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Abstract Background Over 80% of blindness in Kenya is due to curable or preventable causes and 7.5 m Kenyans currently need eye services. Embedding sociodemographic data collection into screening programmes could help identify the groups facing systematic barriers to care. We aimed to determine the sociodemographic characteristics that were associated with access among patients diagnosed with an eye problem and referred for treatment in the Vision Impact Programme, currently operating in Meru County. Method We used an embedded, pragmatic, cross-sectional design. A list of sociodemographic questions was developed with input from key stakeholders. The final question set included the following domains: age, gender, religion, marital status, disability, education, occupation, income, housing, assets, and health insurance. These were integrated into an app that is used to screen, refer, and check-in (register) participants within a major eye screening programme. We gathered data from 4,240 people who screened positive and were referred to their local outreach treatment clinic. We used logistic regression to identify which groups were facing the greatest barriers to accessing care. Results A quarter of those screened between April – July 2023 were found to have an eye problem and were referred, however only 46% of these people were able to access care. In our fully adjusted model, at the 0.05 level there were no statistically significant differences in the odds of attendance within the domains of disability, health insurance, housing, income, or religion. Strong evidence (p

Background Microbial Keratitis (MK) is a leading cause of corneal blindness due to infection and its consequences, with a higher incidence in resource-limited nations. Hospital-based patient records from different parts of Nepal suggest patients often use traditional eye medicine to treat MK. Traditional healers (TH) within the community are often the first point of care for MK management. Little is known of their practice, perceptions, and knowledge around MK management. We aimed to understand the role of traditional healers in the management of MK in south-eastern Nepal. Methods A cross-sectional, mixed method, descriptive study was conducted in the Siraha district of Nepal. A total of 109 traditional healers consented to participate in a survey of knowledge, attitude, and practices. Some participants were also invited to participate in in-depth interviews and focus group discussions. Interviews and focus groups were conducted and recorded in the Maithili language by a native speaking interviewer and transcribed into English. Descriptive analysis was performed for the survey. Data saturation was considered the endpoint for qualitative data collection, and a thematic was analysis applied. Results Traditional healers believe that infection of the eye can be caused by trauma, conjunctivitis, or evil spirits. They were unclear about differentiating MK from other eye conditions. They provided various types of treatment. Some were confident that they could treat severe ulcers that had not responded to medical therapy, while others thought treating larger diameter ulcers would be difficult. Although there were mixed responses in referring patients with MK, the majority of TH were willing to refer. Conclusion In a weak health system, traditional healers may help address barriers to healthcare access and reduce delays to definitive care, upon integration into the formal health system and referral pathway.

BackgroundMuscle wasting is a common finding in critically ill patients associated with increased days of mechanical ventilation in the ICU. Muscle wasting and associated morphological changes are hallmarks of ICU-acquired weakness. Muscle wasting can be diagnosed and quantified by muscle biopsy, but biopsies can cause multiple adverse effects. MuscleSound® has developed a non-invasive, real-time novel MusculoSkeletal (MSK) ultrasound approach to measure the ratio between percentage intramuscular adipose tissue (%IMAT) with muscle cross-section area (MCSA) (termed IMAT-Index). The present study aimed to assess the IMAT-Index in ICU patients longitudinally and compare it to age-matched healthy controls.MethodsTransverse (short-axis) ultrasound images of the rectus femoris muscle were obtained upon admission and discharge in 35 ICU patients and compared to age-matched healthy controls (n = 975). The echo intensity of the image taken from the muscle is used to automatically calculate the ratio between intramuscular adipose tissue by cm2 (IMAT-Index), the cross-sectional area of the muscle (MCSA), and muscle thickness (MT).ResultsIMAT-Index was successfully measured in all subjects. The mean IMAT-index (%IMAT/cm2) upon admission was significantly higher in critically ill patients compared to healthy controls (7.4 ± 4.3 vs. 3.1 ± 0.9, p

IntroductionThe COVID-19 pandemic brought unprecedented challenges to healthcare systems worldwide, particularly the often challenging physical recovery from critical illness. Among the myriad complications faced by these patients, ICU-acquired weakness (ICU-AW) stands out due to its significant impact on patient outcomes. ICU-AW, characterized by skeletal muscle atrophy and weakness, is linked to critical illness polyneuropathy (CIN), myopathy (CIM), and muscle atrophy. Notably, fasciculations, or involuntary muscle twitches, have been observed in patients with ICU-AW, suggesting altered muscle fiber excitability. This study aimed to describe the pattern of fasciculations in critically ill mechanically ventilated COVID-19 patients, assess clinical features associated with fasciculations, and evaluate their prognostic significance.MethodsThe study enrolled patients admitted to the Intensive Care Unit (ICU) with COVID-19 infection requiring intubation and mechanical ventilation. Quadriceps muscles were assessed using muscle skeletal (MSK) ultrasound and Phase Angle (PhA) through multifrequency segmental bioelectrical impedance analysis (MFBIA) every 72 h. PhA is considered a marker of cell membrane integrity and function, with lower PhA values indicating reduced skeletal muscle quality and increased risk of sarcopenia. Fasciculations were classified based on their appearance and frequency.ResultsA total of 35 intubated patients were studied, with 15 patients (43%) displaying scattered fasciculations exclusively in the vastus intermedius muscles. Upon admission, the study found no significant difference in PhA between the fasciculation and non-fasciculation groups. However, PhA decreased significantly from admission to discharge ICU only in the fasciculation group. Patients with fasciculations exhibited higher mortality rates, though not statistically significant, and this correlated with prolonged ICU and hospital lengths of stay.DiscussionThis study is the first to report scattered fasciculations in the vastus intermedius muscles of multiple patients with SARS-CoV-2 infection identified with MSK ultrasound. The findings suggest that the combination of impaired muscle cellular function (PhA) and the onset of fasciculations could serve as a potential biomarker of adverse outcomes and ICU-related muscle dysfunction and muscle loss.

There is currently no single, easy-to-use, reliable indicator to assess whether a face has been washed with soap in the context of trachoma elimination. This study aimed to compare survey report, script-based pictorial recall and facial cleanliness indicators as alternatives to structured observation for measuring face washing behaviour. This method validation study was nested in the Stronger-SAFE trial, Oromia Region, Ethiopia. Structured observation was conducted in randomly selected households for three hours from dawn. The primary caregiver in each household participated in a survey to capture (self)-reported behaviour and/or script-based pictorial recall, a routine-based diary activity to covertly capture information on face washing behaviour of themself and any children aged 1-12. Children 4-12 years old directly participated in the survey and pictorial recall in a subset of households. The facial cleanliness of children aged 1-12 was assessed qualitatively and using the quantitative Personal Hygiene Assessment Tool (qPHAT). Prevalence estimates, sensitivity, specificity and predictive values were computed for each behavioural indicator with observation data as the gold standard. The appropriateness of script-based pictorial recall was assessed using baseline and 3-month follow-up data. Baseline data were collected from 204 households in 68 clusters. Survey estimates of face washing and face washing with soap among caregivers and children were 32% to 60% and 5% to 31% higher than observed behaviour, respectively. Face washing prevalence estimates from pictorial recall were lower than survey estimates and comparable with observations for some face washing with soap indicators (0.3% to 13% higher than observations). Specificity of pictorial recall indicators was high (85% to 99%), but the sensitivity was low (0% to 67%), resulting in a low positive predictive value for all indicators. Both qualitative facial cleanliness indicators and qPHAT scores were poorly correlated with observed face washing earlier that morning. Pictorial recall overestimated face washing with soap among both caregivers and children following intervention delivery but not at baseline. Survey (self)-reported data on face washing is highly inaccurate. Script-based pictorial recall does not correctly classify those who wash their face with soap, and is subject to differential bias following intervention exposure, and facial cleanliness is a poor indicator of recent face washing in settings where faces become rapidly dirty again after washing. Alternatives to structured observation cannot be recommended to monitor the effectiveness of face washing interventions in community settings. Trial Registration ISRCTN registry ISRCTN40760473, https://doi.org/10.1186/ISRCTN40760473.

Background: The cardiopulmonary exercise test (CPET) is considered a gold standard in assessing cardiorespiratory fitness (CRF) but has limited accessibility due to competency requirements and cost. Incorporating portable sensor devices into a simple bedside test of CRF could improve diagnostic and prognostic value. Objectives: The authors sought to evaluate the association of an augmented 6-minute incremental step test (6MIST) with standard CPET. Methods: We enrolled patients undergoing clinically indicated supine cycle ergometry CPET with invasive hemodynamics (iCPET) for the same-day 6MIST. CRF-related variables were simultaneously recorded using a signal morphology-based impedance cardiograph (PhysioFlow Enduro) and a portable metabolic analyzer (VO2 Master Pro) during incremental pace stationary stepping. The correlation between CPET and hemodynamic parameters from both tests was assessed using the intraclass correlation coefficient (ICC). Results: Fifteen patients (mean age 60 ± 14 years, 40% female, 27% Black) were included. All patients who agreed to undergo 6MIST completed the study without any test-related adverse events. We observed good to excellent correlation between iCPET- and 6MIST-measured CPET parameters: peak heart rate (ICC = 0.60; 95% CI: 0.15-0.85), absolute peak O2 consumption (VO2) (ICC = 0.77; 95% CI: 0.44-0.92), relative peak VO2 (ICC = 0.64; 95% CI: 0.20-0.86), maximum ventilation (ICC = 0.59; 95% CI: 0.13-0.84), O2 pulse (ICC = 0.71; 95% CI: 0.33-0.89), and cardiorespiratory optimal point (ICC = 0.82; 95% CI: 0.52-0.94). No significant correlation was determined between iCPET and 6MIST in measuring cardiac index at rest (ICC = 0.19; 95% CI: −0.34 to 0.63) or at peak exercise (ICC = 0.36; 95% CI: −0.17 to 0.73). Conclusions: We demonstrate the feasibility of a novel augmented 6MIST with wearable devices for simultaneous CPET and hemodynamic assessment. 6MIST-measured CPET parameters were strongly correlated with the iCPET-derived measurements. Additional studies are needed to confirm the validity of the 6MIST compared to standard upright CPET.

Musca sorbens (Diptera: Muscidae) flies are thought to be vectors of the blinding eye disease trachoma, carrying the bacterium Chlamydia trachomatis (Ct) between the eyes of individuals. While their role as vectors has been convincingly demonstrated via randomised controlled trials in The Gambia, studies of fly-borne trachoma transmission remain scant and as such our understanding of their ability to transmit Ct remains poor. We examined fly-eye contact and caught eye-seeking flies from 494 individuals (79% aged ≤9 years) in Oromia, Ethiopia. Ct-carrying flies (harbouring Ct DNA) were found to cluster spatially in and nearby to households in which at least one resident had Ct infection. Fly-eye contact was positively associated with the presence of trachoma (disease), lower human body weight and increased human body temperature. Studies of laboratory-reared M. sorbens indicated that Ct is found both externally and internally following feeds on Ct culture, with scanning electron microscopy revealing how Ct bodies can cling to fly hairs (setae). Testing for Ct on field-caught M. sorbens found fly 'bodies' (thorax, wings and abdomen) to consistently test positive for Ct while legs and heads were infrequently Ct-positive. These studies strongly support the role of M. sorbens as vectors of trachoma and highlight the need for improved understanding of fly-borne trachoma transmission dynamics and vector competence.

Abstract Strong positive Indian Ocean Dipole (pIOD) events like those in 1997 and 2019 caused significant flooding in East Africa. While future projections indicate an increase in pIOD events, limited historical data hinders a comprehensive understanding of these extremes, particularly for unprecedented events. To overcome this we utilize a large ensemble of seasonal reforecast simulations, which show that regional rainfall continues to increase with pIOD magnitude, with no apparent limit. In particular we find that extreme rain days are highly sensitive to the pIOD index and their seasonal frequency increases super‐linearly with higher pIOD magnitudes. It is vital that socio‐economic systems and infrastructure are able to handle not only the increasing frequency of events like 1997 and 2019 but also unprecedented seasons of extreme rainfall driven by as‐yet‐unseen pIOD events. Future studies should prioritize understanding the hydrological implications and population exposure to these unprecedented extremes in East Africa.

Our research team is conducting phenomenological interviews with people who have not been able to access health services in Meru County, Kenya, aiming to explore the barriers they face and their perceptions of how we could modify our community outreach services to improve accessibility. We plan to conduct an embedded study that compares in-person and telephone interview modalities in terms of the richness of the data and the resources required for each modality. This is a qualitative mode comparison study, embedded within a broader project to understand and address the issues that lead to inequitable access to local outreach clinics in Kenya. We will recruit at least 40 people who have been referred to local services but who have not been able to attend. We will conduct in-person interviews with half of these people, and telephone interviews with the other half. We will use random numbers to determine the modality that is used for each participant. All interviews will be conducted in the same month by a team of six research assistants who will use the same topic guide and analytic matrix for each interview. For all interviews conducted in each mode we will record and compare the mean duration; mean number of themes reported by each participant; total number of themes reported; interviewer rating of perceived richness; interviewer rating of perceived ease of building rapport; number of days taken by the team to complete all interviews; and all costs associated with conducting the interviews. The findings will help us to weigh up the relative strengths and weaknesses of each modality for our research context. Given that we are exploring a focused research question in a fairly homogenous population, we anticipate that there may not be a meaningful difference in the number of themes reported.

Abstract Background Health inequalities are ubiquitous, and as countries seek to expand service coverage, they are at risk of exacerbating existing inequalities unless they adopt equity-focused approaches to service delivery. Main text Our team has developed an equity-focused continuous improvement model that reconciles prioritisation of disadvantaged groups with the expansion of service coverage. Our new approach is based on the foundations of routinely collecting sociodemographic data; identifying left-behind groups; engaging with these service users to elicit barriers and potential solutions; and then rigorously testing these solutions with pragmatic, embedded trials. This paper presents the rationale for the model, a holistic overview of how the different elements fit together, and potential applications. Future work will present findings as the model is operationalised in eye-health programmes in Botswana, India, Kenya, and Nepal. Conclusion There is a real paucity of approaches for operationalising equity. By bringing a series of steps together that force programme managers to focus on groups that are being left behind, we present a model that can be used in any service delivery setting to build equity into routine practice.

Introduction Globally, diabetic retinopathy (DR) is a major cause of blindness. Sub-Saharan Africa is projected to see the largest proportionate increase in the number of people living with diabetes over the next two decades. Screening for DR is recommended to prevent sight loss; however, in many low and middle-income countries, because of a lack of specialist eye care staff, current screening services for DR are not optimal. The use of artificial intelligence (AI) for DR screening, which automates the grading of retinal photographs and provides a point-of-screening result, offers an innovative potential solution to improve DR screening in Tanzania.Methods and analysis We will test the hypothesis that AI-supported DR screening increases the proportion of persons with true referable DR who attend the central ophthalmology clinic following referral after screening in a single-masked, parallel group, individually randomised controlled trial. Participants (2364) will be randomised (1:1 ratio) to either AI-supported or the standard of care DR screening pathway. Participants allocated to the AI-supported screening pathway will receive their result followed by point-of-screening counselling immediately after retinal image capture. Participants in the standard of care arm will receive their result and counselling by phone once the retinal images have been graded in the usual way (typically after 2–4 weeks). The primary outcome is the proportion of persons with true referable DR attending the central ophthalmology clinic within 8 weeks of screening. Secondary outcomes, by trial arm, include the proportion of persons attending the central ophthalmology clinic out of all those referred, sensitivity and specificity, number of false positive referrals, acceptability and fidelity of AI-supported screening.Ethics and dissemination The London School of Hygiene & Tropical Medicine, Kilimanjaro Christian Medical Centre and Tanzanian National Institute of Medical Research ethics committees have approved the trial. The results will be submitted to peer-reviewed journals for publication.Trial registration number ISRCTN18317152.

Background Attendance rates for eye clinics are low across low- and middle-income countries (LMICs) and exhibit marked sociodemographic inequalities. We aimed to quantify the association between a range of sociodemographic domains and attendance rates from vision screening in programmes launching in Botswana, India, Kenya and Nepal. Methods We performed a literature review of international guidance on sociodemographic data collection. Once we had identified 13 core candidate domains (age, gender, place of residence, language, ethnicity/tribe/caste, religion, marital status, parent/guardian status, place of birth, education, occupation, income, wealth) we held workshops with researchers, academics, programme implementers, and programme designers in each country to tailor the domains and response options to the national context, basing our survey development on the USAID Demographic and Health Survey model questionnaire and the RAAB7 eye health survey methodology. The draft surveys were reviewed by health economists and piloted with laypeople before being finalised, translated, and back-translated for use in Botswana, Kenya, India, and Nepal. These surveys will be used to assess the distribution of eye disease among different sociodemographic groups, and to track attendance rates between groups in four major eye screening programmes. We gather data from 3,850 people in each country and use logistic regression to identify the groups that experience the worst access to community-based eye care services in each setting. We will use a secure, password protected android-based app to gather sociodemographic information. These data will be stored using state-of-the art security measures, complying with each country’s data management legislation and UK law. Discussion This low-risk, embedded, pragmatic, observational data collection will enable eye screening programme managers to accurately identify which sociodemographic groups are facing the highest systematic barriers to accessing care at any point in time. This information will be used to inform the development of service improvements to improve equity.

BackgroundTrachoma, the leading infectious cause of blindness, is caused by the bacterium Chlamydia trachomatis (Ct). Despite enormous disease control efforts and encouraging progress, trachoma remains a significant public health problem in 44 countries. Ethiopia has the greatest burden of trachoma worldwide, however, robust data exploring transmission risk factors and the association between socio-economic status is lacking from some regions. This is the first study to investigate these factors in this South-Eastern region of Oromia, Ethiopia.Methodology/principal findingsA total of 1211 individuals were enrolled from 247 households in Shashemene Rural district in Oromia Region between 11th April and 25th June 2018, of whom 628 (51.9%) were female and 526 (43.4%) were children aged 1-9 years. Three standardised ophthalmic nurses examined each participant for the presence of active trachoma using the WHO simplified trachoma grading system. Conjunctival swab samples were collected from the upper tarsal conjunctiva of the left eye of each participant. Ct was detected using quantitative PCR. Risk factor data were collected through structured interviews and direct observations. Clinical signs of trachomatous inflammation-follicular among children aged 1-9 (TF1-9) were observed in at least one eye of 106/526 (20.2%) and trachomatous inflammation-intense among children aged 1-9 (TI1-9) were observed in at least one eye of 10/526 (1.9%). We detected Ct by PCR in 23 individuals, of whom 18 (78.3%) were in children aged 1-9 years. Among the 106 children aged 1-9 years with TF, 12 (11.3%) were Ct PCR positive and among 20 children aged 1-9 years with TI, 4 (20.0%) were Ct PCR positive. In a multivariable model, adjusting for household clustering, active trachoma was associated with younger age, the poorest households (aOR = 2.56, 95% CI 1.21-5.51), presence of flies on the face (aOR = 2.87, 95% CI 1.69-6.46), and ocular discharge (aOR = 1.89, 95% CI 1.03-3.24). Pre-school children face washing more than once a day had lower odds of having active trachoma (aOR = 0.59, 95% CI 0.19-0.84). The same was true for washing children's clothing at least once per week (aOR = 0.27, 95% CI 0.33-1.02).Conclusion/significanceYounger age, personal hygiene in this age group (presence of ocular and nasal discharges, infrequent washing of faces and clothing) and fly-eye contacts are potential risk factors for trachoma in this setting, suggesting that hygiene interventions and environmental improvements are required to suppress transmission to ensure sustained reduction in disease burden Further studies are needed to evaluate these interventions for trachoma control and elimination. Trachoma remains a disease associated with lower socio-economic status, emphasising the need for continued implementation of control measures in addition to poverty reduction interventions in this region.

Diabetic retinopathy (DR) is a leading cause of blindness globally. There is growing evidence to support the use of artificial intelligence (AI) in diabetic eye care, particularly for screening populations at risk of sight loss from DR in low-income and middle-income countries (LMICs) where resources are most stretched. However, implementation into clinical practice remains limited. We conducted a scoping review to identify what AI tools have been used for DR in LMICs and to report their performance and relevant characteristics. 81 articles were included. The reported sensitivities and specificities were generally high providing evidence to support use in clinical practice. However, the majority of studies focused on sensitivity and specificity only and there was limited information on cost, regulatory approvals and whether the use of AI improved health outcomes. Further research that goes beyond reporting sensitivities and specificities is needed prior to wider implementation.

Abstract Background Clinic non-attendance rates are high across the African continent. Emerging evidence suggests that phone-based reminder messages could make a small but important contribution to reducing non-attendance. We will use behavioural economics principles to develop an SMS and voice reminder message to improve attendance rates in a school-based eye screening programme in Botswana. Methods We will test a new theory-informed SMS and voice reminder message in a national school-based eye screening programme in Botswana. The control will be the standard SMS message used to remind parents/guardians to bring their child for ophthalmic assessment. All messages will be sent twice. The primary outcome is attendance for ophthalmic assessment. We will use an automated adaptive approach, starting with a 1:1 allocation ratio. Discussion As far as we are aware, only one other study has used behavioural economics to inform the development of reminder messages to be deployed in an African healthcare setting. Our study will use an adaptive trial design, embedded in a national screening programme. Our approach can be used to trial other forms of reminder message in the future. Trial registration ISRCTN 96528723 . Registered on 5 January 2022.

Introduction There is evidence for increased resistance against the antimicrobials used to treat keratitis. This review aims to provide global and regional prevalence estimates of antimicrobial resistance in corneal isolates and the range of minimum inhibitory concentrations (MIC) with their associated resistance breakpoints.Methods and analysis We report this protocol following Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols guidelines. We will conduct an electronic bibliographic search in MEDLINE, EMBASE, Web of Science and the Cochrane Library. Eligible studies will report in any language data for the resistance or MIC for antimicrobials against bacterial, fungal or amoebic organisms isolated from suspected microbial keratitis. Studies that only report on viral keratitis will not be included. There will be no time restrictions on the date of publication. Screening for eligible studies, assessment of risk of bias and data extraction will be conducted by two reviewers independently, using predefined inclusion criteria and prepiloted data extraction forms. We will resolve disagreements between the reviewers by discussion and, if required, a third (senior) reviewer will arbitrate. We will assess the risk of bias using a tool validated in prevalence studies. The certainty of the evidence will be assessed using the Grades of Recommendation, Assessment, Development and Evaluation approach. Pooled proportion estimates will be calculated using a random-effects model. Heterogeneity will be assessed using the I2 statistic. We will explore differences between Global Burden of Disease regions and temporal trends.Ethics approval and dissemination Ethics approval is not required as this is a protocol for a systematic review of published data. The findings of this review will be published in an open-access, peer-reviewed journal.PROSPERO registration number CRD42023331126.

IntroductionAlthough allogeneic hematopoietic stem cell transplantation (HCT) can be a curative therapy for hematologic disorders, it is associated with treatment-related complications and losses in cardiorespiratory fitness and physical function. High-intensity interval training (HIIT) may be a practical way to rapidly improve cardiorespiratory fitness and physical function in the weeks prior to HCT. The primary aim of this study was to assess the feasibility of implementing a pre-HCT home-based HIIT intervention. The secondary aim was to evaluate pre to post changes in cardiorespiratory fitness and physical function following the intervention.MethodsThis was a single-arm pilot study with patients who were scheduled to undergo allogeneic HCT within six months. Patients were instructed to complete three 30-minute home-based HIIT sessions/week between the time of study enrollment and sign-off for HCT. Sessions consisted of a 5-minute warm-up, 10 high and low intervals performed for one minute each, and a 5-minute cool-down. Prescribed target heart rates (HR) for the high- and low-intensity intervals were 80-90% and 50-60% of HR reserve, respectively. Heart rates during HIIT were captured via an Apple Watch and were remotely monitored. Feasibility was assessed via retention, session adherence, and adherence to prescribed interval number and intensities. Paired t-tests were used to compare changes in fitness (VO2peak) and physical function [Short Physical Performance Battery (SPPB), 30-second sit to stand, and six-minute walk test (6MWT)] between baseline and sign-off. Pearson correlations were used to determine the relationship between intervention length and changes in cardiorespiratory fitness or functional measures.ResultsThirteen patients (58.8±11.6 years) participated in the study, and nine (69.2%) recorded their training sessions throughout the study. Median session adherence for those nine participants was 100% (IQR: 87-107). Adherence to intervals was 92% and participants met or exceeded prescribed high-intensity HR on 68.8±34.8% of intervals. VO2peak improved from baseline to sign-off (14.6±3.1 mL/kg/min to 17.9±3.3 mL/kg/min; pConclusionsFindings demonstrate that implementing a pre-HCT home-based remotely monitored HIIT program is feasible and may provide benefits to cardiorespiratory fitness and physical function.

Background: Surgery to correct trichiasis is a key component of the World Health Organisation trachoma control strategy, however unfavourable outcomes such as eyelid contour abnormalities (ECA) following surgery are relatively common. This study aimed to understand the transcriptional changes associated with the early development of ECA and the impact of doxycycline, which has anti-inflammatory and anti-fibrotic properties, upon these transcription patterns. Methods: One thousand Ethiopians undergoing trichiasis surgery were enrolled in a randomised controlled trial following informed consent. Equal groups of randomly assigned individuals were orally administered with 100mg/day of doxycycline (n=499) or placebo (n=501) for 28 days. Conjunctival swabs were collected immediately prior to surgery and at one- and six-months post-surgery. 3’ mRNA sequencing was performed on paired baseline and one-month samples from 48 individuals; 12 in each treatment/outcome group (Placebo-Good outcome, Placebo-Poor outcome, Doxycycline-Good outcome, Doxycycline-Poor outcome). qPCR validation was then performed for 46 genes of interest in 145 individuals who developed ECA at one month and 145 matched controls, using samples from baseline, one and six months. Results: All treatment/outcome groups upregulated genes associated with wound healing pathways at one month relative to baseline, however no individual differences were detected between groups. The summed expression of a highly coexpressed cluster of pro-fibrotic genes was higher in patients that developed ECA in the placebo group relative to controls. qPCR validation revealed that all genes in this cluster and a number of other pro-inflammatory genes were strongly associated with ECA, however these associations were not modulated by trial arm. Conclusions: The development of post-operative ECA is associated with overexpression of pro-inflammatory and pro-fibrotic genes including growth factors, matrix metalloproteinases, collagens and extracellular matrix proteins. There was no evidence that doxycycline modulated the association between gene expression and ECA.

Measurement(s) evapotranspiration Technology Type(s) computational modeling technique Factor Type(s) temporal interval Sample Characteristic - Environment climate system • hydrological process Sample Characteristic - Location global Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.15060387

Abstract Musca sorbens is a synanthropic filth fly that aggressively attacks people to feed from mucous membranes of the eyes, nose or mouth, from open sores, or from sweat. It has long been suspected that this fly contributes to the transmission of eye infections, particularly trachoma, and recent work has added to the evidence base that M. sorbens is a trachoma vector in Ethiopia. There are few options to control M. sorbens, largely due to a lack of evidence. Space spraying with insecticides is effective, but an environmentally sound and long-term sustainable solution would be better, for example, mass trapping. We tested commercially available and homemade trap types in a pilot (laboratory) study and three field studies. A homemade design, built from a bucket and two empty water bottles, baited with a commercially available lure, The Buzz, was found to be most effective. This trap caught 3848 M . sorbens over 26 trap ‘events’ (3- or 4-day periods); mean/median per 24 h 43.6 (standard deviation 137.10)/2.25 (IQR 0.25–12.67). The Buzz lure is cheap and effective for 4 weeks, and trap components cheap and locally available. Further studies are needed to understand the impact of this trap on local fly populations and the local transmission of trachoma.

