Geographical discrimination of Paw San rice cultivated in different regions of Myanmar using near-infrared spectroscopy, headspace-gas chromatography-ion mobility spectrometry and chemometrics.

Paw San rice, also known as "Myanmar pearl rice", is considered the highest quality rice in Myanmar. There are considerable differences in terms of the premium commercial value of Paw San rice, which is an incentive for fraud, e.g. adulteration with cheaper rice varieties or mislabelling its geographical origin. Shwe Bo District is one of the most popular rice growing areas in the Sagaing region of Myanmar which produces the most valued and highly priced Paw San rice (Shwe Bo Paw San). The verification of the geographical origin of Paw San rice is not readily undertaken in the rice supply chain because the existing analytical approaches are time-consuming and expensive. Therefore, there is a need for rapid, robust and cost-effective analytical techniques for monitoring the authenticity and geographical origin of Paw San rice. In this 4-year study, two rapid screening techniques, Fourier-transform near-infrared (FT-NIR) spectroscopy and headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS), coupled with chemometric modelling, were applied and compared for the regional differentiation of Paw San rice. In addition, low-level fusion of the FT-NIR and HS-GC-IMS data was performed and its effect on the discriminative power of the chemometric models was assessed. Extensive model validation, including the validation using independent samples from a different production year, was performed. Furthermore, the effect of the sample preparation technique (grinding versus no sample preparation) on the performance of the discriminative model, obtained with FT-NIR spectral data, was assessed. The study discusses the suitability of FT-NIR spectroscopy, HS-GC-IMS and the combination of both approaches for rapid determination of the geographical origin of Paw San rice. The results demonstrated the excellent potential of the FT-NIR spectroscopy as well as HS-GC-IMS for the differentiation of Paw San rice cultivated in two distinct geographical regions. The OPLS-DA model, built using FT-NIR data of rice from 3 production years, achieved 96.67% total correct classification rate of an independent dataset from the 4th production year. The DD-SIMCA model, built using FT-NIR data of ground rice, also demonstrated the highest performance: 94% sensitivity and 97% specificity. This study has demonstrated that FT-NIR spectroscopy can be used as an accessible, rapid and cost-effective screening tool to discriminate between Paw San rice cultivated in the Shwe Bo and Ayeyarwady regions of Myanmar.

Evaluation of care with intravitreal aflibercept treatment for UK patients with diabetic macular oedema: DRAKO study 24-month real-world outcomes.

BACKGROUND/ OBJECTIVES: DRAKO (NCT02850263) was a 24-month, prospective, observational, multi-centre cohort study that enrolled patients diagnosed with diabetic macular oedema (DMO) including central involvement. The study aimed to evaluate standard of care intravitreal aflibercept (IVT-AFL) treatment in the UK. This analysis describes the 12-month outcomes for patients with prior anti-vascular endothelial growth factor (VEGF) treatment for DMO other than IVT-AFL (C2), and 2-year outcomes for both anti-VEGF treatment-naïve patients (C1) and C2 patients. METHODS: Study eyes were treated with IVT-AFL as per local standard of care. Mean changes in best-corrected visual acuity (BCVA) in ETDRS letters and central subfield thickness (CST) were stratified by baseline factors. Changes in diabetic retinopathy assessments, glycated haemoglobin A1c levels and vision-related quality of life (QoL) were evaluated alongside numbers of injections administered and safety outcomes. RESULTS: For C1, mean (SD) changes from baseline in BCVA of +0.7 (12.7) letters and CST of -123.3 (104.3) µm were observed at Month 24. For C2, mean (SD) changes from baseline for BCVA of + 0.2 (10.2) letters and -0.3 (13.0) letters, and CST of -79.1 (137.6) µm and -91.6 (132.9) µm, were observed at 12 and 24 months, respectively. In Year 2, C1 and C2 patients received a mean of 3.7 and 4.3 injections, respectively. CONCLUSIONS: Year 2 results indicate that IVT-AFL is an effective treatment for DMO in real-world UK clinical practice, despite relatively low injection numbers. The high baseline visual acuity and QoL scores were maintained and there was further improvement in anatomical outcomes.

