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1.  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
2.  Respiratory symptoms in adults are related to impaired quality of life, regardless of asthma and COPD: results from the European community respiratory health survey 
Background
Respiratory symptoms are common in the general population, and their presence is related to Health-related quality of life (HRQoL). The objective was to describe the association of respiratory symptoms with HRQoL in subjects with and without asthma or COPD and to investigate the role of atopy, bronchial hyperresponsiveness (BHR), and lung function in HRQoL.
Methods
The European Community Respiratory Health Survey (ECRHS) I and II provided data on HRQoL, lung function, respiratory symptoms, asthma, atopy, and BHR from 6009 subjects. Generic HRQoL was assessed through the physical component summary (PCS) score and the mental component summary (MCS) score of the SF-36.
Factor analyses and linear regressions adjusted for age, gender, smoking, occupation, BMI, comorbidity, and study centre were conducted.
Results
Having breathlessness at rest in ECRHS II was associated with mean score (95% CI) impairment in PCS of -8.05 (-11.18, -4.93). Impairment in MCS score in subjects waking up with chest tightness was -4.02 (-5.51, -2.52). The magnitude of HRQoL impairment associated with respiratory symptoms was similar for subjects with and without asthma/COPD. Adjustments for atopy, BHR, and lung function did not explain the association of respiratory symptoms and HRQoL in subjects without asthma and/or COPD.
Conclusion
Subjects with respiratory symptoms had poorer HRQoL; including subjects without a diagnosis of asthma or COPD. These findings suggest that respiratory symptoms in the absence of a medical diagnosis of asthma or COPD are by no means trivial, and that clarifying the nature and natural history of respiratory symptoms is a relevant challenge.
Several community studies have estimated the prevalence of common respiratory symptoms like cough, dyspnoea, and wheeze in adults [1-3]. Although the prevalence varies to a large degree between studies and geographical areas, respiratory symptoms are quite common. The prevalences of respiratory symptoms in the European Community Respiratory Health Study (ECRHS) varied from one percent to 35% [1]. In fact, two studies have reported that more than half of the adult population suffers from one or more respiratory symptoms [4,5].
Respiratory symptoms are important markers of the risk of having or developing disease. Respiratory symptoms have been shown to be predictors for lung function decline [6-8], asthma [9,10], and even all-cause mortality in a general population study [11]. In patients with a known diagnosis of asthma or chronic obstructive pulmonary disease (COPD), respiratory symptoms are important determinants of reduced health related quality of life (HRQoL) [12-15]. The prevalence of respiratory symptoms exceeds the combined prevalences of asthma and COPD, and both asthma and COPD are frequently undiagnosed diseases [16-18]. Thus, the high prevalence of respipratory symptoms may mirror undiagnosed and untreated disease.
The common occurrence of respiratory symptoms calls for attention to how these symptoms affect health also in subjects with no diagnosis of obstructive airways disease. Impaired HRQoL in the presence of respiratory symptoms have been found in two population-based studies [6,19], but no study of respiratory sypmtoms and HRQoL have separate analyses for subjects with and without asthma and COPD, and no study provide information about extensive objective measurements of respiratory health.
The ECRHS is a randomly sampled, multi-cultural, population based cohort study. The ECRHS included measurements of atopy, bronchial hyperresponsiveness (BHR), and lung function, and offers a unique opportunity to investigate how respiratory symptoms affect HRQoL among subjects both with and without obstructive lung disease.
In the present paper we aimed to: 1) Describe the relationship between respiratory symptoms and HRQoL in an international adult general population and: 2) To assess whether this relationship varied with presence of asthma and/or COPD, or presence of objective functional markers like atopy and BHR.
doi:10.1186/1477-7525-8-107
PMCID: PMC2954977  PMID: 20875099
3.  Socioeconomic Factors and All Cause and Cause-Specific Mortality among Older People in Latin America, India, and China: A Population-Based Cohort Study 
PLoS Medicine  2012;9(2):e1001179.
Cleusa Ferri and colleagues studied mortality rates in over 12,000 people aged 65 years and over in Latin America, India, and China and showed that chronic diseases are the main causes of death and that education has an important effect on mortality.
Background
Even in low and middle income countries most deaths occur in older adults. In Europe, the effects of better education and home ownership upon mortality seem to persist into old age, but these effects may not generalise to LMICs. Reliable data on causes and determinants of mortality are lacking.
Methods and Findings
The vital status of 12,373 people aged 65 y and over was determined 3–5 y after baseline survey in sites in Latin America, India, and China. We report crude and standardised mortality rates, standardized mortality ratios comparing mortality experience with that in the United States, and estimated associations with socioeconomic factors using Cox's proportional hazards regression. Cause-specific mortality fractions were estimated using the InterVA algorithm. Crude mortality rates varied from 27.3 to 70.0 per 1,000 person-years, a 3-fold variation persisting after standardisation for demographic and economic factors. Compared with the US, mortality was much higher in urban India and rural China, much lower in Peru, Venezuela, and urban Mexico, and similar in other sites. Mortality rates were higher among men, and increased with age. Adjusting for these effects, it was found that education, occupational attainment, assets, and pension receipt were all inversely associated with mortality, and food insecurity positively associated. Mutually adjusted, only education remained protective (pooled hazard ratio 0.93, 95% CI 0.89–0.98). Most deaths occurred at home, but, except in India, most individuals received medical attention during their final illness. Chronic diseases were the main causes of death, together with tuberculosis and liver disease, with stroke the leading cause in nearly all sites.
Conclusions
Education seems to have an important latent effect on mortality into late life. However, compositional differences in socioeconomic position do not explain differences in mortality between sites. Social protection for older people, and the effectiveness of health systems in preventing and treating chronic disease, may be as important as economic and human development.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, half of all deaths occur in people aged 60 or older. Yet mortality among older people is a neglected topic in global health. In high income countries, where 84% of people do not die until they are aged 65 years or older, the causes of death among older people and the factors (determinants) that affect their risk of dying are well documented. In Europe, for example, the leading causes of death among older people are heart disease, stroke, and other chronic (long-term) diseases. Moreover, as in younger age groups, having a better education and owning a house reduces the risk of death among older people. By contrast, in low and middle income countries (LMICs), where three-quarters of deaths of older people occur, reliable data on the causes and determinants of death among older people are lacking, in part because many LMICs have inadequate vital registration systems—official records of all births and deaths.
Why Was This Study Done?
In many LMICs, chronic diseases are replacing communicable (infectious) diseases as the leading causes of death and disability—health experts call this the epidemiological transition (epidemiology is the study of the distribution and causes of disease in populations)—and the average age of the population is increasing (the demographic transition). Faced with these changes, which occur when countries move from a pre-industrial to an industrial economy, policy makers in LMICs need to introduce measures to improve health and reduce deaths among older people. However, to do this, they need reliable data on the causes and determinants of death in this section of the population. In this longitudinal population-based cohort study (a type of study that follows a group of people from a defined population over time), researchers from the 10/66 Dementia Research Group, which is carrying out population-based research on dementia, aging, and non-communicable diseases in LMICs, investigate the patterns of mortality among older people living in Latin America, India, and China.
What Did the Researchers Do and Find?
Between 2003 and 2005, the researchers completed a baseline survey of people aged 65 years or older living in six Latin American LMICs, China, and India. Three to five years later, they determined the vital status of 12,373 of the study participants (that is, they determined whether the individual was alive or dead) and interviewed a key informant (usually a relative) about each death using a standardized “verbal autopsy” questionnaire that includes questions about date and place of death, and about medical help-seeking and signs and symptoms noted during the final illness. Finally, they used a tool called the InterVA algorithm to calculate the most likely causes of death from the verbal autopsies. Crude mortality rates varied from 27.3 per 1,000 person-years in urban Peru to 70.0 per 1,000 person-years in urban India, a three-fold difference in mortality rates that persisted even after allowing for differences in age, sex, education, occupational attainment, and number of assets among the study sites. Compared to the US, mortality rates were much higher in urban India and rural China; much lower in urban and rural Peru, Venezuela, and urban Mexico; but similar elsewhere. Although several socioeconomic factors were associated with mortality, only a higher education status provided consistent independent protection against death in statistical analyses. Finally, chronic diseases were the main causes of death; stroke was the leading cause of death at all the sites except those in rural Peru and Mexico.
What Do These Findings Mean?
These findings identify the main causes of death among older adults in a range of LMICs and suggest that there is an association of education with mortality that extends into later life. However, these findings may not be generalizable to other LMICs or even to other sites in the LMICs studied, and because some of the information provided by key informants may have been affected by recall error, the accuracy of the findings may be limited. Nevertheless, these findings suggest how health and mortality might be improved in elderly people in LMICs. Specifically, they suggest that efforts to ensure universal access to education should confer substantial health benefits and that interventions that target social and economic vulnerability in later life and promote access to effectively organized health care (particularly for stroke) should be considered.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001179.
The World Health Organization provides information on mortality around the world and projections of global mortality up to 2030
The 10/66 Dementia Research Group is building an evidence base to inform the development and implementation of policies for improving the health and social welfare of older people in LMICs, particularly people with dementia; its website includes background information about demographic and epidemiological aging in LMICs
Wikipedia has a page on the demographic transition (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
Information about the InterVA tool for interpreting verbal autopsy data is available
The US Centers for Disease Control and Prevention has information about healthy aging
doi:10.1371/journal.pmed.1001179
PMCID: PMC3289608  PMID: 22389633
4.  Prevalence, Distribution, and Impact of Mild Cognitive Impairment in Latin America, China, and India: A 10/66 Population-Based Study 
PLoS Medicine  2012;9(2):e1001170.
A set of cross-sectional surveys carried out in Cuba, Dominican Republic, Peru, Mexico, Venezuela, Puerto Rico, China, and India reveal the prevalence and between-country variation in mild cognitive impairment at a population level.
Background
Rapid demographic ageing is a growing public health issue in many low- and middle-income countries (LAMICs). Mild cognitive impairment (MCI) is a construct frequently used to define groups of people who may be at risk of developing dementia, crucial for targeting preventative interventions. However, little is known about the prevalence or impact of MCI in LAMIC settings.
Methods and Findings
Data were analysed from cross-sectional surveys established by the 10/66 Dementia Research Group and carried out in Cuba, Dominican Republic, Peru, Mexico, Venezuela, Puerto Rico, China, and India on 15,376 individuals aged 65+ without dementia. Standardised assessments of mental and physical health, and cognitive function were carried out including informant interviews. An algorithm was developed to define Mayo Clinic amnestic MCI (aMCI). Disability (12-item World Health Organization disability assessment schedule [WHODAS]) and informant-reported neuropsychiatric symptoms (neuropsychiatric inventory [NPI-Q]) were measured. After adjustment, aMCI was associated with disability, anxiety, apathy, and irritability (but not depression); between-country heterogeneity in these associations was only significant for disability. The crude prevalence of aMCI ranged from 0.8% in China to 4.3% in India. Country differences changed little (range 0.6%–4.6%) after standardization for age, gender, and education level. In pooled estimates, aMCI was modestly associated with male gender and fewer assets but was not associated with age or education. There was no significant between-country variation in these demographic associations.
Conclusions
An algorithm-derived diagnosis of aMCI showed few sociodemographic associations but was consistently associated with higher disability and neuropsychiatric symptoms in addition to showing substantial variation in prevalence across LAMIC populations. Longitudinal data are needed to confirm findings—in particular, to investigate the predictive validity of aMCI in these settings and risk/protective factors for progression to dementia; however, the large number affected has important implications in these rapidly ageing settings.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Currently, more than 35 million people worldwide have dementia, a group of brain disorders characterized by an irreversible decline in memory, problem solving, communication, and other “cognitive” functions. Dementia, the commonest form of which is Alzheimer's disease, mainly affects older people and, because more people than ever are living to a ripe old age, experts estimate that, by 2050, more than 115 million people will have dementia. At present, there is no cure for dementia although drugs can be used to manage some of the symptoms. Risk factors for dementia include physical inactivity, infrequent participation in mentally or socially stimulating activities, and common vascular risk factors such as high blood pressure, diabetes, and smoking. In addition, some studies have reported that mild cognitive impairment (MCI) is associated with an increased risk of dementia. MCI can be seen as an intermediate state between normal cognitive aging (becoming increasingly forgetful) and dementia although many people with MCI never develop dementia, and some types of MCI can be static or self-limiting. Individuals with MCI have cognitive problems that are more severe than those normally seen in people of a similar age but they have no other symptoms of dementia and are able to look after themselves. The best studied form of MCI—amnestic MCI (aMCI)—is characterized by memory problems such as misplacing things and forgetting appointments.
Why Was This Study Done?
Much of the expected increase in dementia will occur in low and middle income countries (LAMICs) because these countries have rapidly aging populations. Given that aMCI is frequently used to define groups of people who may be at risk of developing dementia, it would be useful to know what proportion of community-dwelling older adults in LAMICs have aMCI (the prevalence of aMCI). Such information might help governments plan their future health care and social support needs. In this cross-sectional, population-based study, the researchers estimate the prevalence of aMCI in eight LAMICs using data collected by the 10/66 Dementia Research Group. They also investigate the association of aMCI with sociodemographic factors (for example, age, gender, and education), disability, and neuropsychiatric symptoms such as anxiety, apathy, irritability, and depression. A cross-sectional study collects data on a population at a single time point; the 10/66 Dementia Research Group is building an evidence base to inform the development and implementation of policies for improving the health and social welfare of older people in LAMICs, particularly people with dementia.
What Did the Researchers Do and Find?
In cross-sectional surveys carried out in six Latin American LAMICS, China, and India, more than 15,000 elderly individuals without dementia completed standardized assessments of their mental and physical health and their cognitive function. Interviews with relatives and carers provided further details about the participant's cognitive decline and about neuropsychiatric symptoms. The researchers developed an algorithm (set of formulae) that used the data collected in these surveys to diagnose aMCI in the study participants. Finally, they used statistical methods to analyze the prevalence, distribution, and impact of aMCI in the eight LAMICs. The researchers report that aMCI was associated with disability, anxiety, apathy, and irritability but not with depression and that the prevalence of aMCI ranged from 0.8% in China to 4.3% in India. Other analyses show that, considered across all eight countries, aMCI was modestly associated with being male (men had a slightly higher prevalence of aMCI than women) and with having fewer assets but was not associated with age or education.
What Do These Findings Mean?