Abstract Background Alternative models for sustainable antiretroviral treatment (ART) delivery are necessary to meet the increasing demand to maintain population-wide ART for all people living with HIV (PLHIV) in sub-Saharan Africa. We undertook a review of published literature comparing health facility-based care (HFBC) with non-health facility based care (nHFBC) models of ART delivery in terms of health outcomes; viral suppression, loss to follow-up, retention and mortality. Methods We conducted a systematic search of Medline, Embase and Global Health databases from 2010 onwards. UNAIDS reports, WHO guidelines and abstracts from conferences were reviewed. All studies measuring at least one of the following outcomes, viral load suppression, loss-to-follow-up (LTFU) and mortality were included. Data were extracted, and a descriptive analysis was performed. Risk of bias assessment was done for all studies. Pooled estimates of the risk difference (for viral suppression) and hazard ratio (for mortality) were made using random-effects meta-analysis. Results Of 3082 non-duplicate records, 193 were eligible for full text screening of which 21 published papers met the criteria for inclusion. The pooled risk difference of viral load suppression amongst 4 RCTs showed no evidence of a difference in viral suppression (VS) between nHFBC and HFBC with an overall estimated risk difference of 1% [95% CI -1, 4%]. The pooled hazard ratio of mortality amongst 2 RCTs and 4 observational cohort studies showed no evidence of a difference in mortality between nHFBC and HFBC with an overall estimated hazard ratio of 1.01 [95% CI 0.88, 1.16]. Fifteen studies contained data on LTFU and 13 studies on retention. Although no formal quantitative analysis was performed on these outcomes due to the very different definitions between papers, it was observed that the outcomes appeared similar between HFBC and nHFBC. Conclusions Review of current literature demonstrates comparable outcomes for nHFBC compared to HFBC ART delivery programmes in terms of viral suppression, retention and mortality. PROSPERO number CRD42018088194 .

BackgroundThe aim of this study was to describe the health-seeking journey for patients with microbial keratitis (MK) in Nepal and identify factors associated with delay.MethodsProspective cohort study where MK patients attending a large, tertiary-referral eye hospital in south-eastern Nepal between June 2019 and November 2020 were recruited. We collected demographic details, clinical history, and examination findings. Care-seeking journey details were captured including places attended, number of journeys, time from symptom onset, and costs. We compared “direct” with “indirect” presenters, analyzing for predictors of delay.ResultsWe enrolled 643 patients with MK. The majority (96%) self-referred. “Direct” attenders accounted for only 23.6% (152/643) of patients, the majority of “indirect” patients initially presented to a pharmacy (255/491). Over half (328/643) of all cases presented after at least 7 days. The total cost of care increased with increasing numbers of facilities visited (p < 0.001). Those living furthest away were least likely to present directly (p < 0.001). Factors independently associated with delayed presentation included distance >50 km from the eye hospital [aOR 5.760 (95% CI 1.829–18.14, p = 0.003)], previous antifungal use [aOR 4.706 (95% CI 3.139–5.360)], and two or more previous journeys [aOR 1.442 (95% CI 1.111–3.255)].ConclusionsMost patients visited at least one facility prior to our institution, with time to presentation and costs increasing with the number of prior journeys. Distance to the eye hospital is a significant barrier to prompt, direct presentation. Based on these findings, improving access to eye care services, strengthening referral networks and encouraging early appropriate treatment are recommended to reduce delay, ultimately improving clinical outcomes.

Summary: Background: The eye-seeking fly Musca sorbens can act as a vector for ocular Chlamydia trachomatis, causing trachoma, yet there has been very little research on control measures. We investigated whether insect repellent products, specifically insecticide-treated clothing, could provide personal protection to the user from eye-seeking flies. Methods: We first conducted a series of phase I laboratory studies to inform our choice of field intervention. We then conducted a phase II randomised controlled trial testing the efficacy of permethrin-treated scarves (PTS) in reducing fly-face contact in Oromia, Ethiopia. Children aged 4-10 years in full health and with no known adverse reactions to permethrin or other insecticides were allocated to either arm using restricted randomisation. Intervention arm children wore Insect Shield® versatile wraps (as PTS) for 28 days. The primary outcomes, fly-eye, -nose and -mouth contact, were assessed on the first day (0/30/60/180 minutes), on day 7 and on day 28. All participants present per timepoint were included in analyses. This trial was registered with ClinicalTrials.gov (NCT03813069). Findings: Participants were recruited to the field trial between 29/10/2019 and 01/11/2019, 58 were randomised to test or control arm. More fly (-eye, -nose and -mouth) contacts were observed in the PTS arm at baseline. After adjusting for baseline contact rates, across all timepoints there was a 35% decrease in fly-eye contacts in the PTS relative to control arm (rate ratio [RR] 0.65, 95% CI 0.52-0.83). Similar cross-timepoint reductions were seen for fly-nose and fly-mouth contacts (RR 0.69, 95% CI 0.51-0.92 and RR 0.79, 95% CI 0.62-1.01, respectively). All children were included on day 0. Two in the control arm were absent on day 7, one left the study and four were excluded from analysis at day 28. No adverse events occurred in the trial. Interpretation: Musca sorbens flies are sufficiently repelled by PTS to reduce fly-eye contacts for the wearer, thus possibly reducing the risk of trachoma transmission. Permethrin-treated scarves may therefore an alternative to insecticide space spraying for protection from these flies. Funding: Wellcome Trust.

Abstract Background Following the World Health Organization’s (WHO) 2015 guidelines recommending initiation of antiretroviral therapy (ART) irrespective of CD4 count for all people living with HIV (PLHIV), many countries in sub-Saharan Africa have adopted this strategy to reach epidemic control. As the number of PLHIV on ART rises, maintenance of viral suppression on ART for over 90% of PLHIV remains a challenge to government health systems in resource-limited high HIV burden settings. Non facility-based antiretroviral therapy (ART) delivery for stable HIV+ patients may increase sustainable ART coverage in resource-limited settings. Within the HPTN 071 (PopART) trial, two models, home-based delivery (HBD) or adherence clubs (AC), were offered to assess whether they achieved similar viral load suppression (VLS) to standard of care (SoC). In this paper, we describe the trial design and discuss the methodological issues and challenges. Methods A three-arm cluster randomized non-inferiority trial, nested in two urban HPTN 071 trial communities in Zambia, randomly allocated 104 zones to SoC (35), HBD (35), or AC (34). ART and adherence support were delivered 3-monthly at home (HBD), adherence clubs (AC), or clinic (SoC). Adult HIV+ patients defined as “stable” on ART were eligible for inclusion. The primary endpoint was the proportion of PLHIV with virological suppression (≤ 1000 copies HIV RNA/ml) at 12 months (± 3months) after study entry across all three arms. Viral load measurement was done at the routine government laboratories in accordance with national guidelines, annually. The study was powered to determine if either of the community-based interventions would yield a viral suppression rate drop compared to SoC of no more than 5% in its absolute value. Both community-based interventions were delivered by community HIV providers (CHiPs). An additional qualitative study using observations, interviews with PLHIV, and FGDs with community HIV providers was nested in this study to complement the quantitative data. Discussion This trial was designed to provide rigorous randomized evidence of safety and efficacy of non-facility-based delivery of ART for stable PLHIV in high-burden resource-limited settings. This trial will inform policy regarding best practices and what is needed to strengthen scale-up of differentiated models of ART delivery in resource-limited settings. Trial registration ClinicalTrials.gov NCT03025165 . Registered on 19 January 2017

Background: Attendance rates for eye clinics are low across low- and middle-income countries (LMICs) and exhibit marked sociodemographic (SD) inequalities. We aimed to quantify the association between a range of SD domains and attendance rates from vision screening in programmes launching in Botswana, Kenya and Nepal. Methods: We will develop a set of sociodemographic questions and introduce them into routine community-based eye screening programmes in Kenya, Botswana and Nepal, targeting children aged 5-18 years and adults. Our study design is a rolling survey, embedded within the Peek screening programme. The sociodemographic questions will be asked of 10% of all those presenting to be screened, and 100% of those identified with an eye problem. We will also collect data on whether people referred to ophthalmic clinic for treatment or further assessment attended, and we will use logistic regression to report odds ratios for this outcome attendance) for each socioeconomic domain in each country. We hypothesise that attendance rates will be lowest among marginalised sociodemographic groups such as older, less educated, less wealthy women. To identify the most appropriate sociodemographic items we will perform a literature review, and then hold workshops with researchers, academics, programme implementers, and programme designers in each country to tailor the domains and response options to the national context. We will report outcome data at 6 and 12 months, identifying the groups facing the highest barriers to access. Discussion: This low-risk, embedded, pragmatic, observational data collection will enable eye screening programme managers to accurately identify which sociodemographic groups are facing the highest systematic barriers to accessing care at any point in time. This information will be used to inform the development of service improvements to improve equity.

Introduction Gathering data on socioeconomic status (SES) is a prerequisite for any health programme that aims to assess and improve the equitable distribution of its outcomes. Many different modalities can be used to collect SES data, ranging from (1) face-to-face elicitation, to (2) telephone-administered questionnaires, to (3) automated text message-based systems. The relative costs and perceived benefits to patients and providers of these different data collection approaches is unknown. This protocol is for a systematic review that aims to compare the resource requirements, performance characteristics, and acceptability to participants and service providers of these three approaches to collect SES data from those enrolled in health programmes.Methods and analysis An information specialist will conduct searches on the Cochrane Library, MEDLINE, Embase, Global Health, ClinicalTrials.gov, the WHO ICTRP and OpenGrey. All databases will be searched from 1999 to present with no language limits used. We will also search Google Scholar and check the reference lists of relevant articles for further potentially eligible studies. Any empirical study design will be eligible if it compares two or more modalities to elicit SES data from the following three; in-person, voice call, or automated phone-based systems. Two reviewers will independently screen titles, abstracts and full-text articles; and complete data extraction. For each study, we will extract data on the modality characteristics, primary outcomes (response rate and equivalence) and secondary outcomes (time, costs and acceptability to patients and providers). We will synthesise findings thematically without meta-analysis.Ethics and dissemination Ethical approval is not required, as our review will include published and publicly accessible data. This review is part of a project to improve equitable access to eye care services in low-ioncome and middle-income countries. However, the findings will be useful to policy-makers and programme managers in a range of health settings and non-health settings. We will publish our findings in a peer-reviewed journal and develop an accessible summary of results for website posting and stakeholder meetings.PROSPERO registration number CRD42021251959.

Abstract Background People living with diabetes can reduce their risk of vision loss from diabetic retinopathy by attending screening, which enables early detection and timely treatment. The aim of this pilot trial was to assess the feasibility of a full-scale cluster randomized controlled trial of an intervention to increase uptake of retinal examination in this population, as delivered within existing community-based diabetes support groups (DSGs). Methods All 16 DSGs in Kirinyaga county were invited to participate in the study. The first two groups recruited took part in the pilot trial. DSG members who met the eligibility criteria were recruited before the groups that were randomized to the two arms. In the intervention group, two peer educators were trained to deliver monthly DSG-based eye health education and individual telephone reminders to attend screening. The control group continued with usual DSG practice which is monthly meetings without eye health education. The recruitment team and outcome assessors were masked to the allocation. We documented the study processes to ascertain the feasibility, acceptability, and potential effectiveness of the intervention. Feasibility was assessed in terms of clarity of study procedures, recruitment and retention rates, level of acceptability, and rates of uptake of eye examination. We set the target feasibility criteria for continuation to the main study to be recruitment of 50 participants in the trial, 80% monthly follow-up rates for individuals, and no attrition of clusters. Results Of the 122 DSG members who were assessed for eligibility, 104 were recruited and followed up: 51 (intervention) and 53 (control) arm. The study procedures were well understood and easy to apply. We learnt the DSG meeting days were the best opportunities for recruitment. The study had a high acceptance rate (100% for clusters, 95% for participants) and high follow-up and retention rate (100% of those recruited). All clusters and participants were analysed. We observed that the rate of incidence of eye exam was about 6 times higher in the intervention arm as compared to the control arm. No adverse unexpected events were reported in either arm. Conclusions The study is feasible and acceptable in the study population. The results support the development of a full-scale cluster RCT, as the success criteria for the pilot were met. Trial registration Pan African Clinical Trials Registry PACTR201707002430195 Registered on 25 July 2017.

The lives and livelihoods of people around the world are increasingly threatened by climate-related risks as climate change increases the frequency and severity of high-impact weather. In turn, the risk of multiple hazards occurring simultaneously grows and compound impacts become more likely. The World Meteorological Organization (WMO) proposed the use of multi-hazard impact-based forecasting (IbF) to better anticipate and reduce the impacts of concurrent hazards, but as yet, there are few operational examples in the humanitarian sector.Drought is particularly susceptible to multi-hazard influences. However, challenges encountered in the development of drought IbF systems – including poor understanding of compound impacts and specific hazard-focused mandates – raise important questions for the feasibility of multi-hazard IbF as envisioned by the WMO. With these challenges in mind, we propose an interim approach in which real-time assessment of dynamic vulnerability provides a context for drought-based IbF. The incorporation of dynamic vulnerability indicators account for the local effects of non-drought hazards, whilst the use of a drought-based system facilitates effective intervention. The proposed approach will improve our understanding of compound events, enhance adoption of IbF in the humanitarian sector, and better mitigate the impacts of concurrent hazards.

Summary: Background: Glaucoma is a major cause of sight loss worldwide, with the highest regional prevalence and incidence reported in Africa. The most common low-cost treatment used to control glaucoma is long-term timolol eye drops. However, low adherence is a major challenge. We aimed to investigate whether selective laser trabeculoplasty (SLT) was superior to timolol eye drops for controlling intraocular pressure (IOP) in patients with open-angle glaucoma. Methods: We did a two-arm, parallel-group, single-masked randomised controlled trial at the Eye Department of Kilimanjaro Christian Medical Centre, Moshi, Tanzania. Eligible participants (aged ≥18 years) had open-angle glaucoma and an IOP above 21 mm Hg, and did not have asthma or a history of glaucoma surgery or laser. Participants were randomly assigned (1:1) to receive 0·5% timolol eye drops to administer twice daily or to receive SLT. The primary outcome was the proportion of eyes from both groups with treatment success, defined as an IOP below or equal to target pressure according to glaucoma severity, at 12 months following randomisation. Re-explanation of eye drop application or a repeat SLT was permitted once. The primary analysis was by modified intention-to-treat, excluding participants lost to follow-up, using logistic regression; generalised estimating equations were used to adjust for the correlation between eyes. This trial was registered with the Pan African Clinical Trials Registry, number PACTR201508001235339. Findings: 840 patients were screened for eligibility, of whom 201 (24%) participants (382 eligible eyes) were enrolled between Aug 31, 2015, and May 12, 2017. 100 (50%) participants (191 eyes) were randomly assigned to the timolol group and 101 (50%; 191 eyes) to the SLT group. After 1 year, 339 (89%) of 382 eyes were analysed. Treatment was successful in 55 (31%) of 176 eyes in the timolol group (16 [29%] of 55 eyes required repeat administration counselling) and in 99 (61%) of 163 eyes in the SLT group (33 [33%] of 99 eyes required repeat SLT; odds ratio 3·37 [95% CI 1·96–5·80]; p

Within the humanitarian sector, there is a pressing need to scale up anticipatory action as climate change-related disasters increase. This article evaluates forecasts relating to extreme weather events – extreme rainfall, tropical cyclones, river flooding and storm surge – in Myanmar and the Philippines to assess the feasibility of using such forecasts to develop early warning systems and responses. To make best use of limited extant data, a variety of methods (reliability diagrams, hit rates, false alarm ratios, correlations) are employed. We review the skill of the European Centre for Medium-Range Weather Forecasts (ECMWF) tropical cyclone forecasts and find that whilst errors in cyclone position are relatively small, forecasting intensity is more difficult. When a tropical cyclone has formed, the probabilities provided in the ECMWF track forecast are highly reliable and only slightly overconfident. A tropical cyclone activity product is relatively reliable for forecasts less than a week ahead for North Indian Ocean cyclones affecting Myanmar, but becomes very overconfident beyond this. Looking at flood forecasting models, a comparison of the Global Flood Awareness System (GloFAS, produced by the ECMWF and the European Commission as part of the Copernicus Emergency Management Services) with the Global Flood Forecasting Information System (GLOFFIS, produced by Deltares) demonstrates that both GloFAS and GLOFFIS have difficulty simulating 1 in 2 year return period flows or higher, although GloFAS performance is better than GLOFFIS. GloFAS reforecasts show significantly overconfident probabilities over Myanmar where discharge observations are available, whilst the lack of a GLOFFIS reforecast prevents evaluation of this forecast system directly. Evaluation of the ten-day operational storm surge forecast (the Global Storm Surge Information System, GLOSSIS) produced by Deltares was attempted but lack of any data prevented assessment. These findings present valuable insights into how well forecasts perform, which is crucial information for establishing effective humanitarian action mechanisms.

Clinically diagnosing fungal keratitis (FK) is challenging; diagnosis can be assisted by investigations including in vivo confocal microscopy (IVCM), smear microscopy, and culture. The aim of this study was to estimate the sensitivity in detecting fungal keratitis (FK) using IVCM, smear microscopy, and culture in a setting with a high prevalence of FK. In this cross-sectional study nested within a prospective cohort study, consecutive microbial keratitis (MK) patients attending a tertiary-referral eye hospital in south-eastern Nepal between June 2019 and November 2020 were recruited. IVCM and corneal scrapes for smear microscopy and culture were performed using a standardised protocol. Smear microscopy was performed using potassium hydroxide (KOH), Gram stain, and calcofluor white. The primary outcomes were sensitivities with 95% confidence intervals [95% CI] for IVCM, smear microscopy and culture, and for each different microscopy stain independently, to detect FK compared to a composite referent. We enrolled 642 patients with MK; 468/642 (72.9%) were filamentous FK, 32/642 (5.0%) were bacterial keratitis and 64/642 (10.0%) were mixed bacterial-filamentous FK, with one yeast infection (0.16%). No organism was identified in 77/642 (12.0%). Smear microscopy had the highest sensitivity (90.7% [87.9–93.1%]), followed by IVCM (89.8% [86.9–92.3%]) and culture (75.7% [71.8–79.3%]). Of the three smear microscopy stains, KOH had the highest sensitivity (85.3% [81.9–88.4%]), followed by Gram stain (83.2% [79.7–86.4%]) and calcofluor white (79.1% [75.4–82.5%]). Smear microscopy and IVCM were the most sensitive tools for identifying FK in our cohort. In low-resource settings we recommend clinicians perform corneal scrapes for microscopy using KOH and Gram staining. Culture remains an important tool to diagnose bacterial infection, identify causative fungi and enable antimicrobial susceptibility testing.

Summary: Background: There is limited access to eye health services in many low-income and middle-income populations. We aimed to assess the effectiveness in increasing service utilisation of the Peek Community Eye Health (Peek CEH) system, a smartphone-based referral system comprising decision support algorithms (Peek Community Screening app), SMS reminders, and real-time reporting. Methods: In this cluster-randomised controlled trial of eye health in Kenya, community unit clusters were defined as one health centre and its catchment population. Clusters were randomly allocated (1:1) to receive Peek CEH and referral (intervention group) or standard care via periodic health centre-based outreach clinics and onward referral (control group). Individuals in the intervention group were assessed at home by screeners and those referred were asked to present for triage assessment in a central location. They received regular SMS reminders. In both groups, community sensitisation was done followed by a triage clinic at the cluster health centre 4 weeks after sensitisation. During triage, individuals in both groups were assessed and treated and, if necessary, referred to a specific hospital. Individuals in the intervention group received further SMS reminders. The primary outcome was the mean attendance rate (the number of people per 10 000 population) at triage of those with confirmed eye conditions, as assessed at 4 weeks after sensitisation in the intention-to-treat population. We estimated the intervention effect using a Student's t-test on cluster-level rates. This trial is registered with Pan African Clinical Trial Registry, number 201807329096632. Findings: Between Nov 26, 2018, and June 7, 2019, of the 85 community units in Trans Nzoia County, Kenya, 49 were excluded. We randomly allocated 18 community units each to the intervention group (68 348 individuals) and the control group (60 243 individuals). 9387 individuals from the intervention group and 3070 from the control group attended triage assessment. The mean attendance rate at triage by individuals with eye problems was 1429 (92% CI 1228–1629) in the intervention group and 522 (418–625) in the control group (rate difference 906 per 10 000 [95% CI 689–1124; p

Abstract Background Globally, eye care provision is currently insufficient to meet the requirement for eye care services. Lack of access and awareness are key barriers to specialist services; in addition, specialist services are over-utilised by people with conditions that could be managed in the community or primary care. In combination, these lead to a large unmet need for eye health provision. We have developed a validated smartphone-based screening algorithm (Peek Community Screening App). The application (App) is part of the Peek Community Eye Health system (Peek CEH) that enables Community Volunteers (CV) to make referral decisions about patients with eye problems. It generates referrals, automated short messages service (SMS) notifications to patients or guardians and has a program dashboard for visualising service delivery. We hypothesise that a greater proportion of people with eye problems will be identified using the Peek CEH system and that there will be increased uptake of referrals, compared to those identified and referred using the current community screening approaches. Study design A single masked, cluster randomised controlled trial design will be used. The unit of randomisation will be the ‘community unit’, defined as a dispensary or health centre with its catchment population. The community units will be allocated to receive either the intervention (Peek CEH system) or the current care (periodic health centre-based outreach clinics with onward referral for further treatment). In both arms, a triage clinic will be held at the link health facility four weeks from sensitisation, where attendance will be ascertained. During triage, participants will be assessed and treated and, if necessary, referred onwards to Kitale Eye Unit. Discussion We aim to evaluate a M-health system (Peek CEH) geared towards reducing avoidable blindness through early identification and improved adherence to referral for those with eye problems and reducing demand at secondary care for conditions that can be managed effectively at primary care level. Trial registration The Pan African Clinical Trials Registry (PACTR), 201807329096632. Registered on 8 June 2018.

Abstract Background Cerebral visual impairment (CVI), including perceptual visual dysfunction (PVD), is common in children with cerebral palsy (CP). Inventories of questions relating to practical aspects of visual perception in everyday life, in particular the closed-ended Insight Questions Inventory (IQI), can be used to assess CVI/PVD. Studies linking responses to the inventory with specific visual support strategies, aimed at modifying the child’s environment and/or behaviour to minimize the impact of the CVI/PVD, have been piloted. The IQI and tailored strategies have not been used in an African population, nor have they been tested in a controlled trial. This trial will compare the effectiveness of the IQI and linked visual support strategies versus general supportive treatments on the quality of life of children with CVI/PVD and CP through a randomized controlled trial. Methods/design This is a prospective, double-blind, parallel-arm, randomized controlled trial. The primary outcome is change in quality of life scores between the two arms of the trial at 6 weeks, assessed using the Paediatric Quality of Life Inventory (PedsQL) generic 4.0 and CP 3.0 module. All children will undergo baseline assessment including the Open Questions Inventory, IQI, PedsQL 3.0, PedsQL 4.0 generic, and the Strengths and Difficulties Questionnaire (SDQ). Eligible children with CP aged 4 years to

Abstract Background The evidence on diagnostic test accuracy (DTA) of diabetic retinopathy (DR) screening utilising photographic studies by non-ophthalmologist personnel in low and middle-income country (LMIC) settings is scarce. We aimed to assess DTA of DR screening using a nonmydriatic hand-held digital camera by trained general physicians in a non-ophthalmic setting. Methods This study is a validation of a screening intervention. We selected 700 people with diabetes (PwDM) > 18 years of age, not previously screened or treated for DR, presenting at a tertiary medical clinic in Sri Lanka. Two-field retinal imaging was used to capture fundus images before and after pupil dilatation, using a hand-held non-mydriatic (Visuscout 100®-Germany) digital retinal camera. The images were captured and graded by two trained, masked independent physician graders. The DTA of different levels of DR was assessed comparing physician’s grading with a retinologist’s clinical examination by mydriatic bio-microscopy, according to a locally adopted guideline. Results Seven hundred eligible PwDM were screened by physician graders. The mean age of participants was 60.8 years (SD ±10.08) and mean duration of DM was 9.9 years (SD ±8.09). Ungradable image proportion in non-mydriatic imaging was 43.4% (either eye-31.3%, both eyes 12.1%). This decreased to 12.8% (either eye-11.6%, both eyes-1.2%) following pupil dilatation. In comparison to detection of any level of DR, a referable level DR (moderate non-proliferative DR and levels above) showed a higher level of DTA. The sensitivity of the defined referable DR was 88.7% (95% CI 81.7–93.8%) for grader 1 (positive predictive value [PPV] 59.1%) and 92.5% (95% CI 86.4–96.5%) for grader 2 (PPV 68%), using mydriatic imaging, after including ungradable images as screen positives. The specificity was 94.9% (95% CI 93.6–96.0%) for grader 1 (negative predictive value [NPV] 99%) and 96.4% (95% CI 95.3–97.3%) for grader 2 (NPV 99.4%). Conclusions The Physicians grading of images from a digital hand-held non-mydriatic camera at a medical clinic, with dilatation of pupil of those who have ungradable images, provides a valid modality to identify referable level of DR. This could be a feasible alternative modality to the existing opportunistic screening to improve the access and coverage. Trial registration Current Controlled Trials ISRCTN47559703. Date of Registration 18th March 2019, Retrospectively registered.

Acting in advance of floods, drought and cyclones often requires decision-makers to work with weather forecasts. The inherently probabilistic nature of these forecasts can be problematic when deciding whether to act or not. Cost-loss analysis has previously been employed to support forecast based decision-making such as Forecast-based Financing (FbF), providing insight to when an FbF system has ‘potential economic value’ relative to a no-forecast alternative. One well-known limitation of cost-loss analysis is the difficulty of estimating losses (which vary with hazard magnitude and extent, and with the dynamics of population vulnerability and exposure). A less-explored limitation is ignorance of the temporal dynamics (sequencing) of costs and losses. That is, even if the potential economic value of a forecast system is high, the stochastic nature of the atmosphere and the probabilistic nature of forecasts could conspire over the first few forecasts to increase the expense of using the system over the no-forecast alternative. Thus, for a forecast-based action system to demonstrate value, it often needs to be used over a prolonged length of time. However, knowing exactly how long it must be used to guarantee value is unquantified. This presents difficulties to institutions mandated to protect those at risk, who must justify the use of limited funds to act in advance of a potential, but not definite disaster, whilst planning multi-year strategies. Here we show how to determine the period over which decision makers must use forecasts in order to be confident of achieving ‘value’ over a no-forecast alternative. Results show that in the context of seasonal forecasting it is plausible that more than a decade may pass before a FbF system will have some certainty of showing value, and that if a particular user requires an almost-certain guarantee that using a forecast will be better than a no-forecast strategy, they must hold out until a near-perfect forecast system is available. The implication: there is potential value in seasonal forecasts, but to exploit it one must be prepared to play the long game.

BackgroundWHO endorsed the use of epilation as an alternative treatment to surgery for the management of both minor unoperated TT (UTT) and postoperative TT (PTT). However, some trachoma control programmes hesitated to implement epilation citing concerns that it would hamper TT surgical acceptance and result in larger numbers of and stiffer trichiatic eyelashes than the original TT lashes. We investigated the burden and phenotypes of post-epilation trichiatic eyelashes, and willingness to accept surgical management separately in unoperated and postoperative TT cases.Methodology/principal findingsWe recruited cases with minor (≤5 eyelashes from the upper eyelid touching the eye or evidence of epilation in Conclusions/significanceIn this study setting, frequent epilation neither hampers surgical acceptance nor results in more damaging trichiatic eyelashes than the pre-epilation lashes; and can be used as an alternative to the programmatic management of minor unoperated and postoperative TT cases.

BackgroundThe presence of Chlamydia trachomatis (Ct) DNA at non-ocular sites suggests that these sites may represent plausible routes of Ct transmission in trachoma. However, qPCR cannot discriminate between DNA from viable and non-viable bacteria. Here we use a propodium monoazide based viability PCR to investigate how long Ct remains viable at non-ocular sites under laboratory-controlled conditions.MethodsCultured Ct stocks (strain A2497) were diluted to final concentrations of 1000, 100, 10 and 1 omcB copies/μL and applied to plastic, woven mat, cotton cloth and pig skin. Swabs were then systemically collected from each surface and tested for the presence Ct DNA using qPCR. If Ct DNA was recovered, Ct viability was assessed over time by spiking multiple areas of the same surface type with the same final concentrations. Swabs were collected from each surface at 0, 2, 4, 6, 8 and 24 hours after spiking. Viability PCR was used to determine Ct viability at each timepoint.ResultsWe were able to detect Ct DNA on all surfaces except the woven mat. Total Ct DNA remained detectable and stable over 24 hours for all concentrations applied to plastic, pig skin and cotton cloth. The amount of viable Ct decreased over time. For plastic and skin surfaces, only those where concentrations of 100 or 1000 omcB copies/μL were applied still had viable loads detectable after 24 hours. Cotton cloth showed a more rapid decrease and only those where concentrations of 1000 omcB copies/μL were applied still had viable DNA detectable after 24 hours.ConclusionPlastic, cotton cloth and skin may contribute to transmission of the Ct strains that cause trachoma, by acting as sites where reservoirs of bacteria are deposited and later collected and transferred mechanically into previously uninfected eyes.

BackgroundIn 2014, the Joint United Nations Programme on HIV/AIDS (UNAIDS) set the 90-90-90 targets: that 90% of people living with HIV know their HIV status, that 90% of those who know their HIV-positive status are on antiretroviral therapy (ART), and that 90% of those on treatment are virally suppressed. The aim was to reach these targets by 2020. We assessed the feasibility of achieving the first two targets, and the corresponding 81% ART coverage target, as part of the HIV Prevention Trials Network (HPTN) 071 Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART) community-randomized trial.Methods and findingsThe study population was individuals aged ≥15 years living in 14 urban and peri-urban "PopART intervention" communities in Zambia and South Africa (SA), with a total population of approximately 600,000 and approximately 15% adult HIV prevalence. Community HIV care providers (CHiPs) delivered the PopART intervention during 2014-2017. This was a combination HIV prevention package including universal home-based HIV testing, referral of HIV-positive individuals to government HIV clinic services that offered universal ART (Arm A) or ART according to national guidelines (Arm B), and revisits to HIV-positive individuals to support linkage to HIV care and retention on ART. The intervention was delivered in 3 "rounds," each about 15 months long, during which CHiPs visited all households and aimed to contact all individuals aged ≥15 years at least once. In Arm A in Round 3 (R3), 67% (41,332/61,402) of men and 86% (56,345/65,896) of women in Zambia and 56% (17,813/32,095) of men and 71% (24,461/34,514) of women in SA participated in the intervention, among 193,907 residents aged ≥15 years. Following participation, HIV status was known by 90% of men and women in Zambia and by 78% of men and 85% of women in SA. The median time from CHiP referral of HIV-positive individuals to ART initiation was approximately 3 months. By the end of R3, an estimated 95% of HIV-positive women and 85% of HIV-positive men knew their HIV status, and among these individuals, approximately 90% of women and approximately 85% of men were on ART. ART coverage among all HIV-positive individuals was approximately 85% in women and approximately 75% in men, up from about 45% at the start of the study. ART coverage was lowest among men aged 18 to 34 and women aged 15 to 24 years, and among mobile individuals/in-migrants. Findings from Arm B were similar. The main limitations to our study were that estimates of testing and treatment coverage among men relied on considerable extrapolation because, in each round, approximately one-third of men did not participate in the PopART intervention; that our findings are for a service delivery model that was relatively intensive; and that we did not have comparable data from the 7 "standard-of-care" (Arm C) communities.ConclusionsOur study showed that very high HIV testing and treatment coverage can be achieved through persistent delivery of universal testing, facilitated linkage to HIV care, and universal treatment services. The ART coverage target of 81% was achieved overall, after 4 years of delivery of the PopART intervention, though important gaps remained among men and young people. Our findings are consistent with previously reported findings from southern and east Africa, extending their generalisability to urban settings with high rates of in-migration and mobility and to Zambia and SA.Trial registrationClinicalTrials.gov NCT01900977.

BackgroundTrachoma elimination efforts are hampered by limited understanding of Chlamydia trachomatis (Ct) transmission routes. Here we aimed to detect Ct DNA at non-ocular sites and on eye-seeking flies.MethodsA population-based household survey was conducted in Oromia Region, Ethiopia. Ocular and non-ocular (faces, hands, clothing, water containers and sleeping surfaces) swabs were collected from all individuals. Flies were caught from faces of children. Flies, ocular swabs and non-ocular swabs were tested for Ct by quantitative PCR.ResultsIn total, 1220 individuals in 247 households were assessed. Active trachoma (trachomatous inflammation-follicular) and ocular Ct were detected in 10% and 2% of all-ages, and 21% and 3% of 1-9-year-olds, respectively. Ct was detected in 12% (95% CI:8-15%) of tested non-ocular swabs from ocular-positive households, but in none of the non-ocular swabs from ocular-negative households. Ct was detected on 24% (95% CI:18-32%) of flies from ocular-positive households and 3% (95% CI:1-6%) of flies from ocular-negative households.ConclusionCt DNA was detected on hands, faces and clothing of individuals living in ocular-positive households suggesting that this might be a route of transmission within Ct infected households. In addition, we detected Ct on flies from ocular-positive households and occasionally in ocular-negative households suggesting that flies might be a vector for transmission within and between Ct infected and uninfected households. These potential transmission routes may need to be simultaneously addressed to suppress transmission.

The putative vector of trachoma, Musca sorbens, prefers to lay its eggs on human faeces on the ground. This study sought to determine whether M. sorbens females were attracted to volatile odours from human faeces in preference to odours from the faeces of other animals, and to determine whether specific volatile semiochemicals mediate selection of the faeces. Traps baited with the faeces of humans and local domestic animals were used to catch flies at two trachoma-endemic locations in The Gambia and one in Ethiopia. At all locations, traps baited with faeces caught more female M. sorbens than control traps baited with soil, and human faeces was the most successful bait compared with soil (mean rate ratios 44.40, 61.40, 10.50 [P

Fungal corneal infection (keratitis) is a common clinical problem in South Asia. However, it is often challenging to distinguish this from other aetiologies, such as bacteria or acanthamoeba. In this prospective study, we investigated clinical and epidemiological features that can predict the microbial aetiology of microbial keratitis in Nepal. We recruited patients presenting with keratitis to a tertiary eye hospital in lowland eastern Nepal between June 2019 and November 2020. A structured assessment, including demographics, history, and clinical signs, was carried out. The aetiology was investigated with in vivo confocal microscopy and corneal scrape for microscopy and culture. A predictor score was developed using odds ratios calculated to predict aetiology from features. A fungal cause was identified in 482/642 (75.1%) of cases, which increased to 532/642 (82.9%) when including mixed infections. Unusually, dematiaceous fungi accounted for half of the culture-positive cases (50.6%). Serrated infiltrate margins, patent nasolacrimal duct, raised corneal slough, and organic trauma were independently associated with fungal keratitis (p < 0.01). These four features were combined in a predictor score. The probability of fungal keratitis was 30.1% if one feature was present, increasing to 96.3% if all four were present. Whilst microbiological diagnosis is the “gold standard” to determine the aetiology of an infection, certain clinical signs can help direct the clinician to find a presumptive infectious cause, allowing appropriate treatment to be started without delay. Additionally, this study identified dematiaceous fungi, specifically Curvularia spp., as the main causative agent for fungal keratitis in this region. This novel finding warrants further research to understand potential implications and any trends over time.

Abstract Background Uganda halved its maternal mortality to 343/100,000 live births between 1990 and 2015, but did not meet the Millennium Development Goal 5. Skilled, timely and good quality antenatal (ANC) and delivery care can prevent the majority of maternal/newborn deaths and stillbirths. We examine coverage, equity, sector of provision and content of ANC and delivery care between 1991 and 2011. Methods We conducted a repeated cross-sectional study using four Uganda Demographic and Health Surveys (1995, 2000, 2006 and 2011).Using the most recent live birth and adjusting for survey sampling, we estimated percentage and absolute number of births with ANC (any and 4+ visits), facility delivery, caesarean sections and complete maternal care. We assessed socio-economic differentials in these indicators by wealth, education, urban/rural residence, and geographic zone on the 1995 and 2011 surveys. We estimated the proportions of ANC and delivery care provided by the public and private (for-profit and not-for-profit) sectors, and compared content of ANC and delivery care between sectors. Statistical significance of differences were evaluated using chi-square tests. Results Coverage with any ANC remained high over the study period (> 90% since 2001) but was of insufficient frequency;

Summary: Background: We re-examined the participants of a clinical trial four years after enrolment to identify which of the two most commonly used eyelid surgery procedures to treat the blinding stage of trachoma (trachomatous trichiasis, TT), the posterior Lamellar Tarsal Rotation (PLTR) and Billamelar Tarsal Rotation (BLTR), gives better results in the long-term. Methods: A randomised, controlled, single masked clinical trial was done in Ethiopia. At baseline, adults (aged >18 years with upper lid unoperated TT were recruited from a community-based screening. Participants were randomly assigned (1:1), to either BLTR or PLTR surgery, stratified by surgeon. At 4 years an independent assessor masked to allocation examined the trial participants’ eyes using the same procedures as for the baseline and earlier follow-ups. The primary outcome was the proportion of individuals who had recurrence (postoperative TT, PTT) at the 4-year examination, or a history of repeat surgery in the 4-year period. The intervention effect was estimated by logistic regression, controlled for surgeon as a fixed effect in the model. The trial is registered with the Pan African Clinical Trials Registry (number PACTR201401000743135). Findings: 1000 participants with TT were enrolled, randomly assigned, and treated (501 in the BLTR group and 499 in the PLTR group) between Feb 13, 2014, and May 31, 2014. At year 4, 943 (94.3%) participants were re-examined (471, PLTR; 472, BLTR) and included in the primary outcome analysis. PTT had developed in 169/943 (17•9%) study eyes, among which 129 (76•3%) had minor trichiasis (≤5 lashes touching the eye). PTT was significantly more frequent at 4-year in the BLTR arm (105/472 [22•2%]) than the PLTR arm (64/471 [13•6%]), adjusted OR 1•82 (95% CI, 1•29–2•56); p = 0•0006, with 8•6% (95%CI 3•8–13•5) risk difference. Interpretation: The PLTR surgical procedure had superior long-term outcomes to the BLTR with significantly lower risk of PTT supporting the current WHO guideline that the PLTR should be the procedure of choice for training new surgeons in the programmatic management of TT. Keywords: Trachoma, Trichiasis, Ethiopia, Surgery, Postoperative, Recurrence

Abstract Background All patients with diabetes are at risk of developing diabetic retinopathy (DR), a progressive and potentially blinding condition. Early treatment of DR prevents visual impairment and blindness. The natural history of DR is that it is asymptomatic until the advanced stages, thus annual retinal examination is recommended for early detection. Previous studies show that the uptake of regular retinal examination among people living with diabetes (PLWD) is low. In the Uptake of Retinal Examination in Diabetes (DURE) study, we will investigate the effectiveness of a complex intervention delivered within diabetes support groups to increase uptake of retinal examination. Methods The DURE study will be a two-arm pragmatic cluster randomized clinical trial in Kirinyaga County, Kenya. Diabetes support groups will be randomly assigned to either the intervention or usual care conditions in a 1:1 ratio. The participants will be 700 PLWD who are members of support groups in Kirinyaga. To reduce contamination, the unit of randomization will be the support group. Peer supporters in the intervention arm will receive training to deliver the intervention. The intervention will include monthly group education on DR and individual member reminders to take the eye examination. The effectiveness of this intervention plus usual care will be compared to usual care practices alone. Participant data will be collected at baseline. The primary outcome is the proportion of PLWD who take up the eye examination at six months. Secondary outcomes include the characteristics of participants and peer supporters associated with uptake of eye examination for DR. Intention-to-treat analysis will be used to evaluate the primary and secondary outcomes. Discussion Eye care programs need evidence of the effectiveness of peer supporter-led health education to improve attendance to retinal screening for the early detection of DR in an African setting. Given that the intervention combines standardization and flexibility, it has the potential to be adopted in other settings and to inform policies to promote DR screening. Trial registration Pan African Clinical Trial Registry PACTR201707002430195, registered 25 July 2017, www.pactr.org

Abstract Background In 2013 five polar explorers attempted to complete the first Trans-Antarctic Winter Traverse (TAWT). This study presents the ophthalmological findings for this group, who overwintered in Antarctica as part of the White Mars Human Science Protocol. Antarctic crews are exposed to extreme cold, chronic hypoxia and altered day-night cycles. Previous studies of Antarctic explorers have focused on the prolonged effect of ultraviolet radiation including the development of ultraviolet keratitis and accelerated cataract formation. This is the first study of its kind to investigate the effect of overwintering in Antarctica on the human eye. Methods Pre and post-expedition clinical observations were made including visual acuity, contrast sensitivity, colour vision, auto-refraction, subjective refraction, retinal examination, retinal autofluoresence and retinal thickness, which were graded for comparison. During the expedition additional observations were made on a monthly basis including LogMAR visual acuity, autorefraction and intraocular pressure. Results No significant differences between pre and post-expedition observations were found, including visual acuity, contrast sensitivity, colour vision, refraction, visual fields, intraocular pressure and retinal examination. There was a small but statistically significant decrease in retinal thickness across all regions of the retina, except for the macular and fovea, in all explorers. Intra-expedition observations remained within normal limits. Conclusion Reassuringly, the human eye remains largely unchanged by exposure to the extreme conditions encountered during the Antarctic winter, however, further research is needed to investigate changes in retinal thickness. This may have implications for scientists who spend prolonged periods of time in the polar regions, as well as those who have prolonged exposure to the extreme cold or chronic hypoxia in other settings.

Abstract Background Diabetic retinopathy (DR) is a significant public health concern that is potentially blinding. Clinical practice guidelines recommend annual eye examination of patients with diabetes for early detection of DR. Our aim was to identify the demand-side factors that influence uptake of eye examination among patients already utilizing diabetes services in three counties of Kenya. Methods We designed a clinic based cross-sectional study and used three-stage sampling to select three counties, nine diabetes clinics in these counties and 270 patients with diabetes attending these clinics. We interviewed the participants using a structured questionnaire. The two outcomes of interest were ‘eye examination in the last 12 months’ and ‘eye examination ever’. The exposure variables were the characteristics of participants living with diabetes. Results The participants had a mean age of 53.3 years (SD 14.1) and an average interval of 4 months between visits to the diabetes clinic. Only 25.6% of participants had ever had an eye examination in their lifetime, while 13.3% had it in the preceding year. The independent predictors of uptake were referral by diabetes services, patient knowledge of diabetes eye complications, comorbid hypertension and urban or semi-urban residence. Conclusions We conclude that access to retinal examination for DR is low in all three counties. An intervention that increases the knowledge of patients with diabetes about eye complications and promotes referral of patients with diabetes for eye examination may improve access to annual eye examination for DR.

Abstract Background In Africa, accessing eye health services is a major challenge. Ocular surface squamous neoplasia (OSSN) is a substantial ocular health problem in Africa related to solar UV light exposure and HIV infection among other risk factors. The disease causes visual loss and even death in advanced cases. This study was conducted to assess referral pathway and treatment delay for patients with OSSN in Kenya. Methods Adults with conjunctival lesions presenting to four eye centres were asked about their occupations, when they noticed the growth, health facilities visited in seeking care, cost of consultation, surgery, medicines and histopathology and dates at each step. The time-to-presentation was divided into quartiles and correlates analysed using ordinal logistic regression. Results We evaluated 158 first-time presenters with OSSN. Most were women (102 [65%]), living with HIV (78/110 tested [71%]), with low to medium income (127 [80%]). Most of the HIV patients (49/78 [63%]) were in antiretroviral care programs. About half (88/158, [56%]) presented directly to the study centres while the rest were referred. Indirect presenters sought care earlier than direct presenters (median 2.0 months vs 5.5 months) and travelled a shorter distance to the first health facility (median 20 km vs 30 km) but had surgery later (median 12.5 months vs 5.5 months). Visits beyond the first health facility for indirect presenters markedly increased delay (median 7.3, 29.0, 37.9, and 32.0 months for 1–4 facilities, respectively). Delay was associated with number of health facilities visited (adjusted ordered OR = 9.12; 95%CI 2.83–29.4, p