62 research outputs found

    Diagnosis and Management of Multiple Sclerosis in Children

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    How to Cite This Article: Najafi MR, Najafi MA, Nasr Z. Diagnosis and Management of Multiple Sclerosis in Children. Iran J Child Neurol. Summer 2016; 10(3): 13-23.AbstractGrowing evidence indicates the safety and well toleration of treatment by Disease-modifying in children suffering multiple sclerosis (MS). The treatment is not straight forward in a great number of patients, thus patients with pediatric MS must be managed by experienced specialized centers. Common treatments of multiple sclerosis for adults are first-line therapies. These therapies (firstline) are safe for children. Failure in treatment that leads to therapy alteration is almost prevalent in pediatric MS. Toleration against current second-line therapies has been shown in multiple sclerosis children. Oral agents have not been assessed in children MS patients. Although clinical trials in children are insufficient, immunomodulating managed children, experience a side effect similar to the adult MS patients. However, further prospective clinical studies, with large sample size and long follow-up are needed to distinguish the benefits and probable side effects of pediatric MS therapies. ReferencesJulian L, Serafin D, Charvet L, Ackerson J, Benedict R, Braaten E, et al. Cognitive Impairment Occurs in Children and Adolescents With Multiple Sclerosis Results From a United States Network.J Child Neurol 2013;28(1):102-7.Inaloo S, Haghbin S. Multiple sclerosis in children. Iran J Child Neurol 2013;7(2):1-10. Epub 2014/03/26.Patel Y, Bhise V, Krupp L. Pediatric multiple sclerosis. Ann Indian Acad Neurol 2009;12(4):238.Saadatnia M, Najafi MR, Najafi F, Davoudi V, Keyhanian K, Maghzi AH. CD24 gene allele variation is not associated with oligoclonal IgG bands and IgG index of multiple sclerosis patients. Neuroimmunomodulation 2012;19(3):195-9.Inaloo S, Haghbin S. Multiple Sclerosis in Children. Iran J Child Neurol 2013 Spring; 7(2): 1–10.Jutta Gartner PH. 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Interferon beta-1a treatment in childhood and juvenile-onset multiple sclerosis. Neurology 2006;67(3):511-3.Pohl D, Waubant E, Banwell B, Chabas D, Chitnis T, Weinstock-Guttman B, et al. Treatment of pediatric multiple sclerosis and variants. Neurology 2007;68(16 suppl 2):S54-S65.Kornek B, Bernert G, Balassy C, Geldner J, Prayer D, Feucht M. Glatiramer acetate treatment in patients with childhood and juvenile onset multiple sclerosis. Neuropediatrics 2003;34(03):120-6.Ghezzi A. Immunomodulatory treatment of early onset multiple sclerosis: results of an Italian Co-operative Study. Neurol Sci 2005;26(4):s183-s6.Tenembaum SN, Banwell B, Pohl D, Krupp LB, Boyko A, Meinel M, et al. Subcutaneous Interferon Beta-1a in Pediatric Multiple Sclerosis A Retrospective Study.J Child Neurol 2013:0883073813488828.Sloka JS, Stefanelli M. The mechanism of action of methylprednisolone in the treatment of multiple sclerosis. Mult Scler (Houndmills, Basingstoke, England) 2005;11(4):425-32. Epub 2005/07/27.Gorman MP, Healy BC, Polgar-Turcsanyi M, Chitnis T. Increased relapse rate in pediatric-onset compared with  adult-onset multiple sclerosis. Arch Neurol 2009;66(1):54.Shahar E, Andraus J, Savitzki D, Pilar G, Zelnik N. Outcome of Severe Encephalomyelitis in Children Effect of High-Dose Methylprednisolone and Immunoglobulins. J Child Neurol 2002;17(11):810-4.Spalice A, Properzi E, Faro VL, Acampora B, Iannetti P. Intravenous immunoglobulin and interferon: successful treatment of optic neuritis in pediatric multiple sclerosis. J Child Neurol 2004;19(8):623-6.Koziolek M, Mühlhausen J, Friede T, Ellenberger D, Sigler M, Huppke B, et al. Therapeutic Apheresis in Pediatric Patients with Acute CNS Inflammatory Demyelinating Disease. Blood Purification 2013;36(2):92-7.Najafi F, Ghaffarpour M, Najafi M, Aghamohammadi A, Saadatnia M. Prognostic value of intrathecal IgG synthesis in multiple sclerosis: a study in 54 patients. Tehran University Medical Journal 2008;66(1):1-6.Yeh E KL, Ness J, Chabas D, et al. Breakthrough disease in pediatric MS patients: a pediatric network experience: Annual Meeting of the American Academy of Neurology. Seattle WA: 2009.Yeh EA. Diagnosis and treatment of multiple sclerosis in pediatric and adolescent patients: current status and future therapies. Adolesc Health Med Ther 2010;1:61-71.Borriello G, Prosperini L, Luchetti A, Pozzilli C. Natalizumab treatment in pediatric multiple sclerosis: a case report. Eur J Paediatr Neurol 2009;13(1):67-71.Huppke P, Stark W, Zurcher C, Huppke B, Bruck W, Gartner J. Natalizumab use in pediatric multiple sclerosis. Arch Neurol 2008;65(12):1655.Makhani N, Gorman M, Branson H, Stazzone L, Banwell B, Chitnis T. Cyclophosphamide therapy in pediatric multiple sclerosis. Neurology 2009;72(24):2076-82.Rice GP, Hartung H-P, Calabresi PA. Anti-α4 integrin therapy for multiple sclerosis Mechanisms and rationale. Neurology 2005;64(8):1336-42.Polman CH, O’Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006;354(9):899-910.Ghezzi A, Pozzilli C, Grimaldi L, Morra VB, Bortolon F, Capra R, et al. Safety and efficacy of natalizumab in children with multiple sclerosis. Neurology   2010;75(10):912-7.Sousa L, de Sa J, Sa MJ, Cerqueira JJ, Martins-Silva A, En Nombre Del Portugal Experience With Natalizumab Study Group Snapshot EN. The efficacy and safety of natalizumab for the treatment of multiple sclerosis in Portugal.: a retrospective study. Revista de Neurologia 2014;59(9):399-406. Epub 2014/10/25. Estudio retrospectivo de la eficacia y seguridad del natalizumab en el tratamiento de la esclerosis multiple en Portugal.Huppke P, Stark W, Zürcher C, Huppke B, Brück W, Gärtner J. Natalizumab use in pediatric multiple sclerosis. Arch Neurol 2008;65(12):1655-8.Hauser SL, Dawson DM, Lehrich JR, Beal MF, Kevy SV, Propper RD, et al. Intensive immunosuppression in progressive multiple sclerosis. A randomized, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange, and ACTH. N Engl J Med 1983;308(4):173-80. Epub 1983/01/27.Weiner HL, Mackin GA, Orav EJ, Hafler DA, Dawson DM, LaPierre Y, et al. Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: final report of the Northeast Cooperative Multiple SclerosisTreatment Group. Neurology 1993;43(5):910-8. Epub 1993/05/01.Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, et al. B-cell depletion with rituximab in relapsing–remitting multiple sclerosis. N Engl J Med 2008;358(7):676-88.Tzaribachev N, Koetter I, Kuemmerle-Deschner JB, Schedel J. Rituximab for the treatment of refractory pediatric autoimmune diseases: a case series. Cases J 2009;2:6609.Carson KR, Focosi D, Major EO, Petrini M, Richey EA, West DP, et al. Monoclonal antibody-associated progressive multifocal leucoencephalopathy in patientstreated with rituximab, natalizumab, and efalizumab: a Review from the Research on Adverse Drug Events and Reports (RADAR) Project. Lancet Oncology 2009;10(8):816-24.Beres SJ, Graves J, Waubant E. Rituximab Use in Pediatric Central Demyelinating Disease. Pediatr Neurol 2014 Jul;51(1):114-8.Wynn D, Kaufman M, Montalban X, Vollmer T, Simon J, Elkins J, et al. Daclizumab in active relapsing multiple  sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta. Lancet Neurol 2010;9(4):381-90.Bielekova B, Howard T, Packer AN, Richert N, Blevins G, Ohayon J, et al. Effect of anti-CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis. Arch Neurol 2009;66(4):483-9.Rose JW, Watt HE, White AT, Carlson NG. Treatment of multiple sclerosis with an anti–interleukin-2 receptor monoclonal antibody. Ann Neurol 2004;56(6):864-7.Ali E, Healy B, Stazzone L, Brown B, Weiner H, Khoury S. Daclizumab in treatment of multiple sclerosis patients. Mult Scler 2009;15(2):272-4.Gorman MP, Tillema J-M, Ciliax AM, Guttmann CR, Chitnis T. Daclizumab use in patients with pediatric multiple sclerosis. Arch Neurol 2012;69(1):78-81.Gorelik L, Lerner M, Bixler S, Crossman M, Schlain B, Simon K, et al. Anti-JC virus antibodies: implications for PML risk stratification. Ann Neurol 2010;68(3):295-303.Bloomgren G, Richman S, Hotermans C, Subramanyam M, Goelz S, Natarajan A, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med 2012;366(20):1870-80.Sørensen PS, Bertolotto A, Edan G, Giovannoni G, Gold R, Havrdova E, et al. Risk stratification for progressive multifocal leukoencephalopathy in patients treated with natalizumab. Mult Scler 2012;18(2):143-52.Yildirim-Toruner C, Diamond B. Current and novel therapeutics in the treatment of systemic lupus erythematosus. J Allergy Clin Immunol 2011;127(2):303-12.Zappitelli M, Duffy CM, Bernard C, Gupta IR. Evaluation of activity, chronicity and tubulointerstitial indices for childhood lupus nephritis. Pediatr Nephrol 2008;23(1):83-91.Di Filippo S. Anti-IL-2 receptor antibody vs. polyclonal anti-lymphocyte antibody as induction therapy in Pediatr Transplant. Pediatr Transplant 2005;9(3):373-80.Gallagher M, Quinones K, Cervantes-Castaneda RA, Yilmaz T, Foster CS. Biological response modifier therapy for refractory childhood uveitis. Br J Ophthalmol 2007;91(10):1341-4.Giovannoni G, Comi G, Cook S, Rammohan K, Rieckmann P, Sørensen PS, et al. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N Engl J Med 2010;362(5):416-26.Kappos L, Radue E-W, O’Connor P, Polman C, Hohlfeld R, Calabresi P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 2010;362(5):387-401.Chun J, Hartung H-P. Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis. Clin Neuropharmacoll 2010;33(2):91.Comi G, O’connor P, Montalban X, Antel J, Radue E, Karlsson G, et al. Phase II study of oral fingolimod (FTY720) in multiple sclerosis: 3-year results. Mult Scler 2010;16(2):197-207.Cohen JA, Barkhof F, Comi G, Hartung H-P, Khatri BO, Montalban X, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis.N Engl J Med 2010;362(5):402-15.Mehling M, Lindberg R, Raulf F, Kuhle J, Hess C, Kappos L, et al. Th17 central memory T cells are reduced by FTY720 in patients with multiple sclerosis. Neurology 2010;75(5):403-10.Edwards JC, Szczepański L, Szechiński J, Filipowicz-Sosnowska A, Emery P, Close DR, et al. Efficacy of B-cell–targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 2004;350(25):2572-81

    RANS SIMULATION OF HYDROFOIL EFFECTS ON HYDRODYNAMIC COEFFICIENTS OF A PLANING CATAMARAN

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    Determination of high-speed crafts’ hydrodynamic coefficients will help to analyze the dynamics of these kinds of vessels and the factors affecting their dynamic stabilities. Also, it can be useful and effective in controlling the vessel instabilities. The main purpose of this study is to determine the coefficients of longitudinal motions of a planing catamaran with and without a hydrofoil using RANS method to evaluate the foil effects on them. Determination of hydrodynamic coefficients by experimental approach is costly, and requires meticulous laboratory equipment; therefore, utilizing numerical methods and developing a virtual laboratory seems highly efficient. In the present study, the numerical results for hydrodynamic coefficients of a high-speed craft are verified against Troesch’s (1992) experimental results. In the following, after determination of hydrodynamic coefficients of a planing catamaran with and without foil, the foil effects on its hydrodynamic coefficients are evaluated. The results indicate that most of the coefficients are frequency independent especially at high frequencies

    Application of Ultrasound Waves to Increase the Efficiency of Oxidative Desulfurization Process

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    One of the key factors for increasing the efficiency of reactions in which catalysts are involved is to increase the contacts and exposure of reagents to the catalysts. Using ultrasonic waves to destabilize the boundary layer between solid catalysts and reagents and mixing the homogeneous catalysts and reagent can increase the rate of reaction. Based on this fact, many industrial processesincludingdesulfurization are enhanced by sonication. In this study a sono desulfurization unit with the capacity of 5 bbl per day, in which oxidative desulfurization is the main mechanism, is designed and tested. Also, the influence of different parameters on the efficiency of the reactions is investigated. Key words: Ultrasonic waves; Desulfurization; Catalyst; Oxidan

    Corneal biomechanical properties distribution in myopic population

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    AIM: To evaluate distribution of corneal biomechanical measurements in normal myopia and myopic-astigmatism population.<p>METHODS:One hundred and eighty eyes with myopia and myopic-astigmatism candidated for laser refractive surgery were included in this study. Complete examination of anterior and posterior segments, manifest refraction spherical equivalent(MRSE), Orbscan and Zywave were performed preoperatively. Ocular response analyzer(ORA)was used to measure corneal hysteresis(CH), corneal resistance factor(CRF), Goldmann-correlated intraocular pressure(IOPg)and corneal compensated IOP(IOPcc). Distribution of all corneal biomechanical properties and correlation between these parameters and MRSE, age and sex were determined. Statistical analysis was performed using SPSS 17 software and a <i>P</i>-Value less than 0.05 was considered significant. <p>RESULTS: Mean age was 28.20±6.78 years. Mean MRSE was -4.21±1.19D. Mean CH, CRF, IOPg and IOPcc was 10.00±1.28mmHg, 10.17±1.45mmHg, 15.71±2.67mmHg and 16.68±2.41mmHg respectively. 28.4% of all myopic population had CH about 10mmHg, and 71% had CH, 9mmHg up to 11mmHg. CRF in 25.9% of myopic population was 10mmHg, and in 48.7% was 9mmHg up to 11mmHg. There was very poor positive correlation between MRSE& CH(Rs=0.001, <i>P</i>=0.71)and MRSE& CRF(Rs=0.01, <i>P</i>=0.18).<p>CONCLUSION: Our study demonstrated the distribution of corneal biomechanical properties(CH, CRF, IOPg, IOPcc)in normal myopia and myopic-astigmatism population in Iran, and confirmed that, there was no statistically significant correlation between CH, CRF and MRSE, age and sex but there was significant correlation between IOPg, IOPcc and formerly mentioned parameters

    Corneal collagen cross-linking effects on pseudophakic bullous keratopathy

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    AIM: To evaluate the efficacy of riboflavin administration and ultraviolet A(UVA)cross-linking on advanced symptomatic bullous keratopathy. <p>METHODS: Fifteen patients with symptomatic pseudophakic bullous keratopathy(PBK)were included. Slit-lamp examination, visual acuity, foreign body sensation(FBS)questionnaire, corneal clarity grading, ocular pain intensity scale and corneal thickness measures with Pentacam and ultrasound pachymetry(UP), were performed before corneal cross-linking and 1 and 6mo thereafter. After using sodium chloride solution, for one week, the central 8mm(diameter)of the corneal epithelium was removed, and cross-linking, with riboflavin instillation every 3min for 30min, and UVA irradiation for 30min was performed. <p>RESULTS: Five males and 10 females with mean age of 66±13y were included. Mean follow up time was 6.2mo. Corneal transparency in all eyes was statistically significantly better 1 month after treatment than preoperatively(<i>P</i><0.05). At 6mo, however, corneal transparency was better in 8 eyes, the same in 5 eyes, and worse in 2 eyes compared with preoperative levels(<i>P</i>= 0.218). Foreign body sensation subsided in 70% of patients. The average CCT decreased within 1mo after the procedure(<i>P</i><0.05). At 6mo, all but 3 eyes had progressive swelling, and the CCT increased; however, the CCT was still statistically significantly thinner than preoperatively(<i>P</i>=0.006). The improvement in mean CDVA from preoperatively to 1mo postoperatively was statistically significant(<i>P</i>=0.010). At 6mo, no significant differences were observed(<i>P</i>=0.130). The pain scores at 1mo were statistically significantly better than preoperatively(<i>P</i>=0.007). At 6mo, however the mean pain score was higher than at 1mo and not statistically significantly different from the preoperative score(<i>P</i>=0.070). <p>CONCLUSION: Corneal CXL significantly improved corneal transparency, corneal thickness, and ocular pain 1 month postoperatively. However, it did not seem to have a long-lasting effect in decreasing pain and maintaining corneal transparency in patients with PBK. This procedure extends the time interval for corneal transplantation and increases visualization at DSAEK procedure

    Prevalence and predictors of low back pain among the Iranian population: Results from the Persian cohort study

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    Background and objectives: Low back pain (LBP) is a common health condition in populations. Limited large-scale population-based studies evaluated the prevalence and predictors of LBP in developing countries. This study aimed to evaluate the prevalence and factors associated with LBP among the Iranian population. Methods: We used baseline information from the Prospective Epidemiological Research Studies in Iran (PERSIAN), including individuals from 16 provinces of Iran. LBP was defined as the history of back pain interfering with daily activities for more than one week during an individual's lifetime. Various factors hypothesized to affect LBP, such as age, sex, marital status, educational status, ethnicity, living area, employment status, history of smoking, body mass index (BMI), physical activity, sleep duration, wealth score, history of joint pain, and history of morning stiffness in the joints were evaluated. Results: In total, 163770 Iranians with a mean age of 49.37 (SD = 9.15) were included in this study, 44.8% of whom were male. The prevalence of LBP was 25.2% among participants. After adjusting for confounders, the female gender [OR:1.244(1.02-1.50)], middle and older ages [OR:1.23(1.10-1.33) and OR:1.13(1.07-1.42), respectively], being overweight or obese [OR:1.13(1.07-1.19) and OR:1.21(1.16-1.27), respectively], former and current smokers (OR:1.25(1.16-1.36) and OR:1.28(1.17-1.39), respectively], low physical activity [OR:1.07 (1.01-1.14)], and short sleep duration [OR: 1.09(1.02-1.17)] were significantly associated with LBP. Conclusion: In this large-scale study, we found the lifetime prevalence of LBP to be lower among the Iranian population in comparison to the global prevalence of LBP; further studies are warranted to evaluate the causality of risk factors on LBP

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

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    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 of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

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    Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

    Global injury morbidity and mortality from 1990 to 2017 : results from the Global Burden of Disease Study 2017

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    Correction:Background Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. Methods We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). Findings In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). Interpretation Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.Peer reviewe

    Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

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    Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019
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