnosis of vertical deviation strabismus (squint) from measurements taken in the standard prism cover test. The deviations are represented as optical powers in prism dioptres using the graphic representation of strabismus (after Jampolsky). The expert is implemented in MatLab (Mathworks Ltd., Cambridge, UK) both as a stand-alone program on a PC and as a web application available over the Internet (see http://www.strabnet.com ). In trial and clinical datasets a diagnostic accuracy of 100% was achieved.

Corneal topographic features in a family with nanophthalmos.

PURPOSE: To characterize the corneal topographic features in a family with nanophthalmos. METHODS: Two observational case reports and a review of the literature. Corneal shape was analyzed using a topographic modeling system (TMS) and an Orbscan topographic system, with further analysis based on Fourier series and Zernicke polynomials. A control group was used for comparison. RESULTS: Two female family members with nanophthalmos belonging to the same generation showed significant irregular corneal astigmatism and corneal steepening. CONCLUSION: Topographic corneal steepening and irregular astigmatism seems to be associated in 1 family with inherited nanophthalmos. Higher degrees of irregular astigmatism, which were not evident without a topographic analysis, may account, in part, for the unexplained visual reduction.

Terrien marginal degeneration presenting with spontaneous corneal perforation.

PURPOSE: To report spontaneous corneal perforation as a presenting sign of unilateral Terrien marginal degeneration in a young adult. METHODS: A 19-year-old woman presented with sudden loss of vision in her left eye of 1-day duration. Examination revealed superior corneal thinning with superficial vascularization and secondary lipid keratopathy. There was an area of corneal perforation at the 11 o'clock position, leading to a shallow anterior chamber, ocular hypotony, and a hypotonic maculopathy. The right eye was normal on biomicroscopy. RESULTS: The area of perforation was confirmed by a positive Seidel test. A 22-mm-diameter bandage contact lens was fitted, which led to closure of the perforation and reformation of the anterior chamber. Orbscan corneal topography confirmed superior corneal thinning, 2.3 D of against-the-rule astigmatism, and 3.4 D of irregular astigmatism in the central 3-mm zone. Topography of the right showed no apparent abnormality. CONCLUSION: Terrien marginal degeneration is an unusual cause for a spontaneous corneal perforation. Patients with this disorder should be warned about this possibility.

A New Multi-Ingredient Recipe for the Treatment of Localized Advanced Periodontal Disease following the Surgical Removal of Impacted Wisdom Teeth.

Periodontal disease is a chronic inflammation of the tooth supporting structures. It leads to bone and attachment loss which is irreversible. Extraction of horizontally impacted lower third molar (L3M) teeth may result in localized periodontal pockets at the distal aspect of the adjacent lower second molars (L2M). We present a case of a 21-year-old male who suffered from a swelling and pain around his lower right second molar following surgical removal of a mesioangular impacted lower right third molar. We showed that oral hygiene measures, surgical access, mixture of autogenous and synthetic bone graft, and guided tissue regeneration (GTR) were enough to control the problem.

Systematic Review of Soft Tissue Alterations and Esthetic Outcomes Following Immediate Implant Placement and Restoration of Single Implants in the Anterior Maxilla.

BACKGROUND: The aim of this review is to assess the outcome of single-tooth immediate implant placement and restoration (IPR) in the maxillary anterior region, with a particular emphasis on soft tissue and esthetic outcomes. METHODS: An electronic search in Medline, EBSCOhost, and Ovid (PubMed) was performed to identify studies that reported on soft tissue outcomes following immediate placement and restoration of implants in the maxillary esthetic region with a mean follow-up of ≥1 year. RESULTS: Nineteen studies on single implants inserted immediately into fresh extraction sockets and provisionally restored in the maxillary esthetic region were included. Soft tissue changes were found to be acceptable, with most studies reporting mean gingival recession of 0.27 ± 0.38 mm and mean papillary height loss of 0.23 ± 0.27 mm after follow-up of ≥1 year. Advanced buccal recession (>1 mm) occurred in 11% of cases. Long-term follow-up studies (>2 years) reported that the interdental papillae, in particular, showed a tendency to rebound over time. The few studies that reported on patient-centered outcomes showed a high level of patient satisfaction with the outcomes of IPR treatment. CONCLUSIONS: The IPR protocol resulted in generally acceptable soft tissue and esthetic outcomes, with suboptimal results reported in ≈11% of low-risk cases. Factors such as preoperative tissue biotype or use of a flap or connective tissue graft did not significantly influence soft tissue and esthetic outcomes. Long-term prospective controlled clinical trials are necessary to identify factors that may influence the esthetic outcomes associated with IPR.

