Lumbini Medical College

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: 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.

Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in hospitals worldwide. The cornerstones of effective treatment of IAIs include early recognition, adequate source control, appropriate antimicrobial therapy, and prompt physiologic stabilization using a critical care environment, combined with an optimal surgical approach. Together, the World Society of Emergency Surgery (WSES), the Global Alliance for Infections in Surgery (GAIS), the Surgical Infection Society-Europe (SIS-E), the World Surgical Infection Society (WSIS), and the American Association for the Surgery of Trauma (AAST) have jointly completed an international multi-society document in order to facilitate clinical management of patients with IAIs worldwide building evidence-based clinical pathways for the most common IAIs. An extensive non-systematic review was conducted using the PubMed and MEDLINE databases, limited to the English language. The resulting information was shared by an international task force from 46 countries with different clinical backgrounds. The aim of the document is to promote global standards of care in IAIs providing guidance to clinicians by describing reasonable approaches to the management of IAIs.

BACKGROUND: Smoking is the leading behavioural risk factor for mortality globally, accounting for more than 175 million deaths and nearly 4·30 billion years of life lost (YLLs) from 1990 to 2021. The pace of decline in smoking prevalence has slowed in recent years for many countries, and although strategies have recently been proposed to achieve tobacco-free generations, none have been implemented to date. Assessing what could happen if current trends in smoking prevalence persist, and what could happen if additional smoking prevalence reductions occur, is important for communicating the effect of potential smoking policies. METHODS: In this analysis, we use the Institute for Health Metrics and Evaluation's Future Health Scenarios platform to forecast the effects of three smoking prevalence scenarios on all-cause and cause-specific YLLs and life expectancy at birth until 2050. YLLs were computed for each scenario using the Global Burden of Disease Study 2021 reference life table and forecasts of cause-specific mortality under each scenario. The reference scenario forecasts what could occur if past smoking prevalence and other risk factor trends continue, the Tobacco Smoking Elimination as of 2023 (Elimination-2023) scenario quantifies the maximum potential future health benefits from assuming zero percent smoking prevalence from 2023 onwards, whereas the Tobacco Smoking Elimination by 2050 (Elimination-2050) scenario provides estimates for countries considering policies to steadily reduce smoking prevalence to 5%. Together, these scenarios underscore the magnitude of health benefits that could be reached by 2050 if countries take decisive action to eliminate smoking. The 95% uncertainty interval (UI) of estimates is based on the 2·5th and 97·5th percentile of draws that were carried through the multistage computational framework. FINDINGS: Global age-standardised smoking prevalence was estimated to be 28·5% (95% UI 27·9-29·1) among males and 5·96% (5·76-6·21) among females in 2022. In the reference scenario, smoking prevalence declined by 25·9% (25·2-26·6) among males, and 30·0% (26·1-32·1) among females from 2022 to 2050. Under this scenario, we forecast a cumulative 29·3 billion (95% UI 26·8-32·4) overall YLLs among males and 22·2 billion (20·1-24·6) YLLs among females over this period. Life expectancy at birth under this scenario would increase from 73·6 years (95% UI 72·8-74·4) in 2022 to 78·3 years (75·9-80·3) in 2050. Under our Elimination-2023 scenario, we forecast 2·04 billion (95% UI 1·90-2·21) fewer cumulative YLLs by 2050 compared with the reference scenario, and life expectancy at birth would increase to 77·6 years (95% UI 75·1-79·6) among males and 81·0 years (78·5-83·1) among females. Under our Elimination-2050 scenario, we forecast 735 million (675-808) and 141 million (131-154) cumulative YLLs would be avoided among males and females, respectively. Life expectancy in 2050 would increase to 77·1 years (95% UI 74·6-79·0) among males and 80·8 years (78·3-82·9) among females. INTERPRETATION: Existing tobacco policies must be maintained if smoking prevalence is to continue to decline as forecast by the reference scenario. In addition, substantial smoking-attributable burden can be avoided by accelerating the pace of smoking elimination. Implementation of new tobacco control policies are crucial in avoiding additional smoking-attributable burden in the coming decades and to ensure that the gains won over the past three decades are not lost. FUNDING: Bloomberg Philanthropies and the Bill & Melinda Gates Foundation.

BACKGROUND: To estimate global and regional trends from 2000 to 2020 of the number of persons visually impaired by cataract and their proportion of the total number of vision-impaired individuals. METHODS: A systematic review and meta-analysis of published population studies and gray literature from 2000 to 2020 was carried out to estimate global and regional trends. We developed prevalence estimates based on modeled distance visual impairment and blindness due to cataract, producing location-, year-, age-, and sex-specific estimates of moderate to severe vision impairment (MSVI presenting visual acuity <6/18, ≥3/60) and blindness (presenting visual acuity <3/60). Estimates are age-standardized using the GBD standard population. RESULTS: In 2020, among overall (all ages) 43.3 million blind and 295 million with MSVI, 17.0 million (39.6%) people were blind and 83.5 million (28.3%) had MSVI due to cataract blind 60% female, MSVI 59% female. From 1990 to 2020, the count of persons blind (MSVI) due to cataract increased by 29.7%(93.1%) whereas the age-standardized global prevalence of cataract-related blindness improved by -27.5% and MSVI increased by 7.2%. The contribution of cataract to the age-standardized prevalence of blindness exceeded the global figure only in South Asia (62.9%) and Southeast Asia and Oceania (47.9%). CONCLUSIONS: The number of people blind and with MSVI due to cataract has risen over the past 30 years, despite a decrease in the age-standardized prevalence of cataract. This indicates that cataract treatment programs have been beneficial, but population growth and aging have outpaced their impact. Growing numbers of cataract blind indicate that more, better-directed, resources are needed to increase global capacity for cataract surgery.

BACKGROUND: The global burden of sepsis, a life-threatening dysregulated host response to infection leading to organ dysfunction, remains challenging to quantify. We aimed to comprehensively estimate the global, regional, and national burden of sepsis, including the impact of the COVID-19 pandemic and underlying causes of sepsis-related deaths with co-occurring infectious syndromes. METHODS: We used multiple cause-of-death, hospital, minimally invasive tissue sampling, and linked death certificate and hospital record data representing 149 million deaths, covering 4290 location-years with mortality estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 to capture explicit and implicit sepsis cases and deaths. We estimated age-location-sex-specific fractions of sepsis-related deaths from 195 underlying causes of death and 22 infectious syndromes from 1990 to 2021 using binomial logistic regression models, and estimated sepsis-related deaths using GBD cause-specific mortality estimates. Using 250 million hospital admissions and 7·82 million deaths from hospital data, representing 1310 location-years, we modelled case fatality rates by use of binomial logistic regression, applied to sepsis death estimates to estimate sepsis incidence by age, location, and year. FINDINGS: In 2021, we estimated 166 million (95% uncertainty interval 135-201) sepsis cases and 21·4 million (20·3-22·5) all-cause sepsis-related deaths globally, representing 31·5% of total global deaths. Sepsis-related deaths decreased between 1990 and 2019, followed by a surge in 2020 and 2021. As of 2021, individuals aged 15 years and older experienced increases across incidence (230%) and mortality (26·3%) since 1990. Those aged 70 years and older had the highest sepsis-related mortality in 2021 (9·28 million [8·74-9·86] deaths). Sepsis-related deaths from infectious underlying causes decreased from 11·8 million (11·1-12·5) in 1990 to 8·34 million (7·72-9·01) in 2019, then increased by 86·4% to 15·5 million (14·7-16·4) in 2021. Sepsis-related mortality due to non-infectious underlying causes of death increased from 4·69 million (4·35-5·05) in 1990 to 5·81 million (5·40-6·25) in 2021; the leading non-infectious underlying causes of death with sepsis were stroke, chronic obstructive pulmonary disease, and cirrhosis. In 2021, bloodstream infections inclusive of HIV and malaria (3·08 million [2·83-3·35]) and lower respiratory infections inclusive of COVID-19 (11·33 million [1·20-1·47]) were the most prominent infectious syndromes complicating sepsis-related deaths from non-infectious underlying causes, representing a consistent trend since 1990. INTERPRETATION: The global burden of sepsis increased in 2020 and 2021, reversing progress from 1990. Sepsis incidence and mortality increased in people aged 15 years and older, especially those aged 70 years and older, and as a complication of non-infectious underlying causes of death such as stroke, primarily through bloodstream infections and lower respiratory infections. The global burden of sepsis is substantial, and sepsis is increasingly a complication of non-infectious causes of death. FUNDING: Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.

Earthquakes are a major natural calamity with pervasive effects on human life and nature. Similar effects are mimicked by man-made disasters such as fuel crises and power outages in developing countries. Natural and man-made disasters can cause intangible human suffering and often leave scars of lifelong psychosocial damage. Lessons from these disasters are frequently not implemented. The main objective of this study was to review the effects of the 2015 earthquakes, fuel crisis, and power outages on the health services of Nepal and formulate recommendations for the future. The impacts of earthquakes on health can be divided into immediate, intermediate, and long-term effects. Power outages and fuel crises have health hazards at all stages. It is imperative to understand the temporal effects of earthquakes, because the major needs soon after the earthquake (emergency care) are vastly different from long-term needs such as rehabilitation and psychosocial support. In Nepal, the inadequate and nearly nonexistent specialized health care at the peripheral level claimed many lives during the earthquakes and left many people disproportionately injured. Preemptive strategies such as mobile critical care units at primary health centers, intensive care training for health workers, and alternative plans for emergency care must be prioritized. Similarly, infrastructural damage led to poor sanitation, and alternative plans for temporary settlements (water supply, food, settlements logistics, space for temporary settlements) must be in place where the danger of disease outbreak is imminent. While much of these strategies are implementable and are often set as priorities, long-term effects of earthquakes such as physical and psychosocial supports are often overlooked. The burden of psychosocial stresses, including depression and physical disabilities, needs to be prioritized by facilitating human resources for mental health care and rehabilitation. In addition, inclusion of mental health and rehabilitation facilities in government health care services of Nepal needs to be prioritized. Similarly, power outages and fuel crises affect health care disproportionately. In the current context where permanent solutions may not be possible, mitigating health hazards, especially cold chain maintenance for essential medicines and continuation of life-saving procedures, are mandatory and policies to regulate all health care services must be undertaken. (Disaster Med Public Health Preparedness. 2017;11:625-632).

igital medical education is in its infancy in the geographically challenging and mountainous country of Nepal. To limit the spread of the Covid-19 pandemic, educational institutions in Nepal have remained closed for more than a month and medical colleges are no exception. Recently, however, Kathmandu University has instructed its affiliated institutions to run online classes for students so that there would be no lag in the academic calendar.

The current outbreak of corona virus disease (COVID-19), declared as public health emergency of national and international concern by World Health Organization (WHO), led to unprecedented public health responses in Nepal and many countries around the world including travel restriction, closure of educational institutions, curfews in some places and quarantines. This pandemic has affected lives of millions in different ways in different geographic locations worldwide. Beyond the immediate threat to health, unemployment, insecurity, etc., education is one of the sensitive areas which has been affected tremendously, students in Nepal not being an exception. The closure of all educational institutions effective from 18th March, 2020 followed by the nationwide lockdown from 24th March, 2020 till date enforced by Government of Nepal (GoN) as an effort to limit the spread of COVID-19 has shed a light on numerous issues affecting the access to education. As per the United NationsEducational, Scientific and Cultural Organization (UNESCO) report 2020, a total of 1,190,287,189learners are currently affected constituting 68% of the total enrolled learners worldwide because of temporary or indefinite country wide school closures implemented by the respective governments in an attempt to slow the spread of COVID-19. In Nepal alone 8,796,624 students have reportedly been affected.

