Estimating the Prevalence of Dementia in India Using a Semi-Supervised Machine Learning Approach.

INTRODUCTION: Accurate estimation of dementia prevalence is essential for making effective public and social care policy to support individuals and families suffering from the disease. The purpose of this paper is to estimate the prevalence of dementia in India using a semi-supervised machine learning approach based on a large nationally representative sample. METHODS: The sample of this study is adults 60 years or older in the wave 1 (2017-2019) of the Longitudinal Aging Study in India (LASI). A subsample in LASI received extensive cognitive assessment and clinical consensus ratings and therefore has diagnoses of dementia. A semi-supervised machine learning model was developed to predict the status of dementia for LASI participants without diagnoses. After obtaining the predictions, sampling weights and age standardization to the World Health Organization (WHO) standard population were applied to generate the estimate for prevalence of dementia in India. RESULTS: The prevalence of dementia for those aged 60 years and older in India was 8.44% (95% CI: 7.89%-9.01%). The age-standardized prevalence was estimated to be 8.94% (95% CI: 8.36%-9.55%). The prevalence of dementia was greater for those who were older, were females, received no education, and lived in rural areas. DISCUSSION: The prevalence of dementia in India may be higher than prior estimates derived from local studies. These prevalence estimates provide the information necessary for making long-term planning of public and social care policy. The semi-supervised machine learning approach adopted in this paper may also be useful for other large population aging studies that have a similar data structure.

Cohort Profile: Real-Time Insights of COVID-19 in India (RTI COVID-India).

BACKGROUND: The coronavirus disease (COVID) pandemic caused disruption globally and was particularly distressing in low- and middle-income countries such as India. This study aimed to provide population representative estimates of COVID-related outcomes in India over time and characterize how COVID-related changes and impacts differ by key socioeconomic groups across the life course. METHODS: The sample was leveraged from an existing nationally representative study on cognition and dementia in India: Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD). The wave-1 of LASI-DAD enrolled 4096 older adults aged 60 years and older in 3316 households from 18 states and union territories of India. Out of the 3316 LASI-DAD households, 2704 with valid phone numbers were contacted and invited to participate in the Real-Time Insights COVID-19 in India (RTI COVID-India) study. RTI COVID-India was a bi-monthly phone survey that provided insight into the individual's knowledge, attitudes, and behaviour towards COVID-19 and changes in the household's economic and health conditions throughout the pandemic. The survey was started in May 2020 and 9 rounds of data have been collected. FINDINGS TILL DATE: Out of the 2704 LASI-DAD households with valid phone numbers, 1766 households participated in the RTI COVID-India survey at least once. Participants were in the age range of 18-102 years, 49% were female, 66% resided in rural area. Across all rounds, there was a higher report of infection among respondents aged 60-69 years. There was a greater prevalence of COVID-19 diagnosis reported in urban (23.0%) compared to rural areas (9.8%). Respondents with higher education had a greater prevalence of COVID-19 diagnosis compared to those with lower or no formal education. Highest prevalence of COVID-19 diagnosis was reported from high economic status compared to middle and low economic status households. Comparing education gradients in experiencing COVID-19 symptoms and being diagnosed, we observe an opposite pattern: respondents with no formal schooling reported the highest level of experiencing COVID-19 symptoms, whereas the greatest proportion of the respondents with secondary school or higher education reported being diagnosed with COVID-19. FUTURE PLANS: The study group will analyse the data collected showing the real-time changes throughout the pandemic and will make the data widely available for researchers to conduct further studies.

Performance of the Informant Questionnaire on Cognitive Decline for the Elderly (IQCODE) in a nationally representative study in India: the LASI-DAD study.

BACKGROUND: Low and middle-income countries like India anticipate rapid population aging and increases in dementia burden. In India, dementia screening scales originally developed in other contexts need to be assessed for feasibility and validity, given the number of different languages and varying levels of literacy and education. METHOD: Using data from the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (N = 4,028), we characterize the performance of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). We described patterns and correlates of missingness, evaluated the psychometric properties of the scale, and assessed criterion validity against the Hindi Mental State Examination (HMSE) using linear regression. RESULTS: Several IQCODE items had high levels of missingness, which was associated with urbanicity, respondent's gender, and informant's generation (same vs. younger generation). Full IQCODE scores showed strong criterion validity against the HMSE; each 1-point increase in IQCODE score was associated with a 3.03-point lower score on the HMSE, controlling for age, gender, and urbanicity. The statistically significant association between IQCODE and HMSE was stronger in urban than rural settings (p-value for interaction = 0.04). Associations between IQCODE and HMSE remained unchanged after removing the three items with the highest levels of differential missingness (remembering addresses and telephone numbers, ability to work with familiar machines, ability to learn to use new gadget or machine). CONCLUSION: Findings raise questions about the value of including items with high proportions of missingness, which may signal cultural irrelevance, while removing them did not affect criterion validity.

Serum sestrins: potential predictive molecule in human sarcopenia.

BACKGROUND: The aging trajectory from a state of robustness and good health proceeds from sarcopenia to frailty followed by disability and death due to decline in skeletal muscle mass and function. Sarcopenia is now formally recognized as a muscle disease with an ICD-10-MC diagnosis code. The autophagic response seems to be affected in the skeletal muscle during aging contributing to sarcopenia. Sestrins (Sesns) proteins play a critical role in autophagy induction under cellular stress conditions. AIMS: The study aims to identify sarcopenia in older adults using Asian Working group guidelines (AWGS) to determine clinically relevant cut-off levels for diagnosis and their association with antioxidant protein Sesns. METHODS: The study recruited 102 older adults attending Geriatric medicine OPD AIIMS, New Delhi, India. The level of serum Sesns were evaluated by Surface Plasmon Resonance (SPR) and validated by immunoblotting. Fifty older adults were diagnosed as sarcopenics according to AWGS. RESULTS: Sesn 1 (p = 0.0448) and Sesn 2 (p < 0.0001) levels were significantly reduced in sarcopenic compared to non-sarcopenic. ROC analysis showed a better cut-off of Sesn 2; 10.104 ng/µL with 92% sensitivity and 84% specificity. Even after adjusting the values with respect to confounding factors, Sesn levels remained significantly reduced in sarcopenics (p < 0.030). DISCUSSION: The level of Sesn 2 showed positive co-relation with the characteristics of sarcopenia. This study first time reported the concentration of serum sestrin in sarcopenic older adults. CONCLUSION: It can be concluded that sarcopenia can be diagnosed at the early stage by using the serum sestrin scale as one of the potential biomarker.

Programmed death-1+ T cells inhibit effector T cells at the pathological site of miliary tuberculosis.

Optimal T cell activation is vital for the successful resolution of microbial infections. Programmed death-1 (PD-1) is a key immune check-point receptor expressed by activated T cells. Aberrant/excessive inhibition mediated by PD-1 may impair host immunity to Mycobacterium tuberculosis infection, leading to disseminated disease such as miliary tuberculosis (MTB). PD-1 mediated inhibition of T cells in pulmonary tuberculosis and TB pleurisy is reported. However, their role in MTB, particularly at the pathological site, remains to be addressed. The objective of this study was to investigate the role of PD-1-PD-ligand 1 (PD-L1) in T cell responses at the pathological site from patients of TB pleurisy and MTB as clinical models of contained and disseminated forms of tuberculosis, respectively. We examined the expression and function of PD-1 and its ligands (PD-L1-PD-L2) on host immune cells among tuberculosis patients. Bronchoalveolar lavage-derived CD3 T cells in MTB expressed PD-1 (54·2 ± 27·4%, P ≥ 0·0009) with significantly higher PD-1 ligand-positive T cells (PD-L1: 19·8 ± 11·8%; P ≥ 0·019, PD-L2: 12·6 ± 6·2%; P ≥ 0·023), CD19+ B cells (PD-L1: 14·4 ± 10·4%; P ≥ 0·042, PD-L2: 2·6 ± 1·43%; not significant) and CD14+ monocytes (PD-L1: 40·2 ± 20·1%; P ≥ 0·047, PD-L2: 22·4 ± 15·6%; P ≥ 0·032) compared with peripheral blood (PB) of MTB and healthy controls. The expression of PD-1 was associated with a diminished number of cells producing effector cytokines interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-2 and elevated apoptosis. Locally accumulated T cells were predominantly PD-1+ -PD-L1+ , and blocking this pathway restores the protective T cell response. We conclude that M. tuberculosis exploits the PD-1 pathway to evade the host immune response by altering the T helper type 1 (Th1) and Th2 balance at the pathological site of MTB, thereby favouring disease dissemination.

Association between dental prosthesis need, nutritional status and quality of life of elderly subjects.

PURPOSE: To determine the effect of prosthesis need on nutritional status and oral health-related quality of life (OHrQoL) in elderly and to check the disparity between prosthesis need and prosthesis want in the Indian elderly. METHODS: A total of 946 geriatric participants reporting to a geriatric medicine clinic were recruited in the study. Mini-nutritional assessment (MNA), geriatric oral health assessment (GOHAI) indices, prosthesis need according to WHO criteria, and prosthesis want was recorded along with age, gender, socioeconomic status and posterior occluding pair. RESULTS: Significant associations exist between prosthesis need and age (p = 0.005), MNA (p = 0.006) and GOHAI (p = 0.000). Prosthesis demand too was influenced by age (p = 0.004), posterior occluding pairs (p = 0.000), MNA (p = 0.012) and GOHAI (p = 0.000). GOHAI was negatively correlated with upper (r = -0.445) and lower prosthesis need (r = -0.460). Participants with some prosthesis need had significantly lower MNA and GOHAI scores as compared to those with no prosthesis need. Though prosthesis need was high (79.7 %), demand was low (39.3 %). CONCLUSION: Prosthesis need affects nutritional status and OHrQoL in elderly, and a wide gap exists between need and want of prosthesis.

Prevalence of DSM-5 mild and major neurocognitive disorder in India: Results from the LASI-DAD.

INTRODUCTION: India, with its rapidly aging population, faces an alarming burden of dementia. We implemented DSM-5 criteria in large-scale, nationally representative survey data in India to characterize the prevalence of mild and major Neurocognitive disorder. METHODS: The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) (N = 4,096) is a nationally representative cohort study in India using multistage area probability sampling methods. Using neuropsychological testing and informant reports, we defined DSM-5 mild and major neurocognitive disorder, reported its prevalence, and evaluated criterion and construct validity of the algorithm using clinician-adjudicated Clinical Dementia Ratings (CDR)®. RESULTS: The prevalence of mild and major neurocognitive disorder, weighted to the population, is 17.6% and 7.2%. Demographic gradients with respect to age and education conform to hypothesized patterns. Among N = 2,390 participants with a clinician-adjudicated CDR, CDR ratings and DSM-5 classification agreed for N = 2,139 (89.5%) participants. DISCUSSION: The prevalence of dementia in India is higher than previously recognized. These findings, coupled with a growing number of older adults in the coming decades in India, have important implications for society, public health, and families. We are aware of no previous Indian population-representative estimates of mild cognitive impairment, a group which will be increasingly important in coming years to identify for potential therapeutic treatment.

50,000 years of Evolutionary History of India: Insights from ~2,700 Whole Genome Sequences.

India has been underrepresented in whole genome sequencing studies. We generated 2,762 high coverage genomes from India-including individuals from most geographic regions, speakers of all major languages, and tribal and caste groups-providing a comprehensive survey of genetic variation in India. With these data, we reconstruct the evolutionary history of India through space and time at fine scales. We show that most Indians derive ancestry from three ancestral groups related to ancient Iranian farmers, Eurasian Steppe pastoralists and South Asian hunter-gatherers. We uncover a common source of Iranian-related ancestry from early Neolithic cultures of Central Asia into the ancestors of Ancestral South Indians (ASI), Ancestral North Indians (ANI), Austro-asiatic-related and East Asian-related groups in India. Following these admixtures, India experienced a major demographic shift towards endogamy, resulting in extensive homozygosity and identity-by-descent sharing among individuals. At deep time scales, Indians derive around 1-2% of their ancestry from gene flow from archaic hominins, Neanderthals and Denisovans. By assembling the surviving fragments of archaic ancestry in modern Indians, we recover ~1.5 Gb (or 50%) of the introgressing Neanderthal and ~0.6 Gb (or 20%) of the introgressing Denisovan genomes, more than any other previous archaic ancestry study. Moreover, Indians have the largest variation in Neanderthal ancestry, as well as the highest amount of population-specific Neanderthal segments among worldwide groups. Finally, we demonstrate that most of the genetic variation in Indians stems from a single major migration out of Africa that occurred around 50,000 years ago, with minimal contribution from earlier migration waves. Together, these analyses provide a detailed view of the population history of India and underscore the value of expanding genomic surveys to diverse groups outside Europe.

Region-based analysis with functional annotation identifies genes associated with cognitive function in South Asians from India.

The prevalence of dementia among South Asians across India is approximately 7.4% in those 60 years and older, yet little is known about genetic risk factors for dementia in this population. Most known risk loci for Alzheimer's disease (AD) have been identified from studies conducted in European Ancestry (EA) but are unknown in South Asians. Using whole-genome sequence data from 2680 participants from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study of India (LASI-DAD), we performed a gene-based analysis of 84 genes previously associated with AD in EA. We investigated associations with the Hindi Mental State Examination (HMSE) score and factor scores for general cognitive function and five cognitive domains. For each gene, we examined missense/loss-of-function (LoF) variants and brain-specific promoter/enhancer variants, separately, both with and without incorporating additional annotation weights (e.g., deleteriousness, conservation scores) using the variant-Set Test for Association using Annotation infoRmation (STAAR). In the missense/LoF analysis without annotation weights and controlling for age, sex, state/territory, and genetic ancestry, three genes had an association with at least one measure of cognitive function (FDR q<0.1). APOE was associated with four measures of cognitive function, PICALM was associated with HMSE score, and TSPOAP1 was associated with executive function. The most strongly associated variants in each gene were rs429358 (APOE ε4), rs779406084 (PICALM), and rs9913145 (TSPOAP1). rs779406084 is a rare missense mutation that is more prevalent in LASI-DAD than in EA (minor allele frequency=0.075% vs. 0.0015%); the other two are common variants. No genes in the brain-specific promoter/enhancer analysis met criteria for significance. Results with and without annotation weights were similar. Missense/LoF variants in some genes previously associated with AD in EA are associated with measures of cognitive function in South Asians from India. Analyzing genome sequence data allows identification of potential novel causal variants enriched in South Asians.

Molecular detection of Mycoplasma pneumoniae by quantitative real-time PCR in patients with community acquired pneumonia.

BACKGROUND & OBJECTIVES: Mycoplasma pneumoniae is the most important and common cause of community-acquired pneumonia (CAP). The conventional detection methods (culture and serology) lack sensitivity. PCR offers a better approach for rapid detection but is prone to carry over contamination during manipulation of amplification products. Quantitative real-time PCR (qRT-PCR) method offers an attractive alternative detection method. In the present study, qRT-PCR, PCR and serology methods were used to detect M. pneumoniae infection in cases of pneumonias and findings compared. METHODS: A total of 134 samples consisting of blood (for serology) and respiratory secretions (for PCR and qRT-PCR) from 134 patients were collected. The blood samples were tested for IgG, IgM and IgA using commercially available kits. For standardization of PCR of M. pneumoniae P1 gene was cloned in pGEMTEasy vector. Specific primers and reporter sequence were designed and procured for this fragment. The qRT-PCR assay was performed to prepare the standard curve for M. pneumoniae positive control DNA template and detection in patient samples. RESULTS: Of the 134 patients, 26 (19%) were positive for antibodies against M. pneumoniae. IgG was positive in 14.92 per cent (20) cases, IgM in 4.47 per cent (6) and IgA was positive in 5.22 per cent (7) cases. In the qRT-PCR assay 19 per cent (26) samples were positive. Of the 26 qRT-PCR positive samples, nine could be detected by serology. PCR was positive for 25 samples. An extra sample negative by PCR was detected by qRT-PCR. Thus, real-time PCR assay, PCR and serology in combination could detect M. pneumoniae infection in 43 patients. INTERPRETATION & CONCLUSIONS: The study shows that 17 patients were detected by serology alone, 17 were detected by qRT-PCR only and nine patients were positive by both serology and real-time PCR. Of the 134 samples tested, 25 were positive by conventional PCR, but qRT-PCR could detect one more sample that was negative by PCR and serology. These results suggest that a combination of two or three methods may be required for reliable identification of CAP due to M. pneumoniae.

