Acute severe asthma and its predictors of mortality in rural Southwestern Nigeria: a-five year retrospective observational study.

OBJECTIVES: There is an observed paucity of data regarding the predictors of asthma mortality in Nigeria. This study aimed to ascertain the clinical presentations and predictors of acute severe asthma mortality in rural Southwestern Nigeria. METHODS: A retrospective observational study using a data form and a standardized questionnaire was used to review the 124 patients admitted at Emergency Department between January 2015 and December 2019. The data were analyzed using SPSS Version 22.0. The results were presented in descriptive and tabular formats. Binary logistic regression analysis was used to determine the predictors of asthma mortality and a p-value <.05 was considered statistically significant. RESULTS: A total of 124 patients were studied. The acute severe asthma mortality was 4.8% and its predictors were older age (Crude odds Ratio (COR), 14.857; 95% CI: 2.489-88.696, p < .001), Tobacco smoking (COR, 6.741; 95% CI: 1.170-38.826, p = .016), more than three co-morbidities (COR, 2.750; 95% CI: 1.147-26.454, p = 0.012), diabetes mellitus (COR, 13.750; 95% CI: 2.380-79.433, p < .001), Human Immunodeficiency virus (COR, 117.000; 95% CI: 9.257-1479.756, p < .001), ≥2 days before presentation (COR, 7.440; 95% CI: 1.288-42.980, p = .039), and Short-acting-B2-agonists overuse (COR, 7.041; 95% CI: 1.005-62.165, p = .044). CONCLUSION: The mortality rate was 4.8% and its predictors were older age patients, tobacco smoking, multiple co-morbidities, diabetes mellitus, HIV, SP02 <90%, delay presentation, and Short-acting-B2-agonists over use, The study showed that there is high prevalence of asthma mortality in rural Southwestern Nigeria. The findings may be used to plan for asthma preventions and control programs in rural settings, and may also provide an impetus for prospective research on these outcomes.

Caribbean Latinx with moderate-severe asthma bear greater asthma morbidity than other Latinx.

BACKGROUND: Hispanic/Latinx (HL) ethnicity encompasses racially and culturally diverse subgroups. Studies suggest that Puerto Ricans (PR) may bear greater asthma-related morbidity than Mexicans, but these were conducted in children or had limited clinical characterization. OBJECTIVES: This study sought to determine whether disparities in asthma morbidity exist among HL adult subgroups. METHODS: Adults with moderate-severe asthma were recruited from US clinics, including from Puerto Rico, for the Person Empowered Asthma Relief (PREPARE) trial. Considering the shared heritage between PR and other Caribbean HL (Cubans and Dominicans [C&D]), the investigators compared baseline self-reported clinical characteristics between Caribbean HL (CHL) (PR and C&D: n = 457) and other HLs (OHL) (Mexicans, Spaniards, Central/South Americans; n = 141), and between CHL subgroups (C&D [n = 56] and PR [n = 401]). This study compared asthma morbidity measures (self-reported exacerbations requiring systemic corticosteroids, emergency department/urgent care (ED/UC) visits, hospitalizations, health care utilization) through negative binomial regression. RESULTS: CHL compared to OHL were similar in age, body mass index, poverty status, blood eosinophils, and fractional exhaled nitric oxide but were prescribed more asthma controller therapies. Relative to OHL, CHL had significantly increased odds of asthma exacerbations (odds ratio [OR]: 1.84; 95% CI: 1.4-2.4), ED/UC visits (OR: 1.88; 95% CI: 1.4-2.5), hospitalization (OR: 1.98; 95% CI: 1.06-3.7), and health care utilization (OR: 1.91; 95% CI: 1.44-2.53). Of the CHL subgroups, PR had significantly increased odds of asthma exacerbations, ED/UC visits, hospitalizations, and health care utilization compared to OHL, whereas C&D only had increased odds of exacerbations compared to OHL. PR compared to C&D had greater odds of ED/UC and health care utilization. CONCLUSIONS: CHL adults, compared with OHL, adults reported nearly twice the asthma morbidity; these differences are primarily driven by PR. Novel interventions are needed to reduce morbidity in this highly impacted population.

Short-term PM1 and PM2.5 exposure and asthma mortality in Jiangsu Province, China: What's the role of neighborhood characteristics?

