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Marcelino Correia,1 Taraprasad Das,2,3 Julia Magno,1 Bernadette M Pereira,1 Valerio Andrade,1 Hans Limburg,4 John Trevelyan,5 Jill Keeffe,3 Nitin Verma,6 Yuddha Sapkota2 1National Eye Center, Guido Valadares National Hospital, Dili, Timor-Leste; 2International Agency for Prevention of Blindness South East Asia Regional Office, LV Prasad Eye Institute, Banjara Hills, Hyderabad, India; 3LV Prasad Eye Institute, Hyderabad, India; 4International Centre for Eye Health, London, UK; 5International Agency for Prevention of Blindness, London, UK; 6Ophthalmology Department, University of Tasmania and Sydney, Royal Hobart Hospital, North Hobart, TAS, Australia Purpose: To estimate the prevalence and causes of blindness and visual impairment, cataract surgical coverage (CSC), visual outcome of cataract surgery, and barriers to uptake cataract surgery in Timor-Leste.Method: In a nationwide rapid assessment of avoidable blindness (RAAB), the latest population (1,066,409) and household data were used to create a sampling frame which consists of 2,227 population units (study clusters) from all 13 districts, with populations of 450–900 per unit. The sample size of 3,350 was calculated with the assumed prevalence of blindness at 4.5% among people aged ≥50 years with a 20% tolerable error, 95% CI, and a 90% response rate. The team was trained in the survey methodology, and inter-observer variation was measured. Door-to-door visits, led by an ophthalmologist, were made in preselected study clusters, and data were collected in line with the RAAB5 survey protocol. An Android smart phone installed with mRAAB software was used for data collection.Result: The age–gender standardized prevalence of blindness, severe visual impairment, and visual impairment were 2.8%, (1.8–3.8), 1.7% (1.7–2.3), and 8.1% (6.6–9.6), respectively. Cataract was the leading cause of blindness (79.4%). Blindness was more prevalent in the older age group and in women. CSC was 41.5% in cataract blind eyes and 48.6% in cataract blind people. Good visual outcome in the cataract-operated eyes was 62% (presenting) and 75.2% (best corrected). Two important barriers to not using available cataract surgical services were accessibility (45.5%) and lack of attendants to accompany (24.8%).Conclusion: The prevalence of blindness and visual impairment in Timor-Leste remains high. CSC is unacceptably low; gender inequity in blindness and CSC exists. Lack of access is the prominent barrier to cataract surgery. Keywords: blindness, prevalence, Timor, RAAB, population based survey

This is the protocol for a Campbell systematic review. The objectives are as follows. The objective of this review is to identify and synthesize empirical research on the impacts of interest-holder engagement on the guideline development process and content. Our research questions are as follows: (1) What are the empirical examples of impact on the process in health guideline development across any of the 18 steps of the GIN-McMaster checklist? (2) What are the empirical examples of impact on the content in health guideline development across any of the 18 steps of the GIN-McMaster checklist?, (© 2024 The Author(s). Campbell Systematic Reviews published by John Wiley & Sons Ltd on behalf of The Campbell Collaboration.)

Objective: To determine the prevalence and causes of vision loss and calculate the effective cataract surgery coverage (eCSC) in adults aged 60 years and older in Latin America and the Caribbean in 2020., Methods: The International Agency for the Prevention of Blindness Vision Atlas and the Rapid Assessment of Avoidable Blindness databases were used as data source. The collected data were used to estimate the prevalence and causes of vision loss in people aged 60 years and older, and to determine the eCSC., Results: The overall prevalence of moderate to severe vision impairment (MSVI) and blindness in Latin America and the Caribbean were 14.14% and 2.94%, respectively. Tropical Latin America was the subregion with the highest prevalence of blindness (3.89%) while Southern Latin America had the lowest (0.96%). For both MSVI and blindness, cataract was the main cause of vision loss. The eCSC rates showed great variation, ranging from 4.0% in Guatemala to 75.2% in Suriname., Conclusions: The prevalence of vision loss in adults aged 60 years and older in Latin America and the Caribbean was higher than previous estimates on younger groups. Cataract was the main cause of blindness, and the eCSC indicates that the outcomes from cataract surgery should be improved. Specific actions associated with improving access, integrating eye assessment with primary care programs, expanding the use of telemedicine, and improving data quality should be taken by public health authorities aiming to address vision loss in this group., Competing Interests: Conflict of interest. None declared.

Purpose: This study assessed the prevalence of cataract blindness, cataract surgical coverage (CSC), effective CSC, visual outcome after cataract surgery, and barriers to cataract surgery in a population aged 50 years and older in Armenia using Rapid Assessment of Avoidable Blindness (RAAB) methodology., Methods: The study sample included 2258 individuals aged 50 years and older who were randomly selected from 11 provinces of Armenia in 2019 following the RAAB methodology. The study team randomly selected 50 clusters, 50 people in each. The RAAB survey form was used to collect information on cataract blindness, visual outcome after cataract surgery, and barriers to cataract surgery., Results: The mean age of the participants was 65.3 (SD = 9.9) ranging from 50 to 99. The majority of participants were women (65.6%). Age- and sex-adjusted prevalence of blindness due to all causes was 1.5%; of which 36.4% was bilaterally blind due to cataract. The CSC and effective CSC at a cataract surgical threshold of <6/12 were 55.1% and 24.4%, respectively. Good outcome was reported in 43.7% of eyes after cataract surgery, borderline in 37.2% of eyes, and poor outcome in 19.1%. The main barriers to cataract surgery included "cost," "need not felt," or "fear.", Conclusion: The prevalence of cataract blindness in our study was higher compared to high-income regions and lower than estimates from South/Southeast Asia. This study suggests the urgent need to update the National Strategic Plan to prevent blindness in Armenia with a focus on improving the quality and coverage of cataract surgery.

