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1.  Mind the gap—reaching the European target of a 2-year increase in healthy life years in the next decade 
Background: The European Innovation Partnership on Active and Healthy Ageing seeks an increase of two healthy life years (HLY) at birth in the EU27 for the next 10 years. We assess the feasibility of doing so between 2010 and 2020 and the differential impact among countries by applying different scenarios to current trends in HLY. Methods: Data comprised HLY and life expectancy (LE) at birth 2004–09 from Eurostat. We estimated HLY in 2010 in each country by multiplying the Eurostat projections of LE in 2010 by the ratio HLY/LE obtained either from country and sex-specific linear regression models of HLY/LE on year (seven countries retaining same HLY question) or extrapolating the average of HLY/LE in 2008 and 2009 to 2010 (20 countries and EU27). The first scenario continued these trends with three other scenarios exploring different HLY gap reductions between 2010 and 2020. Results: The estimated gap in HLY in 2010 was 17.5 years (men) and 18.9 years (women). Assuming current trends continue, EU27 HLY increased by 1.4 years (men) and 0.9 years (women), below the European Innovation Partnership on Active and Healthy Ageing target, with the HLY gap between countries increasing to 18.3 years (men) and 19.5 years (women). To eliminate the HLY gap in 20 years, the EU27 must gain 4.4 HLY (men) and 4.8 HLY (women) in the next decade, which, for some countries, is substantially more than what the current trends suggest. Conclusion: Global targets for HLY move attention from inter-country differences and, alongside the current economic crisis, may contribute to increase health inequalities.
doi:10.1093/eurpub/ckt030
PMCID: PMC3784798  PMID: 23487547
2.  The joint action on healthy life years (JA: EHLEIS) 
Background
Life expectancy has been increasing during the last century within the European Union (EU). To measure progress in population health it is no longer sufficient to focus on the duration of life but quality of life should be considered. Healthy Life Years (HLY) allow estimating the quality of the remaining years that a person is expected to live, in terms of being free of long-standing activity limitation. The Joint Action on Healthy Life Years (JA: EHLEIS) is a joint action of European Member States (MS) and the European Union aiming at analysing trends, patterns and differences in HLY, as well as in other Summary Measures of Population Health (SMPH) indicators, across the European member states.
Methods
The JA: EHLEIS consolidates existing information on life and health expectancy by maximising the European comparability; by analysing trends in HLY within the EU; by analysing the evolution of the differences in HLY between Member States; and by identifying both macro-level as micro-level determinants of the inequalities in HLY. The JA: EHLEIS works in collaboration with the USA, Japan and OECD on the development of new SMPHs to be used globally. To strengthen the utility of the HLY for policy-making, annual meetings with policy-makers are planned.
Results
The information system allows the estimation of a set of health indicators (morbidity and disability prevalence, life and health expectancies) for Europe, Member States and shortly their regional levels. An annual country report on HLY in the national languages is available. The JA: EHLEIS is developing statistical attribution and decomposition tools which will be helpful to determine the impact of specific diseases, life styles or other determinants on differences in HLY. Through a set of international workshops the JA: EHLEIS aims to develop a blueprint for an international harmonized Summary Measure of Population Health.
Conclusion
The JA: EHLEIS objectives are to monitor progress towards the headline target of the Europe 2020 strategy of increasing HLY by 2 years by 2020 and to support policy development by identifying the main determinants of active and healthy ageing in Europe.
doi:10.1186/0778-7367-71-2
PMCID: PMC3598905  PMID: 23379576
Health status indicators; Gender; Socioeconomic status; Public health; Health expectancy; Healthy life years; EU
3.  Using mortality follow-up of surveys to estimate social inequalities in healthy life years 
Background
The estimation of healthy life years (HLY) by socio-economic status (SES) requires two types of data: the prevalence of activity limitation by SES generally extracted from surveys and mortality rates by SES generally derived from a linkage between the SES information in population databases (census, register) and mortality records. In some situations, no population-wide databases are available to produce mortality rates by SES, and therefore some alternatives must be explored. This paper assesses the validity of calculating HLY by SES using mortality rates derived from a linkage between surveys and mortality records.
Methods
Two surveys were chosen to explore the validity of the proposed approach: The Belgian Health Interview Survey (HIS) and the Belgian Survey on Income and Living Conditions (SILC). The mortality follow-up of these surveys were used to calculate HLY by educational level at age 25. These HLY were compared with HLY estimates calculated using the mortality follow-up of the 2001 census. The validity of this approach was evaluated against two criteria. First, the HLY calculated using the census and those calculated using the surveys must not be significantly different. Second, survey-based HLY must show significant social inequalities since such inequalities have been consistently reported with census-based HLY.
Results
Both criteria were met. First, for each educational category, no statistically significant difference was found when comparing census-based and survey-based HLY estimates. For instance, men in the lowest educational category have shown a HLY of 34 years according to the HIS, and while this figure was 35.5 years according to the census, this difference was not statistically significant. Second, the survey-based HLY have shown a significant social gradient. For instance, men in the highest educational category are expected to live 9.5 more HLY than their counterparts in the lowest educational category based on the HIS estimates, compared with 7.3 HLY based on the census estimates.
Conclusions
This article suggests that using the mortality follow-up of a nationally representative cross-sectional survey is a valid approach to monitor social inequalities in HLY in the absence of population-wide data.
doi:10.1186/1478-7954-12-13
PMCID: PMC4030465  PMID: 24855457
Healthy life years; Socioeconomic status; Surveys; Mortality follow-up; Monitoring
4.  Gender differences in healthy life years within the EU: an exploration of the “health–survival” paradox 
Objectives
To evaluated the female–male health–survival paradox by estimating the contribution of women’s mortality advantage versus women’s disability disadvantage.
Methods
Disability prevalence was measured from the 2006 Survey on Income and Living Conditions in 25 European countries. Disability prevalence was applied to life tables to estimate healthy life years (HLY) at age 15. Gender differences in HLY were split into two parts: that due to gender inequality in mortality and that due to gender inequality in disability. The relationship between women’s mortality advantage or disability disadvantage and the level of population health between countries was analysed using random-effects meta-regression.
Results
Women’s mortality advantage contributes to more HLY in women; women’s higher prevalence of disability reduces the difference in HLY. In populations with high life expectancy women’s advantage in HLY was small or even a men’s advantage was found. In populations with lower life expectancy, the hardship among men is already evident at young ages.
Conclusions
The results suggest that the health–survival paradox is a function of the level of population health, dependent on modifiable factors.
doi:10.1007/s00038-012-0361-1
PMCID: PMC3557379  PMID: 22618297
Europe; Gender; Health expectancy; Health inequality; Healthy life years; Health–survival paradox
5.  The Reversal of Fortunes: Trends in County Mortality and Cross-County Mortality Disparities in the United States  
PLoS Medicine  2008;5(4):e66.
Background
Counties are the smallest unit for which mortality data are routinely available, allowing consistent and comparable long-term analysis of trends in health disparities. Average life expectancy has steadily increased in the United States but there is limited information on long-term mortality trends in the US counties This study aimed to investigate trends in county mortality and cross-county mortality disparities, including the contributions of specific diseases to county level mortality trends.
Methods and Findings
We used mortality statistics (from the National Center for Health Statistics [NCHS]) and population (from the US Census) to estimate sex-specific life expectancy for US counties for every year between 1961 and 1999. Data for analyses in subsequent years were not provided to us by the NCHS. We calculated different metrics of cross-county mortality disparity, and also grouped counties on the basis of whether their mortality changed favorably or unfavorably relative to the national average. We estimated the probability of death from specific diseases for counties with above- or below-average mortality performance. We simulated the effect of cross-county migration on each county's life expectancy using a time-based simulation model. Between 1961 and 1999, the standard deviation (SD) of life expectancy across US counties was at its lowest in 1983, at 1.9 and 1.4 y for men and women, respectively. Cross-county life expectancy SD increased to 2.3 and 1.7 y in 1999. Between 1961 and 1983 no counties had a statistically significant increase in mortality; the major cause of mortality decline for both sexes was reduction in cardiovascular mortality. From 1983 to 1999, life expectancy declined significantly in 11 counties for men (by 1.3 y) and in 180 counties for women (by 1.3 y); another 48 (men) and 783 (women) counties had nonsignificant life expectancy decline. Life expectancy decline in both sexes was caused by increased mortality from lung cancer, chronic obstructive pulmonary disease (COPD), diabetes, and a range of other noncommunicable diseases, which were no longer compensated for by the decline in cardiovascular mortality. Higher HIV/AIDS and homicide deaths also contributed substantially to life expectancy decline for men, but not for women. Alternative specifications of the effects of migration showed that the rise in cross-county life expectancy SD was unlikely to be caused by migration.
Conclusions
There was a steady increase in mortality inequality across the US counties between 1983 and 1999, resulting from stagnation or increase in mortality among the worst-off segment of the population. Female mortality increased in a large number of counties, primarily because of chronic diseases related to smoking, overweight and obesity, and high blood pressure.
Majid Ezzati and colleagues analyze US county-level mortality data for 1961 to 1999, and find a steady increase in mortality inequality across counties between 1983 and 1999.
Editors' Summary
Background.
It has long been recognized that the number of years that distinct groups of people in the United States would be expected to live based on their current mortality patterns (“life expectancy”) varies enormously. For example, white Americans tend to live longer than black Americans, the poor tend to have shorter life expectancies than the wealthy, and women tend to outlive men. Where one lives might also be a factor that determines his or her life expectancy, because of social conditions and health programs in different parts of the country.
Why Was the Study Done?
While life expectancies have generally been rising across the United States over time, there is little information, especially over the long term, on the differences in life expectancies across different counties. The researchers therefore set out to examine whether there were different life expectancies across different US counties over the last four decades. The researchers chose to look at counties—the smallest geographic units for which data on death rates are collected in the US—because it allowed them to make comparisons between small subgroups of people that share the same administrative structure.
What Did the Researchers Do and Find?
The researchers looked at differences in death rates between all counties in US states plus the District of Columbia over four decades, from 1961 to 1999. They obtained the data on number of deaths from the National Center for Health Statistics, and they obtained data on the number of people living in each county from the US Census. The NCHS did not provide death data after 2001. They broke the death rates down by sex and by disease to assess trends over time for women and men, and for different causes of death.
Over these four decades, the researchers found that the overall US life expectancy increased from 67 to 74 years of age for men and from 74 to 80 years for women. Between 1961 and 1983 the death rate fell in both men and women, largely due to reductions in deaths from cardiovascular disease (heart disease and stroke). During this same period, 1961–1983, the differences in death rates among/across different counties fell. However, beginning in the early 1980s the differences in death rates among/across different counties began to increase. The worst-off counties no longer experienced a fall in death rates, and in a substantial number of counties, mortality actually increased, especially for women, a shift that the researchers call “the reversal of fortunes.” This stagnation in the worst-off counties was primarily caused by a slowdown or halt in the reduction of deaths from cardiovascular disease coupled with a moderate rise in a number of other diseases, such as lung cancer, chronic lung disease, and diabetes, in both men and women, and a rise in HIV/AIDS and homicide in men. The researchers' key finding, therefore, was that the differences in life expectancy across different counties initially narrowed and then widened.
What Do these Findings Mean?
The findings suggest that beginning in the early 1980s and continuing through 1999 those who were already disadvantaged did not benefit from the gains in life expectancy experienced by the advantaged, and some became even worse off. The study emphasizes how important it is to monitor health inequalities between different groups, in order to ensure that everyone—and not just the well-off—can experience gains in life expectancy. Although the “reversal of fortune” that the researchers found applied to only a minority of the population, the authors argue that their study results are troubling because an oft-stated aim of the US health system is the improvement of the health of “all people, and especially those at greater risk of health disparities” (see, for example http://www.cdc.gov/osi/goals/SIHPGPostcard.pdf).
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050066.
A study by Nancy Krieger and colleagues, published in PLoS Medicine in February 2008, documented a similar “fall and rise” in health inequities. Krieger and colleagues reported that the difference in health between rich and poor and between different racial/ethnic groups, as measured by rates of dying young and of infant deaths, shrank in the US from 1966 to 1980 then widened from 1980 to 2002
Murray and colleagues, in a 2006 PLoS Medicine article, calculated US mortality rates according to “race-county” units and divided into the “eight Americas,” and found disparities in life expectancy across them
The US Centers for Disease Control has an Office of Minority Health and Health Disparities. The office “aims to accelerate CDC's health impact in the US population and to eliminate health disparities for vulnerable populations as defined by race/ethnicity, socioeconomic status, geography, gender, age, disability status, risk status related to sex and gender, and among other populations identified to be at-risk for health disparities”
Wikipedia has a chapter on health disparities (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
In 2001 the US Agency for Healthcare Research and Quality sponsored a workshop on “strategies to reduce health disparities”
doi:10.1371/journal.pmed.0050066
PMCID: PMC2323303  PMID: 18433290
6.  In Italy, healthy life expectancy drop dramatically: from 2004 to 2008 there was a 10 years drop among newborn girls 
Introduction
In this short essay, we would like to address a severe divergence observed in Italy between Life Expectancy (LE) and Healthy Life Expectancy (Healthy LE) and a unique trend of worsening in Healthy LE, compared to the other European countries. Both issues emerge in recent data by EUROSTAT Report.
Methods
The analysis used by the authors of the EUROSTAT report is based on Sullivan method which combines 2 type of variables: mortality and morbidity data.
Results
While several European countries started to deal with comparable data about LE since 1960, in Italy, analogous data were available for the first time in EUROSTAT Report only in 1985. In Italy, in the period 1985-2008, there was a good progressive increase in L.E., following the best European values. Nevertheless, while until 2004 Italy was among the European best countries in terms of both LE and Healthy LE at birth, four years later in 2008 there was a shocking loss of 10 years of Healthy LE at birth in newborn girls. In the process, they lost their 2-years previous advantage with respect to males (the latter lost only 6 years of Healthy LE, in the same time span). Looking at healthy LE at age 65 in respect to 2004, Italian women in 2008 could expect to live healthy only about 7 years (as much as men) versus the almost 15 years of the European best values (14 years for men).
Conclusions
It is legitimate to wonder why no one official comment has been produced as a reaction after the first year of spectacular decline in Healthy Life Years in Italy: in counter-tendency with European values, from 2004 to 2008 there is a clear evidence of a 10 years drop in Healthy LE among newborn girls. The problem has not been taken into consideration even when the situation clearly appeared to worsen in the following years, dropping 4-6 more years for males and females in 2006 (for newborn babies); two more years of healthy life expectancy have been lost between 2006 and 2007 for each gender. One more year of Healthy Life Expectancy is lost in 2008. And data have not been made available any more, since then, from Italy.
doi:10.1186/1824-7288-38-19
PMCID: PMC3408327  PMID: 22607773
7.  Adult Mortality Attributable to Preventable Risk Factors for Non-Communicable Diseases and Injuries in Japan: A Comparative Risk Assessment 
PLoS Medicine  2012;9(1):e1001160.
Using a combination of published data and modeling, Nayu Ikeda and colleagues identify tobacco smoking and high blood pressure as major risk factors for death from noncommunicable diseases among adults in Japan.
Background
The population of Japan has achieved the longest life expectancy in the world. To further improve population health, consistent and comparative evidence on mortality attributable to preventable risk factors is necessary for setting priorities for health policies and programs. Although several past studies have quantified the impact of individual risk factors in Japan, to our knowledge no study has assessed and compared the effects of multiple modifiable risk factors for non-communicable diseases and injuries using a standard framework. We estimated the effects of 16 risk factors on cause-specific deaths and life expectancy in Japan.
Methods and Findings
We obtained data on risk factor exposures from the National Health and Nutrition Survey and epidemiological studies, data on the number of cause-specific deaths from vital records adjusted for ill-defined codes, and data on relative risks from epidemiological studies and meta-analyses. We applied a comparative risk assessment framework to estimate effects of excess risks on deaths and life expectancy at age 40 y. In 2007, tobacco smoking and high blood pressure accounted for 129,000 deaths (95% CI: 115,000–154,000) and 104,000 deaths (95% CI: 86,000–119,000), respectively, followed by physical inactivity (52,000 deaths, 95% CI: 47,000–58,000), high blood glucose (34,000 deaths, 95% CI: 26,000–43,000), high dietary salt intake (34,000 deaths, 95% CI: 27,000–39,000), and alcohol use (31,000 deaths, 95% CI: 28,000–35,000). In recent decades, cancer mortality attributable to tobacco smoking has increased in the elderly, while stroke mortality attributable to high blood pressure has declined. Life expectancy at age 40 y in 2007 would have been extended by 1.4 y for both sexes (men, 95% CI: 1.3–1.6; women, 95% CI: 1.2–1.7) if exposures to multiple cardiovascular risk factors had been reduced to their optimal levels as determined by a theoretical-minimum-risk exposure distribution.
Conclusions
Tobacco smoking and high blood pressure are the two major risk factors for adult mortality from non-communicable diseases and injuries in Japan. There is a large potential population health gain if multiple risk factors are jointly controlled.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, a small number of modifiable risk factors are responsible for many premature or preventable deaths. For example, having high blood pressure (hypertension) increases a person's risk of developing life-threatening heart problems and stroke (cardiovascular disease). Similarly, having a high blood sugar level increases the risk of developing diabetes, a chronic (long-term) disease that can lead to cardiovascular problems and kidney failure, and half of all long-term tobacco smokers in Western populations will die prematurely from diseases related to smoking, such as lung cancer. Importantly, the five major risk factors for death globally—high blood pressure, tobacco use, high blood sugar, physical inactivity, and overweight and obesity—are all modifiable. That is, lifestyle changes and dietary changes such as exercising more, reducing salt intake, and increasing fruit and vegetable intake can reduce an individual's exposure to these risk factors and one's chances of premature death. Moreover, public health programs designed to reduce a population's exposure to modifiable risk factors should reduce preventable deaths in that population.
Why Was This Study Done?
In 2000, the Japanese government initiated Health Japan 21, a ten-year national health promotion campaign designed to prevent premature death from non-communicable (noninfectious) diseases and injuries. This campaign set 59 goals to monitor and improve risk factor management in the Japanese population, which has one of the longest life expectancies at birth in the world (the life expectancy of a person born in Japan in 2009 was 83.1 years). Because the campaign's final evaluation revealed deterioration or no improvement on some of these goals, the Japanese government recently released new guidelines that stress the importance of simultaneously controlling multiple risk factors for chronic diseases. However, although several studies have quantified the impacts on life expectancy and cause-specific death of individual modifiable risk factors in Japan, the effects of multiple risk factors have not been assessed. In this study, the researchers use a “comparative risk assessment” framework to estimate the effects of 16 risk factors on cause-specific deaths and life expectancy in Japan. Comparative risk assessment estimates the number of deaths that would be prevented if current distributions of risk factor exposures were changed to hypothetical optimal distributions.
What Did the Researchers Do and Find?
The researchers obtained data on exposure to the selected risk factors from the 2007 Japanese National Health and Nutrition Survey and from epidemiological studies, and information on the number of deaths in 2007 from different diseases from official records. They used published studies to estimate how much each factor increases the risk of death from each disease and then used a mathematical formula to estimate the effects of the risk factors on the number of deaths in Japan and on life expectancy at age 40. In 2007, tobacco smoking and high blood pressure accounted for 129,000 and 104,000 deaths, respectively, in Japan. Physical inactivity accounted for 52,000 deaths, high blood glucose and high dietary salt intake accounted for 34,000 deaths each, and alcohol use for 31,000 deaths. Life expectancy at age 40 in 2007 would have been extended by 1.4 years for both sexes, the researchers estimate, if exposure to multiple cardiovascular risk factors had been reduced to calculated optimal distributions, or by 0.7 years if these risk factors had been reduced to the distributions defined by national guidelines and goals.
What Do These Findings Mean?
These findings identify tobacco smoking and high blood pressure as the major risk factors for death from non-communicable diseases among adults in Japan, a result consistent with previous findings from the US. They also indicate that simultaneous control of multiple risk factors has great potential for producing health gains among the Japanese population. Although the researchers focused on estimating the effect of these risk factors on mortality and did not include illness and disability in this study, these findings nevertheless identify two areas of public health policy that need to be strengthened to improve health, reduce death rates, and increase life expectancy among the Japanese population. First, they highlight the need to reduce tobacco smoking, particularly among men. Second and most importantly, these findings emphasize the need to improve ongoing programs designed to help people manage multiple cardiovascular risk factors, including high blood pressure.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001160.
The US Centers for Disease Control and Prevention provides information on all aspects of healthy living
The World Health Report 2002—Reducing Risks, Promoting Healthy Life provides a global analysis of how healthy life expectancy could be increased
The American Heart Association and the American Cancer Society provide information on many important risk factors for noncommunicable diseases and include some personal stories about keeping healthy
Details about Health Japan 21 are provided by the Japanese Ministry of Health, Labour and Welfare. Further details about this campaign are available from the World Health Organization
MedlinePlus provides links to further resources on healthy living and on healthy aging (in English and Spanish)
doi:10.1371/journal.pmed.1001160
PMCID: PMC3265534  PMID: 22291576
8.  Using Current Smoking Prevalence to Project Lung Cancer Morbidity and Mortality in Georgia by 2020 
Introduction
Tobacco use is the leading preventable cause of disease and premature death in the United States. In Georgia, approximately 18% of adults smoke cigarettes, and 87% of men’s lung cancer deaths and 70% of women’s lung cancer deaths are due to smoking. From 2004–2008, the age-adjusted lung cancer incidence rate in Georgia was 112.8 per 100,000 population, and the mortality rate was 88.2 per 100,000 population.
Methods
The Georgia Behavioral Risk Factor Surveillance System Survey was used to estimate trends in current adult smoking prevalence (1985–2010). Georgia smoking–attributable cancer mortality was estimated using a method similar to the Centers for Disease Control and Prevention’s Smoking-Attributable Morbidity, Mortality, and Economic Costs application. Data on cancer incidence (1998–2008) were obtained from the Georgia Comprehensive Cancer Registry, and data on cancer deaths (1990–2007) were obtained from the Georgia Department of Public Health Vital Records Program.
