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Trachoma, caused by ocularChlamydia trachomatisinfection, is targeted for global elimination as a public health problem by 2030. To provide evidence for use of antibodies to monitorC. trachomatistransmission, we collated IgG responses to Pgp3 antigen, PCR positivity, and clinical observations from 19,811 children aged 1– 9 years in 14 populations. We demonstrate that age-seroprevalence curves consistently shift along a gradient of transmission intensity: rising steeply in populations with high levels of infection and active trachoma and becoming flat in populations near elimination. Seroprevalence (range: 0–54%) and seroconversion rates (range: 0–15 per 100 person-years) correlate with PCR prevalence (r: 0.87, 95% CI: 0.57, 0.97). A seroprevalence threshold of 13.5% (seroconversion rate 2.75 per 100 person-years) identifies clusters with any PCR-identified infection at high sensitivity (>90%) and moderate specificity (69-75%). Antibody responses in young children provide a robust, generalizable approach to monitor population progress toward and beyond trachoma elimination.

As trachoma prevalence declines worldwide, performing field surveys with trained trachoma graders to validate its elimination becomes challenging. Graded conjunctival images could be used to train graders, validate field grades, and replace field grading. We review the use of photography to capture conjunctival images for the detection of trachomatous inflammation-follicular (TF) and -intense (TI), Trachomatous trichiasis (TT), and eyelid contour abnormalities. Literature searches were conducted between October 29, 2020 and February 15, 2021. We abstracted kappa scores for agreement between field and image graders, between field graders, and between image graders. The median kappa was calculated for studies discussing grading for TF and TI. Twenty-one studies were included - 19 described the use of imaging tools for grading TF and TI; 1 discussed TT; and 1 discussed eyelid contour abnormalities. For agreement between field and image graders, median kappa for TF was 0.71 (range: 0.57–0.92) and TI was 0.67 (0.37–0.74); between image graders, median kappa for TF was 0.65 (0.37–0.78) and TI was 0.76 (0.39–0.83); and between field graders, median kappa for TF was 0.86 (0.73–1) and TI was 0.82 (0.73–0.91). There is potential for the use of photography for trachoma prevalence surveys. Further research is warranted, particularly for TT and using newer smartphones.

PURPOSE: To estimate and compare cross-sectional scotopic versus mesopic macular sensitivity losses measured by microperimetry, and to report and compare the longitudinal rates of scotopic and mesopic macular sensitivity losses in ABCA4 gene associated Stargardt Disease (STGD1). DESIGN: Multicenter prospective cohort study. METHODS: PARTICIPANTS: 127 molecular confirmed STGD1 patients enrolled from 6 centers in the USA and Europe and followed every 6 months for up to 2 years. OBSERVATION PROCEDURES: The Nidek MP-1S device was used to measure macular sensitivities of the central 20° under mesopic and scotopic conditions. The mean deviations (MD) from normal for mesopic macular sensitivity for the fovea (within 2° eccentricity) and extrafovea (4°−10° eccentricity), and the MD for scotopic sensitivity for the extrafovea were calculated. Linear mixed effects models were used to estimate mesopic and scotopic changes. MAIN OUTCOME MEASURES: Baseline mesopic mean deviation (mMD) and scotopic MD (sMD) and rates of longitudinal changes in the mMDs and sMD. RESULTS: At baseline, all eyes had larger sMD, and the difference between extrafoveal sMD and mMD was 10.7 dB (p

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective, early degeneration of motor neurons in the brain and spinal cord. Motor neurons have long axonal projections, which rely on the integrity of neuronal cytoskeleton and mitochondria to regulate energy requirements for maintaining axonal stability, anterograde and retrograde transport, and signaling between neurons. The formation of protein aggregates which contain cytoskeletal proteins, and mitochondrial dysfunction both have devastating effects on the function of neurons and are shared pathological features across several neurodegenerative conditions, including ALS, Alzheimer's disease, Parkinson's disease, Huntington’s disease and Charcot-Marie-Tooth disease. Furthermore, it is becoming increasingly clear that cytoskeletal integrity and mitochondrial function are intricately linked. Therefore, dysregulations of the cytoskeletal network and mitochondrial homeostasis and localization, may be common pathways in the initial steps of neurodegeneration. Here we review and discuss known contributors, including variants in genetic loci and aberrant protein activities, which modify cytoskeletal integrity, axonal transport and mitochondrial localization in ALS and have overlapping features with other neurodegenerative diseases. Additionally, we explore some emerging pathways that may contribute to this disruption in ALS.

Purpose To evaluate whether home hazards and lighting levels are associated with higher fall rates in adults with varying degrees of visual field (VF) damage from glaucoma. Methods Participants with diagnosed or suspected glaucoma provided three years of prospective falls data via monthly falls diaries. A post-fall telephone questionnaire determined fall locations. Seven home areas were evaluated for hazards and lighting via an in-home assessment. Multivariate models adjusting for relevant confounders, including age, sex, comorbidity, and severity of VF damage, evaluated the influence of hazards and lighting on fall rates in each home region. Results Mean baseline age for the 170 participants was 71.0 (7.6) years and 78 (46%) of participants were female. Fifty-nine participants experienced a total of 83 home falls, with the greatest number of falls occurring on the indoor stairs (n = 24, 29%) and bedroom (n = 17, 21%). Neither the number nor the percentage of hazardous items graded as hazardous was associated with the rate of falls (P > .26). Each 10-fold increase in room lighting was associated with 35% fewer falls in that home region (P = .02). The relation between lighting and the rate of falls did not differ with the degree of visual field damage (P > .3), and a lower fall rate was noted with better lighting even in participants with mild or no VF damage (rate ratio = 0.52/10-fold better lighting; P = 0.01). Conclusions Fewer home falls were found with better lighting, but not with fewer home hazards. Lighting improvements at home may reduce fall rates in older adults. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Because transmission of ocular strains of Chlamydia trachomatis is greatest among preschool-aged children, limiting azithromycin distributions to this age group may conserve resources and result in less antimicrobial resistance, which is a potential advantage in areas with hypoendemic trachoma and limited resources.To determine the efficacy of mass azithromycin distributions to preschool-aged children as a strategy for trachoma elimination in areas with hypoendemic disease.In this cluster randomized clinical trial performed from November 23, 2014, until July 31, 2017, thirty rural communities in Niger were randomized at a 1:1 ratio to biannual mass distributions of either azithromycin or placebo to children aged 1 to 59 months. Participants and study personnel were masked to treatment allocation. Data analyses for trachoma outcomes were performed from October 19, 2021, through June 10, 2022.Every 6 months, a single dose of either oral azithromycin (20 mg/kg using height-based approximation for children who could stand or weight calculation for small children) or oral placebo was provided to all children aged 1 to 59 months.Trachoma was a prespecified outcome of the trial, assessed as the community-level prevalence of trachomatous inflammation-follicular and trachomatous inflammation-intense through masked grading of conjunctival photographs from a random sample of 40 children per community each year during the 2-year study period. A secondary outcome was the seroprevalence of antibodies to C trachomatis antigens.At baseline, 4726 children in 30 communities were included; 1695 children were enrolled in 15 azithromycin communities and 3031 children were enrolled in 15 placebo communities (mean [SD] proportions of boys, 51.8% [4.7%] vs 52.0% [4.2%]; mean [SD] age, 30.8 [2.8] vs 30.6 [2.6] months). The mean coverage of study drug for the 4 treatments was 79% (95% CI, 75%-83%) in the azithromycin group and 82% (95% CI, 79%-85%) in the placebo group. The mean prevalence of trachomatous inflammation-follicular at baseline was 1.9% (95% CI, 0.5%-3.5%) in the azithromycin group and 0.9% (95% CI, 0-1.9%) in the placebo group. At 24 months, trachomatous inflammation-follicular prevalence was 0.2% (95% CI, 0-0.5%) in the azithromycin group and 0.8% (95% CI, 0.2%-1.6%) in the placebo group (incidence rate ratio adjusted for baseline: 0.18 [95% CI, 0.01-1.20]; permutation P = .07).The findings of this trial do not show that biannual mass azithromycin distributions to preschool-aged children were more effective than placebo, although the underlying prevalence of trachoma was low. The sustained absence of trachoma even in the placebo group suggests that trachoma may have been eliminated as a public health problem in this part of Niger.ClinicalTrials.gov Identifier: NCT02048007.

BACKGROUND: Older adults with visual impairments experience a higher risk of falling, and are more vulnerable to adverse health consequences associated with falls than those with normal vision. This study characterizes longitudinal changes in objectively measured physical activity and fear of falling (FoF) occurring after various types of falls in visually impaired older adults. DESIGN: Prospective cohort study. SETTING: Hospital-based enrollment. PARTICIPANTS: People with glaucoma or suspected glaucoma. MEASUREMENTS: Falls were defined as unintentionally coming to rest on the ground or a lower level, and injurious falls were determined though follow-up calls. Study participants were categorized into three groups–fallers with injurious consequences, fallers without injurious consequences, and non-fallers based on fall status in the first year. Physical activity was assessed by waist-bound accelerometer. FoF was evaluated by questionnaire, with Rasch modeling generating FoF scores where higher scores reflected worse FoF. The three-year longitudinal changes of physical activity and FoF were modeled using mixed-effects models. RESULTS: In linear models fully adjusted for visual field damage and other covariates, physical activity among injurious fallers showed greater annual (per year) declines in daily steps (−425 steps/day, 95% confidence interval [CI]: −793, −57), daily active minutes (−13 minutes/day, 95% CI: −21, −6), and daily moderate and vigorous physical activity (MVPA) minutes (−3 MVPA minutes/day, 95% CI: −5, 0) over the three-year period as compared to non-fallers; however, physical activity did not significantly decline among non-injurious fallers. No longitudinal increases in FoF scores were observed in injurious or non-injurious fallers when compared to non-fallers. CONCLUSION: Among visually impaired older adults, injurious falls identified prospectively over 12 months contributed to a significant decline in physical activity over a three-year period, while minimal changes were observed in FoF.

A simplified grading system for trachoma was published by the World Health Organization (WHO) in 1987. Intended for use by non-specialist personnel working at community level, the system includes five signs, each of which can be present or absent in any eye: (i) trachomatous trichiasis; (ii) corneal opacity; (iii) trachomatous inflammation-follicular; (iv) trachomatous inflammation-intense; and (v) trachomatous scarring. Though neither perfectly sensitive nor perfectly specific for trachoma, these signs have been essential tools for identifying populations that need interventions to eliminate trachoma as a public health problem. In 2018, at WHO's 4th global scientific meeting on trachoma, the definition of one of the signs, trachomatous trichiasis, was amended to exclude trichiasis that affects only the lower eyelid. This paper presents the amended system, updates its presentation, offers notes on its use and identifies areas of ongoing debate.En 1987, l'Organisation mondiale de la Santé a publié un système de codage simplifié du trachome. Destiné au personnel non qualifié travaillant au sein des communautés, il comporte cinq signes, chacun pouvant être présent ou absent dans l'un ou l'autre œil: (i) le trichiasis trachomateux; (ii) l'opacité cornéenne; (iii) l'inflammation trachomateuse — folliculaire; (iv) l'inflammation trachomateuse — intense; et enfin, (v) la cicatrice trachomateuse. Bien qu'ils ne soient ni parfaitement précis, ni totalement spécifiques au trachome, ces signes constituent des outils essentiels pour identifier les populations qui nécessitent une intervention afin d'éliminer le trachome en tant que problème de santé publique. En 2018, lors de la quatrième réunion scientifique mondiale sur le trachome, la définition de l'un des signes, le trichiasis trachomateux, a été modifiée pour exclure du système de codage le trichiasis qui n'affecte que la paupière inférieure. Ce document expose le nouveau système, actualise sa présentation, formule des remarques sur son utilisation et identifie les domaines qui font encore l'objet de débats.En 1987, la Organización Mundial de la Salud (OMS) publicó un sistema de clasificación simplificado para el tracoma. Este sistema fue diseñado para que lo utilice el personal no especializado que trabaja a nivel comunitario e incluye cinco signos, cada uno de los cuales puede estar presente o ausente en los ojos: i) la triquiasis tracomatosa; ii) la opacidad corneal; iii) la inflamación tracomatosa-folicular; iv) la inflamación tracomatosa-intensa; y v) la cicatrización tracomatosa. Si bien no son perfectamente sensibles ni muy específicos del tracoma, estos signos han sido herramientas esenciales para identificar a las poblaciones que requieren intervenciones para eliminar el tracoma como problema de salud pública. En 2018, se modificó la definición de uno de los signos, la triquiasis tracomatosa, en la 4.ª Reunión Científica Mundial sobre el Tracoma de la OMS, para descartar la triquiasis que solo afecta al párpado inferior. En el presente documento se describe el sistema modificado, se actualiza su presentación, se ofrecen observaciones sobre su aplicación y se identifican los ámbitos de debate en curso.تم نشر نظام تصنيف مبسط للتراكوما من جانب منظمة الصحة العالمية (WHO) في عام 1987. وهو مخصص للاستخدام بواسطة الأشخاص غير المتخصصين الذين يعملون على مستوى المجتمع، ويشمل النظام خمس علامات يمكن أن يكون كل منها موجودًا أو غير موجود في أي عين: (1) داء الشعرة التراكومي؛ و(2) عتامة القرنية؛ و(3) الالتهاب الجريبي التراكومي؛ و(4) الالتهاب التراكومي الشديد؛ و(5) التندب التراكومي. وبالرغم من أن هذه العلامات لم تكن حساسة للغاية أو محددة للإصابة بالتراكوما، إلا أنها كانت مؤشرات أساسية لتحديد السكان الذين يحتاجون إلى تدخلات طبية للقضاء على التراكوما كمشكلة صحية عامة. في عام 2018، في الاجتماع العلمي العالمي الرابع لمنظمة الصحة العالمية حول التراكوما، تم تعديل تعريف إحدى العلامات، وهو داء الشعرة التراكومي، وذلك لاستبعاد داء الشعرة الذي يصيب الجفن السفلي فقط. تعرض هذه الورقة النظام المعدل، وتقوم بتحديث عرضه التقديمي، وتقدم ملاحظات حول استخدامه، وتحدد مجالات النقاش الدائر.1987 年,世界卫生组织 (WHO) 公布了沙眼简化分级系统。该系统旨在供社区非专业工作人员使用，具备五种体征，其中每个体征都可出现于任一眼睛中，也可能不出现：(I) 沙眼性倒睫；(ii) 角膜混浊； (iii) 沙眼性炎症-滤泡； (iv) 沙眼性剧烈-炎症；以及 (v) 沙眼性疤痕。尽管对沙眼而言，这些体征即非特别敏感，也非专属于沙眼，但其已是确定哪些民众需通过干预消除沙眼这个公共卫生问题的关键。2018 年世卫组织第四届全球沙眼科学会议对沙眼性倒睫的定义进行了修正，排除了仅影响下眼睑的倒睫。本文介绍了修正后的系统，并更新了其介绍，给出了使用说明，并确定了正在讨论中的领域。.В 1987 году Всемирная организация здравоохранения (ВОЗ) опубликовала упрощенную систему оценки трахомы. Предназначенная для использования неспециализированным персоналом, работающим на местном уровне, система включает пять признаков, каждый из которых может присутствовать или отсутствовать в любом глазу: (i) трахоматозный трихиаз; (ii) помутнение роговицы; (iii) трахоматозное воспаление фолликулярное; (iv) трахоматозное воспаление интенсивное; (v) трахоматозное рубцевание. Хотя эти признаки не являются ни абсолютно чувствительными, ни абсолютно специфичными для трахомы, они были важными инструментами для выявления групп населения, которым необходимы вмешательства для устранения трахомы как проблемы общественного здравоохранения. В 2018 году на 4-й Всемирной научной конференции ВОЗ по вопросам трахомы определение одного из признаков, трахоматозного трихиаза, было изменено, чтобы исключить трихиаз, поражающий только нижнее веко. В данном документе приведена измененная система, обновлено ее представление, даны примечания по ее использованию и определены сферы текущих дискуссий.

A cluster-randomized clinical trial showed that biannual single-dose azithromycin reduced mortality in preschool children; we sought to determine the effect on anemia. A simple random sample of 30 communities from Kilosa district, Tanzania, were themselves randomized to receive either 6-monthly treatment of children aged 1–59 months with single-dose azithromycin or placebo. From each community, 40 preschool children were randomly selected at baseline, 12 months, and 24 months. At surveys, the children underwent hemoglobin testing; WHO definitions for anemia were applied. After adjusting for community clustering, the prevalence of anemia was not significantly different by treatment assignment at baseline, 12 months, and 24 months. In each of the cross-sectional surveys, anemia prevalence was associated with younger age; the odds of being anemic was highest in those aged < 12 months. There was also a general decrease in the prevalence of anemia during the study. Although azithromycin was not shown to affect anemia, significantly, the study highlights burden of anemia in rural, African communities.

The Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance study showed that administration of biannual, single-dose azithromycin to preschool children reduces mortality. We sought to evaluate its impact on azithromycin resistance. Thirty randomly selected communities in Kilosa district, Tanzania, were randomized to receive 6-monthly single-dose azithromycin (∼20 mg/kg) versus placebo treatment of children aged 1–59 months. From each community, 40 children (aged 1–59 months) were randomly selected at baseline, 12 and 24 months. Isolation and resistance testing of Streptococcus pneumoniae and Escherichia coli were evaluated using nasopharyngeal and rectal swabs, respectively. The carriage prevalence and the proportion of azithromycin-resistant isolates were determined using disk diffusion. At baseline, the characteristics of the randomly selected children were similar by treatment arms. Both at baseline and in annual cross-sectional surveys, rates of S. pneumoniae and E. coli isolation between treatment arms were similar. The proportions of azithromycin-resistant S. pneumoniae isolates in the children in communities treated with azithromycin versus placebo at baseline, 12 months, and 24 months were 26.5% (18.1%; P = 0.26), 26.8% (16.5%; P = 0.29), and 13.4% (17.0%; P = 0.57), respectively. The proportions of azithromycin-resistant E. coli isolates at baseline, 12 months, and 24 months in the azithromycin (versus placebo) arms were 14.9% (18.9%; P = 0.16), 21.5% (16.6%; P = 0.10), and 14.9% (14.7%; P = 0.95), respectively. Over the 24 months, the mean treatment coverage for the azithromycin and placebo was 76.9% and 74.8%, respectively (P = 0.49). Biannual administration of single-dose azithromycin to children did not appear to result in excess azithromycin resistance in S. pneumoniae and E. coli isolates over 24 months of follow-up.

PURPOSE: Antiretroviral therapy reduced infectious eye diseases (EDs) in HIV infected people. There is limited data on age-related EDs and visual impairment (VI) in people living with HIV. We report prevalence of VI and spectrum of EDs in HIV infected people in an ART era in Rakai, Uganda. METHODS: A philanthropic campaign during 2009-2012 provided ophthalmic services to HIV+ patients in care. Unilateral presenting visual acuity (VA) was assessed by a trained staff in HIV clinics using a 6-meter Snellen chart. A slit lamp examination by an ophthalmologist evaluated eyes with impaired acuity. A retrospective chart review was later conducted retrieving data of patients participating the ophthalmic service. VI was defined referencing WHO’s ICD-11. Ophthalmic diagnosis was summarized by VI level. Logistic regressions estimated demographic associations with cataract diagnosis. RESULTS: 688 HIV+ patients were evaluated, median age was 44 (IQR: 37-50) years, 69% were female. 51% were on ART (median duration 4, IQR: 2-5 years). Crude prevalence of moderate/severe VI and blindness were both 2%. The main diagnoses were refractive error (55%), conjunctivitis (18%), cataract (15%), and pterygium (11%). Cataract prevalences were 10%, 12% and 26% among age groups of 19-34, 35-49 and ≥ 50 years, respectively. Cataract was found in 73% of the HIV+s with blindness and in 63% of those with moderate/severe VI. Older age and male sex were significantly associated with higher cataract prevalence. CONCLUSION: VI in HIV+ patients in Rakai was mainly due to refractive error and cataract. Cataract was common in all age groups.

Coaching, an evidence-based approach in other fields, is relatively novel within occupational therapy (OT) and is not yet widely taught in OT programs. In recent studies, experienced occupational therapists have reported that coaching added value to their practice, but OT students’ perspectives are missing from the literature. This phenomenological study explored OT students’ ( n = 14 ) perceptions of the value of learning to coach while in fieldwork. Three themes emerged from the inductive qualitative analysis: Coaching Requires a Mindset Shift, Change is a Journey, and Impact on Clients. Occupational therapy students perceived that coaching required a different way of thinking and reimagining their role, saw the value of learning to coach in the clients’ outcomes, and recognized the potential for their future practice regardless of settings. The study findings suggest that incorporating coaching skills into OT education could be beneficial to students when they enter the profession.

Background Unintentional falls among older adults are associated with an ensuing decline in physical activity. Our objective is to evaluate the associations between fall status and changes in excursions after a fall. Methods Prospective cohort study of older adults with glaucoma or suspected glaucoma who reported falls for 1 year and wore a GPS device for 1-week at the baseline and 1 year later. GPS data were quantified into average: daily excursions, daily time away from home, and time per excursion. Fall status was categorized as fallers, injurious fallers, recurrent fallers, and recurrent injurious fallers. Multivariable negative binomial regression and generalized estimating equations models were employed to evaluate relationship between excursion parameters and fall status. Results A total of 192 eligible participants were included in the analyses. Approximately half were males (50.5%) with a mean age of 70.1 years and one-fourth were Black (28.1%). There were no significant associations between fall status and end-of-study excursion parameters (p > 0.06 for all), and visual field damage did not modify these relationships (p > 0.07 for all). For instance, patients with multiple falls during a one-year study period did not demonstrate more daily excursions (incident rate ratio [IRR] = 1.16, 95% confidence interval [CI] = 0.85 to 1.57), longer time per excursion (IRR = 0.79, 95% CI =0.59 to 1.06), or more average daily time away (IRR = 1.05, 95% CI = 0.84 to 1.30) conducted at the end-of-the study. Excursion parameters at the final assessment were not significantly different from those at baseline (p > 0.09 for all) and the changes did not vary by fall status (p > 0.23 for all). Conclusions Older adults with glaucoma did not modify their travel away from home after experiencing a fall. Additional research is necessary to understand how often maintenance of travel outside the home after a fall reflects proper compensation for greater fall risk or continued activity despite the risk of falling.

Summary: Background: We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations. Methods: Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists. Findings: Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46%) of 336 were women, 180 (54%) were men. The proportion of participants who worked in each region ranged from 104 (31%) in sub-Saharan Africa to 21 (6%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity. Interpretation: This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenges. Funding: The Queen Elizabeth Diamond Jubilee Trust, Moorfields Eye Charity, National Institute for Health Research Moorfields Biomedical Research Centre, Wellcome Trust, Sightsavers, The Fred Hollows Foundation, The Seva Foundation, British Council for the Prevention of Blindness, and Christian Blind Mission. Translations: For the French, Spanish, Chinese, Portuguese, Arabic and Persian translations of the abstract see Supplementary Materials section.

Background As the prevalence of trachoma declines worldwide, it is becoming increasingly expensive and challenging to standardize graders in the field for surveys to document elimination. Photography of the tarsal conjunctiva and remote interpretation may help alleviate these challenges. The purpose of this study was to develop, and field test an Image Capture and Processing System (ICAPS) to acquire hands-free images of the tarsal conjunctiva for upload to a virtual reading center for remote grading. Methodology/Principal findings This observational study was conducted during a district-level prevalence survey for trachomatous inflammation—follicular (TF) in Chamwino, Tanzania. The ICAPS was developed using a Samsung Galaxy S8 smartphone, a Samsung Gear VR headset, a foot pedal trigger and customized software allowing for hands-free photography. After a one-day training course, three trachoma graders used the ICAPS to collect images from 1305 children ages 1–9 years, which were expert-graded remotely for comparison with field grades. In our experience, the ICAPS was successful at scanning and assigning barcodes to images, focusing on the everted eyelid with adequate examiner hand visualization, and capturing images with sufficient detail to grade TF. The percentage of children with TF by photos and by field grade was 5%. Agreement between grading of the images compared to the field grades at the child level was kappa = 0.53 (95%CI = 0.40–0.66). There were ungradable images for at least one eye in 199 children (9.1%), with more occurring in children ages 1–3 (18.5%) than older children ages 4–9 (4.2%) (χ2 = 145.3, p, Author summary Trachoma is the leading infectious cause of blindness worldwide, caused by the bacterium Chlamydia trachomatis. Programs targeting trachoma elimination in endemic regions largely rely on periodic prevalence surveys to monitor progress, but training field graders requires active cases, which is becoming challenging as prevalence declines. Photography of the tarsal conjunctiva with remote interpretation via telemedicine may serve as a more auditable, effective, and cost-efficient method for surveys. We developed and evaluated the Image Capture and Processing System (ICAPS), a smartphone-based, hands-free, head-mounted camera system (Samsung Galaxy S8 with custom app, Samsung Gear VR headset, and a Bluetooth-linked foot pedal trigger). The ICAPS was easy to use in challenging field conditions, was able to upload images from Tanzania and link images to field data. The percentage of TF was 5% by both field grade and photo grade, with agreement kappa = 0.53. Additional field training and enhanced certification of photographers may help reduce the proportion of ungradable images; further research on reasons for mismatch of grades between field and photo is needed.

Background Trachoma, a chronic conjunctivitis caused by Chlamydia trachomatis, is the leading infectious cause of blindness worldwide. Trachoma has been targeted for elimination as a public health problem which includes reducing trachomatous inflammation—follicular prevalence in children and reducing trachomatous trichiasis prevalence in adults. The rate of development of trachomatous trichiasis, the potentially blinding late-stage trachoma sequelae, depends on the rate of trachomatous scarring development and progression. Few studies to date have evaluated the progression of trachomatous scarring in communities that have recently transitioned to a low trachomatous inflammation—follicular prevalence. Methodology/Principal findings Women aged 15 and older were randomly selected from households in 48 communities within Kongwa district, Tanzania and followed over 3.5 years for this longitudinal study. Trachomatous inflammation—follicular prevalence was 5% at baseline and at follow-up in children aged 1–9 in Kongwa, Tanzania. 1018 women aged 15 and older had trachomatous scarring at baseline and were at risk for trachomatous scarring progression; 691 (68%) completed follow-up assessments. Photographs of the upper tarsal conjunctiva were obtained at baseline and follow-up and graded for trachomatous scarring using a previously published four-step severity scale. The overall cumulative 3.5-year progression rate of scarring was 35.3% (95% CI 31.6–39.1). The odds of TS progression increased with an increase in age in women younger than 50, (OR 1.03, 95% CI 1.01–1.05, p = 0.005) as well as an increase in the household poverty index (OR 1.29, 95% CI 1.13–1.48, p = 0.0002). Conclusions/Significance The 3.5-year progression of scarring among women in Kongwa, a formerly hyperendemic now turned hypoendemic district in central Tanzania, was high despite a low active trachoma prevalence. This suggests that the drivers of scarring progression are likely not related to on-going trachoma transmission in this district., Author summary Trachoma, a chronic conjunctivitis caused by Chlamydia trachomatis, presents with follicles (trachomatous inflammation—follicular, TF) in children which leads to trachomatous conjunctival scarring (TS) in young adults. TS can progress to the in-turning of eyelashes, trachomatous trichiasis (TT) which places individuals at high risk of irreversible vision loss. Few studies to date have evaluated the progression of TS in communities that have recently transitioned to a low trachoma prevalence. We studied the progression of TS in women in Kongwa, Tanzania a district that recently transitioned to a low prevalence of trachoma. We found that the overall cumulative progression of scarring was 35.3% over 3.5 years. The scarring progression rate observed is very similar to what we observed a decade prior in Kongwa when the trachoma prevalence was very high. Our findings suggest that once scarring has developed it continues to progress irrespective of the current trachoma environment. This has potential ramifications for trachoma elimination efforts. An area could achieve the elimination of TF and still have to deal with scarring progression, which may lead to the development of TT. If this occurs: 1) elimination of TT will be delayed which will delay the overall elimination of trachoma as a public health problem, and 2) the limited resources available to elimination programs may need to be re-allocated.

Background Having a clean face is protective against trachoma. In the past, long distances to water were associated with unclean faces and increased trachoma. Other environmental factors have not been extensively explored. We need improved clarity on the environmental factors associated with facial cleanliness and trachoma prevalence, especially when the disease burden is low. Methodology/Principle findings A cross-sectional survey focusing on household environments was conducted in all 92 villages in Kongwa, Tanzania, in a random selection of 1798 households. Children aged 0–5 years in these households were examined for facial cleanliness. In each of the 50 randomly-selected villages, 50 children aged 1–9 years were randomly selected and examined for trachoma. In a multivariate model adjusting for child age, we found that children were more likely to have clean faces if the house had a clean yard (OR 1.62, 95% CI 1.37–1.91), an improved latrine (OR 1.11, 95% CI 1.01–1.22), and greater water storage capacity (OR 1.02, 95% CI 1.00–1.04), and if there were clothes washed and drying around the house (OR 1.30, 95% CI 1.09–1.54). However, measures of crowding, wealth, time spent on obtaining water, or the availability of piped water was not associated with clean faces. Using a cleanliness index (clean yard, improved latrine, washing clothes, ≥1 child in the household having a clean face), the community prevalence of trachoma decreased with an increase in the average value of the index (OR 2.28, 95% CI 1.17–4.80). Conclusions/Significance Access to water is no longer a significant limiting factor in children’s facial cleanliness in Kongwa. Instead, water storage capacity and the way that water is utilized are more important in facial cleanliness. A household cleanliness index with a holistic measure of household environment is associated with reduced community prevalence of trachoma., Author summary Trachoma, a leading cause of blindness, is caused by repeated infection that is spread from person to person via contaminated ocular and nasal discharge. Having a clean face is protective against trachoma. In the past, long distances to water were associated with unclean faces. Other environmental elements have not been extensively explored. We need improved clarity on the environmental factors affecting facial cleanliness and trachoma prevalence, especially when the disease burden is low but still above 5%. We conducted a household survey in every village in Kongwa district, Tanzania, and found that access to water has significantly improved and is no longer a limiting factor in children’s facial cleanliness. When households have more storage capacity for water used for washing, wash their clothes frequently and clean their yards, young children in the households are more likely to have clean faces. We then created a household cleanliness index that comprises a clean yard, washed clothes, an improved latrine and at least one child in the household having a clean face. We found that an increased average index score in the community is associated with a decreased prevalence of trachoma, suggesting that a multi-pronged approach to improve household cleanliness is valuable.

Background The International Trachoma Initiative (ITI) provides azithromycin for mass drug administration (MDA) to eliminate trachoma as a public health problem. Azithromycin is given as tablets for adults and powder for oral suspension (POS) is recommended for children aged Methods MDA was observed in three regions of Ethiopia and data were collected on azithromycin administration and ASEs. Results A total of 6477 azithromycin administrations were observed; 97.9% of children received the exact recommended dose. Of children aged 6 mo to Conclusions There is a high level of adherence to the revised azithromycin dosing guidelines and low incidence of choking and ASEs.

The MORDOR study, a masked, community-level randomized clinical trial conducted in Niger, Malawi and Tanzania (2015 to 2017), showed that biannual administration of single-dose azithromycin to preschool children reduced all-cause mortality. We sought to evaluate its impact on causes of death in children aged 1–59 months in Tanzania. A random sampling of 614 communities was conducted in Kilosa District, Tanzania, with simple random assignment of communities to receive either azithromycin or placebo. In these communities, a census was carried out every 6 months and children aged 1–59 months received biannual (every 6 months), single-dose azithromycin (~20mg/kg) or placebo depending on community assignment, over a 2-year period. Mortality was determined at the time of the biannual census. For child deaths, a verbal autopsy was performed to ascertain the cause using a standardized diagnostic classification. A total of 190- (0.58 /100 person-years) and 200 deaths (0.59/100 person-years) were reported in the azithromycin and placebo arms, respectively. Malaria, pneumonia and diarrhea, accounted for 71% and 68% of deaths in the respective arms. Overall, the mortality was not different by treatment arm, nor were the distribution of causes of death after adjusting for community clustering. The cause-specific mortality for diarrhea/pneumonia was no different over time. In children aged 1–5 months, 32 deaths occurred in the placebo arm and 25 deaths occurred in the azithromycin arm; 20 (62.5%) deaths in the placebo- and 10 (40%) in the azithromycin arm were attributed to diarrhea or pneumonia. Neither differences in the number of deaths nor the diarrhea/pneumonia attribution was statistically significant after adjusting for community clustering. In conclusion, azithromycin was not associated with a significant decline in deaths by specific causes compared to placebo. The non-significant lower rates of diarrhea or pneumonia in children Trial registration: NCT02048007.

Background The MORDOR study, a cluster randomized clinical trial, showed that single-dose azithromycin (20 mg/kg) administered biannually for 2 years to preschool children reduced mortality; a study was conducted to determine its effect on clinical symptomatic episodes of malaria as a potential mechanism for mortality benefit. Methods A randomized control trial (RCT) was conducted, whereby 30 randomly selected communities in Kilosa District, Tanzania were randomized to receive 6-monthly treatment of children ages 1–59 months with single-dose azithromycin (20 mg/kg) vs. placebo. A prospective cohort study was nested within the RCT: children, aged 1 to 35 months at baseline, were randomly selected in each community and evaluated at 6-monthly intervals for 2 years. At each visit, the children were assessed for recent or ongoing fever and anti-malarial treatment; a rapid diagnostic test (RDT) for malaria was performed. The two major outcomes of interest were prevalence of RDT positivity and clinical malaria. The latter was defined as RDT-positivity with fever at time of evaluation and/or reported fever in the 3 days prior to evaluation. Methods that account for correlations at community level and within individuals over time were used to evaluate associations. Results At baseline, the prevalence rates in the children in the azithromycin and placebo arms were 17.6% vs. 15.5% for RDT positivity (p = 0.76) and 6.1% vs. 4.3% (p = 0.56) for clinical malaria. There was a decline in both RDT-positivity and clinical malaria over time in both arms. The difference by treatment assignment was not significant for clinical malaria; it was significant for RDT-positivity with greater odds of decline in the placebo arm (p = 0.01). Conclusions Lack of evidence for a significant difference in the prevalence of clinical malaria in children at any visit following treatment suggests that the effect of single-dose azithromycin on malaria is at best transient and limited in scope. Chance overrepresentation of non-seasonal transmission in the communities in the azithromycin arm may account for higher rates of RDT-positivity and less decline over time. Trial registration Clinicaltrials.gov NCT02047981

Mass drug administration (MDA) for trachoma control using azithromycin has generated concern for the development of resistant organisms. However, the contribution from azithromycin available in local pharmacies has not been studied. In Kilosa district, Tanzania, MDA stopped over 4 years ago, and this study sought to determine the availability of azithromycin in local pharmacies and correlate it with azithromycin resistance in children born after MDA. A cross-sectional survey was conducted in 644 randomly selected hamlets in Kilosa district, in which the presence of a pharmacy and the availability of azithromycin and erythromycin were determined. In 30 randomly selected hamlets, a random sample of 60 children less than 5 years were tested for azithromycin-resistant Streptococcus pneumoniae (Spn) and Escherichia coli (Ec), from nasopharyngeal and rectal swabs, based on disk diffusion criteria. Only 26.6% of hamlets had a pharmacy. Azithromycin and erythromycin were available in 30.8% and 89.1% of pharmacies closest to the hamlets, respectively. In the 30 communities tested for resistance, the overall prevalence of azithromycin-resistant Spn isolates was 14%. Six of seven (87%) hamlets where azithromycin was available had resistant Spn, compared with 14 of 23 (61%) hamlets without availability. Similarly, six of seven (87%) hamlets where azithromycin was available had resistant Ec isolates compared with 21 of 23 (70%) hamlets without availability. However, the differences were not statistically significant (P = 0.46 and 0.49, respectively). The availability of azithromycin in pharmacies in the district was limited, and a strong correlation with azithromycin-resistant Spn or Ec was not observed.

Background:Older adults, especially those above age 80, are the fastest growing segment of the population in the United States and at risk for age-related cognitive decline and dementia. There is growing evidence that cognitive activity and training may allow adults to maintain or improve cognitive functioning, but little is known about the potential benefit in the oldest old. In this randomized trial, the effectiveness of a computerized cognitive training program (CCT program) was compared to an active control games program to improve cognition in cognitively normal individuals aged 80 and older.Methods:Sixty-nine older adults were randomized to a 24-session CCT program (n= 39) or an active control program (n= 30). Participants completed a pre- and post- training neuropsychological assessment. The primary outcome measure was a global cognitive composite, and the secondary outcomes were the scores on specific cognitive domains (of memory, executive function/attention, and language).Results:Using linear mixed models, there were no significant differences between the CCT and the active control program on the primary (p= 0.662) or any of the secondary outcomes (language functioning,p= .628; attention/executive functioning,p= .428; memory,p= .749).Conclusion:This study suggests that short-term CCT had no specific benefit for cognitive functioning in non-demented individuals aged 80 and older.

OBJECTIVE: To determine where glaucoma patients most often fall and how integrated visual field (IVF) damage affects falls rates per year (falls/year) and per step (falls/step) at and away from home. DESIGN: Prospective, observational cohort study METHODS: In 225 patients with glaucoma or suspected glaucoma, falls data were collected via calendars, fall location was classified through follow-up questionnaires, and steps taken at and away from home judged by integrating data from annual week-long accelerometer and GPS trials. Main outcome measures were the association of IVF sensitivity with fall rates per year or step, stratified by location. RESULTS: Participants took more away steps than home steps (2,366 vs. 1,524, p0.1 for both), but was associated with a higher rate of home falls/step (RR=1.34/5 dB worse sensitivity, p=0.03) and away falls/step (RR=1.47/5 dB worse sensitivity, p=0.003). CONCLUSIONS: In this glaucoma population, most falls occurred at home, and the risk of any step resulting in a fall was higher at home. Those with greater VF damage were more likely to fall for each step taken both at and away from home. Efforts such as home environmental modification should be considered in the visually impaired to prevent falls while maintaining physical activity.

Purpose Posttreatment Lyme disease (PTLD) is marked by neurologic symptoms, cognitive impairment, and significant symptom burden, including fatigue and ocular complaints. The purpose of this study was to determine whether contrast sensitivity (CS) is altered in patients with PTLD compared with healthy controls and, second, whether CS is associated with cognitive and/or neurologic deficits. Methods CS was measured using a Pelli-Robson chart with forced-choice procedures, and the total number of letters read was recorded for each eye. CS impairment was defined for age

Eye health and vision have widespread and profound implications for many aspects of life, health, sustainable development, and the economy. Yet nowadays, many people, families, and populations continue to suffer the consequences of poor access to high-quality, affordable eye care, leading to vision impairment and blindness.\ud In 2020, an estimated 596 million people had distance vision impairment worldwide, of whom 43 million were blind. Another 510 million people had uncorrected near vision impairment, simply because of not having reading spectacles. A large proportion of those affected (90%), live in low-income and middle-income countries (LMICs). However, encouragingly, more than 90% of people with vision impairment have a preventable or treatable cause with existing highly cost-effective interventions. Eye conditions affect all stages of life, with young children and older people being particularly affected. Crucially, women, rural populations, and ethnic minority groups are more likely to have vision impairment, and this pervasive inequality needs to be addressed. By 2050, population ageing, growth, and urbanisation might lead to an estimated 895 million people with distance vision impairment, of whom 61 million will be blind. Action to prioritise eye health is needed now.\ud This Commission defines eye health as maximised vision, ocular health, and functional ability, thereby contributing to overall health and wellbeing, social inclusion, and quality of life. Eye health is essential to achieve many of the Sustainable Development Goals (SDGs). Poor eye health and impaired vision have a negative effect on quality of life and restrict equitable access to and achievement in education and the workplace. Vision loss has substantial financial implications for affected individuals, families, and communities. Although high-quality data for global economic estimates are scarce, particularly for LMICs, conservative assessments based on the latest prevalence figures for 2020 suggest that annual global productivity loss from vision impairment is approximately US$410·7 billion purchasing power parity. Vision impairment reduces mobility, affects mental wellbeing, exacerbates risk of dementia, increases likelihood of falls and road traffic crashes, increases the need for social care, and ultimately leads to higher mortality rates.\ud By contrast, vision facilitates many daily life activities, enables better educational outcomes, and increases work productivity, reducing inequality. An increasing amount of evidence shows the potential for vision to advance the SDGs, by contributing towards poverty reduction, zero hunger, good health and wellbeing, quality education, gender equality, and decent work. Eye health is a global public priority, transforming lives in both poor and wealthy communities. Therefore, eye health needs to be reframed as a development as well as a health issue and given greater prominence within the global development and health agendas.\ud Vision loss has many causes that require promotional, preventive, treatment, and rehabilitative interventions. Cataract, uncorrected refractive error, glaucoma, age-related macular degeneration, and diabetic retinopathy are responsible for most global vision impairment. Research has identified treatments to reduce or eliminate blindness from all these conditions; the priority is to deliver treatments where they are most needed. Proven eye care interventions, such as cataract surgery and spectacle provision, are among the most cost-effective in all of health care. Greater financial investment is needed so that millions of people living with unnecessary vision impairment and blindness can benefit from these interventions.\ud Lessons from the past three decades give hope that this challenge can be met. Between 1990 and 2020, the age-standardised global prevalence of blindness fell by 28·5%. Since the 1990s, prevalence of major infectious causes of blindness—onchocerciasis and trachoma—have declined substantially. Hope remains that by 2030, the transmission of onchocerciasis will be interrupted, and trachoma will be eliminated as a public health problem in every country worldwide. However, the ageing population has led to a higher crude prevalence of age-related causes of blindness, and thus an increased total number of people with blindness in some regions.\ud Despite this progress, business as usual will not keep pace with the demographic trends of an ageing global population or address the inequities that persist in each country. New threats to eye health are emerging, including the worldwide increase in diabetic retinopathy, high myopia, retinopathy of prematurity, and chronic eye diseases of ageing such as glaucoma and age-related macular degeneration. With the projected increase in such conditions and their associated vision loss over the coming decades, urgent action is needed to develop innovative treatments and deliver services at a greater scale than previously achieved.\ud Good eye health at the community and national level has been marginalised as a luxury available to only wealthy or urban areas. Eye health needs to be urgently brought into the mainstream of national health and development policy, planning, financing, and action.\ud The challenge is to develop and deliver comprehensive eye health services (promotion, prevention, treatment, rehabilitation) that address the full range of eye conditions within the context of universal health coverage. Accessing services should not bring the risk of falling into poverty and services should be of high quality, as envisaged by the WHO framework for health-care quality: effective, safe, people-centred, timely, equitable, integrated, and efficient. To this framework we add the need for services to be environmentally sustainable. Universal health coverage is not universal without eye care.\ud Multiple obstacles need to be overcome to achieve universal coverage for eye health. Important issues include complex barriers to availability and access to quality services, cost, major shortages and maldistribution of well-trained personnel, and lack of suitable, well maintained equipment and consumables. These issues are particularly widespread in LMICs, but also occur in underserved communities in high-income countries. Strong partnerships need to be formed with natural allies working in areas affected by eye health, such as non-communicable diseases, neglected tropical diseases, healthy ageing, children's services, education, disability, and rehabilitation. The eye health sector has traditionally focused on treatment and rehabilitation, and underused health promotion and prevention strategies to lessen the impact of eye disease and reduce inequality.\ud Solving these problems will depend on solutions established from high quality evidence that can guide more effective implementation at scale. Evidence-based approaches will need to address existing deficiencies in the supply and demand. Strategic investments in discovery research, harnessing new findings from diverse fields, and implementation research to guide effective scale up are needed globally. Encouragingly, developments in telemedicine, mobile health, artificial intelligence, and distance learning could potentially enable eye care professionals to deliver higher quality care that is more plentiful, equitable, and cost-effective.\ud This Commission did a Grand Challenges in Global Eye Health prioritisation exercise to highlight key areas for concerted research and action. This exercise has identified a broad set of challenges spanning the fields of epidemiology, health systems, diagnostics, therapeutics, and implementation. The most compelling of these issues, picked from among 3400 suggestions proposed by 336 people from 118 countries, can help to frame the future research agenda for global eye health.\ud In this Commission, we harness lessons learned from over two decades, present the growing evidence for the life-transforming impact of eye care, and provide a thorough understanding of rapid developments in the field. This report was created through a broad consultation involving experts within and outside the eye care sector to help inform governments and other stakeholders about the path forward for eye health beyond 2020, to further the SDGs (including universal health coverage), and work towards a world without avoidable vision loss.\ud The next few years are a crucial time for the global eye health community and its partners in health care, government, and other sectors to consider the successes and challenges encountered in the past two decades, and at the same time to chart a way forward for the upcoming decades. Moving forward requires building on the strong foundation laid by WHO and partners in VISION 2020 with renewed impetus to ultimately deliver high quality universal eye health care for all.

Background There is evidence of the occurrence of trachoma in Peru, and studies have shown that soil-transmitted helminthiases (STH) are affecting rural communities in the Amazon basin in Loreto Department. This study was done to estimate trachoma prevalence, STH prevalence, and the associated factors for both diseases in children aged 1–9 years in rural communities of Peru. Methodology A population-based cross-sectional survey was carried out in rural communities of Loreto. A standardized survey questionnaire with individual and household risk factors related to both diseases was used. Ocular examination was done for all participants aged one year and above, and eye swab samples were collected from children with follicular trachoma (TF). Anthropometric measurements, stool samples for STH, and blood samples for hemoglobin measurement were taken from children. Principal findings TF prevalence was 7.74% (95% CI 5.08–11.63%), STH prevalence was 49.49% (95% CI 25.00–52.43%), and prevalence of co-occurrence of both diseases was 5.06% (95% CI 2.80–8.98%) in children aged 1–9 years. Being at age 3–8 years old (AOR = 6.76; 95% CI 1.346–33.947), have an unclean face (AOR = 24.64; 95% CI 6.787–89.444), and having been dewormed in the last six months (AOR = 2.47; 95% CI 1.106–5.514), were risk factors of TF. Being a female (AOR = 0.22; 95% CI 0.103–0.457) was associated with decreased odds of TF. Having been dewormed in the last six months (AOR = 0.30; 95% CI 0.139–0.628) was a preventative factor for STH. Risk factors for children with both diseases mirrored the findings for risk factors for individual diseases. Conclusions Neglected tropical diseases and associated risk factors overlap in communities living in vulnerable conditions in the Amazon basin of Peru. These findings support the need to implement integrated interventions, including mass drug administration, water, sanitation, and hygiene for both diseases in the study area.

Background Serologic testing for chlamydial antibodies is one potential tool for trachoma monitoring. Understanding the dynamics of seroconversion and seroreversion in low endemic districts is critical for determining the value of using serology. Methodology/Principal findings We surveyed a random sample of 2536 children aged 1–9 years in Kongwa, Tanzania, over three years; 1719 (67.8%) participants had all three follow-ups. Surveys assessed trachomatous inflammation—follicular (TF), Chlamydia trachomatis infection, and anti-pgp3 antibodies. Mass drug administration occurred immediately after the first and second follow-up surveys. The cohort was classified into trajectories of change in serostatus, and risk factors were evaluated for seroconversion and seroreversion. We found that 86.2% of seropositives remained seropositive throughout the study, whereas 12.1% seroreverted. Seroreverters were younger (Odds Ratio [OR] = 0.88 for every one-year increase in age, 95% CI = 0.79–0.99). 84.5% of seronegatives remained seronegative, and 13.0% seroconverted. Seroconverters were also younger (OR = 0.92, 95% CI = 0.87–0.98). Seroconversion and seroreversion were not explained by indeterminate values for the intensity of antibody response. Less than 1% of the cohort had unstable changes in serostatus, mostly explained by values in the indeterminate range. TF and infection in the cohort declined over time, while seropositivity increased from 31.5% to 36.4%. Conclusions/Significance Antibody status is relatively stable over time. Both seroconversion and seroreversion occurred over the three years in this low endemic district, especially in younger children. Modeling seroreversion is important for accurate determination of seroconversion. The use of serology as a monitoring tool should target the younger aged children as they will most likely capture recent changes in serostatus.

