Interrelationships between physical multimorbidity, depressive symptoms and cognitive function among older adults in China, India and Indonesia: A four-way decomposition analysis.

OBJECTIVE: This paper explores the role of depressive symptoms (mediator/moderator) in the association between physical multimorbidity (exposure) and cognitive function (outcome) among older adults in the three most populous middle-income countries. METHODS: This study used cross-sectional data from China (2015 China Health and Retirement Longitudinal Study), India (2017/2018 Longitudinal Ageing Study in India), and Indonesia (2014/2015 Indonesian Family Life Survey), with a total sample of 73,199 respondents aged ≥ 45 years. Three domains of cognitive tests were harmonised across surveys, including time orientation, word recall, and numeracy. The four-way decomposition analysis assessed the mediation and interaction effects between exposure, mediator/moderator, and outcome, adjusted for covariates. RESULTS: The mean age of the respondents (in years) was slightly younger in Indonesia (56.0, SD = 8.8) than in China (59.5, SD = 9.3) and India (60.0, SD = 10.5). The proportion of male respondents was 49.3 % in China, 47.3 % in India, and 47.5 % in Indonesia. Respondents in China had the highest mean cognitive function z scores (54.7, SD = 19.9), followed by India (51.1, SD = 20.0) and Indonesia (51.0, SD = 18.4). Physical multimorbidity was associated with lower cognitive function in China and India (p < 0.0001), with 48.4 % and 40.0 % of the association explained by the mediating effect of depressive symptoms ('overall proportion due to mediation'). The association was not found in Indonesia. CONCLUSION: Cognitive functions were lower among individuals with physical multimorbidity, and depressive symptoms mainly explained the association. Addressing depressive symptoms among persons with physical multimorbidity is likely to have not only an impact on their mental health but could prevent cognitive decline.

"I Would Rather Die Drinking than take the Medicine": Role of Alcohol Use Disorder in Loss-to-follow-up of Tuberculosis Treatment in a Rural Area of Ballabgarh, Haryana.

Introduction: Alcohol use disorder (AUD) is a significant risk factor for tuberculosis (TB) treatment loss-to-follow-up (LTFU). This field-based study was undertaken to understand the role of AUD and TB treatment LTFU and the reasons behind this association in a rural area of Ballabgarh, Haryana. Material and Methods: TB patients who had completed their treatment and who had been LTFU were included in the study, along with the National TB Elimination Program (NTEP) staff, healthcare providers, family, and community members from Ballabgarh block of the north Indian state of Haryana. In-depth interviews (IDIs) and focused group discussions (FGDs) were conducted to gauge the perceptions of stakeholders regarding reasons for LTFU, especially in the context of alcohol use. Inductive analysis of the transcripts was done in keeping with the grounded theory, and themes with their sub-themes were identified. A conceptual framework of TB-AUD was constructed, and potential areas for intervention were determined. Results: Fifty-eight IDIs and four FGDs were conducted in mid-2018. Almost all key informants and many patient participants believed that alcohol use makes TB patients highly susceptible to treatment LTFU. Key themes identified were shared personality traits and attitudes, combined side effects of anti-tubercular drugs and alcohol use, lack of family support, and an adverse financial situation. Conclusion: These findings call for a change in NTEP's approach to AUD-TB. Interventions may include collecting alcohol use information at patient enrolment and closure, integrating brief interventions for alcohol cessation in NTEP, and linking patients to deaddiction centers with the provision of appropriate dietary and financial support.

The burden of headache disorders in North India: methodology, and validation of a Hindi version of the HARDSHIP questionnaire, for a community-based survey in Delhi and national capital territory region.

BACKGROUND: Knowledge of the prevalence and attributable burden of headache disorders in India is sparse, with only two recent population-based studies from South and East India. These produced conflicting results. A study in North India is needed. We report the methodology of such a study using, and validating, a Hindi translation of the Headache-Attributed Restriction, Disability, Social Handicap, and Impaired Participation (HARDSHIP) questionnaire developed by Lifting The Burden (LTB). Almost half of the Indian population speak Hindi or one of its dialects. METHODS: The study adopted LTB's standardized protocol for population-based studies in a cross-sectional survey using multistage random sampling conducted in urban Delhi and a surrounding rural area. Trained interviewers visited households unannounced, randomly selected one adult member from each and applied the Hindi version of HARDSHIP in face-to-face interviews. The most bothersome headache reported by participants was classified algorithmically into headache on ≥ 15 days/month (H15 +), migraine (including definite and probable) or tension-type headache (including definite and probable). These diagnoses were mutually exclusive. All participants diagnosed with H15 + and a 10% subsample of all others were additionally assessed by headache specialists and classified as above. We estimated the sensitivity and specificity of HARDSHIP diagnoses by comparison with the specialists' diagnoses. RESULTS: From 3,040 eligible households, 2,066 participants were interviewed. The participating proportions were 98.3% in rural areas but 52.9% in urban Delhi. In the validation subsample of 291 participants (149 rural, 142 urban), 61 did not report any headache (seven of those assessed by HARDSHIP, eight by headache specialists and 46 by both) [kappa = 0.83; 95% CI: 0.74-0.91]. In the remaining 230 participants who reported headache in the preceding year, sensitivity, specificity and kappa with (95% CI) were 0.73 (0.65-0.79), 0.80 (0.67-0.90) and 0.43 (0.34-0.58) for migraine; 0.71 (0.56-0.83), 0.80 (0.730.85) and 0.43 (0.37-0.62) for TTH and 0.75 (0.47-0.94), 0.93 (0.89-0.96) and 0.46 (0.34-0.58) for H15 + respectively. CONCLUSION: This study validates the Hindi version of HARDSHIP, finding its performance similar to those of other versions. It can be used to conduct population surveys in other Hindi-speaking regions of India.

Seasonal variations in social contact patterns in a rural population in north India: Implications for pandemic control.

Social contact mixing patterns are critical to model the transmission of communicable diseases, and have been employed to model disease outbreaks including COVID-19. Nonetheless, there is a paucity of studies on contact mixing in low and middle-income countries such as India. Furthermore, mathematical models of disease outbreaks do not account for the temporal nature of social contacts. We conducted a longitudinal study of social contacts in rural north India across three seasons and analysed the temporal differences in contact patterns. A contact diary survey was performed across three seasons from October 2015-16, in which participants were queried on the number, duration, and characteristics of contacts that occurred on the previous day. A total of 8,421 responses from 3,052 respondents (49% females) recorded characteristics of 180,073 contacts. Respondents reported a significantly higher number and duration of contacts in the winter, followed by the summer and the monsoon season (Nemenyi post-hoc, p<0.001). Participants aged 0-9 years and 10-19 years of age reported the highest median number of contacts (16 (IQR 12-21), 17 (IQR 13-24) respectively) and were found to have the highest node centrality in the social network of the region (pageranks = 0.20, 0.17). A large proportion (>80%) of contacts that were reported in schools or on public transport involved physical contact. To the best of our knowledge, our study is the first from India to show that contact mixing patterns vary by the time of the year and provides useful implications for pandemic control. We compared the differences in the number, duration and location of contacts by age-group and gender, and studied the impact of the season, age-group, employment and day of the week on the number and duration of contacts using multivariate negative binomial regression. We created a social network to further understand the age and gender-specific contact patterns, and used the contact matrices in each season to parameterise a nine-compartment agent-based model for simulating a COVID-19 epidemic in each season. Our results can be used to parameterize more accurate mathematical models for prediction of epidemiological trends of infections in rural India.

Cost of acute respiratory illness episode and its determinants among community-dwelling older adults: a four-site cohort study from India.

