Efficacy of montelukast for prevention of upper respiratory tract infection in children: A randomized, placebo-controlled trial

Background: Upper Respiratory tract infection (URTI) or common cold is very prevalent in children particularly in young children. Leukotriene receptor antagonists (LTRAs) like montelukast are effective drugs in asthma and some other respiratory diseases. Our purpose was to study preventive effects of montelukast on pediatric URTI. Methods: This randomized, placebo-controlled, and double blind trial was performed on 450 healthy children aged 1-5 year in Amir Kabir Hospital, Arak, Iran. Children were randomized 1:1 to placebo group or montelukast group for 12 weeks. Number of URTI episodes and duration were the primary end points and were compared at baseline and after termination of treatment. Results: Mean age was 28 ± 12.3 months. Mean of URTI episodes was 0.7 ± 0.57 in children treated with montelukast and 1.27 ± 0.72 in children treated with placebo, respectively. Differences were statistically significant (P =0.01). A significant difference was seen in URTI duration between two study groups (6.3 ± 6.1 vs 4.1 ± 3.9, P = 0.05). In addition, duration of fever was shorter in children receiving montelukast (P=0.001). Conclusion: Our study indicates that 3 month treatment with montelukast is effective for reducing the incidence of URTI in young children. This treatment has an acceptable safety without any serious concern. © 2020 Tabriz University of Medical Sciences. All rights reserved

Rituximab and risk of COVID-19 infection and its severity in patients with MS and NMOSD

Background: Choosing a safe disease modifying therapy during the COVID-19 pandemic is challenging. This case series study was conducted to determine the incidence rate and the course of Covid-19 infection in MS/NMOSD patients treated with Rituximab. Methods: In this study, we designed a web-based questionnaire. Baseline information such as patient- reported walking disability, total number of Rituximab infusions received, delayed injections, occurrence of any relapse, and the use of corticosteroids during the pandemic were collected. Also, information regarding the Covid-19 pandemic such as adherence to self-isolation, any recent exposure to an infected individual and the presence of suggestive symptoms were collected. In case of positive test results, patients were grouped into 2 categories; mild to moderate and seriously ill and outcomes were evaluated as favorable (improved/ discharged) and unfavorable (expired). Results: Two hundred fifty-eight patients with Multiple Sclerosis were enrolled in this study, 9 of the subjects (3.4) were confirmed positive for Covid-19, five of which required hospitalizations (55.5), two patients required ICU admission (22.2) and 2 two patients died (22.2). None of these patients ever mentioned using corticosteroids during the pandemic. In comparison to MS patients who were not receiving disease modifying therapy (DMT), our study indicated a higher incidence of Covid-19 infection, higher ratio of serious illness and a higher fatality ratio. Conclusions: Rituximab seems not to be safe enough during the pandemic. © 2021, The Author(s)

The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019

BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden

Global, regional, and national age-sex-specific mortality and life expectancy, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

BACKGROUND: Assessments of age-specific mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Affairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. METHODS: The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specific mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in different components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950. FINDINGS: Globally, 18·7% (95% uncertainty interval 18·4–19·0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58·8% (58·2–59·3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48·1 years (46·5–49·6) to 70·5 years (70·1–70·8) for men and from 52·9 years (51·7–54·0) to 75·6 years (75·3–75·9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49·1 years (46·5–51·7) for men in the Central African Republic to 87·6 years (86·9–88·1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216·0 deaths (196·3–238·1) per 1000 livebirths in 1950 to 38·9 deaths (35·6–42·83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5·4 million (5·2–5·6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult males, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development. INTERPRETATION: This analysis of age-sex-specific mortality shows that there are remarkably complex patterns in population mortality across countries. The findings of this study highlight global successes, such as the large decline in under-5 mortality, which reflects significant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, women, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing

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. Funding: Bill & Melinda Gates Foundation

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.</p

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol�which is a marker of cardiovascular risk�changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95 credible interval 3.7 million�4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world. © 2020, The Author(s), under exclusive licence to Springer Nature Limited

The effect of metformin on memory retention of inhibitory avoidance learning in streptozotocin-induced rat model of alzheimer's disease

Background: Alzheimer's disease (AD) is closely associated with impaired insulin signaling in brain, suggesting it to be a brain-specific form of diabetes and thus termed as the 'type 3 diabetes'. Metformin is one of the most widely used agent against insulin resistance. The present study aimed to investigate the therapeutic effect of metformin on memory retention in streptozotocin (STZ)-induced model of AD in rats using an inhibitory avoidance learning. Materials and Methods: In this experimental study, 56 male Wistar rats were randomly allocated into 7 groups: control STZ-treated, STZ plus saline or metformin. For the induction of AD, STZ (3 mg/kg) was administered bilaterally into lateral ventricles. All rats were trained in shuttle box for inhibitory avoidance learning. Metformin (50, 100, 200 mg/kg, i.p) or saline were injected immediately after the training. The retention test was performed after two days. Results: The results showed that post-training injection of metformin dose-dependently increased the time spent in the light chamber before entering to the dark chamber in STZ-treated rats. Moreover, metformin dose-dependently improved the memory retention in the rats. Conclusion: Post-training injection of metformin dose-dependently enhanced the memory retention in STZ-induced model of AD

Dilemma in Parkinson's Treatment; Levodopa Monotherapy May be the Best Choice

Introduction: Several treatment strategies have been claimed for Parkinson's disease (PD) so far. However, there remains controversies over the best possible treatment. The aim of this study is to compare Levodopa monotherapy versus Pramipexole in combination with Levodopa L in patients with PD with regards to the efficacy and side effects. Methods: Patients being treated with levodopa alone and Pramipexole add-on therapy to Levodopa were enrolled in the study. Factors regarding efficacy and side effects were assessed and analyzed between both groups by appropriate tests. Results: 176 Patients were enrolled in the study. Results showed significant higher total MDS-UPDRS (worse total disease severity score) among patients being treated with Pramipexole add-on therapy which was particularly higher in parts 1 (Mentation, behavior and mood), 2 (Activity of daily living) and 3 (Motor examination) (P-values < 0.05). Psychosis global score with significantly higher frequency of hallucination and depression, statistically higher in combination therapy group compared to Levodopa monotherapy group (P-value < 0.05). Patients in the Pramipexole add-on group reported lower scores of Health-related quality of life (HRQoL) (P-value < 0.05). Significant correlation was between disease duration and psychosis score among Levodopa monotherapy group (P-value < 0.05). Conclusions: Compared to Levodopa monotherapy, Add-on therapy with Pramipexole shows less efficiency yet more side effects. This indicates that single administration of Levodopa still remains the best available treatment for Parkinson's disease. © 2020 Elsevier Lt

Comparison of antibacterial activity of four cultivars of olive (Olea europaea) leaf extract on Bacillus cereus

In recent years, plant extracts have been used as antimicrobial agents. One of these extracts is olive leaf extract, which has antimicrobial properties due to its phenolic compounds. In current study the leaf extract of four olive (Olea europaea) cultivars (Shiraz, Zard, Roghani and Dezfool) was extracted by different solvents (acetone, methanol and ethanol) using microwave-assisted extraction method. Then the antibacterial activity of the extracts was assessed on Bacillus cereus. The antibacterial activity of the extracts was determined using the standard and micro broth-dilution methods. All experiments were carried out in triplicate. Minimum inhibitory concentration (MIC) of eleven extracts was estimated as 20 mg/ml, and only MIC of the methanolic extract of Roghani cultivar was 10 mg/ml. Bacterial growth curve of B. cereus in the presence of olive leaf extracts was drawn after 24 h incubation at 37 °C and the mean percentage of growth inhibition of each extract was measured after 24 hours. The results showed that in comparison with the other cultivars, the methanolic extract of Roghani cultivar with the percentage of growth inhibition of 91.3% and 87.8% (in the concentrations of 10 and 20 mg/ml, respectively), demonstrated stronger antibacterial effect on B. cereus. This study indicated that olive leaf extract from inexpensive agricultural waste might be a valuable bioactive source with antibacterial activity, and seem to be applicable as a safe food additive