High Polygenic Risk Is Associated with Earlier Initiation and Escalation of Treatment in Early Primary Open-Angle Glaucoma.

PURPOSE: To assess the association between a glaucoma polygenic risk score (PRS) and treatment outcomes in primary open-angle glaucoma. DESIGN: Prospective, observational cohort study. PARTICIPANTS: Participants from the Progression Risk of Glaucoma: Relevant SNPs with Significant Association Study were divided into a cohort with suspect glaucoma who were treatment naive at enrollment and one with early manifest and suspect glaucoma receiving treatment at enrollment. METHODS: A per-allele weighted glaucoma PRS was calculated for 1107 participants. Multivariable mixed-effects Cox proportional regression analysis assessed the association between PRS and time to commencement of intraocular pressure (IOP)-lowering therapy in 416 patients with suspect glaucoma who were treatment naive at study enrollment. Secondary analysis evaluated the association between PRS and escalation of IOP-lowering therapy among 691 patients with suspect and early manifest glaucoma who were receiving IOP-lowering therapy at enrollment. MAIN OUTCOME MEASURES: Commencement or escalation of IOP-lowering therapy. RESULTS: A higher PRS was associated with a greater risk of commencing IOP-lowering therapy within 5 years (hazard ratio [HR], 1.45 per 1 standard deviation [/SD]; 95% confidence interval [CI], 1.27-1.62; P < 0.001). Participants in the upper population-based quintile showed a 3.3 times greater risk of commencing therapy by 5 years than those in the lowest quintile (HR, 3.30; 95% CI, 1.63-6,70; P < 0.001) and a 5.4 times greater risk of commencing IOP-lowering therapy by 2 years than the those in the lowest quintile (HR, 5.45; 95% CI, 2.08-14.25; P < 0.001). A higher PRS was associated with a greater risk of treatment escalation among patients receiving treatment at enrollment (HR, 1.19/SD; 95% CI, 1.09-1.31; P < 0.001). In combined analysis of all participants, participants in the top population-based quintile were at 2.3 times greater risk of requiring initiation or escalation of IOP-lowering therapy than those in the lowest quintile (HR, 2.33; 95% CI, 1.75-3.01; P < 0.001). CONCLUSIONS: This study demonstrated novel associations between glaucoma polygenic risk and risk of commencement or escalation of IOP-lowering therapy, building on previous work highlighting the potential clinical usefulness of genetic risk stratification in glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Genetic Risk Assessment of Degenerative Eye Disease (GRADE): study protocol of a prospective assessment of polygenic risk scores to predict diagnosis of glaucoma and age-related macular degeneration.

BACKGROUND: Glaucoma and age-related macular degeneration (AMD) account for a substantial portion of global blindness. Both conditions are highly heritable, with recognised monogenic and polygenic inheritance patterns. Current screening guidelines lack decisive recommendations. Polygenic risk scores (PRS) allow for cost-effective broad population risk stratification for these conditions. The predictive potential of PRS could facilitate earlier diagnosis and treatment, and prevent unnecessary vision loss. METHODS: The Genetic Risk Assessment of Degenerative Eye disease (GRADE) study is a prospective study designed to generate high-quality evidence about the feasibility of PRS to stratify individuals from the general population, enabling identification of those at highest risk of developing glaucoma or AMD. The targeted recruitment is 1000 individuals aged over 50 years, from which blood or saliva samples will be used for genotyping and an individual PRS for glaucoma and AMD will be derived. Individuals with PRS values in the bottom decile (n = 100), top decile (n = 100) and middle 80% (n = 100) for both glaucoma and AMD will undergo a detailed eye examination for glaucoma and/or AMD. DISCUSSION: The primary objective will be to compare the prevalence of glaucoma and AMD cases between low, intermediate, and high PRS risk groups. We expect to find a higher prevalence of both diseases in the high PRS risk group, as compared to the middle and low risk groups. This prospective study will assess the clinical validity of a PRS for glaucoma and AMD in the general Australian population. Positive findings will support the implementation of PRS into clinical practice.

Physical Activity Is Associated With Macular Thickness: A Multi-Cohort Observational Study.

Purpose: To assess the association between physical activity and spectral-domain optical coherence tomography (SD-OCT)-measured rates of macular thinning in an adult population with primary open-angle glaucoma. Methods: The correlation between accelerometer-measured physical activity and rates of macular ganglion cell-inner plexiform layer (GCIPL) thinning was measured in 735 eyes from 388 participants of the Progression Risk of Glaucoma: RElevant SNPs with Significant Association (PROGRESSA) study. The association between accelerometer-measured physical activity and cross-sectional SD-OCT macular thickness was then assessed in 8862 eyes from 6152 participants available for analysis in the UK Biobank who had SD-OCT, ophthalmic, comorbidity, and demographic data. Results: Greater physical activity was associated with slower rates of macular GCIPL thinning in the PROGRESSA study (beta = 0.07 µm/y/SD; 95% confidence interval [CI], 0.03-0.13; P = 0.003) after adjustment for ophthalmic, demographic and systemic predictors of macular thinning. This association persisted in subanalyses of participants characterized as glaucoma suspects (beta = 0.09 µm/y/SD; 95% CI, 0.03-0.15; P = 0.005). Participants in the upper tertile (greater than 10,524 steps/d) exhibited a 0.22-µm/y slower rate of macular GCIPL thinning than participants in the lower tertile (fewer than 6925 steps/d): -0.40 ± 0.46 µm/y versus -0.62 ± 0.55 µm/y (P = 0.003). Both time spent doing moderate/vigorous activity and mean daily active calories were positively correlated with rate of macular GCIPL thinning (moderate/vigorous activity: beta = 0.06 µm/y/SD; 95% CI, 0.01-0.105; P = 0.018; active calories: beta = 0.06 µm/y/SD; 95% CI, 0.006-0.114; P = 0.032). Analysis among 8862 eyes from the UK Biobank revealed a positive association between physical activity and cross-sectional total macular thickness (beta = 0.8 µm/SD; 95% CI, 0.47-1.14; P < 0.001). Conclusions: These results highlight the potential neuroprotective benefits of exercise on the human retina.

Association Between Body Mass Index and Primary Open Angle Glaucoma in Three Cohorts.

PURPOSE: To evaluate the relationship between body mass index (BMI) and glaucoma progression. DESIGN: Multicohort observational study. METHODS: This study combined a retrospective longitudinal analysis of suspect and early manifest primary open angle glaucoma cases from the Progression Risk of Glaucoma: RElevant SNPs with Significant Association (PROGRESSA) study with 2 replication cohorts from the UK Biobank and the Canadian Longitudinal Study of Ageing (CLSA). In the PROGRESSA study, multivariate analysis correlated BMI with longitudinal visual field progression in 471 participants. The BMI was then associated with glaucoma diagnosis and cross-sectional vertical cup-disc ratio (VCDR) measurements in the UK Biobank, and finally prospectively associated with longitudinal change in VCDR in the CLSA study. RESULTS: In the PROGRESSA study, a lower BMI conferred a faster rate of visual field progression (mean duration of monitoring (5.28 ± 1.80 years (10.6 ± 3.59 visits) (ß 0.04 dB/year/SD95% CI [0.005, 0.069]; P = .013). In the UK Biobank, a 1 standard deviation lower BMI was associated with a worse cross-sectional VCDR (ß -0.048/SD 95% CI [-0.056, 0.96]; P < .001) and a 10% greater likelihood of glaucoma diagnosis, as per specialist grading of retinal fundus imaging (OR 0.90 95% CI [0.84, 0.98]; P = .011). Similarly, a lower BMI was associated with a greater risk of glaucoma diagnosis as per International Classification of Disease data (OR 0.94/SD; 95% CI [0.91, 0.98]; P = .002). Body mass index was also positively correlated with intraocular pressure (ß 0.11/SD; 95% CI [0.06, 0.15]; P < .001). Finally, a lower BMI was then associated with greater VCDR change in the CLSA (ß -0.007/SD; 95% CI [-0.01, -0.001]; P = .023). CONCLUSIONS: Body mass index correlated with longitudinal and cross-sectional glaucomatous outcomes. This supports previous work illustrating a correlation between BMI and glaucoma.

Genomic epidemiological analysis of mcr-1-harboring Escherichia coli collected from livestock settings in Vietnam.

Livestock has been implicated as a reservoir for antimicrobial resistance (AMR) genes that can spread to humans when antimicrobials are used in animals for food production to treat clinical diseases and prevent and control common disease events. In Vietnam, mcr-1-harboring Escherichia coli (MCRPEC) strains have been isolated from humans, animals (chickens, pigs, and dogs) feces, flies, foods, and the environment (rainwater, well water, and irrigation water) in communities and from clinical specimens in hospitals. The relationship between levels of AMR in livestock and its occurrence in humans is complex and is driven by many factors. We conducted whole genome sequencing of MCRPEC to analyze the molecular epidemiological characteristics, history, and relatedness of 50 isolates obtained in 2019 from different reservoirs in farms and markets in Ha Nam province, Vietnam. 34 sequence types (STs) with 3 new STs were identified in multilocus sequence typing analysis: ST12945 and ST12946 from chicken feces, and ST12947 from flies. The AMR phenotypes of 50 MCRPEC isolates were as follows: ampicillin (100%, 50/50), cefotaxime (10%, 5/50), gentamicin (60%, 30/50), amikacin (8%, 4/50), meropenem (6%, 3/50), ceftazidime (18%, 9/50), colistin (24%, 12/50) and ciprofloxacin (80%, 40/50). All 50 MCRPEC isolates were identified as MDR. 100% (50/50) isolates carried AMR genes, ranging from 5 to 22 genes. The most prevalent plasmid replicon types carrying mcr-1 were IncP-1 (17/37, 45.9%), IncX4 (7/37, 18.9%), and IncHI2/IncHI2A (6/37, 16.2%). These data suggest that the epidemiology of the mcr-1 gene is mostly determined by plasmid spreading instead of clonal dissemination of MCRPE strains. The co-occurrence of several STs such as ST10, ST48, ST155, ST206, ST2705 in various sample types, joined to the higher prevalence of a few types of Inc plasmids, confirms the dissemination of the mcr-1 carrying plasmids in E. coli clones established in livestock. 5 over 8 STs identified in flies (ST206, ST2705, ST155, ST10, and ST48) suggested the fly contribution in the transmission of AMR bacteria in environments. These popular STs also occur in human samples and 100% of the human samples were positive for the mcr-1 gene.

Vietnam Climate Change and Health Vulnerability and Adaptation Assessment, 2018.

BACKGROUND: The Global Climate Risk Index 2020 ranked Vietnam as the sixth country in the world most affected by climate variability and extreme weather events over the period 1999-2018. Sea level rise and extreme weather events are projected to be more severe in coming decades, which, without additional action, will increase the number of people at risk of climate-sensitive diseases, challenging the health system. This article summaries the results of a health vulnerability and adaptation (V&A) assessment conducted in Vietnam as evidences for development of the National Climate Change Health Adaptation Plan to 2030. METHODS: The assessment followed the first 4 steps outlined in the World Health Organization's Guidelines in conducting "Vulnerability and Adaptation Assessments." A framework and list of indicators were developed for semi-quantitative assessment for the period 2013 to 2017. Three sets of indicators were selected to assess the level of (1) exposure to climate change and extreme weather events, (2) health sensitivity, and (3) adaptation capacity. The indicators were rated and analyzed using a scoring system from 1 to 5. RESULTS: The results showed that climate-sensitive diseases were common, including dengue fever, diarrheal, influenza, etc, with large burdens of disease that are projected to increase. From 2013 to 2017, the level of "exposure" to climate change-related hazards of the health sector was "high" to "very high," with an average score from 3.5 to 4.4 (out of 5.0). For "health sensitivity," the scores decreased from 3.8 in 2013 to 3.5 in 2017, making the overall rating as "high." For "adaptive capacity," the scores were from 4.0 to 4.1, which meant adaptive capacity was "very low." The overall V&A rating in 2013 was "very high risk" (score 4.1) and "high risk" with scores of 3.8 in 2014 and 3.7 in 2015 to 2017. CONCLUSIONS: Adaptation actions of the health sector are urgently needed to reduce the vulnerability to climate change in coming decades. Eight adaptation solutions, among recommendations of V&A assessment, were adopted in the National Health Climate Change Adaptation Plan.

An outbreak of influenza A(H1N1)pdm09 virus in a primary school in Vietnam.

BACKGROUND: Despite school pupils being at greatest risk during the 2009 influenza pandemic there are limited data on outbreaks of influenza A(H1N1)pdm09 in primary schools in South-East Asia. This prospective cohort study describes an outbreak of influenza A(H1N1)pdm09 in a primary school in rural Vietnam. FINDINGS: In total 103 cases of influenza-like illness were found among the 407 pupils in the primary school. Ten of these were laboratory confirmed cases of influenza A(H1N1)pdm09 virus. The overall attack rate (AR) was 25% (103/407), and was highest (41%) in grade 4 pupils, where the outbreak started. All cases in the outbreak presented with a mild and self-limiting illness, acute respiratory symptoms and fever. Public health interventions to contain the outbreak could explain the lower attack rates in other grades. Ill pupils were asked to stay at home. Oseltamivir was not given to pupils and the school did not close during the outbreak. The last detected case occurred 12 days following identification of the first case. CONCLUSIONS: This is the first report of an outbreak of influenza A(H1N1)pdm09 among pupils in a primary school in Vietnam. High attack rates in Grade 4 pupils suggest shared activities contributed to transmission. The public health response using non-pharmaceutical measures may have played a role in ending the outbreak.

Acceptability and Feasibility of Delivering Pentavalent Vaccines in a Compact, Prefilled, Autodisable Device in Vietnam and Senegal.

BACKGROUND: Prefilled syringes are the standard in developed countries but logistic and financial barriers prevent their widespread use in developing countries. The current study evaluated use of a compact, prefilled, autodisable device (CPAD) to deliver pentavalent vaccine by field actors in Senegal and Vietnam. METHODS: We conducted a logistic, programmatic, and anthropological study that included a) interviews of immunization staff at different health system levels and parents attending immunization sessions; b) observation of immunization sessions including CPAD use on oranges; and c) document review. RESULTS: Respondents perceived that the CPAD would improve safety by being non-reusable and preventing needle and vaccine exposure during preparation. Preparation was considered simple and may reduce immunization time for staff and caretakers. CPAD impact on cold storage requirements depended on the current pentavalent vaccine being used; in both countries, CPAD would reduce the weight and volume of materials and safety boxes thereby potentially improving outreach strategies and waste disposal. CPAD also would reduce stock outages by bundling vaccine and syringes and reduce wastage by using a non-breakable plastic presentation. Respondents also cited potential challenges including ability to distinguish between CPAD and other pharmaceuticals delivered via a similar mechanism (such as contraceptives), safety, and concerns related to design and ease of administration (such as activation, ease of delivery, and needle diameter and length). CONCLUSIONS: Compared to current pentavalent vaccine presentations in Vietnam and Senegal, CPAD technology will address some of the main barriers to vaccination, such as supply chain issues and safety concerns among health workers and families. Most of the challenges we identified can be addressed with health worker training, minor design modifications, and health messaging targeting parents and communities. Potentially the largest remaining barrier is the marginal increase in pentavalent cost--if any--from CPAD use, which we did not assess in our study.

Human papillomavirus vaccine introduction in Vietnam: formative research findings.

BACKGROUND: Formative research is a useful tool for designing new health interventions. This paper presents key findings from formative research conducted in Vietnam to guide human papillomavirus (HPV) vaccine introduction. METHODS: We explored the sociocultural environment, health system capacity and the policy-making process using a combined quantitative and qualitative methodology. Data collection was done through literature review, in-depth interviews, focus group discussions, observation checklists and a structured questionnaire on knowledge, attitudes and practices. Populations of interest included 11- to 14-year-old girls, their parents, community leaders, teachers, health workers, health and education officials, and policy-makers at all levels. RESULTS: Although HPV vaccines are new, we found high potential acceptance among parents and girls. HPV vaccine introduction was also favourably supported by health professionals if assurances for system preparedness, e.g. cold chain and human resources, were made. There were no significant barriers from the policy perspective that would prevent the introduction of a new vaccine. However, several concerns related to this new vaccine would need to be adequately addressed before implementation. CONCLUSION: Our findings provide options for potential vaccine delivery strategies, appropriate communication strategies and targeted advocacy strategies to introduce HPV vaccines in the Vietnamese context.

Community knowledge, attitudes, and practices toward rabies prevention in North Vietnam.

In recent years, despite the accessibility to vaccines (both for humans and animals), rabies remains a problem in many areas of Vietnam. While the number of rabies deaths decreased by 90% from 1994 to 2003, the number of rabies deaths increased from 2004 to 2007. In 2007, the number of rabies victims was 2-3 times higher than in 2003 and 131 people died as a result of rabies. In order to better understand Knowledge, Attitudes, and Practices (KAP) toward rabies in areas of both high and low incidence of rabies mortality in Vietnam, and KAP between pet and non-pet owners, a cross-sectional study was carried out by administering a structured questionnaire to 585 respondents from selected households in Thanh Son District-Phu Tho Province and Viet Yen District-Bac Giang Province, Vietnam. KAP in both high and low incidence areas, especially in groups with pets, need to be improved, particularly regarding treatment practices after a dog-bite and recommended pet care. We recommend not only enhanced IEC activities, but also the development of a Behavior Change Communication Strategy (BCC).