All India Institute of Medical Sciences Bhubaneswar

The gut microbiota is emerging as a promising target for the management or prevention of inflammatory and metabolic disorders in humans. Many of the current research efforts are focused on the identification of specific microbial signatures, more particularly for those associated with obesity, type 2 diabetes, and cardiovascular diseases. Some studies have described that the gut microbiota of obese animals and humans exhibits a higher Firmicutes/Bacteroidetes ratio compared with normal-weight individuals, proposing this ratio as an eventual biomarker. Accordingly, the Firmicutes/Bacteroidetes ratio is frequently cited in the scientific literature as a hallmark of obesity. The aim of the present review was to discuss the validity of this potential marker, based on the great amount of contradictory results reported in the literature. Such discrepancies might be explained by the existence of interpretative bias generated by methodological differences in sample processing and DNA sequence analysis, or by the generally poor characterization of the recruited subjects and, more particularly, the lack of consideration of lifestyle-associated factors known to affect microbiota composition and/or diversity. For these reasons, it is currently difficult to associate the Firmicutes/Bacteroidetes ratio with a determined health status and more specifically to consider it as a hallmark of obesity.

INTRODUCTION: To mitigate the spread of the pandemic coronavirus infection (COVID-19), governments across the world have adopted "lockdowns" which have confined many individuals to their homes. This disrupts normal life routines, elements of which are important circadian cues. The pandemic is also associated with new stressors, altered roles, and uncertainties about health and economic security, which are also likely to affect sleep. The current study is an online survey of sleep experience, routines, physical activity, and symptoms of anxiety and depression, to study the alterations associated with the lockdown. MATERIALS AND METHODS: The survey was conducted in early May 2020 using a questionnaire circulated through social media platforms. Questions related to demographic characteristics, current and previous sleep schedules, routine, and working patterns. Insomnia (Insomnia Severity Index - 4), Stress (Perceived Stress Scale - 4), anxiety and depressive symptoms (Patient Health Questionnaire - 4) and physical activity (International Physical Activities Questionnaire) were assessed using standardized instruments. RESULTS: A total of 958 valid responses were received. Compared to the prelockdown period, there was a shift to a later bedtime and waking time, with a reduction in night-time sleep and an increase in day-time napping. These effects were visible across occupational groups, but mostly affected working individuals except health professionals. Sleep quality deteriorated across groups. Reductions in sleep duration were associated with depressive symptoms. CONCLUSIONS: The COVID-19 lockdown is associated with changes in sleep schedule and in the quantity and quality of night-time sleep. Although these changes are associated with elevated rates of emotional symptoms, it is unclear from these cross-sectional results, whether sleep deterioration produces psychological distress, or vice versa.

BACKGROUND: Neurodevelopmental disorders (NDDs) compromise the development and attainment of full social and economic potential at individual, family, community, and country levels. Paucity of data on NDDs slows down policy and programmatic action in most developing countries despite perceived high burden. METHODS AND FINDINGS: We assessed 3,964 children (with almost equal number of boys and girls distributed in 2-<6 and 6-9 year age categories) identified from five geographically diverse populations in India using cluster sampling technique (probability proportionate to population size). These were from the North-Central, i.e., Palwal (N = 998; all rural, 16.4% non-Hindu, 25.3% from scheduled caste/tribe [SC-ST] [these are considered underserved communities who are eligible for affirmative action]); North, i.e., Kangra (N = 997; 91.6% rural, 3.7% non-Hindu, 25.3% SC-ST); East, i.e., Dhenkanal (N = 981; 89.8% rural, 1.2% non-Hindu, 38.0% SC-ST); South, i.e., Hyderabad (N = 495; all urban, 25.7% non-Hindu, 27.3% SC-ST) and West, i.e., North Goa (N = 493; 68.0% rural, 11.4% non-Hindu, 18.5% SC-ST). All children were assessed for vision impairment (VI), epilepsy (Epi), neuromotor impairments including cerebral palsy (NMI-CP), hearing impairment (HI), speech and language disorders, autism spectrum disorders (ASDs), and intellectual disability (ID). Furthermore, 6-9-year-old children were also assessed for attention deficit hyperactivity disorder (ADHD) and learning disorders (LDs). We standardized sample characteristics as per Census of India 2011 to arrive at district level and all-sites-pooled estimates. Site-specific prevalence of any of seven NDDs in 2-<6 year olds ranged from 2.9% (95% CI 1.6-5.5) to 18.7% (95% CI 14.7-23.6), and for any of nine NDDs in the 6-9-year-old children, from 6.5% (95% CI 4.6-9.1) to 18.5% (95% CI 15.3-22.3). Two or more NDDs were present in 0.4% (95% CI 0.1-1.7) to 4.3% (95% CI 2.2-8.2) in the younger age category and 0.7% (95% CI 0.2-2.0) to 5.3% (95% CI 3.3-8.2) in the older age category. All-site-pooled estimates for NDDs were 9.2% (95% CI 7.5-11.2) and 13.6% (95% CI 11.3-16.2) in children of 2-<6 and 6-9 year age categories, respectively, without significant difference according to gender, rural/urban residence, or religion; almost one-fifth of these children had more than one NDD. The pooled estimates for prevalence increased by up to three percentage points when these were adjusted for national rates of stunting or low birth weight (LBW). HI, ID, speech and language disorders, Epi, and LDs were the common NDDs across sites. Upon risk modelling, noninstitutional delivery, history of perinatal asphyxia, neonatal illness, postnatal neurological/brain infections, stunting, LBW/prematurity, and older age category (6-9 year) were significantly associated with NDDs. The study sample was underrepresentative of stunting and LBW and had a 15.6% refusal. These factors could be contributing to underestimation of the true NDD burden in our population. CONCLUSIONS: The study identifies NDDs in children aged 2-9 years as a significant public health burden for India. HI was higher than and ASD prevalence comparable to the published global literature. Most risk factors of NDDs were modifiable and amenable to public health interventions.

BACKGROUND: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. METHODS: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. FINDINGS: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). INTERPRETATION: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. FUNDING: Gates Foundation and Bloomberg Philanthropies.

BACKGROUND: There is lack of information on the magnitude of depression among elderly population in India. This systematic review and meta-analysis aimed to estimate the prevalence of depression among elderly population in India. METHODS: PubMed, Scopus, Web of Science, Embase, PsycINFO, IndMed, and Google Scholar were searched to identify articles reported community-based prevalence of depression among elderly population using screening tools. This study included the articles published during the years 1997 to 2016. Studies conducted in the special population groups, hospitals, reported only a subcategory of depression, and not specified the screening tool were excluded. Data were extracted from published reports and any missing information was requested from authors. Estimates were pooled using random-effects meta-analyses. Subgroup and sensitivity analysis were performed. The publication bias was evaluated by using Egger's test and visual inspection of the symmetry in funnel plots. RESULTS: Fifty-one studies from 16 States of India were included as 56 datasets, which estimated the prevalence of depression among Indian elderly population as 34.4% (95% CI: 29.3-39.7). In sub-group analysis, the pooled prevalence was higher among females, rural populations, and in the eastern part of the country. Studies using non-probability sampling, and GDS and CES-D screening tool showed higher prevalence. Exclusion of the studies with sample size less than 100 and low-quality studies (score < 5/8) had no effect on the estimate of the prevalence. The studies that excluded dementia before assessment of depression had lower prevalence. CONCLUSION: About one third elderly population of India suffered from depression with female preponderance. The estimates varied with type of study tool, geographic region, sampling methods, and presence of dementia. The pooled estimate should be interpreted with caution as the studies included in this review had varied methodological approach and screening tools.

