Improvement studies for equitable and evidence-based innovation: an overview of the 'IM-SEEN' model.

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.

Cost-effectiveness of basic vision rehabilitation (The basic VRS-effect study): study protocol for a randomised controlled trial.

PURPOSE: To investigate the cost-effectiveness of a basic vision rehabilitation service (basic-VRS) in Portugal. We designed a parallel group, randomised controlled trial whose aim is to compare the effects and costs of 'usual low vision care' with a 'basic-VRS intervention' on self-reported visual ability and other psychosocial and health-related quality-of-life outcomes. METHODS: The trial will recruit participants that meet the following inclusion criteria: (1) visual acuity between 0.4-1.0 logMAR in the better-seeing eye, (2) cause of vision loss is diabetic retinopathy or age-related macular degeneration, (3) 18 years or older and iv) live in the community (not in nursing homes or other type of institution). Participants will be randomised to one of the study arms consisting of immediate intervention and delayed intervention. The delayed intervention group will receive 'usual care' or no intervention in the first 12 weeks. Visual acuity, contrast sensitivity and retinal structure will be assessed during the study. RESULTS: The primary outcome measure is visual ability, which will be evaluated with the Massof Activity Inventory, we expect that the intervention will raise the overall person measure or visual ability. Reading, health-related quality-of-life, anxiety and depression and social support will be also assessed. The analysis will be undertaken on an intention-to-treat basis. A cost-effectiveness analysis will be performed to provide information about the cost per unit of utility. To evaluate the cost-effectiveness of the intervention we will adopt the perspective of the healthcare system. CONCLUSION: This study will provide additional evidence about the effects of basic-VRS on self-reported visual ability. Findings from this study should also contribute to better planning of low vision provision and, consequently, may contribute to reduce barriers to basic-VRS.

Direct and lost productivity costs associated with avoidable hospital admissions.

BACKGROUND: Hospitalizations for ambulatory care sensitive conditions are commonly used to evaluate primary health care performance, as the hospital admission could be avoided if care was timely and adequate. Previous evidence indicates that avoidable hospitalizations carry a substantial direct financial burden in some countries. However, no attention has been given to the economic burden on society they represent. The aim of this study is to estimate the direct and lost productivity costs of avoidable hospital admissions in Portugal. METHODS: Hospitalizations occurring in Portugal in 2015 were analyzed. Avoidable hospitalizations were defined and their associated costs and years of potential life lost were calculated. Direct costs were obtained using official hospitalization prices. For lost productivity, there were estimated costs for absenteeism and premature death. Costs were analyzed by components, by conditions and by variations on estimation parameters. RESULTS: The total estimated cost associated with avoidable hospital admissions was €250 million (€2515 per hospitalization), corresponding to 6% of the total budget of public hospitals in Portugal. These hospitalizations led to 109,641 years of potential life lost. Bacterial pneumonia, congestive heart failure and urinary tract infection accounted for 77% of the overall costs. Nearly 82% of avoidable hospitalizations were in patients aged 65 years or older, therefore did not account for the lost productivity costs. Nearly 84% of the total cost comes from the direct cost of the hospitalization. Lost productivity costs are estimated to be around €40 million. CONCLUSION: The age distribution of avoidable hospitalizations had a significant effect on costs components. Not only did hospital admissions have a substantial direct economic impact, they also imposed a considerable economic burden on society. Substantial financial resources could potentially be saved if the country reduced avoidable hospitalizations.

The impact of diabetes on multiple avoidable admissions: a cross-sectional study.

