The Influence of Sex and/or Gender on the Occurrence of Colorectal Cancer in the General Population in Developed Countries: A Scoping Review.

Objective: Gender as the "sociocultural role of sex" is underrepresented in colorectal cancer incidence studies, potentially resulting in underestimated risk factors' consequences and inequalities men/women. We aim to explore how literature focusing on differences between men and women in the incidence of colorectal cancer interprets these differences: through sex- or gender-related mechanisms, or both? Methods: We conducted a scoping review using PubMed and Google Scholar. We categorized studies based on their definitions of sex and/or gender variables. Results: We reviewed 99 studies, with 7 articles included in the analysis. All observed differences between men and women. Six articles examined colorectal cancer incidence by gender, but only 2 used the term "gender" to define exposure. One article defined its "sex" exposure variable as gender-related mechanisms, and two articles used "sex" and "gender" interchangeably to explain these inequalities. Gender mechanisms frequently manifest through health behaviors. Conclusion: Our results underscore the need for an explicit conceptual framework to disentangle sex and/or gender mechanisms in colorectal cancer incidence. Such understanding would contribute to the reduction and prevention of social health inequalities.

Aspirin for Secondary Prevention of Cardiovascular Disease in 51 Low-, Middle-, and High-Income Countries.

Importance: Aspirin is an effective and low-cost option for reducing atherosclerotic cardiovascular disease (CVD) events and improving mortality rates among individuals with established CVD. To guide efforts to mitigate the global CVD burden, there is a need to understand current levels of aspirin use for secondary prevention of CVD. Objective: To report and evaluate aspirin use for secondary prevention of CVD across low-, middle-, and high-income countries. Design, Setting, and Participants: Cross-sectional analysis using pooled, individual participant data from nationally representative health surveys conducted between 2013 and 2020 in 51 low-, middle-, and high-income countries. Included surveys contained data on self-reported history of CVD and aspirin use. The sample of participants included nonpregnant adults aged 40 to 69 years. Exposures: Countries' per capita income levels and world region; individuals' socioeconomic demographics. Main Outcomes and Measures: Self-reported use of aspirin for secondary prevention of CVD. Results: The overall pooled sample included 124 505 individuals. The median age was 52 (IQR, 45-59) years, and 50.5% (95% CI, 49.9%-51.1%) were women. A total of 10 589 individuals had a self-reported history of CVD (8.1% [95% CI, 7.6%-8.6%]). Among individuals with a history of CVD, aspirin use for secondary prevention in the overall pooled sample was 40.3% (95% CI, 37.6%-43.0%). By income group, estimates were 16.6% (95% CI, 12.4%-21.9%) in low-income countries, 24.5% (95% CI, 20.8%-28.6%) in lower-middle-income countries, 51.1% (95% CI, 48.2%-54.0%) in upper-middle-income countries, and 65.0% (95% CI, 59.1%-70.4%) in high-income countries. Conclusion and Relevance: Worldwide, aspirin is underused in secondary prevention, particularly in low-income countries. National health policies and health systems must develop, implement, and evaluate strategies to promote aspirin therapy.

Global Variations in Heart Failure Etiology, Management, and Outcomes.

Importance: Most epidemiological studies of heart failure (HF) have been conducted in high-income countries with limited comparable data from middle- or low-income countries. Objective: To examine differences in HF etiology, treatment, and outcomes between groups of countries at different levels of economic development. Design, Setting, and Participants: Multinational HF registry of 23 341 participants in 40 high-income, upper-middle-income, lower-middle-income, and low-income countries, followed up for a median period of 2.0 years. Main Outcomes and Measures: HF cause, HF medication use, hospitalization, and death. Results: Mean (SD) age of participants was 63.1 (14.9) years, and 9119 (39.1%) were female. The most common cause of HF was ischemic heart disease (38.1%) followed by hypertension (20.2%). The proportion of participants with HF with reduced ejection fraction taking the combination of a ß-blocker, renin-angiotensin system inhibitor, and mineralocorticoid receptor antagonist was highest in upper-middle-income (61.9%) and high-income countries (51.1%), and it was lowest in low-income (45.7%) and lower-middle-income countries (39.5%) (P < .001). The age- and sex- standardized mortality rate per 100 person-years was lowest in high-income countries (7.8 [95% CI, 7.5-8.2]), 9.3 (95% CI, 8.8-9.9) in upper-middle-income countries, 15.7 (95% CI, 15.0-16.4) in lower-middle-income countries, and it was highest in low-income countries (19.1 [95% CI, 17.6-20.7]). Hospitalization rates were more frequent than death rates in high-income countries (ratio = 3.8) and in upper-middle-income countries (ratio = 2.4), similar in lower-middle-income countries (ratio = 1.1), and less frequent in low-income countries (ratio = 0.6). The 30-day case-fatality rate after first hospital admission was lowest in high-income countries (6.7%), followed by upper-middle-income countries (9.7%), then lower-middle-income countries (21.1%), and highest in low-income countries (31.6%). The proportional risk of death within 30 days of a first hospital admission was 3- to 5-fold higher in lower-middle-income countries and low-income countries compared with high-income countries after adjusting for patient characteristics and use of long-term HF therapies. Conclusions and Relevance: This study of HF patients from 40 different countries and derived from 4 different economic levels demonstrated differences in HF etiologies, management, and outcomes. These data may be useful in planning approaches to improve HF prevention and treatment globally.

Ear and hearing care programs for First Nations children: a scoping review.

BACKGROUND: Ear and hearing care programs are critical to early detection and management of otitis media (or middle ear disease). Otitis media and associated hearing loss disproportionately impacts First Nations children. This affects speech and language development, social and cognitive development and, in turn, education and life outcomes. This scoping review aimed to better understand how ear and hearing care programs for First Nations children in high-income colonial-settler countries aimed to reduce the burden of otitis media and increase equitable access to care. Specifically, the review aimed to chart program strategies, map the focus of each program against 4 parts of a care pathway (prevention, detection, diagnosis/management, rehabilitation), and to identify the factors that indicated the longer-term sustainability and success of programs. METHOD: A database search was conducted in March 2021 using Medline, Embase, Global Health, APA PsycInfo, CINAHL, Web of Science Core Collection, Scopus, and Academic Search Premier. Programs were eligible or inclusion if they had either been developed or run at any time between January 2010 to March 2021. Search terms encompassed terms such as First Nations children, ear and hearing care, and health programs, initiatives, campaigns, and services. RESULTS: Twenty-seven articles met the criteria to be included in the review and described a total of twenty-one ear and hearing care programs. Programs employed strategies to: (i) connect patients to specialist services, (ii) improve cultural safety of services, and (iii) increase access to ear and hearing care services. However, program evaluation measures were limited to outputs or the evaluation of service-level outcome, rather than patient-based outcomes. Factors which contributed to program sustainability included funding and community involvement although these were limited in many cases. CONCLUSION: The result of this study highlighted that programs primarily operate at two points along the care pathway-detection and diagnosis/management, presumably where the greatest need lies. Targeted strategies were used to address these, some which were limited in their approach. The success of many programs are evaluated as outputs, and many programs rely on funding sources which can potentially limit longer-term sustainability. Finally, the involvement of First Nations people and communities typically only occurred during implementation rather than across the development of the program. Future programs should be embedded within a connected system of care and tied to existing policies and funding streams to ensure long term viability. Programs should be governed and evaluated by First Nations communities to further ensure programs are sustainable and are designed to meet community needs.

Rheumatic fever in a developed country - is it still relevant? A retrospective, 25 years follow-up.

BACKGROUND: Our aims were to clinically and epidemiologically characterize rheumatic fever (RF) in the current era in Israel. Although there has been a steady decline in the incidence of RF in the western world, evidence of disease resurgence in developed countries continues to be published. The paucity of recent epidemiological data prompted our study. METHODS: Medical files were retrospectively reviewed for all children with RF in our tertiary pediatric university-affiliated hospital from 1993 to 2017. Main outcome measures were patients and disease related characteristics, incidence trends, risk factors, disease course, relapse rates and secondary prophylaxis. RESULTS: The cohort included 307 children. Sixty-four percent presented with arthritis, interestingly including hips and small joints of hands and feet at presentation, 52% presented with carditis. Severe carditis developed in 31 patients (19.5%), of whom 21 (13.2% of all carditis patients) acquired heart failure, 5 required intensive care monitoring, with one recent death. The percentage of patients with acute carditis of the overall RF patients remained relatively stable. Thirty-two patients (10% of patients with RF) relapsed, including 11 with a cardiac relapse (3.6% of all cardiac patients). The recurrence rate of RF continued to rise up to 9 years from the initial episode. One of 147 patients (< 0.7%) with a non-cardiac initial presentation had carditis at relapse. CONCLUSION: RF and rheumatic heart disease remain an important cause of morbidity and mortality including developed countries, with relapse rate continuing after 9 years of prophylaxis. Presentation of small joints as well as hips, although uncommon, should not exclude the diagnosis.

Progress Toward Rubella and Congenital Rubella Syndrome Control and Elimination - Worldwide, 2012-2020.

Rubella virus is a leading cause of vaccine-preventable birth defects and can cause epidemics. Although rubella virus infection usually produces a mild febrile rash illness in children and adults, infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, stillbirth, or an infant born with a constellation of birth defects known as congenital rubella syndrome (CRS). A single dose of rubella-containing vaccine (RCV) can provide lifelong protection against rubella (1). The Global Vaccine Action Plan 2011-2020 (GVAP) included a target to achieve elimination of rubella in at least five of the six World Health Organization (WHO) regions* by 2020 (2), and WHO recommends capitalizing on the accelerated measles elimination activities as an opportunity to introduce RCV (1). This report updates a previous report (3) and summarizes global progress toward control and elimination of rubella and CRS from 2012, when accelerated rubella control activities were initiated, through 2020. Among 194 WHO Member States, the number with RCV in their immunization schedules has increased from 132 (68%) in 2012 to 173 (89%) in 2020; 70% of the world's infants were vaccinated against rubella in 2020. Reported rubella cases declined by 48%, from 94,277 in 2012 to 49,136 in 2019, and decreased further to 10,194 in 2020. Rubella elimination has been verified in 93 (48%) of 194 countries including the entire Region of the Americas (AMR). To increase the equity of protection and make further progress to eliminate rubella, it is important that the 21 countries that have not yet done so should introduce RCV. Likewise, countries that have introduced RCV can achieve and maintain rubella elimination with high vaccination coverage and surveillance for rubella and CRS. Four of six WHO regions have established rubella elimination goals; the two WHO regions that have not yet established an elimination goal (the African [AFR] and Eastern Mediterranean [EMR] regions) have expressed a commitment to rubella elimination and should consider establishing a goal.

Variations in risks from smoking between high-income, middle-income, and low-income countries: an analysis of data from 179 000 participants from 63 countries.

BACKGROUND: Separate studies suggest that the risks from smoking might vary between high-income (HICs), middle-income (MICs), and low-income (LICs) countries, but this has not yet been systematically examined within a single study using standardised approaches. We examined the variations in risks from smoking across different country income groups and some of their potential reasons. METHODS: We analysed data from 134 909 participants from 21 countries followed up for a median of 11·3 years in the Prospective Urban Rural Epidemiology (PURE) cohort study; 9711 participants with myocardial infarction and 11 362 controls from 52 countries in the INTERHEART case-control study; and 11 580 participants with stroke and 11 331 controls from 32 countries in the INTERSTROKE case-control study. In PURE, all-cause mortality, major cardiovascular disease, cancers, respiratory diseases, and their composite were the primary outcomes for this analysis. Biochemical verification of urinary total nicotine equivalent was done in a substudy of 1000 participants in PURE. FINDINGS: In PURE, the adjusted hazard ratio (HR) for the composite outcome in current smokers (vs never smokers) was higher in HICs (HR 1·87, 95% CI 1·65-2·12) than in MICs (1·41, 1·34-1·49) and LICs (1·35, 1·25-1·46; interaction p<0·0001). Similar patterns were observed for each component of the composite outcome in PURE, myocardial infarction in INTERHEART, and stroke in INTERSTROKE. The median levels of tar, nicotine, and carbon monoxide displayed on the cigarette packs from PURE HICs were higher than those on the packs from MICs. In PURE, the proportion of never smokers reporting high second-hand smoke exposure (≥1 times/day) was 6·3% in HICs, 23·2% in MICs, and 14·0% in LICs. The adjusted geometric mean total nicotine equivalent was higher among current smokers in HICs (47·2 µM) than in MICs (31·1 µM) and LICs (25·2 µM; ANCOVA p<0·0001). By contrast, it was higher among never smokers in LICs (18·8 µM) and MICs (11·3 µM) than in HICs (5·0 µM; ANCOVA p=0·0001). INTERPRETATION: The variations in risks from smoking between country income groups are probably related to the higher exposure of tobacco-derived toxicants among smokers in HICs and higher rates of high second-hand smoke exposure among never smokers in MICs and LICs. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Secular Trends in Musculoskeletal Rehabilitation Needs in 191 Countries and Territories From 1990 to 2019.

Importance: It is hard for policy makers and health professionals to develop musculoskeletal rehabilitation strategies because secular trends for musculoskeletal rehabilitation by region and country remain unknown. Objective: To evaluate the secular trends in global musculoskeletal rehabilitation needs by sex, age, region, country, and health condition. Design, Setting, and Participants: This cross-sectional study included data from 191 countries and territories from the World Health Organization Rehabilitation Need Estimator between January 1, 1990, and December 31, 2019. Data analyses were performed from February to May 2021. Main Outcomes and Measures: Prevalence and years lived with disability (YLDs) of musculoskeletal disorders in need of rehabilitation, overall and by sex, age, region, country, and health condition. Trends in rehabilitation needs were evaluated by the estimated annual percentage changes (EAPCs) in age-standardized rates. Pearson correlation analysis was used to examine the associations between EAPCs and the age-standardized rates in 1990. The associations between the age-standardized rates and universal health coverage (UHC) effective coverage index were assessed by fitting a restricted cubic spline in a linear model. Results: From 1990 to 2019, the global number of prevalent cases of musculoskeletal disorders in need of rehabilitation increased from 1060.6 (95% uncertainty interval [UI], 1009.1-1116.4) million to 1713.6 (95% UI, 1632.4-1800.4) million, with a steady increase in the number of YLDs from 93.9 (95% UI, 67.7-123.6) million to 149.0 (95% UI, 107.5-198.6) million. Overall, 55 countries and territories (28.8%) had annual increase in age-standardized prevalence rates, and 18 countries and territories (9.4%) had annual increase in YLD rates. The global age-standardized prevalence and YLD rates of musculoskeletal disorders decreased annually with EAPCs of 0.34 (95% CI, -0.37 to -0.31) and 0.42 (95% CI, -0.51 to -0.32), respectively. Specifically, the global age-standardized prevalence and YLD rates decreased for low back pain (prevalence: EAPC, -0.52; 95% CI, -0.57 to -0.47; YLD: EAPC, -0.52; 95% CI, -0.66 to -0.37), fractures (prevalence: EAPC, -0.35; 95% CI, -0.41 to -0.30; YLD: EAPC, -0.42; 95% CI, -0.65 to -0.19), other injuries (prevalence: EAPC, -0.75; 95% CI, -0.82 to -0.68; YLD: EAPC, -1.04; 95% CI, -1.38 to -0.71), and amputation (prevalence: EAPC, -0.64; 95% CI, -0.73 to -0.55; YLD: EAPC, -1.13; 95% CI, -1.60 to -0.65). The age-standardized prevalence rate decreased for neck pain (EAPC, -0.10; 95% CI, -0.18 to -0.02) but increased for osteoarthritis (EAPC, 0.13; 95% CI, 0.06-0.19) and rheumatoid arthritis (EAPC, 0.37; 95% CI, 0.04-0.70). In contrast, the age-standardized YLD rates remained stable for neck pain (EAPC, -0.09; 95% CI, -0.35 to 0.16), osteoarthritis (EAPC, 0.14; 95% CI, -0.14 to 0.42), and rheumatoid arthritis (EAPC, 0.38; 95% CI, -0.40 to 1.16). The age-standardized prevalence rate of neck pain decreased faster in male individuals, with an EAPC of -0.10 (95% CI, -0.19 to -0.02), while the age-standardized prevalence rate of low back pain decreased faster in female individuals, with an EAPC of -0.55 (95% CI, -0.60 to -0.51). EAPCs were significantly associated with the baseline age-standardized rates (prevalence: ρ = -0.49; P < .001; YLD: ρ = -0.55; P < .001), except for those of neck pain and rheumatoid arthritis. Excess rehabilitation needs were observed in countries with both higher and lower UHC effective coverage indexes (prevalence: ß = 749.04; SE, 288.52; P = .01; YLD: ß = 49.70; SE, 22.89; P = .03). Conclusions and Relevance: In this cross-sectional study, substantial increases in musculoskeletal rehabilitation needs were found across locations, suggesting rehabilitation needs have become a global health concern. Mitigating risk factors, strengthening rehabilitation in primary health care, and allocating sufficient funds are encouraged to satisfy rehabilitation needs.

Understanding breast cancer as a global health concern.

Breast cancer is now the most commonly diagnosed cancer in the world. The most recent global cancer burden figures estimate that there were 2.26 million incident breast cancer cases in 2020 and the disease is the leading cause of cancer mortality in women worldwide. The incidence is strongly correlated with human development, with a large rise in cases anticipated in regions of the world that are currently undergoing economic transformation. Survival, however, is far less favourable in less developed regions. There are a multitude of factors behind disparities in the global survival rates, including delays in diagnosis and lack of access to effective treatment. The World Health Organization's new Global Breast Cancer Initiative was launched this year to address this urgent global health challenge. It aims to improve survival across the world through three pillars: health promotion, timely diagnosis, and comprehensive treatment and supportive care. In this article, we discuss the key challenges of breast cancer care and control in a global context.

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies.

BACKGROUND: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. METHODS: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. FINDINGS: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H2O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p<0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75-0·86]; p<0·0001). INTERPRETATION: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. FUNDING: No funding.

A methodology for identifying high-need, high-cost patient personas for international comparisons.

OBJECTIVE: To establish a methodological approach to compare two high-need, high-cost (HNHC) patient personas internationally. DATA SOURCES: Linked individual-level administrative data from the inpatient and outpatient sectors compiled by the International Collaborative on Costs, Outcomes, and Needs in Care (ICCONIC) across 11 countries: Australia, Canada, England, France, Germany, the Netherlands, New Zealand, Spain, Sweden, Switzerland, and the United States. STUDY DESIGN: We outline a methodological approach to identify HNHC patient types for international comparisons that reflect complex, priority populations defined by the National Academy of Medicine. We define two patient profiles using accessible patient-level datasets linked across different domains of care-hospital care, primary care, outpatient specialty care, post-acute rehabilitative care, long-term care, home-health care, and outpatient drugs. The personas include a frail older adult with a hip fracture with subsequent hip replacement and an older person with complex multimorbidity, including heart failure and diabetes. We demonstrate their comparability by examining the characteristics and clinical diagnoses captured across countries. DATA COLLECTION/EXTRACTION METHODS: Data collected by ICCONIC partners. PRINCIPAL FINDINGS: Across 11 countries, the identification of HNHC patient personas was feasible to examine variations in healthcare utilization, spending, and patient outcomes. The ability of countries to examine linked, individual-level data varied, with the Netherlands, Canada, and Germany able to comprehensively examine care across all seven domains, whereas other countries such as England, Switzerland, and New Zealand were more limited. All countries were able to identify a hip fracture persona and a heart failure persona. Patient characteristics were reassuringly similar across countries. CONCLUSION: Although there are cross-country differences in the availability and structure of data sources, countries had the ability to effectively identify comparable HNHC personas for international study. This work serves as the methodological paper for six accompanying papers examining differences in spending, utilization, and outcomes for these personas across countries.

Effects of covid-19 pandemic on life expectancy and premature mortality in 2020: time series analysis in 37 countries.

OBJECTIVE: To estimate the changes in life expectancy and years of life lost in 2020 associated with the covid-19 pandemic. DESIGN: Time series analysis. SETTING: 37 upper-middle and high income countries or regions with reliable and complete mortality data. PARTICIPANTS: Annual all cause mortality data from the Human Mortality Database for 2005-20, harmonised and disaggregated by age and sex. MAIN OUTCOME MEASURES: Reduction in life expectancy was estimated as the difference between observed and expected life expectancy in 2020 using the Lee-Carter model. Excess years of life lost were estimated as the difference between the observed and expected years of life lost in 2020 using the World Health Organization standard life table. RESULTS: Reduction in life expectancy in men and women was observed in all the countries studied except New Zealand, Taiwan, and Norway, where there was a gain in life expectancy in 2020. No evidence was found of a change in life expectancy in Denmark, Iceland, and South Korea. The highest reduction in life expectancy was observed in Russia (men: -2.33, 95% confidence interval -2.50 to -2.17; women: -2.14, -2.25 to -2.03), the United States (men: -2.27, -2.39 to -2.15; women: -1.61, -1.70 to -1.51), Bulgaria (men: -1.96, -2.11 to -1.81; women: -1.37, -1.74 to -1.01), Lithuania (men: -1.83, -2.07 to -1.59; women: -1.21, -1.36 to -1.05), Chile (men: -1.64, -1.97 to -1.32; women: -0.88, -1.28 to -0.50), and Spain (men: -1.35, -1.53 to -1.18; women: -1.13, -1.37 to -0.90). Years of life lost in 2020 were higher than expected in all countries except Taiwan, New Zealand, Norway, Iceland, Denmark, and South Korea. In the remaining 31 countries, more than 222 million years of life were lost in 2020, which is 28.1 million (95% confidence interval 26.8m to 29.5m) years of life lost more than expected (17.3 million (16.8m to 17.8m) in men and 10.8 million (10.4m to 11.3m) in women). The highest excess years of life lost per 100 000 population were observed in Bulgaria (men: 7260, 95% confidence interval 6820 to 7710; women: 3730, 2740 to 4730), Russia (men: 7020, 6550 to 7480; women: 4760, 4530 to 4990), Lithuania (men: 5430, 4750 to 6070; women: 2640, 2310 to 2980), the US (men: 4350, 4170 to 4530; women: 2430, 2320 to 2550), Poland (men: 3830, 3540 to 4120; women: 1830, 1630 to 2040), and Hungary (men: 2770, 2490 to 3040; women: 1920, 1590 to 2240). The excess years of life lost were relatively low in people younger than 65 years, except in Russia, Bulgaria, Lithuania, and the US where the excess years of life lost was >2000 per 100 000. CONCLUSION: More than 28 million excess years of life were lost in 2020 in 31 countries, with a higher rate in men than women. Excess years of life lost associated with the covid-19 pandemic in 2020 were more than five times higher than those associated with the seasonal influenza epidemic in 2015.

Variations in disease burden of laryngeal cancer attributable to alcohol use and smoking in 204 countries or territories, 1990-2019.

BACKGROUND: Alcohol consumption and smoking are the leading risk factors for laryngeal cancer (LC). Understanding the variations in disease burden of LC attributable to alcohol use and smoking is critical for LC prevention. METHODS: Disease burden data of LC were retrieved from the Global Burden of Disease Study 2019. We used estimated average percentage change (EAPC) to measure the temporal trends of the age-standardized mortality rate (ASMR) of LC. RESULTS: Globally, while the ASMR of LC decreased by 1.49% (95% CI, 1.41-1.57%) per year between 1990 and 2019, the number of deaths from LC has increased 41.0% to 123.4 thousand in 2019. In 2019, 19.4 and 63.5% of total LC-related deaths were attributable to alcohol use and smoking worldwide, respectively. The ASMR of alcohol- and smoking-related LC decreased by 1.78 and 1.93% per year, whereas the corresponding death number has increased 29.2 and 25.1% during this period, respectively. The decreasing trend was more pronounced in developed countries. In some developing countries, such as Guinea and Mongolia, the LC mortality has shown an unfavorable trend. CONCLUSION: The ubiquitous decrease in LC mortality was largely attributed to the smoking control and highlighted the importance of smoking control policies. However, the disease burden of LC remained in increase and more effective strategies are needed to combat the global increase of alcohol consumption.

The mechanism between mortality, population growth and ageing of the population in the European lower and upper middle income countries.

This paper analyses the effect of mortality rates (under-five and adult mortality) and population growth on the population ageing in a pooled sample of nine lower and upper middle European countries. Therefore, the main goal of this research is to investigate the ageing process of the population in the context of mortality mechanisms (under five and adult mortality) and of population growth in nine European LUMIs. The analysis is implemented in terms of Pooled least squares with cross-section fixed effects methodology. The novelty used within this research is White two-way cluster standard errors & covariance. This study is based on a database from the World Bank and UN covering the period 1995-2019. The expected results are making available quantitative analysis and insights in the context of mechanisms between the ageing process of population, mortality and population growth across these European LUMIs. Results are consistent with the notion that the increasing ageing process within these countries may be a consequence of the negative impact of population growth and from the influence of adult mortality for both sexes. The research results confirm the presence of solid ties of the mechanism between mortality, population growth and population ageing. Therefore, a clear point was provided that mortality acceleration will depend primarily on the level of population growth.

Applicability of the GAIA Maternal and Neonatal Outcome Case Definitions for the Evaluation of Adverse Events Following Vaccination in Pregnancy in High-income Countries.

BACKGROUND: The Brighton Collaboration Global Alignment of Immunization Safety in Pregnancy (GAIA) project developed case definitions for the assessment of adverse events in mothers and infants following maternal immunization. This study evaluated the applicability of these definitions to data collected in routine clinical care and research trial records across 7 sites in high-resource settings. METHODS: Data collection forms were designed and used to retrospectively abstract the key elements of the GAIA definitions from records for 5 neonatal and 5 maternal outcomes, as well as gestational age. Level of diagnostic certainty was assessed by the data abstractor and an independent clinician, and then verified by Automated Brighton Case logic. The ability to assign a level of diagnostic certainty for each outcome and the positive predictive value (PPV) for their respective ICD-10 codes were evaluated. RESULTS: Data from 1248 case records were abstracted: 624 neonatal and 622 maternal. Neonatal outcomes were most likely to be assessable and assigned by the level of diagnostic certainty. PPV for preterm birth, low birth weight, small for gestational age and respiratory distress were all above 75%. Maternal outcomes for preeclampsia and fetal growth restriction showed PPV over 80%. However, microcephaly (neonatal outcome) and dysfunctional labor (maternal outcome) were often nonassessable, with low PPVs. CONCLUSIONS: The applicability of GAIA case definitions to retrospectively ascertain and classify maternal and neonatal outcomes was variable among sites in high-resource settings. The implementation of the case definitions is largely dependent on the type and quality of documentation in clinical and research records in both high- and low-resource settings. While designed for use in the prospective evaluation of maternal vaccine safety, the GAIA case definitions would likely need to be specifically adapted for observational studies using alternative sources of data, linking various data sources and allowing flexibility in the ascertainment of the elements and levels of certainty of the case definition.

Economic convergence in a globalized world: The role of business cycle synchronization.

Increasing economic integration and global synchronization can be key for countries aiming to catch up in GDP per capita terms. Little attention has hitherto been placed in synchronization as determinant of convergence. In this paper we estimate the effect of economic globalization and synchronization on income convergence for a sample of 89 developed and developing countries in the period 1970-2015. We use a dynamic factor model and panel data techniques to undertake the objectives of the paper. We show that synchronized countries (those correlated with the factor) exhibit a higher response on GDP per capita growth with variations on the global business cycle. This implies that synchronization improves growth for that group in global expansionary phases, but also implies risks during global recessions. On the contrary, the effect on growth of an economic globalization index is less relevant for synchronized countries than for asynchronized countries. The latter result implies that asynchronized countries can benefit more increasing their levels of economic globalization.

Large Pediatric Randomized Clinical Trials in ClinicalTrials.gov.

BACKGROUND: Large, randomized controlled trials (RCTs) are essential in answering pivotal questions in child health. METHODS: We created a bird's eye view of all large, noncluster, nonvaccine pediatric RCTs with ≥1000 participants registered in ClinicalTrials.gov (last search January 9, 2020). We analyzed the funding sources, countries, outcomes, publication status, and correlation with the pediatric global burden of disease (GBD) for eligible trials. RESULTS: We identified 247 large, nonvaccine, noncluster pediatric RCTs. Only 17 mega-trials with ≥5000 participants existed. Industry funding was involved in only 52 (21%) and exclusively funded 47 (19%) trials. Participants were from high-income countries (HICs) in 100 (40%) trials, from lower-middle-income countries (LMICs) in 122 (49%) trials, and from both HICs and LMICs in 19 (8%) trials; 6 trials did not report participants' country location. Of trials conducted in LMIC, 43% of investigators were from HICs. Of non-LMIC participants trials (HIC or HIC and LMIC), 39% were multicountry trials versus 11% of exclusively LMIC participants trials. Few trials (18%; 44 of 247) targeted mortality as an outcome. 35% (58 of 164) of the trials completed ≥12 months were unpublished at the time of our assessment. The number of trials per disease category correlated well with pediatric GBD overall (ρ = 0.76) and in LMICs (ρ = 0.69), but not in HICs (ρ = 0.29). CONCLUSIONS: Incentivization of investigator collaborations across diverse country settings, timely publication of results of large pediatric RCTs, and alignment with the pediatric GBD are of pivotal importance to ultimately improve child health globally.