Publications by authors named "Preeti Gupta"

148 Publications

Knowledge, attitudes, and practice towards COVID-19 among multi-ethnic elderly Asian residents in Singapore: a mixed methods study.

Singapore Med J 2021 Oct 11. Epub 2021 Oct 11.

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.

Introduction: We investigated knowledge, attitudes, and practice (KAP) about COVID-19 and related preventive measures in Singaporeans aged ≥ 60 years.

Methods: This was a population-based, cross-sectional, mixed-methods study (13 May 2020-9 June 2020) of participants aged ≥60 years. Self-reported KAP about ten COVID-19 symptoms and six government-endorsed preventive measures were evaluated. Multivariable regression models identified sociodemographic and health-related factors associated with knowledge, attitudes and practices in our sample. Associations between knowledge/attitude scores, and practice categories were determined using logistic regression. 78 participants were interviewed qualitatively about practice of additional preventive measures and data were analysed thematically.

Results: Mean awareness score of the symptoms was 7.2/10. Fever (93.0%) and diarrhoea (33.5%) were the most- and least-known symptoms, respectively. Most knew all six preventive measures (90.4%), perceived them as effective (78.7%), and practiced 'wear a mask' (97.2%). Indians, Malays, and those in smaller housing had poorer mean knowledge of COVID-19 symptoms scores. Older participants had poorer attitudes towards preventive measures. Compared to Chinese, Indians had lower odds of practicing 3/6 recommendations. A one-point increase in knowledge of and attitudes towards preventive measures score had higher odds of always practicing 3/6 and 2/6 measures, respectively. Qualitative interviews revealed use of other preventive measures, e.g. maintaining a healthy lifestyle.

Conclusion: Elderly Singaporeans displayed high levels of KAP about COVID-19 and related preventive measures, with a positive association between levels of knowledge/attitude, and practice. However, important ethnic and socioeconomic disparities were evident, suggesting key vulnerabilities remain, requiring immediate attention.
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http://dx.doi.org/10.11622/smedj.2021152DOI Listing
October 2021

A natural history museum visitor survey of perception, attitude and knowledge (PAK) of microbes and antibiotics.

PLoS One 2021 22;16(9):e0257085. Epub 2021 Sep 22.

American Museum of Natural History, Sackler Institute for Comparative Genomics, New York, NY, United States of America.

A kiosk-based survey at the American Museum of Natural History in New York City in 2016-2018 allowed us to assess public knowledge of antibiotics and public attitudes toward microbes in museum goers. Over 22,000 visitors from 172 countries and territories answered several carefully designed questions about microbes and antibiotics. These visitors also entered age, gender, and country demographic data that allowed for stratification along these demographic and geographic divisions. Because museum goers are likely to be better informed about these and other science-based topics, the results described here can set a potential upper bound for public knowledge on these topics. Surprisingly, the results of our analysis of museum goers' answers about microbes and antibiotics indicate a substantial lack of familiarity with both topics. For example, overall only about 50% of respondents can correctly identify penicillin as an antibiotic and less than 50% of museum visitors view microbes as beneficial. The results described here suggest that we are perhaps off target with our educational efforts in this area and that a major shift in approach toward more basic microbial topics is warranted in our educational efforts.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257085PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457478PMC
September 2021

Comparison of efficacy of lignocaine, ropivacaine, and bupivacaine in pain control during extraction of mandibular posterior teeth.

Natl J Maxillofac Surg 2021 May-Aug;12(2):238-243. Epub 2021 Jul 15.

Private Practitioner, Chandigarh, India.

Background: The management of pain during extraction of mandibular third molars is an important requisite to achieve patient comfort and to obtain desired result in an effective manner. There are various anesthetics that can be used to achieve regional or local anesthetic effect in this regard.

Aim: The aim of this study was to compare the efficacy of 2% lignocaine with 1:80,000 adrenaline, 0.75% ropivacaine and bupivacaine in pain control during extraction of mandibular posterior teeth.

Materials And Methods: This prospective, cross-sectional study included 300 study participants indicated for mandibular third molar surgical extractions. The study subjects were categorized into three broad groups - (a) Group I ( = 100): Third molar extractions performed using 2% Lignocaine with 1: 80,000 epinephrine; (b) Group II ( = 100): This group included subjects who underwent extractions of mandibular third molars using 0.75% ropivacaine and (c) Group III ( = 100): This group included patients who underwent extractions of mandibular third molars with bupivacaine. Inclusion criteria were: (a) partially impacted mandibular third molars which were symptomatic; (b) written informed consent. Exclusion criteria were - (a) any systemic diseases and/or undergoing any medication for same; (b) subjects not willing for extraction after clinical and radiographic examination and opinion and (c) subjects undergoing orthodontic therapy. Subject response for pain was recorded using - (a) visual analog scale (VAS) and (b) Verbal Rating scale (VRS). Postoperative pain was assessed using requirement of analgesics after extraction. SPSS version 21.0 was employed as statistical software. Statistical tool used was the Analysis of Variance test which was used for determining statistical significance which was set at a value of lesser than 0.05 (significant).