BACKGROUND: Multiple admissions for ambulatory care sensitive conditions (ACSC) are responsible for an important proportion of health care expenditures. Diabetes is one of the conditions consensually classified as an ACSC being considered a major public health concern. The aim of this study was to analyse the impact of diabetes on the occurrence of multiple admissions for ACSC. METHODS: We analysed inpatient data of all public Portuguese NHS hospitals from 2013 to 2015 on multiple admissions for ACSC among adults aged 18 or older. Multiple ACSC users were identified if they had two or more admissions for any ACSC during the period of analysis. Two logistic regression models were computed. A baseline model where a logistic regression was performed to assess the association between multiple admissions and the presence of diabetes, adjusting for age and sex. A full model to test if diabetes had no constant association with multiple admissions by any ACSC across age groups. RESULTS: Among 301,334 ACSC admissions, 144,209 (47.9%) were classified as multiple admissions and from those, 59,436 had diabetes diagnosis, which corresponded to 23,692 patients. Patients with diabetes were 1.49 times (p < 0,001) more likely to be admitted multiple times for any ACSC than patients without diabetes. Younger adults with diabetes (18-39 years old) were more likely to become multiple users. CONCLUSION: Diabetes increases the risk of multiple admissions for ACSC, especially in younger adults. Diabetes presence is associated with a higher resource utilization, which highlights the need for the implementation of adequate management of chronic diseases policies.

Optimization of Chitosan-α-casein Nanoparticles for Improved Gene Delivery: Characterization, Stability, and Transfection Efficiency.

Among non-viral vectors, the cationic polymer chitosan has gained attention as a gene delivery system. We hypothesized that the addition of casein into the nanoparticle's structure would facilitate a proper gene transfer. The work herein presented aimed to optimize the production method of chitosan-casein nanoparticles (ChiCas NPs) and to test their ability as a gene delivery system. ChiCas NPs formulation optimization was carried out by analyzing several characteristics such as NP size, zeta potential, and chitosan and casein incorporation efficacy. The best formulation developed presented small and homogenous particle size (around 335 nm) and positive zeta potential (≈ + 38 mV), and showed to be stable for 34 weeks both, at 4°C and 20°C. The particles were further used to entrap or to adsorb DNA and form NPs-DNA complexes. In vitro transfection studies, carried out in COS-7 cells, suggested a low transfection efficiency of the different NPs:DNA ratios tested, comparatively to the positive control. Nonetheless, we could observe that the complexes with larger sizes presented better transfection results than those with smaller diameters. To conclude, ChiCas NPs have great technological potential since the preparation process is very simple, and the DNA incorporation efficacy is very high and shows to be physically very stable. The NPs:DNA ratio still needs to be optimized with the aim of achieving better transfection results and being able to anticipate a high gene expression on DNA-based vaccination studies.

Dipeptidyl peptidase IV (DPP-IV) inhibition prevents fibrosis in adipose tissue of obese mice.

BACKGROUND: During the development of obesity the expansion of white adipose tissue (WAT) leads to a dysregulation and an excessive remodeling of extracellular matrix (ECM), leading to fibrosis formation. These ECM changes have high impact on WAT physiology and may change obesity progression. Blocking WAT fibrosis may have beneficial effects on the efficacy of diet regimen or therapeutical approaches in obesity. Since dipeptidyl peptidase IV (DPP-IV) inhibitors prevent fibrosis in tissues, such as heart, liver and kidney, the objective of this study was to assess whether vildagliptin, a DPP-IV inhibitor, prevents fibrosis in WAT in a mouse model of obesity, and to investigate the mechanisms underlying this effect. METHODS: We evaluated the inhibitory effect of vildagliptin on fibrosis markers on WAT of high-fat diet (HFD)-induced obese mice and on 3T3-L1 cell line of mouse adipocytes treated with a fibrosis inducer, transforming growth factor beta 1 (TGFß1). RESULTS: Vildagliptin prevents the increase of fibrosis markers in WAT of HFD-fed mice and reduces blood glucose, serum triglycerides, total cholesterol and leptin levels. In the in vitro study, the inhibition of DPP-IV with vildagliptin, neuropeptide Y (NPY) treatment and NPY Y1 receptor activation prevents ECM deposition and fibrosis markers increase induced by TGFß1 treatment. CONCLUSIONS: Vildagliptin prevents fibrosis formation in adipose tissue in obese mice, at least partially through NPY and NPY Y1 receptor activation. GENERAL SIGNIFICANCE: This study highlights the importance of vildagliptin in the treatment of fibrosis that occur in obesity.

Predicting participation of people with impaired vision in epidemiological studies.

BACKGROUND: The characteristics of the target group and the design of an epidemiologic study, in particular the recruiting methods, can influence participation. People with vision impairment have unique characteristics because those invited are often elderly and totally or partially dependent on help to complete daily activities such as travelling to study sites. Therefore, participation of people with impaired vision in studies is less predictable than predicting participation for the general population. METHODS: Participants were recruited in the context of a study of prevalence and costs of visual impairment in Portugal (PCVIP-study). Participants were recruited from 4 Portuguese public hospitals. Inclusion criteria were: acuity in the better eye from 0.5 decimal (0.30logMAR) or worse and/or visual field of less than 20 degrees. Recruitment involved sending invitation letters and follow-up phone calls. A multiple logistic regression model was used to assess determinants of participation. The J48 classifier, chi-square and Fisher's exact tests were applied to investigate the possible differences between subjects in our sample. RESULTS: Individual cases were divided into 3 groups: immediate, late and non-participants. A participation rate of 20% was obtained (15% immediate, 5% late). Factors positively associated with participation included years of education, annual hospital attendance, and intermediate visual acuity. Females and greater distance to the hospital were inversely associated with participation. CONCLUSION: In our study, a letter followed by a phone call was efficient to recruit a significant number of participants from a larger group of people with impaired vision. However, the improvement in participation observed after the phone call might not be cost-effective. People with low levels of education and women were more difficult to recruit. These findings need to be considered to avoid studies whose results are biased by gender or socio-economic inequalities of their participants. Young subjects and those at intermediate stages of vision impairment, or equivalent conditions, may need more persuasion than other profiles.

Can Vertical Integration Reduce Hospital Readmissions? A Difference-in-Differences Approach.

BACKGROUND: Vertical integration is expected to improve communication and coordination between inpatient care and care after discharge. Despite being used across health systems worldwide, evidence about its impact on readmissions is sparse and contradictory. OBJECTIVE: To assess the impact of vertical integration on hospital readmissions. RESEARCH DESIGN, SUBJECTS, AND MEASURES: Using difference-in-differences we compared readmissions before and after vertical integration in 6 Portuguese hospitals for years 2004-2013. A control group with 6 similar hospitals not integrated was utilized. Considered outcome was 30-day unplanned readmission. We used logistic regression at the admission level and accounted for patients' risk factors using claims data. Analyses for each hospital and selected conditions were also run. RESULTS: Our results suggest that readmissions decreased overall after vertical integration [odds ratio (OR)=0.900; 95% confidence interval (CI), 0.812-0.997]. Hospital analysis indicated that there was no impact for 2 hospitals (OR=0.960; 95% CI, 0.848-1.087 and OR=0.944; 95% CI, 0.857-1.038), and a positive effect in 4 hospitals (greatest effect: OR=0.811; 95% CI, 0.736-0.894). A positive evolution was observed for a limited number of conditions, with better results for diabetes with complications (OR=0.689; 95% CI, 0.525-0.904), but no impact regarding congestive heart failure (OR=1.067; 95% CI, 0.827-1.377). CONCLUSIONS: Merging acute and primary care providers was associated with reduced readmissions, even though improvements were not found for all institutions or condition-specific groups. There are still challenges to be addressed regarding the success of vertical integration in reducing 30-day hospital readmissions.

Hypoxia mimetic induces lipid accumulation through mitochondrial dysfunction and stimulates autophagy in murine preadipocyte cell line.