OBJECTIVES: To determine the prevalence of metabolic syndrome and to identify predictors for the same, specific to an underdeveloped urban locale of Eastern India. STUDY DESIGN: Population-based cross-sectional study, with multistage random sampling technique. SETTING: Urban city-dwellers in Orissa one of the poorest states of Eastern India bordering a prosperous state of Andhra Pradesh of Southern India. PARTICIPANTS: 1178 adults of age 20-80 years randomly selected from 37 electoral wards of the urban city. Definition of Metabolic Syndrome: We followed a unified definition of the metabolic syndrome by joint interim statement of five major scientific organizations - the International Diabetes Federation, the National Heart, Lung, and Blood Institute, the American Heart Association, the World Heart Federation, the International Atherosclerosis Society, and the International Association of the Study of Obesity. Individuals who meet at least three of five clinical criteria of abdominal obesity, hypertriglyceredimia, low HDL, hypertension, and hyperglycemia are diagnosed as having the condition; presence of none of these criteria is mandatory. Explicit cut points are defined for all criteria, except elevated waist circumference, which must rely on population and country-specific definitions. MAIN OUTCOME MEASURE: Prevalence and significant predictors of metabolic syndrome. STATISTICAL ANALYSIS: Both descriptive and multivariable logistic regression analyses. RESULTS: Age-standardized prevalence rates of metabolic syndrome were 33.5% overall, 24.9 % in males and 42.3% in females. Older age, female gender, general obesity, inadequate fruit intake, hypercholesterolemia, and middle-to-high socioeconomic status significantly contributed to increased risk of metabolic syndrome. CONCLUSION: Metabolic syndrome is a significant public health problem even in one of the poorest states of India that needs to be tackled with proven strategies.

Traumatic brain injury (TBI) is among the significant causes of morbidity and mortality in the present world. Around 1.6 million persons sustain TBI, whereas 200,000 die annually in India, thus highlighting the rising need for appropriate cognitive rehabilitation strategies. This literature review assesses the current knowledge of various cognitive rehabilitation training strategies. The entire spectrum of TBI severity; mild to severe, is associated with cognitive deficits of varying degree. Cognitive insufficiency is more prevalent and longer lasting in TBI persons than in the general population. A multidisciplinary approach with neuropsychiatric evaluation is warranted. Attention process training and tasks for attention deficits, compensatory strategies and errorless learning training for memory deficits, pragmatic language skills and social behavior guidance for cognitive-communication disorder, meta-cognitive strategy, and problem-solving training for executive disorder are the mainstay of therapy for cognitive deficits in persons with TBI. Cognitive impairments following TBI are common and vary widely. Different cognitive rehabilitation techniques and combinations in addition to pharmacotherapy are helpful in addressing various cognitive deficits.

INTRODUCTION: Mental health concerns and treatment usually take a backseat when the limited resources are geared for pandemic containment. In this global humanitarian crisis of the COVID-19 pandemic, mental health issues have been reported from all over the world. OBJECTIVES: In this study, we attempt to review the prevailing mental health issues during the COVID-19 pandemic through global experiences, and reactive strategies established in mental health care with special reference to the Indian context. By performing a rapid synthesis of available evidence, we aim to propose a conceptual and recommendation framework for mental health issues during the COVID-19 pandemic. METHODS: A search of the PubMed electronic database and google scholar were undertaken using the search terms 'novel coronavirus', 'COVID-19', 'nCoV', SARS-CoV-2, 'mental health', 'psychiatry', 'psychology', 'anxiety', 'depression' and 'stress' in various permutations and combinations. Published journals, magazines and newspaper articles, official webpages and independent websites of various institutions and non-government organizations, verified social media portals were compiled. RESULTS: The major mental health issues reported were stress, anxiety, depression, insomnia, denial, anger and fear. Children and older people, frontline workers, people with existing mental health illnesses were among the vulnerable in this context. COVID-19 related suicides have also been increasingly common. Globally, measures have been taken to address mental health issues through the use of guidelines and intervention strategies. The role of social media has also been immense in this context. State-specific intervention strategies, telepsychiatry consultations, toll free number specific for psychological and behavioral issues have been issued by the Government of India. CONCLUSION: Keeping a positive approach, developing vulnerable-group-specific need-based interventions with proper risk communication strategies and keeping at par with the evolving epidemiology of COVID-19 would be instrumental in guiding the planning and prioritization of mental health care resources to serve the most vulnerable.