These findings suggest that aMCI, as diagnosed using the algorithm developed by the researchers, is consistently associated with higher disability and with neuropsychiatric symptoms in the LAMICs studied but not with most sociodemographic factors. Because prevalidated and standardized measurements were applied consistently in all the countries and a common algorithm was used to define aMCI, these findings also suggest that the prevalence of aMCI varies markedly among LAMIC populations and is similar to or slightly lower than the prevalence most often reported for European and North American populations. Although longitudinal studies are now needed to investigate the extent to which aMCI can be used as risk marker for further cognitive decline and dementia in these settings, the large absolute numbers of older people with aMCI in LAMICs revealed here potentially has important implications for health care and social service planning in these rapidly aging and populous regions of the world.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001170.
Alzheimer's Disease International is the international federation of Alzheimer associations around the world; it provides links to individual associations, information about dementia, and links to three World Alzheimer Reports; information about the 10/66 Dementia Research Group is also available on this web site
The Alzheimer's Society provides information for patients and carers about dementia, including information on MCI and personal stories about living with dementia
The Alzheimer's Association also provides information for patients and carers about dementia and about MCI, and personal stories about dementia
A BBC radio program that includes an interview with a man with MCI is available
MedlinePlus provides links to further resources about MCI and dementia (in English and Spanish)
doi:10.1371/journal.pmed.1001170
PMCID: PMC3274506  PMID: 22346736
5.  Veterans and Risk of Heart Disease in the United States: A Cohort with 20 Years of Follow Up 
Background:
The aim of the current study was twofold: To investigate the effect of veteran status on risk of developing heart disease over a period of 20 years in the United States and to test if socio-economic characteristics, chronic conditions, health behaviors, body mass index (BMI) and depressive symptoms explain the association between veteran status and risk of heart disease.
Methods:
Data came from the Health and Retirement Study, a 20 year national cohort from 1992 to 2012. The study enrolled a representative sample of Americans over the age of 50. We included 8,375 individuals who were older than 50 years at entry, did not have heart disease at baseline and provided data on heart disease over the next 20 years. Veteran status was considered to be the independent variable. Self-reported data on physician diagnosis of heart disease, which was measured on a biannual basis, was the outcome. Baseline socio-economic data (i.e. age, gender, race, marital status and education), chronic conditions (diabetes and hypertension), health behaviors (i.e. drinking, smoking, and exercise), BMI and depressive symptoms (modified Center for Epidemiologic Studies Depression Scale) were entered into logistic regressions. Logistic regression was used for data analysis.
Results:
Veterans were at higher risk of having a new onset of heart disease (unadjusted relative risk [RR] = 1.996, 95% confidence interval [CI] =1.694-2.351), compared with non-veterans. Logistic regression confirmed the association between veteran status and heart disease (adjusted RR = 1.483, 95% CI = 1.176-1.871) after controlling for all covariates.
Conclusions:
Veterans may be at higher risk for heart disease over time and this link may be independent of baseline socio-economic characteristics, chronic medical conditions, health behaviors, BMI and depressive symptoms. Veterans may require more rigorous cardiovascular prevention programs.
PMCID: PMC4085922  PMID: 25013689
Cohort; depression; drinking; exercise; heart disease; smoking; veterans
6.  Child Mortality Estimation: Consistency of Under-Five Mortality Rate Estimates Using Full Birth Histories and Summary Birth Histories 
PLoS Medicine  2012;9(8):e1001296.
Romesh Silva assesses and analyzes differences in direct and indirect methods of estimating under-five mortality rates using data collected from full and summary birth histories in Demographic and Health Surveys from West Africa, East Africa, Latin America, and South/Southeast Asia.
Background
Given the lack of complete vital registration data in most developing countries, for many countries it is not possible to accurately estimate under-five mortality rates from vital registration systems. Heavy reliance is often placed on direct and indirect methods for analyzing data collected from birth histories to estimate under-five mortality rates. Yet few systematic comparisons of these methods have been undertaken. This paper investigates whether analysts should use both direct and indirect estimates from full birth histories, and under what circumstances indirect estimates derived from summary birth histories should be used.
Methods and Findings
Usings Demographic and Health Surveys data from West Africa, East Africa, Latin America, and South/Southeast Asia, I quantify the differences between direct and indirect estimates of under-five mortality rates, analyze data quality issues, note the relative effects of these issues, and test whether these issues explain the observed differences. I find that indirect estimates are generally consistent with direct estimates, after adjustment for fertility change and birth transference, but don't add substantial additional insight beyond direct estimates. However, choice of direct or indirect method was found to be important in terms of both the adjustment for data errors and the assumptions made about fertility.
Conclusions
Although adjusted indirect estimates are generally consistent with adjusted direct estimates, some notable inconsistencies were observed for countries that had experienced either a political or economic crisis or stalled health transition in their recent past. This result suggests that when a population has experienced a smooth mortality decline or only short periods of excess mortality, both adjusted methods perform equally well. However, the observed inconsistencies identified suggest that the indirect method is particularly prone to bias resulting from violations of its strong assumptions about recent mortality and fertility. Hence, indirect estimates of under-five mortality rates from summary birth histories should be used only for populations that have experienced either smooth mortality declines or only short periods of excess mortality in their recent past.
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
In 1990, 12 million children died before they reached their fifth birthday. Faced with this largely avoidable loss of young lives, in 2000, world leaders set a target of reducing under-five mortality (death) to one-third of its 1990 level by 2015 as Millennium Development Goal 4 (MDG 4); this goal, together with seven others, aims to eradicate extreme poverty globally. To track progress towards MDG 4, experts need accurate estimates of the global and country-specific under-five mortality rate (U5MR, the probability of a child dying before age five). The most reliable sources of data for U5MR estimation are vital registration systems—national records of all births and deaths. Unfortunately, developing countries, which are where most childhood deaths occur, rarely have such records, so full or summary birth histories provide the data for U5MR estimation instead. In full birth histories (FBHs), which are collected through household surveys such as those conducted by Demographic and Health Surveys (DHS), women are asked for the date of birth of all their children and the age at death of any children who have died. In summary birth histories (SBHs), which are collected through household surveys and censuses, women are asked how many children they have had and how many are alive at the time of the survey.
Why Was This Study Done?
“Direct” estimates of U5MRs can be obtained from FBHs because FBHs provide detailed information about the date of death and the exposure of children to the risk of dying. By contrast, because SBHs do not contain information on children's exposure to the risk of dying, “indirect” estimates of U5MR are obtained from SBHs using model life tables (mathematical models of the variation of mortality with age). Indirect estimates are often also derived from FBHs, but few systematic comparisons of direct and indirect methods for U5MR estimation have been undertaken. In this study, Romesh Silva investigates whether direct and indirect methods provide consistent U5MR estimates from FBHs and whether there are any circumstances under which indirect methods provide more reliable U5MR estimates than direct methods.
What Did the Researcher Do and Find?
The researcher used DHS data from West Africa, East Africa, Latin America, and South/Southeast Asia to quantify the differences between direct and indirect estimates of U5MR calculated from the same data and analyzed possible reasons for these differences. Estimates obtained using a version of the “Brass” indirect estimation method were uniformly higher than those obtained using direct estimation. Indirect and direct estimates generally agreed, however, after adjustment for changes in fertility—the Brass method assumes that country-specific fertility (the number of children born to a woman during her reproductive life) remains constant—and for birth transference, an important source of data error in FBHs that arises because DHS field staff can lessen their workload by recording births as occurring before a preset cutoff date rather than after that date. Notably, though, for countries that had experienced political or economic crises, periods of excess mortality due to conflicts, or periods during which the health transition had stalled (as countries become more affluent, overall mortality rates decline and noncommunicable diseases replace infectious diseases as the major causes of death), marked differences between indirect and direct estimates of U5MR remained, even after these adjustments.
What Do These Findings Mean?
Because the countries included in this study do not have vital registration systems, these findings provide no information about the validity of either direct or indirect estimation methods for U5MR estimation. They suggest, however, that for countries where there has been a smooth decline in mortality or only short periods of excess mortality, both direct and indirect methods of U5MR estimation work equally well, after adjustment for changes in fertility and for birth transference, and that indirect estimates add little to the insights provided into childhood mortality by direct estimates. Importantly, the inconsistencies observed between the two methods that remain after adjustment suggest that indirect U5MR estimation is more susceptible to bias (systematic errors that arise because of the assumptions used to estimate U5MR) than direct estimation. Thus, indirect estimates of U5MR from SBHs should be used only for populations that have experienced either smooth mortality declines or only short periods of excess mortality in their recent past.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001296.
This paper is part of a collection of papers on Child Mortality Estimation Methods published in PLOS Medicine
The United Nations Childrens Fund (UNICEF) works for children's rights, survival, development, and protection around the world; it provides information on Millennium Development Goal 4, and its Childinfo website provides detailed statistics about child survival and health, including a description of the United Nations Inter-agency Group for Child Mortality Estimation; the 2011 UN IGME report Levels & Trends in Child Mortality is available
The World Health Organization has information about Millennium Development Goal 4 and provides estimates of child mortality rates (some information in several languages)
Further information about the Millennium Development Goals is available
Information is available about infant and child mortality data collected by Demographic and Health Surveys
doi:10.1371/journal.pmed.1001296
PMCID: PMC3429405  PMID: 22952436
7.  Domestic Violence and Perinatal Mental Disorders: A Systematic Review and Meta-Analysis 
PLoS Medicine  2013;10(5):e1001452.
Louise Howard and colleagues conduct a systematic review and meta-analysis to estimate the prevalence and odds of experience of domestic violence experience among women with antenatal and postnatal mental health disorders.
Please see later in the article for the Editors' Summary
Background
Domestic violence in the perinatal period is associated with adverse obstetric outcomes, but evidence is limited on its association with perinatal mental disorders. We aimed to estimate the prevalence and odds of having experienced domestic violence among women with antenatal and postnatal mental disorders (depression and anxiety disorders including post-traumatic stress disorder [PTSD], eating disorders, and psychoses).
Methods and Findings
We conducted a systematic review and meta-analysis (PROSPERO reference CRD42012002048). Data sources included searches of electronic databases (to 15 February 2013), hand searches, citation tracking, update of a review on victimisation and mental disorder, and expert recommendations. Included studies were peer-reviewed experimental or observational studies that reported on women aged 16 y or older, that assessed the prevalence and/or odds of having experienced domestic violence, and that assessed symptoms of perinatal mental disorder using a validated instrument. Two reviewers screened 1,125 full-text papers, extracted data, and independently appraised study quality. Odds ratios were pooled using meta-analysis.
Sixty-seven papers were included. Pooled estimates from longitudinal studies suggest a 3-fold increase in the odds of high levels of depressive symptoms in the postnatal period after having experienced partner violence during pregnancy (odds ratio 3.1, 95% CI 2.7–3.6). Increased odds of having experienced domestic violence among women with high levels of depressive, anxiety, and PTSD symptoms in the antenatal and postnatal periods were consistently reported in cross-sectional studies. No studies were identified on eating disorders or puerperal psychosis. Analyses were limited because of study heterogeneity and lack of data on baseline symptoms, preventing clear findings on causal directionality.
Conclusions
High levels of symptoms of perinatal depression, anxiety, and PTSD are significantly associated with having experienced domestic violence. High-quality evidence is now needed on how maternity and mental health services should address domestic violence and improve health outcomes for women and their infants in the perinatal period.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Domestic violence—physical, sexual, or emotional abuse by an intimate partner or family member—is a major public health problem and although more common in women, can also affect men. Due to the nature of the problem, it is difficult to collect accurate figures on the scale of domestic violence, but a study by the World Health Organization in ten countries found that 15%–71% of women aged 15–49 years reported physical and/or sexual violence by an intimate partner at some point in their lives. Women experiencing domestic violence have significant short- and long-term health problems, particularly regarding their mental health: experience of domestic violence can lead to a range of mental health disorders such as depression, psychosis, eating disorders, and even suicide attempts.
Why Was This Study Done?
As perinatal mental health disorders are among the commonest health problems in pregnancy and the postpartum period, and given the rate of domestic violence during pregnancy (previous studies have suggested a domestic violence prevalence of 4%–8% during pregnancy and the postnatal period), it is plausible that there may be a link between perinatal mental health disorders and having experienced domestic violence. Indeed, previous reviews have suggested the existence of such an association but were limited by the small number of included studies and focused on depression only, rather than the full range of antenatal and postnatal mental health disorders. So in this study the researchers systematically reviewed published studies to provide more robust estimates of the prevalence of having experienced domestic violence among women with antenatal and postnatal mental health disorders; the researchers also used a meta-analysis to estimate the odds (chance) of having experienced domestic violence among women with antenatal and postnatal mental health disorders.
What Did the Researchers Do and Find?
The researchers searched multiple databases and hand searched three relevant journals using key search terms to identify all types of relevant studies. Using specific criteria, the researchers retrieved and assessed over 1,000 full papers, of which 67 met the criteria for their systematic review. The researchers assessed the quality of each selected study and included only those studies that used validated diagnostic instruments and screening tools to assess mental health disorders in their calculations of the pooled (combined) odds ratio (OR) through meta-analysis.
Using these methods, in cross-sectional studies (studies conducted at one point in time), the researchers found that women with probable depression in the antenatal period reported a high prevalence and increased odds of having experienced partner violence during their lifetime (OR = 3), during the past year (OR = 2.8), and during pregnancy (OR = 5). The results were similar for the postnatal period. The evidence was less robust for anxiety disorders: among women with probable anxiety in the antenatal period, the researchers found an OR of 2.9 of having experienced lifetime partner violence. The odds were less in the postnatal period (OR = 1.4) In their analysis of longitudinal studies (follow-up studies over a period of time), the researchers found an increased odds of probable postnatal depression both among women who reported having ever experienced partner violence in their lifetime (OR = 2.9) and among women who reported having experienced partner violence during pregnancy (OR = 3.1). The researchers also found a combined prevalence estimate of 12.7% for probable depression during the postnatal period following experiences of partner violence during pregnancy. Because of limited data, the researchers could not calculate an OR of the association between probable antenatal depression and later experiences of partner violence.
What Do These Findings Mean?
These findings suggest that women with high levels of symptoms of perinatal mental health disorders—antenatal and postnatal anxiety, depression, and post-traumatic stress disorder—have a high prevalence and increased odds of having experienced domestic violence both over their lifetime and during pregnancy. However, these findings cannot prove causality, they fail to show a two-way association (that is, perinatal mental health disorders leading to subsequent domestic violence), and no information on other perinatal mental disorders, such as eating disorders and puerperal psychosis, was available. The variation of the quality of the included studies also limits the results, highlighting the need for high-quality data to suggest how maternity and mental health services could address domestic violence and improve health outcomes for women and their infants in the future. Nevertheless, this study emphasizes the importance of identifying and responding to possible domestic violence among women attending antenatal and mental health services.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001452.
The World Health Organization provides information and statistics about violence against women and also about mental health disorders during pregnancy
The UK Royal College of Psychiatrists has information for professionals and patients about mental health disorders during pregnancy
doi:10.1371/journal.pmed.1001452
PMCID: PMC3665851  PMID: 23723741
8.  Drivers of Inequality in Millennium Development Goal Progress: A Statistical Analysis 
PLoS Medicine  2010;7(3):e1000241.
David Stuckler and colleagues examine the impact of the HIV and noncommunicable disease epidemics on low-income countries' progress toward the Millennium Development Goals for health.
Background
Many low- and middle-income countries are not on track to reach the public health targets set out in the Millennium Development Goals (MDGs). We evaluated whether differential progress towards health MDGs was associated with economic development, public health funding (both overall and as percentage of available domestic funds), or health system infrastructure. We also examined the impact of joint epidemics of HIV/AIDS and noncommunicable diseases (NCDs), which may limit the ability of households to address child mortality and increase risks of infectious diseases.
Methods and Findings
We calculated each country's distance from its MDG goals for HIV/AIDS, tuberculosis, and infant and child mortality targets for the year 2005 using the United Nations MDG database for 227 countries from 1990 to the present. We studied the association of economic development (gross domestic product [GDP] per capita in purchasing-power-parity), the relative priority placed on health (health spending as a percentage of GDP), real health spending (health system expenditures in purchasing-power-parity), HIV/AIDS burden (prevalence rates among ages 15–49 y), and NCD burden (age-standardised chronic disease mortality rates), with measures of distance from attainment of health MDGs. To avoid spurious correlations that may exist simply because countries with high disease burdens would be expected to have low MDG progress, and to adjust for potential confounding arising from differences in countries' initial disease burdens, we analysed the variations in rates of change in MDG progress versus expected rates for each country. While economic development, health priority, health spending, and health infrastructure did not explain more than one-fifth of the differences in progress to health MDGs among countries, burdens of HIV and NCDs explained more than half of between-country inequalities in child mortality progress (R2-infant mortality  = 0.57, R2-under 5 mortality  = 0.54). HIV/AIDS and NCD burdens were also the strongest correlates of unequal progress towards tuberculosis goals (R2 = 0.57), with NCDs having an effect independent of HIV/AIDS, consistent with micro-level studies of the influence of tobacco and diabetes on tuberculosis risks. Even after correcting for health system variables, initial child mortality, and tuberculosis diseases, we found that lower burdens of HIV/AIDS and NCDs were associated with much greater progress towards attainment of child mortality and tuberculosis MDGs than were gains in GDP. An estimated 1% lower HIV prevalence or 10% lower mortality rate from NCDs would have a similar impact on progress towards the tuberculosis MDG as an 80% or greater rise in GDP, corresponding to at least a decade of economic growth in low-income countries.
Conclusions
Unequal progress in health MDGs in low-income countries appears significantly related to burdens of HIV and NCDs in a population, after correcting for potentially confounding socioeconomic, disease burden, political, and health system variables. The common separation between NCDs, child mortality, and infectious syndromes among development programs may obscure interrelationships of illness affecting those living in poor households—whether economic (e.g., as money spent on tobacco is lost from child health expenditures) or biological (e.g., as diabetes or HIV enhance the risk of tuberculosis).
Please see later in the article for the Editors' Summary
Editors' Summary
Background
In 2000, 189 countries adopted the United Nations (UN) Millennium Declaration, which commits the world to the eradication of extreme poverty by 2015. The Declaration lists eight Millennium Development Goals (MDGs), 21 quantifiable targets, and 60 indicators of progress. So, for example, MDG 4 aims to reduce child mortality (deaths). The target for this goal is to reduce the number of children who die each year before they are five years old (the under-five mortality rate) to two-thirds of its 1990 value by 2015. Indicators of progress toward this goal include the under-five mortality rate and the infant mortality rate. Because poverty and ill health are inextricably linked—ill health limits the ability of individuals and nations to improve their economic status, and poverty contributes to the development of many illnesses—two other MDGs also tackle public health issues. MDG 5 sets a target of reducing maternal mortality by three-quarters of its 1990 level by 2015. MDG 6 aims to halt and begin to reverse the spread of HIV/AIDS, malaria, and other major diseases such as tuberculosis by 2015.
Why Was This Study Done?
Although progress has been made toward achieving the MDGs, few if any of the targets are likely to be met by 2015. Worryingly, low-income countries are falling furthest behind their MDG targets. For example, although child mortality has been declining globally, in many poor countries there has been little or no progress. What is the explanation for this and other inequalities in progress toward the health MDGs? Some countries may simply lack the financial resources needed to combat epidemics or may allocate only a low proportion of their gross domestic product (GDP) to health. Alternatively, money allocated to health may not always reach the people who need it most because of an inadequate health infrastructure. Finally, coexisting epidemics may be hindering progress toward the MDG health targets. Thus, the spread of HIV/AIDS may be hindering attempts to limit the spread of tuberculosis because HIV infection increases the risk of active tuberculosis, and ongoing epidemics of diabetes and other noncommunicable diseases (NCDs) may be affecting the attainment of health MDGs by diverting scarce resources. In this study, the researchers investigate whether any of these possibilities is driving the inequalities in MDG progress.
What Did the Researchers Do and Find?
The researchers calculated how far 227 countries were from their MDG targets for HIV, tuberculosis, and infant and child mortality in 2005 using information collected by the UN. They then used statistical methods to study the relationship between this distance and economic development (GDP per person), health spending as a proportion of GDP (health priority), actual health system expenditures, health infrastructure, HIV burden, and NCD burden in each country. Economic development, health priority, health spending, and health infrastructure explained no more than one-fifth of the inequalities in progress toward health MDGs. By contrast, the HIV and NCD burdens explained more than half of inequalities in child mortality progress and were strongly associated with unequal progress toward tuberculosis goals. Furthermore, the researchers calculated that a 1% reduction in the number of people infected with HIV or a 10% reduction in rate of deaths from NCDs in a population would have a similar impact on progress toward the tuberculosis MDG target as a rise in GDP corresponding to at least a decade of growth in low-income countries.
What Do These Findings Mean?
These findings are limited by the quality of the available data on health indicators in low-income countries and, because the researchers used country-wide data, their findings only reveal possible drivers of inequalities in progress toward MDGs in whole countries and may mask drivers of within-country inequalities. Nevertheless, as one of the first attempts to analyze the determinants of global inequalities in progress toward the health MDGs, these findings have important implications for global health policy. Most importantly, the finding that unequal progress is related to the burdens of HIV and NCDs in populations suggests that programs designed to achieve health MDGs must consider all the diseases and factors that can trap households in vicious cycles of illness and poverty, especially since the achievement of feasible reductions in NCDs in low-income countries could greatly enhance progress towards health MDGs.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000241.
The United Nations Millennium Development Goals website provides detailed information about the Millennium Declaration, the MDGs, their targets and their indicators
The Millennium Development Goals Report 2009 and its progress chart provide an up-to-date assessment of progress towards the MDGs
The World Health Organization provides information about poverty and health and health and development
doi:10.1371/journal.pmed.1000241
PMCID: PMC2830449  PMID: 20209000
9.  Recent advances in oesophageal diseases 
Abstract
Dong Y, Qi B, Feng XY, Jiang CM. Meta-analysis of Barrett's esophagus in China. World J Gastroenterol 2013;19(46):8770-8779
The disease pattern of Barrett's esophagus (BE) in China is poorly characterised particularly in comparison with other developed countries. This meta-analysis of 3873 cases of BE collated from 69 clinical studies conducted in 25 provinces between 2000 and 2011 investigated the epidemiology and characteristics of BE in China compared to Western countries. The total endoscopic detection rate of BE was 1.0% (95%CI: 0.1%-1.8%) with an average patient age of 49.07 ± 5.09 years, lower than many Western countries.The authors postulate this may be attributed to environmental risk factor variation, distinct genetics and different medical practice including diagnostic criteria for BE and expertise in endoscopy. This study identified a 1.781 male predominancefor BE in China, consistent with Western reports. Short-segment BE accounted for 80.3% of cases with island type and cardiac type the most common endoscopic (44.8%) and histological (40.0%) manifestations respectively. Of the 1283 BE cases followed up for three to 36 months the incidence of esophageal cancer was 1.418 per 1000 person-years, lower than the incidence reported in Western countries.
Lee HS, Jeon SW. Barrett esophagus in Asia: same disease with different pattern. ClinEndosc 2014;47(1):15-22
Barrett's esophagus (BE) is a common, pre-cancerous condition characterised by intestinal metaplasia of squamous esophageal epithelium usually attributed to chronic gastric acid exposure. This review article explores important differences in the disease pattern of BE between Asian and the Western countries.
Overall the prevalence of BE is lower in Asia compared to the West with a greater proportion of short-segment type. The authors identify great variability in the endoscopic and pathologic diagnostic criteria for BE. Many of the studies in Asian countries did not use a standardised four-quadrant biopsy protocol which may have led to an underestimation of BE prevalence. The review highlights an increasing incidence of esophageal adenocarcinoma in the West but unclear disease trend in Asia with inter-country variability. Similarly in Asian and Western countries BE is associated with the presence of hiatus hernia, advancing age, male gender, alcohol consumption, smoking, abdominal obesity and longer duration of gastro-esophageal reflux disease. The authors postulate that Helicobacter pylori infection, more prevalent in Asia than the West, may have a protective effect on BE.
There is a need for larger, prospective studies to further clarify the disease pattern of BE in Asian countries. Clearly standardisation of the diagnostic process for BE is important to validate the differences in disease trends between Asian and Western countries.
Kiadaliri AA. Gender and social disparities in esophagus cancer incidence in Iran, 2003-2009: a time trend province-level study.Asian Pac J Cancer Prev 2014;15(2):623-7
Esophageal cancer (EC) is a major cause of morbidity and mortality particuarly in Iran where the incidence rate exceeds the global average. An understanding of the factors influencing the province-specific incidence of EC in Iran is important to inform disease-prevention strategies and address health inequalities. This ecological study used cancer registry data to investigate the relationship between gender and social class and the incidence of EC in Iran at province-level between 2003 and 2009. The age standardised incidence rates (ASIR) of EC were greatest in the Northern provinces of Iran, specifically Razavi Khorasan in males and Kordestan in females. Overall the EC incidence did not significantly differ according to gender.
Interestingly, during the study period the ASIR increased by 4.6% per year in females (p=0.08) and 6.5% per year in males (p=0.02). This may reflect increasing rates of establised risk factors for EC including obsesity and gastro-esophageal reflux disease alongside more vigilant recording of new cases. Social class was inversely associated with the ASIR of EC regardless of gender which may be attributed to class differences in risk factor distribution particularly smoking, diet and obesity. An appreciation for the limitations of an epidemiological study is important when interpreting results which should be further evaluated in future studies.
Islami F et al.Determinants of gastroesophageal reflux disease, including hookah smoking and opium use- A cross-sectional analysis of 50,000 individuals. PLoS One 2014;9(2):e89256
Gastroesophageal reflux disease (GERD) is a highly prevalent cause of gastrointestinal symptoms worldwide incurring great cost to the primary and secondary healthcare sectors. An improved understanding of the factors which influence GERD symptoms in low- to medium- income countries may inform public health initiatives. This study analysed prospective data from the Golestan cohort study, primarily established to investigate determinants of upper gastrointestinal cancers, toexplore the risk factors influencing GERD symptoms (regurgitation and/or heartburn) in 50,045 individuals aged 40-75 years in Golestan Province, Iran enrolled between 01/2004 and 06/2008.Of note, 39.12% of individuals denied ever experiencing GERD symptoms. A further 19.89% reported at least once weekly GERD symptoms with 11.83% experiencing daily symptoms. Severe symptoms, defined as disturbing daily work or sleep, were recorded by 11.33% of individuals.
Separately the occurrence of daily GERD symptoms and severe symptoms were inversely associated with male gender (OR 0.36, 95% CI 0.33-0.39 both), level of formal education (p=0.01 and p=0.001 respectively), wealth score (p<0.001 both) and regular nass chewing (OR 0.86, 95% CI 0.75-0.98 and OR 0.87, 95% CI 0.76-0.99 respectively)and were positively associated with body mass index (p<0.001 both), intensity of physical activity (p=0.04 both), cigarette pack years (p<0.001 both), alcohol consumption (OR 1.36, 95% CI 1.13-1.64 and OR 1.53, 95% CI 1.28-1.83 respectively) and opium use (OR 1.82, 95% CI 1.67-1.99 and OR 1.70, 95% CI 1.55-1.87 respectively).In addition hookah smoking had a borderline significant correlation with mild and moderate severity GERD symptoms in individuals who had never smoked cigarettes (OR 1.41, 95% CI 1.00-1.99 and OR 1.25, 95% CI 0.99-1.57 respectively).
Overall this large study contributes useful data to inform the prevention and management of GERD symptoms particularly regarding the use of hookah, opium and nass which was previously unclear.
Barbera M et al. The human squamous oesophagus has widespread capacity for clonal expansion from cells at diverse stages of differentiation. Gut 2014;0:1–9. doi:10.1136/gutjnl-2013-306171
Current knowledge on human esophageal tissue homeostasis and injury repair is derived predominantly from murine models and hence may be inaccurate due to cellular and architectural differences. This study used 3D imaging in conjunction withstaining for cell lineage markers to investigate the cellular mechanisms involved in homeostasis of the normal human squamous esophagus in 10 participants undergoing esophagectomy for esophageal cancer. The self-renewal potential of cell subpopulations was also assessed using in vitro and in vivo assays.
A decreasing gradient of cell proliferation was observed from the inter-papillary basal layer to the tip of the papilla where there was no evidence of mitosis. The expression ofβ1-integrin, a putative stem cell marker, was consistent throughout the basal layer and therefore the entire basal layer can be considered undifferentiated. Quiescent β1-integrin/CD34-positive cells which failed to stain for CD45, S-100 or F4-80were identified at the tip of the papilla suggesting this is an extension of the basal layer. Contrary to previous data, this study found progenitor cells widely distributed in human esophageal tissue and included already differentiated epithelial cells. This insight into esophageal homeostasis may inform future studies exploring the pathological mechanisms underpinning homeostatic disruption in disease states such as Barrett's esophagus.
Papers were prepared by:
Drs Ishfaq Ahmad and Luke Materacki, Department of Medicine, Alexandra Hospital, Redditch, UK
PMCID: PMC4129572  PMID: 25120902
10.  A Transdiagnostic Community-Based Mental Health Treatment for Comorbid Disorders: Development and Outcomes of a Randomized Controlled Trial among Burmese Refugees in Thailand 
PLoS Medicine  2014;11(11):e1001757.
In a randomized controlled trial, Paul Bolton and colleagues investigate whether a transdiagnostic community-based intervention is effective for improving mental health symptoms among Burmese refugees in Thailand.
Please see later in the article for the Editors' Summary
Background
Existing studies of mental health interventions in low-resource settings have employed highly structured interventions delivered by non-professionals that typically do not vary by client. Given high comorbidity among mental health problems and implementation challenges with scaling up multiple structured evidence-based treatments (EBTs), a transdiagnostic treatment could provide an additional option for approaching community-based treatment of mental health problems. Our objective was to test such an approach specifically designed for flexible treatments of varying and comorbid disorders among trauma survivors in a low-resource setting.
Methods and Findings
We conducted a single-blinded, wait-list randomized controlled trial of a newly developed transdiagnostic psychotherapy, Common Elements Treatment Approach (CETA), for low-resource settings, compared with wait-list control (WLC). CETA was delivered by lay workers to Burmese survivors of imprisonment, torture, and related traumas, with flexibility based on client presentation. Eligible participants reported trauma exposure and met severity criteria for depression and/or posttraumatic stress (PTS). Participants were randomly assigned to CETA (n = 182) or WLC (n = 165). Outcomes were assessed by interviewers blinded to participant allocation using locally adapted standard measures of depression and PTS (primary outcomes) and functional impairment, anxiety symptoms, aggression, and alcohol use (secondary outcomes). Primary analysis was intent-to-treat (n = 347), including 73 participants lost to follow-up. CETA participants experienced significantly greater reductions of baseline symptoms across all outcomes with the exception of alcohol use (alcohol use analysis was confined to problem drinkers). The difference in mean change from pre-intervention to post-intervention between intervention and control groups was −0.49 (95% CI: −0.59, −0.40) for depression, −0.43 (95% CI: −0.51, −0.35) for PTS, −0.42 (95% CI: −0.58, −0.27) for functional impairment, −0.48 (95% CI: −0.61, −0.34) for anxiety, −0.24 (95% CI: −0.34, −0.15) for aggression, and −0.03 (95% CI: −0.44, 0.50) for alcohol use. This corresponds to a 77% reduction in mean baseline depression score among CETA participants compared to a 40% reduction among controls, with respective values for the other outcomes of 76% and 41% for anxiety, 75% and 37% for PTS, 67% and 22% for functional impairment, and 71% and 32% for aggression. Effect sizes (Cohen's d) were large for depression (d = 1.16) and PTS (d = 1.19); moderate for impaired function (d = 0.63), anxiety (d = 0.79), and aggression (d = 0.58); and none for alcohol use. There were no adverse events. Limitations of the study include the lack of long-term follow-up, non-blinding of service providers and participants, and no placebo or active comparison intervention.
Conclusions
CETA provided by lay counselors was highly effective across disorders among trauma survivors compared to WLCs. These results support the further development and testing of transdiagnostic approaches as possible treatment options alongside existing EBTs.
Trial registration
ClinicalTrials.gov NCT01459068
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, one in four people will experience a mental health disorder at some time during their life. Although many evidence-based treatments (EBTs), most involving some sort of cognitive behavioral therapy (talking therapies that help people manage their mental health problems by changing the way they think and behave), are now available, many people with mental health disorders never receive any treatment for their condition. The situation is particularly bad for people living in low-resource settings, where a delivery model for EBTs based on referral to mental health professionals is problematic given that mental health professionals are scarce. To facilitate widespread access to mental health care among poor and/or rural populations in low-resource settings, EBTs need to be deliverable at the primary or community level by non-professionals. Moreover, because there is a large burden of trauma-related mental health disorders in low-resource settings and because trauma increases the risk of multiple mental health problems, treatment options that address comorbid (coexisting) mental health problems in low-resource settings are badly needed.
Why Was This Study Done?
One possible solution to the problem of delivering EBTs for comorbid mental health disorders in low-resource settings is “transdiagnostic” treatment. Many mental health EBTs for different disorders share common components. Transdiagnostic treatments recognize these facts and apply these common components to a range of disorders rather than creating a different structured treatment for each diagnosis. The Common Elements Treatment Approach (CETA), for example, trains counselors in a range of components that are similar across EBTs and teaches counselors how to choose components, their order, and dose, based on their client's problems. This flexible approach, which was designed for delivery by non-professional providers in low-resource settings, provides counselors with the skills needed to treat depression, anxiety, and posttraumatic stress—three trauma-related mental health disorders. In this randomized controlled trial, the researchers investigate the use of CETA among Burmese refugees living in Thailand, many of whom are survivors of decades-long harsh military rule in Myanmar. A randomized controlled trial compares the outcomes of individuals chosen to receive different interventions through the play of chance.
What Did the Researchers Do and Find?
The researchers assigned Burmese survivors or witnesses of imprisonment, torture, and related traumas who met symptom criteria for significant depression and/or posttraumatic stress to either the CETA or wait-list control arm of their trial. Lay counselors treated the participants in the CETA arm by delivering CETA components—for example, “psychoeducation” (which teaches clients that their symptoms are normal and experienced by many people) and “cognitive coping” (which helps clients understand that how they think about an event can impact their feelings and behavior)—chosen to reflect the client's priority problems at presentation. Participants in the control arm received regular calls from the trial coordinator to check on their safety but no other intervention. Participants in the CETA arm experienced greater reductions of baseline symptoms of depression, posttraumatic stress, anxiety, and aggression than participants in the control arm. For example, there was a 77% reduction in the average depression score from before the intervention to after the intervention among participants in the CETA arm, but only a 40% reduction in the depression score among participants in the control arm. Importantly, the effect size of CETA (a statistical measure that quantifies the importance of the difference between two groups) was large for depression and posttraumatic stress, the primary outcomes of the trial. That is, compared to no treatment, CETA had a large effect on the symptoms of depression and posttraumatic stress experienced by the trial participants.
What Do These Findings Mean?
These findings suggest that, among Burmese survivors and witnesses of torture and other trauma living in Thailand, CETA delivered by lay counselors was a highly effective treatment for comorbid mental disorders compared to no treatment (the wait-list control). These findings may not be generalizable to other low-resource settings, they provide no information about long-term outcomes, and they do not identify which aspects of CETA were responsible for symptom improvement or explain the improvements seen among the control participants. Given that the study compared CETA to no treatment rather than a placebo (dummy) or active comparison intervention, it is not possible to conclude that CETA works better that existing treatments. Nevertheless, these findings support the continued development and assessment of transdiagnostic approaches for the treatment of mental health disorders in low-resource settings where treatment access and comorbid mental health disorders are important challenges.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001757.
The World Health Organization provides background information about mental health
The US National Institute of Mental Health provides information about a range of mental health disorders and about cognitive behavioral therapy
The UK National Health Service Choices website has information about cognitive behavioral therapy, including some personal stories and links to other related mental health resources on the Choices website
A short introduction to transdiagnosis and CETA written by one of the trial authors is available
Information about this trial is available on the ClinicalTrials.gov website
The UN Refugee Agency provides information about Burmese (Myanmar) refugees in Thailand
doi:10.1371/journal.pmed.1001757
PMCID: PMC4227644  PMID: 25386945
11.  Enhanced External Counterpulsation (EECP) 
Executive Summary
Objective
To assess the effectiveness, and cost effectiveness of EECP in patients with severe anginal symptoms, secondary to chronic coronary disease, who are unresponsive to exhaustive pharmacotherapy and not candidates for surgical/percutaneous revascularization procedures (e.g., angioplasty, coronary bypass surgery).
To assess the effectiveness, and cost effectiveness of EECP in patients with heart failure.
Clinical Need
Angina
Angina is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back or arm. Angina usually occurs in patients with coronary artery disease (CAD) involving ≥1 large epicardial artery. However it can also occur in people with valvular heart disease, hypertrophic cardiomyopathy, and uncontrolled hypertension.
Conventional approaches to restoring the balance between oxygen supply and demand focus on the disruption of the underlying disease through: drug therapy (β blockers, calcium channel blockers, nitrates, antiplatelet agents, ACE inhibitors, statins); life-style modifications (smoking cessation, weight loss); or revascularization techniques such as coronary artery bypass graft surgery (CABG) or percutaneous coronary interventions (PCI). (1) Limitations of each of these approaches include: adverse drug effects, procedure-related mortality and morbidity, restenosis after PCI, and time dependent graft attrition after CABG. Furthermore, an increasing number of patients are not appropriate candidates for standard revascularization options, due to co-morbid conditions (HF, peripheral vascular disease), poor distal coronary artery targets, and patient preference. The morbidity and mortality associated with repeat surgical revascularization procedures are significantly higher, and often excludes these patients from consideration for further revascularizations. (2)
Patients with CAD who have chronic ischemic symptoms that are unresponsive to both conventional medical therapy and revascularization techniques have refractory angina pectoris. It has been estimated that greater than 100,000 patients each year in the US may be diagnosed as having this condition. (3) Patients with refractory angina have marked limitation of ordinary physical activity or are unable to perform any ordinary physical activity without discomfort (CCS functional class III/IV). Also, there must be some objective evidence of ischemia as demonstrated by exercise treadmill testing, stress imaging studies or coronary physiologic studies. (1)
Dejongste et al. (4)estimated that the prevalence of chronic refractory angina is about 100,000 patients in the United States. This would correspond to approximately 3,800 (100,000 x 3.8% [Ontario is approximately 3.8% of the population of the United States]) patients in Ontario having chronic refractory angina.
Heart Failure
Heart failure results from any structural or functional cardiac disorder that impairs the ability of the heart to act as a pump.
A recent study (5) revealed 28,702 patients were hospitalized for first-time HF in Ontario between April 1994 and March 1997. Women comprised 51% of the cohort. Eighty-five percent were aged 65 years or older, and 58% were aged 75 years or older.
Patients with chronic HF experience shortness of breath, a limited capacity for exercise, high rates of hospitalization and rehospitalization, and die prematurely. (6) The New York Heart Association (NYHA) has provided a commonly used functional classification for the severity of HF (7):
Class I: No limitation of physical activity. No symptoms with ordinary exertion.
Class II: Slight limitations of physical activity. Ordinary activity causes symptoms.
Class III: Marked limitation of physical activity. Less than ordinary activity causes symptoms. Asymptomatic at rest.
Class IV: Inability to carry out any physical activity without discomfort. Symptoms at rest.
The National Heart, Lung, and Blood Institute (7) estimates that 35% of patients with HF are in functional NYHA class I; 35% are in class II; 25%, class III; and 5%, class IV. Surveys (8) suggest that from 5% to 15% of patients with HF have persistent severe symptoms, and that the remainder of patients with HF is evenly divided between those with mild and moderately severe symptoms.
To date, the diagnosis and management of chronic HF has concentrated on patients with the clinical syndrome of HF accompanied by severe left ventricular systolic dysfunction. Major changes in treatment have resulted from a better understanding of the pathophysiology of HF and the results of large clinical trials. Treatment for chronic HF includes lifestyle management, drugs, cardiac surgery, or implantable pacemakers and defibrillators. Despite pharmacologic advances, which include diuretics, angiotensin-converting enzyme inhibitors, beta-blockers, spironolactone, and digoxin, many patients remain symptomatic on maximally tolerated doses. (6)
The Technology
Patients are typically treated by a trained technician in a medically supervised environment for 1 hour daily for a total of 35 hours over 7 weeks. The procedure involves sequential inflation and deflation of compressible cuffs wrapped around the patient’s calves, lower thighs and upper thighs. In addition to 3 sets of cuffs, the patient has finger plethysmogram and electrocardiogram (ECG) attachments that are connected to a control and display console.
External counterpulsation was used in the United States to treat cardiogenic shock after acute myocardial infarction. (9;10) More recently, an enhanced version namely “enhanced external counterpulsation” (EECP) was introduced as a noninvasive procedure for outpatient treatment of patients with severe, uncontrollable cardiac ischemia. EECP is said to increase coronary perfusion pressure and reduce the myocardial oxygen demand. Currently, EECP is not applicable for all patients with refractory angina pectoris. For example, many patients are considered ineligible for therapy due to co-morbidities, including those with severe pulmonary vascular disease, deep vein thrombosis, phlebitis and irregular heart rhythms, and heart failure. (1)
Very recently, investigation began into EECP as an adjunctive treatment for patients with HF. Anecdotal reports suggested that EECP may benefit patients with coronary disease and left ventricular dysfunction. The safety and effectiveness of EECP in patients with symptomatic heart failure and coronary disease and its role in patients with nonischemic heart failure secondary to LV dysfunction is unclear. Furthermore, the safety and effectiveness of EECP in the different stages of HF and whether it is only for patients who are refractive to pharmacotherapy is unknown.
2003 Health Technology Assessment by the Medical Advisory Secretariat
The Medical Advisory Secretariat health technology assessment (originally published in February 2003) reported on the effectiveness of EECP for patients with angina and HF. The report concluded that there was insufficient evidence to support the use of EECP in patients with refractory stable CCS III/IV angina as well as insufficient evidence to support the use of EECP in patients with HF.
Review Strategy
The aim of this literature review was to assess the effectiveness, safety, and cost effectiveness of EECP for the treatment of refractory stable CCS III/IV angina or HF.
The standard search strategy used by the Medical Advisory Secretariat was used. This included a search of all international health technology assessments as well as a search of the medical literature from December 2002 to March 2006.
A modification of the GRADE approach (11) was used to make judgments about the quality of evidence and strength of recommendations systematically and explicitly. GRADE provides a framework for structured reflection and can help to ensure that appropriate judgments are made. GRADE takes into account a study’s design, quality, consistency, and directness in judging the quality of evidence for each outcome. The balance between benefits and harms, quality of evidence, applicability, and the certainty of the baseline risks are considered in judgments about the strength of recommendations.
Summary of Findings
The Cochrane and INAHTA databases yielded 3 HTAs or systematic reviews on EECP treatment (Blue Cross Blue Shield Technology Evaluation Center [BCBS TEC], ECRI, and the Centers for Medicare and Medicaid Services [CMS]). A search of Medline and Embase December 2005 – March 2006 (after the literature search cutoff from the most recent HTA) was conducted using key words enhanced external counterpulsation, EECP, angina, myocardial ischemia, congestive heart failure. This search produced 1 study which met the inclusion criteria. This level 4a study was inferior in quality to the RCT which formed the basis of the 2003 Medical Advisory Secretariat recommendation.
BCBS reviewed the evidence through November 2005 to determine if EECP improves health outcomes for refractory chronic stable angina pectoris or chronic stable HF. (12) BCBS concluded that the available evidence is not sufficient to permit conclusions of the effect of EECP on health outcomes. Both controlled trials had methodologic flaws (MUST EECP and MUST EECP quality of life studies). The case series and observational studies for both indications while suggestive of a treatment benefit from EECP have shortcomings as well.
On March 20 2006, CMS posted their proposed coverage decision memorandum for external counterpulsation therapy. (13) Overall, CMS stated that the evidence is not adequate to conclude that external counterpulsation therapy is reasonable and necessary for:
Canadian Cardiovascular Society Classification (CCSC) II angina
Heart failure
NYHA class II/III stable HF symptoms with an EF≤35%
NYHA class II/III stable HF symptoms with an EF≤40%
NYHA class IV HF
Acute HF
Cardiogenic shock
Acute MI
In January 2005, ECRI (14) stated that there was insufficient evidence available to draw conclusions about the long-term effectiveness of EECP, with respect to morbidity, survival, or quality of life, for any coronary indication (refractory angina, congestive heart failure, cardiogenic shock and acute MI).
GRADE Quality of the Studies
According to the GRADE Working Group criteria, the quality of the trials was examined (Table 1). (11)
Quality refers to the criteria such as the adequacy of allocation concealment, blinding and followup.
Consistency refers to the similarity of estimates of effect across studies. If there is important unexplained inconsistency in the results, our confidence in the estimate of effect for that outcome decreases. Differences in the direction of effect, the size of the differences in effect and the significance of the differences guide the decision about whether important inconsistency exists.
Directness refers to the extent to which the people interventions and outcome measures are similar to those of interest. For example, there may be uncertainty about the directness of the evidence if the people of interest are older, sicker or have more comorbidity than those in the studies.
As stated by the GRADE Working Group, the following definitions were used in grading the quality of the evidence. (11)
GRADE Quality of Studies
Economic Analysis - Literature Review
No economic analysis of EECP was identified in the published literature.
Estimated Prevalence of Angina in Ontario
3,800 patients with chronic refractory angina:
The number of patients with chronic refractory angina in the US is estimated to be approximately 100,000 (4), this corresponds to about 3,800 patients in Ontario (3.8% × 100,000) with refractory angina.
3,800 patients × $7,000 Cdn (approximate cost for a full course of therapy) ~ $26.6M Cdn.
Estimated Prevalence of Heart Failure in Ontario
23,700 patients EF ≤ 0.35:
This estimate is from an expert (personal communication) at the Institute for Clinical Evaluative Sciences (ICES), where they examined a sample of echocardiography studies drawn from a diagnostic lab in 2001. They found that the prevalence of EF ≤ 0.35 was 8.3%, and if generalized to all patients undergoing echocardiography, there would be 23,700 patients.
23,700 patients with EF ≤35% × $7,000 Cdn ~ $166 M Cdn.
Conclusions
There is insufficient evidence to support the effectiveness and safety of EECP treatment for patients with refractory stable CCS III-IV angina or HF.
As per the GRADE Working Group, overall recommendations consider 4 main factors. (11)
The tradeoffs, taking into account the estimated size of the effect for the main outcome, the confidence limits around those estimates and the relative value placed on the outcome.
The quality of the evidence.
Translation of the evidence into practice in a specific setting, taking into consideration important factors that could be expected to modify the size of the expected effects such as proximity to a hospital or availability of necessary expertise.
Uncertainty about the baseline risk for the population of interest.
The GRADE Working Group also recommends that incremental costs of healthcare alternatives should be considered explicitly alongside the expected health benefits and harms. (11) Recommendations rely on judgments about the value of the incremental health benefits in relation to the incremental costs. The last column in Table 2 is the overall trade-off between benefits and harms and incorporates any risk/uncertainty.
For angina and heart failure, the overall GRADE and strength of the recommendations is “weak” – the quality of the evidence is “low” (uncertainties due to methodological limitations in the study design in terms of study quality and directness), and the corresponding risk/uncertainty is increased due to a budget impact of approximately $26.6 M Cdn or $166 M Cdn respectively while the cost-effectiveness of EECP is unknown and difficult to estimate considering that there are no high quality studies of effectiveness.
Overall GRADE and Strength of Recommendation (Including Uncertainty)
PMCID: PMC3379533  PMID: 23074496
12.  Health Seeking Behaviour and Utilization of Health Facilities for Schistosomiasis-Related Symptoms in Ghana 
Background
Schistosomiasis causes long-term illness and significant economic burden. Morbidity control through integration within existing health care delivery systems is considered a potentially sustainable and cost-effective approach, but there is paucity of information about health-seeking behaviour.
Methods
A questionnaire-based study involving 2,002 subjects was conducted in three regions of Ghana to investigate health-seeking behaviour and utilization of health facilities for symptoms related to urinary (blood in urine and painful urination) and intestinal schistosomiasis (diarrhea, blood in stool, swollen abdomen and abdominal pain). Fever (for malaria) was included for comparison.
Results
Only 40% of patients with urinary symptoms sought care compared to >70% with intestinal symptoms and >90% with fever. Overall, about 20% of schistosomiasis-related symptoms were reported to a health facility (hospital or clinic), compared to about 30% for fever. Allopathic self-medication was commonly practiced as alternative action. Health-care seeking was relatively lower for patients with chronic symptoms, but if they took action, they were more likely to visit a health facility. In a multivariate logistic regression analysis, perceived severity was the main predictor for seeking health care or visiting a health facility. Age, socio-economic status, somebody else paying for health care, and time for hospital visit occasionally showed a significant impact, but no clear trend. The effect of geographic location was less marked, although people in the central region, and to a lesser extent the north, were usually less inclined to seek health care than people in the south. Perceived quality of health facility did not demonstrate impact.
Conclusion
Perceived severity of the disease is the most important determinant of seeking health care or visiting a health facility in Ghana. Schistosomiasis control by passive case-finding within the regular health care delivery looks promising, but the number not visiting a health facility is large and calls for supplementary control options.
Author Summary
The World Health Organization recommends that long-term benefit of schistosomiasis control should include treatment in local health facilities. This means that patients should visit a hospital or clinic with their complaints. However, little is known about whether they do so. We conducted a study in three regions of Ghana and interviewed two thousand people about whether they recently had schistosomiasis-related symptoms such as blood in urine or blood in faeces, and what they had done about it. We included fever (mostly caused by malaria) for comparison. We found that 40% of patients with urinary symptoms sought care compared to 70% of those with intestinal symptoms and 90% with fever. Overall, only 20% of all schistosomiasis-related symptoms were reported to a hospital or clinic, compared to 30% for fever. Self-medication with allopathic (i.e., orthodox) medicines was the main alternative. Our study showed that the most important determinant for seeking health care or visiting a health facility is perceived severity of the symptom. Factors such as age, sex, socio-economic status and geographic region showed no impact or a clear pattern. We conclude that many schistosomiasis patients do not visit a health facility, the only place with effective drugs, necessitating additional control measures.
doi:10.1371/journal.pntd.0000867
PMCID: PMC2970540  PMID: 21072229
13.  Sleep-Disordered Breathing and Mortality: A Prospective Cohort Study 
PLoS Medicine  2009;6(8):e1000132.
In a cohort of 6,441 volunteers followed over an average of 8.2 years, Naresh Punjabi and colleagues find sleep-disordered breathing to be independently associated with mortality and identify predictive characteristics.
Background
Sleep-disordered breathing is a common condition associated with adverse health outcomes including hypertension and cardiovascular disease. The overall objective of this study was to determine whether sleep-disordered breathing and its sequelae of intermittent hypoxemia and recurrent arousals are associated with mortality in a community sample of adults aged 40 years or older.
Methods and Findings
We prospectively examined whether sleep-disordered breathing was associated with an increased risk of death from any cause in 6,441 men and women participating in the Sleep Heart Health Study. Sleep-disordered breathing was assessed with the apnea–hypopnea index (AHI) based on an in-home polysomnogram. Survival analysis and proportional hazards regression models were used to calculate hazard ratios for mortality after adjusting for age, sex, race, smoking status, body mass index, and prevalent medical conditions. The average follow-up period for the cohort was 8.2 y during which 1,047 participants (587 men and 460 women) died. Compared to those without sleep-disordered breathing (AHI: <5 events/h), the fully adjusted hazard ratios for all-cause mortality in those with mild (AHI: 5.0–14.9 events/h), moderate (AHI: 15.0–29.9 events/h), and severe (AHI: ≥30.0 events/h) sleep-disordered breathing were 0.93 (95% CI: 0.80–1.08), 1.17 (95% CI: 0.97–1.42), and 1.46 (95% CI: 1.14–1.86), respectively. Stratified analyses by sex and age showed that the increased risk of death associated with severe sleep-disordered breathing was statistically significant in men aged 40–70 y (hazard ratio: 2.09; 95% CI: 1.31–3.33). Measures of sleep-related intermittent hypoxemia, but not sleep fragmentation, were independently associated with all-cause mortality. Coronary artery disease–related mortality associated with sleep-disordered breathing showed a pattern of association similar to all-cause mortality.
Conclusions
Sleep-disordered breathing is associated with all-cause mortality and specifically that due to coronary artery disease, particularly in men aged 40–70 y with severe sleep-disordered breathing.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 1 in 10 women and 1 in 4 men have a chronic condition called sleep-disordered breathing although most are unaware of their problem. Sleep-disordered breathing, which is commonest in middle-aged and elderly people, is characterized by numerous, brief (10 second or so) interruptions of breathing during sleep. These interruptions, which usually occur when relaxation of the upper airway muscles decreases airflow, lower the level of oxygen in the blood and, as a result, affected individuals are frequently aroused from deep sleep as they struggle to breathe. Symptoms of sleep-disordered breathing include loud snoring and daytime sleepiness. Treatments include lifestyle changes such as losing weight (excess fat around the neck increases airway collapse) and smoking cessation. Affected people can also use special devices to prevent them sleeping on their backs, but for severe sleep-disordered breathing, doctors often recommend continuous positive airway pressure (CPAP), a machine that pressurizes the upper airway through a face mask to keep it open.
Why Was This Study Done?
Sleep-disordered breathing is a serious condition. It is associated with several adverse health conditions including coronary artery disease (narrowing of the blood vessels that supply the heart, a condition that can cause a heart attack) and daytime sleepiness that can affect an individual's driving ability. In addition, several clinic- and community-based studies suggest that sleep-disordered sleeping may increase a person's risk of dying. However, because these studies have been small and have often failed to allow for other conditions and characteristics that affect an individual's risk of dying (“confounding factors”), they provide inconsistent or incomplete information about the potential association between sleep-disordered breathing and the risk of death. In this prospective cohort study (part of the Sleep Heart Health Study, which is researching the effects of sleep-disordered breathing on cardiovascular health), the researchers examine whether sleep-disordered breathing is associated with all-cause mortality (death from any cause) in a large community sample of adults. A prospective cohort study is one in which a group of participants is enrolled and then followed forward in time (in this case for several years) to see what happens to them.
What Did the Researchers Do and Find?
At enrollment, the study participants—more than 6,000 people aged 40 years or older, none of whom were being treated for sleep-disordered breathing—had a health examination. Their night-time breathing, sleep patterns, and blood oxygen levels were also assessed and these data used to calculate each participant's apnea-hypopnea index (AHI)—the number of apneas and hypopneas per hour. During the study follow-up period, 1,047 participants died. Compared to participants without sleep-disordered sleeping, participants with severe sleep-disordered breathing (an AHI of ≥30) were about one and a half times as likely to die from any cause after adjustment for potential confounding factors. People with milder sleep-disordered breathing did not have a statistically significant increased risk of dying. After dividing the participants into subgroups according to their age and sex, men aged 40–70 years with severe sleep-disordered breathing had a statistically increased risk of dying from any cause (twice the risk of men of a similar age without sleep-disordered breathing). Finally, death from coronary artery disease was also associated with sleep-disordered breathing in men but not in women.
What Do These Findings Mean?
These findings indicate that sleep-disordered breathing is associated with an increased risk of all-cause mortality, particularly in men aged 40–70 years, even after allowing for known confounding factors. They also suggest that the increased risk of death is specifically associated with coronary artery disease although further studies are needed to confirm this finding because it was based on the analysis of a small subgroup of study participants. Although this study is much larger than previous investigations into the association between sleep-disordered breathing and all-cause mortality, it has several limitations including its reliance on a single night's measurements for the diagnosis of sleep-disordered breathing. Nevertheless, these findings suggest that clinical trials should now be started to assess whether treatment can reduce the increased risk of death that seems to be associated with this common disorder.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000132.
The US National Heart Lung and Blood Institute has information (including a video) about sleep-disordered breathing (sleep apnea) (in English and Spanish)
The UK National Heath Service also provides information for patients about sleep apnea
MedlinePlus provides links to further information and advice about sleep-disordered breathing (in English and Spanish)
More information on the Sleep Heart Health Study is available
doi:10.1371/journal.pmed.1000132
PMCID: PMC2722083  PMID: 19688045
14.  Reproductive health and access to healthcare facilities: risk factors for depression and anxiety in women with an earthquake experience 
BMC Public Health  2011;11:523.
Background
The reproductive and mental health of women contributes significantly to their overall well-being. Three of the eight Millennium Development Goals are directly related to reproductive and sexual health while mental disorders make up three of the ten leading causes of disease burden in low and middle-income countries. Among mental disorders, depression and anxiety are two of the most prevalent. In the context of slower progress in achieving Millennium Development Goals in developing countries and the ever-increasing man-made and natural disasters in these areas, it is important to understand the association between reproductive health and mental health among women with post-disaster experiences.
Methods
This was a cross-sectional study with a sample of 387 women of reproductive age (15-49 years) randomly selected from the October 2005 earthquake affected areas of Pakistan. Data on reproductive health was collected using the Centers for Disease Control reproductive health assessment toolkit. Depression and anxiety were measured using the Hopkins Symptom Checklist-25, while earthquake experiences were captured using the Harvard Trauma Questionnaire. The association of either depression or anxiety with socio-demographic variables, earthquake experiences, reproductive health and access to health facilities was estimated using multivariate logistic regression.
Results
Post-earthquake reproductive health events together with economic deprivation, lower family support and poorer access to health care facilities explained a significant proportion of differences in the experiencing of clinical levels of depression and anxiety. For instance, women losing resources for subsistence, separation from family and experiencing reproductive health events such as having a stillbirth, having had an abortion, having had abnormal vaginal discharge or having had genital ulcers, were at significant risk of depression and anxiety.
Conclusion
The relationship between women's post-earthquake mental health and reproductive health, socio-economic status, and health care access is complex and explained largely by the socio-cultural role of women. It is suggested that interventions that consider gender differences and that are culturally appropriate are likely to reduce the incidence.
doi:10.1186/1471-2458-11-523
PMCID: PMC3146866  PMID: 21718519
Reproductive Health; Mental Health; Disaster; Depression; Anxiety; Earthquake; Access to Health Facilities; Pakistan
15.  Correlates of depressive symptoms among Latino and Non-Latino White adolescents: Findings from the 2003 California Health Interview Survey 
BMC Public Health  2007;7:21.
Background
The prevalence of depression is increasing not only among adults, but also among adolescents. Several risk factors for depression in youth have been identified, including female gender, increasing age, lower socio-economic status, and Latino ethnic background. The literature is divided regarding the role of acculturation as risk factor among Latino youth. We analyzed the correlates of depressive symptoms among Latino and Non-Latino White adolescents residing in California with a special focus on acculturation.
Methods
We performed an analysis of the adolescent sample of the 2003 California Health Interview Survey, which included 3,196 telephone-interviews with Latino and Non-Latino White adolescents between the ages of 12 and 17. Depressive symptomatology was measured with a reduced version of the Center for Epidemiologic Studies Depression Scale. Acculturation was measured by a score based on language in which the interview was conducted, language(s) spoken at home, place of birth, number of years lived in the United States, and citizenship status of the adolescent and both of his/her parents, using canonical principal component analysis. Other variables used in the analysis were: support provided by adults at school and at home, age of the adolescent, gender, socio-economic status, and household type (two parent or one parent household).
Results
Unadjusted analysis suggested that the risk of depressive symptoms was twice as high among Latinos as compared to Non-Latino Whites (10.5% versus 5.5 %, p < 0.001). The risk was slightly higher in the low acculturation group than in the high acculturation group (13.1% versus 9.7%, p = 0.12). Similarly, low acculturation was associated with an increased risk of depressive symptoms in multivariate analysis within the Latino subsample (OR 1.54, CI 0.97–2.44, p = 0.07). Latino ethnicity emerged as risk factor for depressive symptoms among the strata with higher income and high support at home and at school. In the disadvantaged subgroups (higher poverty, low support at home and at school) Non-Latino Whites and Latinos had a similar risk of depressive symptoms.
Conclusion
Our findings suggest that the differences in depressive symptoms between Non-Latino Whites and Latino adolescents disappear at least in some strata after adjusting for socio-demographic and social support variables.
doi:10.1186/1471-2458-7-21
PMCID: PMC1805430  PMID: 17313675
16.  Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD) 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html.
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty member_giacomini.htm.
For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx.
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact.
Objective
The objective of this evidence-based analysis was to determine the effectiveness and cost-effectiveness of smoking cessation interventions in the management of chronic obstructive pulmonary disease (COPD).
Clinical Need: Condition and Target Population
Tobacco smoking is the main risk factor for COPD. It is estimated that 50% of older smokers develop COPD and more than 80% of COPD-associated morbidity is attributed to tobacco smoking. According to the Canadian Community Health Survey, 38.5% of Ontarians who smoke have COPD. In patients with a significant history of smoking, COPD is usually present with symptoms of progressive dyspnea (shortness of breath), cough, and sputum production. Patients with COPD who smoke have a particularly high level of nicotine dependence, and about 30.4% to 43% of patients with moderate to severe COPD continue to smoke. Despite the severe symptoms that COPD patients suffer, the majority of patients with COPD are unable to quit smoking on their own; each year only about 1% of smokers succeed in quitting on their own initiative.
Technology
Smoking cessation is the process of discontinuing the practice of inhaling a smoked substance. Smoking cessation can help to slow or halt the progression of COPD. Smoking cessation programs mainly target tobacco smoking, but may also encompass other substances that can be difficult to stop smoking due to the development of strong physical addictions or psychological dependencies resulting from their habitual use.
Smoking cessation strategies include both pharmacological and nonpharmacological (behavioural or psychosocial) approaches. The basic components of smoking cessation interventions include simple advice, written self-help materials, individual and group behavioural support, telephone quit lines, nicotine replacement therapy (NRT), and antidepressants. As nicotine addiction is a chronic, relapsing condition that usually requires several attempts to overcome, cessation support is often tailored to individual needs, while recognizing that in general, the more intensive the support, the greater the chance of success. Success at quitting smoking decreases in relation to:
a lack of motivation to quit,
a history of smoking more than a pack of cigarettes a day for more than 10 years,
a lack of social support, such as from family and friends, and
the presence of mental health disorders (such as depression).
Research Question
What are the effectiveness and cost-effectiveness of smoking cessation interventions compared with usual care for patients with COPD?
Research Methods
Literature Search
Search Strategy
A literature search was performed on June 24, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations (1950 to June Week 3 2010), EMBASE (1980 to 2010 Week 24), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Library, and the Centre for Reviews and Dissemination for studies published between 1950 and June 2010. A single reviewer reviewed the abstracts and obtained full-text articles for those studies meeting the eligibility criteria. Reference lists were also examined for any additional relevant studies not identified through the search. Data were extracted using a standardized data abstraction form.
Inclusion Criteria
English-language, full reports from 1950 to week 3 of June, 2010;
either randomized controlled trials (RCTs), systematic reviews and meta-analyses, or non-RCTs with controls;
a proven diagnosis of COPD;
adult patients (≥ 18 years);
a smoking cessation intervention that comprised at least one of the treatment arms;
≥ 6 months’ abstinence as an outcome; and
patients followed for ≥ 6 months.
Exclusion Criteria
case reports
case series
Outcomes of Interest
≥ 6 months’ abstinence
Quality of Evidence
The quality of each included study was assessed taking into consideration allocation concealment, randomization, blinding, power/sample size, withdrawals/dropouts, and intention-to-treat analyses.
The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence:
Summary of Findings
Nine RCTs were identified from the literature search. The sample sizes ranged from 74 to 5,887 participants. A total of 8,291 participants were included in the nine studies. The mean age of the patients in the studies ranged from 54 to 64 years. The majority of studies used the Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD staging criteria to stage the disease in study subjects. Studies included patients with mild COPD (2 studies), mild-moderate COPD (3 studies), moderate–severe COPD (1 study) and severe–very severe COPD (1 study). One study included persons at risk of COPD in addition to those with mild, moderate, or severe COPD, and 1 study did not define the stages of COPD. The individual quality of the studies was high. Smoking cessation interventions varied across studies and included counselling or pharmacotherapy or a combination of both. Two studies were delivered in a hospital setting, whereas the remaining 7 studies were delivered in an outpatient setting. All studies reported a usual care group or a placebo-controlled group (for the drug-only trials). The follow-up periods ranged from 6 months to 5 years. Due to excessive clinical heterogeneity in the interventions, studies were first grouped into categories of similar interventions; statistical pooling was subsequently performed, where appropriate. When possible, pooled estimates using relative risks for abstinence rates with 95% confidence intervals were calculated. The remaining studies were reported separately.
Abstinence Rates
Table ES1 provides a summary of the pooled estimates for abstinence, at longest follow-up, from the trials included in this review. It also shows the respective GRADE qualities of evidence.
Summary of Results*
Abbreviations: CI, confidence interval; NRT, nicotine replacement therapy.
Statistically significant (P < 0.05).
One trial used in this comparison had 2 treatment arms each examining a different antidepressant.
Conclusions
Based on a moderate quality of evidence, compared with usual care, abstinence rates are significantly higher in COPD patients receiving intensive counselling or a combination of intensive counselling and NRT.
Based on limited and moderate quality of evidence, abstinence rates are significantly higher in COPD patients receiving NRT compared with placebo.
Based on a moderate quality of evidence, abstinence rates are significantly higher in COPD patients receiving the antidepressant bupropion compared to placebo.
PMCID: PMC3384371  PMID: 23074432
17.  Mood Disorder Symptoms and Elevated Cardiovascular Disease Risk in Patients with Bipolar Disorder 
Journal of Affective Disorders  2012;138(3):405-408.
Objectives
We examined the association between mood symptoms and 10-year CVD risk estimated by Framingham risk score in a cohort of patients with bipolar disorder.
Methods
Veterans with bipolar disorder and CVD risk factors (N=118) were recruited from outpatient VA clinics. CVD risk factor data were collected from electronic medical records and patient surveys, and used to calculate patient Framingham Scores. The relationship between mood symptoms (depressive, manic) and Framingham scores was examined, as was the relationship between mental health symptoms and individual CVD risk factors (lipids, blood pressure, weight, smoking, and fasting glucose).
Results
Mean sample age was 53 years (SD=9.9), 17% were female, and 5% were African- American. Almost 70% were obese (BMI ≥30), 84% had hyperlipidemia, 70% were hypertensive, and 25% had diabetes. Nineteen percent had a Framingham score of >20%, indicative of elevated 10-year risk of developing CVD. After adjusting for age, gender, diabetes diagnosis, smoking status, and mood symptoms, patients with clinically significant depressive symptoms had a 6-fold increased odds of having a Framingham score of >20% (OR=6.1, p=0.03) while clinically significant manic symptoms were not associated with the Framingham score (OR=0.6, p=0.36). Depressive symptoms were also associated with elevated BMI, fasting glucose, and blood pressure.
Limitations
Single-site study reliant on cross-sectional and self-reported mood measures.
Conclusion
After controlling for physiologic correlates, depressive symptoms were associated with greater relative 10-year risk for CVD mortality among patients with bipolar disorder. Interventions that address self-management of depressive symptoms may help persons with bipolar disorder decrease CVD risk.
doi:10.1016/j.jad.2012.01.005
PMCID: PMC3306618  PMID: 22357338
cardiovascular disease; bipolar disorder; preventive screening; heart disease; risk factors
18.  Mental health symptoms in relation to socio-economic conditions and lifestyle factors – a population-based study in Sweden 
BMC Public Health  2009;9:302.
Background
Poor mental health has large social and economic consequences both for the individual and society. In Sweden, the prevalence of mental health symptoms has increased since the beginning of the 1990s. There is a need for a better understanding of the area for planning preventive activities and health care.
Methods
The study is based on a postal survey questionnaire sent to a random sample of men and women aged 18–84 years in 2004. The overall response rate was 64%. The area investigated covers 55 municipalities with about one million inhabitants in central part of Sweden. The study population includes 42,448 respondents. Mental health was measured with self-reported symptoms of anxiety/depression (EQ-5D, 5th question). The association between socio-economic conditions, lifestyle factors and mental health symptoms was investigated using multivariate multinomial logistic regression models.
Results
About 40% of women and 30% of men reported that they were moderately or extremely anxious or depressed. Younger subjects reported poorer mental health than older subjects, the best mental health was found at ages 65–74 years.
Factors that were strongly and independently related to mental health symptoms were poor social support, experiences of being belittled, employment status (receiving a disability pension and unemployment), economic hardship, critical life events, and functional disability. A strong association was also found between how burdensome domestic work was experienced and anxiety/depression. This was true for both men and women. Educational level was not associated with mental health symptoms.
Of lifestyle factors, physical inactivity, underweight and risk consumption of alcohol were independently associated with mental health symptoms.
Conclusion
Our results support the notion that a ground for good mental health includes balance in social relations, in domestic work and in employment as well as in personal economy both among men and women. In addition, physical inactivity, underweight and risk consumption of alcohol are associated with mental health symptoms independent of socio-economic factors.
doi:10.1186/1471-2458-9-302
PMCID: PMC2736164  PMID: 19695085
19.  Impact of children's migration on health and health care-seeking behavior of elderly left behind 
BMC Public Health  2011;11:143.
Background
Many countries are facing the burden of accelerated population aging and a lack of institutional support to meet the needs of older individuals. In developing countries, adult children are primarily responsible for the care of their elderly parents. However, out-migration of adult children is common in these countries. This study aims to explore the impact of migration on the health of the elderly left behind and their health care-seeking behavior.
Methods
This paper uses data from a national survey of older persons in Thailand conducted in 2007. The analysis is confined to those who were aged 60 years or above and who had at least one child (biological or step/adopted) (n = 28,677). Logistic regression was used to assess the net effect of migration of adult children on the health of the elderly left behind and their health care-seeking behavior, after controlling for other socio-demographic and economic variables.
Results
More than two-thirds of the elderly (67%) had at least one migrant child. About three-fifths (58%) reported that they had at least one symptom of poor mental health. Almost three in five elderly (56%) rated their health as poor, and 44% had experienced at least one chronic disease. About two-thirds of the elderly (65%) got sick during the 5 years preceding the survey. An overwhelming majority of elderly (88%) who got sick during the five years preceding the survey had sought treatment for their last illness.
After controlling for socio-demographic and economic variables, our study found that those elderly who had a migrant child were more likely (OR = 1.10; 95% CI 1.05-1.17) to have symptoms of poor mental health than those whose children had not migrated. However, no significant association was observed among physical health, such as experience of chronic disease, perceived poor health, and illness of the elderly left behind. Interestingly, however, out-migration of adult children was independently associated with higher utilization of health services. The elderly who had migrant children were more likely (odds ratio = 1.22, CI 1.11-1.33) than those whose children had not migrated to seek treatment for their most recent illness, after controlling for socio-demographic and economic variables.
Conclusion
Our study provides novel evidence on an issue of special importance to countries affected by heavy out-migration of adult children, an issue that has received little attention. Out-migration of adult children was highly associated with poor mental health but it was not associated with the physical health of the elderly left behind. Out-migration of children was also highly associated with higher utilization of health facilities by the elderly. Thus, in order to decrease morbidity among the elderly as well as to maintain and enhance the well-being of families, programs should focus on alleviating the symptoms of poor mental health among the elderly left behind and aim to reduce the differences in utilization of health care-seeking behavior among elderly with children present in the community and elderly left behind.
doi:10.1186/1471-2458-11-143
PMCID: PMC3056748  PMID: 21366920
20.  Prolonged Grief Disorder: Psychometric Validation of Criteria Proposed for DSM-V and ICD-11 
PLoS Medicine  2009;6(8):e1000121.
Holly Prigerson and colleagues tested the psychometric validity of criteria for prolonged grief disorder (PGD) to enhance the detection and care of bereaved individuals at heightened risk of persistent distress and dysfunction.
Background
Bereavement is a universal experience, and its association with excess morbidity and mortality is well established. Nevertheless, grief becomes a serious health concern for a relative few. For such individuals, intense grief persists, is distressing and disabling, and may meet criteria as a distinct mental disorder. At present, grief is not recognized as a mental disorder in the DSM-IV or ICD-10. The goal of this study was to determine the psychometric validity of criteria for prolonged grief disorder (PGD) to enhance the detection and potential treatment of bereaved individuals at heightened risk of persistent distress and dysfunction.
Methods and Findings
A total of 291 bereaved respondents were interviewed three times, grouped as 0–6, 6–12, and 12–24 mo post-loss. Item response theory (IRT) analyses derived the most informative, unbiased PGD symptoms. Combinatoric analyses identified the most sensitive and specific PGD algorithm that was then tested to evaluate its psychometric validity. Criteria require reactions to a significant loss that involve the experience of yearning (e.g., physical or emotional suffering as a result of the desired, but unfulfilled, reunion with the deceased) and at least five of the following nine symptoms experienced at least daily or to a disabling degree: feeling emotionally numb, stunned, or that life is meaningless; experiencing mistrust; bitterness over the loss; difficulty accepting the loss; identity confusion; avoidance of the reality of the loss; or difficulty moving on with life. Symptoms must be present at sufficiently high levels at least six mo from the death and be associated with functional impairment.
Conclusions
The criteria set for PGD appear able to identify bereaved persons at heightened risk for enduring distress and dysfunction. The results support the psychometric validity of the criteria for PGD that we propose for inclusion in DSM-V and ICD-11.
Please see later in the article for Editors' Summary
Editors' Summary
Background
Virtually everyone loses someone they love during their lifetime. Grief is an unavoidable and normal reaction to this loss. After the death of a loved one, bereaved people may feel sadness, anger, guilt, anxiety, and despair. They may think constantly about the deceased person and about the events that led up to the person's death. They often have physical reactions to their loss—problems sleeping, for example—and they may become ill. Socially, they may find it difficult to return to work or to see friends and family. For most people, these painful emotions and thoughts gradually diminish, usually within 6 months or so of the death. But for a few people, the normal grief reaction lingers and becomes increasingly debilitating. Experts call this complicated grief or prolonged grief disorder (PGD). Characteristically, people with PGD have intrusive thoughts and images of the deceased person and a painful yearning for his or her presence. They may also deny their loss, feel desperately lonely and adrift, and want to die themselves.
Why Was This Study Done?
PGD is not currently recognized as a mental disorder although it meets the requirements for one given in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) and in the World Health Organization's International Statistical Classification of Diseases and Related Health Problems, 10thEdition (ICD-10). Before PGD can be recognized as a mental disorder (and included in DSM-V and ICD-11), bereavement and mental-health experts need to agree on standardized criteria for PGD. Such criteria would be useful because they would allow researchers and clinicians to identify risk factors for PGD and to find ways to prevent PGD. They would also help to ensure that people with PGD get appropriate treatments such as psychotherapy to help them change their way of thinking about their loss and re-engage with the world. Recently, a panel of experts agreed on a consensus list of symptoms for PGD. In this study, the researchers undertake a field trial to develop and evaluate algorithms (sets of rules) for diagnosing PGD based on these symptoms.
What Did the Researchers Do and Find?
The researchers used “item response theory” (IRT) to derive the most informative PGD symptoms from structured interviews of nearly 300 people who had recently lost a close family member. These interviews contained questions about the consensus list of symptoms; each participant was interviewed two or three times during the two years after their spouse's death. The researchers then used “combinatoric” analysis to identify the most sensitive and specific algorithm for the diagnosis of PGD. This algorithm specifies that a bereaved person with PGD must experience yearning (physical or emotional suffering because of an unfulfilled desire for reunion with the deceased) and at least five of nine additional symptoms. These symptoms (which include emotional numbness, feeling that life is meaningless, and avoidance of the reality of the loss) must persist for at least 6 months after the bereavement and must be associated with functional impairment. Finally, the researchers show that individuals given a diagnosis of PGD 6–12 months after a death have a higher subsequent risk of mental health and functional impairment than people not diagnosed with PGD.
What Do These Findings Mean?
These findings validate a set of symptoms and a diagnostic algorithm for PGD. Because most of the study participants were elderly women who had lost their husband, further validation is needed to check that these symptoms and algorithm also apply to other types of bereaved people such as individuals who have lost a child. For now, though, these findings support the inclusion of PGD in DSM-V and ICD-11 as a recognized mental disorder. Furthermore, the availability of a standardized way to diagnose PGD will help clinicians identify the minority of people who fail to adjust successfully to the loss of a loved one. Hopefully, by identifying these people and helping them to avoid the onset of PGD (perhaps by providing psychotherapy soon after a death) and/or providing better treatment for PGD, it should now be possible to reduce the considerable personal and societal costs associated with prolonged grief.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000121.
This study is further discussed in a PLoS Medicine Perspective by Stephen Workman
The Dana Farber Cancer Institute has a page describing its Center for Psycho-oncology and Palliative Care Research
The UK Royal College of Psychiatrists has a leaflet on bereavement (in English, Welsh, Urdu, and Chinese)
The US National Cancer Institute also has information about coping with bereavement for patients and health professionals (in English and Spanish)
MedlinePlus has links to other information about bereavement (in English and Spanish)
The Journal of the American Medical Association has a patient page on abnormal grief
Harvard Medical School provides a short family health guide about complicated grief
Information on DSM-IV and ICD-10 is available
doi:10.1371/journal.pmed.1000121
PMCID: PMC2711304  PMID: 19652695
21.  Experiences of Living and Dying With COPD 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html.
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-Term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty_member_giacomini.htm.
For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx.
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact.
Objective of Analysis
The objective of this analysis was to review empirical qualitative research on the experiences of patients with chronic obstructive pulmonary disease (COPD), informal caregivers (“carers”), and health care providers—from the point of diagnosis, through daily living and exacerbation episodes, to the end of life.
Clinical Need and Target Population
Qualitative empirical studies (from social sciences, clinical, and related fields) can offer important information about how patients experience their condition. This exploration of the qualitative literature offers insights into patients’ perspectives on COPD, their needs, and how interventions might affect their experiences. The experiences of caregivers are also explored.
Research Question
What do patients with COPD, their informal caregivers (“carers”), and health care providers experience over the course of COPD?
Research Methods
Literature Search
Search Strategy
Literature searches for studies published from January 1, 2000, to November 2010 were performed on November 29, 2010, using OVID MEDLINE; on November 26, 2010, using ISI Web of Science; and on November 28, 2010, using EBSCO Cumulative Index to Nursing and Allied Health Literature (CINAHL). Titles and abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. One additional report, highly relevant to the synthesis, appeared in early 2011 during the drafting of this analysis and was included post hoc.
Inclusion Criteria
English-language full reports
studies published between January 1, 2000, and November 2010
primary qualitative empirical research (using any descriptive or interpretive qualitative methodology, including the qualitative component of mixed-methods studies) and secondary syntheses of primary qualitative empirical research
studies addressing any aspect of the experiences of living or dying with COPD from the perspective of persons at risk, patients, health care providers, or informal carers; studies addressing multiple conditions were included if COPD was addressed explicitly
Exclusion Criteria
studies addressing topics other than the experiences of living or dying with COPD from the perspective of persons at risk, patients, health care providers, or informal carers
studies labelled “qualitative” but not using a qualitative descriptive or interpretive methodology (e.g., case studies, experiments, or observational analysis using qualitative categorical variables)
quantitative research (i.e., using statistical hypothesis testing, using primarily quantitative data or analyses, or expressing results in quantitative or statistical terms)
studies that did not pose an empirical research objective or question, or involve the primary or secondary analysis of empirical data
Outcomes of Interest
qualitative descriptions and interpretations (narrative or theoretical) of personal and social experiences of COPD
Summary of Findings
Experiences at Diagnosis
Patients typically seek initial treatment for an acute episode rather than for chronic early symptoms of COPD.
Many patients initially misunderstand terms such as COPD, chronic obstructive pulmonary disease, or exacerbation.
Patients may not realize that COPD is incurable and fatal; some physicians themselves do not consider early COPD to be a fatal disease.
Smokers may not readily understand or agree with the idea that smoking caused or worsens their COPD. Those who believe there is a causal link may feel regret or shame.
Experiences of Living Day to Day
COPD patients experience alternating good days and bad days. A roller-coaster pattern of ups and downs becomes apparent, and COPD becomes a way of life.
Patients use many means (social, psychological, medical, organizational) to control what they can, and to cope with what they cannot. Economic hardship, comorbidities, language barriers, and low health literacy can make coping more difficult.
Increasing vulnerability and unpredictable setbacks make patients dependent on others for practical assistance, but functional limitations, institutional living or self-consciousness can isolate patients from the people they need.
For smokers, medical advice to quit can conflict with increased desire to smoke as a coping strategy.
Many of the factors that isolate COPD patients from social contact also isolate them from health care.
Experiences of Exacerbations
Patients may not always attribute repeated exacerbations to advancing disease, instead seeing them as temporary setbacks caused by activities, environmental factors, faltering self-management, or infection.
Lack of confidence in community-based services leads some patients to seek hospital admission, but patients also feel vulnerable when hospitalized. They may feel dependent on others for care or traumatized by hospital care routines.
Upon hospital discharge following an exacerbation, patients may face new levels of uncertainty about their illness, prognosis, care providers, and supports.
Experiences of the End of Life
Patients tend to be poorly informed about the long-term prognosis of COPD and what to expect toward the end of life; this lack of understanding impairs quality of life as the disease progresses.
As the end of life approaches, COPD patients face the usual challenges of daily living, but in a context of increasing exacerbations and deepening dependency. Activities and mobility decrease, and life may become confined.
Some clinicians have difficulty identifying the beginning of “the end of life,” given the unpredictable course of COPD. Long-term physician-patient relationships, familiarity and understanding, trust, good communication skills, sensitivity, and secure discussion settings can help facilitate end-of-life discussions.
Divergent meanings and goals of palliative care in COPD lead to confusion about whether such services are the responsibility of home care, primary care, specialty care, or even critical care. Palliative end-of-life care may not be anticipated prior to referral for such care. A palliative care referral can convey the demoralizing message that providers have “given up.”
Experiences of Carers
Carers’ challenges often echo patients’ challenges, and include anxiety, uncertainty about the future, helplessness, powerlessness, depression, difficulties maintaining employment, loss of mobility and freedoms, strained relationships, and growing social isolation.
Carers feel pressured by their many roles, struggling to maintain patience when they feel overwhelmed, and often feeling guilty about not doing enough.
Carers often face their own health problems and may have difficulty sustaining employment.
Synthesis: A Disease Trajectory Reflecting Patient Experiences
The flux of needs in COPD calls for service continuity and flexibility to allow both health care providers and patients to respond to the unpredictable yet increasing demands of the disease over time.
PMCID: PMC3384365  PMID: 23074423
22.  Schizophrenia and Violence: Systematic Review and Meta-Analysis 
PLoS Medicine  2009;6(8):e1000120.
Seena Fazel and colleagues investigate the association between schizophrenia and other psychoses and violence and violent offending, and show that the increased risk appears to be partly mediated by substance abuse comorbidity.
Background
Although expert opinion has asserted that there is an increased risk of violence in individuals with schizophrenia and other psychoses, there is substantial heterogeneity between studies reporting risk of violence, and uncertainty over the causes of this heterogeneity. We undertook a systematic review of studies that report on associations between violence and schizophrenia and other psychoses. In addition, we conducted a systematic review of investigations that reported on risk of homicide in individuals with schizophrenia and other psychoses.
Methods and Findings
Bibliographic databases and reference lists were searched from 1970 to February 2009 for studies that reported on risks of interpersonal violence and/or violent criminality in individuals with schizophrenia and other psychoses compared with general population samples. These data were meta-analysed and odds ratios (ORs) were pooled using random-effects models. Ten demographic and clinical variables were extracted from each study to test for any observed heterogeneity in the risk estimates. We identified 20 individual studies reporting data from 18,423 individuals with schizophrenia and other psychoses. In men, ORs for the comparison of violence in those with schizophrenia and other psychoses with those without mental disorders varied from 1 to 7 with substantial heterogeneity (I2 = 86%). In women, ORs ranged from 4 to 29 with substantial heterogeneity (I2 = 85%). The effect of comorbid substance abuse was marked with the random-effects ORs of 2.1 (95% confidence interval [CI] 1.7–2.7) without comorbidity, and an OR of 8.9 (95% CI 5.4–14.7) with comorbidity (p<0.001 on metaregression). Risk estimates of violence in individuals with substance abuse (but without psychosis) were similar to those in individuals with psychosis with substance abuse comorbidity, and higher than all studies with psychosis irrespective of comorbidity. Choice of outcome measure, whether the sample was diagnosed with schizophrenia or with nonschizophrenic psychoses, study location, or study period were not significantly associated with risk estimates on subgroup or metaregression analysis. Further research is necessary to establish whether longitudinal designs were associated with lower risk estimates. The risk for homicide was increased in individuals with psychosis (with and without comorbid substance abuse) compared with general population controls (random-effects OR = 19.5, 95% CI 14.7–25.8).
Conclusions
Schizophrenia and other psychoses are associated with violence and violent offending, particularly homicide. However, most of the excess risk appears to be mediated by substance abuse comorbidity. The risk in these patients with comorbidity is similar to that for substance abuse without psychosis. Public health strategies for violence reduction could consider focusing on the primary and secondary prevention of substance abuse.
Please see later in the article for Editors' Summary
Editors' Summary
Background
Schizophrenia is a lifelong, severe psychotic condition. One in 100 people will have at least one episode of schizophrenia during their lifetime. Symptoms include delusions (for example, patients believe that someone is plotting against them) and hallucinations (hearing or seeing things that are not there). In men, schizophrenia usually starts in the late teens or early 20s; women tend to develop schizophrenia a little later. The causes of schizophrenia include genetic predisposition, obstetric complications, illegal drug use (substance abuse), and experiencing traumatic life events. The condition can be treated with a combination of antipsychotic drugs and supportive therapy; hospitalization may be necessary in very serious cases to prevent self harm. Many people with schizophrenia improve sufficiently after treatment to lead satisfying lives although some patients need lifelong support and supervision.
Why Was This Study Done?
Some people believe that schizophrenia and other psychoses are associated with violence, a perception that is often reinforced by news reports and that contributes to the stigma associated with mental illness. However, mental health advocacy groups and many mental health clinicians argue that it is a myth that people with mental health problems are violent. Several large, population-based studies have examined this disputed relationship. But, although some studies found no increased risk of violence among patients with schizophrenia compared with the general population, others found a marked increase in violent offending in patients with schizophrenia. Here, the researchers try to resolve this variation (“heterogeneity”) in the conclusions reached in different studies by doing a systematic review (a study that uses predefined search criteria to identify all the research on a specific topic) and a meta-analysis (a statistical method for combining the results of several studies) of the literature on associations between violence and schizophrenia and other psychoses. They also explored the relationship between substance abuse and violence.
What Did the Researchers Do and Find?
By systematically searching bibliographic databases and reference lists, the researchers identified 20 studies that compared the risk of violence in people with schizophrenia and other psychoses and the risk of violence in the general population. They then used a “random effects model” (a statistical technique that allows for heterogeneity between studies) to investigate the association between schizophrenia and violence. For men with schizophrenia or other psychoses, the pooled odds ratio (OR) from the relevant studies (which showed moderate heterogeneity) was 4.7, which was reduced to 3.8 once adjustment was made for socio-economic factors. That is, a man with schizophrenia was four to five times as likely to commit a violent act as a man in the general population. For women, the equivalent pooled OR was 8.2 but there was a much greater variation between the ORs in the individual studies than in the studies that involved men. The researchers then used “meta-regression” to investigate the heterogeneity between the studies. This analysis suggested that none of the study characteristics examined apart from co-occurring substance abuse could have caused the variation between the studies. Importantly the authors found that risk estimates of violence in people with substance abuse but no psychosis were similar to those in people with substance abuse and psychosis and higher than those in people with psychosis alone. Finally, although people with schizophrenia were nearly 20 times more likely to have committed murder than people in the general population, only one in 300 people with schizophrenia had killed someone, a similar risk to that seen in people with substance abuse.
What Do These Findings Mean?
These findings indicate that schizophrenia and other psychoses are associated with violence but that the association is strongest in people with substance abuse and most of the excess risk of violence associated with schizophrenia and other psychoses is mediated by substance abuse. However, the increased risk in patients with comorbidity was similar to that in substance abuse without psychosis. A potential implication of this finding is that violence reduction strategies that focus on preventing substance abuse among both the general population and among people with psychoses might be more successful than strategies that solely target people with mental illnesses. However, the quality of the individual studies included in this meta-analysis limits the strength of its conclusions and more research into the association between schizophrenia, substance abuse, and violence would assist in clarifying how and if strategies for violence reduction are changed.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000120.
The US National Institute of Mental Health provides information about schizophrenia (in English and Spanish)
The UK National Health Service Choices Web site has information for patients and carers about schizophrenia
The MedlinePlus Encyclopedia has a page on schizophrenia; MedlinePlus provides links to other sources of information on schizophrenia and on psychotic disorders (in English and Spanish)
The Schizophrenia and Related Disorders Alliance of America provides information and support for people with schizophrenia and their families
The time to change Web site provides information about an English campaign to reduce the stigma associated with mental illness
The Schizophrenia Research Forum provides updated research news and commentaries for the scientific community
doi:10.1371/journal.pmed.1000120
PMCID: PMC2718581  PMID: 19668362
23.  Intimate Partner Violence and Incident Depressive Symptoms and Suicide Attempts: A Systematic Review of Longitudinal Studies 
PLoS Medicine  2013;10(5):e1001439.
Karen Devries and colleagues conduct a systematic review of longitudinal studies to evaluate the direction of association between symptoms of depression and intimate partner violence.
Please see later in the article for the Editors' Summary
Background
Depression and suicide are responsible for a substantial burden of disease globally. Evidence suggests that intimate partner violence (IPV) experience is associated with increased risk of depression, but also that people with mental disorders are at increased risk of violence. We aimed to investigate the extent to which IPV experience is associated with incident depression and suicide attempts, and vice versa, in both women and men.
Methods and Findings
We conducted a systematic review and meta-analysis of longitudinal studies published before February 1, 2013. More than 22,000 records from 20 databases were searched for studies examining physical and/or sexual intimate partner or dating violence and symptoms of depression, diagnosed major depressive disorder, dysthymia, mild depression, or suicide attempts. Random effects meta-analyses were used to generate pooled odds ratios (ORs). Sixteen studies with 36,163 participants met our inclusion criteria. All studies included female participants; four studies also included male participants. Few controlled for key potential confounders other than demographics. All but one depression study measured only depressive symptoms. For women, there was clear evidence of an association between IPV and incident depressive symptoms, with 12 of 13 studies showing a positive direction of association and 11 reaching statistical significance; pooled OR from six studies = 1.97 (95% CI 1.56–2.48, I2 = 50.4%, pheterogeneity = 0.073). There was also evidence of an association in the reverse direction between depressive symptoms and incident IPV (pooled OR from four studies = 1.93, 95% CI 1.51–2.48, I2 = 0%, p = 0.481). IPV was also associated with incident suicide attempts. For men, evidence suggested that IPV was associated with incident depressive symptoms, but there was no clear evidence of an association between IPV and suicide attempts or depression and incident IPV.
Conclusions
In women, IPV was associated with incident depressive symptoms, and depressive symptoms with incident IPV. IPV was associated with incident suicide attempts. In men, few studies were conducted, but evidence suggested IPV was associated with incident depressive symptoms. There was no clear evidence of association with suicide attempts.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Depression and suicide are responsible for a substantial proportion of the global disease burden. Depression—an overwhelming feeling of sadness and hopelessness that can last for months or years—affects more than 350 million people worldwide. It is the eleventh leading cause of global disability-adjusted life-years (a measure of overall disease burden), and it affects one in six people at some time during their lives. Globally, about a million people commit suicide every year, usually because they have depression or some other mental illness. Notably, in cross-sectional studies (investigations that look at a population at a single time point), experience of intimate partner violence (IPV, also called domestic violence) is strongly and consistently associated with both depressive disorders and suicide. IPV, like depression and suicide, is extremely common—in multi-country studies, 15%–71% of women report being physically assaulted at some time during their lifetime. IPV is defined as physical, sexual, or psychological harm by a current or former partner or spouse; men as well as women can be the victims of IPV.
Why Was This Study Done?
It may seem obvious to assume that IPV is causally related to subsequent depression and suicidal behavior. However, cross-sectional studies provide no information about causality, and it is possible that depression and/or suicide attempts cause subsequent IPV or that there are common risk factors for IPV, depression, and suicide. For example, individuals with depressive symptoms may be more accepting of partners with characteristics that predispose them to use violence, or early life exposure to violence may predispose individuals to both depression and choosing violent partners. Here, as part of the Global Burden of Disease Study 2010, the researchers investigate the extent to which experience of IPV is associated with subsequent depression and suicide attempts and vice versa in both men and women by undertaking a systematic review and meta-analysis of longitudinal studies that have examined IPV, depression, and suicide attempts. A systematic review uses predefined criteria to identify all the research on a given topic, meta-analysis combines the results of several studies, and longitudinal studies track people over time to investigate associations between specific characteristics and outcomes.
What Did the Researchers Do and Find?
The researchers identified 16 longitudinal studies involving a total of 36,163 participants that met their inclusion criteria. All the studies included women, but only four also included men. All the studies were undertaken in high- and middle-income countries. For women, 11 studies showed a statistically significant association (an association unlikely to have occurred by chance) between IPV and subsequent depressive symptoms. In a meta-analysis of six studies, experience of IPV nearly doubled the risk of women subsequently reporting depressive symptoms. In addition, there was evidence of an association in the reverse direction. In a meta-analysis of four studies, depressive symptoms nearly doubled the risk of women subsequently experiencing IPV. IPV was also associated with subsequent suicide attempts among women. For men, there was some evidence from two studies that IPV was associated with depressive symptoms but no evidence for an association between IPV and subsequent suicide attempt or between depressive symptoms and subsequent IPV.
What Do These Findings Mean?
These findings suggest that women who are exposed to IPV are at increased risk of subsequent depression and that women who are depressed are more likely to be at risk of IPV. They also provide evidence of an association between IPV and subsequent suicide attempt for women. The study provides little evidence for similar relationships among men, but additional studies are needed to confirm this finding. Moreover, the accuracy of these findings is likely to be affected by several limitations of the study. For example, few of the included studies controlled for other factors that might have affected both exposure to IPV and depressive symptoms, and none of the studies considered the effect of emotional violence on depressive symptoms and suicide attempts. Nevertheless, these findings have two important implications. First, they suggest that preventing violence against women has the potential to reduce the global burden of disease related to depression and suicide. Second, they suggest that clinicians should pay attention to past experiences of violence and the risk of future violence when treating women who present with symptoms of depression.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001439.
This study is further discussed in a PLOS Medicine Perspective by Alexander Tsai
The US National Institute of Mental Health provides information on all aspects of depression and of suicide and suicide prevention (in English and Spanish)
The UK National Health Service Choices website provides detailed information about depression, including personal stories about depression, and information on suicide and its prevention; it has a webpage about domestic violence, which includes descriptions of personal experiences
The World Health Organization provides information on depression, on the global burden of suicide and on suicide prevention, and on intimate partner violence (some information in several languages)
MedlinePlus provides links to other resources about depression, suicide, and domestic violence (in English and Spanish)
The charity Healthtalkonline has personal stories about depression and about dealing with suicide
doi:10.1371/journal.pmed.1001439
PMCID: PMC3646718  PMID: 23671407
24.  Neighborhood Environment and Health Status and Mortality Among Veterans 
BACKGROUND
The VHA is the largest integrated US health system and is increasingly moving care into the communities where veterans reside. Veterans who utilize the VA for their care have worse health status than the general population. However, there is limited evidence about the association of neighborhood environment and health outcomes among veterans.
OBJECTIVES
The primary aim of this study is to assess the relative contribution of neighborhood environment, health system, and individual characteristics to health status and mortality of veterans.
METHODS
Information on personal socio-economic indicators, existing medical conditions and health status were obtained from baseline data from a multi-site, randomized trial of primary care patients (n = 15,889). The physical component scale (PCS) and mental component scale (MCS) summarized health status. Census tracts were used as proxies for neighborhoods. A summary score based on census tract data characterized the neighborhood socio-economic environment and walkability. Data were analyzed with multilevel hierarchical models. Analyses of health status were cross-sectional. Mortality analyses were longitudinal as participants were followed for an average of 722.5 days to ascertain vital status.
RESULTS
Neighborhood SES was associated with PCS and MCS scores, controlling for individual socio-economic status, self-reported co-morbid disease, smoking status, and health care access. In the lowest versus highest quartiles of neighborhood SES, adjusted PCS scores were 34.4 vs. 35.4 (p < 0.05) and adjusted MCS scores were 46.2 versus 47.0 (p < 0.05). PCS score was also significantly associated with neighborhood walkability (p < 0.05). Mortality was lower for veterans living in neighborhoods with the highest decile neighborhood SES (HR 0.78, highest vs. lowest decile 95% CI 0.63, 0.97).
CONCLUSIONS
Veterans living in lower SES neighborhoods have poorer health status and a higher risk of mortality, independent of individual characteristics and health care access. Neighborhood walkability was associated with higher PCS scores.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-011-1710-0) contains supplementary material, which is available to authorized users.
doi:10.1007/s11606-011-1710-0
PMCID: PMC3138994  PMID: 21499826
neighborhood; veterans; health status
25.  The importance of childhood and adulthood aspects of gendered life for adult mental ill-health symptoms – a 27-year follow-up of the Northern Swedish Cohort 
BMC Public Health  2012;12:493.
Background
The increasing gender equality during the 20th century, mainly in the Nordic countries, represents a major social change. A well-established theory is that this may affect the mental health patterns of women and men. This study aimed at examining associations between childhood and adulthood gendered life on mental ill-health symptoms.
Methods
A follow-up study of a cohort of all school leavers in a medium-sized industrial town in northern Sweden was performed from age 16 to age 42. Of those still alive of the original cohort, 94% (n = 1007) participated during the whole period. Gendered life was divided into three stages according to whether they were traditional or non-traditional (the latter includes equal): childhood (mother’s paid work position), adulthood at age 30 (ideology and childcare), and adulthood at age 42 (partnership and childcare). Mental ill-health was measured by self-reported anxious symptoms (“frequent nervousness”) and depressive symptoms (“frequent sadness”) at age 42. The statistical method was logistic regression analysis, finally adjusted for earlier mental ill-health symptoms and social confounding factors.
Results
Generally, parents’ gendered life was not decisive for a person’s own gendered life, and adulthood gender position ruled out the impact of childhood gender experience on self-reported mental ill-health. For women, non-traditional gender ideology at age 30 was associated with decreased risk of anxious symptoms (76% for traditional childhood, 78% for non-traditional childhood). For men, non-traditional childcare at age 42 was associated with decreased risk of depressive symptoms (84% for traditional childhood, 78% for non-traditional childhood). A contradictory indication was that non-traditional women in childcare at age 30 had a threefold increased risk of anxious symptoms at age 42, but only when having experienced a traditional childhood.
Conclusion
Adulthood gender equality is generally good for self-reported mental health regardless of whether one opposes or continues one’s gendered history. However, the childcare findings indicate a differentiated picture; men seem to benefit in depressive symptoms from embracing this traditionally female duty, while women suffer anxious symptoms from departing from it, if their mother did not.
doi:10.1186/1471-2458-12-493
PMCID: PMC3488496  PMID: 22747800

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