Background Health promotion is essential to the SAFE strategy for trachoma elimination. Schools are a valuable venue for health promotion. However, there is little literature about the impact of health education and water infrastructure in schools on facial cleanliness and trachoma in the community. Our study aimed to describe the current state of school health promotion in Kongwa, Tanzania, and to examine the transferability of health messages from schools to the community at large. Methodology/Findings A cross-sectional survey was carried out in all 92 villages in Kongwa district, which included 85 primary schools. Data were collected on health messages and water infrastructure in the schools. A random sample of 3084 children aged 0–5 were examined for facial cleanliness in all villages. In 50 villages, a random sample of 50 children aged 1–9 per village were examined for follicular trachoma (TF). Thirty-seven (44.6%) schools had educational materials on face-washing. Fifty (60.2%) schools had a washing station. The presence of a health teacher was correlated with having posters on face washing in classrooms. The presence of face-washing materials was correlated with the availability of washing stations. Neither teachers mentioning face-washing in health curricula nor educational materials in classrooms were associated with clean faces or trachoma in the community. Having a washing station in the school was associated with lower community rates of trachoma. Conclusions Primary school health messages and materials on trachoma were not associated with clean faces or lower rates of trachoma in the community. The target audience for primary school health promotion is likely the students themselves, without immediate rippling effects in the community. A long-term perspective should be considered during the implementation of health promotion in schools. The goal of school health promotion should be training the next generation of parents and community health leaders in combatting trachoma., Author summary Trachoma is caused by repeated infection that is spread from person to person via contaminated ocular and nasal discharge. Education on healthy habits such as face washing is essential to the elimination of trachoma. Schools are one place for health promotion programs because so many children can be reached. In previous studies, students showed increased knowledge about trachoma and healthy behavior after engaging in health education programs. We examined if there was evidence that school-based messages were disseminated to the community at large via the primary school students. We found that school health messages did not impact clean faces in pre-school children or trachoma prevalence in the community in general. Having a washing station in the school was associated with lower community rates of trachoma. The data suggested that schoolchildren were not effective messengers of health knowledge and behavior. Primary school health promotion mainly targets students themselves and may not have rippling effects in the community. We should view school health curricula with a long-term perspective as they train the next generation of caregivers and heads of households to raise their own children with healthier habits.

Background & Aims The prevalence and significance of digestive manifestations in coronavirus disease 2019 (COVID-19) remain uncertain. We aimed to assess the prevalence, spectrum, severity, and significance of digestive manifestations in patients hospitalized with COVID-19. Methods Consecutive patients hospitalized with COVID-19 were identified across a geographically diverse alliance of medical centers in North America. Data pertaining to baseline characteristics, symptomatology, laboratory assessment, imaging, and endoscopic findings from the time of symptom onset until discharge or death were abstracted manually from electronic health records to characterize the prevalence, spectrum, and severity of digestive manifestations. Regression analyses were performed to evaluate the association between digestive manifestations and severe outcomes related to COVID-19. Results A total of 1992 patients across 36 centers met eligibility criteria and were included. Overall, 53% of patients experienced at least 1 gastrointestinal symptom at any time during their illness, most commonly diarrhea (34%), nausea (27%), vomiting (16%), and abdominal pain (11%). In 74% of cases, gastrointestinal symptoms were judged to be mild. In total, 35% of patients developed an abnormal alanine aminotransferase or total bilirubin level; these were increased to less than 5 times the upper limit of normal in 77% of cases. After adjusting for potential confounders, the presence of gastrointestinal symptoms at any time (odds ratio, 0.93; 95% CI, 0.76–1.15) or liver test abnormalities on admission (odds ratio, 1.31; 95% CI, 0.80–2.12) were not associated independently with mechanical ventilation or death. Conclusions Among patients hospitalized with COVID-19, gastrointestinal symptoms and liver test abnormalities were common, but the majority were mild and their presence was not associated with a more severe clinical course.

Background Trachoma is the leading infectious cause of blindness. Repeated or persistent ocular infection with Chlamydia trachomatis in childhood leads to conjunctival scarring, usually in adulthood but often earlier in areas with greater disease burden. There are limited longitudinal data examining change in scarring in children, especially where trachoma rates are low. Methodology/Principal findings A cohort of children, ages 1–9 years, were randomly selected at baseline from 38 communities in Kongwa, Tanzania and followed for 2 years. Rates of trachomatous inflammation—follicular (TF) were, Author summary Trachoma is the leading infectious cause of blindness. The disease is caused by repeated eye infection with the bacterium Chlamydia trachomatis and characterized clinically in its active stage by follicles (TF) and/or severe inflammation (TI). Scarring of the inner surface of the eyelid results from repeated exposure to infection during childhood, and while active trachoma is mostly observed in childhood, scarring and late complications are often only seen in adulthood. In areas with heavy burden of trachoma, scarring may be observed among children, particularly among those with constant, severe trachoma and/or infection. Few studies have examined the incidence and progression of scarring in children in areas where the prevalence of trachoma has been substantially reduced. In this study, we examined the 2-year incidence and progression of scarring in Kongwa district, Tanzania where the prevalence of TF was about 5%. Incidence of new scarring was 0.8%/year and more common among girls. Progression of scarring was 21% in our cohort of children ages 1–9 years. Incidence in children was low in this formerly hyper-endemic area, but a substantial fraction of those with scarring at baseline demonstrated progression over the follow-up period. These data provide support for the thesis that without repeated exposure to trachoma, incident scarring is low, but other mechanisms for progression of scarring apart from ongoing transmission are operating, at least in children.

Mild traumatic brain injury (mTBI) remains a prevalent public health concern. Implementation of an mTBI guideline encouraged screening all patients at risk for mTBI, followed by outpatient follow-up in a "concussion clinic." This resulted in an increase in inpatient concussion evaluations, followed by high-volume referral to the concussion clinic. This prompted the routine use of an outpatient mTBI symptom screening tool. The purpose of this quality improvement study was to analyze the characteristics of an mTBI population at outpatient follow-up and describe the clinicians' care recommendations as determined through the use of an mTBI symptom screening tool.This is a retrospective review of mTBI patients at a Level 1 trauma center. The study includes patients who completed a concussion screening in the outpatient setting over a 6-month period. Patients were included if older than 16 years, sustained blunt trauma, and had a formal neurocognitive evaluation by a certified speech therapist within 48 hr of initial injury.Of the 247 patients included, 197 (79.8%) were referred to the concussion clinic, 33 (13.4%) had no further outpatient needs, and 17 (6.9%) were referred for outpatient neurocognitive rehabilitation. On follow-up, 97 patients were deemed to have no further postconcussion needs by the trauma nurse practitioner; 57 patients were cleared by the speech therapist. In total, 43 outpatient mTBI follow-up encounters resulted in referral for ongoing therapy.Routine screening for concussion symptoms and detailed clinical evaluation allows for prompt recognition of further posttraumatic mTBI needs.

INTRODUCTION: Ocular Chlamydia trachomatis infection, the causative agent for trachoma, is responsible for 1.9 million cases of visual loss world-wide. Mass Drug Administration (MDA) with azithromycin to entire trachoma-endemic districts is part of the World Health Organization’s public health strategy for trachoma elimination. AREAS COVERED: Background on C. trachomatis and the epidemiology of trachoma are presented, followed by a review of the antibiotics for treatment and the need for a public health approach to trachoma elimination. The effectiveness of mass drug administration is presented, concluding with challenges to trachoma elimination in the future. EXPERT OPINION: MDA using azithromycin is a key component of the public health strategy for trachoma elimination. With high coverage in children, there is good evidence that MDA drops the community pool of infection. There are challenges to trachoma elimination by the year 2020, and the drug donation program for country MDAs will be integral to ongoing efforts

A serologic test for antibodies to chlamydia may be a useful tool for trachoma surveillance. However, little is known about the longitudinal stability of antibody status, especially following Mass Drug Administration (MDA), which is critical to understanding serostatus in trachoma-endemic areas. A longitudinal cohort of 1908 children ages 1–9 years in Tanzania from 50 communities were followed at baseline and for 6 months after MDA. They were evaluated for clinical trachoma, conjunctival swabs were tested for chlamydial infection using GeneXpert platform, and blood spots were collected on filter paper and dried to test for antibodies to Chlamydia trachomatis pgp3 using the Luminex platform. 6.3% of children in the study had infection, and coverage with MDA was 97%. 670 (35%) were sero-positive for pgp3 antibodies at baseline, and 4.0% of these seroreverted to negative following MDA. Of those seronegative at baseline, 3.6% seroconverted. The individual change in log median fluorescence intensity(MFI-BG) values was -0.15 overall (p

AIMS/HYPOTHESIS: There are established relationships between adiposity (obesity) and higher dementia risk, faster cognitive decline and associated neural injury. Type 2 diabetes is strongly linked to greater adiposity and has been consistently associated with neural injury and poor cognitive outcomes. However, although obesity is a major cause of type 2 diabetes, there is limited evidence on the association of adiposity with brain atrophy among individuals with type 2 diabetes. METHODS: We examined the association of BMI (a measure of adiposity), and of long-term trajectories of BMI (three empirically identified groups of trajectories—’normal’, ‘overweight’ and ‘obese’—using SAS macro PROC TRAJ), with regional brain volume, in a sample of older individuals (aged 64–84) with type 2 diabetes participating in the Israel Diabetes and Cognitive Decline Study (n=198). RESULTS: Using linear regression, we found that greater BMI was associated with smaller volumes of the inferior frontal gyrus (IFG) (r=−0.25, p=0.001) and the middle temporal gyrus (r=−0.19; p=0.010) after adjusting for sociodemographic covariates and total intracranial volume. In addition, there were significant differences between BMI trajectory groups in IFG volume (F=4.34, p=0.014), such that a long-term trajectory of obesity was associated with a smaller volume. Additional adjustment for cardiovascular and diabetes-related potential confounders did not substantively alter the results. There were no associations of adiposity with superior frontal gyrus, middle frontal gyrus or total grey matter volumes. CONCLUSIONS/INTERPRETATION: In older adults with type 2 diabetes, long-term adiposity may have a detrimental impact on volume of brain regions relevant to cognitive functioning. Further studies to identify the underlying mechanisms are warranted.

Purpose To investigate the association between balance and gait measures with fall rates in glaucoma patients. Methods Balance and gait were measured for 239 participants with glaucoma or suspected glaucoma. Daily falls were evaluated over 24 months. Annual accelerometer trials captured average daily steps. Multivariable negative binomial models evaluated balance and gait associations with average daily steps and rates of falls per time or step, as well as whether balance and gait parameters mediated the association between integrated visual field (IVF) sensitivity and falls. Results Average age was 70.5 years (SD = 7.6), and 22% of the participants had moderate to severe visual field damage. Over the first 12 months of the follow-up, the cumulative probability of falling one or more times was 44.8%, and the cumulative probability of falling two or more times was 17.7%. Gait deficits were associated with fewer daily steps (P < 0.03), but no balance parameters were (P > 0.19). Worse balance was associated with a higher rate of falls per year and step (P < 0.03). No gait measures were associated with the rate of falls per year (P > 0.17). More time in double support and greater swing time variability were associated with higher falls per step, and higher velocity and faster cadence were associated with fewer falls per step (P < 0.05 for all). Neither gait nor balance measures mediated the relationship between visual field damage and fall rates. IVF remained an independent predictor of falls per step (rate ratio = 1.36 to 1.48; P < 0.001 to P < 0.005) in multivariable models including individual balance/gait parameters. Conclusions Although balance and gait measures are associated with fall rates, they do not explain why persons with greater visual field damage fall more frequently, suggesting the importance of other potential factors such as hazard perception.

PURPOSE: To define and quantify patterns of objectively measured daily physical activity by level of visual field (VF) damage in glaucoma patients including: (1) activity fragmentation, a metric of health and physiological decline, and (2) diurnal patterns of activity, a measure of rest/activity rhythms. DESIGN: Prospective cohort study. SUBJECTS: Older adults diagnosed with glaucoma or suspected glaucoma. METHODS: Degree of VF damage was defined by the average VF sensitivity within the integrated VF (IVF). Each participant wore a hip accelerometer for one week to measure daily minute-by-minute activity for seven consecutive days. Activity fragmentation was calculated as the reciprocal of the average activity bout duration in minutes, with higher fragmentation indicating more transient, rather than sustained, activity. Multivariable linear regression was used to test for cross-sectional associations between VF damage and activity fragmentation. Multivariable linear mixed-effects models were used to assess the associations between VF damage and accumulation of activity across six time periods (5am–8am, 8am–11am, 11am–2pm, 2pm–5pm, 5pm–8pm, 8pm–11pm). MAIN OUTCOME MEASURES: Activity fragmentation and amount of activity (steps) over the course of the day. RESULTS: Each 5-unit (dB) decrement in IVF sensitivity was associated with 16.3 fewer active minutes/day (p

BACKGROUND: Mass distributions of azithromycin for trachoma have been associated with secondary benefits, including reductions in child mortality. METHODS: In the Partnership for the Rapid Elimination of Trachoma cluster-randomized trial in Niger, 24 communities were randomized to annual treatment of everyone and 24 communities were randomized to biannual treatment of children under 12 for 3 years (clinicaltrials.gov, NCT00792922). Treatment was a single dose of directly observed oral azithromycin (20 mg/kg up to 1 g in adults). Vital status was assessed during annual census and monitoring visits. In this prespecified secondary analysis, we compared the mortality rate among children 6 months to less than 5 years of age by treatment arm using negative binomial regression. RESULTS: Among children 6 months to less than 5 years of age, 404 deaths occurred during the study period. The mortality rate was 35.6 deaths per 1000 person-years (231 deaths, 95% CI: 30.9-40.9) in the annual arm and 29.0 deaths per 1000 person-years (173 deaths, 95% CI: 24.8-33.8) in the biannual arm. The mortality rate ratio comparing children in the biannual arm to the annual arm was 0.81 (95% CI: 0.66-1.00, P = 0.07; primary outcome). The mortality rate ratio comparing children who died from infectious causes in the biannual arm to the annual arm was 0.73 (95% CI: 0.57-0.94; P = 0.02). No adverse events were reported. CONCLUSIONS: This secondary analysis of a cluster-randomized trial found a nonsignificant 19% decrease in mortality among children 6 months to less than 5 years of age who received biannual azithromycin compared with children who received annual azithromycin. This study was conducted in a high mortality, trachoma-endemic area; thus, results may be specific to this environment only. In addition, the trial was neither designed nor powered to detect a mortality effect, and we cannot rule out the possibility that mortality differences resulted from bias.

Purpose To investigate the natural history of Stargardt disease (STGD1) using fixation location and fixation stability. Design Multicenter, international, prospective cohort study. Methods Fixation testing was performed using the Nidek MP-1 microperimeter as part of the prospective, multicenter, natural history study on the Prog ression of Star gardt disease (ProgStar). A total of 238 patients with ABCA4-related STGD1 were enrolled at baseline (bilateral enrollment in 86.6%) and underwent repeat testing at months 6 and 12. Results Outcome measures included the distance of the preferred retinal locus from the fovea (PRL) and the bivariate contour ellipse area (BCEA). After 12 months of follow-up, the change in the eccentricity of the PRL from the anatomic fovea was −0.0014 degrees (95% confidence interval [CI], −0.27 degrees, 0.27 degrees; P = .99). The deterioration in the stability of fixation as expressed by a larger BCEA encompassing 1 standard deviation of all fixation points was 1.21 degrees squared (deg2) (95% CI, −1.23 deg2, 3.65 deg2; P = .33). Eyes with increases and decreases in PRL eccentricity and/or BCEA values were observed. Conclusions Our observations point to the complexity of fixation parameters. The association of increasingly eccentric and unstable fixation with longer disease duration that is typically found in cross-sectional studies may be countered within individual patients by poorly understood processes like neuronal adaptation. Nevertheless, fixation parameters may serve as useful secondary outcome parameters in selected cases and for counseling patients to explain changes to their visual functionality.

BACKGROUND: The association between caffeine and cognitive performance has not been tested in older individuals with type 2 diabetes (T2D). Its association with brain volume in T2D has been tested only in animals. METHODS: We examined the association of caffeine with cognitive function and brain volume in a sample of elderly diabetics participating in the Israel Diabetes and Cognitive Decline Study (n = 638) and the moderating effect of age on this association. In a subsample (n = 185) with magnetic resonance imaging, we also examined these associations with gray and white matter volumes (GM/WM). RESULTS: Using linear regression adjusting for cognition-related covariates, we found that higher caffeine intake was associated with better function in overall cognition (p = .018), attention/working memory (p = .002), executive functioning (p = .047), and semantic categorization (p = .026). Interaction analyses of caffeine intake with age were significant for semantic categorization (p = .025), and approached significance for overall cognition (p = .066). This association was driven by the older group (above-median) for whom the association of caffeine intake with semantic categorization (p = .001), attention/working memory (p = .007), executive functioning (p = .005), and overall cognition (p = .002) were significant. In the magnetic resonance imaging subsample, there was an interaction (p = .034) of caffeine intake with age for GM volume; in the older group, higher caffeine intake was associated with greater GM volume (β = .198, p = .033). CONCLUSIONS: Caffeine intake may have a beneficial role in cognitive functioning of elderly adults with T2D, which may be moderated by age. Greater GM volume may be a mechanism underlying the association of higher caffeine intake with better cognitive function.

Background/aimsTo describe the genetic characteristics of the cohort enrolled in the international multicentre progression of Stargardt disease 1 (STGD1) studies (ProgStar) and to determine geographic differences based on the allele frequency.Methods345 participants with a clinical diagnosis of STGD1 and harbouring at least one disease-causing ABCA4 variant were enrolled from 9 centres in the USA and Europe. All variants were reviewed and in silico analysis was performed including allele frequency in public databases and pathogenicity predictions. Participants with multiple likely pathogenic variants were classified into four national subgroups (USA, UK, France, Germany), with subsequent comparison analysis of the allele frequency for each prevalent allele.Results211 likely pathogenic variants were identified in the total cohort, including missense (63%), splice site alteration (18%), stop (9%) and others. 50 variants were novel. Exclusively missense variants were detected in 139 (50%) of 279 patients with multiple pathogenic variants. The three most prevalent variants of these patients with multiple pathogenic variants were p.G1961E (15%), p.G863A (7%) and c.5461-10 T>C (5%). Subgroup analysis revealed a statistically significant difference between the four recruiting nations in the allele frequency of nine variants.ConclusionsThere is a large spectrum of ABCA4 sequence variants, including 50 novel variants, in a well-characterised cohort thereby further adding to the unique allelic heterogeneity in STGD1. Approximately half of the cohort harbours missense variants only, indicating a relatively mild phenotype of the ProgStar cohort. There are significant differences in allele frequencies between nations, although the three most prevalent variants are shared as frequent variants.

Objective Currently, 30 US states mandate that radiologists notify women when dense breast tissue is found on mammography. Little is understood about how notifications are perceived by recipients. This qualitative study sought to understand how dense breast notifications (DBNs) impact women’s perceptions and their participation in follow-up care. Methods We assessed rates of DBN recall and conducted semi-structured telephone interviews with 30 English-speaking women ages 40 to 74 after receiving a DBN from a Massachusetts hospital. Content coding characterized women’s recall of the notification content, perceptions of breast density, and planned or actual participation in follow-up care. Results Most women (81%) recalled receiving a DBN, but few could recall specific content. Women described struggling to understand the meaning of breast density and created their own explanatory models of dense breasts that differed from medical explanations. Many women planned to or did talk with their doctors about breast density as a result of receiving the notification. Conclusions Women receiving DBNs have limited knowledge and many misperceptions about the implications of having dense breasts. Practice implications Educational support is needed to promote informed decision- making about breast cancer screening that incorporates personal risk in the setting of dense breast legislation.

The sensitivity of the human visual system is thought to be shaped by environmental statistics. A major endeavour in vision science, therefore, is to uncover the image statistics that predict perceptual and cognitive function. When searching for targets in natural images, for example, it has recently been proposed that target detection is inversely related to the spatial similarity of the target to its local background. We tested this hypothesis by measuring observers’ sensitivity to targets that were blended with natural image backgrounds. Targets were designed to have a spatial structure that was either similar or dissimilar to the background. Contrary to masking from similarity, we found that observers were most sensitive to targets that were most similar to their backgrounds. We hypothesised that a coincidence of phase-alignment between target and background results in a local contrast signal that facilitates detection when target-background similarity is high. We confirmed this prediction in a second experiment. Indeed, we show that, by solely manipulating the phase of a target relative to its background, the target can be rendered easily visible or undetectable. Our study thus reveals that, in addition to its structural similarity, the phase of the target relative to the background must be considered when predicting detection sensitivity in natural images.

Background/aimsTo determine the incidence of scarring in women in a trachoma low endemic district of rural Tanzania and to determine the effects of lifetime cooking fire exposure and markers of lower socioeconomic status on incidence of scarring in these women.MethodsA prospective cohort study was conducted over a 3.5-year period from 2013 to 2016 in 48 villages in Kongwa, Tanzania where trachoma at baseline was 5.2% in children. A random sample of 2966 women aged 15 and older who were at risk for incident scarring were eligible for follow-up. Data on demographic factors, cooking fire exposure and trachomatous scarring were gathered at baseline and follow-up. An index of lifetime exposure to cooking fire exposure was created and bivariate analysis, age-adjusted logistic regression and multivariable logistic models were used to look for associations of demographic factors and cooking fire exposure with incident trachomatous scarring.ResultsThe cumulative incidence of scarring was 7.1% or 2.0% per year. Incidence of scarring increased with age and exposure to markers of lower socioeconomic status. A multivariable logistic regression model adjusting for confounding factors did not find an association between lifetime cooking fire exposure and incidence of scarring (OR=0.92; 95% CI 0.68 to 1.24, P=0.58).ConclusionsThere was still incident scarring in women in Tanzania despite low rates of active trachoma. There was no association between exposure to cooking fires and incident scarring. More research is needed to understand the factors that contribute to new scarring in these women.

Background/Aims: To describe the design and baseline characteristics of patients enrolled in the multicenter, prospective natural history study of Stargardt disease type 4. Methods: Fifteen eligible patients aged 6 years and older at baseline, harboring disease-causing variants in the PROM1 gene, and with specified ocular lesions were enrolled. They were examined at baseline using a standard protocol, with 6 monthly follow-up visits for a 2-year period including best-corrected ETDRS visual acuity, spectral-domain optical coherence tomography, fundus autofluorescence (FAF), mesopic and scotopic microperimetry (MP). Areas of definitely decreased FAF (DDAF) and questionably decreased FAF were outlined and quantified on FAF images. Results: Amongst the 15 patients (29 eyes) that were enrolled at 5 centers in the USA and Europe, 10 eyes (34.5%) had areas of DDAF with an average lesion area of 3.2 ± 3.5 mm2 (range 0.36–10.39 mm2) at baseline. The mean retinal sensitivity of the posterior pole derived from mesopic MP was 8.8 ± 5.8 dB. Conclusions: Data on disease progression in PROM1-related retinopathy from this study will contribute to the characterization of the natural history of disease and the exploration of the utility of several modalities to track progression and therefore to potentially be used in future interventional clinical trials.

IMPORTANCE: Gait dysfunction is common in older people with visual impairment and is a major cause of falls. OBJECTIVE: To compare 3-year longitudinal changes in gait measures across the spectrum of baseline visual field (VF) damage in glaucoma. DESIGN, SETTING, AND PARTICIPANTS: A post hoc analysis was designed on September 1, 2018, following a prospective cohort study, which enrolled older adults with glaucoma or suspected glaucoma from September 2013 to March 2015 and followed up for up to 3 years. Baseline VF damage was defined by integrated VF (IVF) sensitivity and categorized as normal/mild (IVF >28 dB), moderate (IVF, 23-28 dB), and severe (IVF

Background We present a case series of upper extremity fibromuscular dysplasia (UE FMD) consisting of 22 patients from two tertiary referral centers focusing on clinical presentation, diagnostic findings, and interventional outcomes. FMD is a noninflammatory, nonatherosclerotic arteriopathy that has a predisposition for middle-aged women. Involvement of the UE is thought to be rare. Patients with UE FMD can present with claudication or ischemia, or they can be incidentally diagnosed. The treatment approach is dictated by clinical presentation. Methods Data were collected of patients with UE FMD evaluated at two centers. Demographic data, presenting UE symptoms, UE arteries involved, FMD type, diagnostic method, physical examination findings, management, and outcomes were included. Results Twenty-two patients (29 limbs) were diagnosed with UE FMD. The brachial artery was most commonly involved (89.7% of affected limbs). More than half of limbs (n = 15 of 29 limbs [51.7%]) were asymptomatic, and of those who presented with symptoms, the most common symptoms were ischemic fingers or hand (31% of all affected limbs) and hand or arm claudication (27.6% of all affected limbs). UE FMD was noted on catheter angiography in 58.6% (n = 17 of 29 limbs), duplex ultrasound in 41.4% (n = 12 of 29 limbs), and computed tomography angiography in 27.6% (n = 8 of 29 limbs). Of the symptomatic limbs (n = 14), the majority were treated solely with medical therapy as the first intervention (57.1%). For symptomatic limbs treated with vascular intervention (n = 5), angioplasty was most commonly performed. Only 4 of the 14 limbs (28.6%) had complete symptomatic relief after the initial first intervention, in which 2 limbs were treated with medical therapy, 1 limb underwent angioplasty, and 1 limb had resolution of symptoms despite deferment of any therapy. Of the 10 limbs with residual symptoms after the first intervention, 6 limbs underwent a second intervention: angioplasty in 2 limbs initially treated medically (33.3%), surgical bypass in 2 limbs initially treated with angioplasty, surgical bypass in 1 limb initially treated with medical therapy, and sympathectomy in 1 limb (16.7%) initially treated with angioplasty. Both surgical bypass and angioplasty as secondary interventions resulted in complete symptom relief. Conclusions Presenting symptoms for patients with UE FMD vary in severity from asymptomatic disease to digital ischemia. More than half of symptomatic limbs eventually require at least one invasive intervention for complete relief of symptoms.

Summary Background The Macrolides Oraux pour Reduire les Deces avec un Oeil sur la Resistance (MORDOR) trial found that biannual mass distribution of azithromycin to children younger than 5 years in Niger reduced the primary outcome of all-cause mortality by 18%. We aimed to determine the causes of mortality among deceased children using verbal autopsy. Methods In this 2-year cluster-randomised controlled trial, 594 community clusters in Niger were randomly allocated (1:1 ratio) to receive biannual mass distributions of either oral azithromycin (approximately 20 mg per kg of bodyweight) or placebo targeted to children aged 1–59 months. Participants, study investigators, and field workers were masked to treatment allocation. Between Nov 23, 2014, and July 31, 2017, 3615 child deaths were recorded by use of biannual house-to-house censuses, and verbal autopsies were done between May 26, 2015, and May 17, 2018, to identify cause of death. Cause-specific mortality, as assessed by verbal autopsy, was a prespecified secondary outcome. This trial is completed and is registered with ClinicalTrials.gov , NCT02047981 . Findings Between Nov 23, 2014, and July 31, 2017, 303 communities (n=40 375 children at baseline) in Niger received mass azithromycin and 291 communities (n=35 747 children at baseline) received placebo. Treatment coverage was 90·3% (SD 10·6) in the azithromycin group and 90·4% (10·1) in the placebo group. No communities were lost to follow-up. In total, 1727 child deaths in the azithromycin group and 1888 child deaths in the placebo group were reported from the population censuses. Of these, the cause of death for 1566 (90·7%) children in the azithromycin group and 1735 (91·9%) children in the placebo group were ascertained by verbal autopsy interviews. In the azithromycin group, 437 (27·9%) deaths were due to malaria, 252 (16·1%) deaths were due to pneumonia, and 234 (14·9%) deaths were due to diarrhoea. In the placebo group, 493 (28·4%) deaths were due to malaria, 275 (15·9%) deaths were due to pneumonia, and 251 (14·5%) deaths were due to diarrhoea. Relative to communities that received placebo, child mortality in communities that received azithromycin was lower for malaria (incidence rate ratio 0·78, 95% CI 0·66–0·92; p=0·0029), dysentery (0·65, 0·44–0·94; p=0·025), meningitis (0·67, 0·46–0·97; p=0·036), and pneumonia (0·83, 0·68–1·00; p=0·051). The distribution of causes of death did not differ significantly between the two study groups (p=0·98). Interpretation Mass azithromycin distribution resulted in approximately a third fewer deaths in children aged 1–59 months due to meningitis and dysentery, and a fifth fewer deaths due to malaria and pneumonia. The lack of difference in the distribution of causes of death between the azithromycin and placebo groups could be attributable to the broad spectrum of azithromycin activity and the study setting, in which most childhood deaths were due to infections. Funding Bill & Melinda Gates Foundation.