Biopharmaceutical manufacturing processes may include a low pH treatment step as a means of inactivating enveloped viruses. Small scale virus clearance studies are routinely performed using model enveloped viruses such as murine leukemia virus to assess inactivation at the pH range used in the downstream manufacturing process. Further, as a means of bioburden reduction, chromatography resins may be cleaned and stored using sodium hydroxide and this can also inactivate viruses. The susceptibility of SARS-CoV-2 and SARS-CoV to low pH conditions using protein A eluate derived material from a monoclonal antibody production process as well as high pH cleaning conditions was addressed. SARS-CoV-2 was effectively inactivated at pH 3.0, moderately inactivated at pH 3.4, but not inactivated at pH 3.8. Low pH was less effective at inactivating SARS-CoV. Both viruses were inactivated at a high pH of ca.13.4. These studies provide important information regarding the effectiveness of viral clearance and inactivation steps of novel coronaviruses when compared to other enveloped viruses., (Copyright © 2024 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.)

Purpose: Post-operative vision impairment is common among patients who have undergone cataract surgery in low-resource settings, impacting quality of clinical outcomes and patient experience. This prospective, multisite, single-armed, pragmatic validation study aimed to assess whether receiving tailored recommendations via the free Better Operative Outcomes Software Tool (BOOST) app improved surgical outcomes, as quantified by post-operative unaided distance visual acuity (UVA) measured 1-3 days after surgery., Methods: During the baseline data collection round, surgeons in low and middle-income countries recorded clinical characteristics of 60 consecutive cataract cases in BOOST. Additional data on the causes of poor outcomes from 20 consecutive cases with post-operative UVA of <6/60 (4-12 weeks post-surgery) were entered to automatically generate tailored recommendations for improvement, before 60 additional consecutive cases were recorded during the follow-up study round. Average UVA was compared between cases recorded in the baseline study round and those recorded during follow-up., Results: Among 4,233 cataract surgeries performed by 41 surgeons in 18 countries, only 2,002 (47.3%) had post-operative UVA 6/12 or better. Among the 14 surgeons (34.1%) who completed both rounds of the study (1,680 cases total), there was no clinically significant improvement in post-operative average UVA (logMAR units ±SD) between baseline (0.50 ± 0.37) and follow-up (0.47 ± 0.36) rounds (mean improvement 0.03, p  = 0.486)., Conclusions: Receiving BOOST-generated recommendations did not result in improved UVA beyond what could be expected from prospective monitoring of surgical outcomes alone. Additional research is required to assess whether targeted support to implement changes could potentiate the uptake of app-generated recommendations and improve outcomes.

The Rapid Assessment of Avoidable Blindness (RAAB) is a population-based cross-sectional survey methodology used to collect data on the prevalence of vision impairment and its causes and eye care service indicators among the population 50 years and older. RAAB has been used for over 20 years with modifications to the protocol over time reflected in changing version numbers; this paper describes the latest version of the methodology-RAAB7. RAAB7 is a collaborative project between the International Centre for Eye Health and Peek Vision with guidance from a steering group of global eye health stakeholders. We have fully digitised RAAB, allowing for fast, accurate and secure data collection. A bespoke Android mobile application automatically synchronises data to a secure Amazon Web Services virtual private cloud when devices are online so users can monitor data collection in real-time. Vision is screened using Peek Vision's digital visual acuity test for mobile devices and uncorrected, corrected and pinhole visual acuity are collected. An optional module on Disability is available. We have rebuilt the RAAB data repository as the end point of RAAB7's digital data workflow, including a front-end website to access the past 20 years of RAAB surveys worldwide. This website ( https://www.raab.world) hosts open access RAAB data to support the advocacy and research efforts of the global eye health community. Active research sub-projects are finalising three new components in 2024-2025: 1) Near vision screening to address data gaps on near vision impairment and effective refractive error coverage; 2) an optional Health Economics module to assess the affordability of eye care services and productivity losses associated with vision impairment; 3) an optional Health Systems data collection module to support RAAB's primary aim to inform eye health service planning by supporting users to integrate eye care facility data with population data., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 McCormick I et al.)

Purpose: This study aimed to estimate the prevalence and main causes of blindness and visual impairment in population aged 50 years and older in Armenia using Rapid Assessment of Avoidable Blindness (RAAB) methodology., Methods: The study team randomly selected 50 clusters (each consisting of 50 people) from all 11 regions of Armenia. Data on participants' demographics, presenting visual acuity, pinhole visual acuity, principal cause of presenting visual acuity, spectacle coverage, uncorrected refractive error (URE), and presbyopia were collected using the RAAB survey form. Four teams of trained eye care professionals completed data collection in 2019., Results: Overall, 2,258 people of 50 years and older participated in the study. The age- and gender- adjusted prevalence of bilateral blindness, severe and moderate visual impairment were 1.5% (95% CI: 1.0-2.1), 1.6% (95% CI: 1.0-2.2) and 6.6% (95% CI: 5.5-7.7), respectively.The main causes of blindness were cataract (43.9%) and glaucoma (17.1%). About 54.6% and 35.3% of participants had URE and uncorrected presbyopia, respectively. The prevalence of bilateral blindness and functional low vision increased with age and was the highest in participants 80 years and older., Conclusion: The rate of bilateral blindness was comparable with findings from countries that share similar background and confirmed that untreated cataract was the main cause of blindness. Given that cataract blindness is avoidable, strategies should be developed aiming to further increase the volume and quality of cataract care in Armenia.

Competing Interests: Competing interests: None declared.