Results: On analysis of visual analog scale (VAS), it was observed that in Group I (2% Lignocaine with 1:80,000), no pain during the extraction procedure was demonstrated in 30 study participants while minimal or less pain was present in 70 patients, while in Group II (0.75% ropivacaine), 90 patients presented with no pain while ten patients had presented with minimal amount of pain during tooth extraction. While on the other hand, Group III patients whose mandibular third molars were extracted using local anesthesia by injecting bupivacaine, lack of any pain was observed in 69 patients while minimal pain was noted in 31 individuals. While making statistical comparison between three groups, a significant = 0.03 was observed. Also, postoperative pain was noted in 60% of cases who underwent extraction using 2% lignocaine (Group I), 10% patients who had third molar extractions under Bupivacaine anesthesia presented with pain whereas none of the patients (0%), demonstrated the presence of pain following third molar extraction.

Conclusion: 0.75% Ropivacaine is the most effective local anesthetic agent that can be used for extracting mandibular third molars due to its effective pain control both during and following the procedure when compared to 2% lignocaine and bupivacaine.
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http://dx.doi.org/10.4103/njms.NJMS_14_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386260PMC
July 2021

The Study of Prevalence and Pattern of Thyroid Disorder in Pregnant Women: A Prospective Study.

Cureus 2021 Jul 18;13(7):e16457. Epub 2021 Jul 18.

Anatomy, Uttar Pradesh University of Medical Sciences, Saifai, Etawah, IND.

Background The most frequent thyroid disorder in pregnancy is maternal hypothyroidism. The geographical variation in the prevalence of hypothyroidism during pregnancy is very wide and ranges from 2.5% to 11%. The prevalence of hypothyroidism is more in Asian countries as compared to western countries. Thus, this study was conducted to find out the prevalence of thyroid disorder in pregnancy at our center. Methods The present study was conducted in the Department of Physiology in collaboration with the Department of Obstetrics & Gynecology, Index Medical College, Hospital and Research Center, Indore, MP, India over a period of one and a half years from October 2018 to March 2020. It was a cross-sectional study including 865 pregnant women. The patients' demographic profile was noted in all cases. A detailed history and thorough examination were done in all cases. Serum thyroid-stimulating hormone (TSH), Free T3, and Free T4 (FT3 and FT4) were done along with routine blood investigations as per The Federation of Obstetric and Gynaecological Societies of India-Indian College of Obstetricians and Gynaecologists (FOGSI-ICOG) good clinical practice recommendation. Results In this study, the prevalence of thyroid dysfunction was 10.4%. Of these 90 patients with thyroid dysfunction, subclinical and overt hypothyroidism was found in 5.50% and 0.92%, respectively, whereas subclinical and overt hyperthyroidism was observed in 3.12% and 0.81% pregnant females, respectively. A significant association was found between thyroid dysfunction and maternal age, BMI, parity, and education. Conclusions The prevalence of thyroid dysfunction was 10.4% in this study. Hypothyroidism was more common than hyperthyroidism and subclinical thyroid disorders were more common than overt thyroid disorders in pregnancy. Therefore, we should include thyroid function tests with other routine investigations during pregnancy to detect thyroid dysfunction.
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http://dx.doi.org/10.7759/cureus.16457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369967PMC
July 2021

Beyond Visual Acuity-A Comprehensive Assessment of Vision and Cognition in Older Adults With Visual Impairment.

JAMA Netw Open 2021 Jul 1;4(7):e2119033. Epub 2021 Jul 1.

Duke-National University of Singapore Medical School, Singapore.

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http://dx.doi.org/10.1001/jamanetworkopen.2021.19033DOI Listing
July 2021

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

J Clin Ultrasound 2021 Sep 4;49(7):715-719. Epub 2021 Jun 4.

Epidemiology (Johns Hopkins), IIHMR University, Jaipur, India.

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.
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http://dx.doi.org/10.1002/jcu.23026DOI Listing
September 2021

Memory changes following adjuvant temporo-parietal repetitive transcranial magnetic stimulation in schizophrenia.

Indian J Psychiatry 2021 Jan-Feb;63(1):66-69. Epub 2021 Feb 15.

Department of Psychiatry, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand, India.

