Ocular nonsteroidal inflammatory drugs: where do we stand today?

Since their first introduction in ophthalmology, the use of NSAIDs (nonsteroidal anti-inflammatory drugs) has been exponentially expanded, with numerous therapeutic applications. Despite their controversial history, they have proven their efficacy as anti-inflammatory agents in a variety of diseases. Nowadays, NSAIDs are part of surgical protocols of the most commonly performed ophthalmic operations, such as cataract or ocular surgery. They are universally implicated in the management of conjunctivitis, retinal and choroidal disease and miscellaneous inflammatory diseases. Moreover, although linked with serious adverse events and toxicities, their therapeutic magnitude in Ophthalmology should not be affected. This review systematically portrays the variety of ocular NSAIDs available to date, along with their differences in their way of action, indications and potential side effects in various ophthalmologic conditions.

Co-payments for emergency department visits: a quasi-experimental study.

OBJECTIVES: Financial recession in Cyprus has led to health reforms to promote efficiency and reduce public expenditure. In this context, a co-payment fee was introduced in 2013 for all emergency department (ED) visits, with the aim of reducing potentially avoidable visits. The objective of this study was to assess the short-term intended and unintended impacts of introducing these co-payments. STUDY DESIGN: The study design is an interrupted time series analysis. METHODS: We used an autoregressive integrated moving average model for interrupted time series analysis of data on ED visits over 42 consecutive months, from 2013 to 2015 in a regional hospital in Cyprus. The ED visits have been classified to non-avoidable and potentially avoidable visits. RESULTS: The introduction of co-payment had no effect on non-avoidable visits (4% [95% confidence interval {CI}: 4.3-11.08] P = 0.694). However, it had the immediate and sustained effect of reducing potentially avoidable visits, an effect that was statistically significant from the first month onwards (29.8% [95% CI: 22.6-34.1] P < 0.00001). CONCLUSIONS: Co-payments can be a valuable tool for reducing potentially avoidable emergency department visits, without adversely impacting non-avoidable visits. This is a particularly significant finding for countries experiencing financial pressures and struggling to reduce waste in health expenditure. However, the long-term impact of this policy must be assessed, including potential negative effects on public health, to make sure it does not create barriers in obtaining necessary health care that might actually increase expenses in the long run. In particular, timely access to primary care services must be safeguarded.

Single-payer or a multipayer health system: a systematic literature review.

OBJECTIVES: Healthcare systems worldwide are actively exploring new approaches for cost containment and efficient use of resources. Currently, in a number of countries, the critical decision to introduce a single-payer over a multipayer healthcare system poses significant challenges. Consequently, we have systematically explored the current scientific evidence about the impact of single-payer and multipayer health systems on the areas of equity, efficiency and quality of health care, fund collection negotiation, contracting and budgeting health expenditure and social solidarity. STUDY DESIGN: This is a systematic review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. METHODS: A search for relevant articles published in English was performed in March 2015 through the following databases: Excerpta Medica Databases, Cumulative Index of Nursing and Allied Health Literature, Medical Literature Analysis and Retrieval System Online through PubMed and Ovid, Health Technology Assessment Database, Cochrane database and WHO publications. We also searched for further articles cited by eligible papers. RESULTS: A total of 49 studies were included in the analysis; 34 studied clinical outcomes of patients enrolled in different health insurances, while 15 provided a qualitative assessment in this field. CONCLUSION: The single-payer system performs better in terms of healthcare equity, risk pooling and negotiation, whereas multipayer systems yield additional options to patients and are harder to be exploited by the government. A multipayer system also involves a higher administrative cost. The findings pertaining to the impact on efficiency and quality are rather tentative because of methodological limitations of available studies.

The Ariadne's thread in co-payment, primary health care usage and financial crisis: findings from Cyprus public health care sector.