Serological & molecular approaches for diagnosis of leptospirosis in a tertiary care hospital in north India: a 10-year study.

BACKGROUND & OBJECTIVES: Leptospirosis, a spirochetal zoonosis, is underreported from the northern States of India. This study reports results of a 10-year retrospective sero-epidemiological survey of leptospirosis conducted in a tertiary care hospital in New Delhi, India. METHOD: A total of 1453 patients clinically suspected for leptospirosis were included and investigated initially by IgM ELISA. A proportion of these were subjected to culture, microscopic agglutination test (MAT) and polymerase chain reaction (PCR). RESULTS: Of the 1453 patients, 391 (26.90%) were positive serologically by IgM ELISA. Seropositive and seronegative patients revealed no significant difference in clinical features and laboratory parameters. Amongst the IgM seropositive cases, culture for leptospires was positive in 5 of 192 (2.6%), MAT in 50 of 138 (36.23%), PCR from blood and urine in 10 of 115 (8.7%) and 10 of 38 (26.31%) cases, respectively. In Leptospira spp. positive patients co-infections with viral hepatitis E, malaria and dengue fever were diagnosed in 27 cases. INTERPRETATION & CONCLUSIONS: The overall seropositivity for leptospirosis was 26.9 per cent in our study. A decreasing trend in seropositivity was observed in recent years. Co-infections with malaria, dengue, hepatitis A and E were also seen. Since leptospirosis is a treatable disease, correct and rapid diagnosis may help in effective management of patients.

Trajectories and correlates of poor mental health in India over the course of the COVID-19 pandemic: a nation-wide survey.

Introduction: The COVID-19 pandemic had large impacts on mental health; however, most existing evidence is focused on the initial lockdown period and high-income contexts. By assessing trajectories of mental health symptoms in India over two years, we aim to understand the effect of later time periods and pandemic characteristics on mental health in a lower-middle income context. Methods: We used data from the Real-Time Insights of COVID-19 in India (RTI COVID-India) cohort study (N=3,662). We used covariate-adjusted linear regression models with generalized estimating equations to assess associations between mental health (PHQ-4 score) and pandemic periods as well as pandemic characteristics (COVID-19 cases and deaths, government stringency, self-reported financial impact, COVID-19 infection in the household) and explored effect modification by age, gender, and rural/urban residence. Results: Mental health symptoms dropped immediately following the lockdown period but rose again during the delta and omicron waves. Associations between mental health and later pandemic stages were stronger for adults 45 years of age and older (p<0.001). PHQ-4 scores were significantly and independently associated with all pandemic characteristics considered, including estimated COVID-19 deaths (PHQ-4 difference of 0.041 SD units; 95% Confidence Interval 0.030 - 0.053), government stringency index (0.060 SD units; 0.048 - 0.072), self-reported major financial impacts (0.45 SD units; 0.41-0.49), and COVID-19 infection in the household (0.11 SD units; 0.07-0.16). Conclusion: While the lockdown period and associated financial stress had the largest mental health impacts on Indian adults, the effects of the pandemic on mental health persisted over time, especially among middle-age and older adults. Results highlight the importance of investments in mental health supports and services to address the consequences of cyclical waves of infections and disease burden due to COVID-19 or other emerging pandemics.

Mycoplasma pneumoniae among Hospitalized Patients with Acute Respiratory Tract Infections in an Indian Tertiary Care Hospital: an Underreported Health Problem.

The epidemiology of Mycoplasma pneumoniae (Mp) is poorly understood in India. The present study was conducted to identify the prevalence of Mp in a large set of patients with acute respiratory tract infections (ARI) in an Indian tertiary hospital. During 2015-2020, we tested throat swab specimens from patients with the clinical diagnosis of ARI (n = 1,098) by a real-time PCR and compared the demographic, clinical, laboratory, and outcome data of Mp-positive and Mp-negative patients. During the study period, 5% (55/1,098) of the tested samples were positive for Mp by PCR. School-aged children and young adults represented 36% (20/55) of the cases and 47.3% (26/55) of the cases were registered during the summer and monsoon. Among the Mp-positive patients, 61.8% (34/55) had underlying conditions; the most common were malignancy (n = 12; 21.8%) and hypertension (n = 6; 10.9%). Fever (98.2% versus 84.9%; P = 0.006), and pharyngitis (27.3% versus 16.3%; P = 0.034) were significantly common in the Mp-positive group than Mp-negative group. Among the Mp-positive group, 20% (11/55) of patients were admitted to an intensive care unit and a total of 7/55 (12.7%) patients received ventilatory support. The mortality in the Mp-positive cohort was 13.3%. The study provides baseline data regarding Mp prevalence and clinical characteristics. The application of molecular assays for diagnosing this pathogen among hospitalized patients with ARI could reduce inappropriate empirical antibiotic treatment and improve patient outcomes. Further large-scale studies are required to avoid the underdiagnosis of Mp infections in India and such studies should address some research gaps, such as macrolide resistance and molecular typing. IMPORTANCE M. pneumoniae (Mp) is a significant pathogen causing atypical pneumonia but by far these infections are underreported clinical entities in India. In the present study, we report the prevalence of Mp and describe the demographic and baseline clinical data of Mp-positive cases in an Indian tertiary care hospital. Our study may improve the clinician's awareness of this important agent of respiratory infection therefore timely and accurate diagnostic tools can be applied for patient management decisions and outcomes.

Blood Circulatory Level of Seven Sirtuins in Alzheimer's Disease: Potent Biomarker Based on Translational Research.

Alzheimer's disease (AD) is an accelerating neurodegenerative disorder. Dysfunction of mitochondria and oxidative stress contributes to the pathogenesis of AD. Sirtuins play a role in this pathway and can be a potential marker to study neurodegenerative changes. This study evaluated serum levels of all seven sirtuin (SIRT1-SIRT7) proteins in three study groups: AD, mild cognitive impairment (MCI) and geriatric control (GC) by surface plasmon resonance (SPR) technique. Further, it was validated by the Western blot experiment. ROC analysis was performed to differentiate the study group based on the concentration of serum SIRT proteins. Out of seven sirtuins, serum SIRT1, SIRT3 and SIRT6 levels (mean ± SD) were significantly decreased in AD (1.65 ± 0.56, 3.15 ± 0.28, 3.36 ± 0.32 ng/µl), compared to MCI (2.17 ± 0.39, 3.60 ± 0.51, 3.73 ± 0.48 ng/µl) and GC (2.84 ± 0.47, 4.55 ± 0.48, 4.65 ± 0.55 ng/µl). ROC analysis showed the cut-off value with high sensitivity and specificity for cognitive impairment (AD and MCI). The concentration declined significantly with the disease progression. No specific difference was observed in the case of other SIRTs between the study groups. This study reveals an inverse relation of serum SIRT1, SIRT3 and SIRT6 concentration with AD. ROC analysis showed that these serum proteins have greater accuracy in diagnosing of AD. This is the first report of estimation of all seven serum sirtuins and the clinical relevance of SIRT3 and SIRT6 as serum protein markers for AD.

