Discovering Subgroups of Children With High Mortality in Urban Guinea-Bissau: Exploratory and Validation Cohort Study.

BACKGROUND: The decline in global child mortality is an important public health achievement, yet child mortality remains disproportionally high in many low-income countries like Guinea-Bissau. The persisting high mortality rates necessitate targeted research to identify vulnerable subgroups of children and formulate effective interventions. OBJECTIVE: This study aimed to discover subgroups of children at an elevated risk of mortality in the urban setting of Bissau, Guinea-Bissau, West Africa. By identifying these groups, we intend to provide a foundation for developing targeted health interventions and inform public health policy. METHODS: We used data from the health and demographic surveillance site, Bandim Health Project, covering 2003 to 2019. We identified baseline variables recorded before children reached the age of 6 weeks. The focus was on determining factors consistently linked with increased mortality up to the age of 3 years. Our multifaceted methodological approach incorporated spatial analysis for visualizing geographical variations in mortality risk, causally adjusted regression analysis to single out specific risk factors, and machine learning techniques for identifying clusters of multifactorial risk factors. To ensure robustness and validity, we divided the data set temporally, assessing the persistence of identified subgroups over different periods. The reassessment of mortality risk used the targeted maximum likelihood estimation (TMLE) method to achieve more robust causal modeling. RESULTS: We analyzed data from 21,005 children. The mortality risk (6 weeks to 3 years of age) was 5.2% (95% CI 4.8%-5.6%) for children born between 2003 and 2011, and 2.9% (95% CI 2.5%-3.3%) for children born between 2012 and 2016. Our findings revealed 3 distinct high-risk subgroups with notably higher mortality rates, children residing in a specific urban area (adjusted mortality risk difference of 3.4%, 95% CI 0.3%-6.5%), children born to mothers with no prenatal consultations (adjusted mortality risk difference of 5.8%, 95% CI 2.6%-8.9%), and children from polygamous families born during the dry season (adjusted mortality risk difference of 1.7%, 95% CI 0.4%-2.9%). These subgroups, though small, showed a consistent pattern of higher mortality risk over time. Common social and economic factors were linked to a larger share of the total child deaths. CONCLUSIONS: The study's results underscore the need for targeted interventions to address the specific risks faced by these identified high-risk subgroups. These interventions should be designed to work to complement broader public health strategies, creating a comprehensive approach to reducing child mortality. We suggest future research that focuses on developing, testing, and comparing targeted intervention strategies unraveling the proposed hypotheses found in this study. The ultimate aim is to optimize health outcomes for all children in high-mortality settings, leveraging a strategic mix of targeted and general health interventions to address the varied needs of different child subgroups.

A systematic review of the social impact of diseases in Nordic countries.

BACKGROUND: We review the literature on the social impacts of diseases, defined as the social consequences of having a disease on the people around the patient, such as spouses, caregivers and offspring. The two objectives of this study are to summarise the social outcomes commonly associated with diseases and to compare the social impact across a range of diseases. METHODS: A systematic review of the social impact of disease in Nordic countries was conducted using PubMed, PsycINFO and Google Scholar (PROSPERO registration number CRD42022291796). All articles that met the inclusion criteria were reviewed. We tabulated all outcomes and diseases studied, and synthesised the evidence based on the perspectives of patients, spouse/caregiver and offspring. RESULTS: A total of 135 studies met the eligibility criteria, covering 76 diseases and 39 outcomes. From the patient's perspective, diseases impact divorce and marriage rates, social functioning, likelihood of committing a crime and being a victim of crime. From the caregiver's perspective, diseases affect their health-related quality of life and physical and psychological health. From the offspring's perspective, diseases impact their development, health and social adversities in later life. Diseases generally had negative social impacts, but there were some diseases associated with positive impacts. CONCLUSIONS: The review provides a useful summary and gross comparison of the social impact of different diseases. The social impact of diseases can be large and significant. Thus, it should be considered when policymakers are setting priorities across disease areas.

The economic burden of diseases in the Nordic countries: A systematic review.

BACKGROUND: Economic burden studies can provide insights into the drivers leading to increasing healthcare costs. It can also provide a more holistic view of how diseases impact the welfare of patients and their families. Having concrete estimates of the economic burden across multiple diseases can help policymakers determine which diseases are economically more burdensome. This study aimed to review and summarise comprehensively economic burden studies across multiple diseases in the Nordic countries between 2000 and 2020. METHODS: According to the 2020 PRISMA statement, a systematic literature review was conducted in PubMed, CINAHL, Academic Search Premier and Global Health databases using key terms related to the economic burden of any disease in Denmark, Finland, Greenland, Iceland, Norway and Sweden. Grey literature was also reviewed. RESULTS: A total of 10,050 potential titles and abstracts were identified and screened, and 254 full-text papers that met the inclusion criteria were evaluated by two independent reviewers. Of these, 119 articles were included in a qualitative synthesis. Twenty-nine had clearly defined comparison groups, thus able to attribute the costs to the disease. Large variations concerning methodology and cost components were noted. Across diseases, the economic burden ranged from EUR 1668 per patient annually for chronic obstructive pulmonary disease to EUR 93,041 for multiple sclerosis. However, estimates varied widely, even within each disease. CONCLUSIONS: Our review highlights the need for more comparable economic burden studies. Future studies should focus on applying robust methodology and homogeneous cost-reporting methods to inform policymakers about which diseases are economically more burdensome.

Estimating health spending associated with chronic multimorbidity in 2018: An observational study among adults in the United States.

BACKGROUND: The rise in health spending in the United States and the prevalence of multimorbidity-having more than one chronic condition-are interlinked but not well understood. Multimorbidity is believed to have an impact on an individual's health spending, but how having one specific additional condition impacts spending is not well established. Moreover, most studies estimating spending for single diseases rarely adjust for multimorbidity. Having more accurate estimates of spending associated with each disease and different combinations could aid policymakers in designing prevention policies to more effectively reduce national health spending. This study explores the relationship between multimorbidity and spending from two distinct perspectives: (1) quantifying spending on different disease combinations; and (2) assessing how spending on a single diseases changes when we consider the contribution of multimorbidity (i.e., additional/reduced spending that could be attributed in the presence of other chronic conditions). METHODS AND FINDINGS: We used data on private claims from Truven Health MarketScan Research Database, with 16,288,894 unique enrollees ages 18 to 64 from the US, and their annual inpatient and outpatient diagnoses and spending from 2018. We selected conditions that have an average duration of greater than one year among all Global Burden of Disease causes. We used penalized linear regression with stochastic gradient descent approach to assess relationship between spending and multimorbidity, including all possible disease combinations with two or three different conditions (dyads and triads) and for each condition after multimorbidity adjustment. We decomposed the change in multimorbidity-adjusted spending by the type of combination (single, dyads, and triads) and multimorbidity disease category. We defined 63 chronic conditions and observed that 56.2% of the study population had at least two chronic conditions. Approximately 60.1% of disease combinations had super-additive spending (e.g., spending for the combination was significantly greater than the sum of the individual diseases), 15.7% had additive spending, and 23.6% had sub-additive spending (e.g., spending for the combination was significantly less than the sum of the individual diseases). Relatively frequent disease combinations (higher observed prevalence) with high estimated spending were combinations that included endocrine, metabolic, blood, and immune disorders (EMBI disorders), chronic kidney disease, anemias, and blood cancers. When looking at multimorbidity-adjusted spending for single diseases, the following had the highest spending per treated patient and were among those with high observed prevalence: chronic kidney disease ($14,376 [12,291,16,670]), cirrhosis ($6,465 [6,090,6,930]), ischemic heart disease (IHD)-related heart conditions ($6,029 [5,529,6,529]), and inflammatory bowel disease ($4,697 [4,594,4,813]). Relative to unadjusted single-disease spending estimates, 50 conditions had higher spending after adjusting for multimorbidity, 7 had less than 5% difference, and 6 had lower spending after adjustment. CONCLUSIONS: We consistently found chronic kidney disease and IHD to be associated with high spending per treated case, high observed prevalence, and contributing the most to spending when in combination with other chronic conditions. In the midst of a surging health spending globally, and especially in the US, pinpointing high-prevalence, high-spending conditions and disease combinations, as especially conditions that are associated with larger super-additive spending, could help policymakers, insurers, and providers prioritize and design interventions to improve treatment effectiveness and reduce spending.

Visual Function Tests: Visual Fields.

Visual field tests, also known as perimetry tests, are used to assess progression of ophthalmic diseases such as retinitis pigmentosa (RP) by monitoring changes in a patient's visual field (VF). VF loss corresponds to damage at any point in the visual pathway, including the retina, such as in RP. Damage to different parts of this pathway corresponds to characteristic VF defects. Perimetry tests are subjective, as they are functional tests that help physicians identify abnormal fields as well as quantitatively assess VF sensitivity. The results may also be informative of a patient's visual function crucial for performing day-to-day activities. Automated perimetry tests are among the most commonly used, with the most common being automated static perimetry.

Challenges of Treatment Methodologies and the Future of Gene Therapy and Stem Cell Therapy to Treat Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a heterogeneous group of hereditary retinal degenerations for which there is currently no cure. Studies investigating the use of gene therapy, gene editing, and stem cells as potential treatment strategies have shown promising results in animal models and some early clinical trials. Even still, major barriers still exist, including the ability to develop therapies that can target the wide range of mutational etiologies and phenotypic presentations that encompass RP. Additionally, effective screening and early diagnosis are crucial for maximum therapeutic potential, especially because many therapeutic agents require a baseline level photoreceptor function.

One vaccine to counter many diseases? Modeling the economics of oral polio vaccine against child mortality and COVID-19.

Introduction: Recent reviews summarize evidence that some vaccines have heterologous or non-specific effects (NSE), potentially offering protection against multiple pathogens. Numerous economic evaluations examine vaccines' pathogen-specific effects, but less than a handful focus on NSE. This paper addresses that gap by reporting economic evaluations of the NSE of oral polio vaccine (OPV) against under-five mortality and COVID-19. Materials and methods: We studied two settings: (1) reducing child mortality in a high-mortality setting (Guinea-Bissau) and (2) preventing COVID-19 in India. In the former, the intervention involves three annual campaigns in which children receive OPV incremental to routine immunization. In the latter, a susceptible-exposed-infectious-recovered model was developed to estimate the population benefits of two scenarios, in which OPV would be co-administered alongside COVID-19 vaccines. Incremental cost-effectiveness and benefit-cost ratios were modeled for ranges of intervention effectiveness estimates to supplement the headline numbers and account for heterogeneity and uncertainty. Results: For child mortality, headline cost-effectiveness was $650 per child death averted. For COVID-19, assuming OPV had 20% effectiveness, incremental cost per death averted was $23,000-65,000 if it were administered simultaneously with a COVID-19 vaccine <200 days into a wave of the epidemic. If the COVID-19 vaccine availability were delayed, the cost per averted death would decrease to $2600-6100. Estimated benefit-to-cost ratios vary but are consistently high. Discussion: Economic evaluation suggests the potential of OPV to efficiently reduce child mortality in high mortality environments. Likewise, within a broad range of assumed effect sizes, OPV (or another vaccine with NSE) could play an economically attractive role against COVID-19 in countries facing COVID-19 vaccine delays. Funding: The contribution by DTJ was supported through grants from Trond Mohn Foundation (BFS2019MT02) and Norad (RAF-18/0009) through the Bergen Center for Ethics and Priority Setting.

The health-adjusted dependency ratio as a new global measure of the burden of ageing: a population-based study.

BACKGROUND: The old-age dependency ratio (OADR), which is the ratio of older people (aged ≥65 years) to working age people (aged 20-64 years), is the most common way to assess and compare the burden of population ageing in different countries. However, the relationship between chronological age and dependency varies widely across countries. We therefore present the health-adjusted dependency ratio (HADR), a new measure of ageing burden based on the ageing-related health of the adult population. METHODS: In this population-based study we used health data for diseases and injuries for 2017 from the Global Burden of Disease project and population data for 2017 from the UN's Population Division to identify the number of adults (aged >20 years) in each country who have the same or higher ageing-related disease burden as the global average 65-year-old. We then calculated the HADR as the ratio of adults who were less healthy than the average 65-year-old (dependent population) to those in better health (supporting population) and compared the HADR with the OADR for 188 countries. We also used cross-sectional, bivariate regression analysis to investigate whether the HADR is a more powerful predictor of changes in per capita health-care expenditure than the OADR as a measure of predictive validity. FINDINGS: Many demographically younger populations have an earlier onset of ageing-related disease, and many demographically older populations have a later onset. For instance, Pakistan has an OADR of 0·09 and an HADR of 0·19, and France has an OADR of 0·35 and an HADR of 0·13. Relative to the OADR, the HADR suggests that Asia, western Europe, and North America have a lower ageing burden, whereas central Asia, southern Asia, and Africa have a greater burden. While Japan and countries in western Europe have the highest OADR, Russia, Papua New Guinea, and countries in southeast Europe have the highest HADR. Relative to the OADR, the HADR suggests that there is much less variation in the burden of ageing across countries than has previously been assumed. HADR was also more closely associated with growth in health spending than the OADR. A 0·1 increase in the HADR was associated with a 2·9 percentage points larger growth rate in per capita spending (p=0·0001), and a 0·1-point increase in the OADR was associated with a 1·8 percentage point larger growth rate. INTERPRETATION: The OADR probably overestimates the burden of population ageing in many demographically older countries and underestimates the ageing burden in many demographically younger countries, which implies that the challenges associated with ageing are more universal than previously thought, and that the world cannot easily be divided in a young and an old groups of nations. FUNDING: None.

The Role of Intraocular Pressure and Systemic Hypertension in the Progression of Glaucomatous Damage to the Macula.

PRCIS: Macular structural and functional parameters were better correlated with pressure-dependent glaucomatous damage than conventional parameters. Self-reported systemic hypertension (HTN) was not associated with structural or functional progression in this cohort. PURPOSE: The aim was to examine the relationships between intraocular pressure (IOP), systemic HTN, and glaucoma progression using structural testing with optical coherence tomography (OCT) and functional testing with visual field (VF). PATIENTS AND METHODS: A total of 191 eyes of 119 patients enrolled in a prospective, longitudinal study (Structural and Functional Progression of Glaucomatous Damage to the Macula study) with a diagnosis of glaucoma were analyzed. Patients were tested with 10-2 and 24-2 VF and spectral-domain OCT obtained at 4 to 6 month intervals. IOP from each visit was collected. Self-reported diagnoses of HTN were reported in 72 eyes (37%) in the patients included. Linear mixed effects regression was used to test the relationship between summary statistics from VF and OCT and HTN diagnosis. The goodness-of-fit of relationships was assessed with Bayesian information criterion. RESULTS: Mean follow-up IOP was most associated with the following OCT parameters: global macula ganglion cell layer (GCL), inferior macula GCL, mean macular vulnerability zone GCL, and mean less vulnerable zone macula GCL, and with the following VF parameters: 10-2 PSD and 10-2 MD. There was no significant difference in rates of progression between HTN and non-HTN patients for any OCT or VF parameter. Models with the best goodness-of-fit for the relationship between HTN and progression were the same as those observed for IOP. CONCLUSION: Macular structural and functional parameters are more sensitive to IOP in terms of glaucomatous progression when compared with more conventional parameters. While HTN was not significantly associated with progression using any parameter, macular structural and functional parameters had a better goodness-of-fit to model progression and may be useful as endpoints.

Atypical presentation of invasive myoepithelioma in a pediatric patient.

A 15-year-old girl presented with a mobile lesion with yellowish hue on the posterior lamella of the right lower eyelid adjacent to the punctum. Four years prior, a lesion thought to be a chalazion was excised from the same location. There was subsequent progressive painless enlargement. The patient ultimately underwent an internal excision of the mass. Histopathology demonstrated infiltrative nests and cords of epithelioid and plasmacytoid cells with abundant eosinophilic myxoid-collagenous stroma along with focal infiltration of skeletal muscle with immunohistochemical staining consistent with an invasive myoepithelioma of mixed-cell type. Given concern for invasive disease, the patient underwent subsequent Mohs resection resulting in a 25% full thickness eyelid defect, which was repaired with direct closure of the wedge defect. There has been no recurrence of the disease for 7 months since the Mohs resection. This case illustrates the atypical presentation of an invasive myoepithelioma of the eyelid in a pediatric patient.

Modeling the relative risk of incidence and mortality of select vaccine-preventable diseases by wealth group and geographic region in Ethiopia.

Immunization is one of the most effective public health interventions, saving millions of lives every year. Ethiopia has seen gradual improvements in immunization coverage and access to child health care services; however, inequalities in child mortality across wealth quintiles and regions remain persistent. We model the relative distributional incidence and mortality of four vaccine-preventable diseases (VPDs) (rotavirus diarrhea, human papillomavirus, measles, and pneumonia) by wealth quintile and geographic region in Ethiopia. Our approach significantly extends an earlier methodology, which utilizes the population attributable fraction and differences in the prevalence of risk and prognostic factors by population subgroup to estimate the relative distribution of VPD incidence and mortality. We use a linear system of equations to estimate the joint distribution of risk and prognostic factors in population subgroups, treating each possible combination of risk or prognostic factors as computationally distinct, thereby allowing us to account for individuals with multiple risk factors. Across all modeling scenarios, our analysis found that the poor and those living in rural and primarily pastoralist or agrarian regions have a greater risk than the rich and those living in urban regions of becoming infected with or dying from a VPD. While in absolute terms all population subgroups benefit from health interventions (e.g., vaccination and treatment), current unequal levels and pro-rich gradients of vaccination and treatment-seeking patterns should be redressed so to significantly improve health equity across wealth quintiles and geographic regions in Ethiopia.

The determinants and impacts of age-disparate relationships on women in Zimbabwe: A life course perspective.

Age-disparate relationships (ADR) with older men have been studied mostly in the context of HIV and found to be associated with increased HIV prevalence among young women in sub-Saharan Africa. Less is known about the impact of ADR on the broader life course of women. The objectives of this study are to identify the factors associated with being in ADR and estimate the association between ADR and a set of life outcomes in Manicaland, Zimbabwe. We used data from a general population open-cohort survey from 1998 to 2013 in Manicaland. We applied binary logistic regression models to estimate the odds ratios for association between socio-demographic determinants and ADR and multinomial logistic regression models to estimate the association between ADR and women's life outcomes. We found that women with less education, younger age at first sex and first marriage were more likely to be in ADR, and women in ADR have male partners with less education and less skilled employment. In terms of life and relationship outcomes, women in ADR had mostly negative life outcomes compared to women not in ADR. Future policies and research on ADR in women should reflect these complexities and study a wider range of life outcomes, beyond the commonly studied narrower topics such as HIV.

Analysis of SARS-CoV-2 RNA on surfaces in New York City.

BACKGROUND: This study sought to determine the presence of SARS-CoV-2 virus on surfaces that trainees and faculty of an academic eye clinic came into contact with during daily life at the time of the COVID-19 pandemic in New York City. METHODS: This cross-sectional analysis involved collection of at least two samples by teams on four different days (November 9, 2020 - December 18, 2020) using sterile swabs (Puritan HydraFlock, Garden Grove, CA). Collection sites were grouped into four zones depending on proximity and amount of time personnel spent there. Samples were transported to the laboratory in transport medium and RNA was extracted using the QIAamp DSP Viral RNA Mini Kit (Qiagen, Germantown, MD). Presence of viral RNA was investigated using the Luna Universal Probe One-step RT-qPCR kit (New England Biolabs, Ipwsich, MA). RESULTS: 834 samples were submitted. Two were positive for SARS-CoV-2 RNA. The first was a sample from a patient bathroom sink handle in the main emergency department. The second was a nasal swab sample from a staff member who had been assigned to collect samples. Prior to this positive result, this asymptomatic staff member had tested positive for COVID-19, had quarantined for two weeks, and had received a negative test. CONCLUSION: Though COVID-19 is currently widespread in the United States, this study shows that health care personnel working in New York City at the Columbia University Irving Medical Center have a low chance of encountering viral RNA on surfaces they are in close contact with during daily life.

Trends and outcomes in primary health care expenditures in low-income and middle-income countries, 2000-2017.

INTRODUCTION: As the world responds to COVID-19 and aims for the Sustainable Development Goals, the potential for primary healthcare (PHC) is substantial, although the trends and effectiveness of PHC expenditure are unknown. We estimate PHC expenditure for each low-income and middle-income country between 2000 and 2017 and test which health outputs and outcomes were associated with PHC expenditure. METHODS: We used three data sources to estimate PHC expenditures: recently published health expenditure estimates for each low-income and middle-income country, which were constructed using 1662 country-reported National Health Accounts; proprietary data from IQVIA to estimate expenditure of prescribed pharmaceuticals for PHC; and household surveys and costing estimates to estimate inpatient vaginal delivery expenditures. We employed regression analyses to measure the association between PHC expenditures and 15 health outcomes and intermediate health outputs. RESULTS: PHC expenditures in low-income and middle-income countries increased between 2000 and 2017, from $41 per capita (95% uncertainty interval $33-$49) to $90 ($73-$105). Expenditures for low-income countries plateaued since 2014 at $17 per capita ($15-$19). As national income increased, the proportion of health expenditures on PHC generally decrease; however, the fraction of PHC expenditures spent via ambulatory care providers grew. Increases in the fraction of health expenditures on PHC was associated with lower maternal mortality rate (p value≤0.001), improved coverage of antenatal care visits (p value≤0.001), measles vaccination (p value≤0.001) and an increase in the Health Access and Quality index (p value≤0.05). PHC expenditure was not systematically associated with all-age mortality, communicable and non-communicable disease (NCD) burden. CONCLUSION: PHC expenditures were associated with maternal and child health but were not associated with reduction in health burden for other key causes of disability, such as NCDs. To combat changing disease burdens, policy-makers and health professionals need to adapt primary healthcare to ensure continued impact on emerging health challenges.

Health expenditures by services and providers for 195 countries, 2000-2017.

INTRODUCTION: National Health Accounts are a significant source of health expenditure data, designed to be comprehensive and comparable across countries. However, there is currently no single repository of this data and even when compiled major gaps persist. This research aims to provide policymakers and researchers with a single repository of available national health expenditures by healthcare functions (ie, services) and providers of such services. Leveraging these data within statistical methods, a complete set of detailed health expenditures is estimated. METHODS: A methodical compilation and synthesis of all available national health expenditure reports including disaggregation by healthcare functions and providers was conducted. Using these data, a Bayesian multivariate regression analysis was implemented to estimate national-level health expenditures by the cross-classification of functions and providers for 195 countries, from 2000 to 2017. RESULTS: This research used 1662 country-years and 110 070 data points of health expenditures from existing National Health Accounts. The most detailed country-year had 52% of the categories of interest reported. Of all health functions, curative care and medical goods were estimated to make up 51.4% (uncertainty interval (UI) 33.2% to 59.4%) and 17.5% (UI 13.0% to 26.9%) of total global health expenditures in 2017, respectively. Three-quarters of the global health expenditures are allocated to three categories of providers: hospital providers (35.4%, UI 30.3% to 38.9%), providers of ambulatory care (25.5%, UI 21.1% to 28.8%) and retailers of medical goods (14.4%, UI 12.4% to 16.3%). As gross domestic product increases, countries spend more on long-term care and less on preventive care. CONCLUSION: Disaggregated estimates of health expenditures are often unavailable and unable to provide policymakers and researchers a holistic understanding of how expenditures are used. This research aggregates reported data and provides a complete time-series of estimates, with uncertainty, of health expenditures by health functions and providers between 2000 and 2017 for 195 countries.

Orbital Lipofibromatosis in a Pediatric Patient.

A 10-month-old boy presented with a 3-month history of progressive left lower eyelid swelling. Examination demonstrated left lower eyelid fullness and hyperglobus with a fatty appearing inferior fornix mass. Imaging showed a mass isointense to fat in the left lower eyelid extending posteriorly, surrounding the inferior oblique with complete fatty infiltration, obscuration of the inferior rectus, and adherence to the globe. The patient underwent orbitotomy with biopsy and debulking of the tumor. Surgical pathology showed multiple fragments of adipose tissue with foci of plump and spindle-shaped cells arranged in bundles and fascicles, consistent with lipofibromatosis. This case illustrates a rare presentation of orbital lipofibromatosis in a pediatric patient.

Old vaccines for new infections: Exploiting innate immunity to control COVID-19 and prevent future pandemics.

The COVID-19 pandemic triggered an unparalleled pursuit of vaccines to induce specific adaptive immunity, based on virus-neutralizing antibodies and T cell responses. Although several vaccines have been developed just a year after SARS-CoV-2 emerged in late 2019, global deployment will take months or even years. Meanwhile, the virus continues to take a severe toll on human life and exact substantial economic costs. Innate immunity is fundamental to mammalian host defense capacity to combat infections. Innate immune responses, triggered by a family of pattern recognition receptors, induce interferons and other cytokines and activate both myeloid and lymphoid immune cells to provide protection against a wide range of pathogens. Epidemiological and biological evidence suggests that the live-attenuated vaccines (LAV) targeting tuberculosis, measles, and polio induce protective innate immunity by a newly described form of immunological memory termed "trained immunity." An LAV designed to induce adaptive immunity targeting a particular pathogen may also induce innate immunity that mitigates other infectious diseases, including COVID-19, as well as future pandemic threats. Deployment of existing LAVs early in pandemics could complement the development of specific vaccines, bridging the protection gap until specific vaccines arrive. The broad protection induced by LAVs would not be compromised by potential antigenic drift (immune escape) that can render viruses resistant to specific vaccines. LAVs might offer an essential tool to "bend the pandemic curve," averting the exhaustion of public health resources and preventing needless deaths and may also have therapeutic benefits if used for postexposure prophylaxis of disease.

A Review of Studies of the Association of Vision-Related Quality of Life with Measures of Visual Function and Structure in Patients with Glaucoma in the United States.

Purpose: To investigate the association of quality of life (QoL) with ocular structure and function in glaucoma patients, and to identify which aspects of QoL are most closely tied to Visual Field (VF) and Visual Acuity (VA).Methods: We conducted a comprehensive review of studies on QoL in glaucoma patients using PubMed, Web of Science, and Google Scholar (from 1 January 1997 to 7 December 2019). A total of 21 studies in the United States that used the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ) or 51-item NEI VFQ were included. A descriptive analysis of data from the selected studies was conducted. The association between QoL scores and visual function and structure was investigated by ranking the strength of association on a scale from 1 (weakest) to 12 (strongest).Results: Studies reported correlations between QoL scores and Visual Structure. Associations were also reported between QoL and Visual Function both cross-sectionally and longitudinally, with a stronger association of VF and VA with distance activities (average ranking 9.1 and 9.6), vision-specific dependency (8.7 and 8.9), and driving (8.6 and 9.7). Vision-specific mental health (6.5 and 4.9), vision-specific social functioning (8.4 and 6.2), and vision-specific role difficulties (7.1 and 6.6) domains were more associated with VF than with VA.Conclusion: Our study was the first to quantify and rank the strength of association between visual function and QoL domains. Driving and psycho-social QoL domains tended to be most affected by glaucoma-related deterioration of visual function. QoL scores could be used for more patient-centered disease management.