Economic evaluation of population-based, expanded reproductive carrier screening for genetic diseases in Australia.

PURPOSE: This study aimed to evaluate the cost effectiveness of population-based, expanded reproductive carrier screening (RCS) for a 300 recessive gene panel from health service and societal perspectives. METHODS: A microsimulation model (PreConMod) was developed using 2016 Australian Census data as the base population. Epidemiologic, health, and indirect cost data were based on literature review. The study assessed the incremental cost effectiveness ratio of expanded RCS compared with (1) no population screening and (2) 3-condition screening for cystic fibrosis, spinal muscular atrophy, and fragile X syndrome in a single birth cohort. Averted affected births and health service savings with expanded RCS were projected to year 2061. Both one-way and probability sensitivity analyses were conducted to assess the uncertainty of the parameter inputs. RESULTS: Expanded RCS was cost saving compared with no population screening and cost effective compared with the 3-condition screening (incremental cost effectiveness ratio of Australian dollar [AUD] 6287 per quality-adjusted life year gained) at an uptake rate of 50% for RCS, 59% for in vitro fertilization and preimplantation genetic testing, 90% for prenatal diagnosis testing, and 50% for elective termination of affected pregnancies and a cost of AUD595 per couple screened. Our model predicts that expanded RCS would avert one-third of affected births in a single birth cohort and reduce lifetime health service spending by AUD632.0 million. Expanded RCS was estimated to be cost saving from the societal perspective. CONCLUSION: Expanded RCS is cost effective from health service and societal perspectives. Expanded RCS is projected to avert significantly more affected births and result in health service saving beyond those expected from 3-condition screening or no population screening.

Evaluation of standard-of-care intravitreal aflibercept treatment practices in patients with diabetic macular oedema in the UK: DRAKO study outcomes.

BACKGROUND/OBJECTIVES: DRAKO (NCT02850263) was a 24-month, prospective, non-interventional, multi-centre cohort study enrolling patients with diabetic macular oedema (DMO) including central involvement. The study evaluated UK standard-of-care intravitreal aflibercept (IVT-AFL) treatment. This analysis describes the treatment pathway and service provision for the anti-vascular endothelial growth factor (VEGF) treatment-naïve (C1) and non-naïve patients (C2) who received prior anti-VEGF treatment for DMO other than IVT-AFL. METHODS: Mean changes in best-corrected visual acuity and central subfield thickness were measured and stratified by baseline factors, including ethnicity and administration of five initial monthly injections within predefined windows. Clinic visits were classified as treatment only (T1), monitoring assessment only (T2), combined visits (T3) or post-injection visits with no treatment or assessment (T4). RESULTS: Median time from decision to treat to treatment was 6 days. As a percentage of total visits, T1, T2, T3 and T4 were 7%, 42%, 48% and 3% for C1 and 11%, 39%, 48% and 2% for C2. Most IVT-AFL injections were administered by healthcare professionals (HCPs) other than doctors (C1, 57.4%; C2, 58.5%). The percentage of treatments associated with a procedure-related adverse event where at least 75% of injections were completed by the same injector role were similar for doctors and other HCPs (C1, 1.1% and 0.8%; C2, 0.7%, and 1.0%). CONCLUSIONS: Results indicate that upon DMO diagnosis, patients were treated promptly, and most visits were combined (treatment and assessment) or monitoring only. Most IVT-AFL was administered by non-physicians with a similar treatment-related safety profile as IVT-AFL administered by physicians.

Assessment of geographical origin of virgin coconut oil using inductively coupled plasma mass spectrometry along with multivariate chemometrics.

Recently, Virgin coconut oil (VCO) has emerged as one of the most favorable edible oils because of its application in cooking, frying as well as additive used in food, pharmaceuticals, and cosmetic goods. These qualities have established VCO in high consumer demand and there is a great need of establishing a reliable method for the identification of its geographical origin. Through this present study, for the first time, it has been established that Inductively Coupled Plasma-Mass-Spectrometry (ICP-MS) combined with multivariate chemometrics can be used for the identification of the geographical origin of the VCO samples of various provinces. Principal Component Analysis (PCA), and Linear Discriminant Analysis (LDA) were able to differentiate and classify the VCO samples of different geographical origins. Further, calibration models (Principal Component Regression and Partial Least Square Regression) were developed on the calibration dataset of the elemental concentration obtained from the ICP-MS analysis. An external dataset was used to develop the prediction model to predict the geographical origin of an unknown sample. Both PCR and PLS-R models were successfully able to predict the geographical origin with a high R2 value (0.999) and low RMSEP value 0.074 and 0.075% v/v of prediction respectively. In conclusion, ICP-MS combined with regression modelling can be used as an excellent tool for the identification of the geographical origin of the VCO samples of various provinces. This whole technique is the most suitable as it has high sensitivity as well as provides easy multi-metal analysis for a single sample of edible oil.

Evaluation of standard of care intravitreal aflibercept treatment of diabetic macular oedema treatment-naive patients in the UK: DRAKO study 12-month outcomes.

OBJECTIVES: DRAKO (NCT02850263) is a 24-month, prospective, non-interventional, multi-centre cohort study which enroled patients diagnosed with centre-involving diabetic macular oedema (DMO). The study aims to evaluate standard of care with intravitreal aflibercept (IVT-AFL) treatment in the UK. This analysis describes the anti-vascular endothelial growth factor (anti-VEGF) treatment-naive patient cohort after 12-month follow-up. METHODS: Study eyes were treated with IVT-AFL as per local standard of care. The mean change in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline at 12 months were measured and stratified by baseline factors. The number of injections and safety data were also evaluated. RESULTS: A total of 507 patients were enroled from 35 centres. Mean (SD) baseline BCVA was 71.4 (12.0) letters and CST was 448.7 (88.7) µm, with 63.1% of patients presenting with baseline BCVA ≥ 70 letters (mean 78.1). Mean (SD) change in BCVA of 2.5 (12.2) letters and CST of -119.1 (116.4) µm was observed at month 12. A 7.3 letter gain was observed in patients with baseline BCVA < 70 letters. Mean number (SD) of injections in year one was 6.4 (2.1). No significant adverse events were recorded. CONCLUSION: Year one results indicated that IVT-AFL was an effective treatment for DMO in standard of care UK clinical practice, maintaining or improving visual acuity in treatment-naive patients with good baseline visual acuity, despite some patients being undertreated versus the summary of product characteristics. These results also demonstrated the clinical importance and meaningful impact of diabetic retinopathy screening in the UK.

Distinct signaling routes mediate intercellular and intracellular rhizobial infection in Lotus japonicus.

Rhizobial infection of legume roots during the development of nitrogen-fixing root nodules can occur intracellularly, through plant-derived infection threads traversing cells, or intercellularly, via bacterial entry between epidermal plant cells. Although it is estimated that around 25% of all legume genera are intercellularly infected, the pathways and mechanisms supporting this process have remained virtually unexplored due to a lack of genetically amenable legumes that exhibit this form of infection. In this study, we report that the model legume Lotus japonicus is infected intercellularly by the IRBG74 strain, recently proposed to belong to the Agrobacterium clade of the Rhizobiaceae. We demonstrate that the resources available for L. japonicus enable insight into the genetic requirements and fine-tuning of the pathway governing intercellular infection in this species. Inoculation of L. japonicus mutants shows that Ethylene-responsive factor required for nodulation 1 (Ern1) and Leu-rich Repeat Receptor-Like Kinase (RinRK1) are dispensable for intercellular infection in contrast to intracellular infection. Other symbiotic genes, including nod factor receptor 5 (NFR5), symbiosis receptor-like kinase (SymRK), Ca2+/calmodulin dependent kinase (CCaMK), exopolysaccharide receptor 3 (Epr3), Cyclops, nodule inception (Nin), nodulation signaling pathway 1 (Nsp1), nodulation signaling pathway 2 (Nsp2), cystathionine-ß-synthase (Cbs), and Vapyrin are equally important for both entry modes. Comparative RNAseq analysis of roots inoculated with IRBG74 revealed a distinctive transcriptome response compared with intracellular colonization. In particular, several cytokinin-related genes were differentially regulated. Corroborating this observation, cyp735A and ipt4 cytokinin biosynthesis mutants were significantly affected in their nodulation with IRBG74, whereas lhk1 cytokinin receptor mutants formed no nodules. These results indicate a differential requirement for cytokinin signaling during intercellular rhizobial entry and highlight distinct modalities of inter- and intracellular infection mechanisms in L. japonicus.

