Bickerstaff's Encephalitis, Guillain-barré Syndrome And Idiopathic Intracranial Hypertension: Are They Related Conditions?

[No abstract available]663 B744746Hughes, R.A., Cornblath, D.R., Guillain-Barré syndrome. (2005) Lancet, 366, pp. 1653-1666Overell, J.R., Willison, H.J., Recent developments in Miller Fisher syndrome and related disorders (2005) Curr Opin Neurol, 18, pp. 562-566Odaka, M., Yuki, N., Yamada, M., Bickerstaff's brainstem encephalitis: Clinical features of 62 cases and a subgroup associated with Guillain-Barré syndrome (2003) Brain, 126, pp. 2279-2290Ball, A.K., Clarke, C.E., Idiopathic intracranial hypertension (2006) Lancet Neurol, 5, pp. 433-442Walker, R.W., Idiopathic intracranial hypertension: Any light on the mechanism of the raised pressure? (2001) J Neurol Neurosurg Psychiatry, 71, pp. 1-5Weiss, G.B., Bajwa, Z.H., Mehler, M.F., Co-occurrence of pseudotumor cerebri and Guillain-Barré syndrome in an adult (1991) Neurology, 41, pp. 603-604Ropper, A.H., Marmarou, A., Mechanism of pseudotumor in Guillain-Barré syndrome (1984) Arch Neurol, 41, pp. 259-261Pulitanò, S., Viola, L., Genovese, O., Miller-Fisher syndrome mimicking intracranial hypertension following head trauma (2005) Childs Nerv Syst, 21, pp. 473-476Fisher, M., An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia, ataxia and areflexia) (1956) N Engl J Med, 255, pp. 57-65Bickerstaff, E.R., Brain-stem encephalitisfurther observations on a grave syndrome with benign prognosis (1957) Br Med J, 1, pp. 1384-1387Al-Din, A.N., The nosological position of the ophthalmoplegia, ataxia and areflexia syndrome: "the spectrum hypothesis (1987) Acta Neurol Scand, 75, pp. 287-294Chiba, A., Kusunoki, S., Obata, H., Serum anti-GQ1b IgG antibody is associated with ophthalmoplegia in Miller Fisher syndrome and Guillain-Barré syndrome: Clinical and immunohistochemical studies (1993) Neurology, 43, pp. 1911-1917Nagaoka, U., Kato, T., Kurita, K., Cranial nerve enhancement on three-dimensional MRI in Miller Fisher syndrome (1996) Neurology, 47, pp. 1601-1602Kornberg, A.J., Pestronk, A., Blume, G.M., Selective staining of the cerebellar molecular layer by serum IgG in Miller Fisher and related syndromes (1996) Neurology, 47, pp. 1317-1320Lo, Y.L., Chan, L.L., Pan, A., Ratnagopal, P., Acute ophthalmoparesis in the anti-GQ1b antibody syndrome: Electrophysiological evidence of neuromuscular transmission defect in the orbicularis oculi (2004) J Neurol Neurosurg Psychiatry, 75, pp. 436-440Yuki, N., Koga, M., Bacterial infections in Guillain-Barré and Fisher syndromes (2006) Curr Opin Neurol, 19, pp. 451-457Kwon, H.M., Hong, Y.H., Sung, J.J., A case of Bickerstaff's brainstem encephalitisthe evidence of cerebellum involvement by SPM analysis using PET (2006) Clin Neurol Neurosurg, 108, pp. 418-420Urushitani, M., Udaka, F., Kameyama, M., Miller Fisher-Guillain-Barré overlap syndrome with enhancing lesions in the spinocerebellar tracts (1995) J Neurol Neurosurg Psychiatry, 58, pp. 241-243Ogawara, K., Kuwabara, S., Yuki, N., Fisher syndrome or Bickerstaff brainstem encephalitis? Anti-GQ1b IgG antibody syndrome involving both the peripheral and central nervous systems (2002) Muscle Nerve, 26, pp. 845-849Overell, J.R., Hsieh, S.T., Odaka, M., Treatment for Fisher syndrome, Bickerstaff's brainstem encephalitis and related disorders (2007) Cochrane Database Syst Rev, 1. , CD00476

Guillain-barré Syndrome In The Elderly: Clinical, Electrophysiological, Therapeutic And Outcome Features

There are few papers devoted to geriatric Guillain-Barré (GBS) and many related issues remain unanswered. Objective: To describe clinical, electrophysiological and therapeutic features in this age. Method: Clinico-epidemiological data and therapy of GBS patients older than 60 years were reviewed. Hughes scores were used to quantify neurological deficit and define outcome. Results: Among 18 patients (mean age 64.8 years), 9 had evident prodrome and 80% noticed initially sensory-motor deficit. Demyelinating GBS was found in 8 and axonal in 6 subjects. There was one Miller-Fisher and 3 unclassified cases. Plasmapheresis (PFX) was single therapy in 12 patients and intravenous immunoglobulin (IVIg) in 2. Disability scores just before therapy were similar in both groups, so as short and long term outcome. Conclusion: Axonal GBS seems to be more frequent in the elderly and this may have prognostic implications. PFX and IVIg were suitable options, but complications were noticed with PFX. Prospective studies are needed to better understand and manage GBS in the elderly.633 B772775Kuwabara, S., Guillain-Barré syndrome: Epidemiology, pathophysiology and management (2004) Drugs, 64, pp. 597-610Hughes, R.A.C., Rees, J.H., Clinical and epidemiological features of Guillain-Barré syndrome (1997) J Infect Dis, 176 (SUPPL. 2), pp. S92-S98Hartung, H.P., Willison, H.J., Kieseier, B.C., Acute immunoinflammatory neuropathy: Update on Guillain-Barré syndrome (2002) Curr Opin Neurol, 15, pp. 571-577Efficiency of plasma exchange in Guillain-Barré syndrome: Role of replacement fluids (1987) Ann Neurol, 22, pp. 753-761Greenwood, R.J., Newsom Davis, J.M., Hughes, R.A.C., Controlled trial of plasma exchange in acute inflammatory polyradiculoneuropathy (1984) Lancet, 1, pp. 877-879Osterman, P.O., Lundemo, G., Pirskanen, R., Beneficial effects of plasma exchange in acute inflammatory polyradiculoneuropathy (1984) Lancet, 2, pp. 1296-1299Plasmapheresis and acute Guillain-Barré syndrome (1985) Neurology, 35, pp. 1096-1104Plasma exchange in Guillain-Barré syndrome: One-year follow-up (1992) Ann Neurol, 32, pp. 94-97Van Der Meché, F.G.A., Schmitz, P.I.M., A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain-Barré syndrome (1992) N Engl J Med, 326, pp. 1123-1129Randomised trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barré syndrome (1997) Lancet, 349, pp. 225-230Sridharan, G.V., Tallis, R.C., Gautam, P.C., Guillain-Barré syndrome in the elderly: A retrospective comparative study (1993) Gerontology, 39, pp. 170-175Winner, S.J., Evans, J.G., Guillain-Barré syndrome in Oxfordshire: Clinical features in relation to age (1993) Age Ageing, 22, pp. 164-170Yamashita, S., Morinaga, T., Matsumoto, K., Sakamoto, T., Kaku, N., Matsukura, S., Severe Guillain-Barré syndrome in aged patients: The effect of plasmapheresis (1992) Intern Med, 31, pp. 1313-1316Rana, S.S., Rana, S., Intravenous immunoglobulins versus plasmapheresis in older patients with Guillain-Barré syndrome (1999) J Am Geriatr Soc, 47, pp. 1387-1388Asbury, A.K., Cornblath, D.R., Assessment of current diagnostic criteria for Guillain-Barré syndrome (1990) Ann Neurol, 27 (SUPPL.), pp. S21-S24Seneviratne, U., Guillain-Barré syndrome (2000) Postgrad Med J, 76, pp. 774-782Hughes, R.A.C., Newsom-Davis, J.M., Perkin, G.D., Pierce, J.M., Controlled trial of prednisolone in acute polyneuropathy (1978) Lancet, 2, pp. 750-753Rocha, M.S.G., Brucki, S.M.D., Carvalho, A.A.S., Lima, U.W.P., Epidemiologic features of Guillain-Barre syndrome in São Paulo, Brazil (2004) Arq Neuropsiquiatr, 62, pp. 33-37Van Der Meche, F.G., Visser, L.H., Jacobs, B.C., Endtz, H.P., Meulstee, J., Van Doom, P.A., Guillain-Barré syndrome: Multifactorial mechanisms versus defined subgroups (1997) J Infect Dis, 176 (SUPPL. 2), pp. S99-S102Sheth, R.D., Riggs, J.E., Hobbs, G.R., Gutmann, L., Age and Guillain-Barré syndrome severity (1996) Muscle Nerve, 19, pp. 375-377Dias-Tosta, E., Kuckelhaus, C.S., Guillain-Barre syndrome in a population less than 15 years old in Brazil (2002) Arq Neuropsiquiatr, 60, pp. 367-37

The Impact Of Eeg In The Diagnosis And Management Of Patients With Acute Impairment Of Consciousness [impacto Do Eeg No Diagnóstico E Conduta Dos Pacientes Com Alteração Aguda Do Estado Da Consciência]

Objectives: To assess the frequency of electroencephalogram (EEG) requests in the emergency room (ER) and intensive care unit (ICU) for patients with impairment of consciousness (IC) and its impact in the diagnosis and management. Methods: We followed patients who underwent routine EEG from ER and ICU with IC until discharge or death. Results: During the study, 1679 EEGs were performed, with 149 (8.9%) from ER and ICU. We included 65 patients and 94 EEGs to analyze. Epileptiform activity was present in 42 (44.7%). EEG results changed clinical management in 72.2% of patients. The main reason for EEG requisition was unexplained IC, representing 36.3% of all EEGs analyzed. Eleven (33%) of these had epileptiform activity. Conclusion: EEG is underused in the acute setting. The frequency of epileptiform activity was high in patients with unexplained IC. EEG was helpful in confirming or ruling out the suspected initial diagnosis and changing medical management in 72% of patients.7013439Bauer, G., Trinka, E., Nonconvulsive status epilepticus and coma (2010) Epilepsia, 51, pp. 177-190Niedermeyer, E., Silva, F.H.L., (1999) Electroencephalography: Basic Principles, Clinical Applications and Related Fields, , Mariland, USA: William & WilkinsPraline, J., Grujic, J., Corcia, P., Emergent EEG in clinical practice (2007) Clin Neurophysiol, 118, pp. 2149-2155Young, G.B., Jordan, K.G., Doig, G.S., An assessment of nonconvulsive seizures in the intensive care unit using continuous EEG monitoring: An investigation of variables associated with mortality (1996) Neurology, 47, pp. 83-89Towne, A.R., Waterhouse, E.J., Boggs, J.G., Prevalence of nonconvulsive status epilepticus in comatose patients (2000) Neurology, 54, pp. 340-345Vespa, P.M., O'Phelan, K., Shah, M., Acute seizures after intracerebral hemorrhage: A factor in progressive midline shift and outcome (2003) Neurology, 60, pp. 1441-1446Quigg, M., Shneker, B., Domer, P., Current practice in administration and clinical criteria of emergent EEG (2001) J Clin Neurophysiol, 18, pp. 162-165Drislane, F.W., Lopez, M.R., Blum, A.S., Schomer, D.L., Detection and treatment of refractory status epilepticus in the intensive care unit (2008) J Clin Neurophysiol, 25, pp. 181-186Misra, U.K., Kalita, J., Seizures in encephalitis: Predictors and outcome (2009) Seizure, 18, pp. 583-587Alroughani, R., Javidan, M., Qasem, A., Alotaibi, N., Non-convulsive status epilepticusthe rate of occurrence in a general hospital (2009) Seizure, 18, pp. 38-42Kaplan, P.W., The EEG in metabolic encephalopathy and coma (2004) J Clin Neurophysiol, 21, pp. 307-318Bahamon-Dussan, J.E., Celesia, G.G., Grigg-Damberger, M.M., Prognostic significance of EEG triphasic waves in patients with altered state of consciousness (1989) J Clin Neurophysiol, 6, pp. 313-319Firosh, K.S., Ashalatha, R., Thomas, S.V., Sarma, P.S., Emergent EEG is helpful in neurology critical care practice (2005) Clin Neurophysiol, 116, pp. 2454-2459Duffy, F.H., Iyer, V.G., Surwillo, W.W., (1989) Clinical Electroencephalography and Topographic Brain Mapping, , New York: Spring-VerlagGuideline 6: A proposal for standard montages to be used in clinical EEG (2006) J Clin Neurophysiol, 23, pp. 111-117. , American Clinical Neurophysiology SocietyVarelas, P.N., Spanaki, M.V., Hacein-Bey, L., Hether, T., Terranova, B., Emergent EEG: Indications and diagnostic yield (2003) Neurology, 61, pp. 702-704Kilbride, R.D., Costello, D.J., Chiappa, K.H., How seizure detection by continuous electroencephalographic monitoring affects the prescribing of antiepileptic medications (2009) Arch Neurol, 66, pp. 723-728van Cott, A., Brenner, R.P., Technical advantages of digital EEG (1998) J Clin Neurophysiol, 15, pp. 464-475So, E.L., Interictal epileptiform discharges in persons without a history of seizures: What do they mean? (2010) J Clin Neurophysiol, 27, pp. 229-238Claassen, J., Mayer, S.A., Kowalski, R.G., Emerson, R.G., Hirsch, L.J., Detection of electrographic seizures with continuous EEG monitoring in critically ill patients (2004) Neurology, 62, pp. 1743-1748Privitera, M., Hoffman, M., Moore, J.L., Jester, D., EEG detection of nontonic-clonic status epilepticus in patients with altered consciousness (1994) Epilepsy Res, 18, pp. 155-166Selim, M., Kumar, S., Fink, J., Schlaug, G., Caplan, L.R., Linfante, I., Seizure at stroke onset: Should it be an absolute contraindication to thrombolysis? (2002) Cerebrovasc Dis, 14, pp. 54-57Cohn, H.R., Mulder, D.W., Neumann, M.H., Cerebral vascular lesions: Electroencephalographic and neuropathologic correlations (1948) Arch Neurol, 60, pp. 163-181Camilo, O., Goldstein, L.B., Seizures and epilepsy after ischemic stroke (2004) Stroke, 35, pp. 1769-1775Burn, J., Dennis, M., Bamford, J., Sandercock, P., Wade, D., Warlow, C., Epileptic seizures after a first stroke: The Oxfordshire Community Stroke Project (1997) BMJ, 315, pp. 1582-1587Sternbach, G.L., The Glasgow coma scale (2000) J Emerg Med, 19, pp. 67-71Segatore, M., Way, C., The Glasgow Coma Scale: Time for change (1992) Heart Lung, 21, pp. 548-55

Whipple's Disease With Neurological Manifestations: Case Report

Whipple's disease (WD) is an uncommon multisystem condition caused by the bacillus Tropheryma whipplei. Central nervous system involvement is a classical feature of the disease observed in 20 to 40% of the patients. We report the case of a 62 yeards old man with WD that developed neurological manifestations during its course, and discuss the most usual signs and symptoms focusing on recent diagnostic criteria and novel treatment regimens.622 A342346Whipple, G.H., A hitherto undescribed disease characterized anatomically by deposits of fat and fatty acids in the intestinal and mesenteric lymphatic tissues (1907) Johns Hopkins Hosp Bull, 18, pp. 382-391Marth, T., Raoult, D., Whipple's disease (2003) Lancet, 36, pp. 239-246Gerard, A., Sarrot-Reynauld, F., Liozon, E., Neurologic presentation of Whipple disease: Report of 12 cases and review of the literature (2002) Medicine (Baltimore), 81, pp. 443-457Brown, A.P., Lane, J.C., Murayama, S., Vollmer, D.G., Whipple's disease presenting with isolated neurological symptoms: Case report (1990) J Neurosurg, 73, pp. 623-627Bostwick, D.G., Bensch, K.G., Burke, J.S., Whipple's disease presenting as aortic insufficiency (1981) N Engl J Med, 305, pp. 995-998Raoult, D., A febrile, blood culture-negative endocarditis (1999) Ann Intern Med, 131, pp. 144-146Chan, R.Y., Yannuzzi, L.A., Foster, C.S., Ocular Whipple's disease: Earlier definitive diagnosis (2001) Ophthalmology, 108, pp. 2225-2231Louis, E.D., Lynch, T., Kaufmann, P., Fahn, S., Odel, J., Diagnostic guidelines in central nervous system Whipple's disease (1996) Ann Neurol, 40, pp. 561-568Sieracki, J.C., Whipple's disease: Observations on systemic involvement (1958) Amer Med Asso Arch Pathol, 66, pp. 464-467Anderson, M., Neurology of Whipple's disease (2000) J Neurol Neurosurg Psychiatry, 68, pp. 2-5De Coene, B., Gilliard, C., Indekeu, P., Whipple's disease confined to the central nervous system (1996) Neuroradiology, 38, pp. 325-327Verhagen, W.I.M., Huygen, P.L.M., Dalman, J.E., Schuurmans, M.M.J., Whipple's disease and the central nervous system: A case report and a review of the literature (1996) Clin Neurol Neurosurg, 98, pp. 299-304Feldman, M., Hendler, R.S., Morrison, E.B., Acute meningoencephalitis after withdrawal of antibiotics in Whipple's disease (1980) Ann Intern Med, 93, pp. 709-711Schwartz, M.A., Selhorst, J.B., Ochs, A.L., Oculomasticatory myorhythmia: A unique movement disorder occurring in Whipple's disease (1986) Ann Neurol, 20, pp. 677-683Manzel, K., Tranel, D., Cooper, G., Cognitive and behavioral abnormalities in a case of central nervous system Whipple disease (2000) Arch Neurol, 57, pp. 399-403Halperin, J.J., Landis, D.M., Kleinman, G.M., Whipple's disease of the nervous system (1982) Neurology, 32, pp. 612-617Feurle, G.E., Volk, B., Waldherr, R., Cerebral Whipple's disease with negative jejunal histology (1979) N Engl J Med, 300, pp. 907-908Madoule, P., Ciaudio-Lacroix, C., Halimi, P., Osteoarticular lesions in Whipple's disease, a propos of a destructive form and review of the literature (1985) J Radiol, 66, pp. 345-350Brändle, M., Ammann, P., Spinas, G.A., Relapsing Whipple's disease presenting with hypopituitarism (1999) Clin Endocrinol, 50, pp. 399-403Topper, R., Gartung, C., Block, F., Neurologic complications in inflammatory bowel diseases (2002) Nervenarzt, 73, pp. 489-499Clarke, C.E., Falope, Z.F., Abdelhadi, H.A., Cervical myelopathy caused by Whipple's disease (1998) Neurology, 50, pp. 1505-1506Ramzan, N.N., Loftus, E., Burgart, L.J., Diagnosis and monitoring of Whipple disease by polymerase chain reaction (1997) Ann Intern Med, 126, pp. 520-527Von Herbay, A., Ditton, H.J., Scuhmacher, F., Whipple's disease: Staging and monitoring by cytology and polymerase chain reaction analysis of cerebrospinal fluid (1997) Gastroenterology, 113, pp. 434-441Kremer, S., Besson, G., Bonaz, B., Pasquier, B., Le Bas, J.F., Grand, S., Diffuse lesions in the CNS revealed by MR imaging in a case of Whipple disease (2001) Am J Neuroradiol, 22, pp. 493-495Romanul, F.C., Radvany, J., Rosales, R.K., Whipple's disease confined to the brain: A case studied clinically and pathologically (1977) J Neurol Neurosurg Psychiatry, 40, pp. 901-909Thompson, D.G., Leidingham, J.M., Howard, A.J., Brown, C.L., Meningitis in Whipple's disease (1978) BMJ, 2, pp. 14-15Feurle, G.E., Marth, T., An evaluation of antimicrobial treatment for Whipple's disease: Tetracycline versus trimethoprim-sulfamethoxazole (1994) Dig Dis Sci, 39, pp. 1642-1648Misbah, S.A., Mapstone, N.P., Whipple's disease revisited (2000) J Clin Pathol, 53, pp. 750-755Schnider, P.J., Reisinger, E.C., Berger, T., Krejs, G.J., Auff, E., Treatment guidelines in central nervous system Whipple's disease (1997) Ann Neurol, 41, pp. 561-56

Astronomical Distance Determination in the Space Age: Secondary Distance Indicators

The formal division of the distance indicators into primary and secondary leads to difficulties in description of methods which can actually be used in two ways: with, and without the support of the other methods for scaling. Thus instead of concentrating on the scaling requirement we concentrate on all methods of distance determination to extragalactic sources which are designated, at least formally, to use for individual sources. Among those, the Supernovae Ia is clearly the leader due to its enormous success in determination of the expansion rate of the Universe. However, new methods are rapidly developing, and there is also a progress in more traditional methods. We give a general overview of the methods but we mostly concentrate on the most recent developments in each field, and future expectations. © 2018, The Author(s)

Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980�2015: a systematic analysis for the Global Burden of Disease Study 2015

Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14�294 geography�year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, life expectancy from birth increased from 61·7 years (95 uncertainty interval 61·4�61·9) in 1980 to 71·8 years (71·5�72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7�17·4), to 62·6 years (56·5�70·2). Total deaths increased by 4·1 (2·6�5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0 (15·8�18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1 (12·6�16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1 (11·9�14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1, 39·1�44·6), malaria (43·1, 34·7�51·8), neonatal preterm birth complications (29·8, 24·8�34·9), and maternal disorders (29·1, 19·3�37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146�000 deaths, 118�000�183�000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393�000 deaths, 228�000�532�000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost YLLs) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death. Interpretation At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems. Funding Bill & Melinda Gates Foundation. © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY licens

Global, regional, and national levels of maternal mortality, 1990�2015: a systematic analysis for the Global Burden of Disease Study 2015

Background In transitioning from the Millennium Development Goal to the Sustainable Development Goal era, it is imperative to comprehensively assess progress toward reducing maternal mortality to identify areas of success, remaining challenges, and frame policy discussions. We aimed to quantify maternal mortality throughout the world by underlying cause and age from 1990 to 2015. Methods We estimated maternal mortality at the global, regional, and national levels from 1990 to 2015 for ages 10�54 years by systematically compiling and processing all available data sources from 186 of 195 countries and territories, 11 of which were analysed at the subnational level. We quantified eight underlying causes of maternal death and four timing categories, improving estimation methods since GBD 2013 for adult all-cause mortality, HIV-related maternal mortality, and late maternal death. Secondary analyses then allowed systematic examination of drivers of trends, including the relation between maternal mortality and coverage of specific reproductive health-care services as well as assessment of observed versus expected maternal mortality as a function of Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Findings Only ten countries achieved MDG 5, but 122 of 195 countries have already met SDG 3.1. Geographical disparities widened between 1990 and 2015 and, in 2015, 24 countries still had a maternal mortality ratio greater than 400. The proportion of all maternal deaths occurring in the bottom two SDI quintiles, where haemorrhage is the dominant cause of maternal death, increased from roughly 68 in 1990 to more than 80 in 2015. The middle SDI quintile improved the most from 1990 to 2015, but also has the most complicated causal profile. Maternal mortality in the highest SDI quintile is mostly due to other direct maternal disorders, indirect maternal disorders, and abortion, ectopic pregnancy, and/or miscarriage. Historical patterns suggest achievement of SDG 3.1 will require 91 coverage of one antenatal care visit, 78 of four antenatal care visits, 81 of in-facility delivery, and 87 of skilled birth attendance. Interpretation Several challenges to improving reproductive health lie ahead in the SDG era. Countries should establish or renew systems for collection and timely dissemination of health data; expand coverage and improve quality of family planning services, including access to contraception and safe abortion to address high adolescent fertility; invest in improving health system capacity, including coverage of routine reproductive health care and of more advanced obstetric care�including EmOC; adapt health systems and data collection systems to monitor and reverse the increase in indirect, other direct, and late maternal deaths, especially in high SDI locations; and examine their own performance with respect to their SDI level, using that information to formulate strategies to improve performance and ensure optimum reproductive health of their population. Funding Bill & Melinda Gates Foundation. © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY licens

Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980�2015: a systematic analysis for the Global Burden of Disease Study 2015

Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14�294 geography�year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, life expectancy from birth increased from 61·7 years (95 uncertainty interval 61·4�61·9) in 1980 to 71·8 years (71·5�72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7�17·4), to 62·6 years (56·5�70·2). Total deaths increased by 4·1 (2·6�5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0 (15·8�18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1 (12·6�16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1 (11·9�14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1, 39·1�44·6), malaria (43·1, 34·7�51·8), neonatal preterm birth complications (29·8, 24·8�34·9), and maternal disorders (29·1, 19·3�37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146�000 deaths, 118�000�183�000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393�000 deaths, 228�000�532�000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost YLLs) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death. Interpretation At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems. Funding Bill & Melinda Gates Foundation. © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY licens