BACKGROUND: Evidence suggests that particulate matter (PM) with smaller particle sizes (such as PM1, PM with an aerodynamic diameter≤1 µm) may have more toxic health effects. However, the short-term association between PM1 and asthma mortality remains largely unknown. OBJECTIVE: This study aimed to examine the short-term effects of PM1 and PM2.5 on asthma mortality, as well as to investigate how neighborhood characteristics modified this association. METHODS: Daily data on asthma mortality were collected from 13 cities in Jiangsu Province, China, between 2016 and 2017. A time-stratified case-crossover design was attempted to examine the short-term effects of PM1 and PM2.5 on asthma mortality. Individual exposure levels of PM1 and PM2.5 on case and control days were determined based on individual's residential addresses. Stratified analyses by neighborhood characteristics (including green space, tree canopy, blue space, population density, nighttime light and street connectivity) were conducted to identify vulnerable living environments. RESULTS: Mean daily concentrations of PM1 and PM2.5 on case days were 33.8 µg/m3 and 54.3 µg/m3. Each 10 µg/m3 increase in three-day-averaged (lag02) PM1 and PM2.5 concentrations were associated with an increase of 6.66% (95%CI:1.18%,12.44%) and 2.39% (95%CI: 0.05%-4.78%) asthma mortality, respectively. Concentration-response curves showed a consistent increase in daily asthma mortality with increasing PM1 and PM2.5 concentrations. Subgroup analyses indicated that the effect of PM1 appeared to be evident in neighborhood characteristics with high green space, low urbanization level and poor street connectivity. CONCLUSION: This study suggested an association between short-term PM1 and PM2.5 exposures and asthma mortality. Several neighborhood characteristics (such as green space and physical supportive environment) that could modify the effect of PM1 on asthma mortality should be further explored.

Respiratory-related death in individuals with incident asthma and COPD: a competing risk analysis.

BACKGROUND: Distinguishing between mortality attributed to respiratory causes and other causes among people with asthma, COPD, and asthma-COPD overlap (ACO) is important. This study used electronic health records in England to estimate excess risk of death from respiratory-related causes after accounting for other causes of death. METHODS: We used linked Clinical Practice Research Datalink (CPRD) primary care and Office for National Statistics mortality data to identify adults with asthma and COPD from 2005 to 2015. Causes of death were ascertained using death certificates. Hazard ratios (HR) and excess risk of death were estimated using Fine-Gray competing risk models and adjusting for age, sex, smoking status, body mass index and socioeconomic status. RESULTS: 65,021 people with asthma and 45,649 with COPD in the CPRD dataset were frequency matched 5:1 with people without the disease on age, sex and general practice. Only 14 in 100,000 people with asthma are predicted to experience a respiratory-related death up to 10 years post-diagnosis, whereas in COPD this is 98 in 100,000. Asthma is associated with an 0.01% excess incidence of respiratory related mortality whereas COPD is associated with an 0.07% excess. Among people with asthma-COPD overlap (N = 22,145) we observed an increased risk of respiratory-related death compared to those with asthma alone (HR = 1.30; 95% CI 1.21-1.40) but not COPD alone (HR = 0.89; 95% CI 0.83-0.94). CONCLUSIONS: Asthma and COPD are associated with an increased risk of respiratory-related death after accounting for other causes; however, diagnosis of COPD carries a much higher probability. ACO is associated with a lower risk compared to COPD alone but higher risk compared to asthma alone.

Asthma in paediatric intensive care in England residents: observational study.

Despite high prevalence of asthma in children in the UK, there were no prior report on asthma admissions in paediatric intensive care units (PICU). We investigated the epidemiology and healthcare resource utilisation in children with asthma presenting to PICUs in England. PICANet, a UK national PICU database, was queried for asthma as the primary reason for admission, of children resident in England from April 2006 until March 2013. There were 2195 admissions to PICU for a median stay of 1.4 days. 59% were males and 51% aged 0-4 years. The fourth and fifth most deprived quintiles represented 61% (1329) admissions and 73% (11) of the 15 deaths. Deaths were most frequent in 10-14 years age (n = 11, 73%), with no deaths in less than 5 years age. 38% of admissions (828/2193) received invasive ventilation, which was more frequent with increasing deprivation (13% (108/828) in least deprived to 31% (260/828) in most deprived) and with decreasing age (0-4-year-olds: 49%, 409/828). This first multi-centre PICU study in England found that children from more deprived neighbourhoods represented the majority of asthma admissions, invasive ventilation and deaths in PICU. Children experiencing socioeconomic deprivation could benefit from enhanced asthma support in the community.

Advances in clinical outcomes: What we have learned during the COVID-19 pandemic.