BACKGROUND: Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations. METHODS: GBD 2023 produced estimates for 292 causes of death disaggregated by age-sex-location-year in 204 countries and territories and 660 subnational locations for each year from 1990 until 2023. We used a modelling tool developed for GBD, the Cause of Death Ensemble model (CODEm), to estimate cause-specific death rates for most causes. We computed YLLs as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. Probability of death was calculated as the chance of dying from a given cause in a specific age period, for a specific population. Mean age at death was calculated by first assigning the midpoint age of each age group for every death, followed by computing the mean of all midpoint ages across all deaths attributed to a given cause. We used GBD death estimates to calculate the observed mean age at death and to model the expected mean age across causes, sexes, years, and locations. The expected mean age reflects the expected mean age at death for individuals within a population, based on global mortality rates and the population's age structure. Comparatively, the observed mean age represents the actual mean age at death, influenced by all factors unique to a location-specific population, including its age structure. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 250-draw distribution for each metric. Findings are reported as counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2023 include a correction for the misclassification of deaths due to COVID-19, updates to the method used to estimate COVID-19, and updates to the CODEm modelling framework. This analysis used 55 761 data sources, including vital registration and verbal autopsy data as well as data from surveys, censuses, surveillance systems, and cancer registries, among others. For GBD 2023, there were 312 new country-years of vital registration cause-of-death data, 3 country-years of surveillance data, 51 country-years of verbal autopsy data, and 144 country-years of other data types that were added to those used in previous GBD rounds. FINDINGS: The initial years of the COVID-19 pandemic caused shifts in long-standing rankings of the leading causes of global deaths: it ranked as the number one age-standardised cause of death at Level 3 of the GBD cause classification hierarchy in 2021. By 2023, COVID-19 dropped to the 20th place among the leading global causes, returning the rankings of the leading two causes to those typical across the time series (ie, ischaemic heart disease and stroke). While ischaemic heart disease and stroke persist as leading causes of death, there has been progress in reducing their age-standardised mortality rates globally. Four other leading causes have also shown large declines in global age-standardised mortality rates across the study period: diarrhoeal diseases, tuberculosis, stomach cancer, and measles. Other causes of death showed disparate patterns between sexes, notably for deaths from conflict and terrorism in some locations. A large reduction in age-standardised rates of YLLs occurred for neonatal disorders. Despite this, neonatal disorders remained the leading cause of global YLLs over the period studied, except in 2021, when COVID-19 was temporarily the leading cause. Compared to 1990, there has been a considerable reduction in total YLLs in many vaccine-preventable diseases, most notably diphtheria, pertussis, tetanus, and measles. In addition, this study quantified the mean age at death for all-cause mortality and cause-specific mortality and found noticeable variation by sex and location. The global all-cause mean age at death increased from 46·8 years (95% UI 46·6-47·0) in 1990 to 63·4 years (63·1-63·7) in 2023. For males, mean age increased from 45·4 years (45·1-45·7) to 61·2 years (60·7-61·6), and for females it increased from 48·5 years (48·1-48·8) to 65·9 years (65·5-66·3), from 1990 to 2023. The highest all-cause mean age at death in 2023 was found in the high-income super-region, where the mean age for females reached 80·9 years (80·9-81·0) and for males 74·8 years (74·8-74·9). By comparison, the lowest all-cause mean age at death occurred in sub-Saharan Africa, where it was 38·0 years (37·5-38·4) for females and 35·6 years (35·2-35·9) for males in 2023. Lastly, our study found that all-cause 70q0 decreased across each GBD super-region and region from 2000 to 2023, although with large variability between them. For females, we found that 70q0 notably increased from drug use disorders and conflict and terrorism. Leading causes that increased 70q0 for males also included drug use disorders, as well as diabetes. In sub-Saharan Africa, there was an increase in 70q0 for many non-communicable diseases (NCDs). Additionally, the mean age at death from NCDs was lower than the expected mean age at death for this super-region. By comparison, there was an increase in 70q0 for drug use disorders in the high-income super-region, which also had an observed mean age at death lower than the expected value. INTERPRETATION: We examined global mortality patterns over the past three decades, highlighting-with enhanced estimation methods-the impacts of major events such as the COVID-19 pandemic, in addition to broader trends such as increasing NCDs in low-income regions that reflect ongoing shifts in the global epidemiological transition. This study also delves into premature mortality patterns, exploring the interplay between age and causes of death and deepening our understanding of where targeted resources could be applied to further reduce preventable sources of mortality. We provide essential insights into global and regional health disparities, identifying locations in need of targeted interventions to address both communicable and non-communicable diseases. There is an ever-present need for strengthened health-care systems that are resilient to future pandemics and the shifting burden of disease, particularly among ageing populations in regions with high mortality rates. Robust estimates of causes of death are increasingly essential to inform health priorities and guide efforts toward achieving global health equity. The need for global collaboration to reduce preventable mortality is more important than ever, as shifting burdens of disease are affecting all nations, albeit at different paces and scales. FUNDING: Gates Foundation.

