Effect of aescin on β-cell physiology in fructose fed rat model

Objective: To determine the effects of Aescin on blood glucose homeostasis in fructose fed Diabetic albino Wistar rats Methodology: This Quasi Experimental study was conducted at the Department of Physiology from July 2018 to January 2019. Sixty albino (Wistar) rats were equally divided into five groups according to diet as; Group A (normal diet) and Group B (Fructose 10 g/kg/day) and all the other experimental groups were given Fructose (10 g/kg/day) with the administration of aescin as; Group C (0.9 mg/kg/day), Group D (1.8 mg/kg/day) and Group E (3.6 mg/kg/day). After four weeks body weight was calculated and blood samples were taken from all animals to assess the blood glucose level and serum insulin level. All the data was recorded in self-made proforma. Results: Mean of blood glucose in control group A (165.0±14.29 mg/dL) was significantly lower in contrast to experimental groups B, C and D (357.17±21.73, 246.08±21.73 and 235.67±25.73 respectively); p-0.001, while the mean difference was insignificant as compared to experimental group E (194.0±22.16 mg/dl); p=0.078. Serum insulin level was significantly lower in experimental group B (17.45± 5.17) as compared to control group A (16.88± 4.78); p-0.001, while Aescin administered groups C and D showed serum insulin level (19.05± 5.81 and 25.08± 2.42 respectively) almost equal to control group A; p-0.092. Mean serum insulin level in Aescin (3.6 mg/kg/day) administrated group E was significantly higher (29.10± 1.64 IU/L) as compared control and other experimental groups; p-0.001. Conclusion: The Aescin showed exerts ameliorating effects on glucose homeostasis in fructose fed Diabetic albino Wistar rats. By Aescin administration, serum insulin level can be increases to control the diabetes

Sleep deprivation and its associated factors among general ward patients at a tertiary care hospital in Pakistan

Objective: To estimate the occurrence rate of sleep deprivation and to identify the environmental, staff-related and patient-related factors associated with SD among general ward patients of a tertiary care hospital in Pakistan.Methods: In a cross-sectional study, a pre-tested questionnaire was administered to 108 patients admitted into the general medical and general surgical wards of Aga Khan University Hospital, Karachi.Results: In all, 50 (46.3%) respondents felt deprived of adequate sleep in the hospital. Worry about illness disturbed the night-time sleep of 47 (43.5%) patients; most of these had SD (70%) (p \u3c 0.001). Other patients\u27 noise disturbed 31.5% of study subjects and a significant majority (68%) of these had SD (p = 0.003). Over 17% of study subjects reported cell phone\u27s ringing as a disturbing factor; more by those with SD (68%) compared to those with no SD (32%); again the difference was significant (p = 0.003). Physical discomfort and presence of cannula were reported as disturbing factors by 41.7% and 28.7% of the study subjects respectively but these were not significantly associated with SD.CONCLUSION: Our study revealed that sleep deprivation occurs commonly among general ward patients in tertiary care setting. Factors found to be associated with SD were amenable to modification to a greater extent

Factors associated with HIV infection among children in Larkana District, Pakistan: a matched case-control study.

