Multispectral label-free in vivo cellular imaging of human retinal pigment epithelium using adaptive optics fluorescence lifetime ophthalmoscopy improves feasibility for low emission analysis and increases sensitivity for detecting changes with age and eccentricity.

Significance: Adaptive optics fluorescence lifetime ophthalmoscopy (AOFLIO) provides a label-free approach to observe functional and molecular changes at cellular scale in vivo. Adding multispectral capabilities improves interpretation of lifetime fluctuations due to individual fluorophores in the retinal pigment epithelium (RPE). Aim: To quantify the cellular-scale changes in autofluorescence with age and eccentricity due to variations in lipofuscin, melanin, and melanolipofuscin in RPE using multispectral AOFLIO. Approach: AOFLIO was performed on six subjects at seven eccentricities. Four imaging channels ( λ ex / λ em ) were used: 473/SSC, 473/LSC, 532/LSC, and 765/NIR. Cells were segmented and the timing signals of each pixel in a cell were combined into a single histogram, which were then used to compute the lifetime and phasor parameters. An ANOVA was performed to investigate eccentricity and spectral effects on each parameter. Results: A repeatability analysis revealed < 11.8 % change in lifetime parameters in repeat visits for 532/LSC. The 765/NIR and 532/LSC had eccentricity and age effects similar to previous reports. The 473/LSC had a change in eccentricity with mean lifetime and a phasor component. Both the 473/LSC and 473/SSC had changes in eccentricity in the short lifetime component and its relative contribution. The 473/SSC had no trend in eccentricity in phasor. The comparison across the four channels showed differences in lifetime and phasor parameters. Conclusions: Multispectral AOFLIO can provide a more comprehensive picture of changes with age and eccentricity. These results indicate that cell segmentation has the potential to allow investigations in low-photon scenarios such as in older or diseased subjects with the co-capture of an NIR channel (such as 765/NIR) with the desired spectral channel. This work represents the first multispectral, cellular-scale fluorescence lifetime comparison in vivo in the human RPE and may be a useful method for tracking diseases.

Evaluating Safety of Ring Versus Clamp Devices in Neonatal Circumcision: A Meta-Analysis.

BACKGROUND: While device-based circumcision is considered non-inferior to traditional dissection, there is no consensus on the efficacy and safety of ring devices in comparison with clamp devices. We aimed to compare the safety outcomes of ring-based versus clamp-based circumcision techniques in neonates. METHODS: MEDLINE, EMBASE, Scopus, and CINAHL were searched following the Cochrane collaboration (PRISMA guidelines), without language restrictions, to identify relevant randomized controlled trials. Adverse events, bleeding events, infection events, and procedure time were extracted and analyzed from the selected studies. RESULTS: From 1661 citations, seven trials were included, encompassing 3390 patients. These studies compared ring-based to clamp-based circumcision devices in neonates. No significant difference was found in overall adverse events between the two groups. However, ring devices showed significantly fewer bleeding events compared to clamp devices. Infection events and procedure time were similar for both groups. CONCLUSIONS: Both ring and clamp devices have similar safety profiles, with ring devices potentially offering a reduced risk of bleeding. A comprehensive understanding of ring-specific complications and cosmetic outcomes is necessary for a more complete evaluation of these circumcision techniques. Our analysis is limited from a lack of detailed examination of ring-specific complications and their impact on cosmetic results. The included studies varied in quality, and some exhibited a risk of bias. LEVEL OF EVIDENCE: Level IV Treatment Study.

Near Infrared Autofluorescence Lifetime Imaging of Human Retinal Pigment Epithelium Using Adaptive Optics Scanning Light Ophthalmoscopy.

Purpose: To demonstrate the first near-infrared adaptive optics fluorescence lifetime imaging ophthalmoscopy (NIR-AOFLIO) measurements in vivo of the human retinal pigment epithelial (RPE) cellular mosaic and to visualize lifetime changes at different retinal eccentricities. Methods: NIR reflectance and autofluorescence were captured using a custom adaptive optics scanning light ophthalmoscope in 10 healthy subjects (23-64 years old) at seven eccentricities and in two eyes with retinal abnormalities. Repeatability was assessed across two visits up to 8 weeks apart. Endogenous retinal fluorophores and hydrophobic whole retinal extracts of Abca4-/- pigmented and albino mice were imaged to probe the fluorescence origin of NIR-AOFLIO. Results: The RPE mosaic was resolved at all locations in five of seven younger subjects (<35 years old). The mean lifetime across near-peripheral regions (8° and 12°) was longer compared to near-foveal regions (0° and 2°). Repeatability across two visits showed moderate to excellent correlation (intraclass correlation: 0.88 [τm], 0.75 [τ1], 0.65 [τ2], 0.98 [a1]). The mean lifetime across drusen-containing eyes was longer than in age-matched healthy eyes. Fluorescence was observed in only the extracts from pigmented Abca4-/- mouse. Conclusions: NIR-AOFLIO was repeatable and allowed visualization of the RPE cellular mosaic. An observed signal in only the pigmented mouse extract infers the fluorescence signal originates predominantly from melanin. Variations observed across the retina with intermediate age-related macular degeneration suggest NIR-AOFLIO may act as a functional measure of a biomarker for in vivo monitoring of early alterations in retinal health.

Fluorescence Lifetime Imaging of Human Retinal Pigment Epithelium in Pentosan Polysulfate Toxicity Using Adaptive Optics Scanning Light Ophthalmoscopy.

Purpose: Fluorescence lifetime ophthalmoscopy (FLIO) is an emerging clinical modality that could provide biomarkers of retinal health beyond fluorescence intensity. Adaptive optics (AO) ophthalmoscopy provides the confocality to measure fluorescence lifetime (FL) primarily from the retinal pigment epithelium (RPE) whereas clinical FLIO has greater influence from fluorophores in the inner retina and lens. Adaptive optics fluorescence lifetime ophthalmoscopy (AOFLIO) measures of FL in vivo could provide insight into RPE health at different stages of disease. In this study, we assess changes in pentosan polysulfate sodium (PPS) toxicity, a recently described toxicity that has clinical findings similar to advanced age-related macular degeneration. Methods: AOFLIO was performed on three subjects with PPS toxicity (57-67 years old) and six age-matched controls (50-64 years old). FL was analyzed with a double exponential decay curve fit and with phasor analysis. Regions of interest (ROIs) were subcategorized based on retinal features on optical coherence tomography (OCT) and compared to age-matched controls. Results: Twelve ROIs from PPS toxicity subjects met the threshold for analysis by curve fitting and 15 ROIs met the threshold for phasor analysis. Subjects with PPS toxicity had prolonged FL compared to age-matched controls. ROIs of RPE degeneration had the longest FLs, with individual pixels extending longer than 900 ps. Conclusions: Our study shows evidence that AOFLIO can provide meaningful information in outer retinal disease beyond what is obtainable from fluorescence intensity alone. More studies are needed to determine the prognostic value of AOFLIO.

Contemporary trends in incident ischemic stroke, intracranial hemorrhage, and mortality in individuals with atrial fibrillation.

BACKGROUND: The prognosis for atrial fibrillation (AF) patients is based on data that is decades old. Given evolving standards of clinical practice, we sought to evaluate temporal trends in clinically important outcomes among patients with AF. METHODS: California's Department of Health Care Access and Information databases were used to identify adults aged ≥ 18 years with AF receiving hospital-based care in California. We compared 3 time-periods: 2005-2009, 2010-2014, and 2015-2019. ICD codes were used to identify chronic diseases and acute events. The outcomes were incident ischemic stroke, intracranial hemorrhage, and overall mortality. RESULTS: We included 2 009 832 patients with AF (52.7% males, 70.7% Whites, and mean age of 75.0 years), divided in 3 cohorts: 2005-2009 (n = 738 954), 2010-2014 (n = 609 447), and 2015-2019 (n = 661 431). Each outcome became substantially less common with time: compared to 2005-2009, AF patients diagnosed in 2015-2019 experienced a 34% (adjusted hazard ratio [HR] 0.66, 95% CI 0.64-0.69), 22% (HR 0.78, 0.75-0.82), and 24% (HR 0.76, 0.75-0.77) reduction in risk of incident ischemic stroke, intracranial hemorrhage, and mortality, respectively. Between 2005-2009 and 2015-2019, patients aged ≥ 65 years experienced more reductions in each outcome compared to younger patients (p < 0.001 for all), and declines in each outcome were significantly lower for Hispanics and Blacks compared to white patients. CONCLUSION: The risks of stroke, intracranial hemorrhage, and death have significantly declined among AF patients, although differences in the magnitude of improvement of these outcomes by demographic groups were observed. Commonly described estimates of the prognosis for AF patients should be updated to reflect contemporary care.

Systemic infarcts among patients with atrial fibrillation.

BACKGROUND: The epidemiology of atrial fibrillation (AF)-associated thromboembolic complications outside of ischemic strokes has not been thoroughly elucidated. OBJECTIVE: The aim of this study was to describe the epidemiology of AF-associated systemic infarcts and relevant interactions by sex and race/ethnicity. METHODS: Using the Office of Statewide Health Planning and Development, we performed a longitudinal analysis of patients aged ≥18 years who received ambulatory surgery, emergency, or inpatient medical care in California between 2005 and 2015. We determined the distribution of infarct locations and risks of systemic infarcts for patients with AF. Interaction analyses by sex and race/ethnicity were conducted. RESULTS: Of 1,321,694 patients with AF, the average annual rate of systemic infarct was 2.1% ± 0.18% compared with 0.56% ± 0.06% in the 22,944,488 patients without AF. The increased frequency of these infarcts was observed for every body area investigated. After adjustment for potential confounders and mediators, patients with AF experienced a 45% increased risk of a systemic infarct (hazard ratio, 1.45; 95% confidence interval, 1.44-1.47; P < .001). Women, Asians, Blacks, and Hispanics each exhibited a statistically significant heightened relative risk of systemic infarcts in the presence of AF. CONCLUSION: AF increases the risk of infarcts throughout the body. Susceptibility to these systemic infarcts varies by sex and race/ethnicity in patterns similar to differential risks for stroke. The presence of a systemic infarct in the absence of a clear cause should raise suspicion for AF, and the potential benefits of AF prevention and anticoagulation should be considered beyond only infarcts to the brain.

Preceding Night Sleep Quality and Atrial Fibrillation Episodes in the I-STOP-AFIB Randomized Trial.

BACKGROUND: Chronic sleep disruption is associated with incident atrial fibrillation (AF), but it is unclear whether poor sleep quality acutely triggers AF. OBJECTIVES: The aim of this study was to characterize the relationship between a given night's sleep quality and the risk of a discrete AF episode. METHODS: Patients with symptomatic paroxysmal AF in the I-STOP-AFIB (Individualized Studies of Triggers of Paroxysmal Atrial Fibrillation) trial reported sleep quality on a daily basis. Participants were also queried daily regarding AF episodes and were provided smartphone-based mobile electrocardiograms (ECGs) (KardiaMobile, AliveCor). RESULTS: Using 15,755 days of data from 419 patients, worse sleep quality on any given night was associated with a 15% greater odds of a self-reported AF episode the next day (OR: 1.15; 95% CI: 1.10-1.20; P < 0.0001) after adjustment for the day of the week. No statistically significant associations between worsening sleep quality and mobile ECG-confirmed AF events were observed (OR: 1.04; 95% CI: 0.95-1.13; P = 0.43), although substantially fewer of these mobile ECG-confirmed events may have limited statistical power. Poor sleep was also associated with longer self-reported AF episodes, with each progressive category of worsening sleep associated with 16 (95% CI: 12-21; P < 0.001) more minutes of AF the next day. CONCLUSIONS: Poor sleep was associated with an immediately heightened risk for self-reported AF episodes, and a dose-response relationship existed such that progressively worse sleep was associated with longer episodes of AF the next day. These data suggest that sleep quality may be a potentially modifiable trigger relevant to the near-term risk of a discrete AF episode.

Cannabis use and incident atrial fibrillation in a longitudinal cohort.

BACKGROUND: Cannabis use is increasing worldwide. While prior studies have reported an association between cannabis use and a higher risk of atrial fibrillation (AF), most were cross-sectional and generally relied on diagnostic coding to identify cannabis users, which may not be representative of the typical recreational cannabis user. OBJECTIVE: The purpose of this study was to examine the association between recreational cannabis use and lifetime AF risk. METHODS: We evaluated the AF risk of participants of the UK Biobank cohort who completed the cannabis use lifestyle questionnaire. Cannabis exposure was categorized as "Occasional Use" for less than 100 times used, "Frequent Use" for more than 100 times used, and "Never" users. AF events were identified using International Classification of Diseases codes. Cox models were used to estimate the hazard ratios (HRs) between cannabis use and incident AF and were subsequently adjusted for age, sex, race, alcohol, coffee, smoking, education, and baseline cardiovascular comorbidities. RESULTS: A total of 150,554 participants (mean age 63.4 ± 7.7 years; 86,487 (57.4%) female; and 33,442 (22.2%) using cannabis at least once) were followed for a mean period of 6.1 ± 0.6 years. After multivariable adjustment, there were no statistically significant differences in incident AF among occasional users (HR 0.98; 95% confidence interval 0.89-1.08) nor frequent users (HR 1.03; 95% confidence interval 0.81-1.32) as compared with never users. CONCLUSION: In a large prospective cohort study, there was no evidence that cannabis use was associated with a higher risk of incident AF. An evaluation of cannabis ingestion methods and quantification was not possible using the current data set.

Erratum: Adaptive optics fluorescence lifetime imaging ophthalmoscopy of in vivo human retinal pigment epithelium: erratum.

[This corrects the article on p. 1737 in vol. 13, PMID: 35414970.].

Cannabis, cocaine, methamphetamine, and opiates increase the risk of incident atrial fibrillation.

AIMS: Atrial fibrillation (AF) is now regarded as a preventable disease, requiring a search for modifiable risk factors. With legalization of cannabis and more lenient laws regarding the use of other illicit substances, investigation into the potential effects of methamphetamine, cocaine, opiate, and cannabis exposure on incident AF is needed. METHODS AND RESULTS: Using Office of Statewide Health Planning and Development databases, a longitudinal analysis was performed of adult Californians ≥18 years of age who received care in an emergency department, outpatient surgery facility, or hospital from 1 January 2005 to 31 December 2015. Associations between healthcare coding for the use of each substance and a new AF diagnosis were assessed. Among 23,561,884 patients, 98 271 used methamphetamine, 48 701 used cocaine, 10 032 used opiates, and 132 834 used cannabis. Of the total population, 998 747 patients (4.2%) developed incident AF during the study period. After adjusting for potential confounders and mediators, use of methamphetamines, cocaine, opiates, and cannabis was each associated with increased incidence of AF: hazard ratios 1.86 [95% confidence interval (CI) 1.81-1.92], 1.61 (95% CI 1.55-1.68), 1.74 (95% CI 1.62-1.87), and 1.35 (95% CI 1.30-1.40), respectively. Negative control analyses in the same cohort failed to reveal similarly consistent positive relationships. CONCLUSION: Methamphetamine, cocaine, opiate, and cannabis uses were each associated with increased risk of developing incident AF. Efforts to mitigate the use of these substances may represent a novel approach to AF prevention.

FBP1-Altered Carbohydrate Metabolism Reduces Leukemic Viability through Activating P53 and Modulating the Mitochondrial Quality Control System In Vitro.

Acute myeloid leukemia (AML)-the most frequent form of adult blood cancer-is characterized by heterogeneous mechanisms and disease progression. Developing an effective therapeutic strategy that targets metabolic homeostasis and energy production in immature leukemic cells (blasts) is essential for overcoming relapse and improving the prognosis of AML patients with different subtypes. With respect to metabolic regulation, fructose-1,6-bisphosphatase 1 (FBP1) is a gluconeogenic enzyme that is vital to carbohydrate metabolism, since gluconeogenesis is the central pathway for the production of important metabolites and energy necessary to maintain normal cellular activities. Beyond its catalytic activity, FBP1 inhibits aerobic glycolysis-known as the "Warburg effect"-in cancer cells. Importantly, while downregulation of FBP1 is associated with carcinogenesis in major human organs, restoration of FBP1 in cancer cells promotes apoptosis and prevents disease progression in solid tumors. Recently, our large-scale sequencing analyses revealed FBP1 as a novel inducible therapeutic target among 17,757 vitamin-D-responsive genes in MV4-11 or MOLM-14 blasts in vitro, both of which were derived from AML patients with FLT3 mutations. To investigate FBP1's anti-leukemic function in this study, we generated a new AML cell line through lentiviral overexpression of an FBP1 transgene in vitro (named FBP1-MV4-11). Results showed that FBP1-MV4-11 blasts are more prone to apoptosis than MV4-11 blasts. Mechanistically, FBP1-MV4-11 blasts have significantly increased gene and protein expression of P53, as confirmed by the P53 promoter assay in vitro. However, enhanced cell death and reduced proliferation of FBP1-MV4-11 blasts could be reversed by supplementation with post-glycolytic metabolites in vitro. Additionally, FBP1-MV4-11 blasts were found to have impaired mitochondrial homeostasis through reduced cytochrome c oxidase subunit 2 (COX2 or MT-CO2) and upregulated PTEN-induced kinase (PINK1) expressions. In summary, this is the first in vitro evidence that FBP1-altered carbohydrate metabolism and FBP1-activated P53 can initiate leukemic death by activating mitochondrial reprogramming in AML blasts, supporting the clinical potential of FBP1-based therapies for AML-like cancers.

Valvular disease burden in the modern era of percutaneous and surgical interventions: the UK Biobank.

BACKGROUND: The burden of valvular heart disease (VHD) has increased significantly among ageing populations, yet remains poorly understood in the present-day context of percutaneous and surgical interventions. OBJECTIVE: To define the incidence, clinical correlates and associated mortality of VHD in the UK Biobank cohort. METHODS: We interrogated data collected in the UK Biobank between 1 January 2000 and 30 June 2020. VHD incidence was determined using International Classification of Disease-10 codes for aortic stenosis (AS), aortic regurgitation (AR), mitral stenosis, mitral regurgitation (MR) and mitral valve prolapse. We calculated HRs for incident VHD and all-cause mortality. Clinical correlates of VHD included demographics, coronary artery disease, heart failure and atrial fibrillation. Surgical and percutaneous interventions for mitral and aortic VHD were considered time-dependent variables. RESULTS: Among 486 187 participants, the incidence of any VHD was 16 per 10 000 person-years, with highest rates for MR (8.2), AS (7.2) and AR (5.0). Age, heart failure, coronary artery disease and atrial fibrillation were significantly associated with all types of VHD. In our adjusted model, aortic and mitral VHD had an increased risk of all-cause death compared with no VHD (HR 1.62, 95% CI 1.44 to 1.82, p<0.001 and HR 1.25, 95% CI 1.09 to 1.44, p=0.002 for aortic and mitral VHD, respectively). CONCLUSION: VHD continues to constitute a significant public health burden, with MR and AS being the most common. Age and cardiac comorbidities remain strong risk factors for VHD. In the modern era of percutaneous and surgical interventions, mortality associated with VHD remains high.

Adaptive optics fluorescence lifetime imaging ophthalmoscopy of in vivo human retinal pigment epithelium.

The intrinsic fluorescence properties of lipofuscin - naturally occurring granules that accumulate in the retinal pigment epithelium - are a potential biomarker for the health of the eye. A new modality is described here which combines adaptive optics technology with fluorescence lifetime detection, allowing for the investigation of functional and compositional differences within the eye and between subjects. This new adaptive optics fluorescence lifetime imaging ophthalmoscope was demonstrated in 6 subjects. Repeated measurements between visits had a minimum intraclass correlation coefficient of 0.59 Although the light levels were well below maximum permissible exposures, the safety of the imaging paradigm was tested using clinical measures; no concerns were raised. This new technology allows for in vivo adaptive optics fluorescence lifetime imaging of the human RPE mosaic.

Digital Health Skillsets and Digital Preparedness: Comparison of Veterans Health Administration Users and Other Veterans Nationally.

BACKGROUND: As health care systems shift to greater use of telemedicine and digital tools, an individual's digital health literacy has become an important skillset. The Veterans Health Administration (VA) has invested resources in providing digital health care; however, to date, no study has compared the digital health skills and preparedness of veterans receiving care in the VA to veterans receiving care outside the VA. OBJECTIVE: The goal of the research was to describe digital health skills and preparedness among veterans who receive care within and outside the VA health care system and examine whether receiving care in the VA is associated with digital preparedness (reporting more than 2 digital health skills) after accounting for demographic and social risk factors. METHODS: We used cross-sectional data from the 2016-2018 National Health Interview Survey to identify veterans (aged over 18 years) who obtain health care either within or outside the VA health care system. We used multivariable logistic regression models to examine the association of sociodemographic (age, sex, race, ethnicity), social risk factors (economic instability, disadvantaged neighborhood, low educational attainment, and social isolation), and health care delivery location (VA and non-VA) with digital preparedness. RESULTS: Those who received health care within the VA health care system (n=3188) were younger (age 18-49 years: 33.3% [95% CI 30.7-36.0] vs 24.2% [95% CI 21.9-26.5], P<.01), were more often female (34.7% [95% CI 32.0-37.3] vs 6.6% [95% CI 5.5-7.6], P<.01) and identified as Black (13.1% [95% CI 11.2-15.0] vs 10.2% [95% CI 8.7-11.8], P<.01), and reported greater economic instability (8.3% [95% CI 6.9-9.8] vs 5.5% [95% CI 4.6-6.5], P<.01) and social isolation (42.6% [95% CI 40.3-44.9] vs 35.4% [95% CI 33.4-37.5], P<.01) compared to veterans who received care outside the VA (n=3393). Veterans who obtained care within the VA reported more digital health skills than those who obtained care outside the VA, endorsing greater rates of looking up health information on the internet (51.8% [95% CI 49.2-54.4] vs 45.0% [95% CI 42.6-47.3], P<.01), filling a prescription using the internet (16.2% [95% CI 14.5-18.0] vs 11.3% [95% CI 9.6-13.0], P<.01), scheduling a health care appointment on the internet (14.1% [95% CI 12.4-15.8] vs 11.6% [95% CI 10.1-13.1], P=.02), and communicating with a health care provider by email (18.0% [95% CI 16.1-19.8] vs 13.3% [95% CI 11.6-14.9], P<.01). Following adjustment for sociodemographic and social risk factors, receiving health care from the VA was the only characteristic associated with higher odds (adjusted odds ratio [aOR] 1.36, 95% CI 1.12-1.65) of being digitally prepared. CONCLUSIONS: Despite these demographic disadvantages to digital uptake, veterans who receive care in the VA reported more digital health skills and appear more digitally prepared than veterans who do not receive care within the VA, suggesting a positive, system-level influence on this cohort.

Association of Social Determinants of Health and Their Cumulative Impact on Hospitalization Among a National Sample of Community-Dwelling US Adults.

IMPORTANCE: While the association between Social Determinants of Health (SDOH) and health outcomes is well known, few studies have explored the impact of SDOH on hospitalization. OBJECTIVE: Examine the independent association and cumulative effect of six SDOH domains on hospitalization. DESIGN: Using cross-sectional data from the 2016-2018 National Health Interview Surveys (NHIS), we used multivariable logistical regression models controlling for sociodemographics and comorbid conditions to assess the association of each SDOH and SDOH burden (i.e., cumulative number of SDOH) with hospitalization. SETTING: National survey of community-dwelling individuals in the US PARTICIPANTS: Adults ≥18 years who responded to the NHIS survey EXPOSURE: Six SDOH domains (economic instability, lack of community, educational deficits, food insecurity, social isolation, and inadequate access to medical care) MEASURES: Hospitalization within 1 year RESULTS: Among all 55,186 respondents, most were ≤50 years old (54.2%), female (51.7%, 95% CI 51.1-52.3), non-Hispanic (83.9%, 95% CI 82.4-84.5), identified as White (77.9%, 95% CI 76.8-79.1), and had health insurance (90%, 95% CI 88.9-91.9). Hospitalized individuals (n=5506; 8.7%) were more likely to be ≥50 years old (61.2%), female (60.7%, 95% CI 58.9-62.4), non-Hispanic (87%, 95% CI 86.2-88.4), and identify as White (78.5%, 95% CI 76.7-80.3), compared to those who were not hospitalized. Hospitalized individuals described poorer overall health, reporting higher incidence of having ≥5 comorbid conditions (38.9%, 95% CI 37.1-40.1) compared to those who did not report a hospitalization (15.9%, 95% CI 15.4-16.5). Hospitalized respondents reported higher rates of economic instability (33%), lack of community (14%), educational deficits (67%), food insecurity (14%), social isolation (34%), and less access to health care (6%) compared to non-hospitalized individuals. In adjusted analysis, food insecurity (OR: 1.36, 95% CI 1.22-1.52), social isolation (OR: 1.17, 95% CI 1.08-1.26), and lower educational attainment (OR: 1.12, 95% CI 1.02-1.25) were associated with hospitalization, while a higher SDOH burden was associated with increased odds of hospitalization (3-4 SDOH [OR: 1.25, 95% CI 1.06-1.49] and ≥5 SDOH [OR: 1.72, 95% CI 1.40-2.06]) compared to those who reported no SDOH. CONCLUSIONS: Among community-dwelling US adults, three SDOH domains: food insecurity, social isolation, and low educational attainment increase an individual's risk of hospitalization. Additionally, risk of hospitalization increases as SDOH burden increases.

Research productivity and impact of Canadian academic ophthalmologists: trends in H-index, gender, subspecialty, and faculty appointment.

OBJECTIVE: H-index has historically functioned as a metric of academic success for acquisition of research grants, awards, and faculty appointments. Our objective was to characterize the landscape of Canadian academic ophthalmology on the basis of research productivity and impact-as measured by H-index-with gender, subspecialty, and faculty appointment. DESIGN: Cross-sectional study based on data abstracted from publicly available databases. PARTICIPANTS: Academic ophthalmologists from all schools in Canada with an ophthalmology residency program. METHODS: Academic ophthalmologists and their faculty appointments were identified from university websites. gender was determined from available provincial College of Physicians and Surgeons or ophthalmology society databases. H-indices were collected from Scopus and Web of Science. Descriptive, univariate, and multivariate statistics were used to analyze the relationship of H-index with gender, faculty appointment, and subspecialty. RESULTS: We included data from 696 academic ophthalmologists. The mean H-indices for lecturers and assistant, associate, and full professors were 4.0 (±5.6), 5.6 (±5.0), 8.8 (±6.3), and 15 (±12), respectively. H-index had a significant positive correlation with faculty appointment (0.521, 95% confidence interval 0.469-0.579, p = 1.77e-41). The mean H-index was 6.7 (±8.2) for women and 8.1(±8.4) for men (p = 0.0635). Women comprised 27% of faculty positions, and men were more likely to have a higher faculty appointment than women (p = 0.0073). The top subspecialties for underrepresentation of women were surgical retina, medical retina, and oculoplastics. CONCLUSIONS: Faculty appointments are associated with research productivity, as measured by H-index. There are significant gender disparities in faculty appointments and subspecialty representation. Future directions include exploring other contributory factors to success in academic ophthalmology.

The effect of time interval of vaginal ring pessary replacement for pelvic organ prolapse on complications and patient satisfaction: A randomised controlled trial.

OBJECTIVES: Limited data are available on the effect of the time interval of vaginal ring pessary replacement for pelvic organ prolapse (POP). This study investigated the effect of different replacement intervals on complications and patient satisfaction. STUDY DESIGN: A double-blinded, randomized controlled trial was conducted in a tertiary urogynecology center. Women with a vaginal ring pessary for POP (stage I to IV) were randomly allocated to two groups: 3-monthly or 6-monthly ring pessary replacement. All women were blinded to the replacement interval. Investigators were blinded during outcome assessment. Subjects were followed up for 6 months. MAIN OUTCOME MEASURES: The primary outcomes were the complication rates and patient satisfaction scores at 6 months. Secondary outcomes were the change in patient-reported symptoms and staging of POP. RESULTS: Of 101 women were screened from June 2016 to November 2017, 60 were recruited and randomly allocated: 30 to the 3-monthly replacement group and 30 to the 6-monthly replacement group. The overall complication rate in the 6-monthly group was higher than that in the 3-monthly group at the third visit (9 [30%] vs. 3[10.3%]; OR 3.71; 95%CI 0.89-15.58), but the difference was not statistically significant (p = 0.061). There were no statistically significant differences between groups in patient satisfaction scores, other prolapse-related symptoms or staging of POP. CONCLUSIONS: We provide evidence on the effect of replacement interval for a vaginal pessary on complications and patient satisfaction. A higher complication rate was found in the 6-monthly group than in the 3-monthly group, although the difference was not statistically significant. Patient satisfaction scores were similar in both groups.

Effect-based approach for screening of chemical mixtures in whole blood of green turtles from the Great Barrier Reef.

Organisms are exposed to mixtures of both known and unknown chemicals which are diverse and variable, and thus difficult and costly to characterise and monitor using traditional target analyses. The objective of this study was to validate and apply in vitro effect-based methods by which whole blood can be used to screen internal exposure to such complex chemical mixtures. For this study, we used whole blood of green sea turtles (Chelonia mydas). To ensure the chemical mixture in blood is transferred with minimal losses or bias, we tested a modified QuEChERS extraction method specifically developed for multi- and non-target instrument analysis. The extracts were dosed to a battery of in vitro bioassays (AhR-CAFLUX, AREc32, NFκB-bla, VM7Luc4E2, Microtox), each with a different mode of action (e.g., AhR receptor mediated xenobiotics, NrF2-mediated oxidative stress, NFκB mediated response to inflammation, estrogen activity and baseline toxicity oxidative stress, respectively) in order to cover a wide spectrum of chemicals. Results confirmed the absence of interferences of the blood extract with the responses of the different assays, thus indicating the methods' compatibility with effect-based screening approaches. To apply this approach, whole blood samples were collected from green turtles foraging in agricultural, urban and remote areas of the Australian Great Barrier Reef. The effect-based screening revealed significant differences in exposure, with higher induction of AhR-CAFLUX, AREc32 and Microtox assays in turtles from the agricultural foraging ground. Overall, these results corroborated with concurrent health, target and non-target analyses in the same animals performed as part of a larger program. This study provides evidence that the proposed effect-based approach is suitable for screening and evaluating internal exposure of organisms to chemical mixtures. The approach could be valuable for advancing understanding on multiple levels ranging from identification of priority chemicals in effect-directed investigations to exploring relationships between exposure and disease, not only in sea turtles, but in any organism.