Intravitreal bevacizumab in diabetic retinopathy. Recommendations from the Pan-American Collaborative Retina Study Group (PACORES): The 2016 knobloch lecture

The advent of intravitreal anti-vascular endothelial growth factor (anti-VEGF) medications has revolutionized the treatment of diabetic eye diseases. Herein, we report the outcomes of clinical studies carried out by the Pan-American Collaborative Retina Study Group (PACORES), with a specific focus on the efficacy of intravitreal bevacizumab in the management of diabetic macular edema and proliferative diabetic retinopathy. We will also discuss the use of intravitreal bevaci-zumab as a preoperative, adjuvant therapy before vitrectomy for prolif-erative diabetic retinopathy. Copyright © 2017 by Asia Pacific Academy of Ophthalmology

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Impact of common cardio-metabolic risk factors on fatal and non-fatal cardiovascular disease in Latin America and the Caribbean: an individual-level pooled analysis of 31 cohort studies

Background: Estimates of the burden of cardio-metabolic risk factors in Latin America and the Caribbean (LAC) rely on relative risks (RRs) from non-LAC countries. Whether these RRs apply to LAC remains un- known. Methods: We pooled LAC cohorts. We estimated RRs per unit of exposure to body mass index (BMI), systolic blood pressure (SBP), fasting plasma glucose (FPG), total cholesterol (TC) and non-HDL cholesterol on fatal (31 cohorts, n = 168,287) and non-fatal (13 cohorts, n = 27,554) cardiovascular diseases, adjusting for regression dilution bias. We used these RRs and national data on mean risk factor levels to estimate the number of cardiovascular deaths attributable to non-optimal levels of each risk factor. Results: Our RRs for SBP, FPG and TC were like those observed in cohorts conducted in high-income countries; however, for BMI, our RRs were consistently smaller in people below 75 years of age. Across risk factors, we observed smaller RRs among older ages. Non-optimal SBP was responsible for the largest number of attributable cardiovascular deaths ranging from 38 per 10 0,0 0 0 women and 54 men in Peru, to 261 (Dominica, women) and 282 (Guyana, men). For non-HDL cholesterol, the lowest attributable rate was for women in Peru (21) and men in Guatemala (25), and the largest in men (158) and women (142) from Guyana. Interpretation: RRs for BMI from studies conducted in high-income countries may overestimate disease burden metrics in LAC; conversely, RRs for SBP, FPG and TC from LAC cohorts are similar to those esti- mated from cohorts in high-income countries

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Physician’s perception, belief, attitude, and knowledge concerning antimicrobial resistance

Purpose: To assess physician’s knowledge, beliefs, perceptions, and attitudes about antimicrobial resistance. To know their barriers and suggestions in order to design more effective interventions. Methods: We conducted a cross sectional survey of physicians at University Hospital of UNIFESP-EPM (Hospital São Paulo), during July 1st and September 30th 2005, by a self-administered questionnaire using the Health Belief Model as a framework. The questionnaire was based in the topics of “Campaign to Prevent Antimicrobial Resistance in Healthcare Setting” for Centers for Diseases Control and Prevention, 2002. Results: The survey was completed by 310 house staff physicians, included medicine residents (89,4%) and medicine attending physicians (10,6%). Antibiotic resistance was perceived as a very important problem by 99% of the respondents. Most of physicians (86,7%) agreed antibiotics are overused in general and 97,7% them believed that widespread and inappropriate antibiotic use were important causes of resistance. One hundred forty physicians (45%) indicated “choose antibiotic using cultures” as effective strategy for preventing antimicrobial resistance. Conclusions: The most of respondents are concerned about antimicrobial resistance as a problem and this perception is correlated with physician’s antimicrobial prescribing experience. Physicians stated that they wanted more antimicrobial education. The most of respondents believed that divulgation of identification and susceptibility tests at hospital is useful. Interventions are more likely to be effective if professional’s beliefs, perceptions and attitudes were known. PDF created with pdfFactory trial version www.pdffactory.comObjetivos: Avaliar o conhecimento, crenças, percepções, atitudes e comportamento de médicos, em relação à resistência aos antimicrobianos e identificar as barreiras e sugestões desses médicos que possam contribuir com o desenvolvimento de estratégias que melhorem a adesão às medidas de prevenção e controle da resistência bacteriana. Método: O estudo foi realizado no Hospital São Paulo, hospital universitário ligado à Universidade Federal de São Paulo. A pesquisa incluiu médicos diretamente ligados à prescrição de antimicrobianos, que responderam um questionário elaborado sob a estrutura do modelo comporta mental de crenças em saúde, durante o período de 01 de junho a 30 de setembro de 2005. As medidas de prevenção sugeridas no questionário foram baseadas nas estratégias apresentadas na Campanha para Prevenção da Resistência Antimicrobiana desenvolvida pelo "Centers for Disease Control and Prevention" em 2002. Resultados: Participaram da pesquisa, 310 médicos, 10,6 por cento preceptores e 89,4 por cento médicos residentes. A maioria dos médicos (99,0 por cento) concordou que a resistência aos antimicrobianos constitui-se em um problema e. a maioria, 97,7 por cento concordou que os médicos usam mais antimicrobianos que o necessário. Muitos (44,0 por cento) afirmaram que gostariam de receber mais informações sobre antimicrobianos. e 86,1 por cento apontaram a falta de conhecimento técnico sobre antimicrobianos como uma dificuldade para a adequação do uso de antimicrobianos. Quarenta e cinco por cento afirmou acreditar que a escolha do antimicrobiano baseado em cultura e antibiograma seria uma medida eficaz no controle da resistência bacteriana. Conclusões: A maioria dos participantes percebe a resistência aos antimicrobianos como um problema e essa percepção está diretamente relacionada à experiência do profissional com a prescrição de antimicrobianos. Os médicos sentem falta de esclarecimentos teóricos sobre antimicrobianos e acreditam que isso possa interferir na adesão às recomendações sobre o tema. A maioria dos participantes acha importante uma divulgação mais ampla do perfil de sensibilidade dos microrganismos isolados no Hospital São Paulo. O conhecimento das crenças, percepções e atitudes dos médicos em relação a um determinado problema, facilitaria a elaboração de manuais, que respeitando as características daqueles profissionais, obteriam uma maior aderência às recomendações propostas.TEDEBV UNIFESP: Teses e dissertaçõe

Physicians' perceptions, beliefs, attitudes, and knowledge concerning antimicrobial resistance in a Brazilian teaching hospital

This cross-sectional survey assessed physicians' perceptions, knowledge and practices concerning antimicrobial resistance. Ninety-nine percent of participants reported that they perceived antimicrobial resistance as an important problem, and 86.7% agreed that antimicrobials are overprescribed, but only 2.9% rated practicing antimicrobial control as the most important strategy for preventing resistance. the results of this study warrant educational programs on antimicrobial resistance and the distribution of information regarding local antimicrobial susceptibility testing.Universidade Federal de São Paulo, Div Infect Dis, Dept Med, BR-04024002 São Paulo, BrazilCtr Dis Control & Prevent, Atlanta, GA USAUniversidade Federal de São Paulo, Div Infect Dis, Dept Med, BR-04024002 São Paulo, BrazilWeb of Scienc