Objective: The use of repetitive transcranial magnetic stimulation (rTMS) in schizophrenia has shown improvement as well as deficits in memory. Though most studies had focused on dorsolateral prefrontal cortex only, but impact of rTMS on cognitive functions remain inconclusive. The need of the study is to assess the impact of rTMS on memory in schizophrenia.

Materials And Methods: Forty right-handed male patients with schizophrenia were included by purposive sampling and rated on Positive and Negative Syndrome Scale (PANSS) before starting the rTMS treatment with the experimental group. Low frequency 1 Hz rTMS including 1200 stimulations were given over temporo-parietal cortex for 20 min as add on to medications. At the end of 10 session treatment (5 days a week for 2 weeks), the patients were re-evaluated.

Results: A total of 39 patients (20 for experimental group and 19 for control group) with mean age of 29.70 ± 9.05 and 31.26 ± 7.78 years, respectively, shows significant difference to pre- and post-treatment mean PANSS score in positive, negative and general psychopathology domains. The pre- and post-treatment mean Postgraduate Institute Memory Scale Scores with multivariate repeated measures analysis of variance revealed significant improvements in all memory domains ( < 0.01) except remote memory in both experimental and control groups.

Conclusion: RTMS in combination with antipsychotics has shown improvement in psychopathology in patients of schizophrenia without any deterioration of memory.
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http://dx.doi.org/10.4103/psychiatry.IndianJPsychiatry_532_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106430PMC
February 2021

Prevalence, Associated Factors and Health-related Quality of Life of Dual Sensory Impairment in Residential Care Facilities in Singapore.

Ophthalmic Epidemiol 2021 May 17:1-9. Epub 2021 May 17.

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.

: To investigate the prevalence of dual sensory impairment (DSI), its associated factors and relationship with health-related quality of life (HR-QoL) in residential care facilities (RCF) in Singapore. This was a cross-sectional study of 123 residents aged ≥40 years from six RCFs, conducted between 2016 and 2018. DSI was defined as concomitant presenting visual acuity (better-eye) >0.3 logarithm of the minimum angle of resolution and a pure-tone air conduction threshold (better-ear) >40 dB HL in any of the four tested frequencies (500, 1000, 2000 and 4000 Hz). HR-QoL was quantified using the EuroQol five-dimension questionnaire. Multivariable Poisson regression was used to determine the associated factors of DSI. Multivariable linear regression was used to determine the association between DSI and HR-QoL adjusted for traditional confounders. Of the 123 residents (age [mean±standard deviation] 75.3 ± 10.8 years; 56.9% male), 97 (78.9%[95% confidence interval(CI):71.6%, 86.1%]) had DSI, with 110 (98.2%) not on follow-up care for their sensory disabilities. In multivariable models, male gender (prevalence ratio(PR) [95%CI] = 1.3[1.1, 1.6]), older age (per 10-year increase (1.2[1.1, 1.3])), education ≤6 years (1.3[1.1, 1.7]) and the presence of cataract (1.3[1.0, 1.7]) were independently associated with DSI. DSI was independently associated with a substantial worsening in HR-QoL (β = -0.61; 95%CI: -0.76, -0.45; < .001). DSI affects four in five residential care residents and is substantially associated with reductions in HR-QoL in these residents. Our finding highlights an urgent need for the implementation of routine vision and hearing screening and follow-up care for residents living in these facilities.
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http://dx.doi.org/10.1080/09286586.2021.1926515DOI Listing
May 2021

Cerebral Venous Thrombosis in Acute Lymphoblastic Leukemia with Severe COVID-19: a Case Report.

SN Compr Clin Med 2021 Apr 30:1-5. Epub 2021 Apr 30.

Department of Medicine, Command Hospital, Kolkata, India.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has brought an unprecedented upheaval in our health-care systems. Amongst the many challenges posed by the disease, increased risk of thromboembolism has presented a distinct new front for increased mortality and morbidity. While there are multiple documented evidences for the same, the exact mechanism, knowledge of groups at-risk, and mitigation strategies are evolving. We present a case of a young individual who was diagnosed with acute lymphoblastic leukemia (ALL), was started on appropriate chemotherapy, and subsequently developed severe COVID-19 pneumonia. He was treated for COVID-19 pneumonia and recovered from the illness. However, his recovery from COVID-19 was further complicated by cortical venous sinus thrombosis (CVT). Contrast enhanced magnetic resonance imaging (CEMRI) brain and magnetic resonance venography (MRV) revealed the diagnosis of CVT with hemorrhagic parenchymal changes. He was managed with therapeutic anticoagulation and cerebral decongestants and was subsequently shifted to oral anticoagulant therapy. While the case was managed at a tertiary care setting, it opened up the question of identifying the high-risk groups and to formulate guidelines for extended thromboprophylaxis in these patients.
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http://dx.doi.org/10.1007/s42399-021-00932-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084587PMC
April 2021

Targeting the Sphingosine Kinase/Sphingosine-1-Phosphate Signaling Axis in Drug Discovery for Cancer Therapy.

Cancers (Basel) 2021 Apr 15;13(8). Epub 2021 Apr 15.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.

Sphingolipid metabolites have emerged as critical players in the regulation of various physiological processes. Ceramide and sphingosine induce cell growth arrest and apoptosis, whereas sphingosine-1-phosphate (S1P) promotes cell proliferation and survival. Here, we present an overview of sphingolipid metabolism and the compartmentalization of various sphingolipid metabolites. In addition, the sphingolipid rheostat, a fine metabolic balance between ceramide and S1P, is discussed. Sphingosine kinase (SphK) catalyzes the synthesis of S1P from sphingosine and modulates several cellular processes and is found to be essentially involved in various pathophysiological conditions. The regulation and biological functions of SphK isoforms are discussed. The functions of S1P, along with its receptors, are further highlighted. The up-regulation of SphK is observed in various cancer types and is also linked to radio- and chemoresistance and poor prognosis in cancer patients. Implications of the SphK/S1P signaling axis in human pathologies and its inhibition are discussed in detail. Overall, this review highlights current findings on the SphK/S1P signaling axis from multiple angles, including their functional role, mechanism of activation, involvement in various human malignancies, and inhibitor molecules that may be used in cancer therapy.
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http://dx.doi.org/10.3390/cancers13081898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071327PMC
April 2021

Emerging role of protein kinases in diabetes mellitus: From mechanism to therapy.

Adv Protein Chem Struct Biol 2021 24;124:47-85. Epub 2020 Nov 24.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India. Electronic address:

Diabetes mellitus has emerged as a severe burden on the medical health system across the globe. Presently, around 422 million people are suffering from diabetes which is speculated to be expanded to about 600 million by 2035. Patients with type 2 diabetes are at increased risk of developing detrimental metabolic and cardiovascular complications. The scientific understanding of this chronic disease and its underlying root cause is not yet fully unraveled. Protein kinases are well known to regulate almost every cellular process through phosphorylation of target protein in diverse signaling pathways. The important role of several protein kinases including AMP-activated protein kinase, IκB kinase and protein kinase C have been well demonstrated in various animal models. They modulate glucose tolerance, inflammation and insulin resistance in the cells via acting on diverse downstream targets and signaling pathways. Thus, modulating the activity of potential human kinases which are significantly involved in diabetes by targeting with small molecule inhibitors could be an attractive therapeutic strategy to tackle diabetes. In this chapter, we have discussed the potential role of protein kinases in glucose metabolism and insulin sensitivity, and in the pathogenesis of diabetes mellitus. Furthermore, the small molecules reported in the literature that can be potentially used for the treatment of diabetes have been discussed in detail.
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http://dx.doi.org/10.1016/bs.apcsb.2020.11.001DOI Listing
May 2021

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

Age Ageing 2021 06;50(4):1236-1242

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.

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.
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http://dx.doi.org/10.1093/ageing/afaa276DOI Listing
June 2021

Six-year incidence and systemic associations of retinopathy in a multi-ethnic Asian population without diabetes.

Br J Ophthalmol 2021 Jan 19. Epub 2021 Jan 19.

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore

Purpose: We described the 6-year incidence and changes of retinopathy, and their associated risk factors in a multi-ethnic Asian population without diabetes.

Methods: We included 4374 participants with non-diabetes from a population-based cohort, the Singapore Epidemiology of Eye Disease Study, with gradable retinal photographs at baseline and 6-year follow-up visit. Retinopathy was assessed according to the modified Airlie House classification system.

Results: Over the 6-year period, the cumulative rates were 2.5% (106/4279) for retinopathy incidence, 1.0% (1/95) for retinopathy progression and 68.4% (65/95) for retinopathy regression. In multivariable analysis, higher diastolic blood pressure (DBP) (risk ratio (RR)=1.02; 95% CI: 1.00 to 1.04; per 10 mm Hg increase in DBP) and wider retinal arteriolar calibre (RR=1.36; 95% CI: 1.13 to 1.63; per SD increase in central retinal artery equivalent) were associated with higher risk of incident retinopathy, while higher level of high-density lipoprotein (HDL) was associated with lower risk of incident retinopathy (RR=0.56; 95% CI: 0.32 to 0.99; per mmol/L increase in HDL). Compared with Chinese, Malays were more likely to have retinopathy regression (RR=1.63; 95% CI: 1.20 to 2.22), while overweight (RR=0.47; 95% CI: 0.26 to 0.84) and higher glycosylated haemoglobin (HbA1c) level (RR=0.58; 95% CI: 0.37 to 0.93; per per cent increase in HbA1c) were associated with lower likelihood of retinopathy regression.

Conclusion: Risk of developing retinopathy in Asians without diabetes is generally low. However, regression of retinopathy over time is common, suggesting that these retinopathy signs may reflect subclinical reversible microvascular dysfunction. Several metabolic risk factors are associated with incidence or regression of retinopathy, suggesting that good metabolic control may still be important in the management of non-diabetic retinopathy.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318126DOI Listing
January 2021

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

Ophthalmology 2021 07 27;128(7):981-992. Epub 2021 Feb 27.

Duke-NUS Medical School, Singapore, Republic of Singapore; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Republic of Singapore; Department of Ophthalmology, The University of Melbourne, Melbourne, Australia. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ophtha.2020.12.010DOI Listing
July 2021

Malignant prolongation of the QTc interval due to severe vitamin D deficiency: an unusual presentation.

BMJ Case Rep 2020 Dec 15;13(12). Epub 2020 Dec 15.

Cardiology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

Long QT syndrome with Torsades de Pointes (TdP) is a life-threatening polymorphic ventricular arrhythmia. The corrected QT (QTc) prolongation >500 milliseconds (ms) has been associated with TdP. Hypocalcaemia due to severe vitamin D deficiency is an uncommon cause of acquired long QT. We hereby present a case of a 40-year-old woman with sensorineural deafness and having symptoms of palpitations and presyncope. She had a QTc interval of 556 ms (reference range, QTc 451-470 ms in adult healthy woman) on 24-hour Holter analysis. Genetic analysis for congenital long QT syndrome was negative. She was diagnosed with severe hypocalcaemia secondary to severe vitamin D deficiency. After treatment with intravenous calcium gluconate, followed by oral vitamin D and calcium supplementation, the QTc became normalised and no further episode of palpitations or presyncope occurred. The causes of vitamin D deficiency was due to inadequate exposure to sunlight and a strict vegan diet.
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http://dx.doi.org/10.1136/bcr-2020-237157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745318PMC
December 2020

Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract.

Commun Biol 2020 12 11;3(1):755. Epub 2020 Dec 11.

Institute of Molecular and Cell Biology, 138673, Singapore, Singapore.

Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N = 14,151 and replication N = 5299) of the International Cataract Genetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468, P = 2.8 × 10) with nuclear cataract and identified five new loci associated with this disease: SOX2-OT (rs9842371, P = 1.7 × 10), TMPRSS5 (rs4936279, P = 2.5 × 10), LINC01412 (rs16823886, P = 1.3 × 10), GLTSCR1 (rs1005911, P = 9.8 × 10), and COMMD1 (rs62149908, P = 1.2 × 10). The results suggest a strong link of age-related nuclear cataract with congenital cataract and eye development genes, and the importance of common genetic variants in maintaining crystalline lens integrity in the aging eye.
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http://dx.doi.org/10.1038/s42003-020-01421-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733496PMC
December 2020

A versatile tool in controlling aggregation and Ag nanoparticles assisted in vitro folding of thermally denatured zDHFR.

Biochem Biophys Rep 2020 Dec 23;24:100856. Epub 2020 Nov 23.

Molecular Biophysics Lab, Amity Institute of Biotechnology, Amity University, Sector 125, Noida, Uttar Pradesh, 201313, India.

Background: Proteins have tendency to form inactive aggregates at higher temperatures due to thermal instability. Maintenance of thermal stability is essential to gain the protein in sufficient quantity and biologically active form during their commercial production.

Methods: BL21-DE3 Rosetta cells which contains plasmid pET43.1a vector was used for producing zDHFR protein commercially. The purification of N-terminal Histidine tagged zDHFR was performed by Immobilized Metal Ion chromatography (IMAC). Investigations were performed in existence and non existence of Silver nanoparticles (AgNPs). The inactivation kinetics of zDHFR in existence and non existence of AgNPs were monitored over a range of 40-80 °C as monitored by UV-Visible absorption spectroscopy.

Results: The protein completely lost its activity at 55 °C. Kinetics of inactivated zDHFR follows first order model in presence and absence of AgNPs. Decrease in rate constant () values at respective temperatures depicts that AgNPs contribute in the thermostability of the protein. AgNPs also assists in regaining the activity of zDHFR protein.

Conclusions: AgNPs helps in maintaining thermostability and reducing the aggregation propensity of zDHFR protein.

General Significance: Result explains that AgNPs are recommended as a valuable system in enhancing the industrial production of biologically active zDHFR protein which is an important component in folate cycle and essential for survival of cells and prevents the protein from being aggregated.
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http://dx.doi.org/10.1016/j.bbrep.2020.100856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695922PMC
December 2020

Rationale and Methodology of The PopulatION HEalth and Eye Disease PRofile in Elderly Singaporeans Study [PIONEER].

Aging Dis 2020 Dec 1;11(6):1444-1458. Epub 2020 Dec 1.

1Singapore Eye Research Institute and Singapore National Eye Centre, Singapore.

To describe the rationale, design and methodology of a geographically-representative and population-based study investigating the epidemiology, impact, personal and economic burden of age-related eye diseases, declining visual and other sensory systems in Asians aged >60 years in Singapore.PIONEER (The PopulatION HEalth and Eye Disease PRofilE in Elderly Singaporeans Study) is currently a cross-sectional study targeting 3152 Chinese, Malay and Indian adults who are Singapore citizens or permanent residents aged 60 years and older living across Singapore. The study is intended to be longitudinal, with several waves of data planned to be collected in the future. The sampling frame consisted of 7000 names derived from age, gender and ethnicity-stratified random sampling of individuals >60 years. Selected individuals were invited via letters, home visits, and telephone calls for a clinical assessment at the Singapore Eye Research Institute. Individuals with limited mobility were examined in a custom-designed mobile eye clinic. Questionnaires were subsequently administered at participants' homes by trained interviewers in their preferred language. A total of 3,299 participants (from East, West, North and South Singapore) were approached from December 2017 to November 2019. Of these, 953 (28.5%) were deemed ineligible. Out of 2,346 eligible participants, 904 (38.5%) refused, and 1,442 (61.5%) attended our clinical testing protocol, giving an initial response rate of 61.5%. Of these, 1,170 (81%) were cognitively able to complete the questionnaire assessment. The mean age±SD of our participants was 73.8±8.6 years; n=798 (55.3%) were female; and 828 (57.4%) were of Chinese ethnicity. The findings from this study will allow a deeper understanding of the risk factors and impact of aging in Asian populations, particularly in relation to the visual function and other functional system.
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http://dx.doi.org/10.14336/AD.2020.0206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673841PMC
December 2020

Balloon Compression Sign During Balloon Mitral Valvotomy: An Old Sign Revisited.

J Invasive Cardiol 2020 Dec;32(12):E378

Assistant Professor in Cardiology, VMMC and Safdarjung Hospital, New Delhi, India.

During inflation of the Inoue balloon during a balloon mitral valvotomy, indentation and compression of the Inoue balloon was seen. This is indirect evidence of severe subvalvular disease.
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December 2020

Knowledge, attitude, and practices regarding COVID-19: A cross-sectional study among rural population in a northern Indian District.

J Family Med Prim Care 2020 Sep 30;9(9):4769-4773. Epub 2020 Sep 30.

Department of Respiratory Medicine, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

Background: First case of COVID-19 was reported in December 2019 and within a timespan of few months, it has become a pandemic. It has created havoc globally and India is no exception. Globally, it is emphasized that preventive measures play an important role in controlling the rapid spread of COVID-19. In India, 68% of population is rural and this population is going to play a crucial role in the containment of the pandemic. Realizing the key position of rural population in COVID control, this study was conducted to assess the knowledge, attitude, and practices of rural population about the disease.

Method And Material: A cross-sectional questionnaire-based study was conducted on patients and their relatives from 1 April, 2020 to 31 May, 2020. A total of 372 participants hailing from rural areas were enrolled.

Results: Most common source of information for the participants was through television (54.8%) and radio (49.2%). Only 77% claimed that they were using face mask and 72% claimed to be following social distancing. A large (60%) proportion of the participants did not know that COVID-19 could spread from asymptomatic patients. Education of participants was a key determinant for use of social distancing and face mask as a preventive tool. With increasing age, the practice of social distancing and the use of face mask were decreasing in our study.

Conclusion: Television/Radio channels form an important source of information and need to be used more effectively to educate the people about the disease and create awareness about effective preventive measures. People need to be educated about the role of asymptomatic carriers in spreading the disease.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_1206_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652126PMC
September 2020

Soft Malleable Vesicles: versatile carriers for efficient topical delivery of fungal therapeutics.

Drug Res (Stuttg) 2021 Feb 2;71(2):54-61. Epub 2020 Nov 2.

Faculty of Pharmacy, Integral University, Lucknow.