Temporary sympathectomy in chronic refractory angina: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Temporary sympathectomy by injection of bupivacaine at the site of the left stellate ganglion is used in the management of refractory angina at several UK centres. Although patients frequently report significant reduction in symptoms, efficacy has not been established by double-blind, randomised placebo-controlled trial (RCT). OBJECTIVE: To investigate the efficacy of the procedure for the first time by a double-blind RCT. METHODS: Consecutive patients referred to the authors' National Health Service (NHS) angina centre who were candidates for temporary sympathectomy were invited to participate in a trial. A total of 65 patients were randomised to receive either bupivacaine or saline injections. Identical syringes were prepared remotely, blinding patients and staff from randomisation. Cardiac autonomic function was measured 3 hours pre- and post-injection using new heart rate variability (HRV) analyses. Angina episodes were recorded contemporaneously by patients in study diaries in the 7-day periods pre- and post-injection. RESULTS: In 51 patients suitable for analysis, no significant differences between the active and placebo groups were found in patient-recorded frequency or intensity of angina episodes pre- and post-injection. However, across both groups combined, a significant difference was found in the frequency of angina episodes pre- and post-injection. CONCLUSION: The reduction in frequency of angina episodes produced by this procedure may not be due to drug pharmacology. It may be a placebo response or due to the mechanical effects of the injection of fluid. There is a need for further work using a larger patient cohort considering both mechanical and psychological factors.

Pilot study of nasal morphine-chitosan for the relief of breakthrough pain in patients with cancer.

Breakthrough pain in patients with cancer is common, often unpredictable, and can rapidly become severe. Treatment using the oral administration of opioids is not optimal due to the slow onset of pain relief. Nasal administration of analgesics potentially offers more rapid pain relief. This study investigates the tolerability and efficacy of a novel morphine-chitosan formulation. Twenty episodes of breakthrough pain were observed in 14 patients with cancer who received 5-80 mg of nasal morphine-chitosan. Nasal symptoms, sedation, giddiness, nausea, and other volunteered symptoms, along with pain scores (pain intensity and pain relief), were recorded at baseline and at regular intervals up to 4 hours after administration, together with an overall satisfaction rating. The formulation was acceptable to patients, generally well tolerated, and had an onset of pain relief 5 minutes after dosing. This formulation warrants further study.

Modelling survival after treatment of intraocular melanoma using artificial neural networks and Bayes theorem.

This paper describes the development of an artificial intelligence (AI) system for survival prediction from intraocular melanoma. The system used artificial neural networks (ANNs) with five input parameters: coronal and sagittal tumour location, anterior tumour margin, largest basal tumour diameter and the cell type. After excluding records with missing data, 2331 patients were included in the study. These were split randomly into training and test sets. Date censorship was applied to the records to deal with patients who were lost to follow-up and patients who died from general causes. Bayes theorem was then applied to the ANN output to construct survival probability curves. A validation set with 34 patients unseen to both training and test sets was used to compare the AI system with Cox's regression (CR) and Kaplan-Meier (KM) analyses. Results showed large differences in the mean 5 year survival probability figures when the number of records with matching characteristics was small. However, as the number of matches increased to > 100 the system tended to agree with CR and KM. The validation set was also used to compare the system with a clinical expert in predicting time to metastatic death. The rms error was 3.7 years for the system and 4.3 years for the clinical expert for 15 years survival. For < 10 years survival, these figures were 2.7 and 4.2, respectively. We concluded that the AI system can match if not better the clinical expert's prediction. There were significant differences with CR and KM analyses when the number of records was small, but it was not known which model is more accurate.