Results
From 1985 through 1993, the prevalence of smoking among Georgians declined by an average of 3% per year in men and 0.2% in women. From 2001 through 2008, lung cancer incidence rates declined in men and increased in women. Lung cancer mortality rates declined in men and women from 2000 through 2007. By 2020, Georgia lung cancer incidence rates are projected to decrease for men and increase for women. Lung cancer mortality is projected to decrease for both men and women.
Conclusion
The lung cancer mortality rates projected in this study are far from meeting the Healthy People 2020 goal (46 per 100,000 population). Full implementation of comprehensive tobacco-use control programs would significantly reduce tobacco-use–related morbidity and mortality.
doi:10.5888/pcd10.120271
PMCID: PMC3664207  PMID: 23660116
9.  Male Circumcision at Different Ages in Rwanda: A Cost-Effectiveness Study 
PLoS Medicine  2010;7(1):e1000211.
Agnes Binagwaho and colleagues predict that circumcision of newborn boys would be effective and cost-saving as a long-term strategy to prevent HIV in Rwanda.
Background
There is strong evidence showing that male circumcision (MC) reduces HIV infection and other sexually transmitted infections (STIs). In Rwanda, where adult HIV prevalence is 3%, MC is not a traditional practice. The Rwanda National AIDS Commission modelled cost and effects of MC at different ages to inform policy and programmatic decisions in relation to introducing MC. This study was necessary because the MC debate in Southern Africa has focused primarily on MC for adults. Further, this is the first time, to our knowledge, that a cost-effectiveness study on MC has been carried out in a country where HIV prevalence is below 5%.
Methods and Findings
A cost-effectiveness model was developed and applied to three hypothetical cohorts in Rwanda: newborns, adolescents, and adult men. Effectiveness was defined as the number of HIV infections averted, and was calculated as the product of the number of people susceptible to HIV infection in the cohort, the HIV incidence rate at different ages, and the protective effect of MC; discounted back to the year of circumcision and summed over the life expectancy of the circumcised person. Direct costs were based on interviews with experienced health care providers to determine inputs involved in the procedure (from consumables to staff time) and related prices. Other costs included training, patient counselling, treatment of adverse events, and promotion campaigns, and they were adjusted for the averted lifetime cost of health care (antiretroviral therapy [ART], opportunistic infection [OI], laboratory tests). One-way sensitivity analysis was performed by varying the main inputs of the model, and thresholds were calculated at which each intervention is no longer cost-saving and at which an intervention costs more than one gross domestic product (GDP) per capita per life-year gained. Results: Neonatal MC is less expensive than adolescent and adult MC (US$15 instead of US$59 per procedure) and is cost-saving (the cost-effectiveness ratio is negative), even though savings from infant circumcision will be realized later in time. The cost per infection averted is US$3,932 for adolescent MC and US$4,949 for adult MC. Results for infant MC appear robust. Infant MC remains highly cost-effective across a reasonable range of variation in the base case scenario. Adolescent MC is highly cost-effective for the base case scenario but this high cost-effectiveness is not robust to small changes in the input variables. Adult MC is neither cost-saving nor highly cost-effective when considering only the direct benefit for the circumcised man.
Conclusions
The study suggests that Rwanda should be simultaneously scaling up circumcision across a broad range of age groups, with high priority to the very young. Infant MC can be integrated into existing health services (i.e., neonatal visits and vaccination sessions) and over time has better potential than adolescent and adult circumcision to achieve the very high coverage of the population required for maximal reduction of HIV incidence. In the presence of infant MC, adolescent and adult MC would evolve into a “catch-up” campaign that would be needed at the start of the program but would eventually become superfluous.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Acquired immunodeficiency syndrome (AIDS) has killed more than 25 million people since 1981 and more than 31 million people (22 million in sub-Saharan Africa alone) are now infected with the human immunodeficiency virus (HIV), which causes AIDS. There is no cure for HIV/AIDS and no vaccine against HIV infection. Consequently, prevention of HIV transmission is extremely important. HIV is most often spread through unprotected sex with an infected partner. Individuals can reduce their risk of HIV infection, therefore, by abstaining from sex, by having one or a few sexual partners, and by always using a male or female condom. In addition, male circumcision—the removal of the foreskin, the loose fold of skin that covers the head of penis—can halve HIV transmission rates to men resulting from sex with women. Thus, as part of its HIV prevention strategy, the World Health Organization (WHO) recommends that male circumcision programs be scaled up in countries where there is a generalized HIV epidemic and where few men are circumcised.
Why Was This Study Done?
One such country is Rwanda. Here, 3% of the adult population is infected with HIV but only 15% of men are circumcised—worldwide, about 30% of men are circumcised. Demand for circumcision is increasing in Rwanda but, before policy makers introduce a country-wide male circumcision program, they need to identify the most cost-effective way to increase circumcision rates. In particular, they need to decide the age at which circumcision should be offered. Circumcision soon after birth (neonatal circumcision) is quick and simple and rarely causes any complications. Circumcision of adolescents and adults is more complex and has a higher complication rate. Although several studies have investigated the cost-effectiveness (the balance between the clinical and financial costs of a medical intervention and its benefits) of circumcision in adult men, little is known about its cost-effectiveness in newborn boys. In this study, which is one of several studies on male circumcision being organized by the National AIDS Control Commission in Rwanda, the researchers model the cost-effectiveness of circumcision at different ages.
What Did the Researchers Do and Find?
The researchers developed a simple cost-effectiveness model and applied it to three hypothetical groups of Rwandans: newborn boys, adolescent boys, and adult men. For their model, the researchers calculated the effectiveness of male circumcision (the number of HIV infections averted) by estimating the reduction in the annual number of new HIV infections over time. They obtained estimates of the costs of circumcision (including the costs of consumables, staff time, and treatment of complications) from health care providers and adjusted these costs for the money saved through not needing to treat HIV in males in whom circumcision prevented infection. Using their model, the researchers estimate that each neonatal male circumcision would cost US$15 whereas each adolescent or adult male circumcision would cost US$59. Neonatal male circumcision, they report, would be cost-saving. That is, over a lifetime, neonatal male circumcision would save more money than it costs. Finally, using the WHO definition of cost-effectiveness (for a cost-effective intervention, the additional cost incurred to gain one year of life must be less than a country's per capita gross domestic product), the researchers estimate that, although adolescent circumcision would be highly cost-effective, circumcision of adult men would only be potentially cost-effective (but would likely prove cost-effective if the additional infections that would occur from men to their partners without a circumcision program were also taken into account).
What Do These Findings Mean?
As with all modeling studies, the accuracy of these findings depends on the many assumptions included in the model. However, the findings suggest that male circumcision for infants for the prevention of HIV infection later in life is highly cost-effective and likely to be cost-saving and that circumcision for adolescents is cost-effective. The researchers suggest, therefore, that policy makers in Rwanda and in countries with similar HIV infection and circumcision rates should scale up male circumcision programs across all age groups, with high priority being given to the very young. If infants are routinely circumcised, they suggest, circumcision of adolescent and adult males would become a “catch-up” campaign that would be needed at the start of the program but that would become superfluous over time. Such an approach would represent a switch from managing the HIV epidemic as an emergency towards focusing on sustainable, long-term solutions to this major public-health problem.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000211.
This study is further discussed in a PLoS Medicine Perspective by Seth Kalichman
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
Information is available from the Joint United Nations Programme on HIV/AIDS (UNAIDS) on HIV infection and AIDS and on male circumcision in relation to HIV and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on HIV and AIDS in Africa, and on circumcision and HIV (some information in English and Spanish)
More information about male circumcision is available from the Clearinghouse on Male Circumcision
The National AIDS Control Commission of Rwanda provides detailed information about HIV/AIDS in Rwanda (in English and French)
doi:10.1371/journal.pmed.1000211
PMCID: PMC2808207  PMID: 20098721
10.  Enterohemorrhagic Escherichia coli Hemolysin Employs Outer Membrane Vesicles to Target Mitochondria and Cause Endothelial and Epithelial Apoptosis 
PLoS Pathogens  2013;9(12):e1003797.
Enterohemorrhagic Escherichia coli (EHEC) strains cause diarrhea and hemolytic uremic syndrome resulting from toxin-mediated microvascular endothelial injury. EHEC hemolysin (EHEC-Hly), a member of the RTX (repeats-in-toxin) family, is an EHEC virulence factor of increasingly recognized importance. The toxin exists as free EHEC-Hly and as EHEC-Hly associated with outer membrane vesicles (OMVs) released by EHEC during growth. Whereas the free toxin is lytic towards human endothelium, the biological effects of the OMV-associated EHEC-Hly on microvascular endothelial and intestinal epithelial cells, which are the major targets during EHEC infection, are unknown. Using microscopic, biochemical, flow cytometry and functional analyses of human brain microvascular endothelial cells (HBMEC) and Caco-2 cells we demonstrate that OMV-associated EHEC-Hly does not lyse the target cells but triggers their apoptosis. The OMV-associated toxin is internalized by HBMEC and Caco-2 cells via dynamin-dependent endocytosis of OMVs and trafficked with OMVs into endo-lysosomal compartments. Upon endosome acidification and subsequent pH drop, EHEC-Hly is separated from OMVs, escapes from the lysosomes, most probably via its pore-forming activity, and targets mitochondria. This results in decrease of the mitochondrial transmembrane potential and translocation of cytochrome c to the cytosol, indicating EHEC-Hly-mediated permeabilization of the mitochondrial membranes. Subsequent activation of caspase-9 and caspase-3 leads to apoptotic cell death as evidenced by DNA fragmentation and chromatin condensation in the intoxicated cells. The ability of OMV-associated EHEC-Hly to trigger the mitochondrial apoptotic pathway in human microvascular endothelial and intestinal epithelial cells indicates a novel mechanism of EHEC-Hly involvement in the pathogenesis of EHEC diseases. The OMV-mediated intracellular delivery represents a newly recognized mechanism for a bacterial toxin to enter host cells in order to target mitochondria.
Author Summary
During the last 30 years, enterohemorrhagic Escherichia coli (EHEC) emerged as worldwide causes of diarrhea and hemolytic uremic syndrome, the most common cause of acute kidney failure in children. EHEC hemolysin (EHEC-Hly) is one of the toxins produced by EHEC during infection that afflict the human host. EHEC-Hly belongs to a large family of toxins, whose members typically kill target cells by inserting themselves into the cell membranes, which results in pore formation and ultimately cell lysis. Here we show that EHEC-Hly associated with outer membrane vesicles (OMVs) secreted by EHEC during growth does not lyse human microvascular endothelial and intestinal epithelial cells, which are the major targets in EHEC-mediated human diseases. Instead, the OMV-associated EHEC-Hly uses the OMVs to enter the cells and acts intracellularly. The toxin separates from its carriers in lysosomes, translocates into mitochondria and triggers apoptotic death of the target cells via the mitochondrial pathway. EHEC-Hly is the first known bacterial toxin, which enters host cells via OMVs in order to attack mitochondria. The apoptotic potential of OMV-associated EHEC-Hly indicates a novel mechanism for this toxin to cause cell death during human EHEC infections.
doi:10.1371/journal.ppat.1003797
PMCID: PMC3861543  PMID: 24348251
11.  Long-Term Risk of Incident Type 2 Diabetes and Measures of Overall and Regional Obesity: The EPIC-InterAct Case-Cohort Study 
PLoS Medicine  2012;9(6):e1001230.
A collaborative re-analysis of data from the InterAct case-control study conducted by Claudia Langenberg and colleagues has established that waist circumference is associated with risk of type 2 diabetes, independently of body mass index.
Background
Waist circumference (WC) is a simple and reliable measure of fat distribution that may add to the prediction of type 2 diabetes (T2D), but previous studies have been too small to reliably quantify the relative and absolute risk of future diabetes by WC at different levels of body mass index (BMI).
Methods and Findings
The prospective InterAct case-cohort study was conducted in 26 centres in eight European countries and consists of 12,403 incident T2D cases and a stratified subcohort of 16,154 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. We used Prentice-weighted Cox regression and random effects meta-analysis methods to estimate hazard ratios for T2D. Kaplan-Meier estimates of the cumulative incidence of T2D were calculated. BMI and WC were each independently associated with T2D, with WC being a stronger risk factor in women than in men. Risk increased across groups defined by BMI and WC; compared to low normal weight individuals (BMI 18.5–22.4 kg/m2) with a low WC (<94/80 cm in men/women), the hazard ratio of T2D was 22.0 (95% confidence interval 14.3; 33.8) in men and 31.8 (25.2; 40.2) in women with grade 2 obesity (BMI≥35 kg/m2) and a high WC (>102/88 cm). Among the large group of overweight individuals, WC measurement was highly informative and facilitated the identification of a subgroup of overweight people with high WC whose 10-y T2D cumulative incidence (men, 70 per 1,000 person-years; women, 44 per 1,000 person-years) was comparable to that of the obese group (50–103 per 1,000 person-years in men and 28–74 per 1,000 person-years in women).
Conclusions
WC is independently and strongly associated with T2D, particularly in women, and should be more widely measured for risk stratification. If targeted measurement is necessary for reasons of resource scarcity, measuring WC in overweight individuals may be an effective strategy, since it identifies a high-risk subgroup of individuals who could benefit from individualised preventive action.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, more than 350 million people have diabetes, and this number is increasing rapidly. Diabetes is characterized by dangerous levels of glucose (sugar) in the blood. Blood sugar levels are usually controlled by insulin, a hormone that the pancreas releases after meals (digestion of food produces glucose). In people with type 2 diabetes (the commonest form of diabetes), blood sugar control fails because the fat and muscle cells that normally respond to insulin by removing sugar from the blood become insulin resistant. Type 2 diabetes can be controlled with diet and exercise, and with drugs that help the pancreas make more insulin or that make cells more sensitive to insulin. The long-term complications of diabetes, which include an increased risk of heart disease and stroke, reduce the life expectancy of people with diabetes by about 10 years compared to people without diabetes.
Why Was This Study Done?
A high body mass index (BMI, a measure of body fat calculated by dividing a person's weight in kilograms by their height in meters squared) is a strong predictor of type 2 diabetes. Although the risk of diabetes is greatest in obese people (who have a BMI of greater than 30 kg/m2), many of the people who develop diabetes are overweight—they have a BMI of 25–30 kg/m2. Healthy eating and exercise reduce the incidence of diabetes in high-risk individuals, but it is difficult and expensive to provide all overweight and obese people with individual lifestyle advice. Ideally, a way is needed to distinguish between people with high and low risk of developing diabetes at different levels of BMI. Waist circumference is a measure of fat distribution that has the potential to quantify diabetes risk among people with different BMIs because it estimates the amount of fat around the abdominal organs, which also predicts diabetes development. In this case-cohort study, the researchers use data from the InterAct study (which is investigating how genetics and lifestyle interact to affect diabetes risk) to estimate the long-term risk of type 2 diabetes associated with BMI and waist circumference. A case-cohort study measures exposure to potential risk factors in a group (cohort) of people and compares the occurrence of these risk factors in people who later develop the disease and in a randomly chosen subcohort.
What Did the Researchers Do and Find?
The researchers estimated the association of BMI and waist circumference with type 2 diabetes from baseline measurements of the weight, height, and waist circumference of 12,403 people who subsequently developed type 2 diabetes and a subcohort of 16,154 participants enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC). Both risk factors were independently associated with type 2 diabetes risk, but waist circumference was a stronger risk factor in women than in men. Obese men (BMI greater than 35 kg/m2) with a high waist circumference (greater than 102 cm) were 22 times more likely to develop diabetes than men with a low normal weight (BMI 18.5–22.4 kg/m2) and a low waist circumference (less than 94 cm); obese women with a waist circumference of more than 88 cm were 31.8 times more likely to develop type 2 diabetes than women with a low normal weight and waist circumference (less than 80 cm). Importantly, among overweight people, waist circumference measurements identified a subgroup of overweight people (those with a high waist circumference) whose 10-year cumulative incidence of type 2 diabetes was similar to that of obese people.
What Do These Findings Mean?
These findings indicate that, among people of European descent, waist circumference is independently and strongly associated with type 2 diabetes, particularly among women. Additional studies are needed to confirm this association in other ethnic groups. Targeted measurement of waist circumference in overweight individuals (who now account for a third of the US and UK adult population) could be an effective strategy for the prevention of diabetes because it would allow the identification of a high-risk subgroup of people who might benefit from individualized lifestyle advice.
Additional Information
Please access these web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001230.
The US National Diabetes Information Clearinghouse provides information about diabetes for patients, health care professionals, and the general public, including detailed information on diabetes prevention (in English and Spanish)
The US Centers for Disease Control and Prevention provides information on all aspects of overweight and obesity (including some information in Spanish)
The UK National Health Service Choices website provides information for patients and carers about type 2 diabetes, about the prevention of type 2 diabetes, and about obesity; it also includes peoples stories about diabetes and about obesity
The charity Diabetes UK also provides detailed information for patients and carers, including information on healthy lifestyles for people with diabetes, and has a further selection of stories from people with diabetes; the charity Healthtalkonline has interviews with people about their experiences of diabetes
More information on the InterAct study is available
MedlinePlus provides links to further resources and advice about diabetes and diabetes prevention and about obesity (in English and Spanish)
doi:10.1371/journal.pmed.1001230
PMCID: PMC3367997  PMID: 22679397
12.  Effect of Facilitation of Local Maternal-and-Newborn Stakeholder Groups on Neonatal Mortality: Cluster-Randomized Controlled Trial 
PLoS Medicine  2013;10(5):e1001445.
Lars Åke Persson and colleagues conduct a cluster randomised control in northern Vietnam to analyze the effect of the activity of local community-based maternal-and-newborn stakeholder groups on neonatal mortality.
Please see later in the article for the Editors' Summary
Background
Facilitation of local women's groups may reportedly reduce neonatal mortality. It is not known whether facilitation of groups composed of local health care staff and politicians can improve perinatal outcomes. We hypothesised that facilitation of local stakeholder groups would reduce neonatal mortality (primary outcome) and improve maternal, delivery, and newborn care indicators (secondary outcomes) in Quang Ninh province, Vietnam.
Methods and Findings
In a cluster-randomized design 44 communes were allocated to intervention and 46 to control. Laywomen facilitated monthly meetings during 3 years in groups composed of health care staff and key persons in the communes. A problem-solving approach was employed. Births and neonatal deaths were monitored, and interviews were performed in households of neonatal deaths and of randomly selected surviving infants. A latent period before effect is expected in this type of intervention, but this timeframe was not pre-specified. Neonatal mortality rate (NMR) from July 2008 to June 2011 was 16.5/1,000 (195 deaths per 11,818 live births) in the intervention communes and 18.4/1,000 (194 per 10,559 live births) in control communes (adjusted odds ratio [OR] 0.96 [95% CI 0.73–1.25]). There was a significant downward time trend of NMR in intervention communes (p = 0.003) but not in control communes (p = 0.184). No significant difference in NMR was observed during the first two years (July 2008 to June 2010) while the third year (July 2010 to June 2011) had significantly lower NMR in intervention arm: adjusted OR 0.51 (95% CI 0.30–0.89). Women in intervention communes more frequently attended antenatal care (adjusted OR 2.27 [95% CI 1.07–4.8]).
Conclusions
A randomized facilitation intervention with local stakeholder groups composed of primary care staff and local politicians working for three years with a perinatal problem-solving approach resulted in increased attendance to antenatal care and reduced neonatal mortality after a latent period.
Trial registration
Current Controlled Trials ISRCTN44599712
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Over the past few years, there has been enormous international effort to meet the target set by Millennium Development Goal 4 to reduce the under-five child mortality rate by two-thirds and to reduce the number of maternal deaths by three-quarters, respectively, from the 1990 level by 2015. There has been some encouraging progress and according to the latest figures from the World Health Organization, in 2011, just under 7 million children aged under 5 years died, a fall of almost 3 million from a decade ago. However, currently, 41% of all deaths among children under the age of 5 years occur around birth and the first 28 days of life (perinatal and neonatal mortality). Simple interventions can substantially reduce neonatal deaths and there have been several international, national, and local efforts to implement effective care packages to help reduce the number of neonatal deaths.
Why Was This Study Done?
In order for these interventions to be most effective, it is important that the local community becomes involved. Community mobilization, especially through local women's groups, can empower women to prioritize specific interventions to help improve their own health and that of their baby. An alternative strategy might be to mobilize people who already have responsibility to promote health and welfare in society, such as primary care staff, village health workers, and elected political representatives. However, it is unclear if the activities of such stakeholder groups result in improved neonatal survival. So in this study from northern Vietnam, the researchers analyzed the effect of the activity of local maternal-and-newborn stakeholder groups on neonatal mortality.
What Did the Researchers Do and Find?
Between 2008 and 2011, the researchers conducted a cluster-randomized controlled trial in 90 communes within the Quang Ninh province of northeast of Vietnam: 44 communes were allocated to intervention and 46 to the control. The local women's union facilitated recruitment to the intervention, local stakeholder groups (Maternal and Newborn Health Groups), which comprised primary care staff, village health workers, women's union representatives, and the person with responsibility for health in the commune. The groups' role was to identify and prioritize local perinatal health problems and implement actions to help overcome these problems.
Over the three-year period, the Maternal and Newborn Health Groups in the 44 intervention communes had 1,508 meetings. Every year 15–27 unique problems were identified and addressed 94–151 times. The problem-solving processes resulted in an annual number of 19–27 unique actions that were applied 297–649 times per year. The top priority problems and actions identified by these groups dealt with antenatal care attendance, post-natal visits, nutrition and rest during pregnancy, home deliveries, and breast feeding. Neonatal mortality in the intervention group did not change over the first two years but showed a significant improvement in the third year. The three leading causes of death were prematurity/low birth-weight (36%), intrapartum-related neonatal deaths (30%), and infections (15%). Stillbirth rates were 7.4 per 1,000 births in the intervention arm and 9.0 per 1,000 births in the control arm. There was one maternal death in the intervention communes and four in the control communes and there was a significant improvement in antenatal care attendance in the intervention arm. However, there were no significant differences between the intervention and control groups of other outcomes, including tetanus immunization, delivery preparedness, institutional delivery, temperature control at delivery, early initiation of breastfeeding, or home visit of a midwife during the first week after delivery.
What Do These Findings Mean?
These findings suggest that local stakeholder groups comprised of primary care staff and local politicians using a problem-solving approach may help to reduce the neonatal mortality rate after three years of implementation (although the time period for an expected reduction in neonatal mortality was not specified before the trial started) and may also increase the rate of antenatal care attendance. However, the intervention had no effect on other important outcomes such as the rate of institutional delivery and breast feeding. This study used a novel approach of community-based activity that was implemented into the public sector system at low cost. A further reduction in neonatal deaths around delivery might be achieved by neonatal resuscitation training and home visits to the mother and her baby.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001445.
The World Health Organization provides comprehensive statistics on neonatal mortality
The Healthy Newborn Network has information on community interventions to help reduce neonatal mortality from around the world
doi:10.1371/journal.pmed.1001445
PMCID: PMC3653802  PMID: 23690755
13.  Roles of human peripheral blood leukocyte protein kinase C and G proteins in inflammatory mediator release by isogenic Escherichia coli strains. 
Infection and Immunity  1991;59(10):3801-3810.
The signal transduction pathway (protein kinase C [PKC], calcium influx, and G protein involvement) was studied with isogenic Escherichia coli strains expressing different types of adhesins (MSH+/- MS-Fim+/-, P-MRH+/- P-Fim+/-, and S-MRH+/- S-Fim+/-) or varying only in the expression of E. coli alpha-hemolysin. As target cells, human polymorphonuclear granulocytes (PMN) and a lymphocyte-monocyte-basophil (LMB) cell suspension were used. The alpha-hemolysin-producing (Hly+) strain E. coli K-12(pANN5211) induced calcium influx in a dose-dependent manner in both cell types. No calcium influx was detected after stimulation with the hemolysin-negative (Hly-) E. coli bacteria independent of the type of fimbriae. With Hly+ bacteria, a dose-dependent activation of PKC was observed in both cell types. The Hly- E. coli K-12 induced PKC to a lesser degree, expressing kinetics different from those of E. coli K-12(pANN5211) (Hly+). E. coli MSH+ MS-Fim+ was the most potent activator for PKC. Membrane preparations from leukocytes stimulated with Hly+ E. coli K-12(pANN5211) showed increased binding of [3H]guanylylimidodiphosphate, a nonhydrolyzable GTP analog, and increased GTPase activity compared with leukocytes stimulated with Hly- E. coli K-12. The amounts of GTPase activation and [3H]guanylylimidodiphosphate binding were similar for all Hly- E. coli bacteria in human PMN as well as in human LMB; no activation was obtained for E. coli bacteria without any type of fimbriae. GTP-gamma-S, a nonhydrolyzable GTP analog, inhibited the leukotriene B4 (LTB4) generation from human PMN by Hly- bacteria, unlike E. coli K-12(pANN5211). However, in the presence of NaF, a predominant activator of Gi, LTB4 generation by Hly+ and by Hly- bacteria was significantly enhanced. For LMBs only LTB4 generation by Hly+ bacteria was increased in the presence of GTP-gamma-S. NaF decreased the chemiluminescence induced by all E. coli strains. Our results thus indicate that (i) Hly+ and Hly- bacteria induce the activation of distinct G proteins, e.g., Gi, to different degrees, (ii) LTB4 generation and chemiluminescence response are differently regulated, and (iii) in comparison with PMN, a different signal transduction pathway is activated by E. coli bacteria in LMBs.
PMCID: PMC258954  PMID: 1654302
14.  The Fall and Rise of US Inequities in Premature Mortality: 1960–2002 
PLoS Medicine  2008;5(2):e46.
Background
Debates exist as to whether, as overall population health improves, the absolute and relative magnitude of income- and race/ethnicity-related health disparities necessarily increase—or derease. We accordingly decided to test the hypothesis that health inequities widen—or shrink—in a context of declining mortality rates, by examining annual US mortality data over a 42 year period.
Methods and Findings
Using US county mortality data from 1960–2002 and county median family income data from the 1960–2000 decennial censuses, we analyzed the rates of premature mortality (deaths among persons under age 65) and infant death (deaths among persons under age 1) by quintiles of county median family income weighted by county population size. Between 1960 and 2002, as US premature mortality and infant death rates declined in all county income quintiles, socioeconomic and racial/ethnic inequities in premature mortality and infant death (both relative and absolute) shrank between 1966 and 1980, especially for US populations of color; thereafter, the relative health inequities widened and the absolute differences barely changed in magnitude. Had all persons experienced the same yearly age-specific premature mortality rates as the white population living in the highest income quintile, between 1960 and 2002, 14% of the white premature deaths and 30% of the premature deaths among populations of color would not have occurred.
Conclusions
The observed trends refute arguments that health inequities inevitably widen—or shrink—as population health improves. Instead, the magnitude of health inequalities can fall or rise; it is our job to understand why.
Nancy Krieger and colleagues found evidence of decreasing, and then increasing or stagnating, socioeconomic and racial inequities in US premature mortality and infant death from 1960 to 2002.
Editors' Summary
Background
One of the biggest aims of public health advocates and governments is to improve the health of the population. Improving health increases people's quality of life and helps the population be more economically productive. But within populations are often persistent differences (usually called “disparities” or “inequities”) in the health of different subgroups—between women and men, different income groups, and people of different races/ethnicities, for example. Researchers study these differences so that policy makers and the broader public can be informed about what to do to intervene. For example, if we know that the health of certain subgroups of the population—such as the poor—is staying the same or even worsening as the overall health of the population is improving, policy makers could design programs and devote resources to specifically target the poor.
To study health disparities, researchers use both relative and absolute measures. Relative inequities refer to ratios, while absolute inequities refer to differences. For example, if one group's average income level increases from $1,000 to $10,000 and another group's from $2,000 to $20,000, the relative inequality between the groups stays the same (i.e., the ratio of incomes between the two groups is still 2) but the absolute difference between the two groups has increased from $1,000 to $10,000.
Examining the US population, Nancy Krieger and colleagues looked at trends over time in both relative and absolute differences in mortality between people in different income groups and between whites and people of color.
Why Was This Study Done?
There has been a lot of debate about whether disparities have been widening or narrowing as overall population health improves. Some research has found that both total health and health disparities are getting better with time. Other research has shown that overall health gains mask worsening disparities—such that the rich get healthier while the poor get sicker.
Having access to more data over a longer time frame meant that Krieger and colleagues could provide a more complete picture of this sometimes contradictory story. It also meant they could test their hypothesis about whether, as population health improves, health inequities necessarily widen or shrink within the time period between the 1960s through the 1990s during which certain events and policies likely would have had an impact on the mortality trends in that country.
What Did the Researchers Do and Find?
In order to investigate health inequities, the authors chose to look at two common measures of population health: rates of premature mortality (dying before the age of 65 years) and rates of infant mortality (death before the age of 1).
To determine mortality rates, the authors used death statistics data from different counties, which are routinely collected by state and national governments. To be able to rank mortality rates for different income groups, they used data on the median family incomes of people living within those counties (meaning half the families had income above, and half had incomes below, the median value). They calculated mortality rates for the total population and for whites versus people of color. They used data from 1960 through 2002. They compared rates for 1966–1980 with two other time periods: 1960–1965 and 1981–2002. They also examined trends in the annual mortality rates and in the annual relative and absolute disparites in these rates by county income level.
Over the whole period 1960–2002, the authors found that premature mortality (death before the age of 65) and infant mortality (death before the age of 1) decreased for all income groups. But they also found that disparities between income groups and between whites and people of color were not the same over this time period. In fact, the economic disparities narrowed then widened. First, they shrank between 1966 and 1980, especially for Americans of color. After 1980, however, the relative health inequities widened and the absolute differences did not change. The authors conclude that if all people in the US population experienced the same health gains as the most advantaged did during these 42 years (i.e., as the whites in the highest income groups), 14% of the premature deaths among whites and 30% of the premature deaths among people of color would have been prevented.
What Do These Findings Mean?
The findings provide an overview of the trends in inequities in premature and infant mortality over a long period of time. Different explanations for these trends can now be tested. The authors discuss several potential reasons for these trends, including generally rising incomes across America and changes related to specific diseases, such as the advent of HIV/AIDS, changes in smoking habits, and better management of cancer and cardiovascular disease. But they find that these do not explain the fall then rise of inequities. Instead, the authors suggest that explanations lie in the social programs of the 1960s and the subsequent roll-back of some of these programmes in the 1980s. The US “War on Poverty,” civil rights legislation, and the establishment of Medicare occurred in the mid 1960s, which were intended to reduce socioeconomic and racial/ethnic inequalities and improve access to health care. In the 1980s there was a general cutting back of welfare state provisions in America, which included cuts to public health and antipoverty programs, tax relief for the wealthy, and worsening inequity in the access to and quality of health care. Together, these wider events could explain the fall then rise trends in mortality disparities.
The authors say their findings are important to inform and help monitor the progress of various policies and programmes, including those such as the Healthy People 2010 initiative in America, which aims to increase the quality and years of healthy life and decrease health disparities by the end of this decade.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed. 0050046.
Healthy People 2010 was created by the US Department of Health and Human Services along with scientists inside and outside of government and includes a comprehensive set of disease prevention and health promotion objectives for the US to achieve by 2010, with two overarching goals: to increase quality and years of healthy life and to eliminate health disparities
Johan Mackenbach and colleagues provide an overview of mortality inequalities in six Western European countries—Finland, Sweden, Norway, Denmark, England/Wales, and Italy—and conclude that eliminating mortality inequalities requires that more cardiovascular deaths among lower socioeconomic groups be prevented, as well as more attention be paid to rising death rates of lung cancer, breast cancer, respiratory disease, gastrointestinal disease, and injuries among women and men in the lower income groups.
The WHO Health for All program promotes health equity
A primer on absolute versus relative differences is provided by the American College of Physicians
doi:10.1371/journal.pmed.0050046
PMCID: PMC2253609  PMID: 18303941
15.  Estimates and Projections of Value of Life Lost From Cancer Deaths in the United States 
Background
Value-of-life methods are increasingly used in policy analyses of the economic burden of disease. The purpose of this study was to estimate and project the value of life lost from cancer deaths in the United States.
Methods
We estimated and projected US age-specific mortality rates for all cancers and for 16 types of cancer in men and 18 cancers in women in the years 2000–2020 and applied them to US population projections to estimate the number of deaths in each year. Cohort life tables were used to calculate the remaining life expectancy in the absence of cancer deaths—the person-years of life lost (PYLL). We used a willingness-to-pay approach in which the value of life lost due to cancer death was calculated by multiplying PYLL by an estimate of the value of 1 year of life ($150 000). We performed sensitivity analyses for female breast, colorectal, lung, and prostate cancers using varying assumptions about future cancer mortality rates through the year 2020.
Results
The value of life lost from all cancer deaths in the year 2000 was $960.6 billion; lung cancer alone represented more than 25% of this value. Projections for the year 2020 with current cancer mortality rates showed a 53% increase in the total value of life lost ($1472.5 billion). Projected annual decreases of cancer mortality rates of 2% reduced the expected value of life lost in the year 2020 from $121.0 billion to $80.7 billion for breast cancer, $140.1 billion to $93.5 billion for colorectal cancer, from $433.4 billion to $289.4 billion for lung cancer, and from $58.4 billion to $39.0 billion for prostate cancer.
