Burden of gout among different WHO regions, 1990-2019: estimates from the global burden of disease study.

The global incidence of gout has increased rapidly, likely secondary to the increase in the prevalence of conditions that predispose to gout, such as obesity. Depending on the population studied, the prevalence of gout ranges from less than 1 to 6.8%. Thus, gout can be a significant burden on healthcare systems. The objective of this study is to observe the trends in the incidence, prevalence, and disability-adjusted life years (DALYs) of gout between 1990 and 2019 globally and in the European Union (EU) 15+ nations. We extracted data from the Global Burden of Disease Study database based on the International Classification of Diseases (ICD) versions 10 and 9. Incidence, prevalence, and disability-adjusted life years (DALYs) were extracted for individual EU15+ countries and globally in males and females between 1990 and 2019. Joinpoint regression analysis was used to describe trends. Between 1990 and 2019, gout prevalence, incidence, and DALYs increased in both males (+ 21.42%, + 16.87%, + 21.49%, respectively) and females (+ 21.06%, + 18.75%, + 20.66%, respectively) globally. The United States of America had the highest increase in prevalence (males: + 90.6%; females + 47.1%), incidence (males: + 63.73%; females: + 39.11%) and DALYs (males: + 90.43%; females: + 42.75%). Incidence, prevalence, and DALYs from gout are increasing worldwide and in most of the EU15+ countries for males and females. Studies have reported the association of gout with comorbidities such as metabolic syndrome, diabetes mellitus, and cardiovascular disease. Health policies and resource allocation are required to increase awareness and modify risk factors globally.

Temporal Analysis of the Incidence, Mortality and Disability-Adjusted Life Years of Benign Gallbladder and Biliary Diseases in High-Income Nations, 1990-2019.

Objective: The aim of this observational study was to analyze trends in the incidence, mortality, and disability-adjusted life years (DALYs) of benign gallbladder and biliary diseases across high-income countries between 1990 and 2019. Background: Benign gallbladder and biliary diseases place a substantial burden on healthcare systems in high-income countries. Accurate characterization of the disease burden may help optimize healthcare policy and resource distribution. Materials and methods: Age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), and DALYs data for gallbladder and biliary diseases in males and females were extracted from the 2019 Global Burden of Disease (GBD) study. A mortality-incidence index (MII) was also calculated. Joinpoint regression analysis was performed. Results: The median ASIRs across the European Union 15+ countries in 2019 were 758/100,000 for females and 282/100,000 for males. Between 1990 and 2019 the median percentage change in ASIR was +2.49% for females and +1.07% for males. The median ASMRs in 2019 were 1.22/100,000 for females and 1.49/100,000 for males with a median percentage change over the observation period of -21.93% and -23.01%, respectively. In 2019, the median DALYs was 65/100,000 for females and 37/100,000 among males, with comparable percentage decreases over the observation period of -21.27% and -19.23%, respectively. Conclusions: International variation in lifestyle factors, diagnostic and management strategies likely account for national and sex disparities. This study highlights the importance of ongoing clinical efforts to optimize treatment pathways for gallbladder and biliary diseases, particularly in the provision of emergency surgical services and efforts to address population risk factors.

Does a "Western Lifestyle" Confer a Higher Burden of Colorectal Cancer? A Comparison of EU15+ Countries versus Global Trends between 1990 and 2019.

The incidence of colorectal cancer (CRC) in the U.S. is declining in adults 50 years and older; however, recent studies suggest an increasing disease burden among adults under age 50. This study aims to compare the incidence, mortality, and mortality-to-incidence ratios (MIRs) of CRC in EU15+ countries to determine if similar age-stratified occurrences are observed across these countries with similar "Western lifestyle"-related risk factors. Incidence and mortality rates for CRC between 1990 and 2019 were extracted using the Global Burden of Disease database. The data were age-stratified into groups between ages 25-49, 50-69, and greater than 69 years. We observed that the incidence of CRC increased globally for all age groups, with the highest increase observed for males (75.9%) and females (27.7%) aged 25-49. A similar trend was observed in 15 of the 19 EU15+ countries for males and 16 of the 19 EU15+ countries for females aged 25-49. Global mortality rates decreased for all age groups in females but increased for males in all age groups. This raises concerns regarding potentially modifiable risk factors contributing to increased CRC development and underscores the importance of implementing standardized screening at an earlier stage to ensure adequate detection in the younger population.

The association between mechanical CPR and outcomes from in-hospital cardiac arrest: An observational cohort study.

AIM: We sought to investigate the relationship between mechanical cardiopulmonary resuscitation (CPR) during in-hospital cardiac arrest and survival to hospital discharge. METHODS: Utilizing the prospectively collected American Heart Association's Get With The Guidelines database, we performed an observational study. Data from 153 institutions across the United States were reviewed with a total of 351,125 patients suffering cardiac arrest between 2011 and 2019 were screened. After excluding patients with cardiac arrests lasting less than 5 minutes, and patients who had incomplete data, a total of 111,143 patients were included. Our primary exposure was mechanical vs. manual CPR, and the primary outcome was survival to hospital discharge. Multivariate logistic regression models and propensity weighted analyses were used. RESULTS: 11.8% of patients who received mechanical CPR survived to hospital discharge versus 16.9% in the manual CPR group. Patients who received mechanical CPR had a lower probability of survival to discharge compared to patients who received manual CPR (OR 0.66 95% CI 0.58-0.75; p < 0.001). This association persisted with multi-variable adjustment (OR 0.57 95% CI 0.46-0.70, p < 0.0001) and propensity weighted analysis (OR 0.68 95% CI 0.44-0 0.92, p < 0.0001). Mechanical CPR was associated with decrease likelihood of return of spontaneous circulation after multivariate adjustment (OR 0.68, 95% CI 0.60-0.76; p < 0.001). CONCLUSIONS: Mechanical CPR was associated with a decreased likelihood of survival to hospital discharge and ROSC compared to manual CPR. This finding should be interpreted within the context of important limitations of this study and randomized trials are needed to better investigate this relationship.

Trends in the incidence of rib and sternal fractures: A nationwide study of the global burden of disease database, 1990-2019.

INTRODUCTION: Fractures of the ribs and sternum are associated with significant morbidity and mortality. Characterization of the injury burden across England is necessary to inform and evaluate developments in trauma care and infrastructure, however is yet to be comprehensively undertaken. Therefore, the aim of this study was to describe trends in the incidence of sternal and rib fractures across England between 1990 and 2019. MATERIALS AND METHODS: Age-standardised incidence rates (ASIRs) for rib and sternal fractures in males and females were extracted from the 2019 Global Burden of Disease (GBD) study by all causes, falls and road traffic collisions for 9 sub-regions of England. Temporal trends within the study period were analysed using Joinpoint regression analysis. RESULTS: The overall ASIRs in England in 2019 were 30.34/100,000 and 46.02/100,000 for females and males, respectively. Between 1990 and 2019, the estimated overall percentage change across England was +0.20 % among females and -7.05 % among males. A statistically significant increase in ASIR was observed in all 9 sub-regions of England among females from 2014-2019 (p<0.001). Among males, a statistically significant increase in ASIR was observed in 7 of the 9 regions from 2014-2019 (p<0.001) and in the remaining 2 regions from 2015-2019 (p<0.001). DISCUSSION: Increasing ASIRs of rib and sternal fractures were observed among females and decreasing ASIRs among males, with overall ASIRs higher among males. Developments in trauma infrastructure and associated variations in diagnostic and management strategies over the observation period likely contribute to changes in the national injury burden. The findings are suggestive of the importance of ongoing financial investment in trauma infrastructure and of clear clinical guidelines to manage an increasing national injury burden.

HLA matching between donors and recipients improves clinical liver transplant graft survival.

BACKGROUND AND AIMS: The importance of human leukocyte antigen (HLA) matching between liver transplant donors and recipients on graft survival remains unclear and is not a clinical consideration in liver transplantation. This study aimed to determine the relationship between HLA matching and liver graft survival using a large-scale multi-centre database (UNOS/OPTN) and multivariate logistic analysis. The secondary aim was to determine whether this relationship was influenced by transplant indication and donor status. METHODS: This retrospective observational analysis was performed using 22 702 liver transplant recipients from the UNOS/OPTN database. Patients were divided into two groups based on number of HLA mismatches (0-3 mismatches vs. 4-6 mismatches) and then subcategorized by indication and donor status. Risk-adjusted outcomes were assessed by multivariate Cox analysis adjusting for donor and recipient characteristics and visualized using Kaplan-Meier survival curves. RESULTS: Allograft survival and risk of acute rejection were associated with degree of HLA mismatch. This association between HLA mismatch and graft survival persisted in individuals who underwent transplant for hepatitis, metabolic, drug toxicity, and congenital indications. Donor status also influenced the relationship between HLA mismatch and graft survival. Graft survival in DBD recipients was longer than in DCD in the 4-6 HLA mismatch group, whereas no significant difference was found in the 0-3 HLA mismatch group. CONCLUSION: HLA mismatch significantly reduced graft survival and increased risk of acute rejection. This association was noted only in specific indications. These findings are of potential clinical relevance to organ allocation, allograft matching algorithms, immunosuppression protocols, and transplant surveillance.