BACKGROUND: In April, 2019, an HIV outbreak predominantly affecting children occurred in Larkana District, Sindh, Pakistan. By December, 2019, 881 (4·0%) of 21 962 children screened for HIV had tested positive. We aimed to assess factors associated with HIV infection in this outbreak. METHODS: In this individually matched case-control study, we sampled 406 cases (individuals aged <16 years who had registered for paediatric HIV care at the HIV Treatment Centre at Shaikh Zayed Children's Hospital in Larkana City, Pakistan) and 406 controls (individuals without HIV matched by age, sex, and neighbourhood residence, recruited through doorknocking at houses adjacent to case participants). An interviewer-administered questionnaire was used to collect data on possible risk factors for HIV acquisition and a blood sample was collected from all participants for hepatitis B and hepatitis C serology. Mothers of all participants underwent HIV testing. Odds ratios were estimated using conditional logistic regression to assess factors associated with HIV infection. FINDINGS: 406 case-control pairs were recruited between July 3 and Dec 26, 2019. Five pairs were excluded (three pairs had an age mismatch and two pairs were duplicate cases) and 401 were analysed. The prevalence of hepatitis B surface antigen was 18·2% (95% CI 14·5-22·3) among cases and 5·2% (3·3-7·9) among controls, and the prevalence of hepatitis C antibodies was 6·5% (95% CI 4·3-9·4) among cases and 1·0% (0·3-2·5) among controls. 28 (7%) of 397 mothers of cases for whom we had data, and no mothers of 394 controls, were HIV positive. In the 6 months before recruitment, 226 (56%) of 401 cases and 32 (8%) of 401 controls reported having more than ten injections, and 291 (73%) cases and 78 (19%) controls had received an intravenous infusion. At least one blood transfusion was reported in 56 (14%) cases and three (1%) controls in the past 2 years. HIV infection was associated with a history of more injections and infusions (adjusted odds ratio 1·63; 95% CI 1·30-2·04, p<0·0001), blood transfusion (336·75; 23·69-4787·01, p<0·0001), surgery (399·75, 13·99-11 419·39, p=0·0005), the child's mother being HIV positive or having died (3·13, 1·20-8·20, p=0·020), and increased frequency of private clinic (p<0·0001) and government hospital visits (p<0·0001), adjusting for confounders. INTERPRETATION: The predominant mode of HIV transmission in this outbreak was parenteral, probably due to unsafe injection practices and poor blood safety practices. General practitioners across Pakistan need training and systems support in reducing injection use, and in providing safe injections and transfusions only when necessary. FUNDING: Department of Pediatrics and Child Health, the Aga Khan University, Karachi, Pakistan

Perceptions of Pakistani medical students about drugs and alcohol: a questionnaire-based survey

BACKGROUND: Drug abuse is hazardous and known to be prevalent among young adults, warranting efforts to increase awareness about harmful effects and to change attitudes. This study was conducted to assess the perceptions of a group of medical students from Pakistan, a predominantly Muslim country, regarding four drugs namely heroin, charas, benzodiazepines and alcohol. RESULTS: In total, 174 self-reported questionnaires were received (87% response rate). The most commonly cited reasons for why some students take these drugs were peer pressure (96%), academic stress (90%) and curiosity (88%). The most commonly cited justifiable reason was to go to sleep (34%). According to 77%, living in the college male hostel predisposed one to using these drugs. Sixty percent of students said that the drugs did not improve exam performance, while 54% said they alleviated stress. Seventy-eight percent said they did not intend to ever take drugs in the future. Females and day-scholars were more willing to discourage a friend who took drugs. Morality (78%), religion (76%) and harmful effects of drugs (57%) were the most common deterrents against drug intake. Five suggestions to decrease drug abuse included better counseling facilities (78%) and more recreational facilities (60%). CONCLUSION: Efforts need to be made to increase student awareness regarding effects and side effects of drugs. Our findings suggest that educating students about the adverse effects as well as the moral and religious implications of drug abuse is more likely to have a positive impact than increased policing. Proper student-counseling facilities and healthier avenues for recreation are also required

Variability in mortality following caesarean delivery, appendectomy, and groin hernia repair in low-income and middle-income countries: a systematic review and analysis of published data