Conclusions
Estimated value of life lost due to cancer deaths in the United States is substantial and expected to increase dramatically, even if mortality rates remain constant, because of expected population changes. These estimates and projections may help target investments in cancer control strategies to tumor sites that are likely to result in the greatest burden of disease and to interventions that are the most cost-effective.
doi:10.1093/jnci/djn383
PMCID: PMC2720776  PMID: 19066267
16.  Disability Transitions and Health Expectancies among Adults 45 Years and Older in Malawi: A Cohort-Based Model 
PLoS Medicine  2013;10(5):e1001435.
Collin Payne and colleagues investigated development of disabilities and years expected to live with disabilities in participants 45 years and older participating in the Malawi Longitudinal Survey of Families and Health.
Please see later in the article for the Editors' Summary
Background
Falling fertility and increasing life expectancy contribute to a growing elderly population in sub-Saharan Africa (SSA); by 2060, persons aged 45 y and older are projected to be 25% of SSA's population, up from 10% in 2010. Aging in SSA is associated with unique challenges because of poverty and inadequate social supports. However, despite its importance for understanding the consequences of population aging, the evidence about the prevalence of disabilities and functional limitations due to poor physical health among older adults in SSA continues to be very limited.
Methods and Findings
Participants came from 2006, 2008, and 2010 waves of the Malawi Longitudinal Survey of Families and Health, a study of the rural population in Malawi. We investigate how poor physical health results in functional limitations that limit the day-to-day activities of individuals in domains relevant to this subsistence-agriculture context. These disabilities were parameterized based on questions from the SF-12 questionnaire about limitations in daily living activities. We estimated age-specific patterns of functional limitations and the transitions over time between different disability states using a discrete-time hazard model. The estimated transition rates were then used to calculate the first (to our knowledge) microdata-based health expectancies calculated for SSA. The risks of experiencing functional limitations due to poor physical health are high in this population, and the onset of disabilities happens early in life. Our analyses show that 45-y-old women can expect to spend 58% (95% CI, 55%–64%) of their remaining 28 y of life (95% CI, 25.7–33.5) with functional limitations; 45-y-old men can expect to live 41% (95% CI, 35%–46%) of their remaining 25.4 y (95% CI, 23.3–28.8) with such limitations. Disabilities related to functional limitations are shown to have a substantial negative effect on individuals' labor activities, and are negatively related to subjective well-being.
Conclusions
Individuals in this population experience a lengthy struggle with disabling conditions in adulthood, with high probabilities of remitting and relapsing between states of functional limitation. Given the strong association of disabilities with work efforts and subjective well-being, this research suggests that current national health policies and international donor-funded health programs in SSA inadequately target the physical health of mature and older adults.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The population of the world is getting older. In almost every country, the over-60 age group is growing faster than any other age group. In 2000, globally, there were about 605 million people aged 60 years or more; by 2050, 2 billion people will be in this age group. Much of this increase in the elderly population will be in low-income countries. In sub-Saharan Africa, for example, 10% of the population is currently aged 45 years or more, but by 2060, a quarter of the population will be so-called mature adults. In all countries, population aging is the result of women having fewer children (falling fertility) and people living longer (increasing life expectancy). Thus, population aging is a demographic transition, a change in birth and death rates. In low- and middle-income countries, population aging is occurring in parallel with an “epidemiological transition,” a shift from communicable (infectious) diseases to non-communicable diseases (for example, heart disease) as the primary causes of illness and death.
Why Was This Study Done?
Both the demographic and the epidemiological transition have public health implications for low-income countries. Good health is important for the independence and economic productivity of older people. Productive older people can help younger populations financially and physically, and help compensate for the limitations experienced by younger populations infected with HIV. Also, low-income countries lack social safety nets, so disabled older adults can be a burden on younger populations. Thus, the health of older individuals is important to the well-being of people of all ages. As populations age, low-income countries will need to invest in health care for mature and elderly adults and in disease prevention programs to prevent or delay the onset of non-communicable diseases, which can limit normal daily activities by causing disabilities. Before providing these services, national policy makers need to know the proportion of their population with disabilities, the functional limitations caused by poor physical health, and the health expectancies (the number of years a person can expect to be in good health) of older people in their country. In this cohort modeling study, the researchers estimate health expectancies and transition rates between different levels of disability among mature adults in Malawi, one of the world's poorest countries, using data collected by the Malawi Longitudinal Survey of Families and Health (MLSFH) on economic, social, and health conditions in a rural population. Because Malawi has shorter life expectancies and earlier onset of disability than wealthier countries, the authors considered individuals aged 45 and older as mature adults at risk for disability.
What Did the Researchers Do and Find?
The researchers categorized the participants in the 2006, 2008, and 2010 waves of the MLSFH into three levels of functional limitation (healthy, moderately limited, and severely limited) based on answers to questions in the SF-12 health survey questionnaire that ask about disabilities that limit daily activities that rural Malawians perform. The researchers estimated age–gender patterns of functional limitations and transition rates between different disability states using a discrete-time hazard model, and health expectancies by running a microsimulation to model the aging of synthetic cohorts with various starting ages but the same gender and functional limitation distributions as the study population. These analyses show that the chance of becoming physically disabled rises sharply with age, with 45-year-old women in rural Malawi expected to spend 58% of their estimated remaining 28 years with functional limitations, and 45-year-old men expected to live 41% of their remaining 25.4 years with functional limitations. Also, on average, a 45-year-old woman will spend 2.7 years with moderate functional limitation and 0.6 years with severe functional limitation before she reaches 55; for men the corresponding values are 1.6 and 0.4 years. Around 50% of moderately and 60%–80% of severely limited individuals stated that pain interfered quite a bit or extremely with their normal work during the past four weeks, suggesting that pain treatment may help reduce disability.
What Do These Findings Mean?
These findings suggest that mature adults in rural Malawi will have some degree of disability during much of their remaining lifetime. The risks of experiencing functional limitations are higher and the onset of persistent disabilities happens earlier in Malawi than in more developed contexts—the proportions of remaining life spent with severe limitations at age 45 in Malawi are comparable to those of 80-year-olds in the US. The accuracy of these findings is likely to be affected by assumptions made during modeling and by the quality of the data fed into the models. Nevertheless, these findings suggest that functional limitations, which have a negative effect on the labor activity of individuals, will become more prominent in Malawi (and probably other sub-Saharan countries) as the age composition of populations shifts over the coming years. Older populations in sub-Saharan Africa are not targeted well by health policies and programs at present. Consequently, these findings suggest that policy makers will need to ensure that additional financial resources are provided to improve health-care provision for aging individuals and to lessen the high rates of functional limitation and associated disabilities.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001435.
This study is further discussed in a PLoS Medicine Perspective by Andreas Stuck, et al.
The World Health Organization provides information on many aspects of aging (in several languages); the WHO Study on Global Ageing and Adult Health (SAGE) is compiling longitudinal information on the health and well-being of adult populations and the aging process
The United Nations Population Fund and HelpAge International publication Ageing in the Twenty-First Century is available
HelpAge International is an international nongovernmental organization that helps older people claim their rights, challenge discrimination, and overcome poverty, so that they can lead dignified, secure, and healthy lives
More information on the Malawi Longitudinal Study of Families and Health is available
doi:10.1371/journal.pmed.1001435
PMCID: PMC3646719  PMID: 23667343
17.  Changing mortality patterns in East and West Germany and Poland. II: Short-term trends during transition and in the 1990s 
OBJECTIVES—To examine trends in life expectancy at birth and age and cause specific patterns of mortality in the former German Democratic Republic (GDR) and Poland during political transition and throughout the 1990s in both parts of Germany and in Poland.
METHODS—Decomposition of life expectancy by age and cause of death. Changes in life expectancy during transition by cause of death were examined using data for 1988/89 and 1990/91 for the former GDR and Poland; examination of life expectancy changes after transition were based on 1992-97 data for Germany and 1991-96 data for Poland.
RESULTS—In both the former GDR and Poland male life expectancy at birth declined by almost one year during transition, mainly attributable to rising death rates from external causes and circulatory diseases. Female life expectancy in Poland deteriorated by 0.3 years, largely attributable to increasing circulatory mortality among the old, while in East German female rising death rates in children and young adults were nearly outbalanced by declining circulatory mortality among those over 70. Between 1991/92 and 1996/97, male life expectancy at birth increased by 2.4 years in the former GDR, 1.2 years in old Federal Republic, and 2.0 years in Poland (women: 2.3, 0.9, and 1.2 years). In East Germany and Poland, the overall improvement was largely attributable to falling mortality among men aged 40-64, while those over 65 contributed the largest proportion to life expectancy gains in women. The change in deaths among men aged 15-39 accounted for 0.4 of a year to life expectancy at birth in East Germany and Poland, attributable largely to greater decreases from external causes. Among those over 40, absolute contributions to changing life expectancy were greater in the former GDR than in the other two entities in both sexes, largely attributable to circulatory diseases. A persisting East-west life expectancy gap in Germany of 2.1 years in men in 1997 was largely attributable to external causes, diseases of the digestive system and circulatory diseases. Higher death rates from circulatory diseases among the elderly largely explain the female life expectancy gap of approximately one year.
CONCLUSIONS—This study provides further insights into the health effects of political transition. Post-transition improvements in life expectancy and mortality have been much steeper in East Germany compared with Poland. Changes in dietary pattern and, in Germany, medical care may have been important factors in shaping post-transition mortality trends. 


Keywords: mortality trends; Germany; Poland; transition
doi:10.1136/jech.54.12.899
PMCID: PMC1731602  PMID: 11076985
18.  Projections of Global Mortality and Burden of Disease from 2002 to 2030 
PLoS Medicine  2006;3(11):e442.
Background
Global and regional projections of mortality and burden of disease by cause for the years 2000, 2010, and 2030 were published by Murray and Lopez in 1996 as part of the Global Burden of Disease project. These projections, which are based on 1990 data, continue to be widely quoted, although they are substantially outdated; in particular, they substantially underestimated the spread of HIV/AIDS. To address the widespread demand for information on likely future trends in global health, and thereby to support international health policy and priority setting, we have prepared new projections of mortality and burden of disease to 2030 starting from World Health Organization estimates of mortality and burden of disease for 2002. This paper describes the methods, assumptions, input data, and results.
Methods and Findings
Relatively simple models were used to project future health trends under three scenarios—baseline, optimistic, and pessimistic—based largely on projections of economic and social development, and using the historically observed relationships of these with cause-specific mortality rates. Data inputs have been updated to take account of the greater availability of death registration data and the latest available projections for HIV/AIDS, income, human capital, tobacco smoking, body mass index, and other inputs. In all three scenarios there is a dramatic shift in the distribution of deaths from younger to older ages and from communicable, maternal, perinatal, and nutritional causes to noncommunicable disease causes. The risk of death for children younger than 5 y is projected to fall by nearly 50% in the baseline scenario between 2002 and 2030. The proportion of deaths due to noncommunicable disease is projected to rise from 59% in 2002 to 69% in 2030. Global HIV/AIDS deaths are projected to rise from 2.8 million in 2002 to 6.5 million in 2030 under the baseline scenario, which assumes coverage with antiretroviral drugs reaches 80% by 2012. Under the optimistic scenario, which also assumes increased prevention activity, HIV/AIDS deaths are projected to drop to 3.7 million in 2030. Total tobacco-attributable deaths are projected to rise from 5.4 million in 2005 to 6.4 million in 2015 and 8.3 million in 2030 under our baseline scenario. Tobacco is projected to kill 50% more people in 2015 than HIV/AIDS, and to be responsible for 10% of all deaths globally. The three leading causes of burden of disease in 2030 are projected to include HIV/AIDS, unipolar depressive disorders, and ischaemic heart disease in the baseline and pessimistic scenarios. Road traffic accidents are the fourth leading cause in the baseline scenario, and the third leading cause ahead of ischaemic heart disease in the optimistic scenario. Under the baseline scenario, HIV/AIDS becomes the leading cause of burden of disease in middle- and low-income countries by 2015.
Conclusions
These projections represent a set of three visions of the future for population health, based on certain explicit assumptions. Despite the wide uncertainty ranges around future projections, they enable us to appreciate better the implications for health and health policy of currently observed trends, and the likely impact of fairly certain future trends, such as the ageing of the population, the continued spread of HIV/AIDS in many regions, and the continuation of the epidemiological transition in developing countries. The results depend strongly on the assumption that future mortality trends in poor countries will have a relationship to economic and social development similar to those that have occurred in the higher-income countries.
The presented projections suggest a dramatic shift in the distribution of deaths from younger to older ages and from communicable, maternal, perinatal, and nutritional causes to non-communicable disease causes. HIV/AIDS and tobacco remain major killers and possible targets for intervention.
Editors' Summary
Background.
For most of human history, little has been known about the main causes of illness in different countries and which diseases kill most people. But public-health officials need to know whether heart disease kills more people than cancer in their country, for example, or whether diabetes causes more disability than mental illness so that they can use their resources wisely. They also have to have some idea about how patterns of illness (morbidity) and death (mortality) are likely to change so that they can plan for the future. In the early 1990s, the World Bank sponsored the 1990 Global Burden of Disease study carried out by researchers at Harvard University and the World Health Organization (WHO). This study provided the first comprehensive, global estimates of death and illness by age, sex, and region. It also provided projections of the global burden of disease and mortality up to 2020 using models that assumed that health trends are related to a set of independent variables. These variables were income per person (as people become richer, they, live longer), average number of years of education (as this “human capital” increases, so does life expectancy), time (to allow for improved knowledge about various diseases), and tobacco use (a major global cause of illness and death).
Why Was This Study Done?
These health projections have been widely used by WHO and governments to help them plan their health policies. However, because they are based on the 1990 estimates of the global burden of disease, the projections now need updating, particularly since they underestimate the spread of HIV/AIDS and the associated increase in death from tuberculosis. In this study, the researchers used similar methods to those used in the 1990 Global Burden of Disease study to prepare new projections of mortality and burden of disease up to 2030 starting from the 2002 WHO global estimates of mortality and burden of disease.
What Did the Researchers Do and Find?
As before, the researchers used projections of socio-economic development to model future patterns of mortality and illness for a baseline scenario, a pessimistic scenario that assumed a slower rate of socio-economic development, and an optimistic scenario that assumed a faster rate of growth. Their analysis predicts that between 2002 and 2030 for all three scenarios life expectancy will increase around the world, fewer children younger than 5 years will die, and the proportion of people dying from non-communicable diseases such as heart disease and cancer will increase. Although deaths from infectious diseases will decrease overall, HIV/AIDS deaths will continue to increase; the exact magnitude of the increase will depend on how many people have access to antiretroviral drugs and the efficacy of prevention programs. But, even given the rise in HIV/AIDS deaths, the new projections predict that more people will die of tobacco-related disease than of HIV/AIDS in 2015. The researchers also predict that by 2030, the three leading causes of illness will be HIV/AIDS, depression, and ischaemic heart disease (problems caused by a poor blood supply to the heart) in the baseline and pessimistic scenarios; in the optimistic scenario, road-traffic accidents will replace heart disease as the third leading cause (there will be more traffic accidents with faster economic growth).
What Do These Findings Mean?
The models used by the researchers provide a wealth of information about possible patterns of global death and illness between 2002 and 2030, but because they include many assumptions, like all models, they can provide only indications of future trends, not absolute figures. For example, based on global mortality data from 2002, the researchers estimate that global deaths in 2030 will be 64.9 million under the optimistic scenario. However, the actual figure may be quite a bit bigger or smaller because accurate baseline counts of deaths were not available for every country in the world. Another limitation of the study is that the models used assume that future increases in prosperity in developing countries will affect their population's health in the same way as similar increases affected health in the past in countries with death registration data (these are mostly developed countries). However, even given these and other limitations, the projections reported in this study provide useful insights into the future health of the world. These can now be used by public-health officials to plan future policy and to monitor the effect of new public-health initiatives on the global burden of disease and death.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030442.
World Health Organization, provides information on the Global Burden of Disease Project and links to other related resources Global Burden of Disease Project
Harvard School of Public Health, Burden of Disease Unit, offers information on the 1990 Global Burden of Disease study and its projections Harvard School of Public Health
doi:10.1371/journal.pmed.0030442
PMCID: PMC1664601  PMID: 17132052
19.  Modeling the Impact and Costs of Semiannual Mass Drug Administration for Accelerated Elimination of Lymphatic Filariasis 
The Global Program to Eliminate Lymphatic Filariasis (LF) has a target date of 2020. This program is progressing well in many countries. However, progress has been slow in some countries, and others have not yet started their mass drug administration (MDA) programs. Acceleration is needed. We studied how increasing MDA frequency from once to twice per year would affect program duration and costs by using computer simulation modeling and cost projections. We used the LYMFASIM simulation model to estimate how many annual or semiannual MDA rounds would be required to eliminate LF for Indian and West African scenarios with varied pre-control endemicity and coverage levels. Results were used to estimate total program costs assuming a target population of 100,000 eligibles, a 3% discount rate, and not counting the costs of donated drugs. A sensitivity analysis was done to investigate the robustness of these results with varied assumptions for key parameters. Model predictions suggested that semiannual MDA will require the same number of MDA rounds to achieve LF elimination as annual MDA in most scenarios. Thus semiannual MDA programs should achieve this goal in half of the time required for annual programs. Due to efficiency gains, total program costs for semiannual MDA programs are projected to be lower than those for annual MDA programs in most scenarios. A sensitivity analysis showed that this conclusion is robust. Semiannual MDA is likely to shorten the time and lower the cost required for LF elimination in countries where it can be implemented. This strategy may improve prospects for global elimination of LF by the target year 2020.
Author Summary
The Global Program to Eliminate Lymphatic Filariasis (LF) employs annual mass drug administration (MDA) of antifilarial drugs to reduce infection rates in populations and interrupt transmission. While this program is working well in many countries, progress has been slow in others, and some countries have not yet started MDA programs. We used computer simulation modeling and cost projections to study how increasing MDA frequency from once to twice per year would affect program duration and costs. Our results suggest that semiannual MDA is likely to reduce the time required to eliminate LF by 50% and reduce total program costs (excluding the cost of donated drugs) in most situations. For these and other reasons, we expect semiannual MDA to be superior to annual MDA in most endemic settings. Semiannual MDA should be considered as a means of accelerating LF elimination in areas where it can be implemented, because this may improve prospects for global elimination of LF by the target year 2020.
doi:10.1371/journal.pntd.0001984
PMCID: PMC3536806  PMID: 23301115
20.  Life Expectancies of South African Adults Starting Antiretroviral Treatment: Collaborative Analysis of Cohort Studies 
PLoS Medicine  2013;10(4):e1001418.
Leigh Johnson and colleagues estimate the life expectancies of HIV positive South African adults who are taking antiretroviral therapy by using information from 6 programmes between 2001 and 2010.
Background
Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low- and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults.
Methods and Findings
Data were collected from six South African ART cohorts. Analysis was restricted to 37,740 HIV-positive adults starting ART for the first time. Estimates of mortality were obtained by linking patient records to the national population register. Relative survival models were used to estimate the excess mortality attributable to HIV by age, for different baseline CD4 categories and different durations. Non-HIV mortality was estimated using a South African demographic model. The average life expectancy of men starting ART varied between 27.6 y (95% CI: 25.2–30.2) at age 20 y and 10.1 y (95% CI: 9.3–10.8) at age 60 y, while estimates for women at the same ages were substantially higher, at 36.8 y (95% CI: 34.0–39.7) and 14.4 y (95% CI: 13.3–15.3), respectively. The life expectancy of a 20-y-old woman was 43.1 y (95% CI: 40.1–46.0) if her baseline CD4 count was ≥200 cells/µl, compared to 29.5 y (95% CI: 26.2–33.0) if her baseline CD4 count was <50 cells/µl. Life expectancies of patients with baseline CD4 counts ≥200 cells/µl were between 70% and 86% of those in HIV-negative adults of the same age and sex, and life expectancies were increased by 15%–20% in patients who had survived 2 y after starting ART. However, the analysis was limited by a lack of mortality data at longer durations.
Conclusions
South African HIV-positive adults can have a near-normal life expectancy, provided that they start ART before their CD4 count drops below 200 cells/µl. These findings demonstrate that the near-normal life expectancies of HIV-positive individuals receiving ART in high-income countries can apply to low- and middle-income countries as well.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
According to the latest figures, more than 34 million people worldwide currently live with HIV/AIDS. In 2011, an estimated 2.5 million people were newly infected with HIV, and in the same year 1.7 million people died from AIDS. Since the beginning of the epidemic in the 1980s, more than 60 million people have contracted HIV and nearly 30 million have died of HIV-related causes. Despite the stark statistics, the life expectancy for people infected with the AIDS virus has dramatically improved over the past decade since the introduction of an effective combination of antiretroviral drugs. In high-income countries, people who are HIV-positive can expect a near-normal life expectancy if they take these drugs (as antiretroviral treatment—ART) throughout their life.
Why Was This Study Done?
Recent studies investigating the life expectancy of people living with HIV have mostly focused on the situation in high-income settings. The situation in low- and middle-income countries is vastly different. People who are diagnosed with HIV are often late in starting treatment, treatments regimes are sometimes interrupted, and a large proportion of patients are lost to follow-up. It is important to gain a realistic estimate of life expectancy in low- and middle-income countries so patients can be given the best information. So in this study the researchers used a model to estimate the life expectancy of patients starting ART in South Africa, using data from several ART programs.
What Did the Researchers Do and Find?
The researchers used data collected from six programs in South Africa based in Western Cape, Gauteng, and KwaZulu-Natal between 2001 and 2010. The researchers calculated the observation time from the time of ART initiation to the date of death or to the end of the study. Then the researchers used a relative survival approach to model the excess mortality attributable to HIV, relative to non-HIV mortality rates in South Africa, over different periods from ART initiation.
