Evaluation of The Medical Board Exam in Portugal

Introduction: There is a high heterogeneity in the structure of postgraduate medical training evaluation worldwide. However, in contrast to other countries, there have been no scientific studies of the final medical board examination, in Portugal. The present study aimed to evaluate the adequacy of the medical board examination including its validity as measured by its association with medical school grade average and national seriation examination. Material and Methods: Cross-sectional, observational study. We analyzed the final results on the medical board examination of 2439 physicians, across 47 specialties, who completed their training in 2016 and 2017, using measures of central tendency and variability. We assessed the association between these grades and the national exam to initiate residency, and the grade average in Medical School. Results: Measures of central tendency and variability, and consequent shape measures, revealed that the distribution of the scores of the final medical board exam is extremely negatively asymmetric and leptokurtic. A positive association was also found between the results in this exam and the score on national exam to initiate residency, and the grade average in Medical School. Conclusion: Although the medical board examination was, in general, positively associated with scores on the national exam to initiate residency, and the mean final Medical School grades, thus indicating its potential validity, our results demonstrate that this exam presents no satisfactory discriminative capacity. Therefore, there is room to improve the actual postgraduate medical examination model, including changes in its classification system and potentially consider other assessment models

Causative Pathogens of Endophthalmitis after Intravitreal Anti-VEGF Injection: An International Multicenter Study

Purpose: The main objective of this study was to investigate the microbiological spectrum of endophthalmitis after anti- VEGF injections and to compare streptococcal with nonstreptococcus- associated cases with regard to baseline characteristics and injection procedure. Methods: Retrospective,international multicenter study of patients with culture-positive endophthalmitis after intravitreal anti-VEGF injection at 17 different retina referral centers. Results: Eighty-three cases with 87 identified pathogens were included. Coagulasenegative staphylococci (59%) and viridans streptococci (15%) were the most frequent pathogens found. The use of postoperative antibiotics and performance of injections in an operating room setting significantly reduced the rate of streptococcus-induced endophthalmitis cases (p = 0.01 for both). Conclusion: We found a statistically significant lower rate of postinjectional local antibiotic therapy and operating room-based procedures among the streptococcus-induced cases compared to cases caused by other organisms

Baseline predictors for visual acuity loss during observation in diabetic macular oedema with good baseline visual acuity

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Urinary Mass Spectrometry Profiles in Age-Related Macular Degeneration

We and others have shown that patients with different severity stages of age-related macular degeneration (AMD) have distinct plasma metabolomic profiles compared to controls. Urine is a biofluid that can be obtained non-invasively and, in other fields, urine metabolomics has been proposed as a feasible alternative to plasma biomarkers. However, no studies have applied urinary mass spectrometry (MS) metabolomics to AMD. This study aimed to assess urinary metabolomic profiles of patients with different stages of AMD and a control group. We included two prospectively designed, multicenter, cross-sectional study cohorts: Boston, US (n = 185) and Coimbra, Portugal (n = 299). We collected fasting urine samples, which were used for metabolomic profiling (Ultrahigh Performance Liquid chromatography-Mass Spectrometry). Multivariable logistic and ordinal logistic regression models were used for analysis, accounting for gender, age, body mass index and use of AREDS supplementation. Results from both cohorts were then meta-analyzed. No significant differences in urine metabolites were seen when comparing patients with AMD and controls. When disease severity was considered as an outcome, six urinary metabolites differed significantly (p < 0.01). In particular, two of the metabolites identified have been previously shown by our group to also differ in the plasma of patients of AMD compared to controls and across severity stages. While there are fewer urinary metabolites associated with AMD than plasma metabolites, this study identified some differences across stages of disease that support previous work performed with plasma, thus highlighting the potential of these metabolites as future biomarkers for AMD

Diabetic Choroidopathy: Choroidal Vascular Density and Volume in Diabetic Retinopathy With Swept-Source Optical Coherence Tomography

Purpose To compare choroidal vascular density (CVD) and volume (CVV) in diabetic eyes and controls, using en face swept-source optical coherence tomography (SS-OCT). Design Prospective cross-sectional study. Methods Setting: Multicenter. Patient Population: Total of 143 diabetic eyes—27 with no diabetic retinopathy (DR), 47 with nonproliferative DR (NPDR), 51 with NPDR and diabetic macular edema (DME), and 18 with proliferative DR (PDR)—and 64 age-matched nondiabetic control eyes. Observation Procedures: Complete ophthalmologic examination and SS-OCT imaging. En face SS-OCT images of the choroidal vasculature were binarized. Main Outcome Measures: CVD, calculated as the percent area occupied by choroidal vessels in the central macular region (6-mm-diameter circle centered on the fovea), and throughout the posterior pole (12 × 9 mm). The central macular CVV was calculated by multiplying the average CVD by macular area and choroidal thickness (obtained with SS-OCT automated software). Multilevel mixed linear models were performed for analyses. Results Compared to controls (0.31 ± 0.07), central macular CVD was significantly decreased by 9% in eyes with NPDR + DME (0.28 ± 0.06; ß = −0.03, P = .02) and by 15% in PDR (0.26 ± 0.05; ß = −0.04, P = .01). The central macular CVV was significantly decreased by 19% in eyes with PDR (0.020 ± 0.005 mm3, ß = −0.01, P = .01) compared to controls (0.025 ± 0.01 mm3). Conclusions Choroidal vascular density and volume are significantly reduced in more advanced stages of diabetic retinopathy. New imaging modalities should allow further exploration of the contributions of choroidal vessel disease to diabetic eye disease pathogenesis, prognosis, and treatment response.info:eu-repo/semantics/publishedVersio

Human Plasma Metabolomics in Age-Related Macular Degeneration: Meta-Analysis of Two Cohorts

The pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness worldwide, remains only partially understood. This has led to the current lack of accessible and reliable biofluid biomarkers for diagnosis and prognosis, and absence of treatments for dry AMD. This study aimed to assess the plasma metabolomic profiles of AMD and its severity stages with the ultimate goal of contributing to addressing these needs. We recruited two cohorts: Boston, United States (n = 196) and Coimbra, Portugal (n = 295). Fasting blood samples were analyzed using ultra-high performance liquid chromatography mass spectrometry. For each cohort, we compared plasma metabolites of AMD patients versus controls (logistic regression), and across disease stages (permutation-based cumulative logistic regression considering both eyes). Meta-analyses were then used to combine results from the two cohorts. Our results revealed that 28 metabolites differed significantly between AMD patients versus controls (false discovery rate (FDR) q-value: 4.1 &times; 10&minus;2&ndash;1.8 &times; 10&minus;5), and 67 across disease stages (FDR q-value: 4.5 &times; 10&minus;2&ndash;1.7 &times; 10&minus;4). Pathway analysis showed significant enrichment of glycerophospholipid, purine, taurine and hypotaurine, and nitrogen metabolism (p-value &le; 0.04). In conclusion, our findings support that AMD patients present distinct plasma metabolomic profiles, which vary with disease severity. This work contributes to the understanding of AMD pathophysiology, and can be the basis of future biomarkers and precision medicine for this blinding condition

Metabolomics, Genetics and Environment: a Novel Integrative Approach to Age-related Macular Degeneration

Tese de Doutoramento do Programa em Ciências da Saúde, Ramo de Medicina, apresentada à Faculdade de Medicina da Universidade de CoimbraAge-related macular degeneration (AMD) is the leading cause of blindness in the elderly in developed countries. The presence of macular drusen or pigmentary changes represent the early phases of the disease, with some subjects progressing to its late forms - choroidal neovascularization or geographic atrophy. The diagnosis and management of AMD currently relies on ophthalmic examination and/or imaging by skilled clinicians. As it is often asymptomatic in its early phases, unless a routine exam is done, AMD early/ intermediate stages may remain undetected. Therefore, it is crucial to develop screening tools for AMD diagnosis and to predict its progression. Several attempts have been made to identify serologic biomarkers of AMD. However, probably due to the complex multifactorial nature of this disease, involving interactions between genetic and environmental risk factors, results have been inconsistent. Thus, there is currently a lack of reliable and accessible AMD biofluid biomarkers. Metabolomics, the study of the small molecules (<1 kDa) comprising a biological system, offers a well-suited tool to address this need. The metabolites are the downstream product of the cumulative effects of the genome and its interaction with environmental exposures. Therefore, the metabolome is thought to closely mirror the phenotype, especially of multifactorial diseases, such as AMD. Metabolomic profiles can be assessed with two main techniques: nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). Our group hypothesized that the metabolome is impacted in AMD, with differences according to its severity stages, and that AMD-progressors have a distinct metabolome. To test our hypotheses, we designed a study including subjects with AMD and a control group (> 50 years with normal macula) from two distinct geographic origins (Coimbra, Portugal and Boston, United States). In addition to a complete ophthalmological exam, we obtained medical history and lifestyle profiles. Fasting blood and urine samples were collected on all subjects, and detailed imaging of the retina, including color fundus photographs (CFP) and optical coherence tomography (OCT), was performed. For a subset of patients, functional assessments, such as dark adaptation, were also obtained. Our initial work focused on the characterization of metabolomic profiles of AMD and its severity stages. Using NMR spectroscopy, we observed a separation of plasma metabolomics profiles between multiple AMD stages for the Boston cohort, and between control and late stages of AMD for the Coimbra cohort. The metabolomic fingerprints of AMD in the two cohorts presented both similarities and differences, thus suggesting the existence of specific signs of the disease and signs of environmental influences, respectively. We are currently finalizing the analysis of urine NMR metabolomic profiles. Compared to blood, urine composition can present greater variations of endogenous metabolites, therefore it may better reflect changes in disease. The encouraging results of the NMR study motivated us to pursue work with MS, a complementary technique with higher sensitivity. A pilot analysis of plasma samples of the Boston cohort using MS revealed that 87 metabolites differed significantly between patients with AMD and controls. Most of them were lipids, with glycerophospholipids playing a major role. Of these metabolites, over half also differed significantly across AMD severity stages. We are now analyzing the remaining plasma MS data (n=500), by using our two independent cohorts (Coimbra and Boston) as a training and validation set, to characterize metabolomic signs of the disease. In our study, AMD classification was based on CFP, the current gold-standard. Due to the variability of CFP on brightness and contrast, we developed software to automatically standardize them. We also did pioneering work in defining structure-functional associations in AMD, namely by studying the relation between OCT features of AMD with visual function, as assessed by dark adaptation. Acknowledging the potential relevance of peripheral changes on AMD, we also defined methodology to assess them using ultra-widefield imaging. In conclusion, this project demonstrated for the first time that metabolomics enables the identification of plasma profiles associated with AMD, thus supporting the development of metabolomic biomarkers of this blinding disease. Integrated with genetic and lifestyle information, this work also has the potential to increase the current knowledge on the mechanisms of AMD, and thus point to druggable targets for its treatment.A degenerescência macular relacionada com a idade (DMI) é a causa líder de cegueira em idosos nos países desenvolvidos. As fases precoces da doença caracterizam-se pela presença de drusen maculares ou alterações pigmentares; alguns indivíduos progridem para as formas tardias – neovascularização coroideia ou atrofia geográfica. O diagnóstico e seguimento da DMI é atualmente baseado num exame oftalmológico efetuado por clínicos experientes e/ou em exames de imagem. Como frequentemente os doentes com DMI são assintomáticos nas suas fases precoces, exceto se um exame de rotina for efetuado, aqueles com estadios precoces ou intermédios podem permanecer por diagnosticar. Assim, é essencial desenvolver ferramentas para rastreio da DMI e para predizer o seu risco de progressão. Várias tentativas têm sido efetuadas para identificar biomarcadores serológicos de DMI. No entanto, provavelmente devido à complexa natureza multifatorial da doença, que envolve fatores genéticos e ambientais, os resultados dos diversos estudos têm sido inconsistentes. Deste modo, não existem atualmente biomarcadores de DMI acessíveis e fidedignos. A metabolómica, definida como o estudo das pequenas moléculas (<1KDa) que formam um sistema, representa uma ferramenta apropriada para enfrentar este desafio. Os metabolitos são o produto último do processo de transcrição genética e das suas interações com as exposições ambientais. Assim sendo, pensa-se que o metaboloma é a representação mais próxima do fenótipo, especialmente em doenças multifatoriais, como a DMI. Os perfis metabolómicos podem ser estudos com duas técnicas principais: espetroscopia por ressonância magnética e espetrometria de massa (MS). O nosso grupo colocou a hipótese de que o metaboloma está alterado na DMI, com diferenças de acordo com os estadios de gravidade da doença, e que os indivíduos que progridem ao longo do tempo (progressores) têm um metaboloma distinto. Para avaliar as nossas hipóteses, desenhámos um estudo que incluiu doentes com DMI e um grupo controlo (>50 anos, mácula normal), de duas origens geográficas distintas (Coimbra, Portugal e Boston, Estados Unidos). Para além de um exame oftalmológico completo, efetuámos a todos os participantes uma história clínica completa e colhemos dados sobre o seu estilo de vida, bem como amostras de sangue e de urina em jejum. Efetuados ainda vários exames de imagem, incluindo retinografias e tomografia de coerência óptica (OCT). Para um subgrupo de doentes, efetuámos também avaliações funcionais, nomeadamente adaptação ao escuro. O nosso trabalho inicial focou-se na caracterização do perfil metabolómico da DMI e dos seus diversos estadios. Utilizando espetroscopia por ressonância magnética, verificámos a presença de uma separação entre os perfis metabolómicos do plasma de vários estadios de DMI, na coorte de Boston. Na coorte portuguesa, verificámos uma separação entre doentes com DMI tardia comparativamente com o grupo controlo. Os perfis metabolómicos nas duas coortes demonstraram tanto semelhanças como diferenças, sugerindo deste modo a existência tanto de sinais específicos da doença como ambientais. Estamos atualmente a finalizar a análise dos perfis metabolómicos de urina utilizando a mesma técnica. Comparada com o sangue, a urina pode apresentar maiores variações de metabolitos endógenos, pelo que pode refletir melhor alterações na doença. Os resultados encorajadores com espetroscopia por ressonância magnética, motivaram-nos a prosseguir o nosso estudo com MS - uma técnica complementar, com maior sensibilidade. Com esta técnica, a nossa análise inicial de amostras de plasma da coorte de Boston demonstrou que 87 metabolitos diferiam significativamente entre doentes com DMI e controlos. A maioria dos metabolitos responsáveis por esta separação eram lípidos, sobretudo glicero-fosfolípidos. Destes metabolitos, mais de metade diferiam também entre os diferentes estadios de DMI. Neste momento, estamos a terminar a análise dos restantes dados obtidos com MS (n= 500), utilizando as nossas duas coortes independentes (Coimbra e Boston) como grupo de teste e de validação, para caracterizar os sinais metabolómicos da DMI. Neste estudo, a classificação de DMI foi baseada em retinografias, já que estas são atualmente o gold-standard. Devido à variabilidade verificada nas mesmas em termos de brilho e contraste, desenvolvemos um programa para as estandardizar automaticamente. Efetuámos também trabalho pioneiro na definição de associações estrutura-função na DMI, nomeadamente através do estudo da relação entre as alterações observadas no OCT e a função visual avaliada através da adaptação ao escuro. Devido ao reconhecimento da potencial relevância das alterações da periferia na DMI, definimos também metodologia para as avaliar utilizando imagens com amplo campo de captação. Em conclusão, este projeto demonstrou pela primeira vez que utilizando metabolómica é possível identificar perfis plasmáticos associados à DMI, suportando assim o desenvolvimento de biomarcadores metabolómicos desta doença. Integrado com o estudo genético e de perfis de vida, este trabalho tem também o potencial de aumentar o atual conhecimento dos mecanismos de DMI e de identificar potenciais novos alvos terapêuticos.Miller Retina Research Fund (Mass. Eye and Ear); Champalimaud Vision Award (Joan W. Miller); unrestricted departmental Grant from Research to Prevent Blindness, Inc. New York

Perfluorocarbon liquid-assisted intraocular foreign body removal

We describe the benefits of perfluoro-N-octane (PFO), a perfluorocarbon liquid, in the removal of nonmagnetic intraocular foreign bodies (IOFBs) from the macula and posterior segment. Two consecutive cases of posterior segment IOFB were reviewed. An 18-year-old male presented to the emergency room after a motor vehicle accident with a zone 1 open globe injury and large glass IOFB in the left eye. A 53-year-old male presented to the emergency room with a history of a 3-week delayed presentation of a zone 1 open globe injury from a nail to the right eye. He was found to have a metallic IOFB. In both cases, PFO was used to slide the nonmagnetic IOFBs outside of the macula for safer retrieval. PFO was also able to protect the posterior pole from IOFB drops during early attempts at removal. PFO can be a useful surgical adjunct to pars plana vitrectomy in the removal of certain nonmagnetic IOFBs