Variations in physical activity (PA) across nations may be driven by socioeconomic position. As national incomes increase, car ownership becomes within reach of more individuals. This report characterizes associations between car ownership and PA in African-origin populations across 5 sites at different levels of economic development and with different transportation infrastructures: US, Seychelles, Jamaica, South Africa, and Ghana.Twenty-five hundred adults, ages 25–45, were enrolled in the study. A total of 2,101 subjects had valid accelerometer-based PA measures  and complete socioeconomic information. Our primary exposure of interest was whether the household owned a car. We adjusted for socioeconomic position using household income and ownership of common goods.Overall, PA levels did not vary largely between sites, with highest levels in South Africa, lowest in the US. Across all sites, greater PA was consistently associated with male gender, fewer years of education, manual occupations, lower income, and owning fewer material goods. We found heterogeneity across sites in car ownership: after adjustment for confounders, car owners in the US had 24.3 fewer minutes of MVPA compared to non-car owners in the US (20.7 vs. 45.1 minutes/day of MVPA); in the non-US sites, car-owners had an average of 9.7 fewer minutes of MVPA than non-car owners (24.9 vs. 34.6 minutes/day of MVPA).PA levels are similar across all study sites except Jamaica, despite very different levels of socioeconomic development. Not owning a car in the US is associated with especially high levels of MVPA. As car ownership becomes prevalent in the developing world, strategies to promote alternative forms of active transit may become important. Physical activity (PA) is assumed to be lower in developed than in non-developed nations, which is thought to contribute to the high rates of obesity observed in the former , althougAlternatively, several compensatory mechanisms may increase PA in developed nations. Labor-saving tools may increase productivity without reducing PA , while gWe report here socioeconomic findings for the 5 international African-origin cohorts that have been recruited for the Modeling the Epidemiologic Transition Study (METS) . Our aimGhana: The in-country study sites include the town of Nkwantakese in the Afigya-Kwabre District of the Ashanti Region of Ghana and its surrounding villages. The town is situated to the southwest of Agona Ashanti the District Capital, and is about 20 km from Kumasi with a population of approximately 17,000.South Africa: Khayelitsha is the 3rd largest township in South Africa and is adjacent to the city of Cape Town. The population is about 500,000 with 80 percent of the residents living in temporary housing and 40 percent unemployed.Jamaica: The study site in Jamaica is in Kingston, the capital and largest city with a population of 651,880.Seychelles: In Seychelles, individuals have been recruited from the main island of the archipelago, Mahé, which includes approximately 75,000 inhabitants for a surface of 155 km2. Mahé can be qualified as semi-urban and its economy is mainly driven by tourism, industrial fishing and services. Seychelles is located approximately 1,600 km east of Kenya in the Indian Ocean, and approximately 2,000 km north of the island of Mauritius, and has a total population of about 87,000.USA (Maywood): Maywood is an African-American working class community adjacent to the western border of Chicago, Illinois, with a population of approximately 24,903 people.Twenty-five hundred adults, ages 25–45, were enrolled in METS between January 2010 and December 2011, as described in detail elsewhere . In brieAll participants were of predominantly African descent. Exclusion criteria included infectious diseases, pregnancy or lactation, and, conditions severely preventing normal physical activities, e.g. lower extremity disability. The study sites were selected to represent a broad range of social and economic development as defined by purchasing power parity adjusted gross national income (PPP-GNI) and the UN Human Development Index (HDI) in 2010. The PPP-GNI per capita is the sum of value added from resident producers, taxes, and primary income from abroad, divided by the midyear population of the country, and adjusted for purchasing power parity; the GNI per capita was $3340 in Ghana, $8170in Jamaica, $11640 in South Africa, $21340 in Seychelles, and $50861 in the US . The HDIThe METS protocol was approved by the Institutional Review Board of Loyola University Chicago, IL, USA; the Health Sciences Institutional Review Board of the University of Wisconsin, Madison, WI, USA; the Research Ethics Committee of the University of Cape Town, South Africa; the Committee on Human Research Publication and Ethics of Kwame Nkrumah University of Science and Technology, Kumasi, Ghana; the Board for Ethics and Clinical Research of the University of Lausanne, Switzerland (the primary institution for the Seychelles site’s director) and the Research and Ethics Committee of Ministry of Health of Seychelles.; and the Ethics Committee of the University of the West Indies, Kingston, Jamaica. We obtained written informed consent from all study participants.Weight (kg) and height (m) were measured to the nearest 0.1 kg and 0.1 cm respectively, on all participants in light clothing and no shoes.PA was assessed using the Actical accelerometer . The monitor was worn at the waist, just behind the right hip. Each participant was asked to wear the monitor at all times over 8 days , including during sleep for all sites except Seychelles, where monitors were only worn during waking time; the only time the monitor should be removed was while bathing, showering, or swimming.Accelerometry data were processed to first infer non-wear time from segments of continuous zero activity counts lasting 90 minutes or longer. Days containing 10+ hours of wear time were considered valid days and we included participants with four or more usable days. MVPA was defined using a published cut-point (1535+ counts per minute) ,23. We sParticipants completed a 54-question survey which covered general household characteristics, participant and partner’s occupation, parental education and household assets and amenities as detailed below.The number of years of education was reported by each respondent. Given that education levels have mostly local meaning within particular labor markets (sites), we created site-specific tertiles of education. We also used years of education as a continuous measure to allow comparisons across sites.The occupation questionnaire was derived from the U.K. National Statistics Socio-economic Classification, 2000 edition . We usedTotal monthly household income was reported in local currencies. Differences in currency values for the equivalent basket of goods across sites were transformed to US equivalent purchasing power parity (PPP) based on the 2010 data for the Penn World Table . PPP adjQuestions capturing household wealth were based on the Core Welfare Indicators Questionnaire from the World Bank, designed to monitor social indicators in Africa. These questionnaires have been used extensively in international research by the World Bank and United Nations to monitor demographic and socioeconomic trends in low and middle income nations, and allow for the creation of permanent income measures which reflect lifetime, rather than current, income, including future expectations of income . BecauseOut of 2,506 participants, we excluded 204 participants with insufficient accelerometer data. A further 201 participants were excluded due to missing socioeconomic covariates, yielding an analysis dataset of 2101 . All analyses were conducted in Stata Version 12 . We calculated means and standard deviations for continuous measures , and proportions for categorical variables . These calculations were done by site. We also calculated mean MVPA by site for various socio-demographic characteristics. Finally, we modeled MVPA in multivariable analysis containing car ownership adjusted for site, age, gender, income, and other household goods (Model 1). A second model (Model 2) additionally adjusted Model 1 for BMI, which tends to be associated with decreased PA, and thus may mediate relationships between socioeconomic characteristics and MVPA. We compared marginal values across sites, holding covariates constant at their overall mean values using the Stata “margins” command.It is common in studies using socioeconomic variables to have imbalances of variables across groups, a problem known as “structural confounding” ,31, whicSite-specific demographics are shown in Table The proportion of goods owned by households varied across the 5 sites, tending to follow the levels of income and HDI Table . OwnershLevels of MVPA varied across sites but did not show a directly linear pattern based on HDI Table . The higRegression analyses were used to distinguish independent relationships between socioeconomic characteristics and BMI and relevant exposure variables, controlling for site Table . The firThe association between household car ownership and MVPA differed across sites Table . Upon adWe have reported a wide range of socioeconomic correlates with MVPA across 5 sites that are vastly different in terms of economic development (by both GNI and HDI) and individual income. Adjusting for socioeconomic variables (including number of goods and car ownership) attenuated differences between sites, with the exception of Jamaica. Notably, car owners show similarly low levels of MVPA whether they lived in the US or in one of the other four sites, while non-car owners in the US showed the highest levels of MVPA.We know of only three other studies that looked internationally across very different levels of socioeconomic development; both studies used self-reported physical activity, and only the INTERHEART (Held and colleagues) and PURE studies (Lear and colleagues) explicitly examined car ownership ,12,36. WStudies of PA conducted only in the US may miss important population-level drivers of activity because there is not enough variation in lifestyle or social and physical environment . LookingNevertheless, the well-documented negative health effects of material disadvantage in the US reflected by not owning a car may be buffered by higher levels of MVPA. The potential protective role of MVPA in economic hardship is supported by the natural experiment of Cuba’s “special period” in the 1990s; with the end of Soviet subsidies, Cuba entered an economic crisis marked in part by extreme fuel scarcity. During this time, walking and bicycling became the only forms of transit available to most Cubans, while the food supply also shrank; this was followed by declining obesity prevalence and diabetes admissions . AlthougOur study had several strengths. This was a large-scale international comparison. We used objectively measured MVPA collected with accelerometers; studies employing only questionnaires may be prone to bias . We furtWe also note limitations of our study. Results presented here are cross-sectional; therefore causality cannot be determined. It is likely that substantial residual confounding remains for socioeconomic characteristics across sites, so the direct effect of site on MVPA just means that the measured variables do not fully account for differences between sites, and there is likely more (and more complexity) at work here. Complex systems approaches such as agent based models of changes to the built environment may be required for a more complete understanding of the mechanisms linking SEP and MVPA ,43.In conclusion, socioeconomic characteristics are associated with objectively-measured MVPA level. This was especially true of car ownership. As car ownership increases across the developing world, extra efforts may be needed to ensure adequate levels of MVPA, for example, by building infrastructure that also supports active commuting ,5. In th


In 2010, ischemic heart disease was the leading cause of disability-adjusted life-years (DALYs) worldwide. More specially, the prevalence of acute myocardial infarctions (AMI) is increasing in the aged population as mortality decreases; South Korea is no exception. This study aims to examine the economic burden of AMI in the Korean population between 2007 and 2012. AMI-related costs were assessed from a societal perspective. A prevalence-based cost-of-illness framework was used for this analysis. The subjects included all South Koreans with AMI-related ICD-10 codes . Data on direct  costs and indirect  costs were collected from the Korean National Health Insurance Service’s claims data. The human capital approach was used to calculate indirect costs. The total estimated cost of AMI in 2012 was $1,177,649,323 USD. The majority (52%) of this amount was made up of medical costs, followed by productivity losses due to mortality and morbidity . Although the total cost declined by approximately 18% compared to 2007 , the cost of AMI in the over 60 age group amounted to 47% of the total cost of AMI in 2012. AMI led to a high economic burden in 2012. This study, which identified not only the size, but also the trends of AMI-related costs, will provide information to evaluate effects of governmental health projects and the effective allocation of public research funds. Acute myocardial infarction (AMI) is a disease associated with high mortality worldwide . HoweverThis cost-of-illness (COI) study provides valuable data, which is comparable to the relative socioeconomic burdens of other disease. It can also be used as objective evidence when policy makers establish policy priorities and allocate resources related to the healthcare system. The objectives of this study were to quantify the economic burden of AMI caused by an increased in the use of health resources in combination with lost productivity between 2007 and 2012, and to provide a detailed breakdown of the costs attributed to AMI by various sex- and age-related groups.th revision) codes I21 (acute MI), I22 (subsequent MI), I23 (certain current complication following acute MI), I25.0 , and I25.1 (atherosclerotic heart disease). Though I25.0 and I25.1 are associated with chronic conditions, we have included those codes in our study in an effort to reflect typical Korean features related to entering AMI codes. In Korea, several medical institutions frequently make claims for health insurance premiums using codes I25.0 and I25.1 when they conduct screening tests (a creatine kinase muscle-brain (CK-MB) and troponin) and administer treatments (coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI)) to AMI patients. Additionally, a previous study showed that the positive rate of MI associated with both codes I25.0 and I25.1 was high [This study evaluated the costs related to AMI in a population-based cost analysis. We used a prevalence-based approach and a macro-costing method. AMI is defined here by the World Health Organization International Classification of Diseases  from the set. The intention behind dropping this data was to prevent an overestimation of expenses related to AMI by excluding comorbidity diseases, which often cost a great deal to treat .We estimated direct costs  and indirect costs  based on a societal perspective.AMI medical costs were divided into three categories: health insurance costs, out-of-pocket medical expenses and drugs. We used health insurance claims data to calculate health insurance costs related AMI throughout 2007 and 2012. Because there is only one insurance system in Korea, the National Health Insurance Service (NHIS) data represents medical information of the entire South Korean population. To account for private expenditures, we used data from health insurance patients’ medical expenditure surveys from 2007 and 2012 . Non-medWe used a human-capital approach to estimate indirect (productivity loss) costs . ProductWe use an annual time frame to assess change in economic burden between 2007 and 2012. The results of epidemiologic analysis  were presented as the trends from 2007 to 2012 and the total cost of AMI was presented by comparing with the results in 2007 and 2012. Though this study used the same basic framework as has previously been used to measure the costs of chronic diseases , 15, empDirect costs include medical costs and non-medical costs. Medical utilization has been divided into three categories: outpatient care, hospital inpatient care and drugs. Non-medical costs include transportation costs and caregiver costs.Medical costs consisted of reimbursement from NHIS and out-of-pocket expenses. First, we calculated both outpatient and inpatient reimbursement using NHIS claims data. Next, using the proportion of out-of-pocket costs for patients with heart disease  categorized by treatment type in the NHIS patient medical costs survey, we estimated out-of-pocket expenses. Once reimbursement and out-of-pocket expenses for outpatient and inpatient care were estimated, the total medical cost was added up.In case of drug expenditures, inpatients costs already included drug costs incurred during hospitalization. Therefore, we only needed to consider outpatients’ drug expenses, which were calculated using the proportion of outpatient, inpatient and outpatients’ drug costs provided by an annual NHIS statistical report .InNHI = NHI payment for hospitalization expenditures, OutNHI = NHI payment for outpatient expenditure, OP = Out-of-pocket payment, OutD = Outpatient payment for Drug, i = 0, 1, …, n (age), and j = 1 or 2 (sex)We defined non-medical costs as transportation costs and caregiver costs. To estimate the transportation costs, we multiplied the number of visits to a medical institution for AMI treatment by travel expense per visit. We used a single fare per visit to outpatient and inpatient institutions from KNHNES in 2005, and final transportation expenditures were estimated in consideration of inflation rates each year. Caregiver costs incurred through patients’ length-of-stay in hospitals and the hours of visits for outpatient care-related AMI were also estimated. The caregiver costs during hospitalization were calculated by multiplying patients’ length-of-stay in hospital by the average city daily workers’ wage. When we estimated the caregiver costs related to outpatient visits, we assumed that patients under the age of 20 and over the age of 70 would require a guardian and approximately 8 hours would be needed to accompany the patient to outpatient services.InV = number of hospitalization visits, OutV = number of outpatient visits, InT = round-trip transportation costs per hospitalization visit, OutT = round-trip transportation costs per outpatient visit, InD = length of hospitalization, CG = caregiver costs per day, i = 0, 1, …, n (age), and j = 1 or 2 (sex)Indirect costs included lost productivity due to AMI-related mortality and morbidity. We estimated productivity costs attributable to mortality as earnings lost due to premature death. For that, we assumed that the ages of the economically productive population were between 15 and 69 years. To estimate productivity loss after premature death due to AMI, we multiplied the number of deaths (categorized by sex and age) by annual average income. We also took the employment rate at the time into account to estimate the final value.t+k = average annual income at (t+k), Pt+k = employment rate, t = age at death, k = 1, 2, …, n (n is the difference between life expectancy and age at the time of death), r = discount rate, i = 0, 1, …, n (age), and j = 1 or 2 (sex)N = number of death, YMorbidity costs due to AMI were calculated and divided into two categories, outpatient and inpatient. We multiplied patients’ length-of-stay in hospital by the daily average wage (in terms of sex and age) to estimate productivity loss due to AMI inpatient care. Though productivity loss related to outpatient care was calculated in the same way, for the purposes of this study, we assumed that 8 hours of productivity was lost due to each outpatient care visit.InD = length of hospitalization, IC = average daily income, E = employment rate, OutV = number of outpatient visits, i = 0, 1, …, n (age), and j = 1 or 2 (sex)The prevalence of AMI continued to rise during the study period. In terms of sex, the number of male patients with AMI  is more than 1.73 times the number of females  in 2012. Even the increase in patients with AMI between 2007 and 2012 includes more male (1.34 times) than female (1.13 times) patients. Mortality due to AMI  decreased further each year from 2007 to 2011. However, the number of deaths due to AMI rose in 2012 to a number similar to that of 2008. In terms of the number of deaths due to AMI by age groups, mortality continued to decline 0.80 times in the under 60 age group between 2007 and 2012 .We estimated the total economic cost of AMI in South Korea to be more than $1,177,649,323 USD in 2012 . This acWe estimated the total cost of AMI in South Korea at to be $1.178 billion USD in 2012, of which, $607 million USD was incurred by direct medical utilization. The other 48% of the economic burden of AMI, however, was incurred in non-health-care systems, with almost $461 million USD in lost productivity attributable to early death. The total costs due to AMI accounted for 1.28% of National Health Expenditure (NHE) in 2012 and this cost showed a 0.7% decrease from the figure in 2007 . The proTotal AMI costs had decreased in 2012 compared with the costs in 2007. We can predict that the decline of the economic burden due to AMI happened since the decreasing rate of AMI mortality exceeded the growth rate of AMI prevalence. In addition, the decline in AMI mortality may be caused mostly by improvements in acute cardiac treatment . HoweverAccording to the economic burden by sex, male AMI costs were higher than female’s costs. Especially, direct costs were 1.85 times and indirect costs (productivity losses) were 15.21 times higher than females in 2012. The higher costs in male were caused by both higher prevalence and mortality of AMI than females. The AMI-related risk factors in males were reported to be smoking and stress , 22, 23.Recently, cost-of-illness studies have continued to progress in order to estimate the impact of diseases with similar frameworks in Korea. Stroke burden evaluations in 2010 estimated direct costs to be $3.528 billion USD, which was much higher than the direct cost of AMI in our 2012 evaluation . AdditioWe found that in other developed countries, the distribution of AMI economic burden was similar to that of our study , 28–30. Even though disease-related costs were estimated, we cannot discuss whether a country is spending too much or too little on a disease. Rather, the main aim of a COI study is to help inform decisions concerning allocation of research funding, by providing a measure of the economic burden of particular health problems . In addiWe used NHIS claims data as a main data source to estimate the cost of AMI. Since NHIS claims data include most of information necessary to calculate direct and indirect costs, such as main and sub disease codes, NHI costs, distinguishable variables for inpatient or outpatient care, and other variables, this data source provided key information. In addition, since statistics of mortality from the Korea National Statistical Office provide information about cause of death, we are confident that number of deaths-by-cause reported in this study is accurate. KNHNES data, which was used to calculate transportation expenses, has been established by the Korea Center for Disease Control and Prevention and is comprised of survey data based on a representative, extracted sample. To calculate caregiver costs, we used the public notice amount as the estimated daily worker’s wage based on legal criteria for payment of caregivers. The variables related to indirect costs calculations, such as daily average wage, annual work days and employment rate, were derived from statistics on employment and labor by the Ministry of Employment and Labor. Therefore, the data used in this study was established based on representative data sources.It is important to note that our study had several limitations. First, our estimates are likely to be low, or conservative. We could not include some costs related to the healthcare expenditures, such as public health promotion activities and health education due to data source limitation. However, other studies have shown that these costs represent a small proportion of total costs , 34. FurOur study is significant because it analyzed trends over the last six years of economic burden and the epidemiological index of AMI using recent data. These analyses demonstrate the importance of improving the quality of disease management, not only to promote awareness of the current epidemiologic status of this disease, but also so that decision makers can implement evidence-based policies. In this respect, our study provides reliable COI data and indirectly reflects the performance of national projects related to prevention of cardiovascular disease. We believe that our study will offer meaningful information to the decision makers of the Korean government.


Flavonoids are a group of phenolic secondary plant metabolites that are ubiquitous in plant-based diets. Data from anthropological, observational and intervention studies have shown that many flavonoids are bioactive. For this reason, there is an increasing interest in investigating the potential health effects of these compounds. The translation of these findings into the context of the health of the general public requires detailed information on habitual dietary intake. However, only limited data are currently available for European populations.The objective of this study is to determine the habitual intake and main sources of anthocyanidins, flavanols, flavanones, flavones, flavonols, proanthocyanidins, theaflavins and thearubigins in the European Union.We use food consumption data from the European Food Safety Authority (EFSA) and the FLAVIOLA Food Composition Database to estimate intake of flavonoids.Mean (±SEM) intake of total flavonoids in Europe was 428±49 mg/d, of which 136±14 mg/d were monomeric compounds. Gallated flavan-3-ols (53±12 mg/d) were the main contributor. The lowest flavonoid intake was observed in Mediterranean countries (monomeric compounds: 95±11 mg/d). The distribution of intake was skewed in many countries, especially in Germany .The habitual intake of flavonoids in Europe is below the amounts found to have a significant health effect. Acacia, catechu, has been described as astringent in European pharmacopoeias since almost 400 years FLAVIOLA eviously , respecteviously . This daeviously –44. Wheneviously , are notWe present estimated mean and median values of flavonoid intake in mg/d. Further tables are based on mean intake values to allow for comparison with other studies. The European countries represented in the EFSA comprehensive database were grouped in regions to allow for observations in each distinctive area . Unless indicated otherwise, all data are given as the mean daily intake of the respective flavonoid.The flavonoid consumption data used in this study is available as The data available do not allow any statistical analyses, for example a comparison between different countries. Means shown are not weighted. Data analyses were conducted with R 3.1 .Data on flavonoid intake in adults was available for fourteen European countries, based on surveys of more than 30,000 participants . All stuThe highest intake of monomeric flavonoids was also found in the Central Region (157 mg/d), followed by the Northern (124 mg/d) and Southern (95 mg/d) Region. The distribution of intake was skewed for all compounds with a considerably lower median intake for all flavonoid classes. The main type of monomeric compounds consumed were flavan-3-ols, of which 53 mg/d were gallated and 24 mg/d non-gallated compounds.There were noticeable differences in flavonoid intake between different countries and European regions . This waWhereas tea was the main contributor to dietary theaflavins and thearubigins, there was a wider variety of sources for proanthocyanidins , Fig 4. The contribution of different compounds to total flavonoid intake is summarised in Epigallocatechin-3-gallate (EGCG) is the main type of gallated compounds consumed (21 mg/d) and (–)-epicatechin the main non-gallated monomeric flavan-3-ol. The consumption of all other types of flavonoids, except for quercetin (14 mg/d), was much lower.vs 3 mg/d) and more than 80-fold higher when including polymeric compounds (523 mg/d vs 7 mg/d). It was noticeable that for some compounds, i.e. gallated flavan-3-ols, anthocyanidins, flavanones and flavones as well as theaflavins and thearubigins, median intake in Germany was 0 mg/d. A similar, although less extreme, distribution was observed in Belgium . Conversely, mean and median intake were very similar both in Ireland, both for monomeric compounds (249 mg/d vs 206 mg/d) and total flavonoids (851 mg/d vs 733 mg/d). The distribution of intake was most skewed for flavanones, were median intake was 0 mg/d in most countries.The data available did not provide much information about the distribution of intake except for median and mean values and these data allows only a limited assessment. The distribution of intake was skewed for most compounds and countries, as median intake was always lower than mean intake. This was in particular noticeable in Germany were mean monomeric flavonoid intake was more than 60-fold higher than median intake  or National Health and Nutrition Examination Survey (NHANES) in the US, would have allowed a better exploration of the data available. However, despite these limitations this study, in particular in combination with our previous research , provideThere is a paucity of data on flavonoid intake in the general public and only few estimates exist.vs 9 mg/d for Ireland; 69 mg/d vs 16 mg/d for the UK) and flavanones , whereas their estimates for monomeric flavan-3-ols are lower . Due to differences in the methodologies used, it is difficult to explain the reason for these differences. Zamaro-Ros et al. conducted one of the most detailed analysis of total flavonoid intake in the different centres of the European Prospective Investigation into Cancer (EPIC) study [vs 23 mg/d), flavanone (35 mg/d vs 14 mg/d), anthocyanidins (31 mg/d vs 19 mg/d) and proanthocyanidin (207 mg/d vs 124 mg/d) intake were considerably higher than in our study. However, there are some important differences: Firstly, the participants of EPIC are not a representative selection of the general public with some cohorts contributing only women or men and the cohorts consisting of mainly healthy, middle-aged participants, and because of volunteer bias, participants are likely to have more interest in diet and health and therefore a different diet. Secondly, intake assessment in EPIC is based on dietary data collected in the 1990s, and it is likely that dietary habits have changed.Johannot and Somerset  reanalysC) study , 52–54. vs 19 mg/d), flavanones  and flavones  was considerably lower and it is mainly monomeric and polymeric flavan-3-ol that is higher , although the consumption of anthocyanidins  is higher in the US population, but intake of flavones (4 mg/d vs 1 mg/d) and in particular anthocyanidins (9 mg/d vs 19 mg/d) is considerably lower. Indeed, the intake of anthocyanidins is lower than in all European countries except for Ireland. It is more difficult to compare intake of flavan-3-ols or total flavonoids, as Bai et al. did not include thearubigins. However, it is noticeable that the intake of gallated compounds is lower than intake in Europe (27 mg/d vs 53 mg/d) whereas the intakes of (–)-epicatechin (68 mg/d vs 14 mg/d) and (+)-catechin (84 mg/d vs 10 mg/d) are much higher. This is surprising as such a pattern of intake is difficult to explain as the main sources of (–)-epicatechin and (+)-catechin also contain similar or higher amounts of gallated compounds and thus it is not clear how such high intakes can be achieved.Based on data from NHANES, Bai et al.  estimateThere were large regional differences, both in the type of flavonoids consumed and the distribution of intake. We have discussed differences in the consumption of flavan-3-ols, in particular gallated compounds and proanthocyanidins, in great detail previously , but theIn this and previous studies , we haveThe distribution of intake is very skewed, with higher mean than median intake. This is in particular noticeable for compounds with high intake such as monomeric and polymeric flavan-3-ols , but alsThe mean intake of flavonoids in Europe is lower than the amounts suspected to result in adverse effects  and it iResults from observational studies are ambiguous and failed to show a clear association between flavonoid intake and health, especially for cardio-vascular diseases and all-cause mortality. Studies investigating these associations did not show significant trends suggestive of a dose-response effect, and beneficial effects are mainly observed when comparing the quantiles with lowest and very low intake , 15. As Previously, we have shown that flavan-3-ol intake in the general public is much lower than the amounts used in most dietary intervention studies  and thatOur results provide a detailed overview of flavonoid consumption in European adults. These results allow for a comparison of habitual intake in the general public with the amounts used in dietary intervention studies. Our data suggest that habitual intake of most compounds is likely too low to result in a reduced risk of cardio-vascular diseases, but also too low to result in adverse effects. However, a lack of systematic reviews and meta-analyses of intervention studies makes these comparisons difficult. Further research is required to investigate the potential health benefits of flavonoids, in particular the primary prevention of chronic diseases in the general public. It is in particular important to use standardised and validated analytical methods and a consistent nomenclature of compounds to ensure that results are comparable. Furthermore, the development of improved dietary assessment methods, especially using nutritional biomarkers, is important to investigate the potential health effects of flavonoids in larger observational studies.An important result of our study was the skewed distribution of flavonoid intake, especially in Belgium and Germany. In both countries, half of the adult population consumed only negligible amounts of monomeric and polymeric flavonoids. Most observational studies conducted so far have found the highest risk of cardio-vascular diseases with very low flavonoid intake –14, and S1 File(CSV)Click here for additional data file.


Infant-directed speech (IDS) provides an environment that appears to play a significant role in the origins of language in the human infant. Differences have been reported in the use of IDS across cultures, suggesting different styles of infant language-learning. Importantly, both cross-cultural and intra-cultural research suggest there may be a positive relationship between the use of IDS and rates of language development, underscoring the need to investigate cultural differences more deeply. The majority of studies, however, have conceptualized IDS monolithically, granting little attention to a potentially key distinction in how IDS manifests across cultures during the first two years. This study examines and quantifies for the first time differences within IDS in the use of baby register (IDS/BR), an acoustically identifiable type of IDS that includes features such as high pitch, long duration, and smooth intonation , and adult register (IDS/AR), the type of IDS that does not include such features and thus sounds as if it could have been addressed to an adult. We studied IDS across 19 American and 19 Lebanese mother-infant dyads, with particular focus on the differential use of registers within IDS as mothers interacted with their infants ages 0–24 months. Our results showed considerable usage of IDS/AR (>30% of utterances) and a tendency for Lebanese mothers to use more IDS than American mothers. Implications for future research on IDS and its role in elucidating how language evolves across cultures are explored. While the language capacity itself may be inherited, languages—including how meanings emerge as well as how they are shared and understood—are passed on through cultures.Language is both a biological and a social phenomenon  and a  produced by mothers as they interacted with their infants. Across many languages and cultures, IDS has been described as a special way of addressing infants, characterized by salient acoustic features such as exaggerated prosody –10, longThe potential importance of the distinction is clear: parents across cultures do not speak with their children using the same vocal range or register throughout the day. They sometimes switch between registers rather seamlessly, one moment addressing their infant in IDS/BR (as in the case of looking at the infant and telling her how cute she is) and another moment using IDS/AR (as in the case of telling the infant it is time for a bath).IDS/BR is thought to have evolved as a species-specific adaptation , 17, whewithin IDS. This lack of quantification of register usage results in the presumably unintentional implication of IDS as a monolithic, static construct . Still,but see, , and thi infants , 38.Recent evidence suggests that IDS is not used uniformly across cultures , nor is In the present study, we focus on cross-cultural similarities and differences in the use of IDS among a group of Lebanese Arabic-speaking and a group of American English-speaking mothers as they communicated with their 0–24 month infants, and we seek answers to the following research questions:What is the relative frequency of usage of IDS/BR and IDS/AR in parents of these Lebanese Arabic-learning infants and parents of these American English-learning infants?Do parents of these Lebanese Arabic-learning infants and parents of these American English-learning infants differ in IDS Utterances per Minute  spoken to their infants?Do parents of these Lebanese Arabic-speaking and American English-speaking parents differ in the relative use of IDS/BR and IDS/AR within their respective cultures as well as across cultures?What is the impact of language, register type, and infant age on IDS Utterances per Minute ?Answers to these questions should better characterize the cross-cultural nature and variability of IDS and help to elucidate how language evolves across cultures. The uniqueness of our approach, to our knowledge, lies not only in the comparison of these particular cultural groups, but also in the fact that we quantify the utilization of IDS/BR and IDS/AR across the languages.This research was approved by the Institutional Review Boards at the University of West Georgia and the University of Memphis. All parents completed an informed written consent to participate in the study. The study combines two independently developed recording sets, one for Lebanese-Arabic families and one for American-English families.Arabic and English served as target languages because they are both among the most widely spoken languages in the world, with English being second and Arabic fourth . In addiThe first author had recorded parent-infant interactions in Lebanon, where virtually everyone’s first language is Arabic. The Arabic-speaking Lebanese mothers and their infants  were recruited from two private and two public pediatric clinics in Lebanon. All mothers spoke to their infants in Ammiya.In collaboration with the Infant Vocalizations Project at the University of Memphis, where an archive of roughly similar recordings exists based on prior research, we sought to develop a maximally matching sample from English-speaking families in the United States to parallel the Lebanese sample in participant demographics, namely infant age, infant gender, and maternal education. The resulting study participants consisted of 38 mother-infant dyads  We emphasize that the samples for this cross-university collaboration were not perfectly matched either in demographics or in recording procedures because the study was opportunistically designed after all the recordings had been obtained from both cultures.The Lebanese Arabic samples were audio-recorded in the infants’ homes using high fidelity equipment  with built-in stereo microphones. Prior to the recording sessions, the Lebanese mothers were instructed by the experimenter to interact for 10 minutes with their infants as they normally did at home. Mother-infant dyads participated in the recording sessions with no children present, and only occasional interaction between the mother and the experimenter  occurred as necessary e.g., to help manage recording equipment. This occurred in 9 out of the 19 Arabic recordings, with minimal adult-to-adult talk  per recording.The American English samples were digitally recorded for audio  in TF32  using wiThe first author, who is a speaker of Arabic as L1, English as L2, and French as L3, served as the primary coder. The second author, who is a speaker of Mandarin as L1, Southern Min as L2, and English as L3, served as the reliability coder. Both the primary and secondary coders coded all 38 sessions completely independently. The primary analysis was based on the first coder’s work, since she knew both target languages.Mothers’ utterances were coded in PRAAT , which iany one of the following nine qualities: (1) pitch or pitch range notably exceeding that of typical adult-to-adult speech; (2) long duration per syllable compared to adult-to-adult speech; (3) smooth intonation with a soothing tone, the kind of intonation described by [A coding scheme was developed for this study classifying parent utterances into a number of mutually exclusive acoustically-based categories that were later collapsed for analysis into IDS/BR and IDS/AR. Utterances were treated at analysis as IDS/BR if they were judged intuitively  to include ribed by , 48; (4)ribed by ; (6) verribed by ; (7) immIDS/AR, which to our knowledge has not been directly quantified in previous cross-cultural research.This coding system is not based on the semantic content of the caregiver utterances. Instead it focuses on IDS features judged on acoustic/prosodic  grounds that are thought to be shared across languages as features marking motherese. We chose them precisely to guide judgments of coders who may or may not be familiar with the target languages, and the coder agreement data to be presented below confirms that the two selected coders, with very different language backgrounds, produced quite concordant codes for IDS/BR and IDS/AR. Some of the features we used to designate IDS/BR have not been considered, to our knowledge, as characteristics of IDS in prior literature. In part the decision to include all these features as properties of IDS/BR was intended to ensure that we did not overestimate the amount of The primary dependent variable in this study was the number of maternal utterances in each of the 10-minute samples expressed in IDS Utterances per Minute. We also determined the duration of maternal utterances and derived IDS Seconds per Minute for an additional analysis which sheds important additional light on the findings. The statistical design entailed a mixed multivariate within-between factorial analysis of covariance (MANCOVA) in SPSS.Session-level intercoder reliability (N = 19) was measured using Intraclass Correlation (ICC), with a Two-way Random model to compute absolute agreement . For AraDescriptive statistics are presented in F  = 45.55, p < .001, partial eta squared = .57, reflecting more IDS/BR than IDS/AR in both Language groups and a statistically significant interaction of Register by Age, Wilks’ Lambda = .62, F  = 21.54, p < .001, partial eta squared = .38, reflecting the fact that mothers in both Language groups produced relatively more IDS/BR Utterances per Minute to their younger infants, while they produced relatively more IDS/AR to their older infants  = .05, p = .82, partial eta squared = .00. There was a statistically significant effect of Language, F  = 8.43, p = .006, partial eta squared = .19, with the Lebanese mothers using more IDS Utterances per Minute across both Registers than the American mothers  = 47.40, p < .001, partial eta squared = .58, and Register by Age, Wilks’ Lambda = .68, F  = 16.62, p < .001, partial eta squared = .32, again indicating that IDS/BR was utilized more than IDS/AR and that the extent of IDS/BR usage was higher with infants at younger ages. No significant interaction of Register by Language was found, Wilks’ Lambda = .99, F  = .12, p = .74, partial eta squared = .00. The Language effect, however, did not reach statistical significance, F  = 2.0, p = .17, partial eta squared = .05 in the Seconds-per-Minute analysis, though it corresponded, as in the case of the Utterances-per-Minute analysis, to a larger amount of IDS by the Lebanese than the American mothers (8% more IDS/BR and 40% more IDS/AR).Another way to measure Seconds per Utterance varied in the two Language groups and across the Registers. The MANCOVA results for the Seconds-per-Utterance analysis were statistically significant for Register, Wilks’ Lambda = .85, F  = 6.38, p < .05, partial eta squared = .15, indicating that IDS/BR was utilized more than IDS/AR. However, the Register by Age interaction did not reach statistical significance, Wilks’ Lambda = 1.0, F  = .01, p = .92, partial eta squared = .00, suggesting that the extent of IDS/BR usage did not differ between infants at younger and older ages. Likewise, no significant interaction of Register by Language was found, Wilks’ Lambda = 1.0, F  = .01, p = .94, partial eta squared = .00. The Language effect did not reach statistical significance, F  = 2.09, p = .16, partial eta squared = .06, though it corresponded to longer utterances by the American than the Lebanese mothers (9% longer IDS/BR and 12% longer IDS/AR). Obviously, since Lebanese mothers’ voices in IDS occupied more time in the recordings than American mothers’ voices, the greater number of Utterances per Minute of the Lebanese mothers more than counterbalanced the tendency for American mothers to use longer utterances. The tendency for American mothers to use longer utterances was not, however, consistent across Age.The differences between these two analyses would not occur if average utterance durations had not varied across groups. within IDS (IDS/BR vs IDS/AR) for different languages. The results revealed the expected higher frequency of IDS/BR compared to IDS/AR for both languages, but the high rate of IDS/AR was unexpected, with mothers producing 33% of their utterances in IDS/AR. Especially surprising was the fact that mothers at all infant ages and in both languages produced at least some IDS/AR in these 10-minute samples. In contrast, the higher rate of IDS/AR at older infant ages for both language groups was not surprising, presumably because infants become increasingly able to understand adult speech as they get older [While others have reported differences in patterns of IDS for different developmental levels  and acroet older  and thuset older , 38.interdependence, courtesy, and social interconnectedness. In keeping with this reasoning, we speculate that the Lebanese mothers may have talked more to their babies  simply as a reflection of a somewhat greater inclination to foster interdependence in the infants.The key difference in IDS between the two language groups was the higher rate in Utterances per Minute of IDS of the Lebanese as opposed to the American mothers. Here, we can only speculate about possible reasons.  suggesteOther possible reasons for more IDS Utterances per Minute in the Lebanese mothers  are similarly speculative. Our inclination is to leave such issues to future research. The current exploratory study was underpowered (with only 19 infants per group across a two-year age span and a single recording) to yield very strong conclusions and does not provide a basis to evaluate many of the possible explanations that might be entertained.Further, our thoughts about language differences in IDS are complicated by the fact that the differences in amount of IDS for the two language groups were statistically significant only for the Utterances-per-Minute analysis. The Seconds-per-Minute analysis also showed more IDS from the Lebanese mothers, but the Language difference in this case was not statistically significant—the pattern was affected by a tendency of American mothers to produce slightly longer utterances and by the fact that this difference across the languages varied with age. Both analyses showed a strong Register effect (more IDS/BR than IDS/AR), and both showed a strong interaction of Register with Age, a pattern that hints that by the end of the second year, IDS/AR could be taking over as the predominant form of IDS in both language groups.This study was opportunistic, resulting in samples that were less than perfectly matched. It also relied on cross-sectional data, relatively brief durations of mother-infant interactions, and slightly different instrumentation for recording mother-infant interactions across the Lebanese and American cultures. The location of the recordings (home versus laboratory) also differed across the two groups. The impact of this difference is less likely to change the pattern of results we obtained, however, as research suggests similar results in mother-child interactions across the home and laboratory settings , 58, espFurther, we only focused on maternal input and did not address the infant’s contribution to the interaction. This is not trivial, especially considering research on mother-child interaction and the bidirectional role that each member of the dyad plays in the process of early vocal development , 61. ImpA final thought is that it would be enormously preferable to obtain recordings in both audio and video so that coding could be conducted across a variety of modalities of parent and infant action, encompassing vocalization, gaze, facial affect, gesture, posture, and physical proximity. A more comprehensive approach including these sorts of improvements would allow a much fuller portrayal, illuminating the role of IDS/BR and IDS/AR in supplying human infants with a human-specific niche for language learning, and presumably with culturally-specific forms of the human language environment.


Psychological stress is common in relation to the care needed for patients with chronic diseases. In addition, diabetes (DM) can present major impact on patients' lives and the degree of satisfaction with the established treatments. Patients without adequate glycemic control may be exposed to greater stress.To assess the impact and the degree of satisfaction in the quality of life of patients with psychological stress related to DM in elderly patients without adequate glycemic control.We performed a historical case-control study of diabetic patients in the Endocrinology Department of a Brazilian tertiary hospital who were treated between June and December 2014. We include patients over 60 yrs. of age, of both sexes, with HbA1c ≥ 8.5% using oral hypoglycemic agents and insulin. Patients were submitted to BPAID (Problems Ares in Diabetes – Brazil) and DQOL  questionnaires, both validated in Portuguese. The first evaluates emotional stress related to DM in 20 questions. On the second, we use the variables “impact” and “satisfaction” to evaluate quality of life. There were 33 issues. We divided the patients into two groups, according the mean of score BPAID (39.45). There are no pre-defined cutoff point for this BPAID questionnaire. The higher the final score, the greater the stress related to DM.Forty-five patients were included. There were no differences between the groups for age, gender, education, race, religion, smoking and alcohol. There was no difference in HbA1c  in the moment of interview. However, the HbA1c levels was greater in the year preceding study in patients with the worst stress scores . Number of medicines used, dose of Insulin UI/kg, number of daily insulin injections or use of Regular insulin, weight, presence of hypoglycemia, blood pressure levels, or presence of chronic complications associated were not different. Patients with higher levels of stress presented greater negative impact of diabetes on quality of life compared to patients with lower levels of stress (p<0.001). Results were similar with respect to the degree of satisfaction (p<0.001).Emotional stress associated with DM can be related with worse quality of life in elderly diabetics and chronic glycemic uncontrol. Differences between social characteristics or relating to the treatment of DM did not differ between groups.


Objective: To compare the incidence of adverse events between active and placebo arms of randomized clinical trials in depressive children and adolescents (C&A) with antidepressant treatments, in order to look for similarities in both groups that allow to establish a possible nocebo effect.Methods: Systematic search strategy (January 1974–March 2013) in electronic databases, conference abstracts, and reference list of systematic reviews and included studies to identify parallel randomized placebo-controlled trials of antidepressants in C&A (<19 years) with major depressive disorder, and one or more interventions of any orally administered antidepressant. The pooled adverse events were calculated based on a fixed-effect model and statistical analysis involved the risk ratio (RR) of adverse events, with 95% confidence intervals (95% CI).Results: Sixteen studies were included in the review, of which seven studies with a sample of 1911 patients had data to include in the meta-analysis. There was similar risk for the incidence of adverse events between non-active and active group .Conclusion: Depressive C&A allocated to placebo or active group had similar risk to develop adverse events. These similarities in both groups are attributed to the nocebo effect. It is of note that defining “nocebo” effects is challenging in clinical populations because adverse effects may be attributed to the intervention or may be manifestation of the disease itself. The inclusion of a no-treatment arm may be warranted. Nocebo effects are likely when adverse events of placebo mimic the adverse events of active treatment, as was the case here. The use of antidepressants for children and adolescents (C&A) is still a matter of debate due to questionable efficacy and risk of adverse events. The efficacy of these medications appears to be influenced by patient such as function indication, age, chronicity, and study characteristics   may be a “nocebo” or it may be somatic manifestations of the disease itself. Additionally, factors related with NE have been identified in the pediatric population that may lead to confusion, such as divergent behaviors of the disease and parental/cultural influence   independently screened the titles and abstracts to determine the potential usefulness of the articles. Eligibility criteria were applied to the full text articles during the final selection. We resolved disagreements by consensus and by a third reviewer (Herney Andres Garcia-Perdomo).All data were collected independently by two authors using a standardized data extraction sheet in Epi-Info™ 7.0 software . An independent reviewer (Francisco Javier Bonilla-Escobar) confirmed all data entries and checked at least twice for completeness and accuracy.We extracted variables related with characteristics of the article, study design, patient’s data, and AE. All types of adverse events were included since authors of included clinical trials did not provide detail on the nature of adverse event reported. When data were not available, this was noted.® (RevMan) to illustrate the judgments for each study.The Cochrane Collaboration risk of bias tool  was the effect measured of the primary outcome, with 95% confidence intervals (95% CI). The efficacy of antidepressant treatment was defined as the standardized mean difference (SMD) between baseline and post-treatment values on depression scales. AE were only evaluated over the course of the intervention.® .Included trials were characterized with descriptive statistics and median with 25th–75th percentiles (p25–p75) such as central tendency and dispersion measures. Quantitative data were analyzed with non-parametric tests, due to their non-normal distribution assessed by Shapiro–Wilk method. The confidence level was 95%, and these analyses were performed on Stata13I2 statistic, which indicates the percentage of variation in the effect size estimate attributable to heterogeneity rather than sampling error   and drug category  through RevManThe relative RR was used for all primary analyses, and the Mantel–Haenszel random effects model was used for sensitivity analysis ; however, there were significantly more adolescents in the SSNRI trials than in TCA trials (p = 0.002). The median age for all included participants was 13 (10–16), and it was similar for participants in the non-active and active group (p = 0.67).In the age group analysis, nine out of 16 studies were carried out in both age groups (C&A), six trials were performed just in adolescents and one trial included only children . There was a significant difference between the proportion of males and females by pharmacologic group, with a higher proportion of males in the TCA studies and a majority of females in SSRI and SNRI studies (p = 0.0074).All studies included both genders. In the 14 trials that reported the participants’ gender (3389 patients), 54% were female. Of those, 40% were allocated in non-active and 60% in an active group .The median intervention period had 56 (56–63) days of exposure to a drug, with 56 (30–84) days to SSRI, 70 (70–70) to SNRI, and 56 (42–56) days to TCAs, without significant differences , 10 using the Children Depression Scales-Revised (CDS-R), and 8 using the Kiddie-Schedule for affective disorders and schizophrenia for school-age children (K-SADS-P). All the trials assessed the efficacy of the drug as the primary outcome. The most frequent primary outcome measure tool used was CDRS-R in 11 trials, while three used Hamilton Depression Rating Scale, one used the Montgomery and Asberg Depression Rating Scale (MADRS) , nor by pharmacologic group (p = 0.93).The total number of dropouts was 779, whereof 63% were allocated in the active group. The total rate of discontinuation was 22% with median discontinuation rate for placebo and active groups of 20% (11–38) and 25% (14–43), respectively. There were no statistically significant difference . Around 90% of the trials had high risk of attrition bias, related to withdrawals and dropouts. All trials had an unclear risk of selection bias, associated to the lack of information about the allocation concealment process. Nearly 85% of trials had low risk of other bias, considering the comparable condition of the arms in their baseline characteristics. In all, 75% of studies were unclear about the masking method, although all trials were defined as double blinded Figure .Cochrane’s tool was applied to 13 published studies, which provided the necessary information in order to do a judgment regarding the conduct and report of adverse events. The most frequent AE evaluation strategy was structured assessment (eight out of 16), using weekly scales, checklist, and questionnaires. The combination of assessment methods (five out of 16) consisted in spontaneous reports, physical examination of patients in each visit, and observation by investigators, while two trials used either spontaneous report of symptoms by the patient or observation and physical examination by the care professional in charge. One trial did not provide information on its assessment strategy for AE , nausea , dizziness , abdominal pain , vomiting , insomnia , somnolence , and decrease appetite ; these are reported according to the rank of frequency of AE in placebo groups. Of the above symptoms, nausea, vomiting, insomnia, and dizziness had more significant risk to be present in patients taking antidepressants, compared to non-active treatment .I2 = 0%), and there was no increased risk in developing them in patients allocated to an active drug and those allocated to non-active . All the trials had similar risk to present AE in patients taking an active drug or taking placebo . The heterogeneity for the adverse effects’ RR was low . Nasopharyngitis was a NE, with RR 0.94 (95% CI 0.64–1.39).Following headache and nausea, abdominal pain upper, dizziness, and somnolence were the most common AE presented by patients of non-active groups . Abdominal pain was a NE with a RR 0.89 (95% CI 0.54–1.44).Following headache and nausea, dizziness, dry mouth, and respiratory disorder were the most common AE presented by patients of non-active groups . Headache and respiratory disorder were NEs, with RR 0.96 (95% CI 0.66–1.39) and 0.58 (95% CI 0.23–1.45), respectively. Of note, dizziness and dry mouth were significantly more common in the active treatment groups.I2 = 96%), and there was a mild, but statistically significant reduction in the depression score scales in patients taking an antidepressant drug as compared to placebo, with the estimates in the same direction   or a SNRI drug  in comparison to non-active drug Figure B. For paThe subgroup analysis by age was only done for efficacy. We included four trials that were conducted solely in adolescents, and one trial that involved only children. There was no difference in the decrease of the depression scales in children or in adolescents who took an active drug in comparison to non-active, although adolescents showed a better improvement   higher frequency in the non-active group. This phenomenon might be explained by random chance or be related to the association between depression and altered immune function  gene   the relative safety of antidepressants and (b) possible NE.Analysis of antidepressants’ efficacy for C&A showed an improvement of depression scales in patients taking SSRIs. Although SSRIs are the first line of pharmacological treatment for depressive C&A, there still remains a gap of knowledge regarding the safety profile due to suicidal-related attempts. For this reason, it is imperative to keep a constant monitoring of adverse events in patients undergoing SSRI treatment.Our findings highlight the similar risk of presenting AE for patients receiving placebo compared to antidepressant treatment. It is of note that in clinical context, as well as in the research arena, there are some aspects to identify and address in depressive C&A in order to decrease the NE. The influence of parents’ expectations, anxiety-related symptoms of depression, and “therapeutic rituals” might influence the nocebo phenomenon.The influence of NE over the adverse events’ profile of antidepressants still remains doubtful, and it may be necessary to conduct further studies that allow understanding of the nature of nocebo phenomenon, perhaps also with no-treatment arms. For future studies, it is necessary to implement standardized methods to assess and report AE in RCTs of antidepressants in C&A.It is imperative to clearly report methodological aspects of clinical trials in order to reduce the risk of bias related to randomization process, blinding of personnel and participants, allocation concealment method, and the report of dropouts and reasons for them. Strengthening these efforts should assure readers a complete understanding of the methodology and the quality of the results.Study concept and design: Dr. Linnman, Dr. Borsook, Dr. Becerra, Dr. Rojas-Mirquez, Dr. Rodriguez, Dr. Bonilla-Escobar, and Dr. Garcia-Perdomo. Acquisition of data: Dr. Rojas and Dr. Rodriguez. Analysis and interpretation of data: Johanna Carolina Rojas-Mirquez, Research Fellow in Anesthesia at Harvard Medical School; Milton Rodriguez-Zuñiga, Research Fellow in Anesthesia at Harvard Medical School; Francisco Bonilla-Escobar, Research Associate at Instituto Cisalva, School of Public Health, Cochrane Center at Universidad del Valle, Cali, Colombia; Herney Garcia-Perdomo, Researcher and Professor, Cochrane Center at Universidad del Valle, Cali, Colombia. Drafting of the manuscript: All authors. Critical revision of the manuscript for important intellectual content: Dr. Bonilla-Escobar, Dr. Garcia-Perdomo, Dr. Borsook, Dr. Linnman, Dr. Rojas-Mirquez, Dr. Rodriguez-Zuñiga, and Mr. Mike Petkov. Study supervision: Dr. Bonilla-Escobar, Dr. Garcia-Perdomo, Dr. Borsook, and Dr. Linnman.Dr. Rojas-Mirquez and Dr. Rodriguez-Zuñiga had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis, and also have contributed equally to the work. The authors report no biomedical financial interests or potential conflicts of interest, neither have published nor submitted any related paper from this study.http://www.frontiersin.org/Journal/10.3389/fnbeh.2014.00375/abstractThe Supplementary Material for this article can be found online at Click here for additional data file.