Our understanding of risk factors and interventions influencing outcomes from coronavirus disease 2019 (COVID-19) has continued to evolve, revealing advances emerging from hypotheses formed at the start of the pandemic. Epidemiologic studies have shown that asthma control, rather than a diagnosis of asthma, is a determinant of COVID-19 severity. Clinical outcomes in patients with primary immunodeficiencies, even in those with impaired cellular immunity, are variable. IL-6 has emerged as a reliable biomarker of COVID-19 severity, and large clinical trials have shown the potential for improving outcomes through inhibition of IL-6 signaling in some patients. Studies of genetic risk factors for severe COVID-19 have also revealed the importance of interferon homeostasis in the defense against severe acute respiratory syndrome coronavirus 2. Because COVID-19 vaccines constitute the primary tool for ending this pandemic, strategies have been developed to address potential allergic and immune-mediated reactions. Here, we discuss advances in our understanding of COVID-19 risk factors and outcomes within the context of allergic and immunologic mechanisms.

Mapping geographic variability of severe uncontrolled asthma in the United States: Management implications.

BACKGROUND: The US population-level data on asthma morbidity and mortality are available primarily through state-level surveys. We hypothesize that considerable county-level heterogeneity may be obscured by state-level data, thus impeding focused initiatives to improve asthma outcomes. OBJECTIVE: To assess heterogeneity in the prevalence of uncontrolled, severe, and severe uncontrolled asthma by evaluating state- and county-level morbidity reflected in large administrative claims data sets and identify relationships between pharmacotherapy-based morbidity and the Centers for Disease Control and Prevention's asthma mortality data. METHODS: Asthma prevalence and morbidity were identified using medical and pharmacy claims from the IQVIA Longitudinal Access and Adjudication Data database (July 2015-June 2018). Heat maps ranked the prevalence of severe uncontrolled asthma by deciles in all 50 states and the District of Columbia, plus 2935 counties. Mortality in states (2016) and 3147 counties (1999-2018) was similarly mapped and ranked and contrasted with claims-based morbidity. RESULTS: Among 4,506,527 individuals with asthma, 640,936 (14.2%) received age-specific therapy for severe asthma. Of those with severe asthma, 144,232 (22.5%) filled 2 or more annual courses of systemic steroids and were designated as having severe uncontrolled asthma. Most states with high mortality had relatively few patients with severe uncontrolled asthma. A marked correlation between mortality and morbidity and trends by urban vs rural and metropolitan status were found at the county level. CONCLUSION: Intrastate heterogeneity in the morbidity and mortality of severe uncontrolled asthma at the county level is not evident in state-level analyses. Increased local awareness of systemic corticosteroid use as an indicator of uncontrolled asthma should prompt regional educational and public health efforts to improve outcomes.

Prevalence, Deaths, and Disability-Adjusted Life-Years Due to Asthma and Its Attributable Risk Factors in 204 Countries and Territories, 1990-2019.

BACKGROUND: Understanding global trends in the point prevalence, deaths, and disability-adjusted life-years (DALYs) for asthma will facilitate evidence-based decision-making. RESEARCH QUESTION: What are the global, regional, and national burdens of asthma in 204 countries and territories between 1990 and 2019 by age, sex, and sociodemographic index (SDI)? STUDY DESIGN AND METHODS: Publicly available data from the Global Burden of Disease study from 1990 through 2019 were used. All estimates were presented as counts and age-standardized rates per 100,000, along with their associated uncertainty intervals. RESULTS: In 2019, the global age-standardized point prevalence and death rates for asthma were 3,415.5 and 5.8 per 100,000, which represent a 24% and 51.3% decrease since 1990, respectively. Moreover, in 2019, the global age-standardized DALY rate was 273.6 and the global point prevalence of asthma was highest in the group 5 to 9 years of age. Also in 2019, the United States (10,399.3) showed the highest age-standardized point prevalence rate of asthma. Generally, the burden of asthma decreased with increasing SDI. Globally, high BMI (16.9%), smoking (9.9%), and occupational asthmagens (8.8%) contributed to the 2019 asthma DALYs. INTERPRETATION: Asthma remains an important public health issue, particularly in regions with low socioeconomic development. Future research is needed to examine thoroughly the associations asthma has with its risk factors and the factors impeding optimal self-management. Further research also is needed to understand and implement better the interventions that have reduced the burden of asthma.

Long-term predictors of severe exacerbations and mortality in a cohort of well-characterised adults with asthma.