Background Surgical interventions occur at lower rates in resource-poor settings, and complication and death rates following surgery are probably substantial but have not been well quantifi ed. A deeper understanding of outcomes is a crucial step to ensure that high quality accompanies increased global access to surgical care. We aimed to assess surgical mortality following three common surgical procedures—caesarean delivery, appendectomy, and groin (inguinal and femoral) hernia repair—to quantify the potential risks of expanding access without simultaneously addressing issues of quality and safety. Methods We collected demographic, health, and economic data for 113 countries classifi ed as low income or lower-middle income by the World Bank in 2005. We did a systematic review of Ovid, MEDLINE, PubMed, and Scopus from Jan 1, 2000, to Jan 15, 2015, to identify studies in these countries reporting all-cause mortality following the three commonly undertaken operations. Reports from governmental and other agencies were also identifi ed and included. We modelled surgical mortality rates for countries without reported data using a two-step multiple imputation method. We fi rst used a fully conditional specifi cation (FCS) multiple imputation method to establish complete datasets for all missing variables that we considered potentially predictive of surgical mortality. We then used regression-based predictive mean matching imputation methods, specifi ed within the multiple imputation FCS method, for selected predictors for each operation using the completed dataset to predict mortality rates along with confi dence intervals for countries without reported mortality data. To account for variability in data availability, we aggregated results by subregion and estimated surgical mortality rates. Findings From an initial 1302 articles and reports identifi ed, 247 full-text articles met our inclusion criteria, and 124 provided data for surgical mortality for at least one of the three selected operations. We identifi ed 42 countries with mortality data for at least one of the three procedures. Median reported mortality was 7·9 per 1000 operations for caesarean delivery (IQR 2·8–19·9), 2·2 per 1000 operations for appendectomy (0·0–17·2), and 4·9 per 1000 operations for groin hernia (0·0–11·7). Perioperative mortality estimates by subregion ranged from 2·8 (South Asia) to 50·2 (East Asia) per 1000 caesarean deliveries, 2·4 (South Asia) to 54·0 (Central sub-Saharan Africa) per 1000 appendectomies, and 0·3 (Andean Latin America) to 25·5 (Southern sub-Saharan Africa) per 1000 hernia repairs. Interpretation All-cause postoperative mortality rates are exceedingly variable within resource-constrained environments. Eff orts to expand surgical access and provision of services must include a strong commitment to improve the safety and quality of care

Global, regional, and national sex-specific burden and control of the HIV epidemic, 1990-2019, for 204 countries and territories: the Global Burden of Diseases Study 2019

Background: The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic. Methods: To estimate age-specific and sex-specific trends in 48 of 204 countries, we extended the Estimation and Projection Package Age-Sex Model to also implement the spectrum paediatric model. We used this model in cases where age and sex specific HIV-seroprevalence surveys and antenatal care-clinic sentinel surveillance data were available. For the remaining 156 of 204 locations, we developed a cohort-incidence bias adjustment to derive incidence as a function of cause-of-death data from vital registration systems. The incidence was input to a custom Spectrum model. To assess progress, we measured the percentage change in incident cases and deaths between 2010 and 2019 (threshold >75% decline), the ratio of incident cases to number of people living with HIV (incidence-to-prevalence ratio threshold <0·03), and the ratio of incident cases to deaths (incidence-to-mortality ratio threshold <1·0). Findings: In 2019, there were 36·8 million (95% uncertainty interval [UI] 35·1–38·9) people living with HIV worldwide. There were 0·84 males (95% UI 0·78–0·91) per female living with HIV in 2019, 0·99 male infections (0·91–1·10) for every female infection, and 1·02 male deaths (0·95–1·10) per female death. Global progress in incident cases and deaths between 2010 and 2019 was driven by sub-Saharan Africa (with a 28·52% decrease in incident cases, 95% UI 19·58–35·43, and a 39·66% decrease in deaths, 36·49–42·36). Elsewhere, the incidence remained stable or increased, whereas deaths generally decreased. In 2019, the global incidence-to-prevalence ratio was 0·05 (95% UI 0·05–0·06) and the global incidence-to-mortality ratio was 1·94 (1·76–2·12). No regions met suggested thresholds for progress. Interpretation: Sub-Saharan Africa had both the highest HIV burden and the greatest progress between 1990 and 2019. The number of incident cases and deaths in males and females approached parity in 2019, although there remained more females with HIV than males with HIV. Globally, the HIV epidemic is far from the UNAIDS benchmarks on progress metrics. Funding: The Bill & Melinda Gates Foundation, the National Institute of Mental Health of the US National Institutes of Health (NIH), and the National Institute on Aging of the NIH

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic