Evaluation of Protective Activity of Curcumin in Reducing Methotrexate Induced Liver Cells Injury: An Experimental Study on Iraqi White Domestic Rabbits

المقدمة: إصابات خلايا الكبد والخلل في وظائفةمنالمشاكل الشائعة في الممارسات الطبية. معظم العقاقير شائعة الاستخدام من الممكن ان تؤدي الى التهاب الكبد او خلل في وظائفة، مثلا المضادات الحيوية، مسكنات الالم مثل الباراسيتامول وغيرة، الأدوية المضادة للسرطان، تناول الكحول، والمواد الكيميائية السامة الأخرى المستخدمة في الصناعة. على الرغم من أن الميثوتريكسيت هو عامل  فعال مضاد للسرطان، فهو كذلك يستخدم على نطاق واسع في علاج العديد من الحالات غير السرطانية كالأمراض الجلدية والروماتيزملانة مضاد للمناعة. الكركميحتوي على مجموعة متنوعة من المواد الطبيعية مع خصائص مضادة للأكسدة قوية وفعالة في مكافحة الإجهاد التأكسدي الناجم عن تناول الميثوتريكسيت. الهدف من الدراسة: أولا لمعرفة تأثير دواء الميثوتريكست على انسجة الكبد، وثانيا دراسة النشاط الوقائي لمادة الكركم في الحد من تاثير هذا الدواء على انسجة الكبد. المواد والطرق: تمت الدراسة على الارانب البيضاء العراقية وقد تم فصل الحيوانات عشوائيا إلى ثلاث مجموعات. مجموعة السيطرة، مجموعة ميثوتريكسيت، ومجموعة الكركم. النتائج: أثبتت نتائج مستويات البيليروبينوإنزيمات الكبد في مصل الدم والفحوصات النسيجية على انسجة الكبد عن التهاب الكبد الحاد نتيجة تأثير علاج الميثوتريكسيت، وتشير البتائج عن توليد الأكسجين التفاعلي (روس)، ونقص في آليات الدفاع المضادللأكسدة. الاستنتاج: أثبتت الدراسة ان لمادة الكركم تأثير مضاد للاكسدة وباستطاعتة التقليل من التاثيرات الجانبية لدواء الميثوتريكسيت على انسجة الكبد. التوصية: توصي الدراسة باستخدام مادة الكركم في الممارسة السريرية وخاصة للمرض الذين يستخدمون العلاجات الكيمياويةكونة مكمل غذائي وكونةمادة طبيعية ومضاد قوي للاكسدة. الكلمات مفتاحيه: الميثوتريكست، الكركم، سمية الخلايا الكبديه.Background: Hepatotoxicity is a common problem in medical practice, most of the commonly used drugs are potentially hepatotoxic. Although Methotrexate is a hepa- toxic drug, it is widely used in the treatment of many cancerous and non-cancerous conditions because of its cytotoxic and immunosuppressant activity. Curcumin con- tains a variety of natural substances with antioxidant properties, it is widely used in  folk medicine.Antioxidant activity of Curcumin can reduce liver cell injury induced by Methotrexate administration. Objective: The research aims to study the methotrexate hepatoxicity on rabbits, and the hepatoprotective activity of Curcumin. Materials and Methods: Thirty white domestic rabbits were bought from animal market and grouped randomly into three groups; control group received intraperitoneal normal saline, methotrexate group received 6.5 mg/Kgm body weight intraperitoneal methotrexate, and curcumin group received oral Curcumin in addition to intraperitoneal methotrexate. Results: The study showed abnormal liver function tests, INR, liver tissues oxida- tive markers, and liver cell injury on histopathology in Methotrexate group, and normal findings in Curcumin groups. Conclusion: It is concluded that the Methotrexate is a hepatotoxic drug. The results also shoe that the concomitant administration of Curcumin reduced hepatotoxicity. Recommendation: It is recommended to use of Curcumin in clinical practice as a food supplement to patient receiving methotrexate to reduce hepatotoxicity

The role of CD38 expression on NAD levels and cell physiology in a leukaemia model

CD38 is a transmembrane glycoprotein with both ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase activities; it is also known as a cell surface receptor. CD38 utilizes NAD(P) as a substrate to produce the second messengers, Nicotinic acid adenine dinucleotide phosphate (NAADP) and Cyclic adenosine diphosphate ribose (cADPR). CD38 has been implicated in several diseases. For instance, in chronic lymphocytic leukemia (CLL), it is known as a poor prognostic marker and as a disease modifier. Also, abundant data are available on the receptor functions of CD38 in CLL. However, the aim of the work described in this thesis was to investigate the enzymatic functions of CD38 in leukemia. The work also addresses the question of why CD38+ subset leukemia patients are characterised by poor outcome. It has been postulated that CD38 is the major NADase in cells, and that knocking it down increases NAD levels significantly. Thus, it was hypothesized that NAD levels might be depleted and result in detrimental consequences on cell physiology when CD38 is significantly expressed. Also, it was suggested that a similar linkage might be also present in leukemia, contributing to poor outcome. To test this hypothesis, a human leukaemia cell line (HL60) was used as a convenient model that differentiates into CD38+ cells when stimulated using all-trans retinoic acid (ATRA). It is shown that CD38 is expressed extracellularly and intracellularly in the differentiated cells, as evaluated by qPCR, FACS, Western blotting and the NGD cyclization assay. However, one of the major consequences of the early expression of CD38 (at 3 h) was a substantial depletion of intracellular NAD+ levels that was apparent by 4 h after treatment with ATRA. These novel data suggest a major role for CD38 as a main regulator of NAD during the differentiation. The main role of CD38 in degradation of NAD was confirmed by using a CD38 inhibitor (kuromanin). Interestingly, the drop in NAD+ levels during the differentiation was reversed after treatment with kuromanin. Furthermore, the CD38 homologue, CD157, and other NAD-consuming enzymes (PARP and SIRT) were all investigated, and it was found that there are no substantial roles of all these enzymes on the NAD+ degradation during the differentiation. In contrast, qPCR results for NAD-biosynthesis enzymes during the differentiation process showed a significant rise in indolamine 2,3-dioxygenase (IDO) mRNA expression, with lesser increases in nicotinamide nucleotide adenyltransferase (NMNAT) and nicotinamide phosphoribosyl transferase (NAMPT) mRNA levels. The consequences of low NAD levels on cell metabolism were also assessed; the results show a reduction in lactate production and glutathione levels with an elevation of TBARS levels. However, the NAD+:NADH ratio remained relatively constant. Moreover, the effects of low NAD levels on DNA repair and cell death were also investigated in response to DNA damage caused by UVB. Preliminary findings show that, in CD38+ cells, there is a resistance to apoptotic cell death. Additionally, CD38 expression was also investigated in leukaemia cells, and was found to be regulated in response to hypoxic environment, or the change in NAD+ levels following FK866, kuromanin and NAD+ application. Altogether, these studies raise the possibility that the impact of CD38 enzymatic function on NAD levels and the negative consequences on NAD(P)-dependent processes might play an important role in the poor prognosis in CD38+ leukemia patients.the Ministry of the Higher Education and Scientific Research, Republic of Ira

Detection of Leishmania tropica Using Nested-PCR and Some of Their Virulence Factors in Thi-Qar Province, Iraq

تعد اللشمانيا الجلدية هي واحدة من الامراض المتوطنة في العراق، وهي تسبب من مشاكل صحية واسعة النطاق فضلا عن كونها أحد الامراض الغير مسيطر عليها. الدراسة الحالية هدفت الى تشخيص أنواع اللشمانيا المسببة للآفات الجلدية بين المرضى في محافظة ذي قار- جنوب العراق، كذلك لتحديد بعض عوامل الضراوة لطفيلي L. tropica. تضمنت هذه الدراسة ثلاث مستشفيات وهي الحسين التعليمي، سوق الشيوخ العام والشطرة العام في المحافظة للفترة من بداية شهر كانون الأول 2018 ولنهاية شهر أيلول 2019. تم جمع العينات من 80 مريض يعانون من الإصابة بداء اللشمانيا الجلدية ومن كلا الجنسين وبأعمار متنوعة، مواقع سكن مختلفة في المحافظة وآفات جلدية مفردة ومتعددة. استخدمت تقنية Nested-PCR لتضخيم جين kDNA لتشخيص أنواع اللشمانيا فضلا عن استخدام تقنية Conventional-PCR في التحري عن تواجد بعض جينات الضراوة. بينت نتائج الدراسة تواجد نوعين من الطفيلي في منطقة الدراسة. وبينت نتائج الترحيل الكهربائي لجين kDNA وجود 65 عينة موجبة لداء اللشمانيا الجلدية وبحجم 750bp للـ L. tropica و560bp للـ L. major. سجل طفيلي L. tropica نسبة بلغت 57.5% وكان النوع الأكثر شيوعا بينما سجل طفيلي L. major نسبة بلغت 23.75% حيث ظهرت بمستوى اقل. لم يلاحظ وجود فروق معنوية عند المقارنة بين إصابات الذكور والاناث، في حين بينت نتائج التحليل الاحصائي وجود فروق معنوية عند المقارنة بين المجاميع العمرية. كشفت الدراسة الحالية وجود جينات الضراوة LPG1, GP63, CPA and PPG1 في كل العزلات لطفيلي L. tropica وبنسبة تواجد بلغت 100%. كذلك كشفت الدراسة عن ان طفيليL. tropica هو النوع الرئيسي المسبب لداء اللشمانيا الجلدي في محافظة ذي قار، وجينات الضراوة هي ضرورية ومهمة لإمراضية الطفيلي.Cutaneous leishmaniasis is one of endemic diseases in Iraq. It is considered as widely health problem and is an uncontrolled disease. The aim of the study is to identify of Leishmania species that cause skin lesions among patients in Thi-Qar Province, South of Iraq, also to detect some virulence factors of L. tropica. This study includes three local locations, Al-Hussein Teaching, Suq Al-Shyokh General and Al-Shatrah General Hospitals in Province for the period from the beginning of December 2018 to the end of September 2019. The samples were collected from 80 patients suffering from cutaneous leishmaniasis, both genders, different ages, various residence places and single and multiple lesions. Nested-PCR technique was used to amplify kinetoplast minicircle fragments DNA (kDNA). Conventional-PCR was performed for determination of some virulence factors (LPG1, GP63, CPA and PPG1 genes). The electrophoresis findings of kDNA gene showed two species of the parasite found in the study area, 65 samples were positive for cutaneous leishmaniasis, L. tropica at 750bp and L. major at 560bp. Generally, L. tropica (57.5%) was the most common specie and L. major (23.75%) appeared in a low level. There are no significant differences between the infections of males and females, while there are significant differences at the comparison between age groups. All virulence genes (LPG1, GP63, CPA and PPG1) appeared in all L. tropica isolates with high percentage (100%). L. tropica is the major specie which that caused CL in Thi-Qar province, while L. major appeared in low incidence. The virulence genes, which were reviewed, are necessary and important in pathogenesis of L. tropica

Global, Regional, and National Burden of Stroke and Its Risk Factors, 1990–2019: A Systematic Analysis for the Global Burden of Disease Study 2019

Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries

Intracellular NAD+ levels are associated with LPS-induced TNF-α release in pro-inflammatory macrophages

Bacterial lipopolysaccharide induces changes in intracellular NAD+ levels in a pro-inflammatory, but not an anti-inflammatory, macrophage model that are correlated with the release of the pro-inflammatory cytokine tumour necrosis factor-α (TNF-α).</jats:p

MgFe[sub]2O[sub]4/CNTs nanocomposite : synthesis, characterization, and photocatalytic activity

Magnesium ferrite is a visible light absorber, and when combined with multiwall carbon nanotubes (MWCNTs), it can lead to low electron–hole recombination rates, thus improving its photocatalytic activity. In this work, a novel MgFe2O4/CNTs nanocomposite catalyst has been synthesized via anchoring MgFe2O4 nanoparticles onto MWCNTs surface by a sol–gel and microwave-assisted route. The prepared catalyst was characterized by X-ray diffraction, Fourier-transform infrared spectroscopy, scanning and transmission electron microscopy, energy-dispersive X-ray analysis and vibrating scanning magnetometry. MgFe2O4 nanoparticles showed a cubic inverse spinel ferrite structure, while MgFe2O4/CNTs nanohybrids showed combinations of both structures. Morphology studies including Brunauer–Emmett–Teller (BET) analysis confirmed a 40 m2 g−1 specific surface area with narrow mesoporous size distribution for the MgFe2O4/CNTs nanocomposite. The photocatalytic performance of the new catalyst was assessed by photodegradation of methylene blue (MB). The experimental results demonstrated that MgFe2O4/CNTs exhibited strong photocatalytic activity, catalysing the photooxidation of about 98% of MB in 25 min under sunlight

Global, regional, and national progress towards Sustainable Development Goal 3.2 for neonatal and child health : all-cause and cause-specific mortality findings from the Global Burden of Disease Study 2019

Background Sustainable Development Goal 3.2 has targeted elimination of preventable child mortality, reduction of neonatal death to less than 12 per 1000 livebirths, and reduction of death of children younger than 5 years to less than 25 per 1000 livebirths, for each country by 2030. To understand current rates, recent trends, and potential trajectories of child mortality for the next decade, we present the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 findings for all-cause mortality and cause-specific mortality in children younger than 5 years of age, with multiple scenarios for child mortality in 2030 that include the consideration of potential effects of COVID-19, and a novel framework for quantifying optimal child survival. Methods We completed all-cause mortality and cause-specific mortality analyses from 204 countries and territories for detailed age groups separately, with aggregated mortality probabilities per 1000 livebirths computed for neonatal mortality rate (NMR) and under-5 mortality rate (USMR). Scenarios for 2030 represent different potential trajectories, notably including potential effects of the COVID-19 pandemic and the potential impact of improvements preferentially targeting neonatal survival. Optimal child survival metrics were developed by age, sex, and cause of death across all GBD location-years. The first metric is a global optimum and is based on the lowest observed mortality, and the second is a survival potential frontier that is based on stochastic frontier analysis of observed mortality and Healthcare Access and Quality Index. Findings Global U5MR decreased from 71.2 deaths per 1000 livebirths (95% uncertainty interval WI] 68.3-74-0) in 2000 to 37.1 (33.2-41.7) in 2019 while global NMR correspondingly declined more slowly from 28.0 deaths per 1000 live births (26.8-29-5) in 2000 to 17.9 (16.3-19-8) in 2019. In 2019,136 (67%) of 204 countries had a USMR at or below the SDG 3.2 threshold and 133 (65%) had an NMR at or below the SDG 3.2 threshold, and the reference scenario suggests that by 2030,154 (75%) of all countries could meet the U5MR targets, and 139 (68%) could meet the NMR targets. Deaths of children younger than 5 years totalled 9.65 million (95% UI 9.05-10.30) in 2000 and 5.05 million (4.27-6.02) in 2019, with the neonatal fraction of these deaths increasing from 39% (3.76 million [95% UI 3.53-4.021) in 2000 to 48% (2.42 million; 2.06-2.86) in 2019. NMR and U5MR were generally higher in males than in females, although there was no statistically significant difference at the global level. Neonatal disorders remained the leading cause of death in children younger than 5 years in 2019, followed by lower respiratory infections, diarrhoeal diseases, congenital birth defects, and malaria. The global optimum analysis suggests NMR could be reduced to as low as 0.80 (95% UI 0.71-0.86) deaths per 1000 livebirths and U5MR to 1.44 (95% UI 1-27-1.58) deaths per 1000 livebirths, and in 2019, there were as many as 1.87 million (95% UI 1-35-2.58; 37% [95% UI 32-43]) of 5.05 million more deaths of children younger than 5 years than the survival potential frontier. Interpretation Global child mortality declined by almost half between 2000 and 2019, but progress remains slower in neonates and 65 (32%) of 204 countries, mostly in sub-Saharan Africa and south Asia, are not on track to meet either SDG 3.2 target by 2030. Focused improvements in perinatal and newborn care, continued and expanded delivery of essential interventions such as vaccination and infection prevention, an enhanced focus on equity, continued focus on poverty reduction and education, and investment in strengthening health systems across the development spectrum have the potential to substantially improve USMR. Given the widespread effects of COVID-19, considerable effort will be required to maintain and accelerate progress

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980–2019 : a systematic analysis for the Global Burden of Disease Study 2020, Release 1

Background: Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. Methods: For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dose-specific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in country-reported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. Findings: By 2019, global coverage of third-dose DTP (DTP3; 81·6% [95% uncertainty interval 80·4–82·7]) more than doubled from levels estimated in 1980 (39·9% [37·5–42·1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38·5% [35·4–41·3] in 1980 to 83·6% [82·3–84·8] in 2019). Third-dose polio vaccine (Pol3) coverage also increased, from 42·6% (41·4–44·1) in 1980 to 79·8% (78·4–81·1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56·8 million (52·6–60·9) to 14·5 million (13·4–15·9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. Interpretation: After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines

Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods: We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings: In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation: The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.Valery L. Feigin … Andrew T Olagunju … Lalit Yadav … et al. (The 2019 Stroke Collaborators

Global, regional, and national burden of stroke and its risk factors, 1990-2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high bodymass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries