Nepal Medical College Teaching Hospital

Updates: This is the fourteenth version (thirteenth update) of the living guideline, replacing earlier versions (available as data supplements). New recommendations will be published as updates to this guideline. Clinical question: What is the role of drugs in the treatment of patients with covid-19? Context: The evidence base for therapeutics for covid-19 is evolving with numerous randomised controlled trials (RCTs) recently completed and underway. Emerging SARS-CoV-2 variants and subvariants are changing the role of therapeutics. What is new?: The guideline development group (GDG) defined 1.5% as a new threshold for an important reduction in risk of hospitalisation in patients with non-severe covid-19. Combined with updated baseline risk estimates, this resulted in stratification into patients at low, moderate, and high risk for hospitalisation. New recommendations were added for moderate risk of hospitalisation for nirmatrelvir/ritonavir, and for moderate and low risk of hospitalisation for molnupiravir and remdesivir. New pharmacokinetic evidence was included for nirmatrelvir/ritonavir and molnupiravir, supporting existing recommendations for patients at high risk of hospitalisation. The recommendation for ivermectin in patients with non-severe illness was updated in light of additional trial evidence which reduced the high degree of uncertainty informing previous guidance. A new recommendation was made against the antiviral agent VV116 for patients with non-severe and with severe or critical illness outside of randomised clinical trials based on one RCT comparing the drug with nirmatrelvir/ritonavir. The structure of the guideline publication has also been changed; recommendations are now ordered by severity of covid-19. About this guideline: This living guideline from the World Health Organization (WHO) incorporates new evidence to dynamically update recommendations for covid-19 therapeutics. The GDG typically evaluates a therapy when the WHO judges sufficient evidence is available to make a recommendation. While the GDG takes an individual patient perspective in making recommendations, it also considers resource implications, acceptability, feasibility, equity, and human rights. This guideline was developed according to standards and methods for trustworthy guidelines, making use of an innovative process to achieve efficiency in dynamic updating of recommendations. The methods are aligned with the WHO Handbook for Guideline Development and according to a pre-approved protocol (planning proposal) by the Guideline Review Committee (GRC). A box at the end of the article outlines key methodological aspects of the guideline process. MAGIC Evidence Ecosystem Foundation provides methodological support, including the coordination of living systematic reviews with network meta-analyses to inform the recommendations. The full version of the guideline is available online in MAGICapp and in PDF on the WHO website, with a summary version here in The BMJ. These formats should facilitate adaptation, which is strongly encouraged by WHO to contextualise recommendations in a healthcare system to maximise impact. Future recommendations: Recommendations on anticoagulation are planned for the next update to this guideline. Updated data regarding systemic corticosteroids, azithromycin, favipiravir and umefenovir for non-severe illness, and convalescent plasma and statin therapy for severe or critical illness, are planned for review in upcoming guideline iterations.

BACKGROUND: Hepatitis E virus (HEV) is an important cause of viral hepatitis. We evaluated the safety and efficacy of an HEV recombinant protein (rHEV) vaccine in a phase 2, randomized, double-blind, placebo-controlled trial. METHODS: In Nepal, we studied 2000 healthy adults susceptible to HEV infection who were randomly assigned to receive three doses of either the rHEV vaccine or placebo at months 0, 1, and 6. Active (including hospital) surveillance was used to identify acute hepatitis and adverse events. The primary end point was the development of hepatitis E after three vaccine doses. RESULTS: A total of 1794 subjects (898 in the vaccine group and 896 in the placebo group) received three vaccine doses; the total vaccinated cohort was followed for a median of 804 days. After three vaccine doses, hepatitis E developed in 69 subjects, of whom 66 were in the placebo group. The vaccine efficacy was 95.5% (95% confidence interval [CI], 85.6 to 98.6). In an intention-to-treat analysis that included all 87 subjects in whom hepatitis E developed after the first vaccine dose, 9 subjects were in the vaccine group, with a vaccine efficacy of 88.5% (95% CI, 77.1 to 94.2). Among subjects in a subgroup randomly selected for analysis of injection-site findings and general symptoms (reactogenicity subgroup) during the 8-day period after the administration of any dose, the proportion of subjects with adverse events was similar in the two study groups, except that injection-site pain was increased in the vaccine group (P=0.03). CONCLUSIONS: In a high-risk population, the rHEV vaccine was effective in the prevention of hepatitis E. (ClinicalTrials.gov number, NCT00287469 [ClinicalTrials.gov].).

Reactive oxygen species (ROS), highly reactive molecules, are produced by living organisms as a result of normal cellular metabolism and environmental factors, and can damage nucleic acids and proteins, thereby altering their functions. The human body has several mechanisms to counteract oxidative stress by producing antioxidants. A shift in the balance between oxidants and antioxidants in favor of oxidants is termed as "oxidative stress". Paradoxically, there is a large body of research demonstrating the general effect of oxidative stress on signaling pathways, less is known about the initial and direct regulation of signaling molecules by ROS, or what we term the "oxidative interface." This review focuses on the molecular mechanisms through which ROS directly interact with critical signaling molecules to initiate signaling in a broad variety of cellular processes, such as proliferation and survival (MAP kinases and PI3 kinase), ROS homeostasis, and antioxidant gene regulation (Ref-1 and Nrf-2). This review also deals with classification as well as mechanisms of formation of free radicals, examining their beneficial and deleterious effects on cellular activities and focusing on the potential role of antioxidants in preventing and repairing damage caused by oxidative stress. A discussion of the role of phytochemical antioxidants in oxidative stress, disease and the epigenome is included.

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.

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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.

BACKGROUND: Substance use is generally initiated in adolescence or early adulthood and is commonly associated with several physical, psychological, emotional and social problems. The objective of this study is to assess the age of onset of substance use differences on psychosocial problems among individuals with substance use disorders (SUDs) residing in drug rehabilitation centers. METHODS: A descriptive cross sectional research design was carried out. Probability Proportional to Size (PPS) sampling technique was used to select the drug rehabilitation centers and all the respondents meeting the inclusion criteria of the selected seven rehabilitation centers were taken as a sample and comprised of 221 diagnosed individuals with SUDs. A semi structured self administered questionnaires were used to collect the information regarding demographic and substance use related characteristics. A standard tool Drug Use Screening Inventory-Revised (DUSI-R) was used to assess the psychosocial problems among individuals with SUDs. Data were analyzed using both descriptive and inferential statistics. Multivariate general linear model (MANOVA and MANCOVA) was used to evaluate differences in psychosocial problems between early vs late onset substance users. RESULT: The age of onset of substance use was significantly associated with psychosocial problems. The mean psychosocial problem scores were higher in early onset substance user (17 years or younger) than late onset substance user (18 years or higher) in various domains of DUSI-R even after controlling confounding factors. The two groups (early vs late) differed significantly in relation to age, gender, occupational status, current types of substance use, frequency of use, mode of substance use and relapse history. CONCLUSION: The study indicated that early onset substance users are at higher risk for psychosocial problems in various areas of life such as Behavior Pattern, Psychiatric disorder, Family system, Peer relationship, Leisure/Recreation and Work adjustment compared to late onset substance users. It highlights the need for early prevention, screening, and timely intervention among those individuals.