Rapid and non-destructive approach for the detection of fried mustard oil adulteration in pure mustard oil via ATR-FTIR spectroscopy-chemometrics.

Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy integrated with chemometrics was effectively applied for the rapid detection and accurate quantification of fried mustard oil (FMO) adulteration in pure mustard oil (PMO). PMO was adulterated with FMO in the range of 0.5-50% v/v. Principal component analysis (PCA) elucidated the studied adulteration using two components with an explained variance of 97%. The linear discriminant analysis (LDA) was adopted to classify the adulterated PMO samples with FMO. LDA model showed 100% accuracy initially, as well as when cross-validated. To enhance the overall quality of models, characteristic spectral regions were optimized, and principal component regression (PCR) and partial least square regression (PLS-R) models were constructed with high accuracy and precision. PLS-R model for the 2nd derivative of the optimized spectral region 1260-1080 cm-1 showed best results for prediction sample sets in terms of high R2 and residual predictive deviation (RPD) value of 0.999 and 31.91 with low root mean square error (RMSE) and relative prediction error (RE %) of 0.53% v/v and 3.37% respectively. Thus, the suggested method can detect up to 0.5% v/v of adulterated FMO in PMO in a short time interval.

Stable isotope analysis of non-exchangeable hydrogen in carbohydrates derivatised with N-methyl-bis-trifluoroacetamide by gas chromatography - Chromium silver reduction/High temperature Conversion-isotope ratio mass spectrometry (GC-CrAg/HTC-IRMS).

A novel procedure for the rapid isotope analysis of the carbon-bound non-exchangeable (CBNE) hydrogen in mono and disaccharides has been developed to demonstrate the feasibility of detecting undeclared addition of exogenous sugar products in foods and beverages susceptible to economically motivated adulteration. The procedure utilizes a simple one-step reaction, with the derivatising agent N-methyl-bis-trifluoroacetamide, to substitute the exchangeable hydroxyl-hydrogens with trifluoroacetate derivatives that are sufficiently volatile to be separated and measured by a gas chromatograph coupled to an isotope ratio mass spectrometer. The conversion of the derivatised sugars into the measuring gas is achieved using a high temperature chromium-silver reactor that retains carbon, oxygen and fluorine whilst releasing hydrogen gas for stable isotope measurement. The new procedure has advantages over existing methods in terms of ease of use, analysis time and compound-specific information. Sugars from fruit juice and honey have been measured to demonstrate the feasibility of using this technique.

Validation of an Analytical Method for the Determination of Pesticide Residues in Vine Leaves by GC-MS/MS.

A modified and miniaturized SweEt/QuEChERS method for pesticide residue analysis applied to vine leaves is presented. The deep-frozen plant material was cryogenically processed. A 2 g analytical portion was hydrated for 30 min and extracted with acidified ethyl acetate after buffering with NaHCO3 and adding Na2SO4. A dispersive solid-phase (d-SPE) cleanup step with primary-secondary amine (PSA) was performed. The pesticide residues were determined using GC-MS/MS. The whole procedure was validated for 54-59 pesticides at 0.01, 0.02, 0.1, and 0.2 mg/kg in fresh vine leaves ( Vitis vinifera). The key method performance parameters investigated were specificity, linearity, trueness, within laboratory repeatability and reproducibility, limit of detection, limit of quantitation, and matrix effects. Recoveries for the 59 pesticides tested ranged from 60 to 110%, and the RSDs were lower than 20% for the majority of the pesticides studied.

Dynamics of Ethylene Production in Response to Compatible Nod Factor.