BACKGROUND: We aimed to explore long-term predictors of severe exacerbations and mortality in adults with well-characterised asthma. STUDY DESIGN AND METHODS: Adults (aged ≥ 15) with an objectively verified diagnosis of asthma were recruited from a Danish respiratory outpatient clinic between 1974 and 1990. All individuals were followed in Danish registries for vital status, hospital admissions for asthma and cause of death until end of 2017. Predictors of exacerbations were obtained from a repeated measures model. Standardised mortality rates (SMR) for all-causes were compared with the Danish background population. Hazard ratios for mortality were obtained from a cox proportional hazards model in a two-step process. RESULTS: At baseline, the cohort comprised 1071 patients (mean age 38, SD 16, 61% women), of whom 357 (33%) died during follow-up, with 93 (26%) dying from asthma (primary diagnosis). We found an SMR of 1.24 (95% CI 1.11-1.37, p < 0.001) for all-cause mortality. Baseline predictors for asthma-related death and repeated severe exacerbations were increasing age, ever smoker, FEV1 < 80% pred., high blood eosinophils, longer duration of symptoms and use of SABA > twice daily. Being non-atopic, having a positive histamine challenge test and symptoms more than twice a week were also predictors of repeated exacerbations. CONCLUSIONS: Markers of poor asthma control, including high use of SABA, are predictors of long-term exacerbation rate and mortality over 30 years in patients with well-characterised asthma. Improving asthma control, including lung function and reducing use of reliever medication, is vital for improving the long-term outcome of asthma.

Morbidity and mortality outcomes of COVID-19 patients with and without hypertension in Lagos, Nigeria: a retrospective cohort study.

BACKGROUND: The current pandemic of coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown epidemiological and clinical characteristics that appear worsened in hypertensive patients. The morbidity and mortality of the disease among hypertensive patients in Africa have yet to be well described. METHODS: In this retrospective cohort study all confirmed COVID-19 adult patients (≥18 years of age) in Lagos between February 27 to July 62,020 were included. Demographic, clinical and outcome data were extracted from electronic medical records of patients admitted at the COVID-19 isolation centers in Lagos. Outcomes included dying, being discharged after recovery or being evacuated/transferred. Descriptive statistics considered proportions, means and medians. The Chi-square and Fisher's exact tests were used in determining associations between variables. Kaplan-Meier survival analysis and Cox regression were performed to quantify the risk of worse outcomes among hypertensives with COVID-19 and adjust for confounders. P-value ≤0.05 was considered statistically significant. RESULTS: A total of 2075 adults with COVID-19 were included in this study. The prevalence of hypertension, the most common comorbidity, was 17.8% followed by diabetes (7.2%) and asthma (2.0%). Overall mortality was 4.2% while mortality among the hypertensives was 13.7%. Severe symptoms and mortality were significantly higher among the hypertensives and survival rates were significantly lowered by the presence of additional comorbidity to 50% from 91% for those with hypertension alone and from 98% for all other patients (P < 0.001). After adjustment for confounders (age and sex), severe COVID-19and death were higher for hypertensives {severe/critical illness: HR = 2.41, P = 0.001, 95%CI = 1.4-4.0, death: HR = 2.30, P = 0.001, 95%CI = 1.2-4.6, for those with hypertension only} {severe/critical illness: HR = 3.76, P = 0.001, 95%CI = 2.1-6.4, death: crude HR = 6.63, P = 0.001, 95%CI = 3.4-1.6, for those with additional comorbidities}. Hypertension posed an increased risk of severe morbidity (approx. 4-fold) and death (approx. 7-fold) from COVID-19 in the presence of multiple comorbidities. CONCLUSION: The potential morbidity and mortality risks of hypertension especially with other comorbidities in COVID-19 could help direct efforts towards prevention and prognostication. This provides the rationale for improving preventive caution for people with hypertension and other comorbidities and prioritizing them for future antiviral interventions.

Increased all-cause mortality in concomitant atopic dermatitis and asthma: A nationwide registry-based study.

BACKGROUND: Excess mortality has been reported for adults with atopic dermatitis (AD) and asthma. OBJECTIVE: To assess the mortality rate in adults with concomitant AD and asthma. METHODS: Adults with hospital-diagnosed AD were matched (1:4) with non-AD individuals from the background population. RESULTS: The study cohort comprised 8,095 adults with AD (of which 1,201 (14.8%) had concomitant asthma) and 32,380 reference individuals without AD from the background population (of which 878 (2.7%) had asthma). A total of 1,057, 330, 55 and 99 deaths were observed among subjects with neither AD nor asthma, AD only, asthma only, and subjects with concomitant AD and asthma, respectively. The mortality rate per 1,000 person-years was 4.75 (95% CI 4.47-5.05) for subjects with neither AD nor asthma, 7.17 (95% CI 5.92-10.05) for asthma only, 7.09 (95% CI 6.37-7.90) for AD only and 10.87 (95% CI 8.92-13.23) for concomitant AD and asthma. Risk for all-cause mortality was increased in subjects with concomitant AD and asthma compared to asthma only (HR 1.52, 95% CI 1.07-2.15) and neither AD nor asthma (HR 2.27, 95% CI 1.83-2.81) but not compared to subjects with AD only (HR 1.10, 95% CI 0.87-1.39). However, compared to AD only subjects with AD and asthma had increased risk of death due to pulmonary disease (HR 1.81, 95% CI 1.04-3.15). CONCLUSION: Adults with AD, asthma or both conditions have increased risk of death, and further concomitant AD and asthma have increased risk of death compared with asthma alone.

Outcomes among patients with COVID-19 and asthma: A systematic review and meta-analysis.

Background: It remains unclear if asthma is a risk factor associated with worse outcomes among patients with coronavirus disease 2019 (COVID-19). Methods: We performed a comprehensive database search for studies published from January 1, 2019, to October 2, 2020. We included studies that evaluated outcomes among patients with COVID-19 and underlying asthma. Outcomes of interest included the need for hospitalization, length of hospitalization, intensive care unit (ICU) admission, and death. The meta-analysis was conducted by using random-effects methodology. Results: A total of 389 studies were identified through data base searches. After abstract and full-text screening, 16 observational studies with 92,275 patients were included in the analysis. Of the 16 studies, 15 were retrospective and 1 was a prospective cohort study. The average age was 39.6 years, with 48% female patients. Six of the studies included pediatric patients, and one of these studies only evaluated pediatric patients. One study only evaluated pregnant patients. Among patients with COVID-19, the presence of asthma was not associated with any significant increase in risk of hospitalization (odds ratio [OR] 1.46 [95% confidence interval {CI}, 0.29-7.28]), length of hospitalization (1.59 days [-0.55 to 3.74]), ICU admission (OR 1.65 [95% CI, 0.56-4.17]), or death (OR 0.73 [95% CI, 0.38-1.40]). The overall risk of bias of the included studies was high. Conclusion: Among the patients with COVID-19, asthma did not seem to significantly increase the risk of hospitalization, length of hospitalization, ICU admission, or death.

Asma en Chile: tendencia de la mortalidad 1992-2017 / Asthma in Chile: mortality trend 1992-2017

OBJETIVOS: El asma, un problema de salud pública, tiene tasas de mortalidad global variables. En Chile, no existen estudios que informen respecto a la situación nacional. Analizamos la tendencia de mortalidad en adultos chilenos durante un período de 26 años. MÉTODOS: Utilizando datos del Departamento de Estadísticas e Información de Salud y el Instituto Nacional de Estadísticas se calcularon las tasas de mortalidad por asma 1992-2017 en personas ≥ 15 años de edad. Para evitar el impacto de los cambios por edad, las tasas de mortalidad ajustadas se calcularon mediante un método de ajuste directo utilizando la población de 2017 como referencia. Se usó Joinpoint para calcular la pendiente de las tasas ajustadas y para análisis de datos se utilizó Excel STATA versión13. RESULTADOS: Durante el período de 26 años, hubo 5.749 muertes relacionadas con el asma, con un promedio de 221 eventos / año. Las tasas de mortalidad ajustadas por edad disminuyeron significativamente de 3,26 en 1992 a 1,4 por 100.000 habitantes en 2017, con un promedio de disminución anual de -3,3%. La mayor proporción de defunciones se produjo en personas de 65 años o más, representando 79% de los casos en 1992 y 88% de los casos en 2017. CONCLUSIONES: las tendencias de las tasas de mortalidad por asma en Chile, ajustadas por edad, muestran una disminución significativa en los 26 años que abarca este estudio, disminución que es menos acentuada en los últimos 15 años.

OBJETIVES: Asthma, a public health problem, has variable global mortality rates. In Chile, there are no studies to report on the national situation. This study analyzes the mortality trend in Chilean adults over a period of 26 years. METHODS: Using data from the Department of Health Statistics and Information and the National Institute of Statistics, asthma mortality rates 1992-2017 were calculated in people ≥ 15 years-old. To avoid the impact of age changes, adjusted mortality rates were calculated using a direct adjustment method using the 2017 population as a reference. Joinpoint was used to calculate the slope of adjusted rates, and Excel STATA version13 was used for data analysis. RESULTS: Over the 26-year period, there were 5,749 asthma-related deaths, with an average of 221 events per year. Age-adjusted mortality rates decreased significantly from 3.26 in 1992 to 1.4 per 100,000 inhabitants in 2017, with an average annual decline of -3.3%. The highest proportion of deaths occurred in people 65 years of age or older, accounting for 79% of cases in 1992 and 88% of cases in 2017. CONCLUSIONS: In Chile trends in asthma mortality rates age-adjusted show a significant decrease in the 26 years covered by this study, a decrease that is less pronounced in the last 15 years.

Triple vs Dual Inhaler Therapy and Asthma Outcomes in Moderate to Severe Asthma: A Systematic Review and Meta-analysis.

IMPORTANCE: The benefits and harms of adding long-acting muscarinic antagonists (LAMAs) to inhaled corticosteroids (ICS) and long-acting ß2-agonists (LABAs) for moderate to severe asthma remain unclear. OBJECTIVE: To systematically synthesize the outcomes and adverse events associated with triple therapy (ICS, LABA, and LAMA) vs dual therapy (ICS plus LABA) in children and adults with persistent uncontrolled asthma. DATA SOURCES: MEDLINE, Embase, CENTRAL, ICTRP, FDA, and EMA databases from November 2017, to December 8, 2020, without language restriction. STUDY SELECTION: Two investigators independently selected randomized clinical trials (RCTs) comparing triple vs dual therapy in patients with moderate to severe asthma. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses, including individual patient-level exacerbation data, were used. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess certainty (quality) of the evidence. MAIN OUTCOMES AND MEASURES: Severe exacerbations, asthma control (measured using the Asthma Control Questionnaire [ACQ-7], a 7-item list with each item ranging from 0 [totally controlled] to 6 [severely uncontrolled]; minimal important difference, 0.5), quality of life (measured using the Asthma-related Quality of Life [AQLQ] tool; score range, 1 [severely impaired] to 7 [no impairment]; minimal important difference, 0.5), mortality, and adverse events. RESULTS: Twenty RCTs using 3 LAMA types that enrolled 11 894 children and adults (mean age, 52 years [range, 9-71 years]; 57.7% female) were included. High-certainty evidence showed that triple therapy vs dual therapy was significantly associated with a reduction in severe exacerbation risk (9 trials [9932 patients]; 22.7% vs 27.4%; risk ratio, 0.83 [95% CI, 0.77 to 0.90]) and an improvement in asthma control (14 trials [11 230 patients]; standardized mean difference [SMD], -0.06 [95% CI, -0.10 to -0.02]; mean difference in ACQ-7 scale, -0.04 [95% CI, -0.07 to -0.01]). There were no significant differences in asthma-related quality of life (7 trials [5247 patients]; SMD, 0.05 [95% CI, -0.03 to 0.13]; mean difference in AQLQ score, 0.05 [95% CI, -0.03 to 0.13]; moderate-certainty evidence) or mortality (17 trials [11 595 patients]; 0.12% vs 0.12%; risk ratio, 0.96 [95% CI, 0.33 to 2.75]; high-certainty evidence) between dual and triple therapy. Triple therapy was significantly associated with increased dry mouth and dysphonia (10 trials [7395 patients]; 3.0% vs 1.8%; risk ratio, 1.65 [95% CI, 1.14 to 2.38]; high-certainty evidence), but treatment-related and serious adverse events were not significantly different between groups (moderate-certainty evidence). CONCLUSIONS AND RELEVANCE: Among children (aged 6 to 18 years) and adults with moderate to severe asthma, triple therapy, compared with dual therapy, was significantly associated with fewer severe asthma exacerbations and modest improvements in asthma control without significant differences in quality of life or mortality.

Clinical Presentation of Iranian Patients Affected with COVID-19: A Thousand Faces Disease.