Aim: To review existing data for the prevalence of corrected, uncorrected, and inadequately corrected refractive errors and spectacle wear in Hungary., Methods: Data from two nationwide cross-sectional studies were analysed. The Rapid Assessment of Avoidable Blindness study collected population-based representative national data on the prevalence of visual impairment due to uncorrected refractive errors and spectacle coverage in 3523 people aged ≥50y (Group I). The Comprehensive Health Test Program of Hungary provided data on the use of spectacles in 80 290 people aged ≥18y (Group II)., Results: In Group I, almost half of the survey population showed refractive errors for distant vision, about 10% of which were uncorrected (3.2% of all male participants and 5.0% of females). The distance spectacle coverage was 90.7% (91.9% in males; 90.2% in females). The proportion of inadequate distance spectacles was found to be 33.1%. Uncorrected presbyopia was found in 15.7% of participants. In all age groups (Group II), 65.4% of females and 56.0% of males used distance spectacles, and approximately 28.9% of these spectacles were found to be inappropriate for dioptric power (with 0.5 dioptres or more). The prevalence of inaccurate distance spectacles was significantly higher in older age groups (71y and above) in both sexes., Conclusion: According to this population-based data, uncorrected refractive errors are not rare in Hungary. Despite recent national initiatives, further steps are required to reduce uncorrected refractive errors and associated negative effects on vision, such as avoidable visual impairment., (International Journal of Ophthalmology Press.)

Competing Interests: Intérêts concurrents: Guylène Thériault a reçu des honoraires pour des présentations dans le cadre des campagnes Choisir avec soin et Pour une pratique éclairée sur des thématiques liées aux recommandations du Groupe d’étude canadien sur les soins de santé préventifs (Groupe d’étude) et sur le surdiagnostic ou la surutilisation des ressources. La Dre Thériault déclare également avoir reçu un soutien du Groupe d’étude pour assister à un congrès sur la prévention du surdiagnostic et d’autres réunions, et de la part de la campagne Choisir avec soin pour assister à sa conférence annuelle. La Dre Thériault fait partie du conseil d’administration de Choisir avec soin Québec. Laure Tessier et Heather Limburg signalent être à l’emploi à temps complet de l’Agence de la santé publique du Canada, qui finance le Groupe d’étude (le financement ne dépend aucunement du contenu de la logne directrice et le Groupe d’étude ne tient pas compte de la position de l’organisme subventionnaire pour formuler ses recommandations). Aucun autre membre du groupe de travail ou du Groupe d’étude n’a déclaré d’intérêts concurrents pertinents.

Many viruses require proteolytic activation of their envelope proteins for infectivity, and relevant host proteases provide promising drug targets. The transmembrane serine protease 2 (TMPRSS2) has been identified as a major activating protease of influenza A virus (IAV) and various coronaviruses (CoV). Increased TMPRSS2 expression has been associated with a higher risk of severe influenza infection and enhanced susceptibility to SARS-CoV-2. Here, we found that Legionella pneumophila stimulates the increased expression of TMPRSS2-mRNA in Calu-3 human airway cells. We identified flagellin as the dominant structural component inducing TMPRSS2 expression. The flagellin-induced increase was not observed at this magnitude for other virus-activating host proteases. TMPRSS2-mRNA expression was also significantly increased by LPS, Pam3Cys, and Streptococcus pneumoniae , although less pronounced. Multicycle replication of H1N1pdm and H3N2 IAV but not SARS-CoV-2 and SARS-CoV was enhanced by flagellin treatment. Our data suggest that bacteria, particularly flagellated bacteria, up-regulate the expression of TMPRSS2 in human airway cells and, thereby, may support enhanced activation and replication of IAV upon co-infections. In addition, our data indicate a physiological role of TMPRSS2 in antimicrobial host response., (© 2023 Schwerdtner et al.)

Background: Fragility fractures are a major health concern for older adults and can result in disability, admission to hospital and long-term care, and reduced quality of life. This Canadian Task Force on Preventive Health Care (task force) guideline provides evidence-based recommendations on screening to prevent fragility fractures in community-dwelling individuals aged 40 years and older who are not currently on preventive pharmacotherapy., Methods: We commissioned systematic reviews on benefits and harms of screening, predictive accuracy of risk assessment tools, patient acceptability and benefits of treatment. We analyzed treatment harms via a rapid overview of reviews. We further examined patient values and preferences via focus groups and engaged stakeholders at key points throughout the project. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to determine the certainty of evidence for each outcome and strength of recommendations, and adhered to Appraisal of Guidelines for Research and Evaluation (AGREE), Guidelines International Network and Guidance for Reporting Involvement of Patients and the Public (GRIPP-2) reporting guidance., Recommendations: We recommend "risk assessment-first" screening for prevention of fragility fractures in females aged 65 years and older, with initial application of the Canadian clinical Fracture Risk Assessment Tool (FRAX) without bone mineral density (BMD). The FRAX result should be used to facilitate shared decision-making about the possible benefits and harms of preventive pharmacotherapy. After this discussion, if preventive pharmacotherapy is being considered, clinicians should request BMD measurement using dual-energy x-ray absorptiometry (DXA) of the femoral neck, and re-estimate fracture risk by adding the BMD T-score into FRAX (conditional recommendation, low-certainty evidence). We recommend against screening females aged 40-64 years and males aged 40 years and older (strong recommendation, very low-certainty evidence). These recommendations apply to community-dwelling individuals who are not currently on pharmacotherapy to prevent fragility fractures., Interpretation: Risk assessment-first screening for females aged 65 years and older facilitates shared decision-making and allows patients to consider preventive pharmacotherapy within their individual risk context (before BMD). Recommendations against screening males and younger females emphasize the importance of good clinical practice, where clinicians are alert to changes in health that may indicate the patient has experienced or is at higher risk of fragility fracture., Competing Interests: Competing interests: Guylène Thériault reports receiving honoraria from presentations for Choosing Wisely and Practicing Wisely and on themes related to Canadian Task Force on Preventive Health Care (task force) recommendations and overdiagnosis or overuse. Dr. Thériault also reports receiving support from the task force for attending Preventing Overdiagnosis Conference and other meetings, and from Choosing Wisely for attending its annual conference. Dr. Thériault is on the board of Choosing Wisely Quebec. Laure Tessier and Heather Limburg report that they are employed full time by the Public Health Agency of Canada, which funds the task force (compensation does not depend on the content of the manuscript, and the task force does not consider the funding body’s views in developing recommendations). No other working group or task force member declared any relevant interests., (© 2023 CMA Impact Inc. or its licensors.)