Type 1 diabetes mellitus disease burden in high health expenditure countries between 1990 and 2019.

OBJECTIVE: This observational study assesses trends in type 1 diabetes mellitus (T1DM) disease burden across the 19 countries of the European Union (EU) 15+ between 1990 and 2019. METHODS: The Global Burden of Disease Study database was used to gather T1DM age-standardised incidence (ASIR), prevalence (ASPR), mortality (ASMR), and disability-adjusted life-year (DALY) rates per 100,000 for each EU15+ country (1990 - 2019). Joinpoint regression analysis was used to describe the trends. RESULTS: From 1990 to 2019, T1DM ASIRs and ASPRs increased globally except for females in Finland (-2.9% and -9.4%), the largest increase in ASPR for males and females was observed in France (+144.4% and +137.5% respectively). All had reductions in ASMRs for males and females, with the largest observed in Spain (-56.7% and -79.0% respectively). Trends in DALYs were variable across countries, with increases in DALYs noted in 14/19 for males, and 9/19 for females. Denmark, Finland, Norway, Netherlands, and Sweden had a reduction in DALYs for both males and females. CONCLUSIONS: Mortality from T1DM is reducing across EU15+ countries, despite concomitant increases in incidence and prevalence rates. Trends in DALYs are variable across countries, reflecting differential trends in the disease burden across countries with similarly high health expenditure.

Trends in Lung Cancer Incidence and Mortality (1990-2019) in the United States: A Comprehensive Analysis of Gender and State-Level Disparities.

PURPOSE: Lung cancer is the leading cause of cancer-related deaths in the United States. This study aims to analyze lung cancer incidence, mortality, and related statistics from 1990 to 2019, focusing on national- and state-level trends and exploring potential disparities between sexes. METHODS: The Global Burden of Disease database was used to extract tracheal, bronchus, and lung cancer mortality data from 1990 to 2019 for both males and females and across all states of the United States. Age-standardized incidence rates, age-standardized mortality rates, disability-adjusted life years (DALYs), and mortality-to-incidence indices (MIIs) were studied to assess for gender-based, geographic, and temporal disparities. Joinpoint regression analysis was performed to further evaluate trends. RESULTS: The incidence of these cancers in the United States decreased between 1990 and 2019 by 23.35%, with a more significant decline in males (37.73%) than females (1.41%). Similarly, for mortality, a decrease was observed for both sexes combined (26.83%), but much more significantly for males (40.23%) than females (6.01%). The MIIs decreased overall, but there were variations across states. DALYs decreased for both sexes combined, with males experiencing a larger reduction, but an increase was noted in some states for females. CONCLUSION: This analysis reveals diverse trends pertaining to the incidence, mortality, and disability burden associated with lung cancer by sex and states in the United States, emphasizing the need for targeted interventions to reduce disparities. These findings contribute to our understanding of the current landscape of lung cancer and can inform future strategies for prevention, early detection, and management.

Burden of AML, 1990-2019: Estimates From the Global Burden of Disease Study.

PURPOSE: AML accounts for 80% of acute leukemia in adults. While progress has been made in treating younger patients in the past 2 decades, there has been limited improvement for older patients until recently. This study examines the global and European Union (EU) 15+ trends in AML between 1990 and 2019. METHODS: We extracted age-standardized incidence rates (ASIRs), age-standardized death rates (ASMRs), and disability-adjusted life years, stratified by sex from the Global Burden of Disease Study database, and mortality-to-incidence ratio (MIR) were computed. Trends were compared using Joinpoint regression. RESULTS: The findings show a global increase in AML incidence for both sexes from 1990 to 2019. In the EU15+ countries, most countries exhibited an increase in ASIR for both sexes. Joinpoint revealed that globally for male patients, ASIR steadily increased until 2010, remained stable until 2015 followed by a decline till 2019. Similar trends were observed in female patients. For ASMR, although there was an increase globally and in most EU15+ countries, there was a statistically significant decrease in mortality rates globally and in the majority of EU15+ countries in recent years. MIR improved in both sexes globally. On age stratification, AML burden was highest among older groups (55 years and older), while the lowest rates were observed in younger than 20 years. CONCLUSION: The findings from our study indicate a global rise in AML incidence and mortality in both sexes and decrease in MIR from 1990 to 2019 suggesting a better survival. However, on Joinpoint analysis, there is no change in MIR in women in the past decade and past 4 years in men indicating plateau in survival trends despite recent advances.