BACKGROUND: Hypoxia occurs within adipose tissue of obese human and mice. However, its role in adipose tissue regulation is still controversial. METHODS: We used murine preadipocyte 3T3-L1 cells and hypoxia was induced by using hypoxia mimetic agents, as CoCl2. To study adipocyte differentiation, we evaluated the adipocyte markers (PPARγ, C/EBPα and aP2), and a preadipocyte marker (pref-1) by qPCR, western blotting and immunofluorescence. Lipid accumulation was evaluated by Oil red-O assay and perilipin levels by western blotting and immunofluorescence. The effect of CoCl2 in microRNA, miR-27a and miR-27b, levels was evaluated by qPCR. We also assessed the mitochondrial membrane potential and reactive oxygen species (ROS), superoxide and ATP production. The effect of hypoxia mimetic in autophagy was determined by LC3B and p62 level evaluation by western blotting. RESULTS: Our results show that the hypoxia mimetic cobalt chloride increases lipid accumulation with no expression of PPARγ2. Furthermore, using qPCR we observed that the hypoxia mimetic increases microRNAs miR-27a and miR-27b, which are known to block PPARγ2 expression. In contrast, cobalt chloride induces mitochondrial dysfunction, and increases ROS production and autophagy. Moreover, an antioxidant agent, glutathione, prevents lipid accumulation induced by hypoxia mimetic indicating that ROS are responsible for hypoxia-induced lipid accumulation. CONCLUSIONS: All these results taken together suggest that hypoxia mimetic blocks differentiation and induces autophagy. Hypoxia mimetic also induces lipid accumulation through mitochondrial dysfunction and ROS accumulation. GENERAL SIGNIFICANCE: This study highlights the importance of adipocyte response to hypoxia, which might impair adipocyte metabolism and compromise adipose tissue function.

Early exposure of dams to a westernized diet has long-term consequences on food intake and physiometabolic homeostasis of the rat offspring.

This study evaluated the long-term effects of a westernized diet during pregnancy and lactation. Female Wistar rats (n = 12) were divided into two groups according to their food intake, namely, control (C) or westernized (W) diet, throughout pregnancy/lactation. On the 21st day, the male pups were weaned on a standard diet as follows: Control diet (CC) (n = 8) and westernized diet in perinatal life followed by control diet post weaning (WC) (n = 8). The levels of fasting (12 h) serum glucose, triglycerides (TG), and total cholesterol and fraction in the pups were determined. During weaning, the WC group showed 14% greater body weight (p < 0.001). In the adulthood, the offspring from dams fed on westernized diet showed hyperphagia, hyperinsulinism, hypertriglyceridemia, higher fat visceral weight, higher very-low-density-lipoprotein cholesterol level, decreased high-density-lipoprotein cholesterol level, and altered glucose tolerance test. In conclusion, maternal western-style diet in early life altered long-term food intake, visceral fat pad, insulin, glucose and lipid serum, and increased risk of metabolic disorders.

Artificial intelligence-supported diabetic retinopathy screening in Tanzania: rationale and design of a randomised controlled trial.

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.

Differentiating stages of functional vision loss from glaucoma using the Disc Damage Likelihood Scale and cup:disc ratio.

BACKGROUND: Glaucoma staging is critical for treatment planning but has rarely been tested in severe/end-stage disease. We compared the performance of the Disc Damage Likelihood Scale (DDLS) and cup:disc ratio (CDR) using a functional glaucoma staging system (GSS) as the reference standard. METHODS: Post hoc analysis of a randomised controlled trial at the Eye Department of Kilimanjaro Christian Medical Centre, Tanzania. Eligible participants (aged ≥18 years) with open-angle glaucoma, intraocular pressure (IOP) of >21 mm Hg, were randomised to timolol 0.5% eye drops or selective laser trabeculoplasty. Fundoscopy established vertical and horizontal CDRs and DDLS. Visual acuity and static visual fields were graded (GSS). The study used area under the receiver operating characteristic (AROC) curves and Spearman's rank correlation coefficients to compare staging systems. Logistic regression with generalised estimating equations determined risk factors of functional severe/end-stage glaucoma. RESULTS: 382 eyes (201 participants) were evaluated; 195 (51%) had severe or end-stage glaucoma; mean IOP was 26.7 (SD 6.9) mm Hg. DDLS yielded an AROC of 0.90 (95% CI 0.87 to 0.93), vertical cup:disc ratio (vCDR) of 0.88 (95% CI 0.85 to 0.91, p=0.048) for identifying severe/end-stage disease. Correlation coefficients comparing GSS to DDLS and vCDRs were 0.73 and 0.71, respectively. Advanced structural stages, vision impairment, higher IOP and less financial resources were risk factors of functional severe/end-stage glaucoma. CONCLUSION: This study indicates that both structural staging systems can differentiate severe/end-stage glaucoma from less severe disease, with a moderate advantage of DDLS over CDR. Clinical examination of the optic disc plays an important role in addition to functional assessment when managing severe/end-stage glaucoma.

The Basic VRS-Effect Study: Clinical Trial Outcomes and Cost-Effectiveness of Low Vision Rehabilitation in Portugal.

INTRODUCTION: The aim of this study was twofold: (1) to investigate the clinical impact of vision rehabilitation in patients with vision impairment and (2) to investigate the cost-effectiveness of a basic vision rehabilitation service in Portugal. METHODS: The trial recruited patients diagnosed with age-related macular degeneration or diabetic retinopathy (DR) and visual acuity in the range 0.4-1.0logMAR in the better-seeing eye. Participants were randomised to one of the study arms consisting of immediate intervention and delayed intervention. The intervention included: new refractive correction, optical reading aids, in-office training and advice about modifications at home. Visual ability, health-related quality of life and costs were measured. Economic analysis was performed to evaluate whether the intervention was cost-effective. The trial compared the outcomes 12 weeks after the start in both arms. RESULTS: Of the 46 participants, 34 (74%) were diagnosed with DR, 25 (54%) were female, and mean age was 70.08 years (SD = 8.74). In the immediate intervention arm visual ability increased a mean of 0.523 logits (SE = 0.11) (p < 0.001). Changes in the delayed intervention arm were not statistically significant (p = 0.95). Acuity in the better-seeing eye, near acuity and critical print size also improved during the study. The mean cost of the intervention was €118.79 (SD = 24.37). The incremental cost-effectiveness ratio using the EQ-5D-5L was 30,421€/QALY and 1186€/QALY when using near acuity. CONCLUSION: The current study gives evidence of positive clinical impact of a basic vision rehabilitation intervention and shows that a basic vision rehabilitation service is cost-effective. These findings are important to clinical and rehabilitation practices and for planning vision rehabilitation services. TRIAL REGISTRATION: Retrospectively registered, 21/01/2019. ISRCTN10894889, https://www.isrctn.com/ISRCTN10894889.

There is limited research addressing the actual impact of vision rehabilitation. The current trial compares the effect of a basic vision rehabilitation intervention with usual care on patients' functioning. The intervention was clinically impactful and cost-effective.

Endoplasmic Reticulum-Mitochondria Contacts Modulate Reactive Oxygen Species-Mediated Signaling and Oxidative Stress in Brain Disorders: The Key Role of Sigma-1 Receptor.

Significance: Mitochondria-Associated Membranes (MAMs) are highly dynamic endoplasmic reticulum (ER)-mitochondria contact sites that, due to the transfer of lipids and Ca2+ between these organelles, modulate several physiologic processes, such as ER stress response, mitochondrial bioenergetics and fission/fusion events, autophagy, and inflammation. In addition, these contacts are implicated in the modulation of the cellular redox status since several MAMs-resident proteins are involved in the generation of reactive oxygen species (ROS), which can act as both signaling mediators and deleterious molecules, depending on their intracellular levels. Recent Advances: In the past few years, structural and functional alterations of MAMs have been associated with the pathophysiology of several neurodegenerative diseases that are closely associated with the impairment of several MAMs-associated events, including perturbation of the redox state on the accumulation of high ROS levels. Critical Issues: Inter-organelle contacts must be tightly regulated to preserve cellular functioning by maintaining Ca2+ and protein homeostasis, lipid metabolism, mitochondrial dynamics and energy production, as well as ROS signaling. Simultaneously, these contacts should avoid mitochondrial Ca2+ overload, which might lead to energetic deficits and deleterious ROS accumulation, culminating in oxidative stress-induced activation of apoptotic cell death pathways, which are common features of many neurodegenerative diseases. Future Directions: Given that Sig-1R is an ER resident chaperone that is highly enriched at the MAMs and that controls ER to mitochondria Ca2+ flux, as well as oxidative and ER stress responses, its potential as a therapeutic target for neurodegenerative diseases such as Amyotrophic Lateral Sclerosis, Alzheimer, Parkinson, and Huntington diseases should be further explored. Antioxid. Redox Signal. 37, 758-780.

Cross-sectional study investigating the prevalence and causes of vision impairment in Northwest Portugal using capture-recapture.

OBJECTIVES: The aim of this study was to estimate the prevalence and causes of vision impairment (VI) in Portugal. SETTING: Information about people with VI was obtained from primary care centres, blind association (ACAPO) and from hospitals (the PCVIP study) in the Northwest of Portugal during a period spanning years 2014-2015. Causes of VI were obtained from hospitals. PARTICIPANTS: Administrative and medical records of people with visual acuity in the better seeing eye of 0.5 decimal (0.30logMAR) or worse and/or visual field less than 20° were investigated. Capture-recapture with log-linear models was applied to estimate the number of individuals missing from lists of cases obtained from available sources. PRIMARY AND SECONDARY OUTCOME MEASURES: Log-linear models were used to estimate the crude prevalence and the category specific prevalence of VI. RESULTS: Crude prevalence of VI was 1.97% (95% CI 1.56% to 2.54%), and standardised prevalence was 1% (95% CI 0.78% to 1.27%). The age-specific prevalence was 3.27% (95% CI 2.36% to 4.90%), older than 64 years, 0.64% (95% CI 0.49% to 0.88%), aged 25-64 years, and 0.07% (95% CI 0.045% to 0.13%), aged less than 25 years. The female-to-male ratio was 1.3, that is, higher prevalence among females. The five leading causes of VI were diabetic retinopathy, cataract, age-related macular degeneration, glaucoma and disorders of the globe. CONCLUSIONS: The prevalence of VI in Portugal was within the expected range and in line with other European countries. A significant number of cases of VI might be due to preventable cases and, therefore, a reduction of the prevalence of VI in Portugal seems possible. Women and old people were more likely to have VI and, therefore, these groups require extra attention. Future studies are necessary to characterise temporal changes in prevalence of VI in Portugal.

Trends, geographical variation and factors associated with the use of anti-VEGF intravitreal injections in Portugal (2013-2018): a retrospective analysis of administrative data.

AIMS: The arrival of anti-vascular endothelial growth factor (anti-VEGF) therapies represented a treatment shift for several ophthalmological disorders and led to an increasing number of patients undergoing intravitreal injections. The aims of this observational study were to assess the expansion of anti-VEGF intravitreal injections in the Portuguese National Health System (NHS) and to identify factors correlated with geographical variations in episode rates. METHODS: Administrative database on discharge from Portuguese NHS hospitals was analysed for annual values and rates of intravitreal anti-VEGF injections at a national and regional level, between 2013 and 2018. RESULTS: The number of episodes of anti-VEGF treatment and patients treated increased 16% and 9% per year, respectively, between 2013 and 2018. During the study period around 72% of patients were treated in the Metropolitan areas of Lisbon and Porto and in the Central region. Intravitreal anti-VEGF treatment rates in 2018 were 560 per 100 000 population and presented high variability between municipalities. Higher anti-VEGF treatment rates at the municipality level were associated with shorter distances between their residence and the hospital. At the hospital level, higher ratio of ophthalmologists and higher organisational level were associated with higher anti-VEGF treatment rates. CONCLUSION: The number of episodes and patients treated with anti-VEGF injections has been growing in recent years. Proximity to healthcare, more access to ophthalmologists and hospitals with higher organisational levels are associated with higher anti-VEGF treatment rates. Improving access is crucial to reduce regional discrepancies and ensure optimal treatment frequency, which may improve health outcomes.

Performance and resource requirements of in-person versus voice call versus automated telephone-based socioeconomic data collection modalities for community-based health programmes: a systematic review protocol.

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.

Performance and Resource Requirements of In-Person, Voice Call, and Automated Telephone-Based Socioeconomic Data Collection Modalities for Community-Based Health Programs: A Systematic Review.

Importance: Gathering data on socioeconomic status (SES) is a prerequisite for health programs that aim to improve equity. There is a lack of evidence on which approaches offer the best combination of reliability, cost, and acceptability. Objective: To compare the performance of different approaches to gathering data on SES in community health programs. Data Sources: A search of the Cochrane Library, MEDLINE, Embase, Global Health, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and OpenGrey from 1999 to June 29, 2021, was conducted, with no language limits. Google Scholar was also searched and the reference lists of included articles were checked to identify further studies. The search was performed on June 29, 2021. Study Selection: Any empirical study design was eligible if it compared 2 or more modalities to elicit SES data from the following 3 categories: in-person, voice call, or automated telephone-based systems. Data Extraction and Synthesis: Two reviewers independently screened titles, abstracts, and full-text articles and extracted data. They also assessed the risk of bias using Cochrane tools and assessed the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach. Findings were synthesized thematically without meta-analysis. Main Outcomes and Measures: Response rate, equivalence, time, costs, and acceptability to patients and health care professionals. Results: The searches returned 3943 records. The 11 included studies reported data on 14 036 individuals from 7 countries, collecting data on 11 socioeconomic domains using 2 or more of the following modes: in-person surveys, computer-assisted telephone interviews (CATIs), and 2 types of automated data collection: interactive voice response calls (IVRs) and web surveys. Response rates were greater than 80% for all modes except IVRs. Equivalence was high across all modes (Cohen κ > 0.5). There were insufficient data to make robust time and cost comparisons. Patients reported high levels of acceptability providing data via IVRs, web surveys, and CATIs. Conclusions and Relevance: Selecting an appropriate and cost-effective modality to elicit SES data is an important first step toward advancing equitable effective service coverage. This systematic review did not identify evidence that remote and automated data collection modes differed from human-led and in-person approaches in terms of reliability, cost, or acceptability.

Untargeted Metabolomics Reveals Antidepressant Effects in a Marine Photosynthetic Organism: The Diatom Phaeodactylum tricornutum as a Case Study.

The increased use of antidepressants, along with their increased occurrence in aquatic environments, is of concern for marine organisms. Although these pharmaceutical compounds have been shown to negatively affect marine diatoms, their mode of action in these non-target, single-cell phototrophic organisms is yet unknown. Using a Fourier-transform ion cyclotron-resonance mass spectrometer (FT-ICR-MS) we evaluated the effects of fluoxetine in the metabolomics of the model diatom Phaeodactylum tricornutum, as well as the potential use of the identified metabolites as exposure biomarkers. Diatom growth was severely impaired after fluoxetine exposure, particularly in the highest dose tested, along with a down-regulation of photosynthetic and carbohydrate metabolisms. Notably, several mechanisms that are normally down-regulated by fluoxetine in mammal organisms were also down-regulated in diatoms (e.g., glycerolipid metabolism, phosphatidylinositol signalling pathway, vitamin metabolism, terpenoid backbone biosynthesis and serotonin remobilization metabolism). Additionally, the present work also identified a set of potential biomarkers of fluoxetine exposure that were up-regulated with increasing fluoxetine exposure concentration and are of high metabolic significance following the disclosed mode of action, reinforcing the use of metabolomics approaches in ecotoxicology.

Advancing the Sustainable Development Goals through improving eye health: a scoping review.

UN member states have committed to achieving the Sustainable Development Goals (SDGs) by 2030. This Review examines the published evidence on how improving eye health can contribute to advancing the SDGs (beyond SDG 3). We identified 29 studies that showed direct benefits from providing eye health services on SDGs related to one or more of poverty (SDGs 1, 2, and 8), education (SDG 4), equality (SDGs 5 and 10), and sustainable cities (SDG 11). The eye health services included cataract surgery, free cataract screening, provision of spectacles, trichiasis surgery, rehabilitation services, and rural community eye health volunteers. These findings provide a comprehensive perspective on the direct links between eye health services and advancing the SDGs. In addition, eye health services likely have indirect effects on multiple SDGs, mediated through one of the direct effects. Finally, there are additional plausible links to other SDGs, for which evidence has not yet been established.