Synergistic Impact of Visual and Cognitive Impairments on Health-Related Quality of Life in a Multiethnic Asian Population.

INTRODUCTION: The concomitant impact of visual impairment (VI) and cognitive impairment (CI) on health-related quality of life (HRQoL) in older adults is unclear. We aimed to determine the synergistic effect of baseline VI and CI on HRQoL decline at 6 years in multiethnic Asians. METHODS: We included Chinese, Malay, and Indian adults aged ≥60 years who participated in baseline (2004-2011) and 6-year (2011-2017) follow-up visits of the Singapore Epidemiology of Eye Diseases Study, a population-based cohort study in Singapore. Visual acuity (VA) was objectively measured at both visits, with VI defined as presenting VA >0.3 LogMAR in the better eye. CI was defined as Abbreviated Mental Test scores of ≤6 and ≤8 for individuals with ≤6 and >6 years of formal education, respectively. HRQoL was measured using the European Quality of Life-5 Dimensions (EQ-5D) questionnaire. HRQoL decline was defined as the difference in the composite EQ-5D scores at baseline and 6-year follow-up and deemed clinically meaningful if the reduction was equal to or larger than the minimal clinically important difference. Multivariable linear regression assessed the independent associations and synergism (ß interaction) between baseline VI and CI on EQ-5D decline. RESULTS: Of the 2,433 participants (mean [SD] age: 67.6 [5.5]) at baseline, 559, 120, and 151 had VI only, CI only, and both impairments, respectively. HRQoL decline in individuals with baseline comorbid VI-CI was clinically meaningful and was 2.0 times (ß = -0.044, 95% confidence interval: -0.077 to -0.010) and 3.7 times (ß = -0.065, 95% confidence interval: -0.11 to -0.022) larger than those with VI only and CI only, respectively. Importantly, there was a significant synergism (ß interaction = -0.048, 95% confidence interval: -0.095 to -0.001) between baseline VI and CI as predictors of HRQoL decline, suggesting that individuals having both conditions concurrently had a greater HRQoL reduction than the sum in those with VI alone and CI alone. The affected HRQoL domains included mobility and usual activities. CONCLUSIONS: Concomitant VI-CI potentiated HRQoL decline to a greater extent than the sum of individual contributions of VI and CI, suggesting synergism. Our results suggest that rehabilitative interventions such as the use of mobility aids and occupational therapy are needed to maintain HRQoL in older adults with concomitant VI-CI. Moreover, preventive interventions targeting at early detection and management of both VI and CI may also be beneficial.

Prevalence, associated risk factors; and patient and economic impact of multiple sensory impairment in a multi-ethnic elderly population in Singapore: the PIONEER study.

BACKGROUND: To determine the prevalence, risk factors; and impact on patient health and economic outcomes across the laterality spectrum of multiple sensory impairment (MSI) in a multi-ethnic older Asian population. METHODS: In this population-based study of Singaporeans aged ≥ 60 years, MSI was defined as concomitant vision (visual acuity > 0.3 logMAR), hearing (pure-tone air conduction average > 25 dB), and olfactory (score < 12 on the Sniffin' Sticks test) impairments across the spectrum of laterality (any, unilateral, combination [of unilateral and bilateral], and bilateral). RESULTS: Among 2,057 participants (mean ± SD 72.2 ± 0.2 years; 53.1% female), the national census-adjusted prevalence rates of any, unilateral, combination, and bilateral MSI were 20.6%, 1.2%, 12.2%, and 7.2%, respectively. Older age, male gender, low socioeconomic status (SES), and smoking (all p < 0.05) were independently associated with higher likelihood of any MSI. Compared to those with no sensory loss, those with MSI had significantly decreased mobility (range 5.4%-9.2%), had poor functioning (OR range 3.25-3.45) and increased healthcare costs (range 4-6 folds) across the laterality spectrum. Additionally, bilateral MSI had a significant decrease in HRQoL (5.5%, p = 0.012). CONCLUSIONS: MSI is a highly prevalent medical condition, with 1 in 5; and almost 1 in 10 community-dwelling older Asians having any and bilateral MSI, respectively, with a higher likelihood in men, smokers, and those with low SES. Critically, MSI has a substantial negative impact on patient health and economic outcomes across the laterality spectrum. Sensory testing is critical to detect and refer individuals with MSI for management to improve their functional independence and QoL.

Individual and combined associations of sarcopenia, osteoporosis and obesity with frailty in a multi-ethnic asian older adult population.

BACKGROUND: We explored the relationships between sarcopenia (SP), osteoporosis (OP), obesity (OB), (alone and in combination) with physical frailty (PF) in a multi-ethnic, population-based study of Asians aged ≥ 60 years. METHODS: Participants were enrolled from the PopulatION HEalth and Eye Disease PRofile in Elderly Singaporeans Study (PIONEER) study. PF was defined using the modified Fried phenotype; SP using the Asian Working Group for Sarcopenia 2019; OP using bone mineral density scores; and OB using the fat mass index. Modified Poisson regression models investigated the associations between exposures and PF, and the relative excess rates of PF due to interactions (RERI) to determine synergistic or antagonistic interactions. RESULTS: Of the 2643 participants, 54.8% was female; and 49.8%, 25.1%, 25.0% were Chinese, Indians, and Malays, respectively. 25%, 19.0% and 6.7% participants had OB only, SP only, and OP only, respectively. A total of 356 (17.5%), 151 (7.4%) and 97 (4.8%) had osteosarcopenia (OSP), sarcopenic obesity (SOB) and osteo-obesity (OOB), respectively; while 70 (3.5%) had all 3 morbid conditions (osteosarcopenic obesity, OSO). Both SP only and OB only were strongly associated with increased rates of PF (RR: 2.53, 95% CI: 1.95, 3.29; RR: 2.05, 95% CI: 1.58, 2.66 respectively); but not OP. Those with OSP, OOB and SOB were also associated with high risks of PF (RR: 2.82, 95% CI: 2.16, 3.68; RR: 2.34, 95% CI: 1.69, 3.23; and RR: 2.58, 95% CI: 1.95, 3.41, respectively) compared to robust individuals. Critically, individuals with OSO had the highest relative risk of having PF (RR: 3.06, CI: 2.28, 4.11). Only the sarcopenia-obesity interaction was significant, demonstrating negative synergism (antagonism). The concurrent presence of SP and OB was associated with a 100% lower rate of PF compared to the sum of the relatively rates of SP only and OB only. CONCLUSION: The prevalence of SP, OB and OP, alone and combined, is substantial in older Asians and their early identification is needed to mitigate the risk of frailty. OB may interact with SP in an antagonistic manner to moderate rates of frailty. Further longitudinal studies are needed to address causality and mechanistic underpinnings our findings.

Synthesis of 1,2,3-triazole-1,3,4-thiadiazole hybrids as novel α-glucosidase inhibitors by in situ azidation/click assembly.

α-Glucosidase inhibition is widely used in the oral management of diabetes mellitus (DM), a disease characterized by high blood sugar levels (hyperglycemia) and abnormal carbohydrate metabolism. In this respect, a series of 1,2,3-triazole-1,3,4-thiadiazole hybrids 7a-j were synthesized, inspired by a copper-catalyzed one-pot azidation/click assembly approach. All the synthesized hybrids were screened for inhibition of the α-glucosidase enzyme, displaying IC50 values ranging from 63.35 ± 0.72 to 613.57 ± 1.98 µM, as compared to acarbose (reference) with IC50 of 844.81 ± 0.53 µM. The hybrids 7h and 7e with 3-nitro and 4-methoxy substituents at the phenyl ring of the thiadiazole moiety were the best active hybrids of this series with IC50 values of 63.35 ± 0.72 µM, and 67.61 ± 0.64 µM, respectively. Enzyme kinetics analysis of these compounds revealed a mixed mode of inhibition. Moreover, molecular docking studies were also performed to gain insights into the structure-activity-relationships of the potent compounds and their corresponding analogs.

Flavone-1,2,3-triazole derivatives as potential α-glucosidase inhibitors: Synthesis, enzyme inhibition, kinetic analysis and molecular docking study.

α-Glucosidase inhibitors are considered prime therapeutics in the management of type-2 diabetes and are preferred due to their localized action ushered by limited side effects. In this regard, nineteen new flavone-1,2,3-triazole derivatives have been designed and synthesized via utilizing an efficient click reaction protocol, and screened for the inhibition of the α-glucosidase enzyme. The reaction conditions were mild, good yielding and required easy work up. All the synthesized flavone-triazole derivatives were found more active against the yeast α-glucosidase with IC50 values ranging from 24.37 ± 0.55-168.44 ± 0.77 µ M as compared to standard inhibitor acarbose (IC50 = 844.81 ± 0.53 µM). The derivatives with 2,5­dichloro 9k (IC50 = 24.37 ± 0.55 µM) and 4­chloro 9d (IC50 = 24.77 ± 0.30 µM) substituent bearing an amide linkage were the most active. In the kinetic study of most active derivatives 9k and 9d, they were found to be mixed and uncompetitive inhibitors, respectively. In molecular docking studies, blind docking of the most active compounds was accomplished to find the interactions between the compounds and α-glucosidase that further confirms the mixed or uncompetitive nature of the inhibitors.

The longitudinal association between cognitive impairment and incident visual impairment in a multiethnic Asian population: a prospective cohort study.

BACKGROUND: The relationship between baseline cognitive impairment (CI) and incident visual impairment (VI) in Asians is unclear. OBJECTIVE: To determine the associations between baseline CI with incident VI and visual acuity (VA) at 6-year follow-up in multiethnic Asians. DESIGN: Cohort. SETTING: Population-based. SUBJECTS: Two thousand three hundred and twenty-four adults aged ≥60 years from the Singapore Epidemiology of Eye Diseases Study (response rate 64%). METHODS: CI was defined using the validated Abbreviated Mental Test (AMT). VA was objectively measured using a LogMAR chart. Any incident VI was defined as having no VI (Snellen's VA better than or equal to 20/40) at baseline but present (VA worse than 20/40) at 6-year follow-up. VI severity was defined according to the International Classification of Diseases, 11th Revision. Associations were assessed using logistic and linear regression models. RESULTS: Of the 2,324 participants, 248 had CI at baseline. Presence of baseline CI was associated with more than twice the odds of any incident VI, incident mild and moderate-severe VI (OR [95% confidence interval]: 2.48 [1.55-3.90], 2.07 [1.17-3.55], and 2.61 [1.36-4.93], respectively) and worse VA (ß [95% confidence interval]: 0.026 [0.006-0.046]) at 6-year follow-up. The leading causes of incident VI were cataract and under-corrected refractive error. CONCLUSIONS: Older adults with CI had more than double the odds of VI development and poorer VA than their cognitively intact counterparts, and most causes of incident VI were correctable. Strategies such as targeted vision screening and early intervention for early detection and management of vision loss in patients with cognitive decline are warranted.

The Differential Impact of Age on Vision-Related Quality of Life across the Visual Impairment Spectrum.

PURPOSE: Visual impairment (VI) can have a detrimental impact on vision-related quality of life (VRQoL), but it is still unclear how this relationship varies with age across the VI spectrum. We determined the age-stratified, cross-sectional, and longitudinal associations between VI severity and VRQoL. DESIGN: The baseline and follow-up Singapore Chinese Eye Studies (SCES-1/-2; 2009-2011 and 2015-2017). PARTICIPANTS: A total of 3068 SCES-1 participants (mean age [standard deviation {SD}]: 59.5 [9.8] years; 50.2% female) and 1919 SCES-2 participants (mean age [SD]: 56.8 [8.3] years; 49.9% female). METHODS: Visual impairment was defined as visual acuity (VA) of > 0.3 logarithm of the minimum angle of resolution (logMAR) units; VI severity as mild-moderate (logMAR scores less than the median of all individuals with VI) and severe (logMAR scores median or greater); and VI incidence as VI absence at baseline, but evident at follow-up. Age was stratified into 40 to 49 years, 50 to 64 years, and ≥65 years. MAIN OUTCOME MEASURES: Rasch-transformed scores from the 32-item Impact of Visual Impairment (IVI) questionnaire were used to measure the "Reading," "Mobility," and "Emotional" domains of VRQoL. Multiple linear regression models determined the age-stratified associations of prevalent and incident VI with all 3 VRQoL outcomes, adjusted for potential confounders. RESULTS: Of the 807 persons with prevalent VI, 55.9% had mild-moderate and 44.1% had severe VI. Compared with no VI, age-stratified analyses showed that VRQoL decrements were significant only in the older age groups (mild-moderate VI: 6.2% and 8.1% reduction in Mobility and Reading scores in those aged ≥ 65 years; severe VI: 8.5% to 13.4% reductions in the 3 VRQoL scores in those aged ≥ 50 years). This interaction with older age became more pronounced with incident VI (N = 168), where decrements in all 3 VRQoL domains were evident only in those aged ≥65 years compared with persons without incident VI. CONCLUSIONS: Our results suggest that the VI-VRQoL associations are driven mainly by older individuals aged ≥65 years, highlighting the need for effective regular screening and early intervention modalities to prevent the presence and onset of VI, and subsequent VRQoL declines, in these individuals.

The Bidirectional Relationship between Vision and Cognition: A Systematic Review and Meta-analysis.

TOPIC: Visual impairment (VI) and cognitive impairment (CIM) are prevalent age-related conditions that impose substantial burden on the society. Findings on the hypothesized bidirectional association of VI and CIM remains equivocal. Hence, we conducted a systematic review and meta-analysis to examine this bidirectional relationship. CLINICAL RELEVANCE: Sixty percent risk of CIM has not been well elucidated in the literature. A bidirectional relationship between VI and CIM may support the development of strategies for early detection and management of risk factors for both conditions in older people. METHODS: PubMed, Embase, and Cochrane Central registers were searched systematically for observational studies, published from inception until April 6, 2020, in adults 40 years of age or older reporting objectively measured VI and CIM assessment using clinically validated cognitive screening tests or diagnostic evaluation. Meta-analyses on cross-sectional and longitudinal associations between VI and CIM outcomes (any CIM assessed using screening tests and clinically diagnosed dementia) were examined. Random effect models were used to generate pooled odds ratios (ORs) and 95% confidence intervals (CIs). We also examined study quality, publication bias, and heterogeneity. RESULTS: Forty studies were included (n = 47 913 570). Meta-analyses confirmed that persons with VI were more likely to have CIM, with significantly higher odds of: (1) any CIM (cross-sectional: OR, 2.38 [95% CI, 1.84-3.07]; longitudinal: OR, 1.66 [95% CI, 1.46-1.89]) and (2) clinically diagnosed dementia (cross-sectional: OR, 2.43 [95% CI, 1.48-4.01]; longitudinal: OR, 2.09 [95% CI, 1.37-3.21]) compared with persons without VI. Significant heterogeneity was explained partially by differences in age, sex, and follow-up duration. Also, some evidence suggested that individuals with CIM, relative to cognitively intact persons, were more likely to have VI, with most articles (8/9 [89%]) reporting significantly positive associations; however, meta-analyses on this association could not be conducted because of insufficient data. DISCUSSION: Overall, our work suggests that VI is a risk factor of CIM, although further work is needed to confirm the association of CIM as a risk factor for VI. Strategies for early detection and management of both conditions in older people may minimize individual clinical and public health consequences.

The longitudinal psychological, physical activity, and financial impact of a COVID-19 lockdown on older adults in Singapore: The PIONEER-COVID population-based study.

BACKGROUND: Several countries have implemented 'lockdown' measures to curb the spread of the coronavirus disease 2019 (COVID-19). AIMS: To examine the psychological, physical activity (PA), and financial impact of a 2-month COVID-19 lockdown on older adults aged ≥60 years in Singapore, and to identify factors associated with adverse lockdown-related outcomes. METHOD: We interviewed 496 community-dwelling adults (mean age [standard deviation]: 73.8 [7.6] years; 54.8% female) during the lockdown who had previously participated in a population-based epidemiological study. Validated questionnaires were utilised to assess loneliness and depressive symptoms at both timepoints, while inhouse questionnaires were used to assess PA and financial difficulty during lockdown. Multivariable regression models determined the lockdown-related change in loneliness and depression scores, and the factors associated with adverse outcomes. RESULTS: Loneliness increased significantly during the lockdown period (p < 0.001) while depressive symptoms decreased (p = 0.022). Decreased PA, greater financial problems, male gender, Indian ethnicity, living alone, having a greater body mass index and perceived susceptibility to COVID-19 were all associated with worsening loneliness scores. A total of 36.9% and 19.6% participants reported decreased PA and had financial problems during the lockdown, respectively. Unemployment was associated with decreased PA, while self-employed individuals, cleaners, retail workers and smokers had greater odds of experiencing financial difficulty. CONCLUSION: Despite a decrease in depressive symptoms, our population of older Asians reported a significant increase in loneliness and decreased PA, with one-fifth experiencing financial problems during lockdown. Our data suggest that more targeted public health efforts are needed to reduce repercussions of future lockdowns.

Vision, vision-specific functioning and mobility, and their relationship with clinically assessed cognitive impairment.

BACKGROUND: The relationship between self-reported visual disability and cognitive impairment in older individuals is unclear. OBJECTIVE: To determine the relationship of vision-specific functioning (VSF), vision-specific mobility (VSM) and visual acuity (VA) with clinically assessed cognitive impairment in the Epidemiology of Dementia in Singapore study. DESIGN: Cross-sectional. SETTING: Population-based. SUBJECTS: Eight hundred and seventy-four adults aged ≥60 years at higher risk of possible cognitive impairment by the Abbreviated Mental Test and progressive forgetfulness question. METHODS: VSF and VSM were measured using Rasch-transformed continuous scores of two Impact of Vision Impairment questionnaire domains. Cognitive impairment was objectively determined using detailed neuropsychological testing and defined as no cognitive impairment (NCI), mild cognitive impairment-no dementia (CIND), moderate CIND only and moderate CIND or dementia. Associations were assessed using multinomial logistic regression models. RESULTS: Of the 874 participants (49.0% males, mean age (SD) 65.5 (7.0) years), 277, 281 and 316 had NCI, mild CIND and moderate CIND or dementia, respectively. Compared to NCI, the odds of moderate CIND, and moderate CIND or dementia increased for every SD worsening in VSF (OR: 1.44, 95% CI 1.14-1.82, and OR: 1.52, 95%CI 1.19-1.94, respectively) and VSM (OR: 1.42, 95%CI 1.11-1.81, and OR: 1.50, 95%CI 1.15-1.95). Similarly, the odds of mild CIND (OR: 1.62, 95%CI 1.19-2.22), moderate CIND (OR: 1.93, 95%CI 1.45-2.58), and moderate CIND or dementia (OR: 2.25, 95%CI 1.62-3.11) increased significantly with every SD worsening of VA. CONCLUSIONS: Our results emphasise the importance of interventions to prevent vision loss and improve quality of life to reduce likelihood of age-related cognitive decline.

Ultrasonographic predictors in chronic kidney disease: A hospital based case control study.

BACKGROUND: Prevalence of Chronic Kidney Disease (CKD) is increasing globally with the concomitant upsurge in diabetes mellitus and hypertension. We explored the research question whether Ultrasonographic (US) renal parameters are potential predictors of CKD? MATERIALS AND METHODS: A case control study was conducted at a tertiary care hospital that included 50 confirmed cases of CKD and 100 nondiseased controls. Renal length, renal parenchymal thickness, and renal cortical thickness were measured in both cases and controls by ultrasound examination. Corticomedullary differentiation and renal cortical echogenicity were also assessed. RESULTS: US parameters of renal length, renal parenchymal thickness, and renal cortical thickness were found to be significantly and strongly associated with the presence of CKD. The strongest association was observed with renal cortical echogenicity (OR 27.33, 95% CI 8.82-84.63). The association of reduced renal cortical thickness (OR 6.14, 95% CI 1.59-23.62), and renal length (OR 2.72, 95% CI 1.13-8.26) were independent and significant predictors of presence of CKD. CONCLUSIONS: Specific US parameters of renal cortical echogenicity, cortical thickness, and length of kidney have a strong potential for independently establishing the diagnosis and evaluation of progression of CKD.

Evaluation of maternal plasma platelet activating factor acetylhydrolase activity and mRNA expression in pre-eclampsia: a case control study.

Preeclampsia (PE) remains a leading cause of maternal morbidity and mortality all over the world. However, its aetiology and pathophysiology remain elusive. Platelet activating factor (PAF) is produced in response to oxidative stress and is a potent hypotensive agent. PAF acetylhydrolase (PAF-AH) inactivates PAF and is seen to decrease in normotensive women. The role of PAF-AH in preeclampsia has been in investigational literature, so far. The few studies done have shown a positive association of elevated levels of PAF-AH with preeclampsia. However, this marker has not been studied in the Indian population to-date and such studies are needed to elucidate the pathogenesis of this condition. Our study aimed to determine the PAF-AH activity by spectrophotometric assay in maternal plasma of 73 PE patients versus 73 normotensive controls and plasma PAF-AH mRNA expression to know the aberration of PAF-AH activity at the genetic level. Relative mRNA expression was calculated by Δ DCT method and a fold change was calculated by 2-ΔDCT. We found that the mean plasma PAF-AH activity levels among cases was significantly higher than the normotensive controls. However, the mRNA expression of the PAF-AH gene was similar between the cases and controls, as well as between severe and non-severe preeclampsia (true fold change =1). To conclude, PAF-AH appears to be increased in women with preeclampsia and hence may contribute to pathophysiology and severity. However, a larger sample size will be required to reiterate this association. Recently, PAF-AH inhibitors such as Darapladib has been tested as a therapeutic option in atherosclerosis. After studying the role of PAF-AH in the pathogenesis of PE, PAF-AH inhibitors may be used as a therapeutic tool in the future in PE.IMPACT STATEMENTWhat is already known on this subject? Platelet activating factor (PAF) is produced in response to oxidative stress and is a potent hypotensive agent. PAF acetylhydrolase (PAF-AH) hydrolyses and inactivates PAF and is seen to decrease in normotensive women. The role of platelet activating factor-acetylhydrolase (PAF-AH) in preeclampsia has been investigational so far. Few studies done have shown a positive association of elevated levels of PAF-AH in preeclamptic women.What do the results of this study add? Our study aimed to determine the activity of PAF-AH in maternal plasma of PE patients versus normal pregnancy and plasma PAF-AH mRNA expression to know the aberration of PAF-AH activity at the level of the gene. We found that plasma PAF-AH activity among preeclamptics was significantly higher than in the controls with a possible role in early-onset preeclampsia (<32 weeks), in the Indian population. This marker has never been studied in this population earlier. The results of our study re-emphasised its role in the pathogenesis of preeclampsia.What are the implications of these findings for clinical practice and/or further research? Such studies are important to not only give us a greater understanding of the various pathways involved in this multifactorial dreaded condition, but can also offer us a marker for early identification of women at risk. Recently, PAF-AH inhibitors like Darapladib has been tested as a therapeutic option in atherosclerosis. After studying the role of PAF-AH in the pathogenesis of PE, PAF-AH inhibitors may be used as a therapeutic tool in the future in PE.

Using Uniocular Visual Acuity Substantially Underestimates the Impact of Visual Impairment on Quality of Life Compared with Binocular Visual Acuity.

PURPOSE: Although the impact of vision-related quality of life (VRQoL) is assessed optimally using binocular visual acuity (VA), uniocular VA remains the preferred measurement method in clinic-based and epidemiologic studies. We compared the impact of distance presenting binocular VA and uniocular VA in the better-seeing (better-eye VA) and worse-seeing (worse-eye VA) eye on VRQoL. DESIGN: The Singapore Chinese Eye Study 2 (2015-2017), a population-based, cross-sectional study. PARTICIPANTS: One thousand eight hundred twenty-two individuals (mean age, 66.2 years [standard deviation, 8.9 years]; 51.1% women) were included. METHODS: Presenting uniocular VA and binocular VA were assessed using a logarithm of the minimum angle of resolution number chart at a distance of 4 m under standard lighting by trained and certified study optometrists. Multiple linear regression models were constructed to determine the independent associations between binocular VA, better-eye VA, and worse-eye VA and the outcome (VRQoL), adjusted for potential confounders, including age, gender, socioeconomic status, and presence of comorbidities. In addition, a cluster sandwich estimator was used to determine if any differences in ß estimates between the associations were statistically significant. MAIN OUTCOME MEASURES: Vision-related quality of life was measured using Rasch-transformed scores from the emotional, mobility, and reading domains of the Impact of Visual Impairment (IVI) questionnaire. RESULTS: Although every 2-line increase (worsening) in binocular VA and uniocular VA was associated independently with decrements in emotional, mobility, and reading IVI scores (P < 0.05 for all), the reductions in all VRQoL domains were substantially lower (P < 0.1) when using either the better-eye VA (compared with binocular VA ß-estimates, -27.8%, -19.4%, and -24.2% difference in emotional, mobility, and reading IVI scores, respectively) or worse-eye VA (compared with binocular VA ß estimates, -38.9%, -58.1%, and -57.5% reduction in emotional, mobility, and reading IVI scores, respectively) to quantify vision loss. CONCLUSIONS: Uniocular VA seems to underestimate the impact of vision loss on VRQoL indices compared with binocular VA. Our data suggest that researchers, clinicians, and policy planners should consider using binocular instead of uniocular measures of VA in patient-reported outcome evaluation of vision loss because it may better reflect its impact on VRQoL.

Mendelian randomization analysis does not support causal associations of birth weight with hypertension risk and blood pressure in adulthood.

Epidemiology studies suggested that low birthweight was associated with a higher risk of hypertension in later life. However, little is known about the causality of such associations. In our study, we evaluated the causal association of low birthweight with adulthood hypertension following a standard analytic protocol using the study-level data of 183,433 participants from 60 studies (CHARGE-BIG consortium), as well as that with blood pressure using publicly available summary-level genome-wide association data from EGG consortium of 153,781 participants, ICBP consortium and UK Biobank cohort together of 757,601 participants. We used seven SNPs as the instrumental variable in the study-level analysis and 47 SNPs in the summary-level analysis. In the study-level analyses, decreased birthweight was associated with a higher risk of hypertension in adults (the odds ratio per 1 standard deviation (SD) lower birthweight, 1.22; 95% CI 1.16 to 1.28), while no association was found between genetically instrumented birthweight and hypertension risk (instrumental odds ratio for causal effect per 1 SD lower birthweight, 0.97; 95% CI 0.68 to 1.41). Such results were consistent with that from the summary-level analyses, where the genetically determined low birthweight was not associated with blood pressure measurements either. One SD lower genetically determined birthweight was not associated with systolic blood pressure (ß = - 0.76, 95% CI - 2.45 to 1.08 mmHg), 0.06 mmHg lower diastolic blood pressure (ß = - 0.06, 95% CI - 0.93 to 0.87 mmHg), or pulse pressure (ß = - 0.65, 95% CI - 1.38 to 0.69 mmHg, all p > 0.05). Our findings suggest that the inverse association of birthweight with hypertension risk from observational studies was not supported by large Mendelian randomization analyses.

Prevalence, determinants and association of unawareness of diabetes, hypertension and hypercholesterolemia with poor disease control in a multi-ethnic Asian population without cardiovascular disease.

BACKGROUND: To explore the prevalence and determinants of unawareness of diabetes, hypertension and hypercholesterolemia and its association with poor disease control in a multi-ethnic Asian population without cardiovascular disease (CVD). METHODS: We included 6904 Chinese, Malay and Indian individuals (mean age [SD] 58.2 [10.2] years; 52.6% female) with diabetes, hypertension and/or hypercholesterolemia from the cross-sectional population-based Singapore Epidemiology of Eye Diseases study (2004-2011). Diabetes was defined as random blood glucose ≥ 11.1 mmol/L or HbA1c > 6.5% or self-reported use of diabetes medication; hypertension as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg or self-reported use of anti-hypertensive treatment; and hypercholesterolemia as total cholesterol ≥ 6.2 mmol/L or self-reported use of lipid-lowering medications. Unawareness was based on participants' answers to the questions: "Did your medical practitioner ever tell you that you have diabetes/hypertension/high cholesterol?" The determinants of unawareness, and its association with poor disease control, were assessed using multivariable binary logistic regression models adjusted for known potential confounders. RESULTS: Of the 2380 (34.5%), 5386 (78.0%) and 3607 (52.2%) with diabetes, hypertension and hypercholesterolemia, respectively, unawareness rates were 30.7%, 43.1% and 40.9%, respectively. Having a higher BMI, particularly if obese, and Malay ethnicity were associated with greater unawareness of diabetes; Malay and Indian ethnicities and current smoking with greater unawareness of hypertension; and education ≤6 years, current smoking, and blue collar jobs or unemployment with greater unawareness of hypercholesterolemia (all P < 0.05). Lack of awareness of each condition was independently associated with poorer disease control in the case of hypertension and hypercholesterolemia, while the converse was true for diabetes (all P < 0.05). CONCLUSIONS: Unawareness of diabetes, hypertension, or hypercholesterolemia is high in Singapore, with risk factors varying across all three diseases, although Malay ethnicity is a consistent one. Unawareness was also associated with poor management for hypertension and hypercholesterolemia. Public health education and screening programs should target at-risk individuals, especially Malays, to reduce the likelihood of incident CVD.

The relationship between diabetic retinopathy and psychosocial functioning: a systematic review.

IMPORTANCE: Previous work has reported a link between diabetic retinopathy/diabetic macular edema (DR/DME) and psychosocial functioning, although the extent and direction of the association remains uncertain. OBJECTIVE: To determine the relationship between DR/DME and psychosocial functioning, the latter an umbrella term used to capture the emotional and social aspects of functioning which may include, for example, depression; depressive disorder; anxiety; vision-specific distress; diabetes-specific distress and emotional and social well-being. EVIDENCE REVIEW: PubMed, Embase, Medline and the Cochrane Central register were systematically searched for relevant interventional and observational quantitative studies using standardised criteria. Studies with DR/DME and psychosocial functioning as exposures or outcomes were accepted. Study quality was evaluated using the modified Newcastle-Ottawa scale for observational studies, and the modified Down's and Black checklist for interventional studies. FINDINGS: Of 1827 titles initially identified, 42 were included in the systematic review. They comprised of four interventions (one RCT, three non-RCTs) and 38 observational studies (33 cross sectional, five prospective). In studies with DR/DME as the exposure (n = 28), its severity and related vision impairment were consistently associated with poor psychosocial outcomes, mostly higher incidence of depression and depressive symptoms. Baseline depression and depressive symptoms were also associated with greater DR incidence and progression of DR. Medical intervention strategies showed significant improvement in psychosocial outcomes in patients with DR, such as significant improvements in mental health domain scores of the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ 25). CONCLUSION AND RELEVANCE: Severity of DR, DME and associated vision loss are significantly associated with poor psychosocial outcomes. Aspects of depression and its symptoms show a bi-directional association, with increased incidence and progression of DR significant in those with baseline depression or depressive symptoms. Based on these findings, we propose two areas that may benefit from targeted interventions: (1) Prevention of development of poor psychological outcomes by preventing and delaying progression of DR/DME; and (2) Improved detection and management of poor psychological functioning by improving screening tools and multidisciplinary care for patients. Subsequent longitudinal studies can further help establish the underlying relationship between the two measures.

Increased antibiotic resistance exhibited by the biofilm of Vibrio cholerae O139.

Background: Vibrio cholerae, the aetiological agent of the deadly diarrhoeal disease cholera, is known to form biofilm. The antibiotic susceptibility status of biofilm of V. cholerae O139, an important epidemic strain in India and other countries, has not previously been studied in detail. Methods: Antibiotic susceptibility status of planktonic and biofilm cultures of V. cholerae O139 was evaluated by determining MIC, MBC and minimum biofilm eradication concentration (MBEC) values of five different classes of antibiotics using established methods. Effects of antibiotic treatment on planktonic and biofilm cultures were analysed by scanning electron microscopy. The virulence of the antibiotic-surviving population (ASP) was evaluated using an infant mouse model. The frequency of spontaneous mutants and inheritability of antibiotic resistance were determined with standard methods. Results: The antibiotic resistance exhibited by biofilm of V. cholerae O139 was found to be significantly higher (P < 0.05) than its planktonic counterpart. The biofilm-associated antibiotic resistance was found to be transient and exclusive to the biofilm culture. The frequency of ASP clones among antibiotic-treated biofilm cultures occurred at a rate of 0.012%-0.95% and these clones were found to retain the virulence and antibiotic resistance of their parent strains. Conclusions: The biofilm of V. cholerae O139 was found to be resistant to different types of antibiotics tested. This unconventional biofilm resistance highlights the hidden danger of antimicrobial escape by V. cholerae, increased risk of cholera transmission and its continued persistence in the environment.

Impact of Incidence and Progression of Diabetic Retinopathy on Vision-Specific Functioning.