Using these methods, the researchers found that over the time period, 37,740 adults started ART and 2,066 deaths were recorded in patient record systems. Of the 16,250 patients who were lost to follow-up, the researchers identified 2,947 further deaths in the population register. When they inputted these figures into their model, the researchers estimated that the mortality rate was 83.2 per 1,000 person-years of observation (PYO), and was higher in males (99.8 per 1,000 PYO) than in females (72.6 per 1,000 PYO). The researchers also found that the most significant factor determining the life expectancy of treated patients was their age at ART initiation: the average life expectancy of men starting ART varied between 27.6 years at age 20 and 10.1 years at age 60, while corresponding estimates in women were 36.8 and 14.4, respectively. Life expectancies were also significantly influenced by baseline CD4 counts; life expectancies in patients with baseline CD4 counts ≥200 cells/µl were between 70% and 86% of those of HIV-negative adults of the same age and sex, while patients starting ART with CD4 counts of <50 cells/µl had life expectancies that were between 48% and 61% of those of HIV-negative adults. Importantly, the researchers found that life expectancies were also 15%–20% higher in patients who survived their first 24 months after starting ART than in patients of the same age who had just started therapy.
What Do These Findings Mean?
These findings suggest that in South Africa, patients starting ART have life expectancies around 80% of normal life expectancy, provided that they start treatment before their CD4 count drops below 200 cells/µl. Although these results are encouraging, this study highlights that health services must overcome major challenges, such as dealing with late diagnosis, low uptake of CD4 testing, loss from pre-ART care, and delayed ART initiation, if near-normal life expectancies are to be achieved for the majority of HIV-positive South Africans. With the anticipated increase in the fraction of patients starting ART at higher CD4 counts in the future, long-term survival can be expected to increase even further. It is therefore critical that appropriate funding systems and innovative ways to reduce costs are put in place, to ensure the long-term sustainability of ART delivery in low- and middle-income countries.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001418.
The International Epidemiologic Databases to Evaluate AIDS has more statistical information from world regions
amfAR, the Foundation for AIDS Research, works with health care workers and AIDS organizations in developing countries to create and implement effective HIV research, treatment, prevention, and education strategies
doi:10.1371/journal.pmed.1001418
PMCID: PMC3621664  PMID: 23585736
21.  Estimation of the past and future burden of mortality from mesothelioma in France 
OBJECTIVES: Firstly to evaluate future mortality from mesothelioma in France with an age-period-cohort approach and evaluate different hypotheses on risk of mesothelioma for the most recent birth cohort. Secondly to compare the results with a British and an American study. Thirdly to study if any trends were detectable on data for women which would be consistent with the consequences of increasing environmental exposure to asbestos. METHODS: Estimates of mortality from mesothelioma among men and women in France from 1950 to 1995 were based on the analysis of the pleural cancer mortality data coded 163 in the ninth revision of the international classification of diseases (ICD-9). Correction factors were used to derive the mortality from mesothelioma from these data, based on two regional registries. The analysis of the past mortality data has been performed by an age-cohort model (with a maximum likelihood technique). Predictions of deaths from mesothelioma over the next 50 years were based on four different assumptions on the risk of death from mesothelioma in future birth cohorts. RESULTS: The predicted lifetime probability of dying from mesothelioma increases until the last birth cohort 1964-8 among men whereas it decreases strongly from the 1954-8 birth cohort among women. The projected numbers of deaths from mesothelioma in France until 2020 are similar, whichever hypothesis is considered: around 20,000 deaths from mesothelioma might occur among men and 2900 among women from 1996 to 2020. CONCLUSIONS: French data show an increasing lifetime probability of death from mesothelioma in the more recent male cohorts. Although the mortality burden can be predicted until 2020, and is intermediate between the United Kingdom and United States estimates, there is still high uncertainty on the figures after 2020. No increase is found in women, and this does not support the hypothesis that current environmental exposure to asbestos could be associated with a detectable risk of death. Specific surveillance should be set up to monitor future trends or their absence.
 
PMCID: PMC1757524  PMID: 9924453
22.  Healthy life expectancy: evaluation of global indicator of change in population health. 
BMJ : British Medical Journal  1991;302(6774):457-460.
OBJECTIVE--To review and evaluate the usefulness of healthy life expectancy as a global indicator of changes in a population's health. DESIGN--Review of all known studies to date from the United States, mainland Europe, Canada, and the United Kingdom that have used Sullivan's method of calculating disability free life expectancy. MAIN OUTCOME MEASURES--Life expectancy and disability free life expectancy. RESULTS--Over the past decade the average healthy life expectancy was 60 years for men and 64 for women, with the proportion of years of disability ranging from 11% to 21% in men and from 14% to 24% in women. At the age of 65 men could expect eight years of disability free life and women 10, with the life expectancy being respectively 14 and 19 years. The difference between the wealthiest and poorest income quintiles was 6.3 years in life expectancy and 14.3 in disability free life expectancy for men and 2.8 and 7.6 respectively for women. These results suggest that disparities in health are greater between social groups than between the sexes. Diseases affect mortality and morbidity differently. The order of importance for affecting life expectancy was circulatory disease, cancer, and accidents and for disability free life expectancy, circulatory disease, locomotor disorders, and respiratory disorders. CONCLUSIONS--Healthy life expectancy is a valuable index for the appreciation of changes in both the physical and the mental health states of the general population, for allocating resources, and for measuring the success of political programmes. Future calculations should also take into account the probability of recovery and thus extend the applicability of the indicator to populations in poor health rather than focusing on the well population.
PMCID: PMC1669345  PMID: 1825931
23.  Decreases in Diabetes-Free Life Expectancy in the U.S. and the Role of Obesity 
Diabetes Care  2011;34(10):2225-2230.
OBJECTIVE
With increasing life expectancy in the U.S., it is important to know whether a longer life expectancy means a longer healthy life span or a prolonged period of later-life morbidity. This study examines changes in lifetime without diabetes, a leading cause of morbidity in later life.
RESEARCH DESIGN AND METHODS
Using demographic methods and nationally representative data, we estimated changes in diabetes-free life expectancy between 1980–1989 and 2000–2004 for adult men and women in the U.S., estimated the contribution of changes in age-specific diabetes rates, and examined the changing effects of weight status on diabetes risks.
RESULTS
While life expectancy at age 18 for men and women increased between the 1980s and the 2000s, diabetes-free life expectancy at age 18 decreased by 1.7 years for men and 1.5 years for women. The proportion of 18-year-olds who would develop diabetes in their lifetimes increased by almost 50% among women and almost doubled among men. Obese individuals experienced the greatest losses in diabetes-free life expectancy during this period, estimated at 5.6 years for men and 2.5 years for women.
CONCLUSIONS
Diabetes-free life expectancy decreased for both men and women between 1980–1989 and 2000–2004, and these decreases are almost entirely attributable to large increases in diabetes incidence among obese individuals.
doi:10.2337/dc11-0462
PMCID: PMC3177736  PMID: 21949220
24.  Economic effects of interventions to reduce obesity in Israel 
Background
Obesity is a major risk factor for many diseases. The paper calculates the economic impact and the cost per Quality-Adjusted Life Year (QALY) resulting from the adoption of eight interventions comprising the clinical and part of the community components of the National Prevention and Health Promotion Program (NPHPP) of the Israeli Ministry of Health (MOH) which represents the obesity control implementation arm of the MOH Healthy Israel 2020 Initiative.
Methods
Health care costs per person were calculated by body mass index (BMI) by applying Israeli cost data to aggregated results from international studies. These were applied to BMI changes from eight intervention programmes in order to calculate reductions in direct treatment costs. Indirect cost savings were also estimated as were additional costs due to increased longevity of program participants. Data on costs and QALYs gained from Israeli and International dietary interventions were combined to provide cost-utility estimates of an intervention program to reduce obesity in Israel over a range of recidivism rates.
Results
On average, persons who were overweight (25 ≤ BMI < 30)had health care costs that were 12.2% above the average health care costs of persons with normal or sub-normal weight to height ratios (BMI < 25). This differential in costs rose to 31.4% and 73.0% for obese and severely obese persons, respectively.
For overweight (25 ≤ BMI < 30) and obese persons (30 ≤ BMI < 40), costs per person for the interventions (including the screening overhead) ranged from 35 NIS for a community intervention to 860 NIS, reflecting the intensity of the clinical setting intervention and the unit costs of the professionals carrying out the intervention [e.g., dietician]. Expected average BMI decreases ranged from 0.05 to 0.90. Higher intervention costs and larger BMI decreases characterized the two clinical lifestyle interventions for the severely obese (BMI ≥ 40).
A program directed at the entire Israeli population aged 20 and over, using a variety of eight different interventions would cost 2.07 billion NIS overall. In the baseline scenario (with an assumed recidivism rate of 50% per annum), approximately 620,000,000 NIS would be recouped in the form of decreased treatment costs and indirect costs, increased productivity and decreased absenteeism. After discounting the 89,000,000 NIS additional health costs attributable to these extra life years, it is estimated that the total net costs to society would be 1.55 billion NIS. This total net cost was relatively stable to increases in the program's recidivism rates, but highly sensitive to reductions in recidivism rates.
Under baseline assumptions, implementation of the cluster of interventions would save 32,671 discounted QALYs at a cost of only 47,559 NIS per QALY, less than half of the Israeli per capita GNP (104,000 NIS). Thus implementation of these components of the NPHPP should be considered very cost-effective.
Conclusion
Despite the large costs of such a large national program to control obesity, cost-utility analysis strongly supports its introduction.
doi:10.1186/2045-4015-1-17
PMCID: PMC3424853  PMID: 22913803
25.  Cardiovascular Health Behavior and Health Factor Changes (1988 –2008) and Projections to 2020 
Circulation  2012;125(21):2595-2602.
Background
The American Heart Association’s 2020 Strategic Impact Goals target a 20% relative improvement in overall cardiovascular health with the use of 4 health behavior (smoking, diet, physical activity, body mass) and 3 health factor (plasma glucose, cholesterol, blood pressure) metrics. We sought to define current trends and forward projections to 2020 in cardiovascular health.
Methods and Results
We included 35 059 cardiovascular disease–free adults (aged ≥20 years) from the National Health and Nutrition Examination Survey 1988–1994 and subsequent 2-year cycles during 1999–2008. We calculated population prevalence of poor, intermediate, and ideal health behaviors and factors and also computed a composite, individual-level Cardiovascular Health Score for all 7 metrics (poor=0 points; intermediate=1 point; ideal=2 points; total range, 0–14 points). Prevalence of current and former smoking, hypercholesterolemia, and hypertension declined, whereas prevalence of obesity and dysglycemia increased through 2008. Physical activity levels and low diet quality scores changed minimally. Projections to 2020 suggest that obesity and impaired fasting glucose/diabetes mellitus could increase to affect 43% and 77% of US men and 42% and 53% of US women, respectively. Overall, population-level cardiovascular health is projected to improve by 6% overall by 2020 if current trends continue. Individual-level Cardiovascular Health Score projections to 2020 (men=7.4 [95% confidence interval, 5.7–9.1]; women=8.8 [95% confidence interval, 7.6–9.9]) fall well below the level needed to achieve a 20% improvement (men=9.4; women=10.1).
Conclusions
The American Heart Association 2020 target of improving cardiovascular health by 20% by 2020 will not be reached if current trends continue.
doi:10.1161/CIRCULATIONAHA.111.070722
PMCID: PMC3914399  PMID: 22547667
cardiovascular disease risk factors; epidemiology; risk factors; trends

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