Atrial Fibrillation and Clonal Hematopoiesis in TET2 and ASXL1.

Importance: Clonal hematopoiesis of indeterminate potential (CHIP) may contribute to the risk of atrial fibrillation (AF) through its association with inflammation and cardiac remodeling. Objective: To determine whether CHIP was associated with AF, inflammatory and cardiac biomarkers, and cardiac structural changes. Design, Setting, and Participants: This was a population-based, prospective cohort study in participants of the Atherosclerosis Risk in Communities (ARIC) study and UK Biobank (UKB) cohort. Samples were collected and echocardiography was performed from 2011 to 2013 in the ARIC cohort, and samples were collected from 2006 to 2010 in the UKB cohort. Included in this study were adults without hematologic malignancies, mitral valve stenosis, or previous mitral valve procedure from both the ARIC and UKB cohorts; additionally, participants without hypertrophic cardiomyopathy and congenital heart disease from the UKB cohort were also included. Data analysis was completed in 2023. Exposures: CHIP (variant allele frequency [VAF] ≥2%), common gene-specific CHIP subtypes (DNMT3A, TET2, ASXL1), large CHIP (VAF ≥10%), inflammatory and cardiac biomarkers (high-sensitivity C-reactive protein, interleukin 6 [IL-6], IL-18, high-sensitivity troponin T [hs-TnT] and hs-TnI, N-terminal pro-B-type natriuretic peptide), and echocardiographic indices. Main Outcome Measure: Incident AF. Results: A total of 199 982 adults were included in this study. In ARIC participants (4131 [2.1%]; mean [SD] age, 76 [5] years; 2449 female [59%]; 1682 male [41%]; 935 Black [23%] and 3196 White [77%]), 1019 had any CHIP (24.7%), and 478 had large CHIP (11.6%). In UKB participants (195 851 [97.9%]; mean [SD] age, 56 [8] years; 108 370 female [55%]; 87 481 male [45%]; 3154 Black [2%], 183 747 White [94%], and 7971 other race [4%]), 11 328 had any CHIP (5.8%), and 5189 had large CHIP (2.6%). ARIC participants were followed up for a median (IQR) period of 7.0 (5.3-7.7) years, and UKB participants were followed up for a median (IQR) period of 12.2 (11.3-13.0) years. Meta-analyzed hazard ratios for AF were 1.12 (95% CI, 1.01-1.25; P = .04) for participants with vs without large CHIP, 1.29 (95% CI, 1.05-1.59; P = .02) for those with vs without large TET2 CHIP (seen in 1340 of 197 209 [0.67%]), and 1.45 (95% CI, 1.02-2.07; P = .04) for those with vs without large ASXL1 CHIP (seen in 314 of 197 209 [0.16%]). Large TET2 CHIP was associated with higher IL-6 levels. Additionally, large ASXL1 was associated with higher hs-TnT level and increased left ventricular mass index. Conclusions and Relevance: Large TET2 and ASXL1, but not DNMT3A, CHIP was associated with higher IL-6 level, indices of cardiac remodeling, and increased risk for AF. Future research is needed to elaborate on the mechanisms driving the associations and to investigate potential interventions to reduce the risk.

Effect of clinical decision support for severe hypercholesterolemia on low-density lipoprotein cholesterol levels.

Severe hypercholesterolemia/possible familial hypercholesterolemia (FH) is relatively common but underdiagnosed and undertreated. We investigated whether implementing clinical decision support (CDS) was associated with lower low-density lipoprotein cholesterol (LDL-C) in patients with severe hypercholesterolemia/possible FH (LDL-C ≥ 190 mg/dL). As part of a pre-post implementation study, a CDS alert was deployed in the electronic health record (EHR) in a large health system comprising 3 main sites, 16 hospitals and 53 clinics. Data were collected for 3 months before ('silent mode') and after ('active mode') its implementation. Clinicians were only able to view the alert in the EHR during active mode. We matched individuals 1:1 in both modes, based on age, sex, and baseline lipid lowering therapy (LLT). The primary outcome was difference in LDL-C between the two groups and the secondary outcome was initiation/intensification of LLT after alert trigger. We identified 800 matched patients in each mode (mean ± SD age 56.1 ± 11.8 y vs. 55.9 ± 11.8 y; 36.0% male in both groups; mean ± SD initial LDL-C 211.3 ± 27.4 mg/dL vs. 209.8 ± 23.9 mg/dL; 11.2% on LLT at baseline in each group). LDL-C levels were 6.6 mg/dL lower (95% CI, -10.7 to -2.5; P = 0.002) in active vs. silent mode. The odds of high-intensity statin use (OR, 1.78; 95% CI, 1.41-2.23; P < 0.001) and LLT initiation/intensification (OR, 1.30, 95% CI, 1.06-1.58, P = 0.01) were higher in active vs. silent mode. Implementation of a CDS was associated with lowering of LDL-C levels in patients with severe hypercholesterolemia/possible FH, likely due to higher rates of clinician led LLT initiation/intensification.

The global, regional, and national burden and quality of care index of kidney cancer; a global burden of disease systematic analysis 1990-2019.

Kidney cancer (KC) is a prevalent cancer worldwide. The incidence and mortality rates of KC have risen in recent decades. The quality of care provided to KC patients is a concern for public health. Considering the importance of KC, in this study, we aim to assess the burden of the disease, gender and age disparities globally, regionally, and nationally to evaluate the quality and inequities of KC care. The 2019 Global Burden of Disease study provides data on the burden of the KC. The secondary indices, including mortality-to-incidence ratio, disability-adjusted life years -to-prevalence ratio, prevalence-to-incidence ratio, and years of life lost-to-years lived with disability ratio, were utilized. These four newly merged indices were converted to the quality-of-care index (QCI) as a summary measure using principal component analysis. QCI ranged between 0 and 100, and higher amounts of QCI indicate higher quality of care. Gender disparity ratio was calculated by dividing QCI for females by males to show gender inequity. The global age-standardized incidence and mortality rates of KC increased by 29.1% (95% uncertainty interval 18.7-40.7) and 11.6% (4.6-20.0) between 1990 and 2019, respectively. Globally, the QCI score for KC increased by 14.6% during 30 years, from 71.3 to 81.6. From 1990 to 2019, the QCI score has increased in all socio-demographic index (SDI) quintiles. By 2019, the highest QCI score was in regions with a high SDI (93.0), and the lowest was in low SDI quintiles (38.2). Based on the World Health Organization regions, the QCI score was highest in the region of America, with Canada having the highest score (99.6) and the lowest in the African Region, where the Central African Republic scored the lowest (17.2). In 1990, the gender disparity ratio was 0.98, and in 2019, it was 0.97 showing an almost similar QCI score for females and males. Although the quality of care for KC has improved from 1990 to 2019, there is a significant gap between nations and different socioeconomic levels. This study provides clinicians and health authorities with a global perspective on the quality of care for KC and identifies the existing disparities.

Joint Association of Polygenic Risk and Social Determinants of Health with Coronary Heart Disease in the United States.

Background: The joint effects of polygenic risk and social determinants of health (SDOH) on coronary heart disease (CHD) in the United States are unknown. Methods: In 67,256 All of Us (AoU) participants with available SDOH data, we ascertained self-reported race/ethnicity and calculated a polygenic risk score for CHD (PRS CHD ). We used 90 SDOH survey questions to develop an SDOH score for CHD (SDOH CHD ). We assessed the distribution of SDOH CHD across self-reported races and US states. We tested the joint association of SDOH CHD and PRS CHD with CHD in regression models that included clinical risk factors. Results: SDOH CHD was highest in self-reported black and Hispanic people. Self-reporting as black was associated with higher odds of CHD but not after adjustment for SDOH CHD . Median SDOH CHD values varied by US state and were associated with heart disease mortality. A 1-SD increase in SDOH CHD was associated with CHD (OR=1.36; 95% CI, 1.29 to 1.46) and incident CHD (HR=1.73; 95% CI, 1.27 to 2.35) in models that included PRS CHD and clinical risk factors. Among people in the top 20% of PRS CHD , CHD prevalence was 4.8% and 7.8% in the bottom and top 20% of SDOH CHD , respectively. Conclusions: Increased odds of CHD in self-reported black people are likely due to higher SDOH burden. SDOH and PRS were independently associated with CHD in the US. Our findings emphasize the need to consider both PRS and SDOH for equitable disease risk assessment.

Burden of Ischemic Heart Disease and Its Attributable Risk Factors in North Africa and the Middle East, 1990 to 2019: Results From the GBD Study 2019.

BACKGROUND: The North Africa and Middle East (NAME) region has one of the highest burdens of ischemic heart disease (IHD) worldwide. This study reports the contemporary epidemiology of IHD in NAME. METHODS AND RESULTS: We estimated the incidence, prevalence, deaths, years of life lost, years lived with disability, disability-adjusted life years (DALYs), and premature mortality of IHD, and its attributable risk factors in NAME from 1990 to 2019 using the results of the GBD (Global Burden of Disease study 2019). In 2019, 0.8 million lives and 18.0 million DALYs were lost due to IHD in NAME. From 1990 to 2019, the age-standardized DALY rate of IHD significantly decreased by 33.3%, mostly due to the reduction of years of life lost rather than years lived with disability. In 2019, the proportion of premature death attributable to IHD was higher in NAME compared with global measures: 26.8% versus 16.9% for women and 18.4% versus 14.8% for men, respectively. The age-standardized DALY rate of IHD attributed to metabolic risks, behavioral risks, and environmental/occupational risks significantly decreased by 28.7%, 37.8%, and 36.4%, respectively. Dietary risk factors, high systolic blood pressure, and high low-density lipoprotein cholesterol were the top 3 risks contributing to the IHD burden in most countries of NAME in 2019. CONCLUSIONS: In 2019, IHD was the leading cause of death and lost DALYs in NAME, where premature death due to IHD was greater than the global average. Despite the great reduction in the age-standardized DALYs of IHD in NAME from 1990 to 2019, this region still had the second-highest burden of IHD in 2019 globally.

Risk factor profile and outcomes of premature acute coronary syndrome after percutaneous coronary intervention: A 1-year prospective design.

BACKGROUND: The prevalence of acute coronary syndrome (ACS) among young adults (premature ACS) has dramatically increased in recent years, especially in developing countries. Yet, the data on these patients' attributed risk factors and outcomes are inconsistent. In this study, we aimed to investigate these data in a cohort of premature ACS cases who underwent percutaneous coronary intervention (PCI) compared to older patients. HYPOTHESIS: We hypothesize that premature ACS patients undergoing PCI will exhibit different risk factor profiles and outcomes compared to non-premature patients. specifically, we anticipate that premature patients do not necessarily have better outcomes than non-premature. METHODS: Overall, 3142 and 10 399 patients were included in premature and non-premature groups, respectively. Patients' pre-operative, post-operative, and follow-up data were retrieved retrospectively from the Tehran Heart Center PCI databank. RESULTS: The mean age of premature and non-premature cohorts was 48.39 and 67 years, respectively. Patients were predominantly male in both groups. Family history of coronary artery disease (CAD), dyslipidemia, smoking, and opium addiction were more prevalent among the younger cohort. After adjustment, in-hospital mortality in younger patients was considerably higher, with all-cause mortality and major cardiovascular and cerebrovascular events (MACCE) exhibiting no noticeable difference among the two groups. CONCLUSIONS: Risk factor profile is different in young patients, and traditional cardiovascular risk factors, such as hypertension and diabetes mellitus, are more prevalent among older adults. Younger age is not equivalent to a better prognosis; hence, similar or even more caution should be taken into consideration regarding secondary prevention for these patients.

Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease.

African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers. Here, we show that the presence of the APOL1 p.N264K missense variant, when co-inherited with the G2 APOL1 risk allele, substantially reduces the penetrance of the G1G2 and G2G2 high-risk genotypes by rendering these genotypes low-risk. These results align with prior functional evidence showing that the p.N264K variant reduces the toxicity of the APOL1 high-risk alleles. These findings have important implications for our understanding of the mechanisms of APOL1-associated nephropathy, as well as for the clinical management of individuals with high-risk genotypes that include the G2 allele.

"Current incidence of injuries in Iran; findings of STEPS survey 2021".

Background: The updated epidemiology of injuries at the national and sub-national levels are required for policymakers to effectively handle the burden of injuries. This paper aimed to assess the incidence and risk factors of different injuries in Iran based on a recent national survey. Methods: We used data from Iran Stepwise approach to surveillance (STEPS) Survey 2021, a population-based study in urban and rural areas of Iran's 31 provinces. A multistage clustered probability design and weighting adjustments were used to select eligible individuals and generate estimations. We estimated the incidence of injuries, assessed sociodemographic variables, and identified potential behavioral risk factors associated with injuries, and results were reported for sociodemographic and geographic stratifications. Result: Data from 27,874 participants of the STEPS survey were assessed, of which 1538 (5.5 %, 95 % CI: [5.2-5.8]) reported having an injury in the past 12 months. Falls (44.4 %) were the most common cause of injury, followed by road traffic injury (21.7 %) and exposure to mechanical forces (16.5 %). Except for falls and burns, males had a higher proportion of all types of injuries. Logistic regression analysis showed that being male (OR: 1.7, [1.5, 2.0]) and being an occasional or heavy alcohol drinker (OR: 2.0, [1.3, 3.0] and OR: 2.7, [1.7, 4.1] respectively) were significant risk factors associated with road traffic injuries. Seatbelt use was 90.0 % among both drivers and front-seat passengers, while the use of safety car seats for children was as low as 9.4 %. Injury incidence varied significantly among provinces, with the highest incidence among males observed in Razavi Khorasan (11.2 %) and among females observed in Tehran (12.0 %). Conclusion: This study investigated the updated epidemiology of injuries in Iran and revealed socioeconomic and geographic disparities across country. This epidemiological information can be used to modify injury prevention programs.

Extensive cardiovascular involvement in a young boy with Gaucher's disease: a case report.

Background: Lysosomal storage diseases (LSDs) are rare, progressive, multi-organ disorders caused by inherited enzyme deficiencies. Gaucher's disease (GD) is the most prevalent form of LSDs. Case summary: A 19-year-old Caucasian male presented with exertional dyspnoea. Physical examination revealed a Grade III/VI systolic diamond murmur at the heart base and a Grade IV/VI systolic murmur at the apex. Electrocardiogram showed signs of left ventricular hypertrophy (LVH). Trans-thoracic echocardiography (TTE) and trans-oesophageal echocardiography (TEE) demonstrated moderate LVH, severe aortic valve stenosis, severe supra-valvular aortic stenosis, and moderate mitral stenosis with severe degenerative mitral valve regurgitation. Bone marrow biopsy and aspiration confirmed the presence of characteristic Gaucher's cells. The patient underwent the Bentall procedure and mitral valve replacement and was discharged in good condition. Discussion: Gaucher's disease exhibits three clinical phenotypes, and cardiovascular involvement is commonly seen in GD Type III. Valvular calcification and ascending aorta involvement are frequent cardiovascular manifestations. Although severe valvular heart involvement is rare in GD, cardiac valve surgery has shown favourable outcomes in previous studies and our case.

Prevalence of plasma lipid abnormalities and associated risk factors among Iranian adults based on the findings from STEPs survey 2021.

The study aimed to estimate the prevalence of lipid abnormalities in Iranian adults by demographic characterization, geographical distribution, and associated risk factors using national and sub-national representative samples of the STEPs 2021 survey in Iran. In this population-based household survey, a total of 18,119 individuals aged over 25 years provided blood samples for biochemical analysis. Dyslipidemia was defined by the presence of at least one of the lipid abnormalities of hypertriglyceridemia (≥ 150 mg/dL), hypercholesterolemia (≥ 200 mg/dL), high LDL-C (≥ 130 mg/dL), and low HDL-C (< 50 mg/dL in women, < 40 mg/dL in men), or self-reported use of lipid-lowering medications. Mixed dyslipidemia was characterized as the coexistence of high LDL-C with at least one of the hypertriglyceridemia and low HDL-C. The prevalence of each lipid abnormality was determined by each population strata, and the determinants of abnormal lipid levels were identified using a multiple logistic regression model. The prevalence was 39.7% for hypertriglyceridemia, 21.2% for hypercholesterolemia, 16.4% for high LDL-C, 68.4% for low HDL-C, and 81.0% for dyslipidemia. Hypercholesterolemia and low HDL-C were more prevalent in women, and hypertriglyceridemia was more prevalent in men. The prevalence of dyslipidemia was higher in women (OR = 1.8), obese (OR = 2.8) and overweight (OR = 2.3) persons, those residents in urban areas (OR = 1.1), those with inappropriate physical activity (OR = 1.2), patients with diabetes (OR = 2.7) and hypertension (OR = 1.9), and participants with a history (OR = 1.6) or familial history of CVDs (OR = 1.2). Mixed dyslipidemia prevalence was 13.6% in women and 11.4% in men (P < 0.05). The prevalence of lipid abnormalities was highly heterogeneous among provinces, and East Azarbaijan with 85.3% (81.5-89.1) and Golestan with 68.5% (64.8-72.2) had the highest and lowest prevalence of dyslipidemia, respectively. Although the prevalence of high cholesterol and LDL-C had a descending trend in the 2016-2021 period, the prevalence of dyslipidemia remained unchanged. There are modifiable risk factors associated with dyslipidemia that can be targeted by the primary healthcare system. To modify these risk factors and promote metabolic health in the country, action plans should come to action through a multi-sectoral and collaborative approach.

Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease.

Black Americans have a significantly higher risk of developing chronic kidney disease (CKD), especially focal segmental glomerulosclerosis (FSGS), than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of Black Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers. Here, we show that the presence of the APOL1 p.N264K missense variant, when co-inherited with the G2 APOL1 risk allele, substantially reduces the penetrance of the G1G2 and G2G2 high-risk genotypes by rendering these genotypes low-risk. These results align with prior functional evidence showing that the p.N264K variant reduces the toxicity of the APOL1 high-risk alleles. These findings have important implications for our understanding of the mechanisms of APOL1 -associated nephropathy, as well as for the clinical management of individuals with high-risk genotypes that include the G2 allele.

Particulate Matter Pollution Remains a Threat for Cardiovascular Health: Findings From the Global Burden of Disease 2019.

Background Particulate matter (PM) pollution is a significant risk factor for cardiovascular diseases, causing substantial disease burden and deaths worldwide. This study aimed to investigate the global burden of cardiovascular diseases attributed to PM from 1990 to 2019. Methods and Results We used the GBD (Global Burden of Disease) study 2019 to investigate disability-adjusted life-years (DALYs), years of life lost (YLLs), years lived with disability (YLDs), and deaths attributed to PM as well as its subgroups. It was shown that all burden measures' age-standardized rates for PM were in the same decreasing trend, with the highest decline recorded for deaths (-36.7%). However, the all-age DALYs increased by 31%, reaching 8.9 million in 2019, to which YLLs contributed the most (8.2 million [95% uncertainty interval, 7.3 million-9.2 million]). Men had higher deaths, DALYs, and YLLs despite lower years lived with disability in 2019 compared with women. There was an 8.1% increase in the age-standardized rate of DALYs for ambient PM; however, household air pollution from solid fuels decreased by 65.4% in the assessed period. Although higher in men, the low and high sociodemographic index regions had the highest and lowest attributed YLLs/YLDs ratio for PM pollution in 2019, respectively. Conclusions Although the total age-standardized rate of DALYs for PM-attributed cardiovascular diseases diminished from 1990 to 2019, the global burden of PM on cardiovascular diseases has increased. The differences between men and women and between regions have clinical and policy implications in global health planning toward more exact funding and resource allocation, in addition to addressing inequity in health care access.

Iran Quality of Care in Medicine Program (IQCAMP): Design and Outcomes.

BACKGROUND: Assessment of quality and cost of medical care has become a core health policy concern. We conducted a nationwide survey to assess these measures in Iran as a developing country. To present the protocol for the Iran Quality of Care in Medicine Program (IQCAMP) study, which estimates the quality, cost, and utilization of health services for seven diseases in Iran. METHODS: We selected eight provinces for this nationally representative short longitudinal survey. Interviewers from each province were trained comprehensively. The standard definition of seven high-burden conditions (acute myocardial infarction [MI], heart failure [HF], diabetes mellitus [DM], stroke, chronic obstructive pulmonary (COPD) disease, major depression, and end-stage renal disease [ESRD]) helped customize a protocol for disease identification. With a 3-month follow-up window, the participants answered pre-specified questions four times. The expert panels developed a questionnaire in four modules (demographics, health status, utilization, cost, and quality). The expert panel chose an inclusive set of quality indicators from the current literature for each condition. The design team specified the necessary elements in the survey to calculate the cost of care for each condition. The utilization assessment included various services, including hospital admissions, outpatient visits, and medication. RESULTS: Totally, 156 specialists and 78 trained nurses assisted with patient identification, recruitment, and interviewing. A total of 1666 patients participated in the study, and 1291 patients completed all four visits. CONCLUSION: The IQCAMP study was the first healthcare utilization, cost, and quality survey in Iran with a longitudinal data collection to represent the pattern, quantity, and quality of medical care provided for high-burden conditions.

Evaluation of the diabetes care cascade and compliance with WHO global coverage targets in Iran based on STEPS survey 2021.

This study aimed to investigate the diabetes mellitus (DM) and prediabetes epidemiology, care cascade, and compliance with global coverage targets. We recruited the results of the nationally representative Iran STEPS Survey 2021. Diabetes and prediabetes were two main outcomes. Diabetes awareness, treatment coverage, and glycemic control were calculated for all population with diabetes to investigate the care cascade. Four global coverage targets for diabetes developed by the World Health Organization were adopted to assess the DM diagnosis and control status. Among 18,119 participants, the national prevalence of DM and prediabetes were 14.2% (95% confidence interval 13.4-14.9) and 24.8% (23.9-25.7), respectively. The prevalence of DM treatment coverage was 65.0% (62.4-67.7), while the prevalence of good (HbA1C < 7%) glycemic control was 28.0% (25.0-31.0) among all individuals with diabetes. DM diagnosis and statin use statics were close to global targets (73.3% vs 80%, and 50.1% vs 60%); however, good glycemic control and strict blood pressure control statistics, were much way behind the goals (36.7% vs 80%, and 28.5% vs 80%). A major proportion of the Iranian population are affected by DM and prediabetes, and glycemic control is poorly achieved, indicating a sub-optimal care for diabetes and comorbidities like hypertension.

Tobacco consumption patterns among Iranian adults: a national and sub-national update from the STEPS survey 2021.

Smoking is recognised as a critical public health priority due to its enormous health and economic consequences. Constant monitoring of the effectiveness of tobacco control programs calls for timely population-based data. This study reports the national and sub-national patterns in tobacco consumption among Iranian adults based on the results from the STEPwise approach to chronic disease risk factor surveillance (STEPS) survey 2021. This study was performed through an analysis of the results of the STEPS survey 2021 which had been conducted as a nationally representative cross-sectional study. Participants included Iranian adults aged ≥ 18 years in all provinces of Iran, who were selected via multistage cluster sampling method. Data were analyzed via survey analysis while considering population weights. The total number of participants was 27,874, including 15,395 (55.23%) women and 12,479 (44.77%) men. The all-ages prevalence of current tobacco smoking was 14.01% overall, 4.44% among women, and 25.88% among men. The all-ages prevalence of current cigarette smoking was 9.33% overall, 0.77% among women, and 19.95% among men. The all-ages prevalence of current hookah smoking was 4.5% overall, 3.64% among women, and 5.56% among men. The mean (SD) number of cigarettes smoked per day was 12.41 (10.27) overall, 7.65 (8.09) among women, and 12.64 (10.31) among men. The mean (SD) monthly times of hookah use was 0.42 (7.87) overall, 2.86 (23.46) among women, and 0.3 (6.2) among men. The national all-ages prevalence of second-hand smoking at home was 24.64% overall, 27.38% among women, and 20.26% among men. The national all-ages prevalence of second-hand smoking at work was 19.49% overall, 17.33% among women, and 22.94% among men. The tobacco consumption in Iran remains alarmingly high, indicating the current tobacco control policy implementation level is ineffective and insufficient. This calls for adopting, implementing, and enforcing comprehensive packages of evidence-based tobacco control policies.

Evaluating the role of intravenous pentoxifylline administration on primary percutaneous coronary intervention success rate in patients with ST-elevation myocardial infarction (PENTOS-PCI).

Ischemia reperfusion injury can lead to further myocardiocyte damage in patients with ST-elevation myocardial infarction (STEMI). Pentoxifylline is a methylxanthine derivative with known anti-inflammatory, antioxidant, vasodilator, and rheological properties which can be a promising agent in preventing reperfusion injury. PENTOS-PCI is a single-center, randomized, double-blind, placebo-controlled trial which evaluated the efficacy and safety of preprocedural administration of intravenous pentoxifylline in patients undergoing primary percutaneous coronary intervention (PCI). Patients with acute STEMI who were eligible for PCI were randomized to receive either 100-mg intravenous infusion of pentoxifylline or placebo, prior to transferring to catheterization laboratory. Overall, 161 patients were included in our study of whom 80 patients were assigned to pentoxifylline and 81 to the control groups. Per-protocol analysis of primary endpoint indexing PCI's success rate as measured by thrombolysis in myocardial infarction (TIMI) flow grade 3 was not significantly different between pentoxifylline and placebo (71.3% and 66.3% respectively, P = 0.40). In addition, pentoxifylline could not improve secondary angiographic endpoints including myocardial blush grade 3 (87.5% and 85.2%, P = 0.79) and corrected TIMI frame count (22.8 [± 9.0] and 24.0 [± 5.1], P = 0.33) in the intervention and placebo groups respectively. The rates of major adverse cardiac and treatment emergent adverse effects were not significantly different between the two groups. Administration of intravenous pentoxifylline before primary PCI did not improve the success rate of the procedure in patients with STEMI. Intravenous administration of pentoxifylline was well tolerated, and there were no significant differences regarding adverse drug reactions in the two groups. Panel A, background: pentoxifylline is a methylxanthine derivative with known anti-inflammatory, antioxidant, vasodilator, and rheological properties which can be a promising agent in preventing reperfusion injury. Panel B: study design and main results of the PENTOS-PCI trial. cTFC corrected TIMI frame count, ED emergency department, IRI ischemia reperfusion injury, MBG myocardial blush grade, PCI percutaneous coronary intervention, PPCI primary PCI, PTX pentoxifylline, ROS reactive oxygen species, SD standard deviation, STEMI ST-elevation myocardial infarction, TIMI thrombolysis in myocardial infarction.

Epidemiology of Brain and Other Central Nervous System Cancers in the North Africa and Middle East Region: A Systematic Analysis of the Global Burden of Disease Study 1990-2019.

OBJECTIVE: To present estimates of prevalence and incidence of and contributors to central nervous system (CNS) cancers, death, years of life lost, years lived with disability, and disability-adjusted life years from 1990 to 2019 in North Africa and the Middle East. METHODS: Primary measures were retrieved from Global Burden of Disease 2019. Contribution of various factors to observed incidence and mortality changes was investigated with decomposition and age-period-cohort analyses. RESULTS: In 2019, 27,529 (95% uncertainty interval [UI]: 18,554-32,579; percent change compared with 1990: +152.5%) new CNS cancers and 17,773 (95% UI:12,096-20,936; percent change compared with 1990: +111.5%) deaths occurred. Meanwhile, 71.0% increase led to 71,6271 (95% UI: 493,932-848,226) disability-adjusted life years in 2019 with a halved years of life lost/years lived with disability ratio of 66.3% (proxy of worse care quality). Altogether, 97,195 (95% UI: 64,216-115,621; percent change compared with 1990: +280.5%) patients with prevalent cases were alive in 2019. All decomposed indices, including aging, cause-specific incidence, and population growth, contributed substantially to increased incidence of CNS cancers. Moreover, age brackets, study period (1990-2019), and 5-year cohorts all demonstrated positive effects, while age had a mixed influence in different age groups. Palestine harbored the highest age-standardized disability-adjusted life years rate in 2019 (232.0 [95% UI: 175.6-279.5]), while Tunisia had the lowest (41.8 [95% UI: 27.6-57.1] per 100,000). The greatest burden increase was found in Saudi Arabia (32.3%). CONCLUSIONS: The burden of CNS cancers is rising in North Africa and the Middle East, with major heterogeneities among countries. Improved early detection and health care access across countries are required to bridge inequalities and address the rising burden of CNS malignancies.

Epidemiology, burden, and attributable risks of infective endocarditis in Iran and its provinces: From 1990 to 2019.

BACKGROUND: Endocarditis is a potentially life-threatening infectious disease associated with significant morbidity and mortality and an escalating incidence in recent decades. In this study, as a part of the global burden of disease (GBD) 2019 study, we intend to report endocarditis burden in Iran at national and provincial levels from 1990 to 2019. METHOD: This study was conducted using GBD 2019 study data on endocarditis from 1990 to 2019. We gathered incidence, prevalence, disability-adjusted life years (DALYs), and mortality rates in Iran and its 31 provinces by sex and age groups as epidemiological indices for endocarditis burden. Further decomposition analysis was also performed to delineate the endocarditis new cases trend. RESULTS: On the country scale, age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate were (16.5 (95% uncertainty interval 13.7 to 19.8), 3.4 (2.9 to 4.1), 0.6 (0.5 to 0.9), and 14.4 (12.0 to 21.1) in 2019, respectively. Decomposition analysis showed that only 59.2% of the overall new cases increase (114.1%) was caused by the incidence rate change. All estimated age-standardized rates were higher in men in 1990 and 2019 with a ratio of 1.1-1.5. CONCLUSION: The ASIR and ASPR of endocarditis increased, and the ASMR and age-standardized DALYs rate declined over the past 30 years in Iran, nearly all the provinces followed the same pattern with North Khorasan having the Highest ASIR, ASPR, ASMR, and DALYs rates in both years. High systolic blood pressure (SBP) had the greatest attributed burden among risk factors.

Rheumatic Heart Disease Is a Neglected Disease Relative to Its Burden Worldwide: Findings From Global Burden of Disease 2019.

Background Rheumatic heart disease (RHD) takes a heavy toll in low- and middle-income countries. We aimed to present worldwide estimates for the burden of the RHD during 1990 to 2019 using the GBD (Global Burden of Disease) study. Methods and Results Sociodemographic index (SDI) and age-period-cohort analysis were used to assess inequity. The age-standardized death, disability-adjusted life years, incidence, and prevalence rates of RHD were 3.9 (95% uncertainty interval, 3.3-4.3), 132.9 (95% uncertainty interval, 115.0-150.3), 37.4 (28.6-46.7), and 513.7 (405.0-636.3) per 100 000 in 2019, respectively. The age-standardized incidence and prevalence rates increased by 14.4% and 13.8%, respectively. However, disability-adjusted life years and death rates decreased by 53.1% and 56.9%, respectively. South Asia superregion had the highest age-standardized disability-adjusted life years and deaths. Sub-Saharan Africa had the highest age-standardized incidence and prevalence rates. There was a steep decline in RHD burden among higher-SDI countries. However, only age-standardized deaths and disability-adjusted life years rates decreased in lower-SDI countries. The age-standardized years of life lost and years lived with disability rates for RHD significantly declined as countries' SDI increased. The coefficients of birth cohort effect on the incidence of RHD showed an increasing trend from 1960 to 1964 to 2015 to 2019; however, the birth cohort effect on deaths attributable to RHD showed unfailingly decreasing trends from 1910 to 1914 to 2015 to 2019. Conclusions There was a divergence in the burden of RHD among countries based on SDI levels, which calls for including RHD in global assistance and funding. Indeed, many countries are still dealing with an unfinished infectious disease agenda, and there is an urgency to act now to prevent an increase in future RHD burden.