OBJECTIVES: Cyprus entered a prolonged financial recession in 2011 and by early 2013 it applied for an international bail-out agreement. This presupposed massive reforms in public governance. Health sector was considerably reformed and one of the measures was the introduction of co-payment for outpatient visits to public health care sector. The scope of this study is to assess the impact of financial crisis and co-payment to public outpatient visits in Nicosia urban and greater Nicosia region. STUDY DESIGN: An Interrupted time-series analysis. METHODS: All outpatient visits to public health care family doctor/general practitioners in Nicosia urban and greater Nicosia region from January 2011 until May of 2014 were registered and analysed. RESULTS: Financial crisis did not alter outpatient visits. Introduction of co-payment led to a statistically significant decrease from the second month after its introduction (p = 0.048) (R(2) = 0.329, Q = 23.75, p = 0.137). This decrease was consistent until the end of the observational period and it did not level off. CONCLUSIONS: Financial crisis did not affect outpatient visits while co-payment can be considered as a potent cost containment measure during financial recession, by normalising utilisation of healthcare resources.

All-silicon monolithic Mach-Zehnder interferometer as a refractive index and bio-chemical sensor.

A complete Mach-Zehnder interferometer monolithically integrated on silicon is presented and employed as a refractive index and bio-chemical sensor. The device consists of broad-band light sources optically coupled to photodetectors through monomodal waveguides forming arrays of Mach-Zehnder interferometers, all components being monolithically integrated on silicon through mainstream silicon technology. The interferometer is photonically engineered in a way that the phase difference of light travelling through the sensing and reference arms is approximately wavelength independent. Consequently, upon effective medium changes, it becomes feasible even with a broad-band source to induce sinusoidal-type of detector photocurrents similar to the classical monochromatic counterparts. The device is completed with its fluidic and interconnect components so that on chip interferometric measurements can be performed. Examples of refractive index and protein sensing are presented to establish the potential of the proposed device for real-time in situ monitoring applications. This is the only silicon device that has achieved complete on-chip interferometry.

Effects of polythiophene surface structure on adsorption and conformation of bovine serum albumin: a multivariate and multitechnique study.

Protein interactions with surfaces of promising conducting polymers are critical for development of bioapplications. Surfaces of spin-cast and postbaked poly(3-alkylthiophenes), regiorandom P3BT, and regioregular RP3HT are examined prior to and after adsorption of model protein, bovine serum albumin, with time-of-flight secondary ion mass spectrometry, atomic force microscopy, and X-ray photoelectron spectroscopy. The multivariate method of principal component analysis applied to ToF-SIMS data maximizes information on subtle differences in surface chemistry: PCA reveals alkyl side chains and conjugated backbones, exposed for RP3HT and P3BT, respectively. Phase imaging AFM shows semicrystalline microstructure of RP3HT and amorphous morphology of P3BT films. A cellular-like pattern of proteins adsorbed on RP3HT develops with coverage to more uniform overlayer, observed always on P3BT. The amount of adsorbed protein, determined by XPS as a function of BSA concentration (up to 10 mg/mL), is ∼21% lower for RP3HT than P3BT (up to 1.1 mg/m(2)). Although PCA differentiates protein from polythiophene, relative protein surface composition evaluated from ToF-SIMS saturates rather than increases with amount of adsorbed BSA from XPS. This reflects ToF-SIMS sensitivity to outermost layer of proteins, enabling multivariate analysis of protein conformation or orientation. PCA distinguishes between amino acids characteristic for external regions of BSA adsorbed to P3BT and RP3HT. These amino acids are identified for P3BT and RP3HT as hydrophilic and hydrophobic, respectively, by relative hydrophobicity of amino acid side chains. Alternative identification with BSA domains fails, pointing to substrate-induced changes in conformation and degree of denaturation rather than orientation of adsorbed protein.

Plasma-assisted nanoscale protein patterning on Si substrates via colloidal lithography.

Selective immobilization of proteins in well-defined patterns on substrates has recently attracted considerable attention as an enabling technology for applications ranging from biosensors and BioMEMS to tissue engineering. In this work, a method is reported for low-cost, large scale and high throughput, selective immobilization of proteins on nanopatterned Si, based on colloidal lithography and plasma processing to define the areas (<300 nm) where proteins are selectively immobilized. A close-packed monolayer of PS microparticles is deposited on oxidized Si and, either after microparticle size reduction or alternatively after metal deposition through the PS close-packed monolayer, is used as etching mask to define SiO2 nanoislands (on Si). C4F8 plasma was used to selectively etch and modify the SiO2 nanoislands while depositing a fluorocarbon layer on the Si surface. The plasma-treated surfaces were chemically characterized in terms of functional group identification through XPS analysis and reaction with specific molecules. Highly selective protein immobilization mainly through physical adsorption on SiO2 nanoislands and not on surrounding Si was observed after C4F8 plasma-induced chemical modification of the substrate. The thickness of the immobilized protein monolayer was estimated by means of AFM image analysis. The method reported herein constitutes a cost-efficient route toward rapid, large surface, and high-density patterning of biomolecules on solid supports that can be easily applied in BioMEMS or microanalytical systems.

High-capacity and high-intensity DNA microarray spots using oxygen-plasma nanotextured polystyrene slides.

Commercially available polystyrene (PS) slides were plasma nanotextured (nano-roughened) through treatment in oxygen plasma discharges to create substrates with increased surface area for microarray applications. Conditions of plasma treatment were determined for maximum and uniform oligonucleotide immobilization on these nanotextured PS slides. Oligonucleotides were immobilized onto the surface in the form of biotinylated oligonucleotide/streptavidin conjugates to take advantage of increased protein binding capacity of the substrate. It was found that the amount of oligonucleotides that could be immobilized was increased up to ten times on plasma treated as compared with untreated slides. The sensitivity of detection of labelled hybridized probes was improved by a factor of 20. Optimized nanotextured PS slides were subsequently used to develop a microarray for the detection of three deleterious BRCA1 gene mutations by immobilizing oligonucleotides corresponding to wild and mutant-type sequences. The microarray developed on the nanotextured PS slides provided higher specific hybridization signal and discrimination ratios as compared with flat untreated PS slides.

Multiple iridociliary cysts: One entity with various clinical presentations.

Purpose: Iris cysts have a wide range of clinical manifestations ranging from totally asymptomatic to full-blown glaucoma. The aim of this report is to present three patients with multiple bilateral iridociliary cysts. Each one of them had a different stage of glaucoma and required individualized management. Observations: All three patients presented to our clinic. Patient 1 was a 25-year old female with no symptoms and normal intraocular pressure (IOP), Patient 2 a 20-year old female with cup-disk asymmetry and nocturnal IOP spikes and Patient 3 a 69-year old male with chronic angle closure, uncontrolled IOP on maximum medical therapy and optic nerve cupping. During clinical evaluation, gonioscopic findings raised the suspicion of possible multiple bilateral iridocilary cysts, which were then verified with ultrasound biomicroscopy in all patients. Each case was managed differently; Patient 1 was opted for observation, Patient 2 was started on prostaglandin analogue and Patient 3 underwent trabeculectomy with Mitomycin-C. Conclusions and Importance: Although iris cysts represent a relatively rare entity, patients with this anomaly can be encountered in our everyday clinical practice. They may be totally asymptomatic, where observation alone suffices, or at the other end of the spectrum, they may present with full-blown glaucoma, requiring traditional glaucoma surgeries. Considering the wide variety of clinical manifestations and that management may differ depending on the diagnosis, it is highly important for clinicians to carry out a careful examination, especially in patients with narrow angle. In cases of high suspicion for iris cysts, ancillary testing, such as Ultrasound Biomicroscopy, should be performed for the definite diagnosis as well as for the exclusion of malignancies.

Pseudo-quadriceps sparing in multiple sclerosis.

BACKGROUND: Sparing of the quadriceps muscle has been reported in various myopathies. In multiple sclerosis (MS) and pyramidal syndromes, in general, such a differential involvement of distinct muscle groups has not been described. METHODS: Muscle power was evaluated in 127 patients with chronic pyramidal syndrome caused by MS and 37 patients with acute or chronic paraparesis from other etiologies (mainly cerebro-vascular events). RESULTS: A striking difference in muscle power of the quadriceps (spared) and the iliopsoas (significantly weakened) was found in the patients suffering from chronic pyramidal syndrome caused by MS. The mean muscle power of the iliopsoas was 1.68±1.1 and that of the quadriceps 4.06±1.4 (P<0.00005). In the control group, the mean muscle power was 2±1.2 and 2.4±1.4 (difference not significant), for the iliopsoas and the quadriceps, respectively. CONCLUSIONS: Quadriceps muscle remains relatively spared in patients with MS, even with severe and long-standing paraparesis. Various neuroanatomical, neurophysiological, and rehabilitational mechanisms may be involved and explain this phenomenon. This observation may contribute to the building of more reliable and linear scales for the assessment of motor disability and disease progression in MS.

Extensive unilateral visual field loss due to peripapillary arteriovenous malformation.

We report on a case of extensive unilateral visual field loss due to a peripapillary arteriovenous communication. Interventional case report. A 27-year-old Caucasian woman who was initially managed for retrobulbar optic neuritis underwent fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) 6 months later that revealed an unusual course of the central retinal vein with focal dilatation and co-existent aneurysmal distention of the adjacent large choroidal vein. Subsequent colour Doppler flow imaging of the dilated area confirmed the existence of arterial flow suggesting a "vascular steal" phenomenon resulting in choroidal and optic disc ischaemia. Brain magnetic resonance imaging (MRI) revealed small focal capillary vessel abnormalities in the parietal cortex. The present case highlights the important role of ICGA and FFA in the assessment of patients with optic disc pallor and visual field loss. In our case an unusual ocular vascular abnormality was attributed to a congenital malformation and therefore an unnecessary therapeutic intervention was avoided.

Plasma nanotextured PMMA surfaces for protein arrays: increased protein binding and enhanced detection sensitivity.

Poly(methyl methacrylate) (PMMA) substrates were nanotextured through treatment in oxygen plasma to create substrates with increased surface area for protein microarray applications. Conditions of plasma treatment were found for maximum uniform protein adsorption on these nanotextured PMMA surfaces. Similar results were obtained using both a high-density plasma (HDP) and a low-density reactive ion etcher (RIE), suggesting independence from the plasma reactor type. The protein binding was evaluated by studying the adsorption of two model proteins, namely, biotinylated bovine serum albumin (b-BSA) and rabbit gamma-globulins (RgG). The immobilization of these proteins onto the surfaces was quantitatively determined through reaction with fluorescently labeled binding molecules. It was found that the adsorption of both proteins was increased up to 6-fold with plasma treatment compared to untreated surfaces and up to 4-fold compared to epoxy-coated glass slides. The sensitivity of detection was improved by 2 orders of magnitude. Moreover, highly homogeneous protein spots were created on optimized plasma-nanotextured surfaces through deposition with an automated microarray spotter, revealing the potential of plasma-nanotextured surfaces as protein microarray substrates.

Disseminated hydatid disease in a child: albendazole treatment of orbital cyst.

PURPOSE: Orbital hydatid cyst is rare and represents a small percentage of all echinococcal systemic locations. It is usually a primary echinococcosis. A new case of orbital hydatid cyst with asymptomatic coexistent lung and liver cysts is described in a child. METHODS AND RESULTS: The patient underwent surgical excision of the lung and liver cysts and successful application of albendazole treatment for orbital echinococcal cyst without evidence of recurrence after a 4-year follow-up. CONCLUSIONS: Hydatid cyst should be included in the differential diagnosis of unilateral exophthalmos in patients from countries where echinococcosis is endemic.

Spontaneous resolution of vitreomacular traction following ranibizumab (Lucentis) injection.

PURPOSE: Spontaneous resolution of vitreomacular traction syndrome in diabetic patients is a rare phenomenon that has been poorly described in the literature. METHODS: Case presentation. RESULTS: The authors present a case of spontaneous resolution of vitreomacular traction following intravitreal administration of ranibizumab. CONCLUSIONS: In patients with vitreomacular traction syndrome and diabetic macular edema, the combination of the possible vitreous liquefaction and mechanical increase of vitreous volume caused by an intravitreal injection with a degree of reduction in retinal thickness caused by the effect of vascular endothelial growth factor inhibition could play a role in the resolution of vitreomacular traction.

Anterior chamber lens implantation in vitrectomised eyes.

PurposeTo investigate long-term visual acuity (VA) outcomes and complication rates in vitrectomised eyes undergoing anterior chamber intraocular lens (ACIOL) insertion.Patients and methodsA single-centre, retrospective case series including all patients who had undergone ACIOL placement at the time of vitrectomy surgery or having had previous vitrectomy, between January 2007 and January 2013. Patients were identified using an electronic database and paper casefile notes were analysed for all patients. Patients were excluded if they had <3 months follow-up.ResultsTwo hundred and seventy-one patients were included in the analysis. Mean follow-up was 27 months. One hundred and forty-eight patients were vitrectomised before ACIOL placement. One hundred and twenty-three patients underwent vitrectomy at the time of ACIOL placement. Mean best-corrected visual acuity (BCVA) before ACIOL placement was 1.27 LogMar (SD 0.95). Mean BCVA at final follow-up was 0.51 LogMar (SD 0.66) (paired-sample T-test P<0.001). Forty (15%) patients developed postoperative cystoid macular oedema (CMO). Eighty-seven (32%) patients had an intraocular pressure (IOP) rise acutely post ACIOL insertion. Fifteen (6%) patients developed corneal decompensation. Five subsequently required corneal grafting. Sixteen patients had ACIOL displacement or instability requiring further surgery.ConclusionsACIOL insertion after vitrectomy is effective. Ninety-two per cent of patients maintained or gained VA, comparable to previous studies of ACIOL insertion post complicated cataract surgery. Raised IOP was the most frequent complication: 61 patients were on topical therapy at most recent follow-up. CMO tended to be acute. Corneal decompensation was infrequent.

Silicone oil versus gas tamponade for giant retinal tear-associated fovea-sparing retinal detachment: a comparison of outcome.

PurposeSilicone oil is the most common choice of tamponade agent used when managing a giant retinal tear (GRT). Concern exists regarding its potential detrimental effect on vision. We herein report on visual and surgical outcomes of all patients treated at Moorfields Eye Hospital for a GRT over a five year period. We further analysed a subgroup of fovea-sparing retinal detachments (RD) treated by pars plana vitrectomy (PPV) with either silicone oil or gas tamponade.MethodsRetrospective comparative, non-randomised, cross-sectional review of patients with a new diagnosis of GRT from 1 September 2005 to 31 August 2010ResultsOne hundred twenty four eyes of 118 patients were identified with mean age of 45.5 years and median follow-up of 24 months. Subgroup analysis of fovea-sparing RDs (Silicone Oil n=49, Gas n=15) revealed visual loss (≥2 Snellen Lines of vision) in 49.0% (n=24) of patients managed with oil compared to 13.3% (n=2) of gas patients (P=0.019). In all, 73.3% (n=11) in the gas group achieved a final vision of 6/12 or better, compared to 36.7% (n=18) in the oil group (P=0.031). No difference was observed in eventual or primary anatomical success rate (100 vs 93.9%, and 66.7 vs 79.6%, gas vs oil, respectively, (P>0.1)). Postoperative complications were absent in 66.7% (n=10) of gas patients compared with 14.3% (n=7) of oil patients (P=0.002). Multiple variable linear regression determined tamponade choice as the only variable predictive of final visual acuity (P=0.046).ConclusionEyes with fovea-sparing GRT-related RDs managed with gas achieved a better visual outcome with fewer postoperative complications and no significant difference in anatomical success. A multicentre approach to investigate this further is advised.

