Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Hydatid Cyst of Ovary: A Case Report

Echinococcus granulosus is considered the major cause of humanhydatid cysts. Usually the duration of cyst formation is 10-20 years. This period shortens significantly upon rupture of aprimary cyst. The literature describes low incidence of primaryinvolvement of ovary as a site of hydatid cyst formation. Ourcase is the first report on ovarian hydatid cyst in Iran. A 60-year-old woman was presented with abdominal pain in the leftlower quadrant area. Paraclinical data were suggestive of neoplasiaand preoperative diagnosis was ovarian tumor. Duringlaparotomy, multiple cysts resembling hydatid cysts were observedin the left ovary. Pathological examination confirmed thediagnosis of hydatid cyst. Although there is a small possibilityof secondary ovarian echinococcal disease, it is more probablefor this case to be primary infection, as the patient had developedovarian hydatid cysts 15 years after hepatic involvementand recurrence after 30 months is very uncommon

Early clinical exposure program in learning renal physiology

Introduction: Teaching renal physiology for undergraduate medical students in an understandable way using methods which improve their deep learning has always been a problem. In this study, Early Clinical Exposure (ECE) was used in teaching renal physiology for the second year medical students in Shiraz Medical School. This article aims to introduce and develop this program and also measure the attitude of medical students toward ECE in learning renal physiology. Methods: This is a mixed method study conducted on 120 second year undergraduate students. After performing the course, both qualitative and quantitative methods were used for measuring the viewpoints of the students. In the qualitative part, 10 high rank medical students were selected. These students participated in brain storming sessions to express their opinion about the program based on the strengths and weaknesses. For trustworthiness of the qualitative part, member check and peer check were done. In the quantitative part, a researcher-made questionnaire was used based on the objectives of the program in a 4 point Likert scale. The validity of questionnaire was determined by medical education experts and reliability was determined after a pilot study. Results: Based on the results of the quantitative part of the study, 98 percent of the students stated that the ECE program was generally a useful program. In the qualitative part, the students’ comments were obtained. The benefits of the program were summarized in 4 main themes. These themes are “understanding of renal physiology”, “Integration of basic and clinical knowledge”, “Improvement of attitude toward importance of physiology”, and “encouragement to study”. In response to the questions about negetive aspects of this program in qualitative part, the two main themes were insufficient time and large grup size. Conclusion: Students reported that ECE was useful, but they stated that they needed to have more encounter with patients and more hospital teaching. The results also reveal that this ECE program is an excellent approach to strengthen learning in a difficult subject like renal physiology. This approach is adjustable to other basic science topics and subjects as well

A Survey on Medical Students\' Viewpoint on Logbook as a Tool for Recording New Ideas and Reflection

Introduction:Reflection promotes self-awareness, self-guidance,and the ability to make crucial descsions in medical doctors.This study was done to determine the viewpoint of the students of medicine,dntistry,and pharmacology studying in Shiraz University of Medical Sciences. Methods: In this descriptive cross-sectional study, a logbook was designed for recording and analyzing ideas in order to prevent them from being forgotten and to reflect on and use them in practice. This logbook was distributed among students of medicine, dentistry and pharmacy after they had attended an educational workshop on creativity and brain storming. A questionnaire was prepared in order to assess the students' views. The questionnaire was validated for content validity and was approved by experts. Its reliability coefficient was proved to be 0.76% using Cornbach's alpha coefficient. After 2 months, the questionnaires were given to the students. The data were analyzed through SPSS 14. Results: 36% of the respondents had used the logbooks and 64.2% of them evaluated them as effective or very effective. The students who used the logbook recorded 11 ideas in it within 2 months . 46.7% of the students did not record any ideas in the logbook and the reason was expressed to be lack of motivation and low mood. Conclusion: Based on the results, lack of both motivation and inclination for activity leads to lack of effective ideas which are to be practiced in the society. Due to the fact that only 25% of the students used daily schedule section of the logbook, it seems that the students are not familiar with time management strategies and they usually waste their time the problem is not lack of time. However, in spite of the fact that using logbooks by the students is beneficial, educational workshops on time management and also devising concept and mind maps from the ideas are necessary

Lumbar sacralization and L4-L5 microdiscectomy, a prospective cohort study on radiologic and clinical outcomes

Aim: To evaluate the role of lumbar sacralization (LS) on the surgical outcomes of L4-L5 microdiscectomy. Methods: This prospective cohort study was conducted in a university referral hospital. The patients with L4-L5 disc herniation and eligible for microdiscectomy were enrolled and allocated in G1 (with LS) and G2 (no LS). After the L4-L5 microdiscectomy patients were followed, clinical and radiological parameters were collected to investigate the influence on the outcomes. Recurrence, low back outcome score (LBOS), and the Oswestry disability index (ODI) were defined as main outcomes. Results: Two hundred and forty patients (n = 120, each), were reviewed in the final analysis. There was no difference between groups regarding baseline characteristics. Postoperative radicular and back pain was more severe in LS(P < 0.05). Univariate analysis showed recurrence was significantly higher in LS with a direct correlation with postoperative back pain persistence and low LBOS (p = 0.001). Age had a negative impact on G2 recurrence(p = 0.008). LS had a negative impact on LBOS and ODI scores. Postoperative radicular pain and higher lumbar lordosis were associated with a higher disability (ODI) index. Conclusion: L4-L5 microdiscectomy in patients with lumbar sacralization was associated with higher recurrence rates, worse ODI and LBOS scores, persistent postoperative axial back pain, and radicular pain. Postoperative axial back pain and poor LBOS results could effectively predict a higher recurrence rate following L4-L5 microdiscectomy in lumbar sacralization

Modeling the efficacy of different anti-angiogenic drugs on treatment of solid tumors using 3D computational modeling and machine learning

Accurate simulation of tumor growth during chemotherapy has significant potential to alleviate the risk of unknown side effects and optimize clinical trials. In this study, a 3D simulation model encompassing angiogenesis and tumor growth was developed to identify the vascular endothelial growth factor (VEGF) concentration and visualize the formation of a microvascular network. Accordingly, three anti-angiogenic drugs (Bevacizumab, Ranibizumab, and Brolucizumab) at different concentrations were evaluated in terms of their efficacy. Moreover, comprehensive mechanisms of tumor cell proliferation and endothelial cell angiogenesis are proposed to provide accurate predictions for optimizing drug treatments. The evaluation of simulation output data can extract additional features such as tumor volume, tumor cell number, and the length of new vessels using machine learning (ML) techniques. These were investigated to examine the different stages of tumor growth and the efficacy of different drugs. The results indicate that brolucizuman has the best efficacy by decreasing the length of sprouting new vessels by up to 16%. The optimal concentration was obtained at 10 mol m with an effectiveness percentage of 42% at 20 days post-treatment. Furthermore, by performing comparative analysis, the best ML method (matching the performance of the reference simulations) was identified as reinforcement learning with a 3.3% mean absolute error (MAE) and an average accuracy of 94.3%. [Abstract copyright: Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.