Establishment of symbiotic nitrogen-fixation in legumes is regulated by the plant hormone ethylene, but it has remained unclear whether and how its biosynthesis is regulated by the symbiotic pathway. We established a sensitive ethylene detection system for Lotus japonicus and found that ethylene production increased as early as 6 hours after inoculation with Mesorhizobium loti This ethylene response was dependent on Nod factor production by compatible rhizobia. Analyses of nodulation mutants showed that perception of Nod factor was required for ethylene emission, while downstream transcription factors including CYCLOPS, NIN, and ERN1 were not required for this response. Activation of the nodulation signaling pathway in spontaneously nodulating mutants was also sufficient to elevate ethylene production. Ethylene signaling is controlled by EIN2, which is duplicated in L. japonicus We obtained a L. japonicus Ljein2a Ljein2b double mutant that exhibits complete ethylene insensitivity and confirms that these two genes act redundantly in ethylene signaling. Consistent with this redundancy, both LjEin2a and LjEin2b are required for negative regulation of nodulation and Ljein2a Ljein2b double mutants are hypernodulating and hyperinfected. We also identified an unexpected role for ethylene in the onset of nitrogen fixation, with the Ljein2a Ljein2b double mutant showing severely reduced nitrogen fixation. These results demonstrate that ethylene production is an early and sustained nodulation response that acts at multiple stages to regulate infection, nodule organogenesis, and nitrogen fixation in L. japonicus.

Mapping standard ophthalmic outcome sets to metrics currently reported in eight eye hospitals.

BACKGROUND: To determine alignment of proposed international standard outcomes sets for ophthalmic conditions to metrics currently reported by eye hospitals. METHODS: Mixed methods comparative benchmark study, including eight eye hospitals in Australia, India, Singapore, Sweden, U.K., and U.S. All are major international tertiary care and training centers in ophthalmology. Main outcome measure is consistency of ophthalmic outcomes measures reported. RESULTS: International agreed standard outcomes (ICHOM) sets are available for cataract surgery (10 metrics) and macular degeneration (7 metrics). The eight hospitals reported 22 different metrics for cataract surgery and 2 for macular degeneration, which showed only limited overlap with the proposed ICHOM metrics. None of the hospitals reported patient reported visual functioning or vision-related quality of life outcomes measures (PROMs). Three hospitals (38%) reported rates for uncomplicated cataract surgeries only. There was marked variation in how and at what point postoperatively visual outcomes following cataract, cornea, glaucoma, strabismus and oculoplastics procedures were reported. Seven (87.5%) measured post-operative infections and four (50%) measured 30 day unplanned reoperation rates. CONCLUSIONS: Outcomes reporting for ophthalmic conditions currently widely varies across hospitals internationally and does not include patient-reported outcomes. Reaching consensus on measures and consistency in data collection will allow meaningful comparisons and provide an evidence base enabling improved sharing of "best practices" to improve eye care globally. Implementation of international standards is still a major challenge and practice-based knowledge on measures should be one of the inputs of the international standardization process.

Pseudophakic cystoid macular edema and spectral-domain optical coherence tomography-detectable central macular thickness changes with perioperative prostaglandin analogs.

PURPOSE: To define the incidence of cystoid macular edema (CME) and spectral-domain optical coherence tomography-detectable (SD-OCT) subclinical changes in central retinal thickness in patients using prostaglandin analog (PGA) eyedrops after phacoemulsification. SETTING: Royal Bolton Hospital, Bolton, United Kingdom. DESIGN: Prospective case series. METHODS: A consecutive analysis of the incidence of postoperative CME after phacoemulsification by a single surgeon was performed in eyes of patients using PGA eyedrops between March 2010 and January 2014. The presence of CME was determined using SD-OCT (Cirrus) 3 weeks and 6 weeks postoperatively. Exclusion criteria included preexisting pathology known to predispose to CME and previous ophthalmic surgery. The paired Wilcoxon signed-rank test was used to compare central retinal thickness measurements at baseline and 3 weeks and 6 weeks postoperatively. RESULTS: All 48 patients (mean age 78.4 years; 60 eyes) had uneventful surgery. There were no cases of clinically significant CME. Subclinical CME detected by SD-OCT was confirmed in 2 eyes of different patients (3.3% of eyes), 1 eye 3 weeks postoperatively and another eye at 6 weeks. Subclinical CME resolved in both cases within 8 weeks. In both cases, the difference in central retinal thickness at baseline and 6 weeks postoperatively was statistically significant (P < .05). CONCLUSIONS: The incidence of subclinical CME detectable on SD-OCT after routine phacoemulsification in patients using PGA eyedrops throughout the perioperative period was 3.3%. There were no cases of clinical CME. These findings might guide clinicians in their decision to use PGAs perioperatively.

The Ethylene Responsive Factor Required for Nodulation 1 (ERN1) Transcription Factor Is Required for Infection-Thread Formation in Lotus japonicus.

Several hundred genes are transcriptionally regulated during infection-thread formation and development of nitrogen-fixing root nodules. We have characterized a set of Lotus japonicus mutants impaired in root-nodule formation and found that the causative gene, Ern1, encodes a protein with a characteristic APETALA2/Ethylene Responsive Factor (AP2/ERF) transcription-factor domain. Phenotypic characterization of four ern1 alleles shows that infection pockets are formed but root-hair infection threads are absent. Formation of root-nodule primordia is delayed and no normal transcellular infection threads are found in the infected nodules. Corroborating the role of ERN1 (ERF Required for Nodulation1) in nodule organogenesis, spontaneous nodulation induced by an autoactive CCaMK and cytokinin-induced nodule primordia were not observed in ern1 mutants. Expression of Ern1 is induced in the susceptible zone by Nod factor treatment or rhizobial inoculation. At the cellular level, the pErn1:GUS reporter is highly expressed in root epidermal cells of the susceptible zone and in the cortical cells that form nodule primordia. The genetic regulation of this cellular expression pattern was further investigated in symbiotic mutants. Nod factor induction of Ern1 in epidermal cells was found to depend on Nfr1, Cyclops, and Nsp2 but was independent of Nin and Nf-ya1. These results suggest that ERN1 functions as a transcriptional regulator involved in the formation of infection threads and development of nodule primordia and may coordinate these two processes.

Severe Ocular Inflammation Following Ranibizumab or Aflibercept Injections for Age-Related Macular Degeneration: A Retrospective Claims Database Analysis.

PURPOSE: Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents including ranibizumab and aflibercept are used to treat patients with ocular disorders such as neovascular age-related macular degeneration (nAMD); however, the injections are associated with rare instances of severe ocular inflammation. This study compared severe ocular inflammation rates in patients treated with ranibizumab versus aflibercept. METHODS: United States physician-level claims data covering an 18-month period for each therapy were analyzed. The primary analysis compared severe ocular inflammation event rates per 1000 injections. Sensitivity and subgroup analyses evaluated the impact of factors including intraocular surgery, intravitreal antibiotic administration, and previous intravitreal injections. RESULTS: The analysis included 432,794 injection claims (ranibizumab n = 253,647, aflibercept n = 179,147); significantly, more unique severe ocular inflammation events occurred in patients receiving aflibercept than ranibizumab (1.06/1000 injections, 95% confidence interval [CI], 0.91-1.21, vs. 0.64/1000 injections, 95% CI 0.54-0.74; p < 0.0001). Comparable results were observed for analyses of patients who had undergone glaucoma or cataract surgeries, had antibiotic-associated endophthalmitis, had non-antibiotic-associated endophthalmitis, and were non-treatment-naive. In contrast, no significant differences in severe ocular inflammation claims were recorded in treatment-naive patients who had no record of anti-VEGF treatment in the 6 months preceding the index claim. No significant change occurred in the rate of severe ocular inflammation claims over time following ranibizumab treatment. CONCLUSIONS: Severe ocular inflammation was more frequent following intravitreal injection with aflibercept than with ranibizumab during routine clinical use in patients with nAMD. This highlights the importance of real-world, post-approval, observational monitoring of novel medicines, and may aid clinical decision-making, including choice of anti-VEGF agent.