Cystic fibrosis-related mortality in the United States from 1999 to 2020: an observational analysis of time trends and disparities.

Cystic fibrosis transmembrane conductance regulator modulators have revolutionized cystic fibrosis (CF) care in the past decade. This study explores the CF-related mortality trends in the US from 1999 to 2020. We extracted CF-related mortality data from the CDC WONDER database. CF age-standardized mortality rates (ASMRs) were identified by ICD-10 code E84 and were stratified by demographic and geographical variables. Temporal trends were analyzed using Joinpoint modeling. CF-related ASMRs decreased from 1.9 to 1.04 per million population (p = 0.013), with a greater reduction in recent years. This trend was replicated in both sexes. The median age of death increased from 24 to 37 years. CF mortality rates decreased across sex, white race, non-Hispanic ethnicity, census regions, and urbanization status. Incongruent trends were reported in non-white races and Hispanic ethnicity. A lower median age of death was observed in women, non-white races, and Hispanic ethnicity. SARS-CoV-2 infection was the primary cause of death in 1.7% of CF decedents in 2020. The national CF-related mortality rates declined and the median age of death among CF decedents increased significantly indicating better survival in the recent years. The changes were relatively slow during the earlier period of the study, followed by a greater decline lately. We observed patterns of sex, ethnic, racial, and geographical disparities associated with the worsening of the gap between ethnicities, narrowing of the gap between races and rural vs. urban counties, and closing of the gap between sexes over the study period.

Pulmonary hypertension associated mortality in the United States from 2003 to 2020: an observational analysis of time trends and disparities.

Background: Pulmonary hypertension (PH) is an independent risk factor for morbidity and mortality. In the last two decades, significant advances have been made in management of World Health Organization (WHO) group 1 PH. However, there are no approved targeted pharmacotherapies for PH secondary to left-sided heart diseases or chronic hypoxic lung diseases which are thought to account for more than 70-80% of the disease burden. No recent investigation has analyzed and compared the mortality burden related to WHO group 1 PH with the mortality burden with WHO groups 2-5 PH at the national level in the United States (US). We hypothesize that WHO group 1 PH-related mortality has improved over the last two decades in comparison to WHO groups 2-5 PH. Methods: In this study, we used data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) the underlying cause of death database to study age-standardized mortality rates related to PH in the US from 2003 to 2020. Results: A total of 126,526 deaths were recorded from PH in the US between 2003 and 2020. Across the study period, PH-related ASMR increased from 17.81 per million population in 2003 to 23.89 in 2020 with a percentage change (PC) of +34%. However, there are contrasting mortality trends in WHO group 1 PH when compared to WHO groups 2-5 PH. Data demonstrated a decline in mortality from group 1 PH regardless of gender. In contrast, an increase in mortality from WHO groups 2-5 PH was observed, accounting for the major proportion of the overall PH mortality burden in recent years. Conclusions: PH-related mortality continues to an increase primarily due to increase in mortality attributed to WHO groups 2-5 PH. These findings have notable public health implications. Screening and risk assessment tools for secondary PH, risk factor modification, and novel management strategies are vital to improve outcomes.

Preference for and impact of telehealth vs in-person asthma visits among Black and Latinx adults.

BACKGROUND: Black and Latinx adults experience disproportionate asthma-related morbidity and limited specialty care access. The severe acute respiratory syndrome coronavirus 2 pandemic expanded telehealth use. OBJECTIVE: To evaluate visit type (telehealth [TH] vs in-person [IP]) preferences and the impact of visit type on asthma outcomes among Black and Latinx adults with moderate-to-severe asthma. METHODS: For this PREPARE trial ancillary study, visit type preference was surveyed by e-mail or telephone post-trial. Emergency medical record data on visit types and asthma outcomes were available for a subset (March 2020 to April 2021). Characteristics associated with visit type preferences, and relationships between visit type and asthma outcomes (control [Asthma Control Test] and asthma-related quality of life [Asthma Symptom Utility Index]), were tested using multivariable regression. RESULTS: A total of 866 participants consented to be surveyed, with 847 respondents. Among the participants with asthma care experience with both visit types, 42.0% preferred TH for regular checkups, which associated with employment (odds ratio [OR] = 1.61; 95% confidence interval [CI], 1.09-2.39; P = .02), lower asthma medication adherence (OR = 1.06; 95% CI, 1.01-1.11; P = .03), and having more historical emergency department and urgent care asthma visits (OR = 1.10 for each additional visit; 95% CI, 1.02-1.18; P = .02), after adjustment. Emergency medical record data were available for 98 participants (62 TH, 36 IP). Those with TH visits were more likely Latinx, from the Southwest, employed, using inhaled corticosteroid-only controller therapy, with lower body mass index, and lower self-reported asthma medication adherence vs those with IP visits only. Both groups had comparable Asthma Control Test (18.4 vs 18.9, P = .52) and Asthma Symptom Utility Index (0.79 vs 0.84, P = .16) scores after adjustment. CONCLUSION: TH may be similarly efficacious as and often preferred over IP among Black and Latinx adults with moderate-to-severe asthma, especially for regular checkups. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02995733.

Trends in pulmonary tuberculosis mortality between 1985 and 2018: an observational analysis.

BACKGROUND: Pulmonary tuberculosis (TB) is a major source of global morbidity and mortality. Latent infection has enabled it to spread to a quarter of the world's population. The late 1980s and early 1990s saw an increase in the number of TB cases related to the HIV epidemic, and the spread of multidrug-resistant TB. Few studies have reported pulmonary TB mortality trends. Our study reports and compares trends in pulmonary TB mortality. METHODS: We utilized the World Health Organization (WHO) mortality database from 1985 through 2018 to analyze TB mortality using the International Classification of Diseases-10 codes. Based on the availability and quality of data, we investigated 33 countries including two countries from the Americas; 28 countries from Europe; and 3 countries from the Western Pacific region. Mortality rates were dichotomized by sex. We computed age-standardized death rates per 100,000 population using the world standard population. Time trends were investigated using joinpoint regression analysis. RESULTS: We observed a uniform decrease in mortality in all countries across the study period except the Republic of Moldova, which showed an increase in female mortality (+ 0.12 per 100,000 population). Among all countries, Lithuania had the greatest reduction in male mortality (-12) between 1993-2018, and Hungary had the greatest reduction in female mortality (-1.57) between 1985-2017. For males, Slovenia had the most rapid recent declining trend with an estimated annual percentage change (EAPC) of -47% (2003-2016), whereas Croatia showed the fastest increase (EAPC, + 25.0% [2015-2017]). For females, New Zealand had the most rapid declining trend (EAPC, -47.2% [1985-2015]), whereas Croatia showed a rapid increase (EAPC, + 24.9% [2014-2017]). CONCLUSIONS: Pulmonary TB mortality is disproportionately higher among Central and Eastern European countries. This communicable disease cannot be eliminated from any one region without a global approach. Priority action areas include ensuring early diagnosis and successful treatment to the most vulnerable groups such as people of foreign origin from countries with a high burden of TB and incarcerated population. Incomplete reporting of TB-related epidemiological data to WHO excluded high-burden countries and limited our study to 33 countries only. Improvement in reporting is crucial to accurately identify changes in epidemiology, the effect of new treatments, and management approaches.

Trends in the mortality, incidence and disability-adjusted life-years of appendicitis in EU15+ countries: an observational study of the Global Burden of Disease Database, 1990-2019.

