Question: what are the mortality rates overall and in specific populations

Title: Estimating Lower Bounds for COVID-19 Mortality from Northern Italian Towns Content: For COVID-19 the Infection Fatality Rate or IFR - a crucial variable in epidemiological modeling - is difficult to estimate because many cases are asymptomatic and the overall infection rate is generally not known. Circumstances in the Italian provinces of Milano, Bergamo, Brescia, and Lodi allow estimation of lower bounds for age- and sex-specific all-cause excess mortality (a proxy for IFR) since anecdotal reports indicate some towns were close to fully infected. Using data from ISTAT on mortality from January 1 through April 15 for 2020 and the three preceding years, I estimate excess mortality by sex and age categories (0-14, 15-54, 55-64, 65-74, and 75+ years) while controlling for town-specific mortality that proxies for town-specific infection rate. The 99th percentile from the tail of the town distribution gives a lower-bound estimate for COVID-19 mortality. The overall population-weighted mortality at the 99th percentile is 1.09 percent (95% CI 1.06-1.14). The age- and sex-specific rates vary considerably: for men age 65-74 the estimate is 2.10 percent (95% CI 1.94-2.28) which is 3.5-times higher than men 55-64 and 2.7-times higher than women 65-74.

Title: Analysis of Austrian COVID-19 deaths by age and sex Content: We analyze the age and sex distribution of the reported COVID-19 deaths in Austria. In accordance with international studies, the Austrian data also suggests that the risk of death increases substantially with age. The observed age dependency of the proportions of registered COVID-19 deaths in relation to the population sizes in the age groups is approximately exponential, similar to the age dependency of the general age specific mortality rate. Furthermore, we compare the general age specific mortality rate in Austria with the estimates of the SARS-CoV‑2 infection fatality rate by Ferguson et al. (2020). The parallels to the general age specific mortality rates do not imply that COVID-19 does not pose an additional risk. On the contrary, it follows from the structure and magnitude of the infection fatality rate that it is substantial, especially for higher age groups. However, since in many cases persons with severe pre-existing conditions are affected, it is not yet possible to estimate what effects COVID-19 will have on life expectancy.

Title: Analysis of Austrian COVID-19 deaths by age and sex Content: We analyze the age and sex distribution of the reported COVID-19 deaths in Austria. In accordance with international studies, the Austrian data also suggests that the risk of death increases substantially with age. The observed age dependency of the proportions of registered COVID-19 deaths in relation to the population sizes in the age groups is approximately exponential, similar to the age dependency of the general age specific mortality rate. Furthermore, we compare the general age specific mortality rate in Austria with the estimates of the SARS-CoV2 infection fatality rate by Ferguson et al. (2020). The parallels to the general age specific mortality rates do not imply that COVID-19 does not pose an additional risk. On the contrary, it follows from the structure and magnitude of the infection fatality rate that it is substantial, especially for higher age groups. However, since in many cases persons with severe pre-existing conditions are affected, it is not yet possible to estimate what effects COVID-19 will have on life expectancy.

Title: Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970-2016: a systematic analysis for the Global Burden of Disease Study 2016. Content: BACKGROUND Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. METHODS We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15-60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0·5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Socio-demographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. FINDINGS Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5-24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates-a measure of relative inequality-increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86·9 years (95% UI 86·7-87·2), and for men in Singapore, at 81·3 years (78·8-83·7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, and the gap between male and female life expectancy increased with progression to higher levels of SDI. Some countries with exceptional health performance in 1990 in terms of the difference in observed to expected life expectancy at birth had slower progress on the same measure in 2016. INTERPRETATION Globally, mortality rates have decreased across all age groups over the past five decades, with the largest improvements occurring among children younger than 5 years. However, at the national level, considerable heterogeneity remains in terms of both level and rate of changes in age-specific mortality; increases in mortality for certain age groups occurred in some locations. We found evidence that the absolute gap between countries in age-specific death rates has declined, although the relative gap for some age-sex groups increased. Countries that now lead in terms of having higher observed life expectancy than that expected on the basis of development alone, or locations that have either increased this advantage or rapidly decreased the deficit from expected levels, could provide insight into the means to accelerate progress in nations where progress has stalled. FUNDING Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health.

Title: EXCESS MORTALITY FROM COVID-19. WEEKLY EXCESS DEATH RATES BY AGE AND SEX FOR SWEDEN. Content: Objectives: Mortality from Covid-19 is monitored in detail both within as well as between countries with different strategies against the virus. However, death counts and relative risks based on crude numbers can be misleading. Instead, age specific death rates should be used for comparability. Given the difficulty of ascertainment of Covid-19 specific deaths, excess all-cause mortality is currently more appropriate for comparisons. By estimating age- and sex-specific death rates we aim to get more accurate estimates of the excess mortality attributed to Covid-19, as well as the difference between men and women in Sweden. Design: We make use of Swedish register data about total weekly deaths, total population at risk, and estimate age- and sex-specific weekly death rates for 2020 and the 5 previous years. The data is provided by Statistics Sweden. Results: From the first week of April and onwards, the death rates at all ages above 60 are higher than those in previous years in Sweden. Persons above age 80 are dis-proportionally more affected, and men suffer higher levels of excess mortality than women at all ages with 75% higher death rates for males and 50% higher for females. Current excess mortality corresponds to a decline in remaining life expectancy of 3 years for men and 2 years for women. Conclusion: The Covid-19 pandemic has so far had a clear and consistent effect on total mortality in Sweden, with male death rates being comparably more affected. What consequences the pandemic will eventually have on mortality and life expectancy will depend on the progression of the pandemic, the extent that some of the deaths would have occurred in the absence of the pandemic, only somewhat later, the consequences for other health conditions, as well as the health care sector at large.

Title: Global Mortality Impact of the 1957–1959 Influenza Pandemic Content: Background. Quantitative estimates of the global burden of the 1957 influenza pandemic are lacking. Here we fill this gap by modeling historical mortality statistics. Methods. We used annual rates of age- and cause-specific deaths to estimate pandemic-related mortality in excess of background levels in 39 countries in Europe, the Asia-Pacific region, and the Americas. We modeled the relationship between excess mortality and development indicators to extrapolate the global burden of the pandemic. Results. The pandemic-associated excess respiratory mortality rate was 1.9/10 000 population (95% confidence interval [CI], 1.2–2.6 cases/10 000 population) on average during 1957–1959. Excess mortality rates varied 70-fold across countries; Europe and Latin America experienced the lowest and highest rates, respectively. Excess mortality was delayed by 1–2 years in 18 countries (46%). Increases in the mortality rate relative to baseline were greatest in school-aged children and young adults, with no evidence that elderly population was spared from excess mortality. Development indicators were moderate predictors of excess mortality, explaining 35%–77% of the variance. Overall, we attribute 1.1 million excess deaths (95% CI, .7 million–1.5 million excess deaths) globally to the 1957–1959 pandemic. Conclusions. The global mortality rate of the 1957–1959 influenza pandemic was moderate relative to that of the 1918 pandemic but was approximately 10-fold greater than that of the 2009 pandemic. The impact of the pandemic on mortality was delayed in several countries, pointing to a window of opportunity for vaccination in a future pandemic.

Title: Mortality of Life‐Insured Swedish Cats during 1999–2006: Age, Breed, Sex, and Diagnosis Content: Background: A cat life insurance database can potentially be used to study feline mortality. Hypothesis: The aim was to describe patterns of mortality in life‐insured Swedish cats. Cats: All cats (<13 years of age) with life insurance during the period 1999–2006 were included. Methods: Age‐standardized mortality rates (MR) were calculated with respect to sex (males and females), age, breed, and diagnosis. Survival to various ages is presented by time period and breed. Results: The total number of cats insured was 49,450 and the number of cat‐years at risk (CYAR) was 142,049. During the period, 6,491 cats died and of these 4,591 cats (71%) had a diagnosis, ie, were claimed for life insurance. The average annual MR was 462 deaths per 10,000 CYAR (95% confidence interval, 431–493). Sex‐specific rates did not differ significantly. The overall mortality of the Persian and the Siamese groups was higher than that of several other breeds. Overall and breed‐specific (for most breeds) survival increased with time when analyzed by 2‐year periods. The 6 most common diagnostic categories (ignoring cats recorded as dead with no diagnosis) were urinary, traumatic, neoplastic, infectious, cardiovascular, and gastrointestinal. The MR within diagnostic categories varied by age and breed. Conclusions and Clinical Importance: In this mainly purebred, insured cat population, the overall mortality varied with age and breed but not with sex. The increase in survival over time is likely a reflection of willingness to keep pet cats longer and increased access to and sophistication of veterinary care.

Title: Mortality among dentists in Taiwan, 1985–2009 Content: Background/Purpose Controversy exists in the literature regarding whether dentists with multiple occupational exposures suffer from premature mortality. A cohort mortality study was conducted to evaluate the survival outcome and determine if potential exposure to harmful agents leads to premature mortality among dentists. Methods Using the Life Table Analysis System, we calculated standardized mortality ratios (SMRs) for a cohort of 11,700 dentists affiliated with the Taiwan Dental Association. These dentists were followed from 1985–2009. Reference rates were derived from cause-, gender-, and age-specific mortality rates of the general population of Taiwan and 18,664 Taiwanese internists, who were considered to be more socioeconomically proximal to dentists. A Cox proportional hazard model was also constructed to determine multiple risk factors associated with mortality. Results Compared with the general population, dentists in Taiwan consistently demonstrated reduced from all-cause mortality. However, compared with internists, significant and excess mortality were observed in dentists for overall mortality (SMR=1.13; 95% confidence interval [CI]=1.00–1.26), drowning (SMR=6.62; 95% CI=2.15–15.45), and heart diseases (SMR=1.66; 95% CI=1.22–2.21). After adjusting for other risk factors, the Cox model showed an increased hazard ratio of 1.17 (95% CI=1.01–1.37) for dentists. Conclusion Taiwanese dentists demonstrated significant elevated SMRs for overall causes, drowning, and heart diseases. Careful precaution should be taken to reduce these trends. Future studies are also needed for in-depth exploration of the mechanisms regarding how professional stress and exposure contribute to the increased risk of mortality in Taiwanese dentists.

Title: Explaining the Neolithic Demographic Transition Content: Three main questions are raised in this chapter. 1. The part of the signal of the NDT which is demographically identifiable, based on the proportion of the immature skeletons in cemeteries, shows that a baby-boom occurred and, beyond that, with the onset of the change in the economic system, a fertility transition towards high values also occurred. What was the biodemographic cause of this fertility explosion, beyond the proxy variable represented by sedentarism? The cause is a major shift in the maternal energetics of farming communities relative to mobile foragers. In the energy balance there was (i) on the intake side, an underlying trend towards a reduction in low-calorie food from hunting and fishing, and a correlative increase in high-calorie food from agriculture, (ii) on the expenditure side, a reduction in the physical energy devoted to mobility and the maternal stress of child transportation. 2. The NDT is detectable from a signal representing a fertility transition, but the transition relating to mortality is missing and must be inferred. If, during the fertility transition, mortality had remained the same as in the preceding forager period, then the population would have grown infinitely. The assumption of unchanged mortality during the entire fertility transition is therefore not realistic. Mortality, in its turn, must have begun to rise well before the end of the fertility transition. But when? Why? One of the answers consists of a model where, except at the start of the process, birth and mortality rates rise more or less simultaneously, bringing about a typical rate of increase for pre-industrial populations of slightly above zero. 3. According to the level and speed of the population growth, what should we expect in terms of population structure? What are the expected effects of this growth, not only on the population in numbers but also on age distribution, the distribution and structure of families, the distribution of households and on family systems?

Title: Belgian Covid-19 Mortality, Excess Deaths, Number of Deaths per Million, and Infection Fatality Rates (8 March - 9 May 2020) Content: Objective. Scrutiny of COVID-19 mortality in Belgium over the period 8 March-9 May 2020 (Weeks 11-19), using number of deaths per million, infection fatality rates, and the relation between COVID-19 mortality and excess death rates. Data. Publicly available COVID-19 mortality (2020); overall mortality (2009-2020) data in Belgium and demographic data on the Belgian population; data on the nursing home population; results of repeated sero-prevalence surveys in March-April 2020. Statistical methods. Reweighing, missing-data handling, rate estimation, visualization. Results. Belgium has virtually no discrepancy between COVID-19 reported mortality (confirmed and possible cases) and excess mortality. There is a sharp excess death peak over the study period; the total number of excess deaths makes April 2020 the deadliest month of April since WWII, with excess deaths far larger than in early 2017 or 2018, even though influenza-induced January 1951 and February 1960 number of excess deaths were similar in magnitude. Using various sero-prevalence estimates, infection fatality rates (IFRs; fraction of deaths among infected cases) are estimated at 0.38-0.73% for males and 0.20-0.39% for females in the non-nursing home population (non-NHP), and at 0.79-1.52% for males and 0.88-1.31% for females in the entire population. Estimates for the NHP range from 38 to 73% for males and over 22 to 37% for females. The IFRs rise from nearly 0% under 45 years, to 4.3% and 13.2% for males in the non-NHP and the general population, respectively, and to 1.5% and 11.1% for females in the non-NHP and general population, respectively. The IFR and number of deaths per million is strongly influenced by extensive reporting and the fact that 66.0% of the deaths concerned NH residents. At 764 (our re-estimation of the figure 735, presented by "Our World in Data"), the number of COVID-19 deaths per million led the international ranking on May 9, 2020, but drops to 262 in the non-NHP. The NHP is very specific: age-related increased risk; highly prevalent comorbidities that, while non-fatal in themselves, exacerbate COVID-19; larger collective households that share inadvertent vectors such as caregivers and favor clustered outbreaks; initial lack of protective equipment, etc. High-quality health care countries have a relatively older but also more frail population [1], which is likely to contribute to this result.

Title: The confounded crude case-fatality rates for COVID-19 hide more than they reveal - a comparison of age-specific and age-adjusted rates between six countries Content: Background The reported crude case-fatality rates (CFRs) vary widely between countries. The serious limitations of using crude rates for comparisons are sometimes overlooked. In this paper we examined to what extent the age distribution of the cases is responsible for the differences in CFRs between countries. Methods Data on COVID-19 were extracted from the reports of individual countries. Overall and age-specific CFRs were available for six countries. The CFRs by country were adjusted for age using the direct method, using the combined age-specific number of cases of all six countries as the standard population. Findings The age distribution of the cases varied widely between countries. The crude CFRs varied between 1.6% and 11%. The differences in the age-specific CFRs were much smaller and the age-adjusted rates were much closer than the crude rates. The ratio of the crude CFR for the country with the highest to that with the lowest, was reduced substantially from 7.4 to 2.3 for the age-adjusted rates. Conclusions The age structure of the cases dramatically impacts on the differences in the crude CFRs between countries. Adjusting for age substantially reduces this variation. Other factors such as the differences in the definition of the denominators, the definition of a case and the standard of healthcare are likely to account for much of the residual variation. It is misleading to compare the crude COVID-19 CFRs between countries and should be avoided. Comparisons should be based on age-specific and age-adjusted rates. Key words: COVID-19, case-fatality rates, age-specific rates, age-adjusted rates, confounding

Title: The COVID-19 mortality effects of underlying health conditions in India: a modelling study Content: Objective: To model how known COVID-19 comorbidities will affect mortality rates and the age distribution of mortality in a large lower middle income country (India), as compared with a high income country (England), and to identify which health conditions drive any differences. Design: Modelling study. Setting: England and India. Participants: 1,375,548 respondents aged 18 to 99 to the District Level Household Survey-4 and Annual Health Survey in India. Additional information on health condition prevalence on individuals aged 18 to 99 was obtained from the Health Survey for England and the Global Burden of Diseases, Risk Factors, and Injuries Studies (GBD). Main outcome measures: The primary outcome was the proportional increase in age-specific mortality in each country due to the prevalence of each COVID-19 mortality risk factor (diabetes, hypertension, obesity, chronic heart disease, respiratory illness, kidney disease, liver disease, and cancer, among others). The combined change in overall mortality and the share of deaths under 60 from the combination of risk factors was estimated in each country. Results: Relative to England, Indians have higher rates of diabetes (10.6% vs. 8.5%), chronic respiratory disease (4.8% vs. 2.5%), and kidney disease (9.7% vs. 5.6%), and lower rates of obesity (4.4% vs. 27.9%), chronic heart disease (4.4% vs. 5.9%), and cancer (0.3% vs. 2.8%). Population COVID-19 mortality in India relative to England is most increased by diabetes (+5.4%) and chronic respiratory disease (+2.3%), and most reduced by obesity (-9.7%), cancer (-3.2%), and chronic heart disease (-1.9%). Overall, comorbidities lower mortality in India relative to England by 9.7%. Accounting for demographics and population health explains a third of the difference in share of deaths under age 60 between the two countries. Conclusions: Known COVID-19 health risk factors are not expected to have a large effect on aggregate mortality or its age distribution in India relative to England. The high share of COVID-19 deaths from people under 60 in low- and middle-income countries (LMICs) remains unexplained. Understanding mortality risk associated with health conditions prevalent in LMICs, such as malnutrition and HIV/AIDS, is essential for understanding differential mortality. Keywords: COVID-19, India, low- and middle-income countries, comorbidity

Title: Human agency and infection rates: implications for social distancing during epidemics Content: Social distancing is an important measure in controlling epidemics. This paper presents a simple theoretical model focussed on the implications of the wide range in interaction rates between individuals, both within the workplace and in the social setting. The model is based on well-mixed populations and so is not intended for studying geographic spread. The model shows that epidemic growth rate is largely determined by the upper interactivity quantiles of society, implying that the most efficient methods of epidemic control are interaction capping approaches rather than overall reductions in interaction. The theoretical model can also be applied to look at the dynamics of epidemic progression under various scenarios. The theoretical model suggests that with no intervention herd immunity would be achieved with a lower overall infection rate than if variation in interaction rate is ignored, because by this stage almost all the most interactive members of society would have had the infection; however the overall mortality with such an approach is very high. Scenarios for mitigation and suppression suggest that, by using interactivity capping, it should be possible to control an epidemic without extreme sanctions on the majority of the population if R0 of the uncontrolled infection is 2.4. However to control the infection rate to a specific level will always require the switching on and off of measures and for this reason eradication is likely to be a less costly policy in the long run. While social distancing alone can be used for eradication it is not be a good mechanism on its own to prevent reinfection. The use of robust testing, quarantining, and contact tracing would strengthen any social distancing measures, speed up eradication, and be a better tool for prevention of infection or reinfection.

Title: The Contribution of Age Structure to the Number of Deaths from Covid-19 in the UK by Geographical Units Content: This study investigates the contribution of population age structure to mortality from Covid-19 in the UK by geographical units. We project death rates at various spatial scales by applying data on age-specific fatality rates to the area's population by age and sex. Our analysis shows a significant variation in the projected death rates between the constituent countries of the UK, between its regions and within regions. First, Scotland and Wales have higher projected fatality levels from Covid-19 than England, whereas Northern Ireland has lower rate. Second, the infection fatality rates are projected to be substantially higher in small towns and rural areas than those in large urban areas. Third, our analysis shows that within urban regions there are also 'pockets' of high projected death rates. Overall, the areas with high and low fatality rates tend to cluster because of the high residential separation of different population age-groups in the UK. Our analysis also reveals that the Welsh-, Gaelic- and Cornish-speaking communities with relatively old populations are likely to experience heavy population losses if the virus spreads widely across the UK.

Title: Behavioural responses to influenza pandemics: what do we know? Content: The emergence of the novel A/H1N1 virus has made pandemic preparedness a crucial issue for public health worldwide. Although the epidemiological aspects of the three 20th century influenza pandemics have been widely investigated, little is known about population behaviour in a pandemic situation. Such knowledge is however critical, notably for predicting population compliance with non pharmaceutical interventions. This paper reviews the relevant scientific literature for the 1918-1920, 1957-1958, 1969-1969 influenza epidemics and the 2003 SARS outbreak. Although the evidence base of most non pharmaceutical interventions (NPIs) and personal protection measures is debated, it appears on the basis of past experience that NPIs implemented the most systematically, the earliest, and for the longest time could reduce overall mortality rates and spread out epidemic peaks. Adequate, transparent, and targeted communication on the part of public health authorities would be also of crucial importance in the event of a serious influenza pandemic.

Title: Viet Nam. Content: Attention in this discussion of Viet Nam focuses on the following: history of the demographic situation; the government's overall approach to population problems; population data systems and development planning; institutional arangements for the integration of population within development planning; the government's view of the importance of population policy in achieving development objectives; population size, growth, and natural increase; morbidity and mortality; fertility; international migration; and spatial distribution. Relatively little information has been available on demographic trends in Viet Nam due to the absence of any major survey or census until the last few decades. The government increasingly has been concerned about the high rate of population growth and is working to change the situation through programs directed at fertility reduction. As part of its program for overall social and economic restructuring, the government seeks to give special attention to health problems, particularly those relating to maternal and child health and environmental sanitation. Population censuses in Viet Nam have been undertaken only in the last 2 decades, with censuses conducted in the North in 1960 and 1974. No population census was undertaken in the South, and any population information available was based upon the periodic population and household surveys conducted alternately in different provinces, cities, and rural areas during 1962, 1967, 1971, and 1974. The government considers the formulation and implementation of population policy to be a critical variable for realizing national development objectives. The population of Viet Nam has grown considerably since the 1950s, increasing from over 30 million in 1950 to 35.4 million in 1960 and reaching 43.1 million by 1970, according to UN estimates. 1979 census results indicate that the population of Viet Nam had reached 52.7 million. The current rate of growth is estimated at 2.2%. The government perceives the current rate of population growth as unsatisfactory because it is too high. The official government policy is to take steps to reduce the rate of population growth as rapidly as possible. All 3 demographic factors--mortality, fertility, and spatial distribution--are viewed as subject to direct policy intervention to achieve this goal. Rates of morbidity and mortality have declined considerably in the past few decades. The government reports a decline in the crude death rate from 12.2 in 1957 to 7.0 in 1980 and an increase in the life expectancy at birth from 34 years in 1936 to 60 in 1978. UN estimates are considerably higher. According to UN estimates, the infant mortality rate was 90.3/1000 live births during 1975-80 for Viet Nam as a whole. The current mortality and morbidity situation is considered to be unacceptable. The government estimates the crude birthrate as 29.3/1000 in 1980, an unsatisfactory level. The government perceives the present levels and trends of immigration as not significant and satisfactory and the spatial distribution as inappropriate.

Title: Is investing in religious institutions a viable pathway to reduce mortality in the population? Content: There is established and consistent findings from epidemiologic studies, among individuals, that religion— broadly assessed through frequency of attending worship services—is associated with lower all-cause and cause-specific mortality attributed to suicide, alcohol, cardiovascular disease and cancer. Religious norms, social support, character, virtue, compassion, love, generosity, and religious community are among some mechanisms purported to explain lower mortality, on aggregate. The religious ecology or characteristics of religion within an area or geographic level (e.g., county, ZIP-code, country), has been linked with overall and cause-specific mortality, but directions of findings are mixed. Mechanisms to explain the links between the religious ecology and mortality included social integration, civic engagement, and social control. The manuscript (SSM-D-19-03928R2) adds a fresh and timely perspective by investigating another mechanism: investment in local healthcare spending. The study found some support of an indirect association from county-level religious denominational composition, through investments in health spending, on Black and White all-cause mortality rates. Should society or government invest finances in religious institutions to indirectly improve population health? This work adds evidence to debate that question. Future work on the topic will need to address several conceptual and methodological challenges. Conceptually, is investigating the market share of religious denominations (i.e., % Catholics vs % Protestants) relevant today given diversity in population and declining trends of worship attendance? Is mortality the most relevant for moving policy or should the focus be on well-being? Methodologically, are there alternate observable measures religious investments/spending in the local economy? Mechanisms, challenges, and opportunities for social epidemiology research on this topic are discussed.

Title: Male mortality and the German response: lessons from COVID‐19 Content: The current COVID‐19 outbreak has raised many questions, amongst them the higher mortality rates in men and the low overall mortality rates in Germany compared to other European countries. Here the authors explore some of the reasons behind both these phenomena and outline what we can learn from them for the future.

Title: Determinants of COVID-19 incidence and mortality: A cross-country analysis Content: Objective: We undertook this study to explore the role of important determinants affecting global COVID-19 incidence and mortality taking multifactorial disease dynamics into consideration. Design: Secondary data as on March 28, 2020 were obtained for 97 countries. Association of COVID-19 cumulative incidence and mortality measures were assessed with ten indictors representing health system characteristics, climate, demography, promptness of international travel restriction and population movement using Generalized Linear Modelling. Main outcome measures: Country-specific COVID-19 cumulative incidence, cumulative cause-specific mortality and case fatality rate. Results: Significant inter-country variation in incidence and mortality rates were observed. Five variables were found to be associated with cumulative incidence: testing rate per 1000 population ({beta} = 0.119, p < 0.01), UHC index ({beta} = 0.043, p = 0.04), percentage elderly population ({beta} = 0.122, p < 0.01), percentage below-poverty line population ({beta} = -0.048, p < 0.01) and disability adjusted life years due to NCDs ({beta} = -0.013, p < 0.01). Case fatality rate was observed to be associated with testing rate per 1000 population ({beta} = -0.058, p = 0.03) and population density ({beta} = 0.002, p = 0.02), while the cumulative cause-specific mortality was associated with only percentage elderly population ({beta} = 0.096, p = 0.04) in the country. Conclusions: Health system response, population susceptibility and demography were the most important factors determining the progression. Policy response should focus towards increasing testing, primarily targeting high population density areas. Health system strengthening and reduction in population risk factors should be long term goals for a better response to such epidemics.

Title: Population-level COVID-19 mortality risk for non-elderly individuals overall and for non-elderly individuals without underlying diseases in pandemic epicenters Content: OBJECTIVE: To provide estimates of the relative rate of COVID-19 death in people <65 years old versus older individuals in the general population, the absolute risk of COVID-19 death at the population level during the first epidemic wave, and the proportion of COVID-19 deaths in non-elderly people without underlying diseases in epicenters of the pandemic. ELIGIBLE DATA: Cross-sectional survey of countries and US states with at least 800 COVID-19 deaths as of April 24, 2020 and with information on the number of deaths in people with age <65. Data were available for 14 countries (Belgium, Canada, France, Germany, India, Ireland, Italy, Mexico, Netherlands, Portugal, Spain, Sweden, Switzerland, UK) and 13 US states (California, Connecticut, Florida, Georgia, Illinois, Indiana, Louisiana, Maryland, Massachusetts, Michigan, New Jersey, New York, Pennsylvania). We also examined available data on COVID-19 deaths in people with age <65 and no underlying diseases. MAIN OUTCOME MEASURES: Proportion of COVID-19 deaths in people <65 years old; relative mortality rate of COVID-19 death in people <65 versus ≥65 years old; absolute risk of COVID-19 death in people <65 and in those ≥80 years old in the general population as of June 17, 2020; absolute COVID-19 mortality rate expressed as equivalent of mortality rate from driving a motor vehicle. RESULTS: Individuals with age <65 account for 4.5–11.2% of all COVID-19 deaths in European countries and Canada, 8.3–22.7% in the US locations, and were the majority in India and Mexico. People <65 years old had 30- to 100-fold lower risk of COVID-19 death than those ≥65 years old in 11 European countries and Canada, 16- to 52-fold lower risk in US locations, and less than 10-fold in India and Mexico. The absolute risk of COVID-19 death as of June 17, 2020 for people <65 years old in high-income countries ranged from 10 (Germany) to 349 per million (New Jersey) and it was 5 per million in India and 96 per million in Mexico. The absolute risk of COVID-19 death for people ≥80 years old ranged from 0.6 (Florida) to 17.5 per thousand (Connecticut). The COVID-19 mortality rate in people <65 years old during the period of fatalities from the epidemic was equivalent to the mortality rate from driving between 4 and 82 miles per day for 13 countries and 5 states, and was higher (equivalent to the mortality rate from driving 106–483 miles per day) for 8 other states and the UK. People <65 years old without underlying predisposing conditions accounted for only 0.7–3.6% of all COVID-19 deaths in France, Italy, Netherlands, Sweden, Georgia, and New York City and 17.7% in Mexico. CONCLUSIONS: People <65 years old have very small risks of COVID-19 death even in pandemic epicenters and deaths for people <65 years without underlying predisposing conditions are remarkably uncommon. Strategies focusing specifically on protecting high-risk elderly individuals should be considered in managing the pandemic.

Title: Pediatrician, watch out for corona-phobia Content: The current outbreak of COVID-19 raging globally is taking a heavy toll on the adult population, with a rapidly growing number of newly infected and critically ill patients. However, to date, mortality rate among children is low as they mostly suffer from a mild disease. Yet, other more routinely encountered childhood diseases do not stand still and continue to be the main share of pediatricians’ everyday challenges. Here we describe a case series of routinely seen pediatric diseases with delayed diagnosis due to different aspects of what we call “Corona-phobia”. These cases were easily collected within a 1-week period which implies that this is a more widespread phenomenon. In conclusion, this raises the possibility that measures taken to mitigate this pandemic may be more damaging to children overall than the virus itself. We believe that pediatricians as well as policy makers should take this important aspect into consideration.

Title: When half of the population died: the epidemic of hemorrhagic fevers of 1576 in Mexico Content: During the 16th century, Mexico suffered a demographic catastrophe with few parallels in world's history. In 1519, the year of the arrival of the Spaniards, the population in Mexico was estimated to be between 15 and 30 million inhabitants. Eighty-one years later, in 1600, only two million remained. Epidemics (smallpox, measles, mumps), together with war, and famine have been considered to be the main causes of this enormous population loss. However, re-evaluation of historical data suggests that approximately 60–70% of the death toll was caused by a series of epidemics of hemorrhagic fevers of unknown origin. In order to estimate the impact of the 1576 epidemic of hemorrhagic fevers on the population we analyzed the historical record and data from the 1570 and 1580 censuses of 157 districts. The results identified several remarkable aspects of this epidemic: First, overall, the population loss for these 157 districts was 51.36%. Second, there was a clear ethnic preference of the disease, the Spanish population was minimally affected whereas native population had high mortality rate. Third, the outbreak originated in the valleys of central Mexico whence it evolved as an expansive wave. Fourth, a positive correlation between altitude and mortality in central Mexico was found. Fifth, a specific climatic sequence of events was associated with the initiation and dissemination of the hemorrhagic fevers. Although the last epidemic of hemorrhagic fevers in Mexico ended in 1815, many questions remain to be answered. Perhaps the most relevant ones are whether there is a possible reemergence of the hemorrhagic fevers and how vulnerable we are to the disease.

Title: Age-Specific Excess Mortality Patterns During the 1918–1920 Influenza Pandemic in Madrid, Spain Content: Although much progress has been made to uncover age-specific mortality patterns of the 1918 influenza pandemic in populations around the world, more studies in different populations are needed to make sense of the heterogeneous death impact of this pandemic. We assessed the absolute and relative magnitudes of 3 pandemic waves in the city of Madrid, Spain, between 1918 and 1920, on the basis of age-specific all-cause and respiratory excess death rates. Excess death rates were estimated using a Serfling model with a parametric bootstrapping approach to calibrate baseline death levels with quantified uncertainty. Excess all-cause and pneumonia and influenza mortality rates were estimated for different pandemic waves and age groups. The youngest and oldest persons experienced the highest excess mortality rates, and young adults faced the highest standardized mortality risk. Waves differed in strength; the peak standardized mortality risk occurred during the herald wave in spring 1918, but the highest excess rates occurred during the fall and winter of 1918/1919. Little evidence was found to support a “W”-shaped, age-specific excess mortality curve. Acquired immunity may have tempered a protracted fall wave, but recrudescent waves following the initial 2 outbreaks heightened the total pandemic mortality impact.

Title: Impact of Political Economy on Population Health: A Systematic Review of Reviews. Content: Background. Although there is a large literature examining the relationship between a wide range of political economy exposures and health outcomes, the extent to which the different aspects of political economy influence health, and through which mechanisms and in what contexts, is only partially understood. The areas in which there are few high-quality studies are also unclear. Objectives. To systematically review the literature describing the impact of political economy on population health. Search Methods. We undertook a systematic review of reviews, searching MEDLINE, Embase, International Bibliography of the Social Sciences, ProQuest Public Health, Sociological Abstracts, Applied Social Sciences Index and Abstracts, EconLit, SocINDEX, Web of Science, and the gray literature via Google Scholar. Selection Criteria. We included studies that were a review of the literature. Relevant exposures were differences or changes in policy, law, or rules; economic conditions; institutions or social structures; or politics, power, or conflict. Relevant outcomes were any overall measure of population health such as self-assessed health, mortality, life expectancy, survival, morbidity, well-being, illness, ill health, and life span. Two authors independently reviewed all citations for relevance. Data Collection and Analysis. We undertook critical appraisal of all included reviews by using modified Assessing the Methodological Quality of Systematic Reviews (AMSTAR) criteria and then synthesized narratively giving greater weight to the higher-quality reviews. Main Results. From 4912 citations, we included 58 reviews. Both the quality of the reviews and the underlying studies within the reviews were variable. Social democratic welfare states, higher public spending, fair trade policies, extensions to compulsory education provision, microfinance initiatives in low-income countries, health and safety policy, improved access to health care, and high-quality affordable housing have positive impacts on population health. Neoliberal restructuring seems to be associated with increased health inequalities and higher income inequality with lower self-rated health and higher mortality. Authors' Conclusions. Politics, economics, and public policy are important determinants of population health. Countries with social democratic regimes, higher public spending, and lower income inequalities have populations with better health. There are substantial gaps in the synthesized evidence on the relationship between political economy and health, and there is a need for higher-quality reviews and empirical studies in this area. However, there is sufficient evidence in this review, if applied through policy and practice, to have marked beneficial health impacts. Public Health Implications. Policymakers should be aware that social democratic welfare state types, countries that spend more on public services, and countries with lower income inequalities have better self-rated health and lower mortality. Research funders and researchers should be aware that there remain substantial gaps in the available evidence base. One such area concerns the interrelationship between governance, polities, power, macroeconomic policy, public policy, and population health, including how these aspects of political economy generate social class processes and forms of discrimination that have a differential impact across social groups. This includes the influence of patterns of ownership (of land and capital) and tax policies. For some areas, there are many lower-quality reviews, which leave uncertainties in the relationship between political economy and population health, and a high-quality review is needed. There are also areas in which the available reviews have identified primary research gaps such as the impact of changes to housing policy, availability, and tenure.

Title: Influenza and the challenge for immunology. Content: The continued westward dissemination of H5N1 influenza A viruses in avian populations and the nearly 50% mortality rate of humans infected with H5N1 are a source of great international concern. A mutant H5N1 virus with the capability to spread rapidly between humans could cause a global catastrophe. Governments have reacted by developing national response plans, stockpiling antiviral drugs and speeding up the development and approval of vaccines. Here we summarize what is known about the interaction between influenza A viruses and the mammalian host response, specifically emphasizing issues that might be of interest to the broader immunology community.

Title: High-dose antithrombin III in the treatment of severe sepsis in patients with a high risk of death: efficacy and safety. Content: OBJECTIVE To explore if patients with severe sepsis and with a predicted high risk of death (according to the Simplified Acute Physiology Score II) might have a treatment benefit from high-dose antithrombin III. DESIGN Subgroup analysis of a randomized, placebo-controlled, double-blind, prospective phase III study. SETTING Unifactorial and multifactorial reanalysis of prospectively defined populations from the KyberSept trial. PATIENTS We studied 1,008 patients (43.6% of the overall intention-to-treat population, n = 2,314) with a predicted mortality rate of 30-60% at study entry as defined by the Simplified Acute Physiology Score II. INTERVENTIONS Patients were randomized in a 1:1 fashion to receive either high-dose antithrombin III (30,000 IU intravenously over the period of 4 days) or placebo. MEASUREMENTS AND MAIN RESULTS In a Kaplan-Meier analysis of patients with a predicted mortality of 30-60%, the survival time when followed up for 90 days after admission was increased in the high-dose antithrombin III group compared with placebo (p = .04). If heparin was avoided during the 4-day treatment phase with high-dose antithrombin III (n = 140) or placebo (n = 162), the treatment effect appeared to be even more pronounced: 28-day mortality rate, 35.7% vs. 44.4% (risk ratio, 0.804; 95% confidence interval, 0.607-1.064); 56-day mortality rate, 39.9% vs. 52.2% (risk ratio, 0.764; 95% confidence interval, 0.593-0.984); 90-day mortality rate, 42.8% vs. 55.1% (risk ratio, 0.776; 95% confidence interval, 0.614-0.986). Like in the overall population, the percentage with any bleeding was increased in patients receiving high-dose antithrombin III compared with placebo. Survival rates were in favor of high-dose antithrombin III in patients both with and without bleeding complications. CONCLUSIONS Treatment with high-dose antithrombin III may increase survival time up to 90 days in patients with severe sepsis and high risk of death. This benefit may even be stronger when concomitant heparin is avoided.

Title: The epidemiology of invasive meningococcal disease and the utility of vaccination in Malta Content: Invasive meningococcal disease (IMD) is a vaccine-preventable devastating infection that mainly affects infants, children and adolescents. We describe the population epidemiology of IMD in Malta in order to assess the potential utility of a meningococcal vaccination programme. All cases of microbiologically confirmed IMD in the Maltese population from 2000 to 2017 were analysed to quantify the overall and capsular-specific disease burden. Mean overall crude and age-specific meningococcal incidence rates were calculated to identify the target age groups that would benefit from vaccination. Over the 18-year study period, 111 out of the 245 eligible notified cases were confirmed microbiologically of which 70.3% had septicaemia, 21.6% had meningitis, and 6.3% had both. The mean overall crude incidence rate was 1.49/100,000 population with an overall case fatality rate of 12.6%. Meningococcal capsular groups (Men) B followed by C were the most prevalent with W and Y appearing over the last 6 years. Infants had the highest meningococcal incidence rate of 18.9/100,000 followed by 6.1/100,000 in 1–5 year olds and 3.6/100,000 in 11–15 year old adolescents. The introduction of MenACWY and MenB vaccines on the national immunization schedule in Malta would be expected to reduce the disease burden of meningococcal disease in children and adolescents in Malta.

Title: Correlation of population mortality of COVID-19 and testing coverage: a comparison among 36 OECD countries and Taiwan Content: Although testing is widely regarded as critical to fighting the Covid-19 pandemic, what measure and level of testing best reflects successful infection control remains unresolved. Our aim was to compare the sensitivity of two testing metrics--population testing number and testing coverage--to population mortality outcomes and identify a benchmark for testing adequacy with respect to population mortality and capture of potential disease burden. This ecological study aggregated publicly available data through April 12 on testing and outcomes related to COVID-19 across 36 OECD (Organization for Economic Development) countries and Taiwan. All OECD countries and Taiwan were included in this population-based study as a proxy for countries with highly developed economic and healthcare infrastructure. Spearman correlation coefficients were calculated between the aforementioned metrics and following outcome measures: deaths per 1 million people, case fatality rate, and case proportion of critical illness. Fractional polynomials were used to generate scatter plots to model the relationship between the testing metrics and outcomes. Testing coverage, but not population testing number, was highly correlated with population mortality (rs= -0.79, P=5.975e-09 vs rs =- 0.3, P=0.05) and case fatality rate (rs= -0.67, P=9.067e-06 vs rs = -0.21, P=0.20). A testing coverage threshold of 15-45 signified adequate testing: below 15, testing coverage was associated with exponentially increasing population mortality, whereas above 45, increased testing did not yield significant incremental mortality benefit. Testing coverage was better than population testing number in explaining country performance and can be used as an early and sensitive indicator of testing adequacy and disease burden. This may be particularly useful as countries consider re-opening their economies.

Title: Epidemiology of Human and Animal Viral Diseases Content: Viral disease epidemiology is the study of the determinants, dynamics, and distribution of viral diseases in populations. The risk of infection or disease in a population is determined by characteristics of the virus, the host, and the host population, as well as behavioral, environmental, and ecological factors that affect virus transmission from one host to another. Viral disease epidemiology has come to have a major role in clarifying the etiologic role of particular viruses and viral variants as the cause of specific diseases, in improving our understanding of the overall nature of specific viral diseases, and in determining factors affecting host susceptibility and immunity, in unraveling modes of transmission, in clarifying the interaction of viruses with environmental determinants of disease, in determining the safety, efficacy, and utility of vaccines and antiviral drugs, and especially in alerting and directing disease prevention and control actions. Information on incidence, prevalence, and morbidity and mortality rates contributes directly to the establishment of priorities for prevention and control programs, whether this involves vaccine or drug development and delivery, environmental and hygienic improvements, enhancement of nutritional status, personal or community behavior, agricultural and food processing enhancements, reservoir host and vector control, and international cooperation and communication.

Title: Estimating excess 1-year mortality associated with the COVID-19 pandemic according to underlying conditions and age: a population-based cohort study Content: BACKGROUND: The medical, societal, and economic impact of the coronavirus disease 2019 (COVID-19) pandemic has unknown effects on overall population mortality. Previous models of population mortality are based on death over days among infected people, nearly all of whom thus far have underlying conditions. Models have not incorporated information on high-risk conditions or their longer-term baseline (pre-COVID-19) mortality. We estimated the excess number of deaths over 1 year under different COVID-19 incidence scenarios based on varying levels of transmission suppression and differing mortality impacts based on different relative risks for the disease. METHODS: In this population-based cohort study, we used linked primary and secondary care electronic health records from England (Health Data Research UK–CALIBER). We report prevalence of underlying conditions defined by Public Health England guidelines (from March 16, 2020) in individuals aged 30 years or older registered with a practice between 1997 and 2017, using validated, openly available phenotypes for each condition. We estimated 1-year mortality in each condition, developing simple models (and a tool for calculation) of excess COVID-19-related deaths, assuming relative impact (as relative risks [RRs]) of the COVID-19 pandemic (compared with background mortality) of 1·5, 2·0, and 3·0 at differing infection rate scenarios, including full suppression (0·001%), partial suppression (1%), mitigation (10%), and do nothing (80%). We also developed an online, public, prototype risk calculator for excess death estimation. FINDINGS: We included 3 862 012 individuals (1 957 935 [50·7%] women and 1 904 077 [49·3%] men). We estimated that more than 20% of the study population are in the high-risk category, of whom 13·7% were older than 70 years and 6·3% were aged 70 years or younger with at least one underlying condition. 1-year mortality in the high-risk population was estimated to be 4·46% (95% CI 4·41–4·51). Age and underlying conditions combined to influence background risk, varying markedly across conditions. In a full suppression scenario in the UK population, we estimated that there would be two excess deaths (vs baseline deaths) with an RR of 1·5, four with an RR of 2·0, and seven with an RR of 3·0. In a mitigation scenario, we estimated 18 374 excess deaths with an RR of 1·5, 36 749 with an RR of 2·0, and 73 498 with an RR of 3·0. In a do nothing scenario, we estimated 146 996 excess deaths with an RR of 1·5, 293 991 with an RR of 2·0, and 587 982 with an RR of 3·0. INTERPRETATION: We provide policy makers, researchers, and the public a simple model and an online tool for understanding excess mortality over 1 year from the COVID-19 pandemic, based on age, sex, and underlying condition-specific estimates. These results signal the need for sustained stringent suppression measures as well as sustained efforts to target those at highest risk because of underlying conditions with a range of preventive interventions. Countries should assess the overall (direct and indirect) effects of the pandemic on excess mortality. FUNDING: National Institute for Health Research University College London Hospitals Biomedical Research Centre, Health Data Research UK.

Title: Estimating excess 1-year mortality associated with the COVID-19 pandemic according to underlying conditions and age: a population-based cohort study Content: BACKGROUND: The medical, societal, and economic impact of the coronavirus disease 2019 (COVID-19) pandemic has unknown effects on overall population mortality. Previous models of population mortality are based on death over days among infected people, nearly all of whom thus far have underlying conditions. Models have not incorporated information on high-risk conditions or their longer-term baseline (pre-COVID-19) mortality. We estimated the excess number of deaths over 1 year under different COVID-19 incidence scenarios based on varying levels of transmission suppression and differing mortality impacts based on different relative risks for the disease. METHODS: In this population-based cohort study, we used linked primary and secondary care electronic health records from England (Health Data Research UK-CALIBER). We report prevalence of underlying conditions defined by Public Health England guidelines (from March 16, 2020) in individuals aged 30 years or older registered with a practice between 1997 and 2017, using validated, openly available phenotypes for each condition. We estimated 1-year mortality in each condition, developing simple models (and a tool for calculation) of excess COVID-19-related deaths, assuming relative impact (as relative risks [RRs]) of the COVID-19 pandemic (compared with background mortality) of 1·5, 2·0, and 3·0 at differing infection rate scenarios, including full suppression (0·001%), partial suppression (1%), mitigation (10%), and do nothing (80%). We also developed an online, public, prototype risk calculator for excess death estimation. FINDINGS: We included 3â862â012 individuals (1â957â935 [50·7%] women and 1â904â077 [49·3%] men). We estimated that more than 20% of the study population are in the high-risk category, of whom 13·7% were older than 70 years and 6·3% were aged 70 years or younger with at least one underlying condition. 1-year mortality in the high-risk population was estimated to be 4·46% (95% CI 4·41-4·51). Age and underlying conditions combined to influence background risk, varying markedly across conditions. In a full suppression scenario in the UK population, we estimated that there would be two excess deaths (vs baseline deaths) with an RR of 1·5, four with an RR of 2·0, and seven with an RR of 3·0. In a mitigation scenario, we estimated 18â374 excess deaths with an RR of 1·5, 36â749 with an RR of 2·0, and 73â498 with an RR of 3·0. In a do nothing scenario, we estimated 146â996 excess deaths with an RR of 1·5, 293â991 with an RR of 2·0, and 587â982 with an RR of 3·0. INTERPRETATION: We provide policy makers, researchers, and the public a simple model and an online tool for understanding excess mortality over 1 year from the COVID-19 pandemic, based on age, sex, and underlying condition-specific estimates. These results signal the need for sustained stringent suppression measures as well as sustained efforts to target those at highest risk because of underlying conditions with a range of preventive interventions. Countries should assess the overall (direct and indirect) effects of the pandemic on excess mortality. FUNDING: National Institute for Health Research University College London Hospitals Biomedical Research Centre, Health Data Research UK.

Title: Injecting epidemiology into population viability analysis: avian cholera transmission dynamics at an arctic seabird colony. Content: Infectious diseases have the potential to spread rapidly and cause high mortality within populations of immunologically naïve hosts. The recent appearance of avian cholera, a highly virulent disease of birds caused by the bacterium Pasteurella multocida, at remote Arctic seabird colonies is an emerging conservation concern. Determining disease risk to population viability requires a quantitative understanding of transmission potential and the factors that regulate epidemic persistence. Estimates of the basic (R0 ) and real-time (Rt ) reproductive number are critical in this regard - enumerating the number of secondary infections caused by each primary infection in a newly invaded host population and the decline in transmission rate as susceptible individuals are removed via mortality or immunized recovery. Here, we use data collected at a closely monitored common eider (Somateria mollissima) breeding colony located in the Canadian Arctic to examine transmission and host population dynamics. Specifically, we infer epidemic curves from daily mortality observations and use a likelihood-based procedure to estimate changes in the reproductive number over a series of annual outbreaks. These data are interpreted in relation to concurrent changes in host numbers to assess local extinction risk. Consistent with expectations for a novel pathogen invasion, case incidence increased exponentially during the initial wave of exposure (R0 = 2·5; generation time = 6·5 days ± 1·1 SD). Disease conditions gradually abated, but only after several years of smouldering infection (Rt ≈ 1). In total, 6194 eider deaths were recorded during outbreaks spanning eight consecutive breeding seasons. Breeding pair abundance declined by 56% from the pre-outbreak peak; however, a robust population of >4000 pairs remained intact upon epidemic fade-out. Overall, outbreak patterns were consistent with herd immunity acting as a mitigating factor governing in the extent and duration of mortality. Disease mortality is frequently modelled as a form of stochastic catastrophe in wildlife population assessments, whereas our approach gives shape to the functional response between transmission and host population dynamics. We conclude that increased emphasis on integrating epidemiological and population processes is essential to predicting the conservation impact of emerging infectious diseases in wildlife.

Title: Impacts of Early Interventions on the Age-Specific Incidence of COVID-19 in New York, Los Angeles, Daegu and Nairobi Content: Background COVID-19 has caused an unprecedented public health crisis and economic shock to the global economy. While many countries were affected, regions with an older population and weaker public health interventions tended to suffer more morbidity and mortality. Here we model and quantify the age-specific incidence of COVID-19 in four pandemic cities under different interventions. Methods We developed an age-specific and multiple-stage susceptible-exposed-infected-recovered-hospitalized-quarantined-dead (SEIR-HQD) dynamical systems model expanded from the more basic SEIR model by incorporating location- and age-specific contact matrices to estimate the outcomes of COVID-19. Utilizing latest estimates of epidemiological parameters and demographic data, we model the potential effects of various interventions in four representative cities with different population structures - New York, Los Angeles, Daegu and Nairobi. We compared the effects of different interventions in the age-structure populations specific to each city. These policy options are then applied to determine the potential for effective containment. We model these dynamic policy scenarios to assess the risks of less-stringent social distancing, as has been proposed by those arguing to enhance economic activity over public health and safety. Finally, we explored the health impacts of different policy action timelines to understand the benefits of early interventions. Findings We find the spread of COVID-19 to be dramatically different in the regions modeled, with the primary drivers the variation of population age structures, and the dynamics of interactions of the younger demographics, whose higher interaction rates can lead to increasing transmission rates across these communities. A city with younger citizens may also have fewer hospitalized cases and deaths. Our modeling quantifies the value of early interventions, which avoided an additional 5%, 16%, 37% and 43% of the infections in Daegu, Nairobi, New York and Los Angeles, respectively, compared to what has been observed in the four cities. The finding is clear: in the absence of pharmaceutical options, delaying strict social policy interventions has resulted in substantial public health cost. This modeling can, and will, be applied to other cities and regions, and conducted in conjunction with other health insults, such as exposure to air pollution. Critically, we find that school closures, working from home, and reduction in other mobility were most beneficial for younger population (0-19 years old), middle-age (20-59 years old) population and older population (60 years and older), respectively across each city. Specifically, school closure avoided 25%, 18%, 16% and 12% of the infections for the population under 20 years old in Daegu, Los Angeles, New York and Nairobi, respectively. A 50% and 80% population working from home policy avoids 8% and 15% of the infections. Reduction in mobility was more effective than the working from home strategy. Any single social distancing policy if enacted alone can delay the spread of COVID-19 but was unable to totally suppress the infection. Coordinated policy action can be highly effective. Increasing the quarantine rate to 10% of infectious cases was more effective than strict social distancing alone in this study, although together they can suppress 80% of the epidemic. A combination of moderate social distancing and quarantine strategies was able to avoid 99% of the infections. Interpretation Moderate social distancing together with high quarantine rates was effective in each of the four cities. COVID-19 caused more deaths and hospitalization in cities with an ageing population than those with a younger population. However, in the cities with a younger population, there is a clear need to implement a social distancing strategy that is even more strict due to the higher transmission rates among younger people. Cities with more older people should prepare more hospital beds and healthcare facilities to save people who are in critical conditions. Cities with ageing population should take targeted action for the elderly to avoid the severe impacts on the vulnerable populations. Increasing quarantine rate is an effective strategy to avoid the substantial infection while also does not influence the economy fiercely. We recommend countries or regions experiencing, or likely to experience the rapid spread of COVID-19, to implement combination of multiple strategies in the early stage of the breakout which can avoid over 90% of infected cases.

Title: Population mortality during the outbreak of Severe Acute Respiratory Syndrome in Toronto Content: BACKGROUND: Extraordinary infection control measures limited access to medical care in the Greater Toronto Area during the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak. The objective of this study was to determine if the period of these infection control measures was associated with changes in overall population mortality due to causes other than SARS. METHODS: Observational study of death registry data, using Poisson regression and interrupted time-series analysis to examine all-cause mortality rates (excluding deaths due to SARS) before, during, and after the SARS outbreak. The population of Ontario was grouped into the Greater Toronto Area (N = 2.9 million) and the rest of Ontario (N = 9.3 million) based upon the level of restrictions on delivery of clinical services during the SARS outbreak. RESULTS: There was no significant change in mortality in the Greater Toronto Area before, during, and after the period of the SARS outbreak in 2003 compared to the corresponding time periods in 2002 and 2001. The rate ratio for all-cause mortality during the SARS outbreak was 0.99 [95% Confidence Interval (CI) 0.93–1.06] compared to 2002 and 0.96 [95% CI 0.90–1.03] compared to 2001. An interrupted time series analysis found no significant change in mortality rates in the Greater Toronto Area associated with the period of the SARS outbreak. CONCLUSION: Limitations on access to medical services during the 2003 SARS outbreak in Toronto had no observable impact on short-term population mortality. Effects on morbidity and long-term mortality were not assessed. Efforts to contain future infectious disease outbreaks due to influenza or other agents must consider effects on access to essential health care services.

Title: Effects of latency and age structure on the dynamics and containment of COVID-19 Content: In this paper we develop an SEIR-type model of COVID-19, with account for two particular aspects: non-exponential distribution of incubation and recovery periods, as well as age structure of the population. For the mean-field model, which does not distinguish between different age groups, we demonstrate that including a more realistic Gamma distribution of incubation and recovery periods may not have an effect on the total number of deaths and the overall size of an epidemic, but it has a major effect in terms of increasing the peak numbers of infected and critical care cases, as well as on changing the timescales of an epidemic, both in terms of time to reach the peak, and the overall duration of an outbreak. In order to obtain more accurate estimates of disease progression and investigate different strategies for introducing and lifting the lockdown, we have also considered an age-structured version of the model, which has allowed us to include more accurate data on age-specific rates of hospitalisation and COVID-19 related mortality. Applying this model to three comparable neighbouring regions in the UK has delivered some fascinating insights regarding the effect of quarantine in regions with different population structure. We have discovered that for a fixed quarantine duration, the timing of its start is very important in the sense that the second epidemic wave after lifting the quarantine can be significantly smaller or larger depending on the specific population structure. Also, the later the fixed-duration quarantine is introduced, the smaller is the resulting final number of deaths at the end of the outbreak. When the quarantine is introduced simultaneously for all regions, increasing quarantine duration postpones and slightly reduces the epidemic peak, though without noticeable differences in peak magnitude between different quarantine durations.

Title: Cytomegalovirus reactivation and mortality in patients with acute respiratory distress syndrome Content: PURPOSE: Cytomegalovirus (CMV) reactivation occurs frequently in patients with the acute respiratory distress syndrome (ARDS) and has been associated with increased mortality. However, it remains unknown whether this association represents an independent risk for poor outcome. We aimed to estimate the attributable effect of CMV reactivation on mortality in immunocompetent ARDS patients. METHODS: We prospectively studied immunocompetent ARDS patients who tested seropositive for CMV and remained mechanically ventilated beyond day 4 in two tertiary intensive care units in the Netherlands from 2011 to 2013. CMV loads were determined in plasma weekly. Competing risks Cox regression was used with CMV reactivation status as a time-dependent exposure variable. Subsequently, in sensitivity analyses we adjusted for the evolution of disease severity until onset of reactivation using marginal structural modeling. RESULTS: Of 399 ARDS patients, 271 (68 %) were CMV seropositive and reactivation occurred in 74 (27 %) of them. After adjustment for confounding and competing risks, CMV reactivation was associated with overall increased ICU mortality (adjusted subdistribution hazard ratio (SHR) 2.74, 95 % CI 1.51–4.97), which resulted from the joint action of trends toward an increased mortality rate (direct effect; cause specific hazard ratio (HR) 1.58, 95 % CI 0.86–2.90) and a reduced successful weaning rate (indirect effect; cause specific HR 0.83, 95 % CI 0.58–1.18). These associations remained in sensitivity analyses. The population-attributable fraction of ICU mortality was 23 % (95 % CI 6–41) by day 30 (risk difference 4.4, 95 % CI 1.1–7.9). CONCLUSION: CMV reactivation is independently associated with increased case fatality in immunocompetent ARDS patients who are CMV seropositive. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00134-015-4071-z) contains supplementary material, which is available to authorized users.

Title: Association of Bacille Calmette-Guerin (BCG), Adult Pneumococcal and Adult Seasonal Influenza Vaccines with Covid-19 Adjusted Mortality Rates in Level 4 European countries Content: Introduction Non-specific effects of vaccines have gained increasing interest during the Covid-19 pandemic. In particular, population use of BCG vaccine has been associated with improved outcomes. This study sought to determine the association of population use of BCG, adult pneumococcal and adult seasonal influenza vaccination with Covid-19 mortality when adjusted for a number of confounding variables. Methods: Using publicly available data, mortality adjusted for the timeframe of crisis, population size and population characteristics was calculated. The primary analysis was the relationship between each of the day 15 and day 30 standardised mortality rates and BCG, adult pneumococcal and influenza vaccination scores using unadjusted measures and with adjustment for population structure and case fatality rates. Secondary analyses were measures of case increases and mortality increases from day 15 to day 30 for each of the relative vaccination scores. Finally, we also analysed the peak Z score reflecting increases in total mortality from historical averages reported by EuroMOMO (Euromomo.eu), Results: Following adjustment for the effects of population size, median age, population density, the proportion of population living in an urban setting, life-expectancy, the elderly dependency ratio (or proportion over 65 years), net migration, days from day 1 to lockdown and case-fatality rate, only BCG vaccination score remained significantly associated with Covid-19 mortality at day 30. In the best fit model, BCG vaccination score was associated with a 64% reduction in log(10) mortality per 10 million population (OR 0.362 reduction [95% CI 0.188 to 0.698]), following adjustment for population size, median age, density, urbanization, elderly dependency ratio, days to lockdown, yearly migration and case fatality rate. Conclusion BCG vaccine was associated with reduced mortality rates in level 4 countries while adult pneumococcal and adult seasonal influenza vaccines were not when adjusted for a number of confounding variables. A number of trials are ongoing to determine if BCG is protective against severe Covid-19 infection.

Title: The potential effect of the African population age structure on COVID-19 mortality Content: Currently (mid May 2020), most active cases of COVID-19 are found in Europe and North America while it is still in the initial phases in Africa. As COVID-19 mortality occurs mainly in elderly and as Africa has a comparably young population, the death rates should be lower than on other continents. We calculated standardised mortality ratios (SMR) using age-specific case fatality rates for COVID-19 and the age structure of the population of Africa and of other continents. Compared to a European or Northern American population, the standardised mortality ratio was only 0.22 and 0.25, respectively, corresponding to reduction of deaths rates to a quarter. Compared to the Asian and Latin American & Caribbean population, the SMR was 0.43 and 0.44, respectively, corresponding to half the death rate for Africa. It is useful to quantify the isolated effect of the African age-structure on potential COVID-19 mortality for illustrative and communication purposes, keeping in mind the importance of public health measures that have been shown to be effective in reducing cases and deaths. The different aspect of age pyramids of a European and an African population are striking and the potential implications for the pandemic are often discussed but rarely quantified.

Title: Addressing inequities in COVID-19 morbidity and mortality: research and policy recommendations Content: The COVID-19 pandemic is the greatest global public health crisis since the 1918 influenza outbreak. As of early June, the novel coronavirus has infected more than 6.3 million people worldwide and more than 1.9 million in the United States (US). The total number of recorded deaths due to COVID-19 are growing at an alarming rate globally (³383,000) and nationally (³109,000) Evidence is mounting regarding the heavier burden of COVID-19 infection, morbidity, and mortality on the underserved populations in the US. This commentary focuses on this global health pandemic and how mitigation of the virus relies heavily on health behavior change to slow its spread, highlighting how the pandemic specifically affects the most socially and economically disadvantaged populations in the US. The commentary also offers short, intermediate and long-term research and policy focused recommendations. Both the research and policy recommendations included in this commentary emphasize equity-driven: (1) research practices, including applying a social determinants and health equity lens on monitoring, evaluation, and clinical trials activities on COVID-19; and (2) policy actions, such as dedicating resources to prioritize high-risk communities for testing, treatment, and prevention approaches and implementing organizational, institutional, and legislative policies that address the social and economic barriers to overall well-being that these populations face during a pandemic. It is our hope that these recommendations will generate momentum in delivering timely, effective, and lifesaving changes.

Title: How Large Was the Mortality Increase Directly and Indirectly Caused by the COVID-19 Epidemic? An Analysis on All-Causes Mortality Data in Italy Content: Objective: Overall mortality is a relevant indicator of the population burden during an epidemic. It informs on both undiagnosed cases and on the effects of health system disruption. Methods: We aimed at evaluating the extent of the total death excess during the COVID-19 epidemic in Italy. Data from 4433 municipalities providing mortality reports until April 15th, 2020 were included for a total of 34.5 million residents from all Italian regions. Data were analyzed by region, sex and age, and compared to expected from 2015-2019. Results: In both genders, overall mortality was stable until February 2020 and abruptly increased from March 1st onwards. Within the municipalities studied, 77,339 deaths were observed in the period between March 1st to April 15th, 2020, in contrast to the 50,822.6 expected. The rate ratio was 1.11 before age 60 and 1.55 afterwards. Both sexes were affected. The excess was greater in the regions most affected by COVID-19 but always exceeded the deaths attributed to COVID-19. The extrapolation to the total Italian population suggests an excess of 45,033 deaths in the study period, while the number of COVID-19 deaths was 21,046. Conclusion: Our paper shows a large death excess during the COVID-19 epidemic in Italy; greater than the number attributed to it. Possible causes included both the undetected cases and the disruption of the Health Service organization. Timely monitoring of overall mortality based on unbiased nationwide data is an essential tool for epidemic control.

Title: How Large Was the Mortality Increase Directly and Indirectly Caused by the COVID-19 Epidemic? An Analysis on All-Causes Mortality Data in Italy Content: Objective: Overall mortality is a relevant indicator of the population burden during an epidemic. It informs on both undiagnosed cases and on the effects of health system disruption. Methods: We aimed at evaluating the extent of the total death excess during the COVID-19 epidemic in Italy. Data from 4433 municipalities providing mortality reports until April 15th, 2020 were included for a total of 34.5 million residents from all Italian regions. Data were analyzed by region, sex and age, and compared to expected from 2015–2019. Results: In both genders, overall mortality was stable until February 2020 and abruptly increased from March 1st onwards. Within the municipalities studied, 77,339 deaths were observed in the period between March 1st to April 15th, 2020, in contrast to the 50,822.6 expected. The rate ratio was 1.11 before age 60 and 1.55 afterwards. Both sexes were affected. The excess was greater in the regions most affected by COVID-19 but always exceeded the deaths attributed to COVID-19. The extrapolation to the total Italian population suggests an excess of 45,033 deaths in the study period, while the number of COVID–19 deaths was 21,046. Conclusion: Our paper shows a large death excess during the COVID-19 epidemic in Italy; greater than the number attributed to it. Possible causes included both the undetected cases and the disruption of the Health Service organization. Timely monitoring of overall mortality based on unbiased nationwide data is an essential tool for epidemic control.

Title: Beyond Deaths per Capita: Three CoViD-19 Mortality Indicators for Temporal and International Comparisons Content: CoViD-19 deaths to population size ratios fail to account for well-documented age and sex differences in CoViD-19 mortality. To assess trends across populations for which CoViD-19 deaths might not be available by age and sex, an indirect age-and-sex adjustment can still be performed. The corresponding Comparative CoViD-19 Mortality Ratio (CCMR) only requires population age and sex compositions. To compare CoViD-19 and overall mortality levels, the Crude Death Rate (CDR) and life expectancy at birth for recent calendar years are the most widely available overall mortality indicators. Readily comparable to an annual CDR, a Crude CoViD-19 Death Rate (CCDR) can be calculated for periods of any duration. CoViD-19-induced declines in projected life expectancy at birth for 2020 can also be calculated from existing life tables. We calculate the CCMR and CCDR for the period from their first CoViD-19 death to the present using US age and sex data and current estimates of CoViD-19 deaths in 166 Countries whose population composition is available from the UN, 28 Provinces in China, the 50 United States and DC. Across these 245 populations, 14 States and 11 Countries have CCMR values above 1—the US value by construction. Most affected to date, the period CCDR in New York exceeds its CDR for the most recent year available (7.83 per thousand in 2017). We also calculate CCMR and CCDR values corresponding to projections for the 50 States and DC, and for 49 countries, for which we can additionally calculate reductions in 2020 life expectancy at birth using UN life tables. This suggests life-expectancy reductions between .5 and 1 year for 7 European Countries, 3 South-American Countries and the US. The .55 reduction in the U.S. amounts to nearly twice the largest single-year decline induced by HIV/AIDS (−.3 between 1992 and 1993) or the total decline induced by opioid overdoses (also −.3 between 2014 and 2017), and would bring US life expectancy at birth down to its lowest level since 2008. As current CoViD-19 death counts likely underestimate the total increase in deaths and current projections do not account for possible new infection waves later this year, the impact on 2020 life expectancies at birth should be expected to exceed these figures.

Title: The Role of Vitamin D in The Age of COVID-19: A Systematic Review and Meta-Analysis Along with an Ecological Approach Content: Background: Following emerge of a novel coronavirus from Wuhan, China, in December 2019, it has affected the whole world and after months of efforts by the medical communities, there is still no specific approach for prevention and treatment against the Coronavirus Disease 2019 (COVID-19). Evidence recommends that vitamin D might be an important supportive agent for the immune system, mainly in cytokine response regulation against COVID-19. Hence, we carried out a rapid systematic review and meta-analysis along with an ecological investigation in order to maximize the use of everything that exists about the role of vitamin D in the COVID-19. Methods: A systematic search was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science and Google Scholar (intitle) as well as preprint database of medRxiv, bioRxiv, Research Square, preprints.org, search engine of ScienceDirect and a rapid search through famous journals up to May 26, 2020. Studies focused on the role of vitamin D in confirmed COVID-19 patients were entered into the systematic review. Along with our main aim, to find the second objective: correlation of global vitamin D status and COVID-19 recovery and mortality we carried out a literature search in PubMed database to identify the national or regional studies reported the vitamin D status globally. CMA v. 2.2.064 and SPSS v.16 were used for data analysis. Results: Out of nine studies entered into our systematic review, six studies containing 3,822 participants entered into the meta-analysis. The meta-analysis indicated that 46.5% of COVID-19 patients were suffering from vitamin D deficiency (95% CI, 28.2%-65.8%) and in 43.3% of patients, levels of vitamin D were insufficient (95% CI, 27.4%-60.8%). In regard to our ecological investigation on 51 countries including 408,748 participants, analyses indicated no correlation between vitamin D levels and recovery rate (r= 0.041) as well as mortality rate (r=-0.073) globally. However, given latitude, a small reverse correlation between mortality rate and vitamin D status was observed throughout the globe (r= -0.177). In Asia, a medium direct correlation was observed for recovery rate (r= 0.317) and a significant reveres correlation for mortality rate (r= -0.700) with vitamin D status in such patients. In Europe, there were no correlations for both recovery (r= 0.040) and mortality rate (r= -0.035). In Middle East, the recovery rate (r= 0.267) and mortality rate (r= -0.217) showed a medium correlation. In North and Sought America, surprisingly, both recovery and mortality rate demonstrated a direct correlation respectively (r= 1.000, r=0.500). In Oceania, unexpectedly, recovery (r= -1.000) and mortality (r= -1.000) rates were in considerable reverse correlation with vitamin D levels. Conclusion: In this systematic review and meta-analysis with an ecological approach, we found a high percentage of COVID-19 patients who suffer from vitamin D deficiency or insufficiency. Much more important, our ecological investigation resulted in substantial direct and reverse correlations between recovery and mortality rates of COVID-19 patients with vitamin D status in different countries. Considering latitudes, a small reverse correlation between vitamin D status and mortality rate was found globally. It seems that populations with lower levels of vitamin D might be more susceptible to the novel coronavirus infection. Nevertheless, due to multiple limitations, if this study does not allow to quantify a value of the Vitamin D with full confidence, it allows at least to know what the Vitamin D might be and that it would be prudent to invest in this direction through comprehensive large randomized clinical trials.

Title: Age separation dramatically reduces COVID-19 mortality rate in a computational model of a large population Content: COVID-19 pandemic has caused a global lock down in many countries throughout the world. Faced with a new reality, and until a vaccine or efficient treatment is found, humanity must figure out ways to keep economy going on one hand, yet keep the population safe on the other hand, especially those that are susceptible to this virus. Here we use a network simulation, with parameters that were drawn from what is known about the virus, to explore 5 different scenarios of partial lock down release. We find that separating age groups by reducing interactions between age groups, protects the general population and reduces mortality rates. Furthermore, addition of new connections within the same age group to compensate for the lost connections outside the age group, still has a strong beneficial influence and reduces the total death toll by 66%. While complete isolation from society may be the most protective scenario for the elderly population, it would have an emotional and possibly cognitive impact that might outweigh its benefit. We therefore propose creating age-related social recommendations or even restrictions, thereby allowing social connections but still strong protection for the older population.

Title: Burden of serious fungal infections in the Netherlands Content: BACKGROUND: Fungal diseases have an ever‐increasing global disease burden, although regional estimates for specific fungal diseases are often unavailable or dispersed. OBJECTIVES: Here, we report the current annual burden of life‐threatening and debilitating fungal diseases in the Netherlands. METHODS: The most recent available epidemiological data, reported incidence and prevalence of fungal diseases were used for calculations. RESULTS: Overall, we estimate that the annual burden of serious invasive fungal infections in the Netherlands totals 3 185 patients, including extrapulmonary or disseminated cryptococcosis (n = 9), pneumocystis pneumonia (n = 740), invasive aspergillosis (n = 1 283), chronic pulmonary aspergillosis (n = 257), invasive Candida infections (n = 684), mucormycosis (n = 15) and Fusarium keratitis (n = 8). Adding the prevalence of recurrent vulvo‐vaginal candidiasis (n = 220 043), allergic bronchopulmonary aspergillosis (n = 13 568) and severe asthma with fungal sensitisation (n = 17 695), the total debilitating burden of fungal disease in the Netherlands is 254 491 patients yearly, approximately 1.5% of the country's population. CONCLUSION: We estimated the annual burden of serious fungal infections in the Netherlands at 1.5% of the population based on previously reported modelling of fungal rates for specific populations at risk. With emerging new risk groups and increasing reports on antifungal resistance, surveillance programmes are warranted to obtain more accurate estimates of fungal disease epidemiology and associated morbidity and mortality.

Title: Confinement strategies in a simple SIR model Content: We propose a simple SIR model in order to investigate the impact of various confinement strategies on a most virulent epidemic. Our approach is motivated by the current COVID-19 pandemic. The main hypothesis is the existence of two populations of susceptible persons, one which obeys confinement and for which the infection rate does not exceed 1, and a population which, being non confined for various imperatives, can be substantially more infective. The model, initially formulated as a differential system, is discretised following a specific procedure, the discrete system serving as an integrator for the differential one. Our model is calibrated so as to correspond to what is observed in the COVID-19 epidemic. Several conclusions can be reached, despite the very simple structure of our model. First, it is not possible to pinpoint the genesis of the epidemic by just analysing data from when the epidemic is in full swing. It may well turn out that the epidemic has reached a sizeable part of the world months before it became noticeable. Concerning the confinement scenarios, a universal feature of all our simulations is that relaxing the lockdown constraints leads to a rekindling of the epidemic. Thus we sought the conditions for the second epidemic peak to be lower than the first one. This is possible in all the scenarios considered (abrupt, progressive or stepwise exit) but typically a progressive exit can start earlier than an abrupt one. However, by the time the progressive exit is complete, the overall confinement times are not too different. From our results, the most promising strategy is that of a stepwise exit. And in fact its implementation could be quite feasible, with the major part of the population (minus the fragile groups) exiting simultaneously but obeying rigorous distancing constraints.

Title: Epidemiological, socio-demographic and clinical features of the early phase of the COVID-19 epidemic in Ecuador Content: Abstract Background: The SARS-CoV-2 virus has spread all over the world infecting more than 3,585,936 people from over 210 countries and caused more than 245,803 deaths worldwide. We report the first epidemiological, socio-demographic, and clinical findings for the first 9,468 confirmed COVID-19 cases in Ecuador. Methods: We conducted a descriptive cross-sectional analysis of 9,468 COVID-19 confirmed cases in Ecuador from 27 February to 18 April 2020. The overall incidence, mortality, and case fatality rate was computed according to the entire population at risk living in a canton or a province. Disability adjusted life years, attack and crude mortality rates as well as relative risk and odds ratios were computed as an outcome. Results: Since the first case reported in Ecuador on 27 Feb 2020, at least 9,468 positive COVID-19 cases of which 474 deaths were officially registered over a 54-day period. Men accounted for 55.40% (n = 5, 247) of the overall cases with an incidence rate of 60.5 per 100,000 while women accounted for 44.60 % (n = 4, 221) representing 47.2 per 100,000. The mortality rate per canton showed that cantons with a lower attack rate had higher mortality rates. Coastal cantons have a lower attack rate than the highlands and living above >2,500 m seems to be linked with a lower risk of dying (RR: 0.63 [CI 95% 0.50 - 0.79]). Fatigue was reported in 53.2% of the patients, followed by headache (43%), dry cough (41.7%), ageusia (37.1%) and anosmia (36.1%). Conclusion: This study is the first of its kind in Ecuador. The results of this analysis show that men are at higher risk of dying from COVID-19 than women, which increases as with age and the presence of comorbidities. Areas with better testing capabilities reported lower CFR% and mortality, additionally cantons located above 2,500 m have lower attack and mortality rates although the risk of dying is greater among highlanders. Keywords: COVID-19; SARS-CoV-2; Ecuador; Epidemiology; Latin America

Title: Viral Infection in the Development and Progression of Pediatric Acute Respiratory Distress Syndrome Content: Viral infections are an important cause of pediatric acute respiratory distress syndrome (ARDS). Numerous viruses, including respiratory syncytial virus (RSV) and influenza A (H1N1) virus, have been implicated in the progression of pneumonia to ARDS; yet the incidence of progression is unknown. Despite acute and chronic morbidity associated with respiratory viral infections, particularly in “at risk” populations, treatment options are limited. Thus, with few exceptions, care is symptomatic. In addition, mortality rates for viral-related ARDS have yet to be determined. This review outlines what is known about ARDS secondary to viral infections including the epidemiology, the pathophysiology, and diagnosis. In addition, emerging treatment options to prevent infection, and to decrease disease burden will be outlined. We focused on RSV and influenza A (H1N1) viral-induced ARDS, as these are the most common viruses leading to pediatric ARDS, and have specific prophylactic and definitive treatment options.

Title: Late mortality in survivors of autologous hematopoietic-cell transplantation: report from the Bone Marrow Transplant Survivor Study. Content: We assessed late mortality in 854 individuals who had survived 2 or more years after autologous hematopoietic cell transplantation (HCT) for hematologic malignancies. Median age at HCT was 36.5 years, and median length of follow-up was 7.6 years. Overall survival was 68.8% +/- 1.8% at 10 years, and the cohort was at a 13-fold increased risk for late death (standardized mortality ratio [SMR] = 13.0) when compared with the general population. Mortality rates approached those of the general population after 10 years among patients at standard risk for relapse at HCT (SMR = 1.1) and in patients undergoing transplantation for acute myeloid leukemia (AML; SMR = 0.9). Relapse of primary disease (56%) and subsequent malignancies (25%) were leading causes of late death. Relapse-related mortality was increased among patients with Hodgkin disease (HD; relative risk [RR] = 3.6), non-Hodgkin lymphoma (NHL; RR = 2.1), and acute lymphoblastic leukemia (ALL; RR = 6.5). Total body irradiation (RR = 0.6) provided a protective effect. Nonrelapse-related mortality was increased after carmustine (RR = 2.3) and with use of peripheral blood stem cells (RR = 2.4). Survivors were more likely to report difficulty in holding jobs (RR = 9.4) and in obtaining health (RR = 7.7) or life insurance (RR = 8.4) when compared with siblings. Although mortality rates approach that of the general population after 10 years in certain subgroups, long-term survivors of autologous HCT continue to face challenges affecting their health and well-being.

Title: An empirical estimate of the infection fatality rate of COVID-19 from the first Italian outbreak Content: Background: The coronavirus 2019 (COVID-19) pandemic has been spread-ing globally for months, yet the infection fatality ratio of the disease is still uncertain. This is partly because of inconsistencies in testing and death reporting standards across countries. Our purpose is to provide accurate estimates which do not rely on testing and death count data directly but only use population level statistics. Methods: We collected demographic and death records data from the Italian Institute of Statistics. We focus on the area in Italy that experienced the initial outbreak of COVID-19 and estimated a Bayesian model fitting age-stratified mortality data from 2020 and previous years. We also assessed the sensitivity of our estimates to alternative assumptions on the proportion of population infected. Findings: We estimate an overall infection fatality rate of 1.29% (95% credible interval [CrI] 0.89 - 2.01), as well as large differences by age, with a low infection fatality rate of 0.05% for under 60 year old (CrI 0-.19) and a substantially higher 4.25% (CrI 3.01-6.39) for people above 60 years of age. In our sensitivity analysis, we found that even under extreme assumptions, our method delivered useful information. For instance, even if only 10% of the population were infected, the infection fatality rate would not rise above 0.2% for people under 60. Interpretation: Our empirical estimates based on population level data show a sharp difference in fatality rates between young and old people and firmly rule out overall fatality ratios below 0.5% in populations with more than 30% over 60 years old.

Title: The overall mortality caused by COVID-19 in the European region is highly associated with demographic composition: A spatial regression-based approach Content: The demographic factors have a substantial impact on the overall casualties caused by the COVID-19. In this study, the spatial association between the key demographic variables and COVID-19 cases and deaths were analyzed using the spatial regression models. Total 13 (for COVID-19 case factor) and 8 (for COVID-19 death factor) key variables were considered for the modelling. Total five spatial regression models such as Geographically weighted regression (GWR), Spatial Error Model (SEM), Spatial Lag Model (SLM), Spatial Error_Lag model (SEM_SLM), and Ordinary Least Square (OLS) were performed for the spatial modelling and mapping of model estimates. The local R2 values, which suggesting the influences of the selected demographic variables on overall casualties caused by COVID-19, was found highest in Italy and the UK. The moderate local R2 was observed for France, Belgium, Netherlands, Ireland, Denmark, Norway, Sweden, Poland, Slovakia, and Romania. The lowest local R2 value for COVID-19 cases was accounted for Latvia and Lithuania. Among the 13 variables, the highest local R2 was calculated for total population (R2 = 0.92), followed by death crude death rate (R2 = 0.9), long time illness (R2 = 0.84), population with age>80 (R2 = 0.59), employment (R2 = 0.46), life expectancy at 65 (R2 = 0.34), crude birth rate (R2 = 0.31), life expectancy (R2 = 0.31), Population with age 65-80 (R2 = 0.29), Population with age 15-24 (R2 = 0.27), Population with age 25-49 (R2 = 0.27), Population with age 0-14 (R2 = 0.23), and Population with age 50-65 (R2 = 0.23), respectively.

Title: On case-fatality rate: review and hypothesis. Content: The relationship between log cumulative number of patients (X) and that of deaths (Y) in an epidemic follows the equation logY = klogX - klogN(0), where k is a constant determining the slope and N(0) is the value of X when Y = 1. Diseases with k = 1 are Ebola hemorrhagic fever, avian influenza H5N1, cholera, and hand, foot, and mouth disease; those with k > 1 are the influenza H1N1 2009 pandemic in countries other than Mexico and the SARS epidemic in some countries; and those with k < 1 include the influenza H1N1 2009 pandemic in Mexico. Epidemics with k > 1 can be simulated by postulating two subpopulations (normal population [NP] and vulnerable population [VP]), where the epidemic proceeds at higher speed and at higher mortality in VP than in NP. Epidemics with k < 1 can be simulated by postulating coexisting high virulence virus (HVV) and low virulence virus (LVV), with the former being propagated at slower speed and with a higher mortality rate than the latter. An epidemic with k > 1 was simulated using parameters that are fractions of subpopulations NP or VP from the total population (f) and NP- or VP-specific patient multiplication (M) and mortality (D) rates. An epidemic with k < 1 was simulated using parameters that are fractions of HVV- or LVV-infected human populations (f), and HVV- or LVV-specific M and D.

Title: Trends in Infectious Disease Mortality, South Korea, 1983–2015 Content: We used national statistics from 1983–2015 to evaluate trends in mortality caused by infectious diseases in South Korea. Age-standardized mortality from infectious disease decreased from 43.5/100,000 population in 1983 to 16.5/100,000 in 1996, and then increased to 44.6/100,000 in 2015. Tuberculosis was the most common cause of death in 1983 and respiratory tract infections in 2015. We observed a significant decline in infant deaths caused by infectious diseases, but mortality in persons age >65 years increased from 135 deaths/100,000 population in 1996 to 307/100,000 in 2015. The relative inequality indices for respiratory tract infections, sepsis, and tuberculosis tended to increase over time. Although substantial progress has been achieved in terms of infant mortality, death rates from infectious disease has not decreased overall. Elderly populations with lower education levels and subgroups susceptible to respiratory infections and sepsis should be the focus of preventive policies.

Title: Differential mortality in COVID-19 patients from India and western countries Content: BACKGROUND AND AIMS: COVID-19 disease has been associated with disproportionate mortality amongst world population. We try to elucidate various reasons for lower mortality rate in the Indian subcontinent due to COVID-19 pandemic. METHOD: We carried out a comprehensive review of the literature using suitable keywords such as ‘COVID-19’, ‘Pandemics’, ‘disease outbreaks’ and ‘India’ on the search engines of PubMed, SCOPUS, Google Scholar and Research Gate in the month of May 2020 during the current COVID-19 pandemic and assessed mortality data. RESULTS: The mortality observed in Indian and south Asian subcontinent is lower than in the west. Multifactorial reasons indicated for this differential mortality due to COVID-19 have been described in the current literature. CONCLUSIONS: The effects of COVID-19 on the health of racial and ethnic minority groups are still emerging with disproportionate burden of illness and death amongst some black and ethnic minority groups. Overall the current COVID-19 related mortality appears to be lower in the health and resource challenged populous Indian subcontinent. Further scientific studies would be helpful to understand this disparity in mortality due to COVID-19 in the world population.

Title: Differential mortality in COVID-19 patients from India and western countries Content: BACKGROUND AND AIMS: COVID-19 disease has been associated with disproportionate mortality amongst world population. We try to elucidate various reasons for lower mortality rate in the Indian subcontinent due to COVID-19 pandemic. METHOD: We carried out a comprehensive review of the literature using suitable keywords such as 'COVID-19', 'Pandemics', 'disease outbreaks' and 'India' on the search engines of PubMed, SCOPUS, Google Scholar and Research Gate in the month of May 2020 during the current COVID-19 pandemic and assessed mortality data. RESULTS: The mortality observed in Indian and south Asian subcontinent is lower than in the west. Multifactorial reasons indicated for this differential mortality due to COVID-19 have been described in the current literature. CONCLUSIONS: The effects of COVID-19 on the health of racial and ethnic minority groups are still emerging with disproportionate burden of illness and death amongst some black and ethnic minority groups. Overall the current COVID-19 related mortality appears to be lower in the health and resource challenged populous Indian subcontinent. Further scientific studies would be helpful to understand this disparity in mortality due to COVID-19 in the world population.

Title: Age- and Sex-Specific Risk Profiles and In-Hospital Mortality in 13,932 Spanish Stroke Patients. Content: BACKGROUND In-hospital stroke death rate is an important sanitary issue. Despite advances in the acute phase management of stroke patients, mortality and disability rates remain high. In aging populations and with different mortality between the sexes in general, the study of sex- and age-related differences becomes increasingly relevant for optimization of post-acute clinical care of stroke patients. METHODS We designed a cohort follow-up study with 13,932 consecutive ischemic stroke (IS) patients from 19 Spanish hospitals. Data was obtained from the Spanish Stroke Registry; transient ischemic attacks and ages <18 years were excluded. Patients were organised by age group and sex. We compared female and male patient cohorts within and across age groups univariately and used multivariable logistic regression to adjust for confounders in differential in-hospital mortality. RESULTS The median (percentiles 2.5 and 97.5%) age was 78 (41-92) years old for women and 71 (41-92) for men. IS women were more likely to be older, to exhibit cardio-embolic aetiology, and less likely to have been admitted to a stroke unit or to have had a stroke code activated. Both pre-stroke modified Rankin Scale and National Institute of Health Stroke Scale (NIHSS) scores at admission increased significantly with age and were higher in women than those in men. Differences in distributions of common risk factors for IS and of in-hospital outcomes between women and men actually changed with patient's age. It is to be noted here that although there were no statistically significant differences (p > 0.05) between the sexes within any age group, in-hospital mortality appeared significantly higher in women than that in men when analysed overall, due to confounding. Death was more closely related to stroke in women than in men and occurred earlier. Although there were some age-specific sex differences between the predictors for in-hospital mortality, stroke severity measured by NIHSS was the main predictor of in-hospital mortality for both sexes. Topographic classifications - partial anterior circulatory infarct and total anterior circulatory infarct - were significant prognostic factors for men aged <60 years and for those in the 60-69 years range respectively. CONCLUSION Although most of our findings were consistent with previous studies, it is important to take into account and highlight differences in in-hospital mortality between the sex and age group. Not to account for age-related differences between the sexes can give false results that may mislead management decisions. As most deaths in women were related to stroke, it is important to improve their early management, stroke code activation, access to stroke units and/or revascularisation therapies, especially in the older age groups.

Title: Preoperative nutritional status is an important predictor of survival in patients undergoing surgery for renal cell carcinoma. Content: BACKGROUND The role of malnutrition has not been well studied in patients undergoing surgery for renal cell carcinoma (RCC). OBJECTIVE Our aim was to evaluate whether nutritional deficiency (ND) is an important determinant of survival following surgery for RCC. DESIGN, SETTING, AND PARTICIPANTS A total of 369 consecutive patients underwent surgery for locoregional RCC from 2003 to 2008. ND was defined as meeting one of the following criteria: body mass index <18.5 kg/m(2), albumin <3.5 g/dl, or preoperative weight loss ≥ 5% of body weight. INTERVENTION All patients underwent radical or partial nephrectomy. MEASUREMENTS Primary outcomes were overall and disease-specific mortality. Covariates included age, Charlson comorbidity index (CCI), preoperative anemia, tumor stage, Fuhrman grade, and lymph node status. Multivariate analysis was performed using a Cox proportional hazards model. Mortality rates were estimated using the Kaplan-Meier product-limit method. RESULTS AND LIMITATIONS Eighty-five patients (23%) were categorized as ND. Three-year overall and disease-specific survival were 58.5% and 80.4% in the ND cohort compared with 85.4% and 94.7% in controls, respectively (p<0.001). ND remained a significant predictor of overall mortality (hazard ratio [HR]: 2.41, 95% confidence interval [CI], 1.40-4.18) and disease-specific mortality (HR: 2.76; 95% CI, 1.17-6.50) after correcting for age, CCI, preoperative anemia, stage, grade, and nodal status. This study is limited by its retrospective nature. CONCLUSIONS ND is associated with higher mortality in patients undergoing surgery for locoregional RCC, independent of key clinical and pathologic factors. Given this mortality risk, it may be important to address nutritional status preoperatively and counsel patients appropriately.

Title: Mortality of people with intellectual disabilities during the 2017/2018 influenza epidemic in the Netherlands: potential implications for the COVID-19 pandemic Content: BACKGROUND: Data on the development of Covid-19 among people with intellectual disabilities (IDs) are scarce and it is uncertain to what extent general population data applies to people with ID. To give an indication of possible implications, this study investigated excess mortality patterns during a previous influenza epidemic. METHODS: Using Dutch population and mortality registers, a historical cohort study was designed to compare mortality during the 2017-2018 influenza epidemic with mortality in the same period in the three previous years. People with ID were identified by entitlements to residential ID-care services as retrieved from a national database. RESULTS: Data covered the entire adult Dutch population (12.6 million; GenPop), of which 91 064 individuals were identified with an ID. During the influenza epidemic, mortality among people with ID increased almost three times as much than in the GenPop (15.2% vs. 5.4%), and more among male individuals with ID (+19.5%) than among female individuals with ID (+10.6%), as compared with baseline. In both cohorts, comparable increases in mortality within older age groups and due to respiratory causes were seen. Particularly in the ID-cohort, excess deaths also occurred in younger age groups, due to endocrine diseases and ID-specific causes. CONCLUSIONS: During the 2017-2018 influenza epidemic, excess mortality among people with ID was three times higher than in the general Dutch population, appeared more often at young age and with a broader range of underlying causes. These findings suggest that a pandemic may disproportionally affect people with ID while population data may not immediately raise warnings. Early detection of diverging patterns and faster implementation of tailored strategies therefore require collection of good quality data.

Title: Mortality of people with intellectual disabilities during the 2017/2018 influenza epidemic in the Netherlands: potential implications for the COVID‐19 pandemic Content: BACKGROUND: Data on the development of Covid‐19 among people with intellectual disabilities (IDs) are scarce and it is uncertain to what extent general population data applies to people with ID. To give an indication of possible implications, this study investigated excess mortality patterns during a previous influenza epidemic. METHODS: Using Dutch population and mortality registers, a historical cohort study was designed to compare mortality during the 2017–2018 influenza epidemic with mortality in the same period in the three previous years. People with ID were identified by entitlements to residential ID‐care services as retrieved from a national database. RESULTS: Data covered the entire adult Dutch population (12.6 million; GenPop), of which 91 064 individuals were identified with an ID. During the influenza epidemic, mortality among people with ID increased almost three times as much than in the GenPop (15.2% vs. 5.4%), and more among male individuals with ID (+19.5%) than among female individuals with ID (+10.6%), as compared with baseline. In both cohorts, comparable increases in mortality within older age groups and due to respiratory causes were seen. Particularly in the ID‐cohort, excess deaths also occurred in younger age groups, due to endocrine diseases and ID‐specific causes. CONCLUSIONS: During the 2017–2018 influenza epidemic, excess mortality among people with ID was three times higher than in the general Dutch population, appeared more often at young age and with a broader range of underlying causes. These findings suggest that a pandemic may disproportionally affect people with ID while population data may not immediately raise warnings. Early detection of diverging patterns and faster implementation of tailored strategies therefore require collection of good quality data.

Title: The projected impact of mitigation and suppression strategies on the COVID-19 epidemic in Senegal: A modelling study Content: Background: Physical distancing measures that reduce social contacts have formed a key part of national COVID-19 containment and mitigation strategies. Many Sub-Saharan African nations are now facing increasing numbers of cases of COVID-19 and there is a need to understand what levels of measures may be required to successfully reduce transmission. Methods: We collated epidemiological data along with information on key COVID-19 specific response policies and health system capacity estimates for services needed to treat COVID-19 patients in Senegal. We calibrated an age-structured SEIR model to these data to capture transmission dynamics accounting for demography, contact patterns, hospital capacity and disease severity. We simulated the impact of mitigation and suppression strategies focussed on reducing social contact rates. Results: Senegal acted promptly to contain the spread of SARS-CoV-2 and as a result has reduced the reproduction number from 1.9 (95% CI 1.7-2.2) to 1.3 (95% CI 1.2-1.5), which has slowed but not fully interrupted transmission. We estimate that continued spread is likely to peak in October, and to overwhelm the healthcare system with an estimated 77,400 deaths(95% CI 55,270-100,700). Further reductions in contact rates to suppress transmission (Rt<1) could significantly reduce this burden on healthcare services and improve overall health outcomes. Conclusions: Our results demonstrate that Senegal has already significantly reduced transmission. Enhanced physical distancing measures and rapid scale up of hospital capacity is likely to be needed to reduce mortality and protect healthcare infrastructure from high levels of demand.

Title: Estimating excess 1- year mortality from COVID-19 according to underlying conditions and age in England: a rapid analysis using NHS health records in 3.8 million adults Content: RAPID COMMUNICATION 22 March 2020 Estimating excess 1- year mortality from COVID-19 according to underlying conditions and age in England: a rapid analysis using NHS health records in 3.8 million adults Background: The medical, health service, societal and economic impact of the COVID-19 emergency has unknown effects on overall population mortality. Previous models of population mortality are based on death over days among infected people, nearly all of whom (to date at least) have underlying conditions. Models have not incorporated information on high risk conditions or their longer term background (pre-COVID-19) mortality. We estimated the excess number of deaths over 1 year under different COVID-19 incidence rates and differing mortality impacts. Methods: Using population based linked primary and secondary care electronic health records in England (HDR UK - CALIBER), we report the prevalence of underlying conditions defined by UK Public Health England COVID-19 guidelines (16 March 2020) in 3,862,012 individuals aged ≥30 years from 1997-2017. We used previously validated phenotypes, openly available (https://caliberresearch.org/portal), for each condition using ICD-10 diagnosis, Read, procedure and medication codes. We estimated the 1-year mortality in each condition, and developed simple models of excess COVID-19-related deaths assuming relative risk (RR) of the impact of the emergency (compared to background mortality) of 1.2, 1.5 and 2.0. Findings: 20.0% of the population are at risk according to current PHE guidelines, of which; 13.7% were age>70 years and 6.3% aged ≤70 years with ≥1 underlying condition (cardiovascular disease (2.3%), diabetes (2.2%), steroid therapy (1.9%), severe obesity (0.9%), chronic kidney disease (0.6%) and chronic obstructive pulmonary disease, COPD (0.5%). Multimorbidity (co-occurrence of ≥2 conditions in an individual) was common (10.1%). The 1-year mortality in the at-risk population was 4.46%, and age and underlying conditions combine to influence background risk, varying markedly across conditions (5.9% in age>70 years, 8.6% for COPD and 13.1% in those with ≥3 or more conditions). In a suppression scenario (at SARS CoV2 rates of 0.001% of the UK population), there would be minimal excess deaths (3 and 7 excess deaths at relative risk, RR, 1.5 and 2.0 respectively). At SARS CoV2 rates of 10% of the UK population (mitigation) the model estimates the numbers of excess deaths as: 13791, 34479 and 68957 (at RR 1.2, 1.5 and 2.0 respectively). At SARS CoV2 rates of 80% in the UK population (do-nothing), the model estimates the number of excess deaths as 110332, 275,830 and 551,659 (at RR 1.2, 1.5 and 2.0) respectively. Interpretation: We provide the public, researchers and policy makers a simple model to estimate the excess mortality over 1 year from COVID-19, based on underlying conditions at different ages. If the relative mortality impact of COVID-19 were to be about 20% (similar magnitude as the established winter vs summer mortality excess), then the excess deaths would be 0 when 1 in 100 000 (suppression), 13791 when 1 in 10 (mitigation) and 110332 when 8 in 10 are infected (do nothing) scenario. However, the relative impact of COVID-19 is unknown. If the emergency were to double the mortality risk, then we estimate 7, 68957 and 551,659 excess deaths in the same scenarios. These results may inform the need for more stringent suppression measures as well as efforts to target those at highest risk for a range of preventive interventions.

Title: Incidence of cervical cancer and age-specific survival of small cell cervical carcinoma in Taiwan. Content: OBJECTIVE To determine the incidence of cervical cancer and the age-specific survival from small cell cervical carcinoma in Taiwan. DESIGN Retrospective study. Setting. Taiwan. POPULATION Women diagnosed with cervical cancer from 1991 to 2005. METHODS Analysis of data from the National Cancer Registration System and National Death Certification System. MAIN OUTCOME MEASURES Incidence and age at diagnosis of cervical carcinoma and age-specific and overall survival from small cell cervical carcinoma. RESULTS During the study period, 36 122 women were diagnosed with cervical cancer, and 81.8% had squamous cell carcinoma (SCC). For the periods 1991-1995, 1996-2000 and 2001-2005, the mean age at diagnosis increased from 53.9 ± 13.3 to 55.0 ± 14.9 and then to 56.7 ± 14.7 years, respectively. The incidence of SCC decreased from 1991 to 2005. During the same period, non-significant increases of adenocarcinoma and small cell carcinoma were noted. For SCC, occurrence peaked in 1991-1995 in patients 50-59 years of age. From 1996 to 2005, it peaked in patients 40-49 years of age. For cervical adenocarcinoma, occurrence peaked in patients 40-49 years of age, with a steady increase in this age group from 1991 to 2005. Occurrence of small cell cervical carcinoma peaked in the period 1991-1995 in patients 30-39 years of age. During the 15 years of the study, the overall mortality rate of the 198 patients with small cell cervical carcinoma was 65.7%. CONCLUSIONS In Taiwan, the incidence of small cell cervical carcinoma and adenocarcinoma tended to increase, but the incidence of squamous cell cervical carcinoma significantly decreased during the period 1991-2005.

Title: Comparison of influenza disease burden in older populations of Hong Kong and Brisbane: the impact of influenza and pneumococcal vaccination Content: BACKGROUND: Influenza and pneumococcal vaccine uptake in the older population aged 65 years or over of Hong Kong dramatically increased since the 2003 SARS outbreak. This study is aimed to evaluate the impact of increased coverage of influenza and pneumococcal vaccines by comparing the change of disease burden in the older population of Hong Kong, with the burden in the older population of Brisbane with relatively high vaccine coverage in the past fifteen years. METHODS: Time series segmented regression models were applied to weekly numbers of cause-specific mortality or hospitalization of Hong Kong and Brisbane. Annual excess rates of mortality or hospitalization associated with influenza in the older population were estimated for the pre-SARS (reference period), post-SARS and post-pandemic period, respectively. The rate ratios (RRs) between these periods were also calculated to assess the relative change of disease burden. RESULTS: Compared to the pre-SARS period, excess rates of mortality associated with influenza during the post-SARS period in Hong Kong decreased for cardiorespiratory diseases (RR = 0.90, 95% CI 0.80, 1.01), stroke (RR = 0.74, 95% CI 0.50, 1.09), and ischemic heart diseases (RR = 0.45, 95% CI 0.34, 0.58). The corresponding RRs in Brisbane were 0.79 (95% CI 0.54, 1.15), 0.33 (0.13, 0.80), and 1.09 (0.62, 1.90), respectively. Only the mortality of ischemic heart diseases showed a greater reduction in Hong Kong than in Brisbane. During the post-pandemic period, excess rates of all-cause mortality increased in Hong Kong, but to a lesser extent than in Brisbane (RR = 1.41 vs 2.39). CONCLUSION: A relative decrease (or less of an increase) of influenza disease burden was observed in the older population of Hong Kong after increased coverage of influenza and pneumococcal vaccines in this population, as compared to those of Brisbane where vaccination rates remained stable. The lack of significant findings in some disease categories highlights the challenges of evaluating the benefits of vaccination at the population level. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-3735-7) contains supplementary material, which is available to authorized users.

Title: Epidemiology of the 2020 pandemic of COVID‐19 in the state of Georgia: Inadequate critical care resources and impact after 7 weeks of community spread Content: OBJECTIVES: Novel coronavirus (COVID‐19) is a global pandemic currently spreading rapidly across the United States. We provide a comprehensive look at COVID‐19 epidemiology across the state of Georgia, which includes vast rural communities that may be disproportionately impacted by the spread of this infectious disease. METHODS: All 159 Georgia counties were included in this study. We examined the geographic variation of COVID‐19 in Georgia from March 3 through April 24, 2020 by extracting data on incidence and mortality from various national and state datasets. We contrasted county‐level mortality rates per 100,000 population (MRs) by county‐level factors. RESULTS: Metropolitan Atlanta had the overall highest number of confirmed cases; however, the southwestern rural parts of Georgia, surrounding the city of Albany, had the highest bi‐weekly increases in incidence rate. Among counties with >10 cases, MRs were highest in the rural counties of Randolph (233.2), Terrell (182.5), Early (136.3), and Dougherty (114.2). Counties with the highest MRs (22.5–2332 per 100,000) had a higher proportion of: non‐Hispanic Blacks residents, adults aged 60+, adults earning <$20,000 annually, and residents living in rural communities when compared with counties with lower MRs. These counties also had a lower proportion of the population with a college education, lower number of ICU beds per 100,000 population, and lower number of primary care physicians per 10,000 population. CONCLUSIONS: While urban centers in Georgia account for the bulk of COVID‐19 cases, high mortality rates and low critical care capacity in rural Georgia are also of critical concern.

Title: Outcomes and Cardiovascular Comorbidities in a Predominantly African-American Population with COVID-19 Content: Importance: Racial disparities in COVID-19 outcomes have been amplified during this pandemic and reports on outcomes in African-American (AA) populations, known to have higher rates of cardiovascular (CV) comorbidities, remain limited. Objective: To examine prevalence of comorbidities, rates of hospitalization and survival, and incidence of CV manifestations of COVID-19 in a predominantly AA population in south metropolitan Chicago. Design, Setting, Participants: This was an observational cohort study of COVID-19 patients encountered from March 16 to April 16, 2020 at the University of Chicago. Deidentified data were obtained from an institutional data warehouse. Group comparisons and logistic regression modeling based on baseline demographics, clinical characteristics, laboratory and diagnostic testing was performed. Exposures: COVID-19 was diagnosed by nasopharyngeal swab testing and clinical management was at the discretion of treating physicians. Main Outcomes and Measures: Primary outcomes were hospitalization and in-hospital mortality, and secondary outcomes included incident CV manifestations of COVID-19 in the context of overall cardiology service utilization. Results: During the 30 day study period, 1008 patients tested positive for COVID-19 and 689 had available encounter data. Of these, 596 (87%) were AA and 356 (52%) were hospitalized, of which 319 (90%) were AA. Age > 60 years, tobacco use, BMI >40 kg/m2, diabetes mellitus (DM), insulin use, hypertension, chronic kidney disease, coronary artery disease (CAD), and atrial fibrillation (AF) were more common in hospitalized patients. Age > 60 years, tobacco use, CAD, and AF were associated with greater risk of in-hospital mortality along with several elevated initial laboratory markers including troponin, NT-proBNP, blood urea nitrogen, and ferritin. Despite this, cardiac manifestations of COVID-19 were uncommon, coincident with a 69% decrease in cardiology service utilization. For hospitalized patients, median length of stay was 6.2 days (3.4-11.9 days) and mortality was 13%. AA patients were more commonly hospitalized, but without increased mortality. Conclusions and Relevance: In this AA-predominant experience from south metropolitan Chicago, CV comorbidities and chronic diseases were highly prevalent and associated with increased hospitalization and mortality. Insulin-requiring DM and CKD emerged as novel predictors for hospitalization. Despite the highest rate of comorbidities reported to date, CV manifestations of COVID-19 and mortality were relatively low. The unexpectedly low rate of mortality merits further study.

Title: Urban Air Pollution May Enhance COVID-19 Case-Fatality and Mortality Rates in the United States Content: BACKGROUND: The novel human coronavirus disease 2019 (COVID-19) pandemic has claimed more than 240,000 lives worldwide, causing tremendous public health, social, and economic damages. While the risk factors of COVID-19 are still under investigation, environmental factors, such as urban air pollution, may play an important role in increasing population susceptibility to COVID-19 pathogenesis. METHODS: We conducted a cross-sectional nationwide study using zero-inflated negative binomial models to estimate the association between long-term (2010–2016) county-level exposures to NO(2), PM(2.5) and O(3) and county-level COVID-19 case-fatality and mortality rates in the US. We used both single and multipollutant models and controlled for spatial trends and a comprehensive set of potential confounders, including state-level test positive rate, county-level healthcare capacity, phase-of-epidemic, population mobility, sociodemographic, socioeconomic status, behavior risk factors, and meteorological factors. RESULTS: 1,027,799 COVID-19 cases and 58,489 deaths were reported in 3,122 US counties from January 22, 2020 to April 29, 2020, with an overall observed case-fatality rate of 5.8%. Spatial variations were observed for both COVID-19 death outcomes and long-term ambient air pollutant levels. County-level average NO(2) concentrations were positively associated with both COVID-19 case-fatality rate and mortality rate in single-, bi-, and tri-pollutant models (p-values<0.05). Per inter-quartile range (IQR) increase in NO(2) (4.6 ppb), COVID-19 case-fatality rate and mortality rate were associated with an increase of 7.1% (95% CI 1.2% to 13.4%) and 11.2% (95% CI 3.4% to 19.5%), respectively. We did not observe significant associations between long-term exposures to PM(2.5) or O(3) and COVID-19 death outcomes (p-values>0.05), although per IQR increase in PM(2.5) (3.4 ug/m(3)) was marginally associated with 10.8% (95% CI: −1.1% to 24.1%) increase in COVID-19 mortality rate. DISCUSSIONS AND CONCLUSIONS: Long-term exposure to NO(2), which largely arises from urban combustion sources such as traffic, may enhance susceptibility to severe COVID-19 outcomes, independent of long-term PM(2.5) and O(3) exposure. The results support targeted public health actions to protect residents from COVID-19 in heavily polluted regions with historically high NO(2) levels. Moreover, continuation of current efforts to lower traffic emissions and ambient air pollution levels may be an important component of reducing population-level risk of COVID-19 deaths.

Title: Relative Coronavirus Disease 2019 Mortality: A Swiss Population-based Study Content: Objective: Severity of the coronavirus disease 2019 (covid-19) has been assessed in terms of absolute mortality in SARS-CoV-2 positive cohorts. An assessment of mortality relative to mortality in the general population is presented. Design: Retrospective population-based study. Setting: Individual information on symptomatic confirmed SARS-CoV-2 patients and subsequent deaths from any cause were compared to the all-cause mortality in the Swiss population of 2018. Starting February 23, 2020, mortality in covid-19 patients was monitored for 80 days and compared to the population mortality observed in the same time-of-year starting February 23, 2018. Participants: 5 160 595 inhabitants of Switzerland aged 35 to 95 without covid-19 (general population in spring 2018) and 20 769 persons tested positively for covid-19 (spring 2020). Measurements: Sex- and age-specific mortality rates were estimated using Cox proportional hazards models. Absolute probabilities of death were predicted and risk was assessed in terms of relative mortality by taking the ratio between the sex- and age-specific absolute mortality in covid19 patients and the corresponding mortality in the 2018 general population. Results: A confirmed SARS-CoV-2 infection substantially increased the probability of death across all patient groups, ranging from nine (6 to 15) times the population mortality in 35-year old infected females to a 53-fold increase (46 to 59) for 95 year old infected males. The highest relative risks were observed among males and older patients. The magnitude of these effects was smaller compared to increases observed in absolute mortality risk. Male covid-19 patients exceeded the population hazard for males (hazard ratio 1.20, 1.00 to 1.44). Each additional year of age increased the population hazard in covid-19 patients (hazard ratio 1.04, 1.03 to 1.05). Limitations: Information about the distribution of relevant comorbidities was not available on population level and the associated risk was not quantified. Conclusions: Health care professionals, decision makers, and societies are provided with an additional population-adjusted assessment of covid-19 mortality risk. In combination with absolute measures of risk, the relative risks presented here help to develop a more comprehensive understanding of the actual impact of covid-19.

Title: Cefepime Efficacy and Safety in Children: A Systematic Review and Meta-analysis. Content: Background Cefepime is a fourth-generation cephalosporin antibiotic used to treat a variety of infections. The US Food and Drug Administration approved its use in certain types of infections among pediatric patients, and yet there have been mixed data about its efficacy and safety in this population. Objective The objective of this review is to compare efficacy and all-cause mortality of cefepime to other clinically indicated antibiotics among children. Methods We conducted a systematic search of MEDLINE, EMBASE, CENTRAL, LILACS, and clinicaltrials.gov databases through February 8, 2016. We included randomized controlled trials comparing cefepime to other clinical antibiotics, placebo, or no treatment in children aged 0-19 years in the inpatient setting with clinical signs of infection. The primary outcome of interest was all-cause mortality. The secondary outcomes were success rate, treatment failure, and incidence of adverse events. Study quality was assessed using the Cochrane Risk of Bias Assessment Tool. Results Seventeen studies met the inclusion criteria. There was a total of 1,285 participants included, 624 participants in the cefepime arm and 661 in the comparison arm. A random effects meta-analysis for all-cause mortality showed no difference in rates of mortality between cefepime and comparator antibiotics with a mortality risk ratio of 0.88 (95% CI: 0.71-1.08). For the secondary outcomes of success rate and treatment failure, a random effects model meta-analysis conducted of the studies showed no difference in rate between cefepime and comparator antibiotics with an overall risk ratio of 0.98 (95% CI: 0.92-1.05) and 1.04 (95% CI: 0.91-1.19), respectively. Adverse events were not statistically assessed given widespread heterogeneity. Overall, the studies had unclear risk of bias and were limited by high heterogeneity and methodological flaws. Conclusion The efficacy and safety of cefepime in pediatric patients remain unclear despite the inclusion of newer trials since the last index systematic review conducted a decade ago.

Title: Identification of Vulnerable Populations and Areas at Higher Risk of COVID-19 Related Mortality in the U.S. Content: Background The role of health-related disparities including sociodemographic, environmental, and critical care capacity in the COVID-19 pandemic are poorly understood. In the present study, we characterized vulnerable populations located in areas at higher risk of COVID-19 related mortality and low critical healthcare capacity in the U.S. Methods Using Bayesian multilevel analysis and small area disease risk mapping, we assessed the spatial variation of COVID-19 related mortality risk for the U.S. in relation with healthcare disparities including race, ethnicity, poverty, air quality, and critical healthcare capacity. Results Overall, highly populated, regional air hub areas, and minorities had an increased risk of COVID-19 related mortality. We found that with an increase of only 1 ug/m3 in long term PM2.5 exposure, the COVID-19 mortality rate increased by 13%. Counties with major air hubs had 18% increase in COVID-19 related death compared to counties with no airport connectivity. Sixty-eight percent of the counties with high COVID-19 related mortality risk were also counties with lower critical care capacity than national average. These counties were primary located at the North- and South-Eastern regions of the country. Conclusion The existing disparity in health and environmental risk factors that exacerbate the COVID-19 related mortality, along with the regional healthcare capacity, determine the vulnerability of populations to COVID-19 related mortality. The results from this study can be used to guide the development of strategies for the identification and targeting preventive strategies in vulnerable populations with a higher proportion of minority groups living in areas with poor air quality and low healthcare capacity.

Title: The effect of public health measures on the 1918 influenza pandemic in U.S. cities. Content: During the 1918 influenza pandemic, the U.S., unlike Europe, put considerable effort into public health interventions. There was also more geographic variation in the autumn wave of the pandemic in the U.S. compared with Europe, with some cities seeing only a single large peak in mortality and others seeing double-peaked epidemics. Here we examine whether differences in the public health measures adopted by different cities can explain the variation in epidemic patterns and overall mortality observed. We show that city-specific per-capita excess mortality in 1918 was significantly correlated with 1917 per-capita mortality, indicating some intrinsic variation in overall mortality, perhaps related to sociodemographic factors. In the subset of 23 cities for which we had partial data on the timing of interventions, an even stronger correlation was found between excess mortality and how early in the epidemic interventions were introduced. We then fitted an epidemic model to weekly mortality in 16 cities with nearly complete intervention-timing data and estimated the impact of interventions. The model reproduced the observed epidemic patterns well. In line with theoretical arguments, we found the time-limited interventions used reduced total mortality only moderately (perhaps 10-30%), and that the impact was often very limited because of interventions being introduced too late and lifted too early. San Francisco, St. Louis, Milwaukee, and Kansas City had the most effective interventions, reducing transmission rates by up to 30-50%. Our analysis also suggests that individuals reactively reduced their contact rates in response to high levels of mortality during the pandemic.

Title: Association of BCG vaccination policy with prevalence and mortality of COVID-19 Content: There is some evidence that tuberculosis vaccine bacillus Calmette-Guérin (BCG) has non-specific beneficial effects against non-related infections. Here, we examined the possible association between BCG vaccination with prevalence and mortality by COVID-19 by using publicly available data of COVID-19 in 199 countries/regions and the BCG World Atlas. By using linear regression modeling, we found that the number of total cases and deaths per one million population were significantly associated with the country's policy concerning BCG vaccine administration. The amount of variance in cases and deaths explained by BCG vaccination policy ranged between 12.5% and 38%. Importantly, this effect remained significant after controlling for the country's life expectancy and the average temperature in February and March 2020, which themselves are significantly correlated with the cases and deaths indices, respectively. By contrast, the ratio between deaths and cases was weakly affected. This latter outcome suggested that BCG vaccination may have hindered the overall spread of the virus or progression of the disease rather than reducing mortality rates (i.e., deaths/cases ratio). Finally, by roughly dividing countries into three categories showing high, middle, or low growth rate of the cases, we found a highly significant difference between the slope categories among the BCG groups, suggesting that the time since the onset of the spread of the virus was not a major confounding factor. While this study potentially suffers from a number of unknown confounding factors, these associations support the idea that BCG vaccination may provide protection against SARS-CoV-2, which, together with its proven safety, encourages consideration of further detailed epidemiological studies, large-scale clinical trials on the efficacy of this vaccine on COVID-19, and/or re-introduction of BCG vaccination practice in the countries which are currently devoid of the practice.

Title: High-Frequency Oscillatory Ventilation in Pediatric Acute Hypoxemic Respiratory Failure: Disease-Specific Morbidity Survival Analysis Content: BACKGROUND: Multiple ventilatory strategies for acute hypoxemic respiratory failure (AHRF) in children have been advocated, including high-frequency oscillatory ventilation (HFOV). Despite the frequent deployment of HFOV, randomized controlled trials remain elusive and currently there are no pediatric trials looking at its use. Our longitudinal study analyzed the predictive clinical outcome of HFOV in pediatric AHRF given disease-specific morbidity. METHODS: A retrospective 8-year review on pediatric intensive care unit admissions with AHRF ventilated by HFOV was performed. Primary outcomes included survival, morbidity, length of stay (LOS), and factors associated with survival or mortality. RESULTS: A total of 102 patients underwent HFOV with a 66 % overall survival rate. Survivors had a greater LOS than nonsurvivors (p = 0.001). Mortality odds ratio (OR) for patients without bronchiolitis was 8.19 (CI = 1.02, 65.43), and without pneumonia it was 3.07 (CI = 1.12, 8.39). A lower oxygenation index (OI) after HFOV commencement and at subsequent time points analyzed predicted survival. After 24 h, mortality was associated with an OI > 35 [OR = 31.11 (CI = 3.25, 297.98)]. Sepsis-related mortality was associated with a higher baseline FiO(2) (0.88 vs. 0.65), higher OI (42 vs. 22), and augmented metabolic acidosis (pH of 7.25 vs. 7.32) evaluated 4 h on HFOV (p < 0.05). CONCLUSION: High-frequency oscillatory ventilation may be safely utilized. It has a 66 % overall survival rate in pediatric AHRF of various etiologies. Patients with morbidity limited to the respiratory system and optimized oxygenation indices are most likely to survive on HFOV.

Title: COVID-19: Modelling Local Transmission and Morbidity effects to provide an estimate of overall Relative Healthcare Resource Impact by General Practice Granularity Content: Introduction Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the name given to the 2019 novel coronavirus. COVID-19 is the name given to the disease associated with the virus. SARS-CoV-2 is a new strain of coronavirus that has not been previously identified in humans. Methods Two key factors were analysed which when multiplied together would give an estimate of relative demand on healthcare utilisation. These factors were case incidence and case morbidity. GP Practice data was used as this provided the most geographically granular source of published public population data. To analyse case incidence, the latest values for indicators that could be associated with infection transmission rates were collected from the Office of National Statistics (ONS) and Quality Outcome Framework (QOF) sources. These included population density, % age >16 at fulltime work/education, % age over 60, % BME ethnicity, social deprivation as IMD 2019, Location as latitude/longitude, and patient engagement as % self-confident in their own long term condition management. Average case morbidity was calculated by applying the international mortality Odds Ratio to the local population relevant age and disease prevalences and then summing and dividing by the equivalent national figure. To provide a comparative measure of overall healthcare resource impact, individual GP practice impact scores were compared against the median practice. Results The case incidence regression is a dynamic situation with the significance of specific factors moderating over time as the balance between external infection, community transmission and impact of mitigation measures feeds through to the number of cases. It showed that currently Urban, % Working and age >60 were the strongest determinants of case incidence. The local population comorbidity remains unchanged. The range of relative HC impact was wide with 80% of practices falling between 20%-250% of the national median. Once practice population numbers were included it showed that the top 33% of GP practices supporting 45% of the patient population would require 68% of COVID-19 healthcare resources. The model provides useful information about the relative impact of Covid-19 on healthcare workload at GP practice granularity in all parts of England. Conclusion Covid-19 is impacting on the utilisation of health and social care resources across the country. This model provides a method for predicting relative local levels of disease burden based on defined criteria and thereby providing a method for targeting limited (and perhaps soon to be scarce) care resources to optimise national, regional and local responses to the COVID-19 outbreak.

Title: A population-based analysis of emergent versus elective paraesophageal hernia repair using the Nationwide Inpatient Sample. Content: BACKGROUND As the life expectancy in the United States continues to increase, more elderly, sometimes frail patients present with sub-acute surgical conditions such as a symptomatic paraesophageal hernia (PEH). While the outcomes of PEH repair have improved largely due to the proliferation of laparoscopic surgery, there is still a defined rate of morbidity and mortality. We sought to characterize the outcomes of both elective and emergent PEH repair using a large population-based data set. METHODS The Nationwide Inpatient Sample was queried for primary ICD-9 codes associated with PEH repair (years 2006-2008). Outcomes were in-hospital mortality and the occurrence of a pre-identified complication. Multivariate analysis was performed to determine the risk factors for complications and mortality following both elective and emergent PEH repair. RESULTS A total of 8,462 records in the data, representing 41,723 patients in the US undergoing PEH repair in the study interval, were identified. Of these procedures, 74.2% was elective and 42.4% was laparoscopic. The overall complication and mortality rates were 20.8 and 1.1%, respectively. Emergent repair was associated with a higher rate of morbidity (33.4 vs. 16.5%, p < 0.001) and mortality (3.2 vs. 0.37%, p < 0.001) than elective repair. Emergent repair patients were more likely to be male, were older, and more likely to be minority. Logistic modeling revealed that younger age, elective case status, and a laparoscopic approach were independently associated with a lower probability of complications and mortality. CONCLUSIONS Patients undergoing emergent PEH repair in the United States tend to be older, more likely a racial minority, and less likely to undergo laparoscopic repair. Elective repair, younger age, and a laparoscopic approach are associated with improved outcomes. Considering all of the above, we recommend that patients consider elective repair with a surgeon experienced in the laparoscopic approach, especially when symptoms related to the hernia are present.

Title: Long-Term Survival after Radiofrequency Ablation of Lung Oligometastases from Five Types of Primary Lesions: A Retrospective Evaluation. Content: PURPOSE To conduct a retrospective evaluation of long-term survival after radiofrequency (RF) ablation for lung oligometastases from 5 types of primary lesions. MATERIALS AND METHODS The study population consisted of 123 patients with lung oligometastases from colorectal cancer (CRC), non-small-cell lung cancer, hepatocellular carcinoma, esophageal cancer, and renal-cell carcinoma treated with RF ablation. Lung oligometastases were defined as 1-5 metastases confined to the lung while the primary cancer and other metastases were eradicated. Overall survival (OS) and recurrence-free survival (RFS) were estimated for the overall study population and for patients with each type of primary lesion. The OS and RFS rates were compared with those of the patients with any of the other four primary lesion types. Finally, various variables were analyzed to determine what factors influenced OS and RFS. RESULTS The median follow-up was 45.7 months, and the 5-year OS and RFS rates for all 123 patients were 62% and 25%, respectively. The OS time for patients with metastases from CRC was significantly longer (P = .042); it was significantly shorter (P = .022) in patients with metastases from esophageal cancer. Longer disease-free interval was significantly (P = .015) associated with better OS. There was no variable significantly associated with OS and RFS on multivariate analyses. CONCLUSIONS Data from this single-center study appear promising in terms of long-term survival after RF ablation of lung oligometastases from 5 primary lesions.

Title: Semi-quantitative visual assessment of chest radiography is associated with clinical outcomes in critically ill patients Content: BACKGROUND: Respiratory pathology is a major driver of mortality in the intensive care unit (ICU), even in the absence of a primary respiratory diagnosis. Prior work has demonstrated that a visual scoring system applied to chest radiographs (CXR) is associated with adverse outcomes in ICU patients with Acute Respiratory Distress Syndrome (ARDS). We hypothesized that a simple, semi-quantitative CXR score would be associated with clinical outcomes for the general ICU population, regardless of underlying diagnosis. METHODS: All individuals enrolled in the Registry of Critical Illness at Brigham and Women’s Hospital between June 2008 and August 2018 who had a CXR within 24 h of admission were included. Each patient’s CXR was assigned an opacification score of 0–4 in each of four quadrants with the total score being the sum of all four quadrants. Multivariable negative binomial, logistic, and Cox regression, adjusted for age, sex, race, immunosuppression, a history of chronic obstructive pulmonary disease, a history of congestive heart failure, and APACHE II scores, were used to assess the total score’s association with ICU length of stay (LOS), duration of mechanical ventilation, in-hospital mortality, 60-day mortality, and overall mortality, respectively. RESULTS: A total of 560 patients were included. Higher CXR scores were associated with increased mortality; for every one-point increase in score, in-hospital mortality increased 10% (OR 1.10, CI 1.05–1.16, p < 0.001) and 60-day mortality increased by 12% (OR 1.12, CI 1.07–1.17, p < 0.001). CXR scores were also independently associated with both ICU length of stay (rate ratio 1.06, CI 1.04–1.07, p < 0.001) and duration of mechanical ventilation (rate ratio 1.05, CI 1.02–1.07, p < 0.001). CONCLUSIONS: Higher values on a simple visual score of a patient’s CXR on admission to the medical ICU are associated with increased in-hospital mortality, 60-day mortality, overall mortality, length of ICU stay, and duration of mechanical ventilation.

Title: Radiofrequency ablation of hepatocellular carcinoma as bridge therapy to liver transplantation: A 10-year intention-to-treat analysis. Content: In a long-term (10-year) study of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) as bridging therapy in patients listed for orthotopic liver transplantation (LT), we evaluated the impact of RFA on waiting list dropout rate, post-LT tumor recurrence, and long-term intention-to-treat, disease-specific survival (DSS). From March 2004 to October 2014, RFA was performed as the initial stand-alone bridge therapy to LT for 121 patients (men/women ratio, 83:38; mean age, 60.0 years) with 156 de novo HCCs (mean size, 2.4 cm). Follow-up period from initial RFA ranged from 1.3 to 128.0 months (median, 42.9 months). We assessed the overall and tumor-specific waiting list dropout rates, post-LT tumor recurrence, and 10-year post-LT and intention-to-treat survival rates. Dropout from the waiting list due to tumor progression occurred in 7.4% of patients. HCC recurrence after LT occurred in 5.6% of patients. The post-LT overall survival (OS) rate at 5 and 10 years was 75.8% and 42.2%, respectively, and the recurrence-free survival (RFS) rate was 71.1% and 39.6%, respectively. Intention-to-treat OS, RFS, and DSS rates for the entire study population at 5 and 10 years were 63.5% and 41.2%, 60.8% and 37.7%, and 89.5% and 89.5%, respectively. CONCLUSION RFA as a first-line stand-alone bridge therapy to LT achieves excellent long-term overall and tumor-specific survivals, with a low dropout rate from tumor progression despite long wait list times and a sustained low tumor recurrence rate upon post-LT follow-up of up to 10 years. (Hepatology 2017;65:1979-1990).

Title: Systematic review on the outcomes of poller screw augmentation in intramedullary nailing of long bone fracture. Content: Various technical tips have been described on the placement of poller screws during intramedullary (IM) nailing; however studies reporting outcomes are limited. Overall there is no consistent conclusion about whether intramedullary nailing alone, or intramedullary nails augmented with poller screws is more advantageous.We conducted a systematic review of PubMed, EMBASE, and Cochrane databases. Seventy-five records were identified, of which 13 met our inclusion criteria. In a systematic review we asked: (1) What is the proportion of nonunions with poller screw usage? (2) What is the proportion of malalignment, infection and secondary surgical procedures with poller screw usage? The overall outcome proportion across the studies was computed using the inverse variance method for pooling.Thirteen studies with a total of 371 participants and 376 fractures were included. Mean follow-up time was 21.1 months. Mean age of included patients was 40.0 years. Seven studies had heterogenous populations of nonunions and acute fractures. Four studies included only acute fractures and two studies examined nonunions only.The results of the present systematic review show a low complication rate of IM nailing augmented with poller screws in terms of nonunion (4%, CI: 0.03-0.07), coronal plane malunion (5%, CI: 0.03-0.08), deep (5%, CI: 0.03-0.11) and superficial (6%, CI: 0.03-0.11) infections, and secondary procedures (8%, CI: 0.04-0.18).When compared with the existing literature our review suggests intramedullary nailing with poller screws has lower rates of nonunion and coronal malalignment when compared with nailing alone. Prospective randomized control trial is necessary to fully determine outcome benefits. Cite this article: EFORT Open Rev 2020;5:189-203. DOI: 10.1302/2058-5241.5.190040.

Title: The effects of environmental stressors on the mortality of the oldest old male population in Hong Kong, 1977-2006. Content: Although age-sex-specific mortality rates were decreasing over the years, such a trend was not observed for the male population aged 85 or above (the oldest old) in Hong Kong. Despite literature suggesting that environmental stressors were associated with higher mortality, the adverse effects of socioeconomic and political events were seldom included. Hence, this study explored the relationship between environmental stressors covering adverse weather conditions as well as key socioeconomic and political events and fluctuations in the oldest old mortality rates in Hong Kong during the period 1977 to 2006. The oldest old mortality rates in Hong Kong were observed to have a likelihood of being associated with these environmental stressors. Furthermore, men appeared to be more susceptible to these risk factors than did women. More care and attention should be given to the oldest old men, in particular, during periods of socioeconomic or political upheavals. A cohort study would be useful to study these stressors in greater detail.

Title: Molecular diagnosis of infectious diseases in São Miguel Island (Azores, Portugal): A hospital-based descriptive study. Content: INTRODUCTION We performed a descriptive analysis of molecular diagnosis of infectious agents in the São Miguel Island population, in order to address questions like what is the frequency of clinical requests, is it observable seasonality of pathogens, and what is the positive rate for the clinical diagnosis. METHODOLOGY This was a retrospective and descriptive study based on 878 individuals suspected of harboring infectious diseases during two consecutive years, 2012-2013. More than 25 different pathogens were investigated by polymerase chain reaction (PCR)-based methods. The individuals were stratified into gender, occupation, and age groups. RESULTS The pathogen with more clinical requests was hepatitis C virus, investigated in 225 individuals (30.0%), followed by Leptospira spp., in 187 (24.9%). Overall, data demonstrated a gender distribution bias, where 72.9% of cases were males. The age group of 25 to 44 years was the class with more clinical requests. Regarding occupation, a predominance of construction workers (12.0%) was observed, followed by retired workers (11.0%). Patient distribution per year showed a higher number of patients in the fall months. Diagnoses of leptospirosis and respiratory virus infections presented seasonality. CONCLUSIONS The present study provides a valid contribution to the knowledge of the epidemiology of infectious diseases in the São Miguel Island (Azores, Portugal) population.

Title: Burden and changes in HIV/AIDS morbidity and mortality in Southern Africa Development Community Countries, 1990–2017 Content: BACKGROUND: The 16 Southern Africa Development Community (SADC) countries remain the epicentre of the HIV/AIDS epidemic with the largest number of people living with HIV/AIDS. Anti-retroviral treatment (ART) has improved survival and prevention of mother-to-child transmission (PMTCT) of HIV, but the disease remains a serious cause of mortality. We conducted a descriptive epidemiological analysis of HIV/AIDS burden for the 16 SADC countries using secondary data from the Global Burden of Diseases, Injuries and Risk Factor (GBD) Study. METHODS: The GBD study is a systematic, scientific effort by the Institute for Health Metrics and Evaluation (IHME) to quantify the comparative magnitude of health loss due to diseases, injuries, and risk factors by age, sex, and geographies for specific points in time. We analyzed the following outcomes: mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to HIV/AIDS for SADC. Input data for GBD was extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service utilisation, disease notifications, and other sources. Country- and cause-specific HIV/AIDS-related death rates were calculated using the Cause of Death Ensemble model (CODEm) and spatiotemporal Gaussian process regression (ST-GPR). Deaths were multiplied by standard life expectancy at each age-group to calculate YLLs. Cause-specific mortality was estimated using a Bayesian meta-regression modelling tool, DisMod-MR. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases to calculate YLDs. Crude and age-adjusted rates per 100,000 population and changes between 1990 and 2017 were determined for each country. RESULTS: In 2017, HIV/AIDS caused 336,175 deaths overall in SADC countries, and more than 20 million DALYs. This corresponds to a 3-fold increase from 113,631 deaths (6,915,170 DALYs) in 1990. The five leading countries with the proportion of deaths attributable to HIV/AIDS in 2017 were Botswana at the top with 28.7% (95% UI; 23.7–35.2), followed by South Africa 28.5% (25.8–31.6), Lesotho, 25.1% (21.2–30.4), eSwatini 24.8% (21.3–28.6), and Mozambique 24.2% (20.6–29.3). The five countries had relative attributable deaths that were at least 14 times greater than the global burden of 1.7% (1.6–1.8). Similar patterns were observed with YLDs, YLLs, and DALYs. Comoros, Seychelles and Mauritius were on the lower end, with attributable proportions less than 1%, below the global proportion. CONCLUSIONS: Great progress in reducing HIV/AIDS burden has been achieved since the peak but more needs to be done. The post-2005 decline is attributed to PMTCT of HIV, resources provided through the US President’s Emergency Plan For AIDS Relief (PEPFAR), and behavioural change. The five countries with the highest burden of HIV/AIDS as measured by proportion of death attributed to HIV/AIDS and age-standardized mortaility rate were Botswana, South Africa, Lesotho, eSwatini, and Mozambique. SADC countries should cooperate, work with donors, and embrace the UN Fast-Track approach, which calls for frontloading investment from domestic or other sources to prevent and treat HIV/AIDS. Robust tracking, testing, and early treatment are required, as well as refinement of individual treatment strategies for transient individuals in the region.

Title: How many lives can be saved? A global view on the impact of testing, herd immunity and demographics on COVID-19 fatality rates Content: In this work, we assess the global impact of COVID-19 showing how demographic factors, testing policies and herd immunity are key for saving lives. We extend a standard epidemiological SEIR model in order to: (a) identify the role of demographics (population size and population age distribution) on COVID-19 fatality rates; (b) quantify the maximum number of lives that can be saved according to different testing strategies, different levels of herd immunity, and specific population characteristics; and (d) infer from the observed case fatality rates (CFR) what the true fatality rate might be. Different from previous SEIR model extensions, we implement a Bayesian Melding method in our calibration strategy which enables us to account for data limitation on the total number of deaths. We derive a distribution of the set of parameters that best replicate the observed evolution of deaths by using information from both the model and the data.

Title: Intracranial hemorrhage in patients with atrial fibrillation receiving anticoagulation therapy. Content: We investigated the frequency and characteristics of intracranial hemorrhage (ICH), the factors associated with the risk of ICH, and outcomes post-ICH overall and by randomized treatment. We identified patients with ICH from the overall trial population enrolled in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial who received ≥1 dose of the study drug (n = 18 140). ICH was adjudicated by a central committee. Cox regression models were used to identify factors associated with ICH. ICH occurred in 174 patients; most ICH events were spontaneous (71.7%) versus traumatic (28.3%). Apixaban resulted in significantly less ICH (0.33% per year), regardless of type and location, than warfarin (0.80% per year). Independent factors associated with increased risk of ICH were enrollment in Asia or Latin America, older age, prior stroke/transient ischemic attack, and aspirin use at baseline. Among warfarin-treated patients, the median (25th, 75th percentiles) time from most recent international normalized ratio (INR) to ICH was 13 days (6, 21 days). Median INR prior to ICH was 2.6 (2.1, 3.0); 78.5% of patients had a pre-ICH INR <3.0. After ICH, the modified Rankin scale score at discharge was ≥4 in 55.7% of patients, and the overall mortality rate at 30 days was 43.3% with no difference between apixaban- and warfarin-treated patients. ICH occurred at a rate of 0.80% per year with warfarin regardless of INR control and at a rate of 0.33% per year with apixaban and was associated with high short-term morbidity and mortality. This highlights the clinical relevance of reducing ICH by using apixaban rather than warfarin and avoiding concomitant aspirin, especially in patients of older age. This trial was registered at www.clinicaltrials.gov as #NCT00412984.

Title: Untangling factors associated with country-specific COVID-19 incidence, mortality and case fatality rates during the first quarter of 2020 Content: At early stages of the COVID-19 pandemic which we are experiencing, the publicly reported incidence, mortality and case fatality rates (CFR) vary significantly between countries. Here we aim to untangle factors that are associated with the differences during the first quarter of the year 2020. Number of performed COVID-19 tests has a strong correlation with country-specific incidence (p <2×10-16) and mortality rate (p = 5.1×10-8). Using multivariate linear regression we show that incidence and mortality rates correlate significantly with GDP per capita (p = 2.6×10-15 and 7.0×10-4, respectively), country-specific duration of the outbreak (2.6×10-4 and 0.0019), fraction of citizens over 65 years old (p = 0.0049 and 3.8×10-4) and level of press freedom (p = 0.021 and 0.019) which cumulatively explain 80% of variability of incidence and more than 60% of variability of mortality of the disease during the period analyzed. Country hemisphere demonstrated significant correlation only with mortality (p = 0.17 and 0.036) whereas population density (p = 0.94 and p = 0.75) and latitude (p = 0.61 and 0.059) did not reach significance in our model. Case fatality rate is shown to rise as the outbreak progresses (p = 0.028). We rank countries by COVID-19 mortality corrected for incidence and the factors that were shown to affect it, and by CFR corrected for outbreak duration, yielding very similar results. Among the countries where the outbreak started after the 15th of February and with at least 1000 registered patients during the period analyzed, the lowest corrected CFR are seen in Israel, South Africa and Chile. The ranking results should be considered with caution as they do not consider all confounding factors or data reporting biases.

Title: Microvascular Disease Confers Additional Risk to COVID-19 Infection Content: The majority of fatalities thus far in the COVID-19 pandemic have been attributed to pneumonia. As expected, the fatality rate reported in China is higher in people with chronic pulmonary disease (6.3%) and those who have cancer (5.6%). According to the American College of Cardiology Clinical Bulletin “COVID-19 Clinical Guidance for the CV Care Team”, there is a significantly higher fatality rate in people who are elderly (8.0% 70-79 years; 14.8% ≥80 years), diabetic (7.3%), hypertensive (6.0%), or have known cardiovascular disease (CVD) (10.5%). We propose a biological reason for the higher mortality risk in these populations that is apparent. We further present a set of pathophysiological reasons for the heightened danger that could lead to therapies for enhanced management and prevention. MVD And COVID Abstract The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-Cov2) results in COVID-19 which can lead to severe illness and death. The majority of fatalities thus far in the pandemic have been attributed to pneumonia. The overall mortality risk reported as of March 28, 2020 varies from 2.3% in China, 2.7% in Iran, and 0.5% in South Korea. As expected, the fatality rate reported in China is higher in people with chronic pulmonary disease (6.3%) and those who have cancer (5.6%). According to the American College of Cardiology Clinical Bulletin “COVID-19 Clinical Guidance for the CV Care Team”, there is a significantly higher fatality rate in people who are elderly (8.0% 70-79; 14.8% ≥80), diabetic (7.3%), hypertensive (6.0%), or have known cardiovascular disease (CVD) (10.5%). We propose a reason for the higher mortality risk in these populations that is not apparent. We further present a set of pathophysiological reasons for the heightened danger could lead to therapies for enhanced management and prevention.

Title: Comparative use of the Ages and Stages Questionnaires in the USA and Scandinavia: a systematic review. Content: AIM The aim of this systematic review was to investigate screening practices with the Ages and Stages Questionnaires (ASQ) and the Ages and Stages Questionnaires: Social-Emotional (ASQ:SE) in the USA and Scandinavia and to identify practical lessons and research opportunities. METHOD The review was performed for ASQ- and ASQ:SE-related studies in children from birth to 5 years. From nine databases and 1689 references (published from 1988-2018), 127 articles were included and categorized using Covidence online software. The Critical Appraisal Skills Programme Checklists were used before data synthesis. RESULTS US studies primarily use the ASQ/ASQ:SE to detect delays in general and at-risk populations in medical settings, which increases early detection, clinician-referral, and intervention rates. Scandinavian studies commonly use the ASQ/ASQ:SE to monitor developmental-behavioural differences in intervention/exposure-based cohorts. Pre-visit screening yields completion/return rates of 83% to more than 90% and fosters same-day interpretation. When referrals are indicated, systemwide care coordination or colocation with a developmental-behavioural specialist is beneficial. INTERPRETATION Practical implementation lessons are reviewed. Research opportunities include investigating and measuring the ASQ/ASQ:SE's 'overall' sections. Danish, Norwegian, and Swedish translations are available but up-to-date norming and validation studies are needed throughout Scandinavia. Randomized controlled trials are needed to investigate outcomes in screened versus unscreened cohorts. WHAT THIS PAPER ADDS General and at-risk populations broadly benefited from periodic Ages and Stages Questionnaires (ASQ) and/or Ages and Stages Questionnaires: Social-Emotional (ASQ:SE) screening. Pre-visit ASQ and/or ASQ:SE screenining implementation systems work best. The ASQ and ASQ:SE 'overall' sections are not quantifiable and under-researched.

Title: Health impact of hospital restrictions on seriously ill hospitalized patients: lessons from the Toronto SARS outbreak. Content: BACKGROUND Restrictions on non-urgent hospital care imposed to control the 2003 Toronto severe acute respiratory syndrome outbreak led to substantial disruptions in hospital clinical practice, admission, and transfer patterns. OBJECTIVES We assessed whether there were unintended health consequences to seriously ill hospitalized patients. STUDY DESIGN, SETTING, AND POPULATION: Population-based longitudinal cohort study of patients residing in Toronto or an urban control region with an incident admission for 1 of 7 serious conditions in the 3 years before, or the 4 months during or after restrictions. OUTCOME MEASURES Short-term mortality, overall readmissions, cardiac readmissions for acute myocardial infarction patients, serious complications for very low birth weight babies, and quality of care measures, comparing adjusted rates across time periods within regions. RESULTS Mortality, readmission, and complication rates did not change for any condition during or after severe acute respiratory syndrome restrictions. Although rates of invasive cardiac procedures for acute myocardial infarction patients decreased 11-37% in Toronto, rates of nonfatal cardiac outcomes did not change. CONCLUSIONS Restrictions on non-urgent hospital utilization and hospital transfers may be a safe public health strategy to employ to control nosocomial outbreaks or provide hospital surge capacity for up to several months, in large, well-developed healthcare systems with good availability of community-based care.

Title: Excess mortality from seasonal influenza is negligible below the age of 50 in Israel: implications for vaccine policy Content: PURPOSE: Evaluation of the severity of pandemic influenza requires reliable estimates of mortality attributable to the seasonal influenza. METHODS: Excess age-specific mortality during periods of influenza activity was evaluated in Israel during the period 1999–2006 for three death categories. For each respiratory year, the lowest monthly moving average for the mortality rate was subtracted from each month in the period of influenza activity. Average mortality rates in years with minimal influenza activity were deducted from corresponding months to exclude winter mortality unrelated to influenza. The sums of these results were used as estimates of excess mortality rates. RESULTS: Overall excess mortality rates ranged from 7.7 to 36.1 per 100,000 for all causes, and from 4.4 to 24.4 per 100,000 for respiratory and circulatory causes. Influenza was associated with an average of 869 (range 280–1,516) deaths annually from respiratory and circulatory diseases during seasons with significant influenza activity. About 90% of the influenza-associated mortality from respiratory and circulatory diseases was in the age group 65+ years and about 1% in the age group <50 years. The age group <50 years accounted for an annual average of seven deaths from respiratory and circulatory diseases. CONCLUSION: Annual mortality associated with seasonal influenza is highly variable. Under the age of 50 years, there is minimal seasonal influenza associated mortality. This information provides an important baseline for evaluating the severity of the A(H1N1) 2009 influenza pandemic, where persons under 50 years of age were often disproportionately represented.

Title: Controlled Avalanche: A Regulated Voluntary Exposure Approach for Addressing Covid19 Content: Background: The ongoing Covid-19 pandemic has driven many countries to take radical suppression measures. While reducing mortality, these measures result in severe economic repercussions, and inhibit the development of herd immunity. Until an effective vaccine will be available, we propose an alternative approach, akin to avalanche control at ski resorts, a practice which intentionally triggers small avalanches in order to prevent a singular catastrophic one. Its main goal is to approach herd immunity faster than the current alternatives, with lower mortality rates and lower demand for critical health-care resources. According to this approach, individuals whose probability of developing serious health conditions is low (i.e. 20-49 years old with no comorbidities) will be offered the option to be voluntarily exposed to the virus under controlled supervision, and will then be issued 'immunity certificates' if they are confirmed to have developed SARS-CoV-2 antibodies. Methods: Using a compartmental model we examine the implications of the controlled avalanche (CA) strategy over the population in Israel. We compare four scenarios: in two scenarios the CA program is applied to the low-risk population (with the rest of the population subject to mitigation measures), followed by mitigation for the entire population or by uncontrolled spread. These are compared to mitigated and uncontrolled scenarios without the CA program. We discuss the economic, ethical and public health implications of the CA strategy. Findings: We show that compared to mitigation of the entire population, the CA strategy reduces the overall mortality by 43%, reduces the maximum number of people in need for ICUs by 62% and decreases the time required for release of 50% of the low-risk population by more than 2 months. Interpretation: This study suggests an ethically acceptable practice, that enables reaching herd immunity faster than the current alternatives, with low mortality and minimal economic damage.

Title: The Longevity-Frailty Hypothesis: Evidence from COVID-19 Death Rates in Europe Content: COVID-19 death rates vary strikingly across Europe. The death rate in Spain, for example, is greater than the death rate in Germany by more than a factor of ten. Few if any epidemiological indicators distinguish the countries of Europe by such a vast margin. Evidence on age-specific case-fatality rates (deaths over observed infections) and age-specific death rates (deaths over population) indicate that COVID-19 disproportionately afflicts the elderly and frail, suggesting that the share of elderly population (≥ 65 years of age) in a country ought to be a strong predictor of the COVID-19 death rate. However, the COVID-19 death rate and the share of elderly population are statistically uncorrelated (r = 0.163, p = 0.399). Share of population ≥ 65 years of age is confounded by mortality selection, as well as other demographic dynamics. By contrast, elderly longevity or life expectancy at 65 more effectively captures population survival and the accumulation of age-related frailty in society. We find a strong statistical relationship between the COVID-19 death rate (r = 0.839, p < .001) and elderly longevity, and a moderately strong relationship between the date of epidemic timing and elderly longevity (r = −0.634, p < .001). These relationships are robust to the inclusion of statistical controls for international tourism inflow and hospital bed capacity. While the countries of Europe vary meaningfully in healthcare system capacity and in the timing and intensity of non-pharmaceutical interventions, the striking variation in COVID-19 death rates across these countries is statistically and intuitively associated with elderly survival and consequent frailty.

Title: Urban Scaling of COVID-19 epidemics Content: Susceptible-Invective-Recovered (SIR) mathematical models are in high demand due to the COVID-19 pandemic. They are used in their standard formulation, or through the many variants, trying to fit and hopefully predict the number of new cases for the next days or weeks, in any place, city, or country. Such is key knowledge for the authorities to prepare for the health systems demand or to apply restrictions to slow down the infectives curve. Even when the model can be easily solved ---by the use of specialized software or by programming the numerical solution of the differential equations that represent the model---, the prediction is a non-easy task, because the behavioral change of people is reflected in a continuous change of the parameters. A relevant question is what we can use of one city to another; if what happened in Madrid could have been applied to New York and then, if what we have learned from this city would be of use for S\~ao Paulo. With this idea in mind, we present an analysis of a spreading-rate related measure of COVID-19 as a function of population density and population size for all US counties, as long as for Brazilian cities and German cities. Contrary to what is the common hypothesis in epidemics modeling, we observe a higher {\em per-capita} contact rate for higher city's population density and population size. Also, we find that the population size has a more explanatory effect than the population density. A contact rate scaling theory is proposed to explain the results.

Title: COVID-19: intensive care units, mechanical ventilators, and latent mortality profiles associated with case-fatality in Brazil. Content: In response to the accelerated increase in the number of COVID-19 cases, countries must increase their supply of beds in intensive care units (ICUs). Respiratory diseases, neoplasms, cardiopathies and hypertension, and diabetes are associated with higher COVID-19 case-fatality. The study aimed to identify the regions of Brazil with higher specific mortality rates from these comorbidities and the regions with the greatest shortage of ICU beds and mechanical ventilators. A cross-sectional ecological study was performed in which the units of analysis were the country's Health Regions. Data were obtained from Brazilian Health Informatics Department - DATASUS (National Registry of Healthcare Establishments - 2019, Mortality Information Systems - 2017, and Population Projections - 2017). We calculated the disease group-specific mortality rates for hypertension, neoplasms, diabetes, cardiac diseases, respiratory diseases and the rates of total ICU beds, private ICU beds, ICU beds in the Brazilian Unified National Health System (SUS), and ventilators in the SUS, per 100,000 inhabitants. The mortality profile was determined by latent profiles analysis, and the cluster analysis of ICU beds and ventilators used the spatial scan method. Kernel maps were constructed for the data's visualization. Level of significance was set at 5%. Four latent mortality profiles were observed. The Health Regions with the highest mean mortality rates were located in regions with shortages of ICU beds and ventilators, especially in parts of the Northeast, Southeast, and South of Brazil. The spatial localization of regions with both the highest mortality and shortages of ICU beds/ventilators requires attention by policymakers and public planners to deal efficiently and fairly with the COVID-19 epidemic in Brazil.

Title: Impact of population mask wearing on Covid-19 post lockdown Content: COVID-19, caused by SARS-CoV2 is a rapidly spreading global pandemic. Although precise transmission routes and dynamics are unknown, SARS-CoV2 is thought primarily to spread via contagious respiratory droplets. Unlike with SARS-CoV, maximal viral shedding occurs in the early phase of illness, and this is supported by models that suggest 40-80% of transmission events occur from pre- and asymptomatic individuals. One widely-discussed strategy to limit transmission of SARS-CoV2, particularly from presymptomatic individuals, has been population-level wearing of masks. Modelling for pandemic influenza suggests some benefit in reducing total numbers infected with even 50% mask-use. COVID-19 has a higher hospitalization and mortality rate than influenza, and the impacts on these parameters, and critically, at what point in the pandemic trajectory mask-use might exert maximal benefit are completely unknown. We derived a simplified SIR model to investigate the effects of near-universal mask-use on COVID-19 assuming 8 or 16% mask efficacy. We decided to model, in particular, the impact of masks on numbers of critically-ill patients and cumulative mortality, since these are parameters that are likely to have the most severe consequences in the COVID-19 pandemic. Whereas mask use had a relatively minor benefit on critical-care and mortality rates when transmissibility (Reff) was high, the reduction on deaths was dramatic as the effective R approached 1, as might be expected after aggressive social-distancing measures such as wide-spread lockdowns. One major concern with COVID-19 is its potential to overwhelm healthcare infrastructures, even in resource-rich settings, with one third of hospitalized patients requiring critical-care. We incorporated this into our model, increasing death rates for when critical-care resources have been exhausted. Our simple model shows that modest efficacy of masks could avert substantial mortality in this scenario. Importantly, the effects on mortality became hyper-sensitive to mask-wearing as the effective R approaches 1, i.e. near the tipping point of when the infection trajectory is expected to revert to exponential growth, as would be expected after effective lockdown. Our model suggests that mask-wearing might exert maximal benefit as nations plan their post-lockdown strategies and suggests that mask-wearing should be included in further more sophisticated models of the current pandemic.

Title: What is the daily practice of mechanical ventilation in pediatric intensive care units? A multicenter study Content: OBJECTIVE: To describe the daily practice of mechanical ventilation (MV), and secondarily, its outcome in pediatric intensive care units (PICUs). DESIGN: Prospective cohort of infants and children who received MV for at least 12 h. SETTING: Thirty-six medical surgical PICUs. PATIENTS: All consecutive patients admitted to the PICUs during 2-month period. MEASUREMENTS AND MAIN RESULTS: Of the 1893 patients admitted, 659 (35%) received MV for a median time of 4 days (25th percentile, 75%: 2, 6). Median of age was 13 months (25th percentile, 75%: 5, 48). Common indications for MV were acute respiratory failure (ARF) in 72% of the patients, altered mental status in 14% of the patients, and ARF on chronic pulmonary disease in 10% of the patients. Median length of stay in the PICUs was 8 days (25th percentile, 75%: 5, 13). Overall mortality rate in the PICUs was 15% (confidence interval 95%: 13–18) for the entire population, 50% (95% CI: 25–74) in patients who received MV because of acute respiratory distress syndrome, 24% (95% CI: 16–35) in patients who received MV for altered mental status and 16% (95% CI: 9–29) in patients who received MV for ARF on chronic pulmonary disease. CONCLUSION: One in every 3 patients admitted to the PICUs requires ventilatory support.. The ARF was the most common reason for MV, and survival of unselected infants and children receiving MV for more than 12 h was 85%. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00134-004-2225-5

Title: Nonpharmaceutical interventions implemented by US cities during the 1918-1919 influenza pandemic. Content: CONTEXT A critical question in pandemic influenza planning is the role nonpharmaceutical interventions might play in delaying the temporal effects of a pandemic, reducing the overall and peak attack rate, and reducing the number of cumulative deaths. Such measures could potentially provide valuable time for pandemic-strain vaccine and antiviral medication production and distribution. Optimally, appropriate implementation of nonpharmaceutical interventions would decrease the burden on health care services and critical infrastructure. OBJECTIVES To examine the implementation of nonpharmaceutical interventions for epidemic mitigation in 43 cities in the continental United States from September 8, 1918, through February 22, 1919, and to determine whether city-to-city variation in mortality was associated with the timing, duration, and combination of nonpharmaceutical interventions; altered population susceptibility associated with prior pandemic waves; age and sex distribution; and population size and density. DESIGN AND SETTING Historical archival research, and statistical and epidemiological analyses. Nonpharmaceutical interventions were grouped into 3 major categories: school closure; cancellation of public gatherings; and isolation and quarantine. MAIN OUTCOME MEASURES Weekly excess death rate (EDR); time from the activation of nonpharmaceutical interventions to the first peak EDR; the first peak weekly EDR; and cumulative EDR during the entire 24-week study period. RESULTS There were 115,340 excess pneumonia and influenza deaths (EDR, 500/100,000 population) in the 43 cities during the 24 weeks analyzed. Every city adopted at least 1 of the 3 major categories of nonpharmaceutical interventions. School closure and public gathering bans activated concurrently represented the most common combination implemented in 34 cities (79%); this combination had a median duration of 4 weeks (range, 1-10 weeks) and was significantly associated with reductions in weekly EDR. The cities that implemented nonpharmaceutical interventions earlier had greater delays in reaching peak mortality (Spearman r = -0.74, P < .001), lower peak mortality rates (Spearman r = 0.31, P = .02), and lower total mortality (Spearman r = 0.37, P = .008). There was a statistically significant association between increased duration of nonpharmaceutical interventions and a reduced total mortality burden (Spearman r = -0.39, P = .005). CONCLUSIONS These findings demonstrate a strong association between early, sustained, and layered application of nonpharmaceutical interventions and mitigating the consequences of the 1918-1919 influenza pandemic in the United States. In planning for future severe influenza pandemics, nonpharmaceutical interventions should be considered for inclusion as companion measures to developing effective vaccines and medications for prophylaxis and treatment.

Title: Response strategies for COVID-19 epidemics in African settings: a mathematical modelling study Content: Background The health impact of COVID-19 may differ in African settings as compared to countries in Europe or China due to demographic, epidemiological, environmental and socio-economic factors. We evaluated strategies to reduce SARS-CoV-2 burden in African countries, so as to support decisions that balance minimising mortality, protecting health services and safeguarding livelihoods. Methods We used a Susceptible-Exposed-Infectious-Recovered mathematical model, stratified by age, to predict the evolution of COVID-19 epidemics in three countries representing a range of age distributions in Africa (from oldest to youngest average age: Mauritius, Nigeria and Niger), under various effectiveness assumptions for combinations of different non-pharmaceutical interventions: self-isolation of symptomatic people, physical distancing, and shielding (physical isolation) of the high-risk population. We adapted model parameters to better represent uncertainty about what might be expected in African populations, in particular by shifting the distribution of severity risk towards younger ages and increasing the case-fatality ratio. Results We predicted median clinical attack rates over the first 12 months of 17% (Niger) to 39% (Mauritius), peaking at 2-4 months, if epidemics were unmitigated. Self-isolation while symptomatic had a maximum impact of about 30% on reducing severe cases, while the impact of physical distancing varied widely depending on percent contact reduction and R 0 . The effect of shielding high-risk people, e.g. by rehousing them in physical isolation, was sensitive mainly to residual contact with low-risk people, and to a lesser extent to contact among shielded individuals. Response strategies incorporating self-isolation of symptomatic individuals, moderate physical distancing and high uptake of shielding reduced predicted peak bed demand by 46% to 54% and mortality by 60% to 75%. Lockdowns delayed epidemics by about 3 months. Estimates were sensitive to differences in age-specific social mixing patterns, as published in the literature. Discussion In African settings, as elsewhere, current evidence suggests large COVID-19 epidemics are expected. However, African countries have fewer means to suppress transmission and manage cases. We found that self-isolation of symptomatic persons and general physical distancing are unlikely to avert very large epidemics, unless distancing takes the form of stringent lockdown measures. However, both interventions help to mitigate the epidemic. Shielding of high-risk individuals can reduce health service demand and, even more markedly, mortality if it features high uptake and low contact of shielded and unshielded people, with no increase in contact among shielded people. Strategies combining self-isolation, moderate physical distancing and shielding will probably achieve substantial reductions in mortality in African countries. Temporary lockdowns, where socioeconomically acceptable, can help gain crucial time for planning and expanding health service capacity.

Title: Deaths from Covid-19: Who are the forgotten victims? Content: Background: With the spreading global pandemic of coronavirus disease 2019 (Covid-19) there has been disruption to normal clinical activity in response to the increased demand on health services. There are reports of a reduction in non-Covid-19 emergency presentations. Consequentially, there are concerns that deaths from non-Covid-19 causes could increase. We examined recent reported population-based mortality rates, compared with expected rates, and compared any excess in deaths with the number of deaths attributed to Covid-19. Methods: National agency and death registration reports were searched for numbers of deaths attributed to Covid-19 and overall mortality that had been publicly reported by 16 April 2020. Data on the number of deaths attributed to Covid-19, the total number of deaths registered in the population and the historical average over at least 3 years were collected. Data were available for 3 Northern European countries (England & Wales, Scotland and the Netherlands) and New York State, United States of America. Results: There was an increase in observed, compared with expected, mortality in Scotland (+27%), England and Wales (+35%), the Netherlands (+60%) and New York state (+26%). Of these deaths, only 43% in Scotland and England and Wales, 49% in the Netherlands and 30% in New York state were attributed to Covid-19 leaving a number of excess deaths not attributed to Covid-19. Conclusions: A substantial proportion of excess deaths observed during the current COVID-19 pandemic are not attributed to COVID-19 and may represent an excess of deaths due to other causes.

Title: Who is going to pay the price of Covid-19? Reflections about an unequal Brazil Content: The COVID-19 pandemic has caused high mortality rates among older people, and in order to avoid a healthcare system crisis, almost all countries worldwide have adopted social isolation measures to prevent the spread of the disease. However, in Brazil, a country demarcated by economic inequalities, in which approximately 25% of the population live below the poverty line, these measures will cost severe economic losses and accentuated starvation. For this reason, the underprivileged population should be immediately prioritized and well informed through good practice to avoid the virus. Since, government discrepancies in dealing with the COVID-19 outbreak leaves the population without congruent guidelines on how to react or what to believe, allowing the spread of fake news and political crises. Here, we discuss who will pay the price of the Brazilian government denying the impact of COVID-19 pandemic and suggest some measures to ensure that clear information and protection reach this population.

Title: Central Hepatectomy versus Extended Hepatectomy for Malignant Tumors: A Propensity Score Analysis of Postoperative Complications. Content: BACKGROUND The specific definition of central hepatectomy (CH) (i.e., resection of segments 4-5-8 ± 1) is not uniformly used, resulting in conflicting comparisons with the more commonly performed extended hepatectomy (EH). The study aimed to compare, using propensity score matching (PSM) analysis, the incidence of postoperative complications between CH and EH for centrally located liver tumors (CLLT). METHODS All consecutive CH and EH procedures for CLLT performed from 1980 to 2011 were retrospectively reviewed. Independent predictors of postoperative complications were identified. CH was compared to EH after PSM. RESULTS The study population consisted of 373 patients, 44 (11.8 %) of whom underwent CH and 329 (88.2 %) of whom underwent EH. Before PSM, the overall 90-day mortality was 7.2 % (27 patients) without a group difference (2 (4.5 %) for CH vs. 25 (7.6 %) for EH, p = 0.756). The CH and EH groups had similar postoperative morbidity rates (43.2 vs. 55.3 %; p = 0.108). Blood transfusion was the only independent predictor of postoperative complications (Hazard Ratio: 1.73; 95 % confidence interval: 1.11-2.68; p = 0.014). After PSM, 43 CH patients were matched with 43 EH patients. No group difference was observed for the postoperative mortality, morbidity, or duration of hospital stay. A higher number of EH patients (30.2 vs. 9.3 %, p = 0.028) presented with more than one postoperative complication. CONCLUSIONS CH and EH yield similar mortality and morbidity. For CLLT, CH may be an attractive procedure with the advantage of sparing the liver parenchyma compared with EH.

Title: Risk factors associated with mortality after Roux-en-Y gastric bypass surgery. Content: OBJECTIVE We sought to identify the major risk factors associated with mortality in Roux-en-Y gastric bypass (RYGB) surgery. BACKGROUND Bariatric surgery has become an established treatment for extreme obesity. Bariatric surgery mortality has steadily declined with current rates of less than 0.5%. However, significant variation in the mortality rates has been reported for specific patient cohorts and among bariatric centers. METHODS Clinical outcome data from 185,315 bariatric surgery patients from the Bariatric Outcome Longitudinal Database were reviewed. Of these, 157,559 patients had either documented 30 or more day follow-up data, including mortality. Multiple demographic, socioeconomic, and clinical factors were analyzed by univariate analysis for their association with 30-day mortality after gastric bypass. Variables found to be significant were entered into a multiple logistic regression model to identify factors independently associated with 30-day mortality. On the basis of these results, a RYGB mortality risk score was developed. RESULTS The overall 30-day mortality rate for the entire bariatric surgery cohort was 0.1%. Of the 81,751 RYGB patients, the mortality rate was 0.15%. Factors significantly associated with 30-day gastric bypass mortality included increasing body mass index (BMI) (P<0.0001), increasing age (P<0.005), male gender (P<0.001), pulmonary hypertension (P<0.0001), congestive heart failure (P=0.0008), and liver disease (P=0.038). When the RYGB risk score was applied, a significant trend (P<0.0001) between increasing risk score and mortality rate is found. CONCLUSIONS Increasing BMI, increasing age, male gender, pulmonary hypertension, congestive heart failure, and liver disease are risk factors for 30-day mortality after RYGB. The RYGB risk score can be used to determine patients at greater risk for mortality after RYGB surgery.