Rate of vision loss in neovascular age-related macular degeneration explored.

PURPOSE: To explore decline in visual acuity in patients with neovascular age-related macular degeneration (n-AMD) awaiting intravitreal bevacizumab or ranibizumab treatment following initial diagnosis and after disease reactivation. METHODS: Retrospective analysis of 74 treatment-naïve patients (84 eyes) in two centers in Córdoba, Argentina. The time between treatment indication and intravitreal injection, and the changes in BCVA produced during this delay were studied in both periods. A linear regression model to search the impact of time on progression visual impairment was conducted. RESULTS: In both periods, a significant reduction in vision occurred awaiting intravitreal injection. The longer the delay, the greater the vision loss (R2 = 0.55 p < 0.01) and the less improvement following treatment (Pearson coefficient -0.26). The result of the model shows that the change in vision as a function of initial delay were best described by a polynomic model with a mean loss of 5 letters in the first 3 weeks, a slowdown in the rate of change of VA, and a dependence of visual acuity at the moment of diagnosis . The loss of visual acuity after reactivation shows the same behavior as at the onset of the disease but independent of visual acuity prior to reactivation. CONCLUSION: Visual loss awaiting injection intravitreal anti-VEGF is clinically significant and with an asymptotic pattern, with early rapid loss of vision in both the onset of the disease and the reactivation. Initiation of anti-VEGF treatment must be undertaken urgently, as should retreatment of disease activation to reduce visual loss.

The impact of chronic conditions of care recipients on the labour force participation of informal carers in Australia: which conditions are associated with higher rates of non-participation in the labour force?

BACKGROUND: Little is known about the effects of personal and other characteristics of care recipients on the behaviour of carers. The aim of this study is to examine the association between the main chronic (disabling) condition of care recipients and the likelihood of their (matched) primary carers aged 15-64 years being out of the labour force. METHODS: We conducted a retrospective analysis of cross-sectional data from the Australian Bureau of Statistics 2009 Survey of Disability, Ageing and Carers (SDAC) for people aged 15-64 years. We estimated the rates of exit from the labour force for primary carers and non-carers; rates of chronic disease occurrence for care recipients living with their main carers; odds ratios of primary carers being out of the labour force associated with the main chronic condition of their care recipient who lives with them. RESULTS: From the 2009 SDAC, we identified 1,268 out of 37,186 eligible participants who were primary carers of a care recipient who lived with them. Of these, 628 (49.5%) were out of the labour force. Most common diseases of care recipients were: back problems (12%); arthritis and related disorders (10%); diseases of the nervous system (such as multiple sclerosis, epilepsy, cerebral palsy) (7.4%); and conditions originating in the perinatal period or congenital malformations, deformations and chromosomal abnormalities (5.1%). When adjusted for age, sex, education and whether have a long term chronic condition of informal carers, the five conditions of care recipients associated with the highest odds of their carers being out of the labour force were: head injury/acquired brain damage; neoplasms, blood diseases, disorders of the immune system; leg/knee/foot/hip damage from injury/accident; dementia, Parkinson's disease, Alzheimer's disease; and diseases of the musculoskeletal system and connective tissue (osteoporosis). CONCLUSIONS: This study identifies the type of conditions that have the greatest impact on the labour force participation of informal carers - previously unavailable information for Australia. Australia, like most developed countries, is facing several skills shortages and an ageing population. These governments will need to adopt novel and more wholistic approaches to increase the labour force participation of diverse groups. Informal carers are one such group.

Incidence and baseline clinical characteristics of treated neovascular age-related macular degeneration in a well-defined region of the UK.

AIMS: To analyse the incidence and baseline clinical characteristics of patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections in a defined UK region. METHODS: A standardised dataset was collected prospectively using an electronic medical record (EMR) system from 1 January 2008 to 21 June 2012 for all patients living in Gloucestershire who received intravitreal anti-VEGF injections for nAMD. RESULTS: Over the study period, 1207 eyes from 1033 patients began intravitreal anti-VEGF injections for nAMD. The annual incidence in the years after National Institute for Health and Care Excellence (NICE) technology appraisal 155 implementation was stable at 120 (95% CI 110 to 138) eyes or 100 (89 to 115) people per 100 000 population. The most common indication was occult choroidal neovascularisation (51%). Median baseline visual acuity (VA) was significantly higher for second treated than first treated eyes (66 and 56 letters, respectively; p<0.0001). Median baseline VA of fellow eyes increased from 47 (2008) to 67 letters (2012; p<0.005). The proportion of patients with baseline VA in the better eye ≥70 letters increased from 27.6% (2008) to 51.4% (2012; p<0.0001), while the proportion eligible at baseline for full or partial certificate of visual impairment decreased from 13.8% (2008) to 7.1% (2012; p<0.05). CONCLUSIONS: The incidence of patients undergoing anti-VEGF therapy for nAMD increased substantially following NICE approval of ranibizumab (August 2008), and has been stable since 2009. This equates to an annual UK incidence of 26 850 (21 320 to 32 440) eyes, similar to NICE estimates. Patients eligible for blindness certification before treatment decreased by half from 2008-2012. Prospective data collection using an EMR system is invaluable for efficient monitoring of real-world clinical care.

Patient safety in vitreoretinal surgery: quality improvements following a patient safety reporting system.

AIMS: Vitreoretinal (VR) surgery is complex. Most clinical conditions that VR surgeons manage have a high risk for blindness or severe visual impairment. Reporting of patient safety incidents (PSI) in VR surgery was introduced at the Moorfields Eye Hospital (MEH) in the 1990s. We examine the role of PSI reporting in making VR surgery safer at our institution. METHODS: Qualitative review of PSIs from 1997 to 2009 at MEH, London, UK. RESULTS: Over the 13-year study period, 38 789 VR procedures were undertaken and 579 VR PSIs occurring in theatre or inpatient were reported. Mean rate of PSI reporting was 1.49% (range 0.12-3.35). In comparison, the mean rate of PSI reporting over the same period across all National Health Service ophthalmology in England was 0.59% (range 0.36-0.49). Overall, 0.9% of VR PSI resulted in 'Severe' harm, 11.6% in 'Moderate' harm and 87.5% in 'No' or 'Low' harm. 15 (2.6%) of PSIs directly resulted in a change in clinical practice, 13 of which occurred in the first half of the study period. 12 (3.6%) critical incidents were violations of pre-existing protocols and guidelines, eight of which occurred in the second half of the study period. 61 (10.9%) of PSIs fell into nine main error subtypes that contributed to a change in practice. The most common were ocular hypotony (2.9%), medical device failure (2.8%) and delay in VR surgery (1.2%). CONCLUSIONS: VR PSI reporting resulted in a change in clinical practice. Longitudinal analysis suggests an accompanying increase in patient safety.

Balancing risk in ophthalmic prescribing: assessing the safety of anti-VEGF therapies and the risks associated with unlicensed medicines.

Vascular endothelial growth factor (VEGF) inhibitor medications such as ranibizumab, pegaptanib and bevacizumab are in use for the treatment of neovascular age-related macular degeneration (AMD) and other retinal conditions, although only ranibizumab and pegaptanib are approved for these conditions. In contrast, bevacizumab was developed for the intravenous systemic treatment of colorectal cancer and is not formulated for intravitreal use, but is commonly used off-label in ophthalmology. European Union legislation permits the use of drugs outside the terms of their licence ('off-label') only under certain circumstances, such as during clinical trials, compassionate/named patient use in the absence of a licensed alternative, emergency scenarios (e.g., pandemics) or at the discretion of a treating physician. In such cases, patients should be fully informed regarding their treatment and any potential risks involved. Off-label drug use can be an important tool to provide patients with treatment in cases of unmet medical need. However, the use of an unlicensed medicinal product, when a suitable licensed alternative is available, puts prescribing physicians at risk of liability if safety issues arise. Emerging clinical evidence suggests safety differences exist between ranibizumab and bevacizumab.