INTRODUCTION: Prior estimates of dementia prevalence in India were based on samples from selected communities, inadequately representing the national and state populations. METHODS: From the Longitudinal Aging Study in India (LASI) we recruited a sample of adults ages 60+ and administered a rich battery of neuropsychological tests and an informant interview in 2018 through 2020. We obtained a clinical consensus rating of dementia status for a subsample (N = 2528), fitted a logistic model for dementia status on this subsample, and then imputed dementia status for all other LASI respondents aged 60+ (N = 28,949). RESULTS: The estimated dementia prevalence for adults ages 60+ in India is 7.4%, with significant age and education gradients, sex and urban/rural differences, and cross-state variation. DISCUSSION: An estimated 8.8 million Indians older than 60 years have dementia. The burden of dementia cases is unevenly distributed across states and subpopulations and may therefore require different levels of local planning and support. HIGHLIGHTS: The estimated dementia prevalence for adults ages 60+ in India is 7.4%. About 8.8 million Indians older than 60 years live with dementia. Dementia is more prevalent among females than males and in rural than urban areas. Significant cross-state variation exists in dementia prevalence.

OBJECTIVES: This systematic review aimed to offer insight and understanding, through synthesis of findings from studies that report on perspectives of student nurses/midwives, clinical instructors, clinical nurses/midwives on the challenges faced by student nurses/midwives in the clinical learning environment (CLE). DESIGN: All primary qualitative research studies published in the English language that reported on the views of student nurses/midwives, clinical instructors and clinical nurses/midwives on the challenges faced by student nurses/midwives in the CLE were included. DATA SOURCES: The electronic databases of Medline EBSCO (1946-), CINAHL (1970), Embase Ovid (1974-), ScielO, WHOLIS (2002-), ASSIA (1985-), Web of Science (1956-), PsycINFO (1800s-) and Maternal and Infant Care (1970-) were searched in November 2019. REVIEW METHODS: Retrieved papers were reviewed independently by two authors for selection by title, abstract and full text, and two authors agreed for inclusion of the papers. The COREQ criteria checklist was used for assessment of methodological quality of the included studies. RESULTS: The review included 32 studies published over 22 years between 1997 and 2019 involving 853 nursing/midwifery students, clinical instructors, and clinical nurses/midwives from 14 countries. Three key themes emerged: 'The support structure', 'Personal factors', and 'Planning and organisation - influence of extrinsic factors'. CONCLUSION: Attitude of clinical staff, instructors, and significant others had a major influence on students' clinical learning. Lack of a sense of belongingness and self-motivation to learn, and perceived fear of doing errors were some of the demotivating factors. Lack of resources to facilitate need-based training, staff shortages, workload and inconsistencies between theory and practice were other key challenges in the CLE. Understanding the challenges faced by students in clinical practice can help overcome the barriers leading to development of competent and confident nurses and midwives.

Much has been written about the well-being and quality of patients in recent years but little attention has been focused on well-being of healthcare workers (HCWs) who provide comprehensive healthcare to patients. It has been found that the HCWs are more stressed because of less staffs, increasing work load, longer working hours, high clientele expectation and peculiar problems and hazards of work place. There is increased morbidity in HCWs in comparison to general population. Though they are aware, measures of well being, engaging the HCWs in promotion of their workplace and making changes to enhance its realization needs to be done to improve their health by themselves, at administrative and institutional level.