BACKGROUND: Appendicitis places a substantial burden on healthcare systems, with acute appendicitis alone being the most common abdominal surgical emergency worldwide. Further characterisation of the disease burden in EU15+ countries may help optimise the distribution of healthcare resources. The aim of this observational study was to assess the trends in mortality, incidence and disability-adjusted life-years (DALYs) of appendicitis across European Union (EU) 15+ countries between the years 1990 and 2019, Supplemental Digital Content 3, http://links.lww.com/JS9/A589 . MATERIALS AND METHODS: Age-standardised mortality rates (ASMRs), age-standardised incidence rates (ASIRs) and DALYs data for appendicitis in males and females were extracted from the 2019 Global Burden of Disease (GBD) study. Temporal trends within the study period were analysed using Joinpoint regression analysis. RESULTS: The median ASMRs across EU15+ countries in 2019 were 0.08/100 000 and 0.13/100 000 for females and males, respectively. Between 1990 and 2019 the median percentage change in ASMR was -52.12% for females and -53.18% in males. The median ASIRs in 2019 for females and males were 251/100 000 and 278/100 000, respectively, with a median percentage change of +7.22% for females and +3.78% for males during the observation period. Decreasing trends in DALYs were observed over the 30-year study period, with median percentage changes of -23.57% and -33.81% for females and males, respectively, Supplemental Digital Content 3, http://links.lww.com/JS9/A589 . CONCLUSION: Overall, a general trend of decreasing appendicitis ASMRs and DALYs was observed across EU15+ countries, despite small overall increases in appendicitis ASIRs, Supplemental Digital Content 3, http://links.lww.com/JS9/A589 . Variations in both diagnostic and management strategies over the study period are likely contributory to the changing trends.

Trends in Hospital Admissions, Operative Approaches, and Mortality Related to Abdominal Aortic Aneurysms in England Between 1998 and 2020.

OBJECTIVE: To assess trends in abdominal aortic aneurysm (AAA) hospital admissions, interventions, and aneurysm related mortality in England, and to examine the impact of endovascular repair on mortality for the years 1998 - 2020. METHODS: Hospital admission and operative approach (endovascular aortic aneurysm repair, or open surgical repair [OSR]) using Hospital Episodes Statistics (HES), and aneurysm related mortality data from the Office for National Statistics for England standardised to the 2013 European Standard Population, were analysed using linear regression and Joinpoint regression analyses. Aneurysm related mortality was compared between the pre-endovascular era (1998 - 2010) and the endovascular era (2011 - 2019). RESULTS: A declining trend in hospital admission incidence was observed, mainly due to a decline in ruptured admissions from 34.6 per 100 000 (95% confidence interval [CI] 33.5 - 35.6) to 13.5 per 100 000 (95% CI 12.9 - 14.2; ßi = -1.04, r2 = .97, p < .001). Operative interventions have been declining over the last 23 years mainly due to the statistically significant decline in open procedures (41.2 per 100 000 in 2000 [95% CI 40 - 42.3] to 9.6 per 100 000 [95% CI 9.1 - 10.1]; ßi = -1.92, r2 = .95; p < .001). There was an increasing trend toward endovascular procedures (5.8 per 100 000 [95% CI 5.3 - 6.2] in 2006 to 16.9 per 100 000 [95% CI 16.2 - 17.5] in 2020; ßi = .82, r2 = .30, p = .040). Reductions in aneurysm related mortality due to AAAs were observed for males and females, irrespective of age and rupture status. CONCLUSION: A significant decrease in hospital admissions for AAAs was observed over the last 23 years in England, paralleled by a shift toward endovascular repair and a decline in OSR. Declines in aneurysm related mortality were observed overall, and in the endovascular era irrespective of age, sex, and rupture status.

As-needed inhaled corticosteroids as add-on therapy versus SMART therapy: an evolving understanding of the two approaches in the management of moderate-to-severe asthma.

PURPOSE OF REVIEW: Asthma is the most common chronic respiratory disorder, characterized by recurring, reversible airflow obstruction due to inflammation and airway hyperresponsiveness. Although biologics have provided significant advances in the treatment of asthma, they are expensive, and their use remains restricted to more severe asthma. Additional approaches in the management of moderate-to-severe asthma are necessary. RECENT FINDINGS: ICS-formoterol as maintenance and reliever therapy in asthma and its effect on improved asthma control has been demonstrated in multiple cohorts of asthma. Although ICS-formoterol as maintenance and reliever therapy has been widely validated, there are significant design considerations including the requirement for exacerbation and bronchodilator response and the lack of evidence for effectiveness in patients who use nebulized reliever therapies, which may limit the use of this therapy in selected populations. More recent trials of as-needed ICS have demonstrated effectiveness in reducing asthma exacerbations and improvements in asthma control and may provide an additional therapeutic strategy for individuals with moderate-to-severe asthma. SUMMARY: Both ICS-formoterol as a maintenance and a reliever as well as as-needed ICS have demonstrated significant improvements in the control of moderate-to-severe asthma. Future investigational work will be necessary to elucidate whether a strategy of ICS-formoterol as maintenance and reliever therapy or an as-needed ICS strategy demonstrates superiority in asthma control in the context of the cost to individual patients and health systems.