Monkeypox (Mpox) is a contagious illness that is caused by the monkeypox virus, which is part of the same family of viruses as variola, vaccinia, and cowpox. It was first detected in the Democratic Republic of the Congo in 1970 and has since caused sporadic cases and outbreaks in a few countries in West and Central Africa. In July 2022, the World Health Organization (WHO) declared a public-health emergency of international concern due to the unprecedented global spread of the disease. Despite breakthroughs in medical treatments, vaccines, and diagnostics, diseases like monkeypox still cause death and suffering around the world and have a heavy economic impact. The 85,189 reported cases of Mpox as of 29 January 2023 have raised alarm bells. Vaccines for the vaccinia virus can protect against monkeypox, but these immunizations were stopped after smallpox was eradicated. There are, however, treatments available once the illness has taken hold. During the 2022 outbreak, most cases occurred among men who had sex with men, and there was a range of 7-10 days between exposure and the onset of symptoms. Three vaccines are currently used against the Monkeypox virus. Two of these vaccines were initially developed for smallpox, and the third is specifically designed for biological-terrorism protection. The first vaccine is an attenuated, nonreplicating smallpox vaccine that can also be used for immunocompromised individuals, marketed under different names in different regions. The second vaccine, ACAM2000, is a recombinant second-generation vaccine initially developed for smallpox. It is recommended for use in preventing monkeypox infection but is not recommended for individuals with certain health conditions or during pregnancy. The third vaccine, LC16m8, is a licensed attenuated smallpox vaccine designed to lack the B5R envelope-protein gene to reduce neurotoxicity. It generates neutralizing antibodies to multiple poxviruses and broad T-cell responses. The immune response takes 14 days after the second dose of the first two vaccines and 4 weeks after the ACAM2000 dose for maximal immunity development. The efficacy of these vaccines in the current outbreak of monkeypox is uncertain. Adverse events have been reported, and a next generation of safer and specific vaccines is needed. Although some experts claim that developing vaccines with a large spectrum of specificity can be advantageous, epitope-focused immunogens are often more effective in enhancing neutralization.

Background: Timing and adequacy of peritoneal source control are the most important pillars in the management of patients with acute peritonitis. Therefore, early prognostic evaluation of acute peritonitis is paramount to assess the severity and establish a prompt and appropriate treatment. The objectives of this study were to identify clinical and laboratory predictors for in-hospital mortality in patients with acute peritonitis and to develop a warning score system, based on easily recognizable and assessable variables, globally accepted. Methods: This worldwide multicentre observational study included 153 surgical departments across 56 countries over a 4-month study period between February 1, 2018, and May 31, 2018. Results: A total of 3137 patients were included, with 1815 (57.9%) men and 1322 (42.1%) women, with a median age of 47 years (interquartile range [IQR] 28-66). The overall in-hospital mortality rate was 8.9%, with a median length of stay of 6 days (IQR 4-10). Using multivariable logistic regression, independent variables associated with inhospital mortality were identified: age > 80 years, malignancy, severe cardiovascular disease, severe chronic kidney disease, respiratory rate 22 breaths/min, systolic blood pressure < 100 mmHg, AVPU responsiveness scale (voice and unresponsive), blood oxygen saturation level (SpO 2 ) < 90% in air, platelet count < 50,000 cells/mm3, and lactate > 4 mmol/l. These variables were used to create the PIPAS Severity Score, a bedside early warning score for patients with acute peritonitis. The overall mortality was 2.9% for patients who had scores of 0-1, 22.7% for those who had scores of 2-3, 46.8% for those who had scores of 4-5, and 86.7% for those who have scores of 7-8. Conclusions: The simple PIPAS Severity Score can be used on a global level and can help clinicians to identify patients at high risk for treatment failure and mortality.

BACKGROUND: The lockdown strategy adopted to contain the spread of current pandemic of coronavirus disease has affected all sectors of life globally. Nepal also instructed all the educational institutions to shut down, medical colleges being no exception. One month into the lockdown all the medical colleges in Nepal started online classes to keep pace with the academic calendar. This preliminary survey analyses the students' perspective on newly introduced online medical education system. METHODS: This cross-sectional survey used an online questionnaire typed in Google forms. The link to the survey was then emailed to the student representative of each semester of Lumbini Medical College, Palpa, Nepal, who were then instructed to forward it to their classmates. The questionnaire consisted of demographic variables and perspective of medical undergraduates towards online classes and also a space to comment or opine their perspective on current medical education. RESULTS: A total of 226 students responded the survey. Almost one-third of the students (n=173, 76.5%) admitted of never having attended the online classes. Most of the students used smartphones to attend online classes; broadband internet service being the source of internet in 65.5%. Two-third of the students rated online classes to be poorer than the traditional classroom teaching and 77.8% of the students preferred traditional classroom teaching in future. CONCLUSIONS: Medical students did not find online classes as effective as the traditional classroom teachings; it could be made more interactive and productive by introducing interactive and brainstorming sessions complementing the conventional face?to?face education.

BACKGROUND: Interpretation of Leprosy as a sickness differs among society. The set of beliefs, knowledge and perceptions towards a disease play a vital role in the construction of stigma towards a disease. The main purpose of this study was to explore the extent and correlates of the perceived stigma towards leprosy in the community living close to the leprosy colony in Non Somboon region of Khon Kaen Province of Thailand. METHODS: A cross-sectional study was conducted among 257 leprosy unaffected community participants, above the age of 18 who were living close to the Leprosy colony in Non Somboon region of Thailand. Each participant was asked a questionnaire containing characteristics of the participants in terms of socio-demographic background and knowledge regarding the disease. In addition perceived stigma towards leprosy was measured using EMIC (Explanatory Model Interview Catalogue) questionnaire. RESULTS: Among EMIC items, shame or embarrassment in the community due to leprosy was felt by 54.5%, dislike to buy food from leprosy affected persons were 49.8% and difficulty to find work for leprosy affected persons were perceived by 47.1%. Higher total EMIC score was found in participants age 61 years or older (p = 0.021), staying longer in the community (p = 0.005), attending fewer years of education (p = 0.024) and who were unemployed (p = 0.08). Similarly, perceptions about leprosy such as difficult to treat (p = 0.015), severe disease (p = 0.004) and punishment by God (p = 0.011) were significantly associated with higher perceived stigma. CONCLUSIONS: Perceived stigma towards leprosy was found highest among participants with age 61 years or older, longer duration of stay in community close to the leprosy colony, lower duration of education and participants who were unemployed had higher perceived stigma. Similarly, participants with perceptions of leprosy such as difficult to treat, severe disease and punishment by God had higher perceived stigma towards leprosy. There is an urgent need of stigma reduction strategies focused on education and awareness concerning leprosy.

Nepal underwent two major earthquakes during 2015 which claimed 9,000 deaths, left more than 23,000 injured, displaced about 2 million people and destroyed about 1,000 health facilities. Emerging health issues and disease outbreaks soon after the earthquakes were major priorities. However, preventive measures such as health education, health promotion and trainings embedded in community engagement remained largely unimplemented. Establishing community preparedness by delivering knowledge about the disasters, preparing contingency plans and conducting disaster drills can be promising in Nepal where geographical inaccessibility invariably impedes the on time management during disasters. The steps that could be taken in Nepal without additional resources include identifying community leaders and volunteers who could participate in health promotion initiatives, training of thus identified community volunteers, formation of community task force, devolvement of responsibilities with continual support (trainings and resources) and supervision of the community task force.

BACKGROUND: Injury remains a major concern to public health in the European region. Previous iterations of the Global Burden of Disease (GBD) study showed wide variation in injury death and disability adjusted life year (DALY) rates across Europe, indicating injury inequality gaps between sub-regions and countries. The objectives of this study were to: 1) compare GBD 2019 estimates on injury mortality and DALYs across European sub-regions and countries by cause-of-injury category and sex; 2) examine changes in injury DALY rates over a 20 year-period by cause-of-injury category, sub-region and country; and 3) assess inequalities in injury mortality and DALY rates across the countries. METHODS: We performed a secondary database descriptive study using the GBD 2019 results on injuries in 44 European countries from 2000 to 2019. Inequality in DALY rates between these countries was assessed by calculating the DALY rate ratio between the highest-ranking country and lowest-ranking country in each year. RESULTS: In 2019, in Eastern Europe 80 [95% uncertainty interval (UI): 71 to 89] people per 100,000 died from injuries; twice as high compared to Central Europe (38 injury deaths per 100,000; 95% UI 34 to 42) and three times as high compared to Western Europe (27 injury deaths per 100,000; 95%UI 25 to 28). The injury DALY rates showed less pronounced differences between Eastern (5129 DALYs per 100,000; 95% UI: 4547 to 5864), Central (2940 DALYs per 100,000; 95% UI: 2452 to 3546) and Western Europe (1782 DALYs per 100,000; 95% UI: 1523 to 2115). Injury DALY rate was lowest in Italy (1489 DALYs per 100,000) and highest in Ukraine (5553 DALYs per 100,000). The difference in injury DALY rates by country was larger for males compared to females. The DALY rate ratio was highest in 2005, with DALY rate in the lowest-ranking country (Russian Federation) 6.0 times higher compared to the highest-ranking country (Malta). After 2005, the DALY rate ratio between the lowest- and the highest-ranking country gradually decreased to 3.7 in 2019. CONCLUSIONS: Injury mortality and DALY rates were highest in Eastern Europe and lowest in Western Europe, although differences in injury DALY rates declined rapidly, particularly in the past decade. The injury DALY rate ratio of highest- and lowest-ranking country declined from 2005 onwards, indicating declining inequalities in injuries between European countries.

BACKGROUND: We aimed to update estimates of global vision loss due to age-related macular degeneration (AMD). METHODS: We did a systematic review and meta-analysis of population-based surveys of eye diseases from January, 1980, to October, 2018. We fitted hierarchical models to estimate the prevalence of moderate and severe vision impairment (MSVI; presenting visual acuity from <6/18 to 3/60) and blindness ( < 3/60) caused by AMD, stratified by age, region, and year. RESULTS: In 2020, 1.85 million (95%UI: 1.35 to 2.43 million) people were estimated to be blind due to AMD, and another 6.23 million (95%UI: 5.04 to 7.58) with MSVI globally. High-income countries had the highest number of individuals with AMD-related blindness (0.60 million people; 0.46 to 0.77). The crude prevalence of AMD-related blindness in 2020 (among those aged ≥ 50 years) was 0.10% (0.07 to 0.12) globally, and the region with the highest prevalence of AMD-related blindness was North Africa/Middle East (0.22%; 0.16 to 0.30). Age-standardized prevalence (using the GBD 2019 data) of AMD-related MSVI in people aged ≥ 50 years in 2020 was 0.34% (0.27 to 0.41) globally, and the region with the highest prevalence of AMD-related MSVI was also North Africa/Middle East (0.55%; 0.44 to 0.68). From 2000 to 2020, the estimated crude prevalence of AMD-related blindness decreased globally by 19.29%, while the prevalence of MSVI increased by 10.08%. CONCLUSIONS: The estimated increase in the number of individuals with AMD-related blindness and MSVI globally urges the creation of novel treatment modalities and the expansion of rehabilitation services.

BACKGROUND: Multidrug resistant Staphylococcus aureus is common in both tertiary and primary health care settings. Emergence of methicillin resistance in S. aureus (MRSA) along with macrolide, lincosamide, streptogramin B (MLSB) has made treatment of Staphylococcal infection more challenging. The main objective of this study was to detect MRSA, MLSB (inducible; MLSBi and constitutive; MLSBc) resistant S. aureus using phenotypic methods and to determine their antibiogram. METHODS: Various samples were collected from 1981 patients who attended Lumbini Medical College and Teaching Hospital (LMCTH) during the period of 6 months from September 2015 to February 2016. Out of a total of 1981 samples, 133 S. aureus were isolated. Cefoxitin was used to detect MRSA by the disk diffusion test. Inducible clindamycin resistance (MLSBi) was detected by the D-zone test. The antibiotic profile of all isolates was tested by a modified Kirby Bauer disk diffusion method. RESULTS: Among 133 S. aureus, there were 58 (43.6%) MRSA, 34 (25.6%) MLSBi and 30 (22.6%) MLSBc. Of a total of 64 MLSB, a significant proportion (62.5%) was MRSA (p < 0.001). Among 11 different antibiotics that were tested for S. aureus, MRSA showed significant resistance to 9 (p < 0.05) with the exception of vancomycin and linezolid. All the isolates were 100% sensitive to linezolid. MLSBi organisms were 100% sensitive to vancomycin and linezolid. Both MLSBi and MLSBc showed a higher degree of resistance to multiple antibiotics (p < 0.05). CONCLUSIONS: Isolation of MRSA, MLSBi and MLSBc were remarkably high. Routine use of simple and cost effective methods such as the disk diffusion test by cefoxitin for MRSA and the D-zone test for MLSBi organisms can easily identify these isolates. Antibiotic resistance profiles from this study can optimize the treatment of multi-drug resistant S. aureus.

BACKGROUND: Experimental unilateral cryptorchidism (ULC) and bilateral cryptorchidism (BLC) are excellent methods to study undescended testis in relation to spermatogenesis against a temperature gradient. OBJECTIVES: In case of ULC, it is possible to compare the testicular functions between normal condition and cryptorchidism in the same animal, whereas BLC shows the necessity of testicular androgens for proper maintenance of reproductive structures and functions. MATERIALS AND METHODS: In the present study, experimental ULC and BLC was done on same-aged adult mature male mice and kept for 15 days and 30 days, respectively, to observe the changes due to the induced cryptorchidism on the different reproductive organs, viz., the testis and accessory sex organs along with epididymal sperm count. Reproductive tissues were collected from individual animals and histopathological studies of testis were done to investigate different cytological changes. RESULTS: The size of the testes and accessory sex organs were found to be significantly reduced in BLC mice, whereas only testicular weight reduction was observed in ULC mice. Histopathological studies showed degenerative changes throughout the seminiferous tubules. CONCLUSION: Thus, the present investigation showed compensatory androgen production in ULC mice, whereas absence of androgen mediated reproductive functions in BLC animals.

Objective: To isolate, identify and phenotypically characterize extended spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella spp in Manipal Teaching Hospital.

INTRODUCTION: The world has been engulfed with the pandemic of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which have created significant impact in the emergency surgical health delivery including acute appendicitis. The main aim of this study was to compare the demographic and clinical parameters between two cohorts before the onset of lockdown and within the pandemic. METHODS: A retrospective analysis was performed between two groups A and B, who presented with acute appendicitis three months prior to and after initiation of lockdown on March 24 2020 respectively in one of the tertiary centers of Nepal. These two cohorts were compared in demographics, clinicopathological characteristics and surgical aspects of acute appendicitis. RESULTS: There were 42 patients in group A and 50 patients in group B. Mean age of the patients was 31.32±17.18 years with male preponderance in group B (N = 29). Mean duration of pain increased significantly in group B [57.8±25.9(B) vs 42.3±25.0(A) hours, P = 0.004] along with mean duration of surgery [51.06±9.4(B) vs 45.27±11.8(A) minutes, P = 0.015]. There was significant decrease in post-operative hospital stay among group B patients [3.04±1.1(B) vs 3.86±0.67(A) days, P = 0.0001]. Complicated cases increased in group B including appendicular perforation in 10 cases. Similarly, mean duration of presentation to hospital significantly increased in group B patients with perforation [69.6±21.01 vs 51.57±17.63 hours, P = 0.008]. CONCLUSION: During the adversity of the current pandemic, increased number of cases of acute appendicitis can be dealt with surgery as the chances of late presentation and complexity of the lesion exists.