Circulatory GSK-3ß: Blood-Based Biomarker and Therapeutic Target for Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is the progressive brain disorder which degenerates brain cells connection and causes memory loss. Although AD is irreversible, it is not impossible to arrest or slow down the progression of the disease. However, this would only be possible if the disease is diagnosed at an early stage, and early diagnosis requires clear understanding of the pathogenesis at molecular level. Overactivity of GSK-3ß and p53 accounts for tau hyperphosphorylation and the formation of amyloid-ß plaques. OBJECTIVE: Here, we explored GSK-3ß and p53 as blood-based biomarkers for early detection of AD. METHODS: The levels of GSK-3ß, p53, and their phosphorylated states were measured using surface plasmon resonance and verified using western blot in serum from AD, mild cognitive impairment (MCI), and geriatric-control (GC) subjects. The neurotoxic SH-SY5Y cell line was treated with antioxidant Emblica Officinalis (EO) for rescue effect. RESULTS: GSK-3ß, p53, and their phosphorylated states were significantly over expressed (p > 0.001) in AD and MCI compared to GC and can differentiate AD and MCI from GC. The expression level of GSK-3ß and p53 proteins were found to be downregulated in a dose-dependent manner after the treatment with EO in amyloid-b-induced neurotoxic cells. CONCLUSION: These proteins can serve as potential blood markers for the diagnosis of AD and EO can suppress their level. This work has translational value and clinical utility in the future.

The changing perspective of clinical trial designs.

Maintaining health and well-being of the population is a universal priority. Governments around the globe are therefore seeking greater efficiency and better outcomes from researches being held. Although large randomized trials or systematic review of several large trials provides the highest level of evidence, the intricate cost, time, and difficulties of conventional trials have led to questions about their sustainability commanding search for alternative approaches. Demands for improved competences in medical research have led to mounting interest in newer clinical trial designs. This article provides an insight into newer clinical trial designs, including cluster trials, adaptive designs, the master protocols along with their strengths, weaknesses, and which trials design should be opted for in different clinical scenarios.

Frailty, Disability, and Mortality in a Rural Community-Dwelling Elderly Cohort from Northern India.

INTRODUCTION: With increasing proportion of the elderly in the world, detecting and preventing frailty assumes importance to improve the quality of life and health. The study aimed to estimate the prevalence of frailty, disability and its determinants and their relation with mortality among community dwelling elderly cohort. MATERIALS AND METHODS: The study was conducted in a cohort in rural Haryana, India, and was followed till October 2018. Frailty was assessed using the Edmonton Frailty Scale and disability was assessed using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) scale by trained physicians. RESULTS: The prevalence of frailty was found to be 47.3% (95% confidence interval [CI]: 44.0-50.8). The median WHODAS-2 score was found to be 10.4 (2.1-29.2). Those who were older (odds ratio [OR] - 2.5; 95% CI: 1.8-3.4), women (OR - 3.3; 95% CI: 2.2-4.9) and those with chronic disease (OR 2.3; 95% CI: 1.7-3.1) had higher rates of frailty. The adjusted hazard ratio of death among frail people was 4.7 (2.3-9.7). CONCLUSION: In this study we found the frailty is associated with the mortality among community dwelling elderly. Thus early identification of the frailty and its determinants may help us to reduce the mortality related to this.

Incidence, risk factors, and viral etiology of community-acquired acute lower respiratory tract infection among older adults in rural north India.

BACKGROUND: There are limited data on incidence, risk factors and etiology of acute lower respiratory tract infection (LRTI) among older adults in low- and middle-income countries. METHODS: We established a cohort of community dwelling older adults ≥60 years and conducted weekly follow-up for acute respiratory infections (ARI) during 2015-2017. Nurses assessed ARI cases for LRTI, collecting combined nasal/throat swabs from all LRTI cases and an equal number of age- and sex-matched asymptomatic neighbourhood controls. Swabs were tested for influenza viruses, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and parainfluenza viruses (PIV) using polymerase chain reaction. LRTI and virus-specific LRTI incidence was calculated per 1000 person-years. We estimated adjusted incidence rate ratios (IRR) for risk factors using Poisson regression and calculated etiologic fractions (EF) using adjusted odds ratios for detection of viral pathogens in LRTI cases vs controls. RESULTS: We followed 1403 older adults for 2441 person-years. LRTI and LRTI-associated hospitalization incidences were 248.3 (95% confidence interval (CI) = 229.3-268.8) and 12.7 (95% CI = 8.9-18.1) per 1000 person-years. Persons with pre-existing chronic bronchitis as compared to those without (incidence rate ratio (IRR) = 4.7, 95% CI = 3.9-5.6); aged 65-74 years (IRR = 1.6, 95% CI = 1.3-2.0) and ≥75 years (IRR = 1.8, 95% CI = 1.4-2.4) as compared to 60-64 years; and persons in poorest wealth quintile (IRR = 1.4, 95% CI = 1.1-1.8); as compared to those in wealthiest quintile were at higher risk for LRTI. Virus was detected in 10.1% of LRTI cases, most commonly influenza (3.8%) and RSV (3.0%). EF for RSV and influenza virus was 83.9% and 83.6%, respectively. CONCLUSION: In this rural cohort of older adults, the incidence of LRTI was substantial. Chronic bronchitis was an important risk factor; influenza virus and RSV were major viral pathogens.

Sero diagnosis of Legionella infection in community acquired pneumonia.

BACKGROUND & OBJECTIVES: Legionella pneumophila has been increasingly recognized as an emerging pathogen responsible for community acquired pneumonia (CAP) worldwide. In India, the actual burden is not known. The present study was thus undertaken to see the presence of Legionella infection in patients with community acquired pneumonia admitted in a tertiary care centre in north India. METHODS: Both children and adults (n=113) with symptoms of pneumonia were included in the study. Clinical samples (blood, urine, nasopharyngeal aspirates, bronchoalveolar lavage, sputum, etc.) were collected and subjected to culture and other tests. Enzyme linked immunosorbent assay (ELISA) was done by commercial kits for all the three classes of immunoglobulins (IgG, IgM & IgA). Urinary antigen was also detected using commercial kits. Culture was performed on 51 respiratory tract fluid samples. Serum samples of 44 healthy controls were also screened for the presence of anti-legionella antibodies (IgG, IgM & IgA). RESULTS: Thirty one of the 113 cases (27.43%) were serologically positive. Anti-legionella IgG, IgM and IgA antibodies were positive in 7.96, 15.92 and 11.50 per cent patients respectively. In controls, seropositivity was 9.09 (4/44). IgA was positive in 3 and IgM, IgG combined in one. Antigenuria detection by Microwell ELISA kit showed 17.69 per cent positivity. Four antigenuria positive patients were also serologically positive; of these two patients were positive for IgM, hence considered as confirmed cases of Legionella infection. None of the sample was culture positive. INTERPRETATION & CONCLUSIONS: Combination of serology and antigenuria detection may be a valuable tool for the diagnosis of Legionella infection in absence of culture positivity. In order to evaluate the actual burden of Legionella in community acquired pneumonia, further studies with larger samples need to be done.

Legionella pneumophila in Patients with Pneumonia at a Referral Hospital, New Delhi, India, 2015-2020.

Legionnaires' disease (LD) is an established cause of pneumonia, and the disease remains largely underdiagnosed. Even though LD has been reported from many parts of the world, only sporadic cases have been reported in India. During February 2015-January 2020, we enrolled 597 patients with radiographically confirmed pneumonia and tested respiratory secretions for Legionella spp. by using real-time PCR, and culture. A commercial urinary antigen test (UAT) was also used to detect the Legionella pneumophila (Lp) serogroup 1 antigen in urine. An LD case was defined as a patient with pneumonia and positive results for Legionella spp. infections determined by real-time PCR (from any respiratory specimen) or culture or UAT. Demographic data, risk factors, clinical, radiological, and outcome data of Lp-positive and Lp-negative patients were compared using logistic regression. Over the study period, 14 (2.3%) patients were positive for Legionella spp. infections by real-time PCR and UAT; eight (57%) were admitted to the intensive care unit, and four (28.6%) in-hospital deaths occurred. Bivariate analysis showed that renal disease, neurological conditions, confusion, leukocytosis, and requirement of oxygen support were more common in the Lp-positive group than in the Lp-negative group. However, multivariate analysis failed to confirm most of these differences; renal disease was the only independent variable remaining significant. All test methods have intrinsic limitations in identifying Legionella; therefore, more than one testing method should be used. Application of molecular assays including real-time PCR has great value because of its high sensitivity, specificity, and rapid diagnostic potency. Increased awareness and improved diagnostic testing could facilitate early detection of cases, pathogen-directed therapy, and improved outcomes for patients.