Class III malocclusion represents a growth-related dentofacial deformity with mandibular prognathism in relation to the maxilla and/or cranial base. Its prevalence varies greatly among and within different races, ethnic groups, and geographic regions studied. Class III malocclusion has a multifactorial etiology, which is the expression of a moderate distortion of normal development as a result of interaction between innate factors or genetic hereditary with environmental factors. Various skeletal topographies of underlying Class III malocclusion are due to discrepancy in the maxillary and mandibular growth along with vertical and/or transverse problems apart from sagittal malformations. The spectrum of complications for Class III malocclusion ranges in gravity from dentoalveolar problems with functional anterior shift of the mandible to true skeletal problems with serious maxillomandibular discrepancies, which makes its diagnosis highly challenging in growing children. Concern regarding early treatment and the need for interceptive care in the case of Class III malocclusion has always been a dilemma, knowing that not all problems will be solved in these cases until maxillomandibular growth is further completed, and the long-term outcome of various treatment approaches may depend on the growth tendency of an individual. Interceptive treatment of Class III malocclusions should be undertaken if it prevents damage to the oral tissues and/or significantly reduces the amount or severity of future orthodontic and surgical interventions. This paper presents an overview of developing Class III malocclusion, with the emphasis on challenges and their solutions based on the best current available evidence.

Exclusive breastfeeding (EBF)-giving infants only breast-milk for the first 6 months of life-is a component of optimal breastfeeding practices effective in preventing child morbidity and mortality. EBF practices are known to vary by population and comparable subnational estimates of prevalence and progress across low- and middle-income countries (LMICs) are required for planning policy and interventions. Here we present a geospatial analysis of EBF prevalence estimates from 2000 to 2018 across 94 LMICs mapped to policy-relevant administrative units (for example, districts), quantify subnational inequalities and their changes over time, and estimate probabilities of meeting the World Health Organization's Global Nutrition Target (WHO GNT) of ≥70% EBF prevalence by 2030. While six LMICs are projected to meet the WHO GNT of ≥70% EBF prevalence at a national scale, only three are predicted to meet the target in all their district-level units by 2030.

Leishmaniasis is broadly classified into three types: cutaneous, mucocutaneous and visceral. The visceral form is most dangerous and can result in death. Although leishmaniasis is an ancient disease, its treatment is still challenging. Several drugs, differing in their cost, toxicity, treatment duration and emergence of drug resistance, are used for different types of leishmaniasis. To overcome these limitations, the search for newer drugs and other treatments continues. In this article, we discuss conventional drugs, other treatments, including newer options such as immunotherapy and immunochemotherapy, and future prospects for leishmaniasis treatment.

The paper presents the most comprehensive and large-scale global study to date on how higher education students perceived the use of ChatGPT in early 2024. With a sample of 23,218 students from 109 countries and territories, the study reveals that students primarily used ChatGPT for brainstorming, summarizing texts, and finding research articles, with a few using it for professional and creative writing. They found it useful for simplifying complex information and summarizing content, but less reliable for providing information and supporting classroom learning, though some considered its information clearer than that from peers and teachers. Moreover, students agreed on the need for AI regulations at all levels due to concerns about ChatGPT promoting cheating, plagiarism, and social isolation. However, they believed ChatGPT could potentially enhance their access to knowledge and improve their learning experience, study efficiency, and chances of achieving good grades. While ChatGPT was perceived as effective in potentially improving AI literacy, digital communication, and content creation skills, it was less useful for interpersonal communication, decision-making, numeracy, native language proficiency, and the development of critical thinking skills. Students also felt that ChatGPT would boost demand for AI-related skills and facilitate remote work without significantly impacting unemployment. Emotionally, students mostly felt positive using ChatGPT, with curiosity and calmness being the most common emotions. Further examinations reveal variations in students' perceptions across different socio-demographic and geographic factors, with key factors influencing students' use of ChatGPT also being identified. Higher education institutions' managers and teachers may benefit from these findings while formulating the curricula and instructions/regulations for ChatGPT use, as well as when designing the teaching methods and assessment tools. Moreover, policymakers may also consider the findings when formulating strategies for secondary and higher education system development, especially in light of changing labor market needs and related digital skills development.

Mycotic keratitis is a major cause of corneal blindness, especially in tropical and subtropical countries. The prognosis is markedly worse compared to bacterial keratitis. Delayed diagnosis and scarcity of effective antifungal agents are the major factors for poor outcome. Over the last decade, considerable progress has been made to rapidly diagnose cases with mycotic keratitis and increase the efficacy of treatment. This review article discusses the recent advances in diagnosis and management of mycotic keratitis with a brief discussion on rare and emerging organisms. A MEDLINE search was carried out for articles in English language, with the keywords, mycotic keratitis, fungal keratitis, emerging or atypical fungal pathogens in mycotic keratitis, investigations in mycotic keratitis, polymerase chain reaction in mycotic keratitis, confocal microscopy, treatment of mycotic keratitis, newer therapy for mycotic keratitis. All relevant articles were included in this review. Considering the limited studies available on newer diagnostic and therapeutic modalities in mycotic keratitis, case series as well as case reports were also included if felt important.

BACKGROUND: Workplace violence (WPV) includes verbal abuse, physical violence, bullying or mobbing, assault and sexual harassment. The area has been well researched in the developed and high-income countries among nurses and healthcare professionals, but in the case of the low and upper-middle-income countries, there remains a paucity of comprehensive data on the prevalence of WPV and its contributing factors. AIMS: To estimate the prevalence and determinants of WPV among nurses working in the South-East Asian Region and Western Pacific Regions. DESIGN: Systematic review and Meta-analysis. METHOD: A comprehensive search was done to retrieve articles based on a PRISMA compliant protocol registered in PROSPERO: CRD 42020223605. Study selection, quality assessment and data abstraction were independently done by the team members and discrepancies addressed through mutual consensus. Random-effect meta-analysis, I2 statistics and subgroup analysis were done. RESULTS: The review included 41 studies conducted among 42,222 nurses from 13 countries. The pooled prevalence of WPV, verbal abuse, physical violence, threatening behaviour, physical assault, sexual harassment and bullying/mobbing were 58% (CI 51%-64%), 64% (CI 59%-70%), 23% (CI 14%-34%), 30(CI-11%-52%), 21% (CI 8%-38%), 12% (CI 7%-17%) and 25% (17%-33%), respectively. The various determinants of WPV included attributes related to the patient, nurses and organisation. Moreover, the impact of WPV included physical, psychological repercussions on nurses and the various measures used to manage it. CONCLUSION: Nurses encounter a high level of WPV especially verbal abuse in their workplace settings. Nursing councils and professional nursing organisations should put in their effort towards the formulation and implementation of occupational safety legislation in their respective countries through appropriate political lobbying. RELEVANCE TO CLINICAL PRACTICE: Our review highlights the emerging need to focus on the prevention of WPV among nurses working in lower, middle and upper-middle-income countries. Legislation changes and organisational commitment are vital for ensuring effective policies to combat WPV.

Toxic effects and chemoresistance are major hurdles in chemotherapy and to avoid these problems caused by traditional chemotherapeutic regimens, a new modality of drug administration called "metronomic chemotherapy" has emerged. Such regimen involves the frequent administration of conventional chemotherapeutic agents at very low doses to target activated endothelial cells in tumors, the advantages of which include minimal adverse effects and a rare chance of developing acquired drug resistance. Previously it was thought that they act by targeting angiogenesis, but recently additional mechanisms have been discovered which has established metronomic chemotherapy as a type of multi-targeted therapy. The knowledge gained from the preclinical studies of metronomic chemotherapy, along with clinical experience, will help to design better therapeutic protocols against cancer. Detailed pharmacogenomic and pharmacoproteomic studies on tumor endothelial cells and large multi-centered clinical trials, integrating bio-marker analyzes, are needed to investigate and validate the best treatment combinations for each tumor type and patient population.

Normal tension glaucoma (NTG) is labelled when typical glaucomatous disc changes, visual field defects and open anterior chamber angles are associated with intraocular pressure (IOP) constantly below 21 mmHg. Chronic low vascular perfusion, Raynaud's phenomenon, migraine, nocturnal systemic hypotension and over-treated systemic hypertension are the main causes of normal tension glaucoma. Goldmann applanation tonometry, gonioscopy, slit lamp biomicroscopy, optical coherence tomography and visual field analysis are the main tools of investigation for the diagnosis of NTG. Management follows the same principles of treatment for other chronic glaucomas: To reduce IOP by a substantial amount, sufficient to prevent disabling visual loss. Treatment is generally aimed to lower IOP by 30% from pre-existing levels to 12-14 mmHg. Betaxolol, brimonidine, prostaglandin analogues, trabeculectomy (in refractory cases), systemic calcium channel blockers (such as nifedipine) and 24-hour monitoring of blood pressure are considered in the management of NTG. The present review summarises risk factors, causes, pathogenesis, diagnosis and management of NTG.