Background: Obese people have a higher prevalence of cardiovascular disease, which is supposed to be due to autonomic dysfunction and/or metabolic disorder. The alterations in cardiac autonomic functions bring out the changes in the heart rate variability (HRV) indicators, an assessing tool for cardiac autonomic conditions. Objective: To compare the cardiac autonomic activity between obese and normal weight adults and find out the highest association between the indices of HRV and obesity. Methods: The study was conducted in 30 adult obese persons (body mass index [BMI] >30 kg/m 2 ) and 29 healthy normal weight controls (BMI 18–24 kg/m 2 ). Short-term HRV variables were assessed using standard protocol. Data were compared between groups using Mann–Whitney U test. Obesity indices such as waist circumference, hip circumference, waist–hip ratio (WHR), and BMI were measured and calculated, and they were correlated with HRV indices using Spearman’s correlation analysis. Results: In the obese group, there was a significant increase in the mean heart rate, whereas the HRV parasympathetic indicators were less (eg, root mean square of differences of successive RR intervals [28.75 {16.72–38.35} vs 41.55 {30.6–56.75} ms, p =0.018], number of RR intervals that differ by >50 ms, that is, NN50 [15.5 {2–39} vs 83.5 {32.75–116.25}, p =0.010], etc) and the sympathetic indicator low frequency (LF)/high frequency (HF) ratio (1.2 [0.65–2.20] vs 0.79 [0.5–1.02], p =0.045) was more than that of the normal weight group. Spearman’s correlation between HRV and obesity indices showed significant positive correlation of WHR with LF in normalized unit (r=0.478, p <0.01) and LF/HF ratio ( r =0.479, p <0.01), whereas it had significant negative correlation with high frequency power ms 2 ( r =−0.374, p <0.05) and HF in normalized unit ( r =−0.478, p <0.01). There was a nonsignificant correlation of BMI with HRV variables in obese individuals. Conclusion: Increased WHR, by far an indicator of visceral adiposity, was strongly associated with reduced cardiac parasympathetic and increased sympathetic activity in obese individuals defined by BMI. However, BMI itself has a weak relationship with HRV cardiac autonomic markers. Thus, even with a slight increase in WHR in an individual, there could be a greater risk of cardiovascular morbidity and mortality brought about by cardiac autonomic alterations. Keywords: obesity, heart rate variability, HRV, body mass index, BMI, waist–hip ratio, WHR, cardiac autonomic regulation

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.

lineage 4 (L4) genomes, we find that dispersal of L4 has been completely dominated by historical migrations out of Europe. We demonstrate an intimate temporal relationship between European colonial expansion into Africa and the Americas and the spread of L4 tuberculosis (TB). Markedly, in the age of antibiotics, mutations conferring antimicrobial resistance overwhelmingly emerged locally (at the level of nations), with minimal cross-border transmission of resistance. The latter finding was found to reflect the relatively recent emergence of these mutations, as a similar degree of local restriction was observed for susceptible variants emerging on comparable time scales. The restricted international transmission of drug-resistant TB suggests that containment efforts at the level of individual countries could be successful.

OBJECTIVES: The objective of this study was to evaluate the immediate effect of slow pace bhastrika pranayama (respiratory rate 6/min) for 5 minutes on heart rate and blood pressure and the effect of the same breathing exercise for the same duration of time (5 minutes) following oral intake of hyoscine-N-butylbromide (Buscopan), a parasympathetic blocker drug. SUBJECTS AND METHODS: Heart rate and blood pressure of volunteers (n = 39, age = 25-40 years) was recorded following standard procedure. First, subjects had to sit comfortably in an easy and steady posture (sukhasana) on a fairly soft seat placed on the floor keeping head, neck, and trunk erect, eyes closed, and the other muscles reasonably loose. The subject is directed to inhale through both nostrils slowly up to the maximum for about 4 seconds and then exhale slowly up to the maximum through both nostrils for about 6 seconds. The breathing must not be abdominal. These steps complete one cycle of slow pace bhastrika pranayama (respiratory rate 6/min). During the practice the subject is asked not to think much about the inhalation and exhalation time, but rather was requested to imagine the open blue sky. The pranayama was conducted in a cool, well-ventilated room (18-20 degrees C). After 5 minutes of this breathing practice, the blood pressure and heart rate again were recorded in the aforesaid manner using the same instrument. The other group (n = 10) took part in another study where their blood pressure and heart rate were recorded following half an hour of oral intake of hyoscine-N-butylbromide 20 mg. Then they practiced the breathing exercise as stated above, and the abovementioned parameters were recorded again to study the effect of parasympathetic blockade on the same pranayama. RESULTS: It was noted that after slow bhastrika pranayamic breathing (respiratory rate 6/min) for 5 minutes, both the systolic and diastolic blood pressure decreased significantly with a slight fall in heart rate. No significant alteration in both blood pressure and heart rate was observed in volunteers who performed the same breathing exercise for the same duration following oral intake of hyoscine-N-butylbromide. DISCUSSION: Pranayama increases frequency and duration of inhibitory neural impulses by activating pulmonary stretch receptors during above tidal volume inhalation as in Hering Bruer reflex, which bring about withdrawal of sympathetic tone in the skeletal muscle blood vessels, leading to widespread vasodilatation, thus causing decrease in peripheral resistance and thus decreasing the diastolic blood pressure. After hyoscine-N-butylbromide, the parasympathetic blocker, it was observed that blood pressure was not decreased significantly as a result of pranayama, as it was observed when no drug was administered. CONCLUSIONS: Vagal cardiac and pulmonary mechanisms are linked, and improvement in one vagal limb might spill over into the other. Baroreceptor sensitivity can be enhanced significantly by slow breathing (supported by a small reduction in the heart rate observed during slow breathing and by reduction in both systolic and diastolic pressure). Slow pace bhastrika pranayama (respiratory rate 6/min) exercise thus shows a strong tendency to improving the autonomic nervous system through enhanced activation of the parasympathetic system.

Abstract Objective: To determine home based newborn care practices in rural Nepal in order to inform strategies to improve neonatal outcome. Design: Cross sectional, retrospective study using structured interviews. Setting: Makwanpur district, Nepal. Participants: 5411 married women aged 15 to 49 years who had given birth to a live baby in the past year. Main outcome measures: Attendance at delivery, hygiene, thermal care, and early feeding practices. Results: 4893 (90%) women gave birth at home. Attendance at delivery by skilled government health workers was low (334, 6%), as was attendance by traditional birth attendants (267, 5%). Only 461 (8%) women had used a clean home delivery kit, and about half of attendants had washed their hands. Only 3482 (64%) newborn infants had been wrapped within half an hour of birth, and 4992 (92%) had been bathed within the first hour. 99% (5362) of babies were breast fed, 91% (4939) within six hours of birth. Practices with respect to colostrum and prelacteals were not a cause for anxiety. Conclusions: Health promotion interventions most likely to improve newborn health in this setting include increasing attendance at delivery by skilled service providers, improving information for families about basic perinatal care, promotion of clean delivery practices, early cord cutting and wrapping of the baby, and avoidance of early bathing. What is already known on this topic Most births in rural south Asia occur at home Neonatal mortality has remained fairly constant in developing countries despite falling infant mortality What this paper adds Only 6% of births in rural Nepal took place in the presence of a skilled attendant Cord cutting implements were often unclean and drying and wrapping of newborn infants was usually delayed 99% of babies were breast fed, 92% of them within six hours of birth, and colostrum was generally given Interventions need to focus on educating women about hygiene, encouraging early wrapping, and delaying bathing of newborn babies

BACKGROUND: Nonadherence to diet and physical activity is a major problem in the management of diabetes mellitus and its complications. This study was undertaken to measure the factors associated with nonadherence to diet and physical activity advice among Nepalese type 2 diabetic patients. METHODS: An analytical cross-sectional study was conducted among type 2 diabetic patients (age, M ± SD, 54.4 ± 11.5 yrs) and interviewed using three days recall method for dietary history and Compendium of Physical Activity for physical activity. Data were analysed by univariate and multivariate statistics. RESULTS: Out of 385 patients, 87.5% were nonadherent and 12.5% poorly adherent to dietary advice. 42.1% were nonadherent, 36.6% partially adherent while 21.3% good adherent to physical activity. Adherence to dietary advice was higher in males than females (M ± SD, 33 ± 16.7 vs 27 ± 15.5, p = 0.001), those staying nearer to hospital than farther (M ± SD, 32 ± 18.6 vs 28 ± 13.5, p = 0.013), those advice by physician than others (p = 0.001) and from nuclear family than joint and extended (p = 0.001). With increasing age, dietary advice adherence decreased (p = 0.06) and was positively correlated with the knowledge about diabetes mellitus (r = 0.115, p = 0.024). Physical activity adherence was higher in those with positive family history of diabetes than others (M ± SD, 74 ± 24.2 vs 65 ± 23.6, p = 0.001), upper middle socioeconomic class respondents than lower ones (p = 0.047) and from extended family than nuclear or joint ones (p = 0.041). Divorced were more nonadherent to physical activity than married and widowed patients (p = 0.021). CONCLUSIONS: Determinants of nonadherence to dietary advice: Female gender, increasing age, joint or extended family members, farther distance from hospital, poor knowledge about diabetes mellitus and advice by others than physicians. Determinants for nonadherence to physical activity: negative family history of DM, divorced status, lower socioeconomic class.

Background: Corona virus disease 2019 (COVID-19) is a highly infectious disease. It is caused by a novel virus belonging to a family known as corona virus. This virus was first identified in the month December 2019 in Wuhan, China Hubei province. Since its first identification it has spread globally. It was declared a public health emergency of international concern on January 30, 2020 by WHO. Despite all efforts the virus continues to spread and WHO declared it a pandemic on March 11, 2020. In Nepal the first case was tested positive on23rd January and ever since numbers are increasing as days passed by. Residents of the country are the most important stakeholders to control the spread of such viruses. Nepal is a land locked country situated between India and China and is one of the vulnerable areas among SAARC nations. In spite of being such a vulnerable nation there was a lack of previous studies detecting the degree of awareness among Nepalese residents towards COVID 19. Aims and Objectives: This study aims to assess the current level of awareness towards COVID 19 among Nepalese residents and to analyze their attitudes and practices towards COVID 19 which is very important for people’s active participation to control this pandemic. In this study we investigated Nepalese residents KAP towards COVID-19. Material and Methods: This is cross sectional online study. A self-developed online questionnaire was completed by the participants. There were a total 29 questions among which 15 questions assessedknowledge, 6 questions assessed attitude and remaining 8 questions assessed practice. Results: Among the respondents (n=760), 65.7 % were male, 50.3 % were healthcare workers, overall range of correct answers for knowledge questionnaire was 60.0-98.7%, that for attitude was 77.9-96.4% and for practice was 78.2-95.0 %. Participants with a medical degree had statistically significant better practice against COVID 19 compared with the general population. Conclusion: Findings of this study show that knowledge among people of Nepal about COVID 19 is satisfactory. Yet a significant number of participants are lacking confidence when compared to other countries. Better practice against COVID requires a sense of responsibility, though the respondents with medical background had better sense of act against COVID prevention practice.

Background. This study was done to assess the maternal and sociodemographic factors associated with low birth weight (LBW) babies. Methods. An unmatched case control study was done involving 159 cases (mothers having LBW singleton babies) and 159 controls (mothers having normal birth weight singleton babies). Results. More than 50% of LBW babies were from the mothers with height ≤145 cm while only 9.43% of NBW babies were from the mothers with that height. Finally, after multivariate logistic regression analysis, maternal height, time of first antenatal care (ANC) visit, number of ANC visits, iron supplementation, calcium supplementation, maternal education, any illness during pregnancy, and hypertension were found as the significant predictors of LBW. However, maternal blood group AB, normal maternal Body Mass Index (BMI), mother's age of 30 or more years, and starting ANC visit earlier were found to be protective for LBW. Conclusion. Study findings suggest that selectively targeted interventions such as delay age at first pregnancy, improving maternal education and nutrition, and iron and calcium supplementation can prevent LBW in Nepal.

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: Menstrual exile, also known as Chhaupadi, is a tradition of "untouchability" in far-western Nepal. Forbidden from touching other people and objects, women and girls are required to live away from the community, typically in a livestock shed, during menstruation. We assessed the lived experiences of Chhaupadi among Nepalese adolescent girls in the far-western Achham district of Nepal, observed the safety and sanitation of their living spaces during Chhaupadi, and assessed the perceptions of local adult stakeholders towards the practice of Chhaupadi. METHODS: We collected data from 107 adolescent girls using a self-administered survey in two local schools in Achham. We also conducted a focus group discussion with seven girls, held key informant interviews, and observed the girls' living spaces during Chhaupadi, using a checklist. Descriptive statistics of the quantitative survey and thematic analyses of qualitative interviews are presented. RESULTS: The majority of the girls (n = 77, 72%) practiced exile, or Chhaupadi, during their menstruation, including 3 (4%) exiled to traditional Chhau sheds, 63 (82%) to livestock sheds, and 11 (14%) to courtyards outside their home. The remaining girls (n = 30, 28%) stayed inside the house, yet practiced some form of menstrual taboos. Of the 77 observed living spaces where the girls stayed during exile, only 30% (n = 23) had a toilet facility. Most exiled girls (97.4%) were restricted from eating dairy products. Participants reported having various psychological problems, including lonliness and difficulty sleeping while practicing Chhaupadi. Three of the girls were physically abused; nine were bitten by a snake. Notably high proportions of the living spaces lacked ventilation/windows (n = 20, 26%), electricity (n = 29, 38%), toilets (n = 54, 70%) and a warm blanket and mattress for sleeping (n = 29, 38%). Our qualitative findings supported our quantitative results. CONCLUSIONS: Chhaupadi has been condemned by human rights organizations. While the government has banned the practice, implementation on the ban is proceeding slowly, especially in far-western Nepal. Thus, as a temporary measure, public health professionals must work towards promoting the health and safety of Nepalese women and girls still practicing Chhaupadi.

The Wilderness Medical Society convened an expert panel to develop a set of evidence-based guidelines for prevention and treatment of frostbite. We present a review of pertinent pathophysiology. We then discuss primary and secondary prevention measures and therapeutic management. Recommendations are made regarding each treatment and its role in management. These recommendations are graded on the basis of the quality of supporting evidence and balance between the benefits and risks or burdens for each modality according to methodology stipulated by the American College of Chest Physicians. This is an updated version of the guidelines published in 2014.

BACKGROUND: Neonatal mortality rates are high in rural Nepal where more than 90% of deliveries are in the home. Evidence suggests that death rates can be reduced by interventions at community level. We describe an intervention which aimed to harness the power of community planning and decision making to improve maternal and newborn care in rural Nepal. METHODS: The development of 111 women's groups in a population of 86 704 in Makwanpur district, Nepal is described. The groups, facilitated by local women, were the intervention component of a randomized controlled trial to reduce perinatal and neonatal mortality rates. Through participant observation and analysis of reports, we describe the implementation of this intervention: the community entry process, the facilitation of monthly meetings through a participatory action cycle of problem identification, community planning, and implementation and evaluation of strategies to tackle the identified problems. RESULTS: In response to the needs of the group, participatory health education was added to the intervention and the women's groups developed varied strategies to tackle problems of maternal and newborn care: establishing mother and child health funds, producing clean home delivery kits and operating stretcher schemes. Close linkages with community leaders and community health workers improved strategy implementation. There were also indications of positive effects on group members and health services, and most groups remained active after 30 months. CONCLUSION: A large scale and potentially sustainable participatory intervention with women's groups, which focused on pregnancy, childbirth and the newborn period, resulted in innovative strategies identified by local communities to tackle perinatal care problems.

Pranayama (breathing exercise), one of the yogic techniques can produce different physiological responses in healthy individuals. The responses of Alternate Nostril Breathing (ANB) the Nadisudhi Pranayama on some cardio-respiratory functions were investigated in healthy young adults. The subjects performed ANB exercise (15 minutes everyday in the morning) for four weeks. Cardio-respiratory parameters were recorded before and after 4-weeks training period. A significant increment in Peak expiratory flow rate (PEFR L/min) and Pulse pressure (PP) was noted. Although Systolic blood pressure (SBP) was decreased insignificantly, the decrease in pulse rate (PR), respiratory rate (RR), diastolic blood pressure (DBP) were significant. Results indicate that regular practice of ANB (Nadisudhi) increases parasympathetic activity.