The coronavirus disease 2019 (COVID-19) pandemic in Iran is part of the worldwide pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The present study aimed to demonstrate the clinical characteristics of patients affected by COVID-19, in our tertiary teaching hospital. Medical records and compiled data of 668 patients with suspected COVID-19 were obtained retrospectively between January to April 2020. The present study outcomes included demographic features of infected patients, underlying diseases and conditions, the relationship between the results of reverse transcription-polymerase chain reaction (RT-PCR) or CT-scan with the manifestations of the disease, mortality rate, and age distribution of fatalities among men and women. The median age of hospitalized patients was 63 years old (from 18 to 94). The patients' chief complaints in the admission time were cough, dyspnea, fever, and gastrointestinal problems, respectively. Hospitalized patients' common comorbidities were hypertension (HTN), and cardiovascular disease (CVD) (24%), diabetes mellitus (DM) (21.5%), asthma, or chronic obstructive pulmonary disease (COPD) (6%), or other underlying diseases (15.5%). One-third of patients had no comorbidity according to the data of medical records. In hospitalized patients, 169 (84.5%) had positive RT-PCR, and 156 (78%) had positive chest CT findings. The mortality rate of males was higher than females (66.3% vs. 33.3%) and in patients with positive RT-PCR compared to patients with positive chest CT-scan findings. The majority of deaths had a history of DM or HTN/CVD in their medical records. The chief complaint of patients was cough. DM and HTN or CVD were the common underlying disease related to death in hospitalized cases. Besides, the hospitalization and mortality rate in males was higher than in females. About 87% of dead hospitalized cases had positive RT-PCR results, and this rate was 82% for chest CT results.

Regular treatment with formoterol and an inhaled corticosteroid versus regular treatment with salmeterol and an inhaled corticosteroid for chronic asthma: serious adverse events.

BACKGROUND: Asthma is characterised by chronic inflammation of the airways and recurrent exacerbations with wheezing, chest tightness, and cough. Treatment with inhaled steroids and bronchodilators can result in good control of symptoms, prevention of further morbidity, and improved quality of life. However, an increase in serious adverse events with the use of both regular formoterol and regular salmeterol (long-acting beta2-agonists) compared with placebo for chronic asthma has been demonstrated in previous Cochrane Reviews. This increase was statistically significant in trials that did not randomise participants to an inhaled corticosteroid, but not when formoterol or salmeterol was combined with an inhaled corticosteroid. The confidence intervals were found to be too wide to ensure that the addition of an inhaled corticosteroid renders regular long-acting beta2-agonists completely safe; few participants and insufficient serious adverse events in these trials precluded a definitive decision about the safety of combination treatments. OBJECTIVES: To assess risks of mortality and non-fatal serious adverse events in trials that have randomised patients with chronic asthma to regular formoterol and an inhaled corticosteroid versus regular salmeterol and an inhaled corticosteroid. SEARCH METHODS: We searched the Cochrane Airways Register of Trials, CENTRAL, MEDLINE, Embase, and two trial registries to identify reports of randomised trials for inclusion. We checked manufacturers' websites and clinical trial registers for unpublished trial data, as well as Food and Drug Administration (FDA) submissions in relation to formoterol and salmeterol. The date of the most recent search was  24 February 2021. SELECTION CRITERIA: We included controlled clinical trials with a parallel design, recruiting patients of any age and severity of asthma, if they randomised patients to treatment with regular formoterol versus regular salmeterol (each with a randomised inhaled corticosteroid) and were of at least 12 weeks' duration. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion in the review, extracted outcome data from published papers and trial registries, and applied GRADE rating for the results. We sought unpublished data on mortality and serious adverse events from study sponsors and authors. The primary outcomes were all cause mortality and non-fatal serious adverse events. We chose not to calculate an average result from all the formulations of formoterol and inhaled steroid, as the doses and delivery devices are too diverse to assume a single class effect. MAIN RESULTS: Twenty-one studies in 11,572 adults and adolescents and two studies in 723 children met the eligibility criteria of the review. No data were available for two studies; therefore these were not included in the analysis. Among adult and adolescent studies, seven compared formoterol and budesonide to salmeterol and fluticasone (N = 7764), six compared formoterol and beclomethasone to salmeterol and fluticasone (N = 1923), two compared formoterol and mometasone to salmeterol and fluticasone (N = 1126), two compared formoterol and fluticasone to salmeterol and fluticasone (N = 790), and one compared formoterol and budesonide to salmeterol and budesonide (N = 229). In total, five deaths were reported among adults, none of which was thought to be related to asthma. The certainty of evidence for all-cause mortality was low, as there were not enough deaths to permit any precise conclusions regarding the risk of mortality on combination formoterol versus combination salmeterol. In all, 201 adults reported non-fatal serious adverse events. In studies comparing formoterol and budesonide to salmeterol and fluticasone, there were 77 in the formoterol arm and 68 in the salmeterol arm (Peto odds ratio (OR) 1.14, 95% confidence interval (CI) 0.82 to 1.59; 5935 participants, 7 studies; moderate-certainty evidence). In the formoterol and beclomethasone studies, there were 12 adults in the formoterol arm and 13 in the salmeterol arm with events (Peto OR 0.94, 95% CI 0.43 to 2.08; 1941 participants, 6 studies; moderate-certainty evidence). In the formoterol and mometasone studies, there were 18 in the formoterol arm and 11 in the salmeterol arm (Peto OR 1.02, 95% CI 0.47 to 2.20; 1126 participants, 2 studies; moderate-certainty evidence). One adult in the formoterol and fluticasone studies in the salmeterol arm experienced an event (Peto OR 0.05, 95% CI 0.00 to 3.10; 293 participants, 2 studies; low-certainty evidence). Another adult in the formoterol and budesonide compared to salmeterol and budesonide study in the formoterol arm had an event (Peto OR 7.45, 95% CI 0.15 to 375.68; 229 participants, 1 study; low-certainty evidence). Only 46 adults were reported to have experienced asthma-related serious adverse events. The certainty of the evidence was low to very low due to the small number of events and the absence of independent assessment of causation. The two studies in children compared formoterol and fluticasone to salmeterol and fluticasone. No deaths and no asthma-related serious adverse events were reported in these studies. Four all-cause serious adverse events were reported: three in the formoterol arm, and one in the salmeterol arm (Peto OR 2.72, 95% CI 0.38 to 19.46; 548 participants, 2 studies; low-certainty evidence). AUTHORS' CONCLUSIONS: Overall, for both adults and children, evidence is insufficient to show whether regular formoterol in combination with budesonide, beclomethasone, fluticasone, or mometasone has a different safety profile from salmeterol in combination with fluticasone or budesonide. Five deaths of any cause were reported across all studies and no deaths from asthma; this information is insufficient to permit any firm conclusions about the relative risks of mortality on combination formoterol in comparison to combination salmeterol inhalers. Evidence on all-cause non-fatal serious adverse events indicates that there is probably little to no difference between formoterol/budesonide and salmeterol/fluticasone inhalers. However events for the other formoterol combination inhalers were too few to allow conclusions. Only 46 non-fatal serious adverse events were thought to be asthma related; this small number in addition to the absence of independent outcome assessment means that we have very low confidence for this outcome. We found no evidence of safety issues that would affect the choice between salmeterol and formoterol combination inhalers used for regular maintenance therapy by adults and children with asthma.

Is birth out-of-hospital associated with mortality and morbidity by seven years of age?

BACKGROUND AND AIMS: Compared to in-hospital births, the long-term outcome of children born out-of-hospital, planned or unplanned, is poorly studied. This study aimed to examine mortality and morbidity by seven years of age in children born out-of-hospital compared to those born in-hospital. METHODS: This study was registered retrospectively and included 790 136 children born in Finland between 1996 and 2013. The study population was divided into three groups according to birth site: in-hospital (n = 788 622), planned out-of-hospital (n = 176), and unplanned out-of-hospital (n = 1338). Data regarding deaths, hospital visits, reimbursement of medical expenses, and disability allowances was collected up to seven years of age or by the year-end of 2018. The association between birth site and childhood morbidity was determined using multivariable-adjusted Cox hazard regression analysis. RESULTS: No deaths were reported during the first seven years after birth in the children born out-of-hospital. The percentage of children with hospital visits due to infection by seven years of age was lower in those born planned out-of-hospital and in the combined planned out-of-hospital and unplanned out-of-hospital group compared to those born in-hospital. Furthermore, the percentage of children with hospital visits and who received disability allowances due to neurological or mental disorders was higher among those born unplanned out-of-hospital and out-of-hospital in total when compared to those born in-hospital. In the multivariable-adjusted Cox proportional hazard regression analysis, the hazard ratio for hospital visits due to asthma and/or allergic diseases (HR 0.84; 95% CI 0.72-0.98) was lower in children born out-of-hospital when compared to those born in-hospital. A similar decreased risk was found due to infections (HR 0.76; 95% CI 0.68-0.84). However, the risk for neurological or mental health disorders was similar between the children born in-hospital and out-of-hospital. CONCLUSIONS: Morbidity related to asthma or allergic diseases and infections by seven years of age appeared to be lower in children born out-of-hospital. Birth out-of-hospital seemed to not be associated with increased risk for neurological morbidity nor early childhood mortality. Our study groups were small and heterogeneous and because of this the results need to be interpreted with caution.