Gram-negative bacteria naturally secrete nano-sized outer membrane vesicles (OMVs), which are important mediators of communication and pathogenesis. OMV uptake by host cells activates TLR signalling via transported PAMPs. As important resident immune cells, alveolar macrophages are located at the air-tissue interface where they comprise the first line of defence against inhaled microorganisms and particles. To date, little is known about the interplay between alveolar macrophages and OMVs from pathogenic bacteria. The immune response to OMVs and underlying mechanisms are still elusive. Here, we investigated the response of primary human macrophages to bacterial vesicles (Legionella pneumophila, Klebsiella pneumoniae, Escherichia coli, Salmonella enterica, Streptococcus pneumoniae) and observed comparable NF-κB activation across all tested vesicles. In contrast, we describe differential type I IFN signalling with prolonged STAT1 phosphorylation and strong Mx1 induction, blocking influenza A virus replication only for Klebsiella, E.coli and Salmonella OMVs. OMV-induced antiviral effects were less pronounced for endotoxin-free Clear coli OMVs and Polymyxin-treated OMVs. LPS stimulation could not mimic this antiviral status, while TRIF knockout abrogated it. Importantly, supernatant from OMV-treated macrophages induced an antiviral response in alveolar epithelial cells (AEC), suggesting OMV-induced intercellular communication. Finally, results were validated in an ex vivo infection model with primary human lung tissue. In conclusion, Klebsiella, E.coli and Salmonella OMVs induce antiviral immunity in macrophages via TLR4-TRIF-signaling to reduce viral replication in macrophages, AECs and lung tissue. These gram-negative bacteria induce antiviral immunity in the lung through OMVs, with a potential decisive and tremendous impact on bacterial and viral coinfection outcome. Video Abstract., (© 2023. The Author(s).)

Background: Cataract is the leading cause of blindness globally. Effective cataract surgical coverage (eCSC) measures the number of people in a population who have been operated on for cataract, and had a good outcome, as a proportion of all people operated on or requiring surgery. Therefore, eCSC describes service access (ie, cataract surgical coverage, [CSC]) adjusted for quality. The 74th World Health Assembly endorsed a global target for eCSC of a 30-percentage point increase by 2030. To enable monitoring of progress towards this target, we analysed Rapid Assessment of Avoidable Blindness (RAAB) survey data to establish baseline estimates of eCSC and CSC., Methods: In this secondary analysis, we used data from 148 RAAB surveys undertaken in 55 countries (2003-21) to calculate eCSC, CSC, and the relative quality gap (% difference between eCSC and CSC). Eligible studies were any version of the RAAB survey conducted since 2000 with individual participant survey data and census population data for people aged 50 years or older in the sampling area and permission from the study's principal investigator for use of data. We compared median eCSC between WHO regions and World Bank income strata and calculated the pooled risk difference and risk ratio comparing eCSC in men and women., Findings: Country eCSC estimates ranged from 3·8% (95% CI 2·1-5·5) in Guinea Bissau, 2010, to 70·3% (95% CI 65·8-74·9) in Hungary, 2015, and the relative quality gap from 10·8% (CSC: 65·7%, eCSC: 58·6%) in Argentina, 2013, to 73·4% (CSC: 14·3%, eCSC: 3·8%) in Guinea Bissau, 2010. Median eCSC was highest among high-income countries (60·5% [IQR 55·6-65·4]; n=2 surveys; 2011-15) and lowest among low-income countries (14·8%; [IQR 8·3-20·7]; n=14 surveys; 2005-21). eCSC was higher in men than women (148 studies pooled risk difference 3·2% [95% CI 2·3-4·1] and pooled risk ratio of 1·20 [95% CI 1·15-1·25])., Interpretation: eCSC varies widely between countries, increases with greater income level, and is higher in men. In pursuit of 2030 targets, many countries, particularly in lower-resource settings, should emphasise quality improvement before increasing access to surgery. Equity must be embedded in efforts to improve access to surgery, with a focus on underserved groups., Funding: Indigo Trust, Peek Vision, and Wellcome Trust., Competing Interests: Declaration of interests MJB declares funding support from the Wellcome Trust (207472/Z/17/Z) via a grant to the London School of Hygiene & Tropical Medicine. AB declares funding from the Wellcome Trust (215633/Z/19/Z); and declares being the Co-Founder and Chief Executive Officer of both the Peek Vision Foundation (UK charity number 1165960) and Peek Vision (UK company number 09937174) which is a wholly owned subsidiary of the Peek Vision Foundation. IM, RB, and IZM declare funding support from Peek Vision via a grant to the London School of Hygiene & Tropical Medicine. JMF declares consulting fees as a technical adviser for SightFirst/Lions Club International Latin America. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening for prostate cancer in adults aged 18 years and older in primary care. This protocol outlines the planned scope and methods for a series of systematic reviews., Methods: Updates of two systematic reviews and a de novo review will be conducted to synthesize the evidence on the benefits and harms of screening for prostate cancer with a prostate-specific antigen (PSA) and/or digital rectal examination (DRE) (with or without additional information) and patient values and preferences. Outcomes for the benefits of screening include reduced prostate cancer mortality, all-cause mortality, and incidence of metastatic prostate cancer. Outcomes for the harms of screening include false-positive screening tests, overdiagnosis, complications due to biopsy, and complications of treatment including incontinence (urinary or bowel), and erectile dysfunction. The quality of life or functioning (overall and disease-specific) and psychological effects outcomes are considered as a possible benefit or harm. Outcomes for the values and preferences review include quantitative or qualitative information regarding the choice to screen or intention to undergo screening. For the reviews on benefits or harms, we will search for randomized controlled trials, quasi-randomized, and controlled studies in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. For the review on values and preferences, we will search for experimental or observational studies in MEDLINE, Embase, and PsycInfo. For all reviews, we will also search websites of relevant organizations, gray literature, and reference lists of included studies. Title and abstract screening, full-text review, data extraction, and risk of bias assessments will be completed independently by pairs of reviewers with any disagreements resolved by consensus or by consulting with a third reviewer. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach will be used to assess the certainty of the evidence for each outcome., Discussion: The series of systematic reviews will be used by the Canadian Task Force on Preventive Health Care to update their 2014 guideline on screening for prostate cancer in adults aged 18 years and older. Systematic review registration This review has been registered with PROSPERO (CRD42022314407) and is available on the Open Science Framework (osf.io/dm32k)., (© 2022. The Author(s).)

Aim: To examine the prevalence and composition of refractive errors in Hungary., Methods: Nationwide cross-sectional data collected between 2014 and 2019 were analysed from the Comprehensive Health Screening Program of Hungary, which provided spectacle dioptric power and autorefractometry data for 68 227 people (35 850 women and 32 377 men). Their age distribution, 18-99y, was similar to the national demographic distributions., Results: Of the total population, 16.50% of the refractive errors exhibited hyperopia, 40.05% emmetropia, and 43.45% myopia. Myopia was 3 times more frequent (58.7%) in younger ages (18-35y of age) compared to older age groups (19.4% of those 56-70y of age; P <0.001). High myopia showed a low prevalence (0.21%), and an increase parallel with ageing ( r =0.716; P =0.009)., Conclusion: Myopia is the most frequent refractive error in Hungary. The prevalence of myopia is especially increased, up to 2-3 times, in the younger age groups. Nationwide actions need to be taken to reduce the onset of myopia and its associated consequences., (International Journal of Ophthalmology Press.)

Background: There is a need for the development of comprehensive, global, evidence-based guidance for stakeholder engagement in guideline development. Stakeholders are any individual or group who is responsible for or affected by health- and healthcare-related decisions. This includes patients, the public, providers of health care and policymakers for example. As part of the guidance development process, Multi-Stakeholder Engagement (MuSE) Consortium set out to conduct four concurrent systematic reviews to summarise the evidence on: (1) existing guidance for stakeholder engagement in guideline development, (2) barriers and facilitators to stakeholder engagement in guideline development, (3) managing conflicts of interest in stakeholder engagement in guideline development and (4) measuring the impact of stakeholder engagement in guideline development. This protocol addresses the second systematic review in the series., Objectives: The objective of this review is to identify and synthesise the existing evidence on barriers and facilitators to stakeholder engagement in health guideline development. We will address this objective through two research questions: (1) What are the barriers to multi-stakeholder engagement in health guideline development across any of the 18 steps of the GIN-McMaster checklist? (2) What are the facilitators to multi-stakeholder engagement in health guideline development across any of the 18 steps of the GIN-McMaster checklist?, Search Methods: A comprehensive search strategy will be developed and peer-reviewed in consultation with a medical librarian. We will search the following databases: MEDLINE, Cumulative Index to Nursing & Allied Health Literature (CINAHL), EMBASE, PsycInfo, Scopus, and Sociological Abstracts. To identify grey literature, we will search the websites of agencies who actively engage stakeholder groups such as the AHRQ, Canadian Institutes of Health Research (CIHR) Strategy for Patient-Oriented Research (SPOR), INVOLVE, the National Institute for Health and Care Excellence (NICE) and the PCORI. We will also search the websites of guideline-producing agencies, such as the American Academy of Pediatrics, Australia's National Health Medical Research Council (NHMRC) and the WHO. We will invite members of the team to suggest grey literature sources and we plan to broaden the search by soliciting suggestions via social media, such as Twitter., Selection Criteria: We will include empirical qualitative and mixed-method primary research studies which qualitatively report on the barriers or facilitators to stakeholder engagement in health guideline development. The population of interest is stakeholders in health guideline development. Building on previous work, we have identified 13 types of stakeholders whose input can enhance the relevance and uptake of guidelines: Patients, caregivers and patient advocates; Public; Providers of health care; Payers of health services; Payers of research; Policy makers; Program managers; Product makers; Purchasers; Principal investigators and their research teams; and Peer-review editors/publishers. Eligible studies must describe stakeholder engagement at any of the following steps of the GIN-McMaster Checklist for Guideline Development., Data Collection and Analysis: All identified citations from electronic databases will be imported into Covidence software for screening and selection. Documents identified through our grey literature search will be managed and screened using an Excel spreadsheet. A two-part study selection process will be used for all identified citations: (1) a title and abstract review and (2) full-text review. At each stage, teams of two review authors will independently assess all potential studies in duplicate using a priori inclusion and exclusion criteria. Data will be extracted by two review authors independently and in duplicate according to a standardised data extraction form., Main Results: The results of this review will be used to inform the development of guidance for multi-stakeholder engagement in guideline development and implementation. This guidance will be official GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group guidance. The GRADE system is internationally recognised as a standard for guideline development. The findings of this review will assist organisations who develop healthcare, public health and health policy guidelines, such as the World Health Organization, to involve multiple stakeholders in the guideline development process to ensure the development of relevant, high quality and transparent guidelines., (© 2022 The Authors. Campbell Systematic Reviews published by John Wiley & Sons Ltd on behalf of The Campbell Collaboration.)

Introduction: Posterior segment diseases are the most common causes of blindness and visual impairment in devel-oped countries among people aged 50 years and older in Hungary. Objective: The purpose of this study was to estimate the prevalence of visual impairment and blindness caused by posterior segment diseases in the population aged 50 years and older in Hungary. Method: 105 census enumeration units were randomly selected with a probability proportional to size by the Hungar-ian Central Statistical Office. The standardised Rapid Assessment of Avoidable Blindness (RAAB) method was used. Participants underwent eye examination with a direct ophthalmoscope. Participants underwent visual acuity testing with a Snellen tumbling E-chart with or without a pinhole. Dilated fundus examination was performed in diabetic participants using an indirect binocular ophthalmoscope. Results: In total, 3523 (95.9%) out of 3675 eligible people were examined, of whom the prevalence of bilateral blind-ness and severe visual impairment was 0.7% and 0.2%, respectively. The most common causes of visual impairment caused by posterior segment diseases were age-related macular degeneration (1.419%), glaucoma (0.397%), diabetic retinopathy (0.341%) and rhegmatogenous retinal detachment (0.198%). The most common causes of blindness caused by posterior segment diseases were age-related macular degeneration (37.5%), glaucoma (16.7%), diabetic retinopathy (8.3%), high myopia (8.3%), rhegmatogenous retinal detachment (8.3%) and retinitis pigmentosa (8.3%). Conclusion: Prevalence of severe visual impairment and blindness caused by posterior segment diseases was lower compared to results of RAAB surveys in other countries. The frequency order of different posterior segment diseases was in line with developed countries. Availability of eye care should be improved and financing should be modernized due to the continuously increasing number of patients with age-related macular degeneration, glaucoma, diabetes and pathologic myopia.

This is the protocol for a Campbell systematic review. The overall objective of this study is to gather and summarize the existing literature on conflict of interest issues when engaging stakeholders in guideline development., (© 2022 The Authors. Campbell Systematic Reviews published by John Wiley & Sons Ltd on behalf of The Campbell Collaboration.)

Purpose : To report the latest data on blindness and visual impairment (VI) in Indonesia. Methods : Rapid Assessment of Avoidable Blindness (RAAB) surveys were done in 15 provinces in Indonesia between 2013 and 2017. The population of the study was people aged 50 +. In each province, the required number of clusters was selected with a probability proportionately to size. A weighted average analysis for prevalence, causes of visual impairment, and cataract surgical coverage (CSC) estimated the values of the country. Results : The prevalence of blindness in East Java was the highest at 4.4% (95% CI: 3.1-5.6%), followed by Nusa Tenggara Barat (NTB) at 4.0% (95% CI: 3.0-5.1%) and South Sumatra at 3.4% (95% CI: 2.4-4.4%). In number, blindness among people aged 50+ in East Java was the highest at 371,599, followed by West Java at 180,666 and Central Java at 176,977. Untreated cataract was the commonest cause of blindness in all provinces (range: 71.7% to 95.5%). CSC person<3/60 and CSC person<6/60 in Bali were the highest at 81.3% and 72.4%, respectively. Indonesia countrywide prevalence of blindness was 3.0%. The total number of people with VI (PVA less than 6/18 in the better eye) in Indonesia was 8,019,427, consisting of 1,654,595 of blindness and 6,364,832 of moderate and severe VI. Conclusion : The burden of blindness in Indonesia is high, and untreated cataract contributes the most. There is an urgent need to increase cataract surgical coverage by providing better access to cataract surgery services for all people in need.

Cleavage of the influenza A virus (IAV) hemagglutinin (HA) by host proteases is indispensable for virus replication. Most IAVs possess a monobasic HA cleavage site cleaved by trypsin-like proteases. Previously, the transmembrane protease TMPRSS2 was shown to be essential for proteolytic activation of IAV HA subtypes H1, H2, H7, and H10 in mice. In contrast, additional proteases are involved in activation of certain H3 IAVs, indicating that HAs with monobasic cleavage sites can differ in their sensitivity to host proteases. Here, we investigated the role of TMPRSS2 in proteolytic activation of avian HA subtypes H1 to H11 and H14 to H16 in human and mouse airway cell cultures. Using reassortant viruses carrying representative HAs, we analyzed HA cleavage and multicycle replication in (i) lung cells of TMPRSS2-deficient mice and (ii) Calu-3 cells and primary human bronchial cells subjected to morpholino oligomer-mediated knockdown of TMPRSS2 activity. TMPRSS2 was found to be crucial for activation of H1 to H11, H14, and H15 in airway cells of human and mouse. Only H9 with an R-S-S-R cleavage site and H16 were proteolytically activated in the absence of TMPRSS2 activity, albeit with reduced efficiency. Moreover, a TMPRSS2-orthologous protease from duck supported activation of H1 to H11, H15, and H16 in MDCK cells. Together, our data demonstrate that in human and murine respiratory cells, TMPRSS2 is the major activating protease of almost all IAV HA subtypes with monobasic cleavage sites. Furthermore, our results suggest that TMPRSS2 supports activation of IAV with a monobasic cleavage site in ducks. IMPORTANCE Human infections with avian influenza A viruses upon exposure to infected birds are frequently reported and have received attention as a potential pandemic threat. Cleavage of the envelope glycoprotein hemagglutinin (HA) by host proteases is a prerequisite for membrane fusion and essential for virus infectivity. In this study, we identify the transmembrane protease TMPRSS2 as the major activating protease of avian influenza virus HAs of subtypes H1 to H11, H14 and H15 in human and murine airway cells. Our data demonstrate that inhibition of TMPRSS2 activity may provide a useful approach for the treatment of human infections with avian influenza viruses that should be considered for pandemic preparedness as well. Additionally, we show that a TMPRSS2-orthologous protease from duck can activate avian influenza virus HAs with a monobasic cleavage site and, thus, represents a potential virus-activating protease in waterfowl, the primary reservoir for influenza A viruses.

Background/aims: The purpose of this study was to estimate the total healthcare cost associated with diabetic retinopathy (DR) in the population aged 18 years and older in Hungary, and its projection for the year 2045., Methods: A cost model was developed based on the standardised rapid assessment of avoidable blindness with the diabetic retinopathy module (RAAB+DRM) methodology and recently reported prevalent-based cost of illness model. Projection for 2045 was made based on the estimation for increasing diabetes mellitus (DM) prevalence of the International Diabetes Federation. Costs were analysed from the perspective of the healthcare system and the patients. Our DR cost model was constructed according to the Scottish DR grading scale and based on the DR severity stadium., Results: The total DR-associated healthcare cost was US$145.8 million in 2016 and will increase to US$169.0 million by 2045. The two major cost drivers were intravitreal antivascular endothelial growth factor injections and vitrectomies in this study (US$126.4 million in 2016 and US$146.5 million in 2045); they amounted to 86.7% of the total treatment cost of DR. The DR-related cost per patient was US$180.5 in Hungary., Conclusions: The cost per patient for treating DR was lower in Hungary than in other countries. Due to the increasing socioeconomic burden of proliferative DR and diabetes-related blindness, it would be important to invest in DR screening, prevention and early treatment. Our new RAAB-based cost of DR model may facilitate comparisons of DR treatment costs across countries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This study aimed to assess the prevalence and causes of vision loss in sub-Saharan Africa (SSA) in 2015, compared with prior years, and to estimate expected values for 2020., Methods: A systematic review and meta-analysis assessed the prevalence of blindness (presenting distance visual acuity <3/60 in the better eye), moderate and severe vision impairment (MSVI; presenting distance visual acuity <6/18 but ≥3/60) and mild vision impairment (MVI; presenting distance visual acuity <6/12 and ≥6/18), and also near vision impairment (

Competing Interests: Intérêts concurrents: Harminder Singh a déclaré être gastroentérologue et effectuer des endoscopies dans le cadre de sa pratique clinique. Le Dr Singh signale aussi avoir reçu des honoraires personnels de Takeda Canada, Pendopharm et Amgen, à l’extérieur des travaux soumis. Aucun autre intérêt concurrent n’a été déclaré.

The novel emerged SARS-CoV-2 has rapidly spread around the world causing acute infection of the respiratory tract (COVID-19) that can result in severe disease and lethality. For SARS-CoV-2 to enter cells, its surface glycoprotein spike (S) must be cleaved at two different sites by host cell proteases, which therefore represent potential drug targets. In the present study, we show that S can be cleaved by the proprotein convertase furin at the S1/S2 site and the transmembrane serine protease 2 (TMPRSS2) at the S2' site. We demonstrate that TMPRSS2 is essential for activation of SARS-CoV-2 S in Calu-3 human airway epithelial cells through antisense-mediated knockdown of TMPRSS2 expression. Furthermore, SARS-CoV-2 replication was also strongly inhibited by the synthetic furin inhibitor MI-1851 in human airway cells. In contrast, inhibition of endosomal cathepsins by E64d did not affect virus replication. Combining various TMPRSS2 inhibitors with furin inhibitor MI-1851 produced more potent antiviral activity against SARS-CoV-2 than an equimolar amount of any single serine protease inhibitor. Therefore, this approach has considerable therapeutic potential for treatment of COVID-19., (© 2020 Bestle et al.)

Competing Interests: Competing interests: Harminder Singh declared that he is a gastroenterologist and performs endoscopy as part of his clinical practice. Dr. Singh also reports receiving personal fees from Takeda Canada, Pendopharm and Amgen, outside the submitted work. No other competing interests were declared.

Aim: To examine the coexistence of diabetes mellitus (DM) and cataract in Hungary. The effects of DM on the cataract surgical results were also in the focus of analysis., Methods: Statistical data analysis of the results of the Rapid Assessment of Avoidable Blindness with Diabetic Retinopathy (RAAB+DR) module conducted in Hungary in 2015. This cross-sectional, population-based, national survey included 3523 people aged 50 years and over. Participants of the survey were examined on-site. Visual acuity, main cause for visual impairment (using direct and indirect ophthalmoscopes), in case of best corrected visual acuity (BCVA) ≤0.5 and blood glucose level (random test with glucometer) were examined., Results: The prevalence of cataract was 23.4%, and DM was 20.0%. The occurrence of cataract steadily increased with age. Among the examined participants with DM, the prevalence of cataract was significantly ( P =0.012) higher (+35%) than that in non-diabetic subjects (29.5% vs 21.8%). Following aging (OR=15.2%, P <0.001), DM proved to be the most independent influencing risk factor (OR=49.9%, P <0.001). The presence of DM was neither an influencing factor for complications of cataract surgery, nor for postoperative visual acuity., Conclusion: DM appears to be one of the main risk factors for developing cataract. Other risk factors, such as age, sex and environment also play an influencing role. Diabetes does not seem to affect the occurrence of cataract surgical complications., (International Journal of Ophthalmology Press.)

Background: To determine the prevalence and causes of blindness and vision impairment (VI) in East Asia in 2015 and to forecast the trend to 2020., Methods: Through a systematic literature review and meta-analysis, we estimated prevalence of blindness (presenting visual acuity <3/60 in the better eye), moderate-to-severe vision impairment (MSVI; 3/60≤presenting visual acuity <6/18), mild vision impairment (mild VI: 6/18≤presenting visual acuity <6/12) and uncorrected presbyopia for 1990, 2010, 2015 and 2020. A total of 44 population-based studies were included., Results: In 2015, age-standardised prevalence of blindness, MSVI, mild VI and uncorrected presbyopia was 0.37% (80% uncertainty interval (UI) 0.12%-0.68%), 3.06% (80% UI 1.35%-5.16%) and 2.65% (80% UI 0.92%-4.91%), 32.91% (80% UI 18.72%-48.47%), respectively, in East Asia. Cataract was the leading cause of blindness (43.6%), followed by uncorrected refractive error (12.9%), glaucoma, age-related macular degeneration, corneal diseases, trachoma and diabetic retinopathy (DR). The leading cause for MSVI was uncorrected refractive error, followed by cataract, age-related macular degeneration, glaucoma, corneal disease, trachoma and DR. The burden of VI due to uncorrected refractive error, cataracts, glaucoma and DR has continued to rise over the decades reported., Conclusions: Addressing the public healthcare barriers for cataract and uncorrected refractive error can help eliminate almost 57% of all blindness cases in this region. Therefore, public healthcare efforts should be focused on effective screening and effective patient education, with access to high-quality healthcare., Competing Interests: Competing interests: JBJ: Consultant for Mundipharma Co. (Cambridge, UK); Patent holder with Biocompatibles UK Ltd. (Farnham, Surrey, UK) (Title: Treatment of eye diseases using encapsulated cells encoding and secreting neuroprotective factor and/or anti-angiogenic factor; Patent number: 20120263794), and Patent application with University of Heidelberg (Heidelberg, Germany) (Title: Agents for use in the therapeutic or prophylactic treatment of myopia or hyperopia; Europäische Patentanmeldung 15 000 771.4). JHK: consultant for Gilead (DSMC Chair), Santen (protocol design). SR: consultant for Brien Holden Vision Institute., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose : Reliable data on eye care needs in Kyrgyzstan are not readily available. The purpose of this study was to determine the prevalence and causes of blindness and visual impairment in persons aged 50 and above in the southwest of Kyrgyzstan and to support the Ministry of Health (MoH) in the planning of eye care in the region. Methods : A population-based survey was conducted in three states (Oblast) in the southwest region of Kyrgyzstan. Sixty clusters of 50 people aged 50 years and older were selected by probability proportionate to size sampling. Ethical approval was obtained from the MoH, consent was obtained from each participant. Results : A total number of 3,000 persons aged 50 and older were sampled. Among these 2,897 (95.9%) were examined. The prevalence of bilateral blindness was 1.7% [95%CI: 1.1-2.4]. Cataract (43.3%) was the main cause of blindness, followed by glaucoma (30%), age-related macular degeneration (ARMD) (8.3%), other posterior segment diseases (6.7%) and non-trachomatous corneal opacities (5%). The prevalence of blindness and visual impairment increased strongly with age. The cataract surgical coverage in blind persons was 59%. Conclusion : Cataract and glaucoma were the major causes of blindness and visual impairment in persons 50 and above. The majority of the causes (85%) were avoidable, with 45% (cataract and uncorrected aphakia) treatable, 6.7% (corneal opacity and phthisis) preventable by primary health care/eye care services and 33.3% (cataract surgical complications, glaucoma) preventable by specialized ophthalmic services. The data suggest that an expansion of eye care services to reduce avoidable blindness is needed, as ageing will lead to an increase in older people at risk and a higher demand for eye care in the future.

Aim: To estimate the prevalence of blindness and visual impairment resulting from cataract in the population aged ≥50y in Hungary, and to assess the cataract surgical services., Methods: A rapid assessment of avoidable blindness (RAAB) was conducted. A total of 3523 eligible people were randomly selected and examined. Each participant underwent surgery for cataract was interviewed with regard to the year, place, and costs of the surgery. Participants with obvious cataract were asked why they had not yet undergone surgery (barriers to surgery)., Results: An estimated 12 514 people were bilaterally blind; the visual acuity (VA) in 19 293 people was <6/60, and the VA in 73 962 people was <6/18 in the better eye due to cataract. An estimated 77 933 eyes are blind; 98 067 eyes had a VA of <6/60, and an estimated 277 493 eyes had a VA of <6/18 due to cataract. Almost all cataract surgeries were conducted in government hospitals. The age- and sex-adjusted cataract surgical coverage with VA<3/60 in eyes was 90.0%. The rate of good visual outcome after surgery was 79.5%. Ocular comorbidity was the main cause of poor outcome (78.1%), followed by late complications (such as posterior capsule opacification) (17.2%), inadequate optical correction (3.1%), and surgical complications (1.6%). The main barrier to surgery in people with bilateral cataract and VA of <6/60 was 'need not felt'., Conclusion: The prevalence of visual impairment resulting from cataract is slightly higher than expected. The quality of the cataract surgical service seems adequate in Hungary. However, the number of cataract operations per year should continue to increase due to the increasing patient demands and the aging population., (International Journal of Ophthalmology Press.)

The Rapid Assessment of Avoidable Blindness, or RAAB, is a relatively simple and low-cost survey methodology to provide data on the prevalence and causes of visual loss. The aim of this article is to reflect on the achievements and challenges of RAAB, and to describe the future developments that are needed to ensure that it remains a relevant and widely used tool. To date, at least 331 RAABs have been undertaken in 79 countries, and these surveys provide an important source of information on visual loss at both the local and global level. A RAAB repository has been developed which includes the site and date of RAABs undertaken, and, where authors have agreed, the core indicators, reports or even raw data from the survey. This dataset has already been used for meta-analyses, and there are further opportunities for its use. Despite these achievements, there are core areas in which RAAB needs to be strengthened so that the full benefits of undertaking the survey can be reaped. Key developments of RAAB are underway, and will include greater use of mobile technologies using a cloud-based platform to enable both digital data collection, real-time survey reviews, reporting and analysis, and a greater emphasis on using the data for planning., Competing Interests: Competing interests: The Peek Vision Foundation (09919543) is a registered charity in England and Wales (1165960), with a wholly owned trading subsidiary, Peek Vision Ltd (09937174). MJB is a trustee of the Peek Vision Foundation and AB is the Chief Executive Officer of the Peek Vision Foundation and Peek Vision Ltd., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)