Fungal infections have become a subject of great concern and the incidence of fungal infections is increasing, presenting an enormous challenge to healthcare professionals. Since most of the fungal infections are occurring over the skin, the treatment option of these infections always involves topical application. However, in topical delivery drug reaches into systemic circulation through different barriers of skin. Nevertheless, due to the low permeability, skin restricts the movement of many drugs. Hence, a delivery system is required, which deliver the medicament into the skin layers or through the skin and into the systemic circulation. Ethosomes or Soft malleable vesicles are the novel lipid vesicular carrier that offer improved skin permeability and efficient delivery due to their structure and composition. They contain high concentration of ethanol, which increases the fluidity of the skin. Therefore, in the present paper, we have explored the utility of ethosomal systems in the topical treatment of fungal infections. Structure, compositions types, mechanism and techniques of preparation of ethosome also discussed in the paper.
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http://dx.doi.org/10.1055/a-1286-5750DOI Listing
February 2021

Iatrogenic Pneumopericardium During Pericardiocentesis.

J Invasive Cardiol 2020 Nov;32(11):E299

VMMC and Safdarjung Hospital, New Delhi, India.

Iatrogenic pneumopericardium after pericardiocentesis due to accidental leakage from the side port of the sheath has been reported in the literature. In the present case, it occurred during passage of the guidewire. Every step needs to be done meticulously. The patient should be advised not to take a deep breath during the puncture.
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November 2020

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

J Obstet Gynaecol 2021 Jul 19;41(5):726-732. Epub 2020 Oct 19.

Department of Biochemistry, UCMS and Guru Teg Bahadur Hospital, Delhi, India.

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 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 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 STATEMENT 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. Our study aimed to determine the activity of PAF-AH in maternal plasma of PE patients 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. 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.
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http://dx.doi.org/10.1080/01443615.2020.1789956DOI Listing
July 2021

Decrease in Choroidal Vascularity Index of Haller's layer in diabetic eyes precedes retinopathy.

BMJ Open Diabetes Res Care 2020 09;8(1)

Singapore National Eye Centre, Singapore

Introduction: The study aimed to evaluate Choroidal Vascularity Index (CVI) of Haller's and Sattler's layers and their relationships with choroidal and retinal thickness, volumes measured on enhanced depth imaging-optical coherence tomography (OCT) scans in the eyes of patients without diabetes, patients with diabetes with no diabetic retinopathy (DR) and patients with diabetes and DR.

Research Design And Methods: Retrospective analysis of 165 eyes from 84 Singapore Indian Eye Study-2 study participants (group 1: no diabetes, group 2: diabetes with no DR and group 3: with DR). Groups 1 and 2 were matched by age and gender from group 3.

Results: In the eyes of patients with diabetes without DR, the macular CVI of Haller's but not Sattler's layer was significantly reduced compared with eyes of patients without diabetes. Eyes with >5 years of diabetes have significantly decreased CVI of Sattler's layers (mean difference=0.06 ± 0.10, p=0.04) and also decreased subfoveal choroidal volume (mean difference=0.89 ± 0.16 mm, p=0.02), compared with those with ≤5 years of diabetes.

Conclusion: Diabetic eyes without DR had significantly lower CVI of macular Haller's layer than those of healthy controls. With a longer duration of diabetes, CVI of subfoveal Sattler's layer and choroidal volume continue to decrease, irrespective of diabetic control, suggesting that early diabetic choroidopathy mainly affects larger choroidal veins initially before medium-sized arterioles. The CVI of macular Haller's layer could potentially be used as a marker on spectral domain OCT imaging in newly diagnosed patients with diabetes for the onset of DR and as a possible prognostication tool in diabetic eyes. Future prospective longitudinal studies in diabetic eyes would be useful in establishing the relationship between CVIs of Haller's and Sattler's layer with visual acuity as a marker of photoreceptor health and visual prognosis.
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http://dx.doi.org/10.1136/bmjdrc-2020-001295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482468PMC
September 2020

Discovery of Harmaline as a Potent Inhibitor of Sphingosine Kinase-1: A Chemopreventive Role in Lung Cancer.

ACS Omega 2020 Sep 20;5(34):21550-21560. Epub 2020 Aug 20.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.

The sphingosine kinase-1/sphingosine-1-phosphate pathway is linked with the cancer progression and survival of the chemotherapy-challenged cells. Sphingosine kinase-1 (SphK1) has emerged as an attractive drug target, but their inhibitors from natural sources are limited. In this study, we have chosen harmaline, one of the β-carboline alkaloids, and report its mechanism of binding to SphK1 and subsequent inhibition. Molecular docking combined with fluorescence binding studies revealed that harmaline binds to the substrate-binding pocket of SphK1 with an appreciable binding affinity and significantly inhibits the kinase activity of SphK1 with an IC value in the micromolar range. The cytotoxic effect of harmaline on non-small-cell lung cancer cells by MTT assay was found to be higher for H1299 compared to A549. Harmaline induces apoptosis in non-small-cell lung carcinoma cells (H1299 and A549), possibly via the intrinsic pathway. Our findings suggest that harmaline could be implicated as a scaffold for designing potent anticancer molecules with SphK1 inhibitory potential.
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http://dx.doi.org/10.1021/acsomega.0c02165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469376PMC
September 2020

To trust or distrust myocardial performance index (MPI) in severe acute malnutrition.