Introduction: Advocacy for the provision of public health resources, including vaccine for the prevention of acute respiratory illnesses (ARIs) among older adults in India, needs evidence on costs and benefits. Using a cohort of community-dwelling adults aged 60 years and older in India, we estimated the cost of ARI episode and its determinants. Methods: We enrolled 6016 participants in Ballabgarh, Chennai, Kolkata and Pune from July 2018 to March 2020. They were followed up weekly to identify ARI and classified them as acute upper respiratory illness (AURI) or pneumonia based on clinical features based on British Thoracic Society guidelines. All pneumonia and 20% of AURI cases were asked about the cost incurred on medical consultation, investigation, medications, transportation, food and lodging. The cost of services at public facilities was supplemented by WHO-Choosing Interventions that are Cost-Effective(CHOICE) estimates for 2019. Indirect costs incurred by the affected participant and their caregivers were estimated using human capital approach. We used generalised linear model with log link and gamma family to identify the average marginal effect of key determinants of the total cost of ARI. Results: We included 2648 AURI and 1081 pneumonia episodes. Only 47% (range 36%-60%) of the participants with pneumonia sought care. The mean cost of AURI episode was US$13.9, while that of pneumonia episode was US$25.6, with indirect costs comprising three-fourths of the total. The cost was higher among older men by US$3.4 (95% CI: 1.4 to 5.3), those with comorbidities by US$4.3 (95% CI: 2.8 to 5.7) and those who sought care by US$17.2 (95% CI: 15.1 to 19.2) but not by influenza status. The mean per capita annual cost of respiratory illness was US$29.5. Conclusion: Given the high community disease and cost burden of ARI, intensifying public health interventions to prevent and mitigate ARI among this fast-growing older adult population in India is warranted.

Mapping of mental health care facilities and psychiatrists in a North Indian district of India.

Introduction: Since 1990, the proportional contribution of mental disorders to India's total disease burden has nearly doubled, but the number of psychiatrists has not increased proportionately. Even after two decades of District Mental Health Programme (DMHP) launch, a considerable treatment gap still exists for mental illness. The present study aimed to map all health facilities providing mental health services and all psychiatrists in district Faridabad, Haryana. Methods: The starting point was the information available with the DMHP and district health office. This was supplemented by web search and snowball sampling. All identified facilities were visited to map the mental health services provided. All the mental health care providers and health care facilities were mapped using "Google my Maps". 2011 census data on population were used. Results: In Faridabad, 0.88 psychiatrists per lakh population were present. Most psychiatrists were concentrated in the urban area. The number of psychiatrists per lakh population was 1.1 in urban, compared to 0.54 in rural Faridabad. Clustering of mental health facilities was also observed more in urban areas (8.7 per 100 Sq Km) compared to rural areas (0.95 per 100 Sq Km) of district Faridabad. Conclusion: There was a scarcity of psychiatric manpower and facilities in the district with a distinct urban skew.

Healthier Food Purchase and Its Determinants in an Urban Resettlement Colony of Delhi.

Dietary risk, one of the major risk factors for the increasing burden of non-communicable diseases, is influenced by household food choices and purchases. A community-based cross-sectional study was conducted in 250 randomly selected households of an urban resettlement colony in Delhi to estimate the proportion of households purchasing different healthier food options during the last purchasing occasion and to identify its key determinants. Purchase of healthier options in staple items like wheat flour with fiber (100%), plant-based oils (97.9%), unpolished pulses (96.2%), and toned milk (94.5%) was high. Affordability and health considerations in food purchases were identified as key determinants.

ABDA Score: A Non-invasive Model to Identify Subjects with Fibrotic Non-alcoholic Steatohepatitis in the Community.

Background: Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH) are prevalent in the community, especially among those with metabolic syndrome. Patients with fibrotic NASH are at increased risk of liver-related-events. Currently available non-invasive tests have not been utilized for screening for fibrotic NASH among the community. We aimed to develop a screening tool for fibrotic NASH among community members. Methods: We included two large cohorts aimed at assessing cardiovascular disease among community members. Fibrotic NASH was defined using the FibroScan-aspartate aminotransferase score of ≥0.67 that identifies ≥F2 fibrosis and a non-alcoholic fatty liver disease activity score ≥4 with a specificity of 90%. Metabolic parameters, biochemical tests and anthropometry were used to develop a multivariate model. Results: The derivation cohort (n = 1660) included a population with a median age 45 years, 42.5% males, metabolic syndrome in 66% and 2.7% (n = 45) with fibrotic NASH. Multivariate analysis identified the four significant variables (Age, body mass index , Diabetes and alanine aminotransferas levels) used to derive an ABDA score. The score had high diagnostic accuracy (the area under receiver-operating characteristic curve, 0.952) with adequate internal validity. An ABDA score ≥-3.52 identified fibrotic NASH in the derivation cohort with a sensitivity and specificity of 88.9% and 88.3%. The score was validated in a second cohort (n = 357) that included 21 patients (5.9%) with fibrotic NASH, where it demonstrated a high area under receiver-operating characteristic curve (0.948), sensitivity (81%) and specificity (89.3%). Conclusions: ABDA score utilizes four easily available parameters to identify fibrotic NASH with high accuracy in the community.

Higher-order dialectic variation and syntactic convergence in the complex warble song of budgerigars.

Dialectic signatures in animal acoustic signals are key in the identification of and association with group members. Complex vocal sequences may also convey information about behavioral state, and may thus vary according to social environment. Some bird species, such as psittaciforms, learn and modify their complex acoustic signals throughout their lives. However, the structure and function of vocal sequences in open-ended vocal learners remains understudied. Here, we examined vocal sequence variation in the warble song of budgerigars, and how these change upon contact between social groups. Budgerigars are open-ended vocal learners which exhibit fission-fusion flock dynamics in the wild. We found that two captive colonies of budgerigars exhibited colony-specific differences in the syntactic structure of their vocal sequences. Individuals from the two colonies differed in the propensity to repeat certain note types, forming repetitive motifs which served as higher-order signatures of colony identity. When the two groups were brought into contact, their vocal sequences converged, and these colony-specific repetitive patterns disappeared, with males from both erstwhile colonies now producing similar sequences with similar syntactic structure. We present data suggesting that the higher-order temporal arrangement of notes/vocal units is modified throughout life by social learning as groups of birds continually associate and dissociate. Our study sheds light on the importance of examining signal structure at multiple levels of organization, and the potential for psittaciform birds as model systems to examine the influence of learning and social environment on acoustic signals.

Prevalence and determinants of delays in care among premature deaths due to acute cardiac conditions and stroke in residents of a district in India.

Background: Lack of timely care is a predictor of poor outcomes in acute cardiovascular emergencies including stroke. We assessed the presence of delay in seeking appropriate care among those who died due to cardiac/stroke emergencies in a community in northern India and identified the reasons and determinants of this delay. Methods: We conducted a social audit among all civil-registered premature (30-69 years) deaths due to acute cardiac event or stroke in the district. The three-delays model was used to qualitatively classify the delays in care-seeking-deciding to seek care, reaching the appropriate health facility (AHF) and initiating definitive treatment. Based on the estimated time from symptom onset to reaching AHF, we classified patients as early (reached within one hour) or delayed arrivers. We used mixed-effect logistic regression with postal code as a random effect to identify determinants of delayed arrival. Findings: Only 10.8% of the deceased reached an AHF within one hour. We noted level-1 delay in 38.4% (60% due to non-recognition of seriousness); level-2 delay in 20% (40% due to going to an inappropriate facility) and level-3 delay in 10.8% (57% due to lack of affordability). Patients with a monthly family income of >270US$ (aOR 0.44; 95% CI 0.21-0.93) were less and those staying farther from AHF (aOR 1.12; 95% CI 1.01-1.25 for each Km) were more likely to have delayed arrival in AHF. Interpretation: A small proportion of patients with cardiac and stroke emergencies reach health facility early with delays at multiple levels. Addressing the reasons for delay could prevent these deaths. Funding: : Indian Council of Medical Research, New Delhi, India.

Low-dose immunotherapy as a potentiator to increase the response with neo-adjuvant chemotherapy in oral cancers.

Neo-adjuvant chemotherapy (NACT) is utilized in locally advanced oral cancers to reduce the tumor burden and downstage the tumor to be amenable for definitive surgical management. Its long-term results compared to upfront surgical resection was not encouraging. Immunotherapy has now been used not only in recurrence and metastatic setting but also in the locally advanced tumor management regimens. The purpose of this concept paper is to bring forward the rationale to use a fixed low-dose immunotherapy agent as a potentiator to the standard NACT regimen and recommend their future investigation in oral cancer management.

Nasal shedding of vaccine viruses after immunization with a Russian-backbone live attenuated influenza vaccine in India.

BACKGROUND: We present post-vaccination nasal shedding findings from the phase IV, community-based, triple-blinded RCT conducted to assess efficacy of trivalent LAIV and inactivated influenza vaccines in rural north India. METHODS: Children aged 2-10 years received LAIV or intranasal placebo across 2015 and 2016, as per initial allocation. On days 2 and 4 post-vaccination, trained study nurses collected nasal swabs from randomly selected subset of trial participants based on operational feasibility, accounting for 10.0% and 11.4% of enrolled participants in 2015 and 2016, respectively. Swabs were collected in viral transport medium and transported under cold chain to laboratory for testing by reverse transcriptase real-time polymerase chain reaction. RESULTS: In year 1, on day 2 post-vaccination, 71.2% (74/104) of LAIV recipients shed at least one of vaccine virus strains compared to 42.3% (44/104) on day 4. During year 1, on day 2 post-vaccination, LAIV-A(H1N1)pdm09 was detected in nasal swabs of 12% LAIV recipients, LAIV-A(H3N2) in 41%, and LAIV-B in 59%. In year 2, virus shedding was substantially lower; 29.6% (32/108) of LAIV recipients shed one of the vaccine virus strains on day 2 compared to 21.3% on day 4 (23/108). CONCLUSION: At day 2 post-vaccination in year 1, two-thirds of LAIV recipients were shedding vaccine viruses. Shedding of vaccine viruses varied between strains and was lower in year 2. More research is needed to determine the reason for lower virus shedding and vaccine efficacy for LAIV-A(H1N1)pdm09.

Feasibility, safety, and patient acceptability of electronic inspiratory muscle training in patients who require prolonged mechanical ventilation in the intensive care unit: A dual-centre observational study.

BACKGROUND: Inspiratory muscle training (IMT) is an intervention that can be used to rehabilitate the respiratory muscle deconditioning experienced by patients with critical illness, requiring prolonged mechanical ventilation. Clinicians are currently using mechanical threshold IMT devices that have limited resistance ranges. OBJECTIVES: The objective of this study was to evaluate the safety, feasibility, and acceptability of using an electronic device to facilitate IMT with participants requiring prolonged mechanical ventilation. METHOD: A dual-centre observational cohort study, with convenience sampling, was conducted at two tertiary intensive care units. Daily training supervised by intensive care unit physiotherapists was completed with the electronic IMT device. A priori definitions for feasibility, safety, and acceptability were determined. Feasibility was defined as more than 80% of planned sessions completed. Safety was defined as no major adverse events and less than 3% minor adverse event rate, and acceptability was evaluated following the acceptability of intervention framework principles. RESULTS: Forty participants completed 197 electronic IMT treatment sessions. Electronic IMT was feasible, with 81% of planned sessions completed. There were 10% minor adverse events and no major adverse events. All the minor adverse events were transient without clinical consequences. All the participants who recalled completing electronic IMT sessions reported that the training was acceptable. Acceptability was demonstrated; over 85% of participants reported that electronic IMT was either helpful or beneficial and that electronic IMT assisted their recovery. CONCLUSION: Electronic IMT is feasible and acceptable to complete with critically ill participants who require prolonged mechanical ventilation. As all minor adverse events were transient without clinical consequences, electronic IMT can be considered a relatively safe intervention with patients who require prolonged mechanical ventilation.

Exosomal miRNAs and breast cancer: a complex theranostics interlink with clinical significance.

Breast cancer (BC) remains the most challenging global health crisis of the current decade, impacting a large population of females annually. In the field of cancer research, the discovery of extracellular vesicles (EVs), specifically exosomes (a subpopulation of EVs), has marked a significant milestone. In general, exosomes are released from all active cells but tumour cell-derived exosomes (TDXs) have a great impact (TDXs miRNAs, proteins, lipid molecules) on cancer development and progression. TDXs regulate multiple events in breast cancer such as tumour microenvironment remodelling, immune cell suppression, angiogenesis, metastasis (EMT-epithelial mesenchymal transition, organ-specific metastasis), and therapeutic resistance. In BC, early detection is the most challenging event, exosome-based BC screening solved the problem. Exosome-based BC treatment is a sign of the transforming era of liquid biopsy, it is also a promising therapeutic tool for breast cancer. Exosome research goes to closer precision oncology via a single exosome profiling approach. Our hope is that this review will serve as motivation for researchers to explore the field of exosomes and develop an efficient, and affordable theranostics approach for breast cancer.

Predictors of Out-of-Pocket Expenditure on Health Incurred by Elderly Persons Residing in a Rural Area of Faridabad District.

BACKGROUND: A significant portion of India's 1.2 billion population consists of elderly individuals, accounting for approximately 8.6%, who incur substantial out-of-pocket (OOP) healthcare expenses. Any policy for the elderly should encompass financial protection from illness-related expenditures. However, the lack of comprehensive information on OOP expenditure and its determinants precludes such action. METHODS: We conducted a cross-sectional study of 400 elderly persons residing in the rural town of Ballabgarh. The participants were randomly selected using the health demographic surveillance system. We utilized questionnaires and tools to assess the costs associated with outpatient and inpatient services in the previous year, as well as gather information on socio-demographics (individual characteristics), morbidity (motivation for seeking care), and social engagement (health-seeking). RESULTS: A total of 396 elderly persons participated, with a mean (SD) age of 69.4 (6.7), and 59.4% females. Nearly 96% and 50% of the elderly availed of outpatient and inpatient services, respectively, in the preceding year. The mean (IQR) annual OOP expenditure, as per the consumer price index 2021, was INR 12,543 (IQR, INR 8,288-16,787), with a median of INR 2,860 (IQR, INR 1,458-7,233), explained significantly by sex, morbidity status, social engagement, and mental health. CONCLUSION: In low-middle-income countries like India, policymakers may consider pre-payment mechanisms like health insurance for the elderly, using such prediction scores.

Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF): An Emerging Therapeutic Target for Neurodegenerative Disorders.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a member of the new family of neurotrophic factors (NTFs) with a unique structure and functions compared to other conventionally known NTFs. MANF is broadly expressed in developing and mature tissues, including the central nervous system and peripheral nervous system tissues. Growing research demonstrated that MANF protects neurons from endoplasmic reticulum (ER) stress-associated complications by restoring ER homeostasis and regulating unfolded protein response. This review discusses MANF signaling in neurodegenerative conditions with specific emphasis given to its overall effect and mechanisms of action in experimental models of Parkinson's disease, Alzheimer's disease, and stroke. Additional perspectives on its potential unexplored roles in other neurodegenerative conditions are also given.