Point-of-Need bioanalytics based on planar optical interferometry.

This review brings about a comprehensive presentation of the research on interferometric transducers, which have emerged as extremely promising candidates for viable, truly-marketable solutions for PoN applications due to the attested performance that has reached down to 10(-8) in term of effective refractive index changes. The review explores the operation of the various interferometric architectures along with their design, fabrication, and analytical performance aspects. The issues of biosensor functionalization and immobilization of receptors are also addressed. As a conclusion, the comparison among them is attempted in order to delve into and acknowledge their current limitations, and define the future trends.

Plasma nanotextured polymeric lab-on-a-chip for highly efficient bacteria capture and lysis.

We describe the design, fabrication, and successful demonstration of a sample preparation module comprising bacteria cell capture and thermal lysis on-chip with potential applications in food sample pathogen analysis. Plasma nanotexturing of the polymeric substrate allows increase of the surface area of the chip and the antibody binding capacity. Three different anti-Salmonella antibodies were directly and covalently linked to plasma treated chips without any additional linker chemistry or other treatment. Then, the Ab-modified chips were tested for their capacity to bind bacteria in the concentration range of 10(2)-10(8) cells per mL; the module exhibited 100% efficiency in Salmonella enterica serovar Typhimurium bacteria capture for cell suspensions below 10(5) cells per mL (10(4) cells injected with a 100 µL sample volume) and efficiency higher than 50% for 10(7) cells per mL. Moreover, thermal lysis achieved on-chip from as low as 10 captured cells was demonstrated and shown to compare well with off-chip lysis. Excellent selectivity (over 1 : 300) was obtained in a sample containing, in addition to S. Typhimurium and E. coli bacteria.

Pilot Experience with an External Quality Assurance Scheme for Acylcarnitines in Plasma/Serum.

The analysis of acylcarnitines (AC) in plasma/serum is established as a useful test for the biochemical diagnosis and the monitoring of treatment of organic acidurias and fatty acid oxidation defects. External quality assurance (EQA) for qualitative and quantitative AC is offered by ERNDIM and CDC in dried blood spots but not in plasma/serum samples. A pilot interlaboratory comparison between 14 European laboratories was performed over 3 years using serum/plasma samples from patients with an established diagnosis of an organic aciduria or fatty acid oxidation defect. Twenty-three different samples with a short clinical description were circulated. Participants were asked to specify the method used to analyze diagnostic AC, to give quantitative data for diagnostic AC with the corresponding reference values, possible diagnosis, and advice for further investigations.Although the reference and pathological concentrations of AC varied among laboratories, elevated marker AC for propionic acidemia, isovaleric acidemia, medium-chain acyl-CoA dehydrogenase, very long-chain acyl-CoA dehydrogenase, and multiple acyl-CoA dehydrogenase deficiencies were correctly identified by all participants allowing the diagnosis of these diseases. Conversely, the increased concentrations of dicarboxylic AC were not always identified, and therefore the correct diagnosis was not reach by some participants, as exemplified in cases of malonic aciduria and 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. Misinterpretation occurred in those laboratories that used multiple-reaction monitoring acquisition mode, did not derivatize, or did not separate isomers. However, some of these laboratories suggested further analyses to clarify the diagnosis.This pilot experience highlights the importance of an EQA scheme for AC in plasma.