BACKGROUND:Left atrial appendage (LAA) occluder embolization is an infrequent but serious complication. OBJECTIVES:We aim to describe timing, management and clinical outcomes of device embolization in a multi-center registry. METHODS:Patient characteristics, imaging findings and procedure and follow-up data were collected retrospectively. Device embolizations were categorized according to 1) timing 2) management and 3) clinical outcomes. RESULTS:Sixty-seven centers contributed data. Device embolization occurred in 108 patients. In 70.4 % of cases, it happened within the first 24 h of the procedure. The device was purposefully left in the LA and the aorta in two (1.9 %) patients, an initial percutaneous retrieval was attempted in 81 (75.0 %) and surgery without prior percutaneous retrieval attempt was performed in 23 (21.3 %) patients. Two patients died before a retrieval attempt could be made. In 28/81 (34.6 %) patients with an initial percutaneous retrieval attempt a second, additional attempt was performed, which was associated with a high mortality (death in patients with one attempt: 2.9 % vs. second attempt: 21.4 %, p < 0.001). The primary outcome (bailout surgery, cardiogenic shock, stroke, TIA, and/or death) occurred in 47 (43.5 %) patients. Other major complications related to device embolization occurred in 21 (19.4 %) patients. CONCLUSIONS:The majority of device embolizations after LAA closure occurs early. A percutaneous approach is often the preferred method for a first rescue attempt. Major adverse event rates, including death, are high particularly if the first retrieval attempt was unsuccessful. CONDENSED ABSTRACT:This dedicated multicenter registry examined timing, management, and clinical outcome of device embolization. Early embolization (70.4 %) was most frequent. As a first rescue attempt, percutaneous retrieval was preferred in 75.0 %, followed by surgical removal (21.3 %). In patients with a second retrieval attempt a higher mortality (death first attempt: 2.9 % vs. death second attempt: 24.1 %, p < 0.001) was observed. Mortality (10.2 %) and the major complication rate after device embolization were high.

Importance Stroke is a leading cause of death and disability in the US. Accurate and updated measures of stroke burden are needed to guide public health policies. Objective To present burden estimates of ischemic and hemorrhagic stroke in the US in 2019 and describe trends from 1990 to 2019 by age, sex, and geographic location. Design, Setting, and Participants An in-depth cross-sectional analysis of the 2019 Global Burden of Disease study was conducted. The setting included the time period of 1990 to 2019 in the US. The study encompassed estimates for various types of strokes, including all strokes, ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs). The 2019 Global Burden of Disease results were released on October 20, 2020. Exposures In this study, no particular exposure was specifically targeted. Main Outcomes and Measures The primary focus of this analysis centered on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100 000 individuals. Results In 2019, the US recorded 7.09 million prevalent strokes (4.07 million women [57.4%]; 3.02 million men [42.6%]), with 5.87 million being ischemic strokes (82.7%). Prevalence also included 0.66 million ICHs and 0.85 million SAHs. Although the absolute numbers of stroke cases, mortality, and DALYs surged from 1990 to 2019, the age-standardized rates either declined or remained steady. Notably, hemorrhagic strokes manifested a substantial increase, especially in mortality, compared with ischemic strokes (incidence of ischemic stroke increased by 13% [95% uncertainty interval (UI), 14.2%-11.9%]; incidence of ICH increased by 39.8% [95% UI, 38.9%-39.7%]; incidence of SAH increased by 50.9% [95% UI, 49.2%-52.6%]). The downturn in stroke mortality plateaued in the recent decade. There was a discernible heterogeneity in stroke burden trends, with older adults (50-74 years) experiencing a decrease in incidence in coastal areas (decreases up to 3.9% in Vermont), in contrast to an uptick observed in younger demographics (15-49 years) in the South and Midwest US (with increases up to 8.4% in Minnesota). Conclusions and Relevance In this cross-sectional study, the declining age-standardized stroke rates over the past 3 decades suggest progress in managing stroke-related outcomes. However, the increasing absolute burden of stroke, coupled with a notable rise in hemorrhagic stroke, suggests an evolving and substantial public health challenge in the US. Moreover, the significant disparities in stroke burden trends across different age groups and geographic locations underscore the necessity for region- and demography-specific interventions and policies to effectively mitigate the multifaceted and escalating burden of stroke in the country.

BACKGROUND:Scarce data exist on the evolution of device-related thrombus (DRT) after left atrial appendage closure (LAAC). OBJECTIVES:This study sought to assess the incidence, predictors, and clinical impact of persistent and recurrent DRT in LAAC recipients. METHODS:Data were obtained from an international multicenter registry including 237 patients diagnosed with DRT after LAAC. Of these, 214 patients with a subsequent imaging examination after the initial diagnosis of DRT were included. Unfavorable evolution of DRT was defined as either persisting or recurrent DRT. RESULTS:DRT resolved in 153 (71.5%) cases and persisted in 61 (28.5%) cases. Larger DRT size (OR per 1-mm increase: 1.08; 95% CI: 1.02-1.15; P = 0.009) and female (OR: 2.44; 95% CI: 1.12-5.26; P = 0.02) were independently associated with persistent DRT. After DRT resolution, 82 (53.6%) of 153 patients had repeated device imaging, with 14 (17.1%) cases diagnosed with recurrent DRT. Overall, 75 (35.0%) patients had unfavorable evolution of DRT, and the sole predictor was average thrombus size at initial diagnosis (OR per 1-mm increase: 1.09; 95% CI: 1.03-1.16; P = 0.003), with an optimal cutoff size of 7 mm (OR: 2.51; 95% CI: 1.39-4.52; P = 0.002). Unfavorable evolution of DRT was associated with a higher rate of thromboembolic events compared with resolved DRT (26.7% vs 15.1%; HR: 2.13; 95% CI: 1.15-3.94; P = 0.02). CONCLUSIONS:About one-third of DRT events had an unfavorable evolution (either persisting or recurring), with a larger initial thrombus size (particularly >7 mm) portending an increased risk. Unfavorable evolution of DRT was associated with a 2-fold higher risk of thromboembolic events compared with resolved DRT.

Background Anaemia is a major health problem worldwide. Global estimates of anaemia burden are crucial for developing appropriate interventions to meet current international targets for disease mitigation. We describe the prevalence, years lived with disability, and trends of anaemia and its underlying causes in 204 countries and territories. Methods We estimated population-level distributions of haemoglobin concentration by age and sex for each location from 1990 to 2021. We then calculated anaemia burden by severity and associated years lived with disability (YLDs). With data on prevalence of the causes of anaemia and associated cause-specific shifts in haemoglobin concentrations, we modelled the proportion of anaemia attributed to 37 underlying causes for all locations, years, and demographics in the Global Burden of Disease Study 2021. Findings In 2021, the global prevalence of anaemia across all ages was 24 center dot 3% (95% uncertainty interval [UI] 23 center dot 9-24 center dot 7), corresponding to 1 center dot 92 billion (1 center dot 89-1 center dot 95) prevalent cases, compared with a prevalence of 28 center dot 2% (27 center dot 8-28 center dot 5) and 1 center dot 50 billion (1 center dot 48-1 center dot 52) prevalent cases in 1990. Large variations were observed in anaemia burden by age, sex, and geography, with children younger than 5 years, women, and countries in sub-Saharan Africa and south Asia being particularly affected. Anaemia caused 52 center dot 0 million (35 center dot 1-75 center dot 1) YLDs in 2021, and the YLD rate due to anaemia declined with increasing Socio-demographic Index. The most common causes of anaemia YLDs in 2021 were dietary iron deficiency (cause-specific anaemia YLD rate per 100 000 population: 422 center dot 4 [95% UI 286 center dot 1-612 center dot 9]), haemoglobinopathies and haemolytic anaemias (89 center dot 0 [58 center dot 2-123 center dot 7]), and other neglected tropical diseases (36 center dot 3 [24 center dot 4-52 center dot 8]), collectively accounting for 84 center dot 7% (84 center dot 1-85 center dot 2) of anaemia YLDs. Interpretation Anaemia remains a substantial global health challenge, with persistent disparities according to age, sex, and geography. Estimates of cause-specific anaemia burden can be used to design locally relevant health interventions aimed at improving anaemia management and prevention. Funding Bill & Melinda Gates Foundation. Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Background The global burden of lower respiratory infections (LRIs) and corresponding risk factors in children older than 5 years and adults has not been studied as comprehensively as it has been in children younger than 5 years. We assessed the burden and trends of LRIs and risk factors across a groups by sex, for 204 countries and territories. Methods In this analysis of data for the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we used dinician-diagnosed pneumonia or bronchiolitis as our case definition for LRIs. We included International Classification of Diseases 9th edition codes 079.6, 466-469, 470.0, 480-482.8, 483.0-483.9, 484.1-484.2, 484.6-484.7, and 487-489 and International Classification of Diseases 10th edition codes A48.1, A70, B97.4 B97.6, 109-115.8, J16 J16.9, J20-121.9, J91.0, P23.0 P23.4, and U04 U04.9. We used the Cause of Death Ensemble modelling strategy to analyse 23109 site-years of vital r *stration data, 825 site-years of sample vital registration data, 1766 site-years of verbal autopsy data, and 681 site-years of mortality surveillance data. We used DisMod-MR 2.1, a Bayesian metaregression tool, to analyse age sex-specific incidence and prevalence data identified via systematic reviews of the literature, population-based survey data, and daims and inpatient data. Additio y, we estimated age sex-specific LRI mortality that is attributable to the independent effects of 14 risk factors. Findings Globally, in 2019, we estimated that there were 257 million (95% uncertainty interval [UI] 240-275) LRI incident episodes in males and 232 million (217-248) in females. In the same year, LRIs accounted for 1.30 million (95% UI 1.18-1.42) male deaths and 1.20 million (1.07-1.33) female deaths. Age-standardised incidence and mortality rates were 1.17 times (95% UI 1.16-1.18) and 1.31 times (95% UI 1.23-1.41) greater in males than in fe es in 2019. Between 1990 and 2019, LRI incidence and mortality rates declined at different rates across age groups and an increase in LRI episodes and deaths was estimated among all adult age groups, with males aged 70 years and older having the highest increase in LRI episodes (126.0% [95% UI 121.4-131.1]) and deaths (100.0% [83.4-115.9]). During the same period, LRI episodes and deaths in children younger than 15 years were estimated to have decreased, and the greatest dedine was observed for LRI deaths in males younger than 5 years (-70.7% [-77.2 to 61.8]). The leading risk factors for LRI mortality varied across age groups and sex. More than half of global LRI deaths in children younger than 5 years were attributable to child wasting (population attributable fraction [PAF] 53.0% [95% UI 37.7-61.8] in males and 56.4% [40.7-65.1] in females), and more than a quarter of LRI deaths among those aged 5-14 years were attributable to household air pollution (PAF 26.0% [95% UI 16.6-35.5] for males and PAF 25.8% [16.3-35.4] for females). PAFs of male LRI deaths attributed to smoking were 20.4% (95% UI 15.4-25.2) in those aged 15-49 years, 305% (24.1-36. 9) in those aged 50-69 years, and 21.9% (16. 8-27. 3) in those aged 70 years and older. PAFs of female LRI deaths attributed to household air pollution were 21.1% (95% UI 14.5-27.9) in those aged 15-49 years and 18 " 2% (12.5-24.5) in those aged 50-69 years. For females aged 70 years and older, the leading risk factor, ambient particulate matter, was responsible for 11-7% (95% UI 8.2-15.8) of LRI deaths. Interpretation The patterns and progress in reducing the burden of LRIs and key risk factors for mortality varied across age groups and sexes. The progress seen in children you - than 5 years was dearly a result of targeted interventions, such as vaccination and reduction of exposure to risk factors. Similar interventions for other age groups could contribute to the achievement of multiple Sustainable Development Goals targets, induding promoting wellbeing at all ages and reducing health inequalities. Interventions, including addressing risk factors such as child wasting, smoking, ambient particulate matter pollution, and household air pollution, would prevent deaths and reduce health disparities. Copyright 2022 The Author(s). Published by Elsevier Ltd.

de la orejuela auricular izquierda Trevor Simard, MD,a, * Richard G. Jung, BSc, b, * Kyle Lehenbauer, MD,c Kerstin Piayda, MD,d,e Radoslaw Pracoń, MD, PhD,f Gregory G. Jackson, MD,g Eduardo Flores-Umanzor, MD,h Laurent Faroux, MD,i Kasper Korsholm, MD, PhD,j Julian K.R. Chun, MD,k Shaojie Chen, MD,k Moniek Maarse, MD,l,m Kristi Montrella, CRNP,n Zakeih Chaker, MD,o Jocelyn N. Spoon, MD,p Luigi E. Pastormerlo, MD,q Felix Meincke, MD,r Abhishek C. Sawant, MD,s Carmen M. Moldovan, MD, PhD,t Mohammed Qintar, MD,u Mehmet K. Aktas, MD,v Luca Branca, MD,w Andrea Radinovic, MD,x Pradhum Ram, MD,y Rayan S. El-Zein, DO,z Thomas Flautt, DO,aa Wern Yew Ding, MD,bb Bassel Sayegh, MD,cc,dd Tomás Benito-González, MD,ee Oh-Hyun Lee, MD,ff Solomon O. Badejoko, MD, MPH,gg Christina Paitazoglou, MD,hh Nabeela Karim, MD,ii Ahmed M. Zaghloul, MD,jj Himanshu Agrawal, MD,kk Rachel M. Kaplan, MD,ll Oluseun Alli, MD,mm Aamir Ahmed, MD,nn Hussam S. Suradi, MD,nn Bradley P. Knight, MD,ll Venkata M. Alla, MD,kk Sidakpal S. Panaich, MD,jj Tom Wong, MD,ii Martin W. Bergmann, MD,hh Rashaad Chothia, MD,gg Jung-Sun Kim, MD,ff Armando Pérez de Prado, MD,ee Raveen Bazaz, MD,cc Dhiraj Gupta, MD,bb Miguel Valderrabano, MD,aa Carlos E. Sanchez, MD,z Mikhael F. El Chami, MD,y Patrizio Mazzone, MD,x Marianna Adamo, MD,w Fred Ling, MD,v Dee Dee Wang, MD,u William O’Neill, MD,u Wojtek Wojakowski, MD,t Ashish Pershad, MD, MS,s Sergio Berti, MD,q Daniel Spoon, MD,p Akram Kawsara, MD,o George Jabbour, MD,n Lucas V.A. Boersma, MD, PhD,l,m Boris Schmidt, MD,k Jens Erik Nielsen-Kudsk, MD,j Josep Rodés-Cabau, MD, PhD,i Xavier Freixa, MD, PhD,h Christopher R. Ellis, MD,g Laurent Fauchier, MD,oo Marcin Demkow, MD, PhD, f Horst Sievert, MD, d Michael L. Main, MD, cBenjamin Hibbert, MD, PhD, bDavid R. Holmes, JR, MD, aMohamad Alkhouli, MDa INVESTIGACIÓN ORIGINAL

Transcatheter tricuspid valve (TV) interventions have increased dramatically in recent years. TV imaging is challenging in many respects. Given the TV's anatomic complexity, multimodality imaging, which is centered on echocardiography (echo), plays a significant part in planning and execution of these interventions. With the help of echo-guided imaging, pathophysiologic mechanisms for TV disease are better understood, and thus, appropriate valve intervention can be strategized. Novel devices for the TV continue to be developed, and thus, intraprocedural echo imaging will continue to evolve in the days ahead.

Transcatheter tricuspid valve (TV) interventions have increased dramatically in recent years. TV imaging is challenging in many respects. Given the TV's anatomic complexity, multimodality imaging, which is centered on echocardiography (echo), plays a significant part in planning and execution of these interventions. With the help of echo-guided imaging, pathophysiologic mechanisms for TV disease are better understood, and thus, appropriate valve intervention can be strategized. Novel devices for the TV continue to be developed, and thus, intraprocedural echo imaging will continue to evolve in the days ahead.

IMPORTANCE:The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE:To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW:The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS:In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE:The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

For patients with heart failure despite optimal medical therapy, orthotopic heart transplantation (OHT) remains the treatment of choice. Since transplanted hearts have variable cardiac denervation and acute coronary syndrome (ACS) often presents silently or atypically, the true impact of ACS within this population needs more study. The aim of this study is to evaluate in-hospital mortality in post-transplant patients with ACS. Utilizing data from the 2002-15 Nationwide Inpatient Sample database, patients with a primary diagnosis of acute coronary syndrome among those with prior OHT were included. A risk adjusted regression analysis was performed to assess the relationship between ACS and mortality among overall study population. A 2:1 propensity matching was used to match ACS patients with and without OHT to assess differences in mortality. 3,224,073 patients with a primary diagnosis of ACS were included, of which 842 (0.03%) were OHT recipients. The type of ACS: NSTEMI (p = 0.32) and STEMI (p = 0.21) between OHT and non-heart transplant patients was similar in both groups. Following ACS, patients with OHT were more likely to have accompanying shock of any etiology (15.6% vs 3.8%; p<0.001) and cardiogenic shock (11.2% vs 2.6%; p<0.001) compared to those with native hearts. OHT patients also had significantly higher in-hospital mortality (14.3% vs. 3.7%; p<0.001) that remained significant following regression analysis (95% CI 2.8-4.5; p<0.001) irrespective of the presence of cardiogenic shock compared to native hearts. This relationship remained consistent following propensity matching where patients with OHT had significantly higher in-hospital mortality (13.5% vs. 7%; p<0.001).

In this systematic review, we seek to clarify the impact of treatment of hyperthyroidism on pulmonary hypertension in patients with both these conditions. We included 39 of 709 articles retrieved, that studied patients with hyperthyroidism and pulmonary hypertension (PH). From these, those with a documented pre-treatment Pulmonary Artery Systolic Pressure (PASP) > 35 mmHg and complete follow up were analyzed, yielding 3 case series and 22 case reports with a total of 81 cases. A significant improvement in PASP was noted with achieving euthyroidism in the 3 case series. The case reports showed a significant reduction in mean PASP from 60.5 ± 13.2 mmHg to 37.5 ± 10.1 mmHg (p < 0.001) in patients with Grave's disease with achieving euthyroidism. No deaths were reported during the follow up period. Achievement of a euthyroid state in patients with hyperthyroidism is associated with statistically significant reductions in PASP.

BACKGROUND:As targeted treatments for amyloid transthyretin cardiomyopathy (ATTR-CM) are becoming available, we aim to characterize the rates of ventricular arrhythmias (VAs), implantable cardioverter-defibrillator (ICD) utilization, and their impact on survival. METHODS:This is a retrospective cohort study of 130 patients with ATTR-CM diagnosed at Emory University's Cardiac Amyloidosis Center between April 2012 and September 2020. VAs were defined as nonsustained or sustained ventricular tachycardia and ventricular fibrillation. RESULTS:Of 130 patients, 42 had wild-type disease (wtATTR) and 88 had hereditary variants (hATTR), most commonly Val122Ile (89%). At ATTR-CM diagnosis, 80 (62%) patients had EF ≤ 40% consistent with systolic heart failure. Of the 69 (53%) patients with documented VAs significantly higher rates occurred among those with EF ≤ 40% compared with EF > 40% (67% vs. 28%, p = .001). Thirty-two patients (25 hATTR, 7 wtATTR) had primary prevention ICDs implanted. Eight (25%) of these patients received appropriate ICD therapy while two (6%) experienced inappropriate therapy. Comparing patients with EF ≤ 35% with and without ICDs did not reveal any survival difference (3.3 ± 0.5 vs. 2.8 ± 0.4 years, p = .699). CONCLUSIONS:High rates of VAs and appropriate ICD therapy were found among a unique cohort of largely hereditary ATTR-CM patients with a high rate of systolic heart failure.

Key Points Question What was the burden of cancer globally and across Sociodemographic Index (SDI) groupings in 2019, and how has incidence, morbidity, and mortality changed since 2010? Findings In this systematic analysis, there were 23.6 million new global cancer cases in 2019 (17.2 million when excluding those with nonmelanoma skin cancer), 10.0 million cancer deaths, and an estimated 250 million disability-adjusted life years estimated to be due to cancer; since 2010, these represent increases of 26.3%, 20.9%, and 16.0%, respectively. Absolute cancer burden increased in all SDI quintiles since 2010, but the largest percentage increases occurred in the low and low-middle SDI quintiles. Meanings The study results suggest that increased cancer prevention and control efforts are needed to equitably address the evolving and increasing burden of cancer across the SDI spectrum.

Interpretation Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence. Findings In 2019, 273 center dot 9 million (95% uncertainty interval 258 center dot 5 to 290 center dot 9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4 center dot 72% (4 center dot 46 to 5 center dot 01). 228 center dot 2 million (213 center dot 6 to 244 center dot 7; 83 center dot 29% [82 center dot 15 to 84 center dot 42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15-19 years was over 10% in seven locations in 2019. Although global agestandardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: -1 center dot 21% [-1 center dot 26 to -1 center dot 16]), similar progress was not observed for chewing tobacco (0 center dot 46% [0 center dot 13 to 0 center dot 79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (-0 center dot 94% [-1 center dot 72 to -0 center dot 14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period. Summary Background Chewing tobacco and other types of smokeless tobacco use have had less attention from the global health community than smoked tobacco use. However, the practice is popular in many parts of the world and has been linked to several adverse health outcomes. Understanding trends in prevalence with age, over time, and by location and sex is important for policy setting and in relation to monitoring and assessing commitment to the WHO Framework Convention on Tobacco Control. Methods We estimated prevalence of chewing tobacco use as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 using a modelling strategy that used information on multiple types of smokeless tobacco products. We generated a time series of prevalence of chewing tobacco use among individuals aged 15 years and older from 1990 to 2019 in 204 countries and territories, including age-sex specific estimates. We also compared these trends to those of smoked tobacco over the same time period. Findings In 2019, 273 & middot;9 million (95% uncertainty interval 258 & middot;5 to 290 & middot;9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4 & middot;72% (4 & middot;46 to 5 & middot;01). 228 & middot;2 million (213 & middot;6 to 244 & middot;7; 83 & middot;29% [82 & middot;15 to 84 & middot;42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15-19 years was over 10% in seven locations in 2019. Although global age standardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: -1 & middot;21% [-1 & middot;26 to -1 & middot;16]), similar progress was not observed for chewing tobacco (0 & middot;46% [0 & middot;13 to 0 & middot;79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (-0 & middot;94% [-1 & middot;72 to -0 & middot;14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period. Interpretation Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence. Copyright (c) 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Background Prevention, control, and treatment of respiratory tract cancers are important steps towards achieving target 3.4 of the UN Sustainable Development Goals (SDGs)-a one-third reduction in premature mortality due to non-communicable diseases by 2030. We aimed to provide global, regional, and national estimates of the burden of tracheal, bronchus, and lung cancer and larynx cancer and their attributable risks from 1990 to 2019. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 methodology, we evaluated the incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs) of respiratory tract cancers (ie, tracheal, bronchus, and lung cancer and larynx cancer). Deaths from tracheal, bronchus, and lung cancer and larynx cancer attributable to each risk factor were estimated on the basis of risk exposure, relative risks, and the theoretical minimum risk exposure level input from 204 countries and territories, stratified by sex and Socio-demographic Index (SDI). Trends were estimated from 1990 to 2019, with an emphasis on the 2010-19 period. Findings Globally, there were 2.26 million (95% uncertainty interval 2.07 to 2.45) new cases of tracheal, bronchus, and lung cancer, and 2.04 million (1.88 to 2.19) deaths and 45.9 million (42.3 to 49.3) DALYs due to tracheal, bronchus, and lung cancer in 2019. There were 209 000 (194 000 to 225 000) new cases of larynx cancer, and 123 000 (115 000 to 133 000) deaths and 3.26 million (3.03 to 3.51) DALYs due to larynx cancer globally in 2019. From 2010 to 2019, the number of new tracheal, bronchus, and lung cancer cases increased by 23.3% (12.9 to 33.6) globally and the number of larynx cancer cases increased by 24.7% (16.0 to 34.1) globally. Global age-standardised incidence rates of tracheal, bronchus, and lung cancer decreased by 7.4% (-16.8 to 1.6) and age-standardised incidence rates of larynx cancer decreased by 3.0% (-10.5 to 5.0) in males over the past decade; however, during the same period, age-standardised incidence rates in females increased by 0.9% (-8.2 to 10.2) for tracheal, bronchus, and lung cancer and decreased by 0.5% (-8.4 to 8.1) for larynx cancer. Furthermore, although age-standardised incidence and death rates declined in both sexes combined from 2010 to 2019 at the global level for tracheal, bronchus, lung and larynx cancers, some locations had rising rates, particularly those on the lower end of the SDI range. Smoking contributed to an estimated 64.2% (61.9-66.4) of all deaths from tracheal, bronchus, and lung cancer and 63.4% (56.3-69.3) of all deaths from larynx cancer in 2019. For males and for both sexes combined, smoking was the leading specific risk factor for age-standardised deaths from tracheal, bronchus, and lung cancer per 100 000 in all SDI quintiles and GBD regions in 2019. However, among females, household air pollution from solid fuels was the leading specific risk factor in the low SDI quintile and in three GBD regions (central, eastern, and western sub-Saharan Africa) in 2019. Interpretation The numbers of incident cases and deaths from tracheal, bronchus, and lung cancer and larynx cancer increased globally during the past decade. Even more concerning, age-standardised incidence and death rates due to tracheal, bronchus, lung cancer and larynx cancer increased in some populations-namely, in the lower SDI quintiles and among females. Preventive measures such as smoking control interventions, air quality management programmes focused on major air pollution sources, and widespread access to clean energy should be prioritised in these settings. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.

Previous studies and meta-analyses have assessed optimal P2Y12 inhibitors following acute coronary syndrome in overall trial cohorts. However, there are insufficient data for the elderly cohort who are prone to high bleeding and ischemic events. We aimed to assess the optimal P2Y12 inhibitor therapy for older patients. PubMed, CENTRAL, and ClinicalTrials.gov databases were searched from inception through July 2020 to identify randomized controlled trials and propensity-matched observational studies including older patients (aged ≥ 65 years) that reported study-defined major adverse cardiovascular events (MACE) or major bleeding events. Outcomes at the mid-term follow-up were pooled to conduct a frequentist network meta-analysis. Fourteen studies involving 12,953 older patients were included in our analysis. No significant difference was observed with MACE when all three P2Y12 inhibitors were compared with each other. Compared with clopidogrel, ticagrelor significantly increased the risk of major bleeding (risk ratio 1.35, 95% confidence interval 1.10–1.67) while prasugrel did not (risk ratio 1.02, 95% confidence interval 0.67–1.57). A sensitivity analysis of only randomized controlled trials yielded similar results for both MACE and major bleeding. The P score displayed prasugrel (0.5871) as the best treatment for MACE, while clopidogrel (0.7701) was the best P2Y12 inhibitor to decrease the risk of major bleeding. Ticagrelor (0.0634) was ranked the lowest because of an increased bleeding risk. No significant difference is observed between the three P2Y12 inhibitors in study-defined MACE. Ranking by p-score suggests prasugrel as the best P2Y12 inhibitor to reduce the risk of MACE while clopidogrel is a better alternative than ticagrelor in older patients with acute coronary syndrome to decrease the risk of major bleeding. Because of a lack of individual-patient data analysis and heterogeneity amongst studies, future studies representing older patients with acute coronary syndrome are required to strengthen evidence regarding optimal antithrombotic therapy in this cohort.

Rheumatoid Arthritis associated valvular heart disease (RA-VHD) may occur in patients in varying degrees of severity. Aortic valve involvement leading to severe symptomatic aortic insufficiency is a rare complication of rheumatoid arthritis. This entity has not been well characterized and its clinical predictors are undefined. The pathology of RA-VHD can extend from benign nodular development to acute valvulitis with late-stage leaflet fibrosis and severe valvular regurgitation. In this report, we describe a rare case of acute heart failure (AHF) resulting from severe aortic valve destruction and insufficiency due to persistent chronic inflammation in a patient with long-standing RA. Persistent systemic inflammation of RA involved the aortic valve causing nodular thickening and leaflet destruction. Our patient had compensated chronic heart failure due to progressive aortic insufficiency resulting from gradual leaflet destruction. However, she suddenly developed AHF requiring valve replacement. Her clinical presentation, gross and histological images suggest an acute/subacute disruption of the friable aortic leaflets that resulted in AHF.

Background The burden of fatal police violence is an urgent public health crisis in the USA. Mounting evidence shows that deaths at the hands of the police disproportionately impact people of certain races and ethnicities, pointing to systemic racism in policing. Recent high-profile killings by police in the USA have prompted calls for more extensive and public data reporting on police violence. This study examines the presence and extent of under-reporting of police violence in US Government-run vital registration data, offers a method for correcting under-reporting in these datasets, and presents revised estimates of deaths due to police violence in the USA. Methods We compared data from the USA National Vital Statistics System (NVSS) to three non-governmental, opensource databases on police violence: Fatal Encounters, Mapping Police Violence, and The Counted. We extracted and standardised the age, sex, US state of death registration, year of death, and race and ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic of other races, and Hispanic of any race) of each decedent for all data sources and used a network meta-regression to quantify the rate of under-reporting within the NVSS. Using these rates to inform correction factors, we provide adjusted estimates of deaths due to police violence for all states, ages, sexes, and racial and ethnic groups from 1980 to 2019 across the USA. Findings Across all races and states in the USA, we estimate 30 800 deaths (95% uncertainty interval [UI] 30 300-31 300) from police violence between 1980 and 2018; this represents 17 100 more deaths (16 600-17 600) than reported by the NVSS. Over this time period, the age-standardised mortality rate due to police violence was highest in non-Hispanic Black people (0.69 [95% UI 0.67-0.71] per 100 000), followed by Hispanic people of any race (0.35 [0.34-0.36]), nonHispanic White people (0.20 [0.19-0.20]), and non-Hispanic people of other races (0.15 [0.14- 0.16]). This variation is further affected by the decedent's sex and shows large discrepancies between states. Between 1980 and 2018, the NVSS did not report 55.5% (54.8-56.2) of all deaths attributable to police violence. When aggregating all races, the age-standardised mortality rate due to police violence was 0.25 (0.24-0.26) per 100 000 in the 1980s and 0.34 (0.34-0.35) per 100 000 in the 2010s, an increase of 38.4% (32.4-45.1) over the period of study. Interpretation We found that more than half of all deaths due to police violence that we estimated in the USA from 1980 to 2018 were unreported in the NVSS. Compounding this, we found substantial differences in the agestandardised mortality rate due to police violence over time and by racial and ethnic groups within the USA. Proven public health intervention strategies are needed to address these systematic biases. State-level estimates allow for appropriate targeting of these strategies to address police violence and improve its reporting. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.

Background: The Corona Virus 19 (COVID-19) infection is associated with worse outcomes in blacks, although the mechanisms are unclear. We sought to determine the significance of black race, pre-existing cardiovascular disease (pCVD), and acute kidney injury (AKI) on cardiopulmonary outcomes and in-hospital mortality of COVID-19 patients. Methods: We conducted a retrospective cohort study of blacks with/without pCVD and with/without in-hospital AKI, hospitalized within Grady Memorial Hospital in Georgia between February and July 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on qualitative polymerase-chain-reaction assay. The primary outcome was a composite of in-hospital cardiac events. Results: Of the 293 patients hospitalized with COVID-19 in this study, 71 were excluded from the primary analysis (for race/ethnicity other than black non-Hispanic). Of the 222 hospitalized COVID-19 patients included in our analyses, 41.4% were female, 78.8% had pCVD, and 30.6% developed AKI during the admission. In multivariable analyses, pCVD (OR 4.7, 95% C1 1.5-14.8, P=0.008) and AKI (OR 2.7, 95% CI 1.3-5.5, P=0.006) were associated with increased odds of inhospital cardiac events. AKI was associated with increased odds of in-hospital mortality (OR 8.9, 95% CI 3.3-23.9, P<0.0001). The presence of AKI was associated with increased odds of ICU stay, mechanical ventilation, and acute respiratory distress syndrome (ARDS). Conclusion: pCVD and AKI were associated with higher risk of in-hospital cardiac events, and AKI was associated with a higher risk of in-hospital mortality in blacks.