PURPOSE: To investigate the independent impact of the incidence and progression of diabetic retinopathy (DR) on visual functioning (VF). DESIGN: Population-based cohort study. PARTICIPANTS: A total of 518 participants aged 40 to 80 years (baseline visit 2007-2009 and second visit 6 years later, 2013-2015), with diabetes, clinical data, and VF information at both visits. MAIN OUTCOME MEASURES: VF-7 scores, converted to interval-level person measures (in logits) using Rasch analysis. METHODS: Incident DR was defined using the Modified Airlie House classification as "none or minimal" DR at baseline and at least mild nonproliferative DR at follow-up; incident vision-threatening DR (VTDR; severe nonproliferative DR, proliferative DR, and/or clinically significant macular edema) as no VTDR at baseline, and present at follow-up; and DR progression as at least a 1-step worsening in DR at follow-up from mild or worse status at baseline. The longitudinal associations between incident DR, VTDR, and DR progression, as well as change in composite and individual item scores of VF, were assessed using multivariable linear regression models. RESULTS: Of the 518 participants (mean age ± standard deviation [SD] 59.8±9.0 years; 47.7% female), 42 (9.8%), 14 (2.8%), and 32 (42.7%) had incident DR, incident VTDR, and DR progression, respectively, at follow-up. In models adjusting for traditional confounders, persons with incident DR and VTDR had a 13.7% (ß = -0.60; 95% confidence interval [CI], -0.96 to -0.24; P = 0.001) and 23% (ß = -1.00; 95% CI, -1.61 to -0.38; P = 0.001) reduction in mean VF scores at follow-up. Furthermore, individuals with incident DR had similar independent reductions in scores for 7 individual items of the VF-7, whereas those with incident VTDR had the largest reductions for activities like cooking (31%; P = 0.003), reading the newspaper (29.6%; P < 0.001), and seeing street signs (28%, P = 0.001) at follow-up. Progression of DR was not independently associated with change in overall VF (ß = -0.18; 95% CI, -1.00, 0.64; P = 0.660). CONCLUSIONS: Incident DR, particularly vision-threatening stages, has a substantial negative impact on people's overall vision-dependent functioning and specific activities such as cooking, seeing street signs, and reading the newspaper. Our findings reinforce the need for strategies to prevent or delay the development of DR.

Generation and In Vivo Characterization of Tn5-Induced Biofilm Mutants of Vibrio cholerae O139.

The Gram-negative bacterium Vibrio cholerae is a unique pathogen with an ability to colonize human intestine as well as outside environments. The biofilm, an organized polymeric structure produced by this bacterium known to be a significant factor for the survival and persistence in hostile conditions. However, the direct role of biofilm formation by this bacterium in environmental persistence, in vivo colonization, and pathogenesis remains unexplored. In this study, we have generated biofilm-altered Tn5 mutants of V. cholerae O139 and evaluated their in vivo colonization ability on mouse model. These Tn5 mutants were found to harbor an independent, single Tn5 insertion in their genome. The DNA sequence analysis revealed that genomic region wherein Tn5 insertion occurred is identified to be involved in functions like LPS biosynthesis, efflux transporters, motility, purine metabolism, stringent response, VPS synthesis, and a hypothetical protein of unknown function. In single-strain infection with the planktonic culture, the biofilm-altered as well as the biofilm intermediate mutants were found to be more or less similar in their intestinal colonization ability, however infection with their biofilm form, a marked difference was observed between the biofilm deficient and other biofilm forming strains. Further, in the competition experiments, biofilm deficient and proficient mutants were found reduced in their colonization ability and outcompeted by their parent strain. In conclusion, biofilm formation in V. cholerae O139 is a genetically complex process and the controlled and regulated production of biofilm appeared to be necessary for its efficient colonization of mouse intestine.

Diet soft drink is associated with increased odds of proliferative diabetic retinopathy.

IMPORTANCE: While consumption of soft drink may increase the risk of cardiovascular disease, the relationship between soft drink consumption and diabetes complications is unknown. BACKGROUND: To explore the association between regular and diet soft drink consumption, and diabetic retinopathy (DR) and diabetic macular oedema (DME). DESIGN: Clinical, cross-sectional study. PARTICIPANTS: Adult patients with diabetes recruited from a tertiary eye hospital (Melbourne, Australia) answered a Food Frequency Questionnaire. METHODS: None, moderate and high soft drink consumption was defined as <1, 1-4 and >4 cans/bottles (375 mL) per week, respectively. Due to missing data, data were imputed using the multiple imputation chained equation procedure. Multivariable logistic regression models determined the associations between soft drink consumption, and presence and severity of DR/DME. MAIN OUTCOME MEASURES: Presence and severity of DR/DME. RESULTS: Of the 609 participants (mean age ± standard deviation: 64.6 ± 11.6 years; males = 210), 285 (46.8%) and 190 (31.2%) consumed diet and regular soft drink, respectively. A total of 230 (37.8%), 36 (5.9%), 154 (25.3%), 28 (4.6%) and 146 (24.0%) had no DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR and proliferative DR (PDR), respectively. High diet soft drink consumption was independently associated with increased likelihood of having PDR (odds ratio = 2.51, 95% confidence interval = 1.05-5.98), compared to no consumption. In contrast, regular soft drink was not associated with DR or DME. CONCLUSIONS AND RELEVANCE: Consuming >4 cans (1.5 L)/week of diet soft drink is associated with a more than twofold risk of having PDR in patients with diabetes. Longitudinal studies are needed to further elucidate the association and its underpinning mechanisms.