Indian Heart J 2020 Jul - Aug;72(4):329. Epub 2020 May 22.

Department of Cardiology, VMMC and Safdarjung Hospital, New Delhi, 110029, India. Electronic address:

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http://dx.doi.org/10.1016/j.ihj.2020.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474110PMC
March 2021

Rates and Determinants of Eyecare Utilization and Eyeglass Affordability Among Individuals With Visual Impairment in a Multi-Ethnic Population-Based Study in Singapore.

Transl Vis Sci Technol 2020 04 18;9(5):11. Epub 2020 Apr 18.

Singapore Eye Research Institute and Singapore National Eye Centre, Singapore.

Purpose: The purpose of this study was to determine the rates of, and factors associated with, eyecare utilization and spectacle affordability among Singaporeans with vision impairment (VI).

Methods: We included adults with VI from their second visit of the Singapore Epidemiology of Eye Disease Study. Data on eyecare utilization and spectacle affordability were collected. Low eyecare utilization was defined as no eye check ever or eye checks not even once per year in reference to at least once per year. Difficulty affording glasses was defined as glasses being rated as expensive in reference to not expensive.

Results: There were 985 adults (14.5%; 415 Malays, 260 Indian, and 310 Chinese; mean age [SD]: 69.5 [10.2] years; 55.4% women) with VI who answered the above questions, were included. Of these, 624 (63.4%) wore glasses. The rates of low eyecare utilization and difficulty affording eyeglasses were 31% and 63%, respectively. Compared to Chinese (23.8%) and Indians (18.8%), Malays (57.4%) had the highest rates of low eyecare utilization ( < 0.001), and most difficulty affording eyeglasses (47.2% vs. 26.1% and 26.6% in Chinese and Indians, respectively; < 0.001). Younger age, low socioeconomic status, absence of diabetes, absence of self-reported eye conditions, and poor vision were independently associated with low eyecare utilization, whereas older age and female sex was associated with difficulty affording glasses.

Conclusions: In this multi-ethnic population with VI, almost one-third had low eyecare utilization and nearly two-thirds reported difficulty affording eyeglasses.

Translational Relevance: This will inform strategies, such as tailored eyecare utilization awareness campaigns and awareness of available subsidy schemes for at-risk Singaporeans, such as Malays.
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http://dx.doi.org/10.1167/tvst.9.5.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401894PMC
April 2020

Mechanistic insights into the urea-induced denaturation of human sphingosine kinase 1.

Int J Biol Macromol 2020 Oct 7;161:1496-1505. Epub 2020 Aug 7.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India. Electronic address:

Sphingosine kinase 1 (SphK1) plays a significant role in various cellular processes, including cell proliferation, apoptosis, and angiogenesis. SphK1 is considered as an attractive target for drug development owing to its connection with several diseases, including cancer. In the current work, the urea-induced unfolding of SphK1 was performed at pH 8.0 and 25 °C using CD and fluorescence spectroscopy. SphK1 follows a biphasic unfolding transition (N ⇌ I ⇌ D) with an intermediate (I) state populated around 4.0 M urea concentration. The circular dichroism ([θ]) and fluorescence emission spectra (λ) of SphK1 with increasing concentrations of urea were analyzed to calculate Gibbs free energy (ΔG) for both the transitions (N ⇌ I and I ⇌ D). A significant overlap of both the transitions obtained by two spectroscopic properties ([θ] and λ) was observed, indicating that both N ⇌ I and I ⇌ D transition follow two-step equilibrium unfolding pattern. Also, we performed 100 ns molecular dynamics (MD) simulations to get atomistic insights into the structural changes in SphK1 with increasing urea concentrations. Our results showed a consistent pattern of the SphK1 unfolding with increasing urea concentrations. Together, spectroscopic and MD simulation findings provide deep insights into the unfolding mechanism and conformational features of SphK1.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.07.280DOI Listing
October 2020

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

Ophthalmology 2021 03 29;128(3):354-363. Epub 2020 Jul 29.

Singapore Eye Research Institute and Singapore National Eye Centre, Singapore; Duke-NUS Medical School, Singapore; National University of Singapore, Singapore. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ophtha.2020.07.046DOI Listing
March 2021
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