The present study analyses the relation between smoking status and the parameters used to assess vascular structure and function.This cross-sectional, multi-centre study involved a random sample of 1553 participants from the EVIDENT study. Measurements: The smoking status, peripheral augmentation index and ankle-brachial index were measured in all participants. In a small subset of the main population (265 participants), the carotid intima-media thickness and pulse wave velocity were also measured.After controlling for the effect of age, sex and other risk factors, present smokers have higher values of carotid intima-media thickness (p = 0.011). Along the same lines, current smokers have higher values of pulse wave velocity and lower mean values of ankle-brachial index but without statistical significance in both cases.Among the parameters of vascular structure and function analysed, only the IMT shows association with the smoking status, after adjusting for confounders. A consistent relationship has been demonstrated between cigarette smoke exposure and the progression of carotid atherosclerosis , with a The EVIDENT study is a cross-sectional and multi-centre study of six patient groups distributed throughout Spain. Participants, aged 20–80 years, were selected by stratified random sampling. The following exclusion criteria were applied: known coronary or cerebrovascular atherosclerotic disease, heart failure, moderate or severe chronic obstructive pulmonary disease, walking-limiting musculoskeletal disease, advanced respiratory, renal or hepatic disease, severe mental disease, treated oncological disease diagnosed in the past 5 years and terminal illness. The study was approved by an independent ethics committee from Salamanca University Hospital (Spain), and all participants provided written informed consent according to the general recommendations of the Declaration of Helsinki. The recruitment and data collection were conducted between 2011 and 2012. A total of 1553 individuals were included in the study. The sample size calculation indicated that this number was sufficient to detect a difference of 5 units in the peripheral augmentation index between 3 smoking statuses  in a two-sided test, assuming a common standard deviation (SD) of 21 units with a significance level of 95% and a power of 90%. The IMT and PWV were measured in only 265 participants, but this number was sufficient to detect a 0.05 mm difference in the IMT between the 3 groups, assuming a SD of 0.1, a significance level of 95% and a power of 80%. The findings presented in this manuscript are a subanalysis of the EVIDENT study, the main results of which were recently published .Smoking history was assessed by asking questions about the participant’s smoking status. For the analyses, the participants were classified as non-smokers, former (>1 year without smoking) or present smokers. Carotid ultrasonography to assess intima-media thickness of the common carotid artery (C-IMT) was performed with the Sonosite Micromax ultrasound device  paired with a 5–10 MHz multi-frequency high-resolution linear transducer. Sonocal software was used to perform automatic IMT measurements. Six measurements were performed on each carotid artery using average values (average IMT) and maximum values (maximum IMT) automatically calculated by the software. The measurements were taken following the recommendations of the Manheim Carotid Intima-Media Thickness Consensus . CarotidStatistical normality was checked using the Kolmogorov–Smirnov test. Normally distributed continuous variables were expressed as the mean ± standard deviation, while non-normally distributed variables were presented as median and 75–25th percentile. Frequency distribution was used for the categorical variables. The difference in means in continuous variables between the smoking categories was analysed using a one-way analysis of variance for independent samples and the post-hoc Scheffé contrast, with alpha <0.05 and the Kruskal–Wallis test when the variables were not normal. Chi-squared tests were used to compare the differences in categorical variables.Age, sex, blood pressure, heart rate, and the presence of obesity, diabetes and vascular drugs have shown to affect the PWV, IMT or augmentation index values. Therefore, it is necessary to control the effect of these variables in the relationship between smoking status and the parameters of vascular structure and function. To analyse the relationship between the vascular structure and function  and smoking status , a general linear model (GLM) analysis was performed, including age, sex, systolic blood pressure, heart rate, body mass index, HDL cholesterol, diabetes and the presence of antihypertensive, antidiabetic and lipid-lowering drugs as the adjustment variables. The non-normal variables were modelled as continuous variables with log transformation to achieve normality in the multivariate analysis. Data were analysed using the SPSS version 18.0 statistical package , and p < 0.05 was considered to be statistically significant.Table Table Table After controlling for the effects of age, sex, systolic blood pressure, heart rate, body mass index, HDL-cholesterol, diabetes and the presence of antihypertensive, antidiabetic and lipid-lowering drugs, the multivariate analysis shows that present smokers have higher IMT values (p = 0.011). PWV behaves likewise, although it does not reach the level of statistical significance. ABI has no modifications, and PAIx75 has higher values in current smokers than in former smokers Figure . More deIn this paper, we present data about the relationship between smoking status and a large variety of parameters that assess vascular structure and function in a general population sample from primary care clinics. To assess vascular structure and function, parameters differ in their relationships with cardiovascular risk factors. The results of this work show that IMT is the parameter that best relates to smoking status in a representative sample of adult population. After controlling for the effects of sex and other confounders, present smokers have higher mean IMT values (p = 0.011), while the differences in PWV, PAIx75 and ABI did not reach the level of statistical significance.The study results concerning the effects of smoking status on subclinical arterial disease align with those of other authors ,2, indicAfter controlling for confounders, we found no association between the presence of smoking and increased arterial stiffness. In a systematic literature review, Doonan RJ et al.  found thPrevious studies have demonstrated an association between AIx and cardiovascular risk factors, including smoking ,23. In oPresent smokers have lower ABI values, similar to the results of other authors ,26. HoweThe main limitation of this study is the cross-sectional design that prevents the establishment of causal relationships between smoking and vascular structure and function. The participants of the three smoking categories differed in terms of age and the prevalence of other risk factors. This limitation is, to some extent, addressed by the statistical analysis that controls the effect of these variables in the interpretation of results. Another limitation of this study is that the smoking status was self-reported and not determined by objective measures, such as CO in the expired air analysis; however, such questionnaires have been used previously in other studies to explore the relationship between arterial stiffness and smoking . Lastly,Among the parameters vascular structure and function analysed, only the IMT shows association with the smoking status, after adjusting for confounders. Further studies focusing on the smoking statuses of participants are necessary to clarify the role of the chronic effects of smoking on the parameters of vascular structure and function and the effects of passive smoking exposure.BMI: Body mass index; PAIx75: Peripheral or radial augmentation index adjusted for heart rate at 75 bpm; ABI: Ankle brachial index; IMT: Intima-media thickness of the common carotid artery; PWV: Pulse wave velocity.The author’s declare that they have no competing interests.JIR devised the study, designed the protocol, assisted with fund raising and results interpretation, prepared the draft of the manuscript and corrected the final version of the manuscript. MAG, CM, EI and AM participated in the study design, results interpretation, and manuscript review. CA participated in the study design, data collection and manuscript review. MCP performed all analytical methods, results interpretation, and manuscript review. LG participated in the protocol design, fund raising, analysis of results, and final review of the manuscript. Finally, all authors reviewed and approved the final version of the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/13/109/prepubCharacteristics of patients by smoking status in the 265 subjects for whom the IMT and the PWV was assessed.Click here for fileMultivariate analysis of structure and function vascular parameters with smoking status (GLM).Click here for file


Diagnostic laboratory tests are routinely defined in terms of their sensitivity, specificity, and ease of use. But the actual clinical impact of a diagnostic test also depends on its availability and price. This is especially true in resource-limited settings such as sub-Saharan Africa. We present a first-of-its-kind report of diagnostic test types, availability, and prices in Kampala, Uganda.Availability Index (AI). AI is the combined daily testing volumes of laboratories offering a given test, divided by the combined daily testing volumes of all laboratories in Kampala. Test prices were based on a sampling of prices collected in person and via telephone surveys in 2015.Test types (identity) and availability were based on menus and volumes obtained from clinical laboratories in late 2011 in Kampala using a standard questionnaire. As a measure of test availability, we used the Test volumes and menus were obtained for 95% (907/954) of laboratories in Kampala city. These 907 laboratories offered 100 different test types. The ten most commonly offered tests in decreasing order were Malaria, HCG, HIV serology, Syphilis, Typhoid, Urinalysis, Brucellosis, Stool Analysis, Glucose, and ABO/Rh. In terms of AI, the 100 tests clustered into three groups: high (12 tests), moderate (33 tests), and minimal (55 tests) availability. 50% and 36% of overall availability was provided through private and public laboratories, respectively. Point-of-care laboratories contributed 35% to the AI of high availability tests, but only 6% to the AI of the other tests. The mean price of the most commonly offered test types was $2.62 (range $1.83–$3.46).One hundred different laboratory test types were in use in Kampala in late 2011. Both public and private laboratories were critical to test availability. The tests offered in point-of-care laboratories tended to be the most available tests. Prices of the most common tests ranged from $1.83-$3.46. The impact of a laboratory test on health outcomes depends on characteristics that are intrinsic to the test such as its diagnostic accuracy, complexity, and result interpretability. It also depends on characteristics that are extrinsic to the test such as commercial demand, price, and availability.,2 These According to estimates of the Institute for Health Metrics and Evaluation (IHME), HIV, TB, and malaria accounted for 29% of deaths in this region in 2010. Thus in et al. showed that 96% of laboratories in Kampala were private and these private laboratories produced 65% of the aggregate testing volume.[Where comprehensive, international initiatives do exist to document health and laboratory services, they are focused on the public sector. This selg volume.This deficit of knowledge of the full landscape of laboratory testing outside of the public sector deprives policy makers, funders, and test developers of the ‘on the ground’ information they require to understand diagnostic needs. In an effort to address this knowledge deficit, we report on test identity, availability, and prices in Kampala, Uganda. The data derive from a comprehensive survey of clinical laboratories in Kampala in late 2011, including the public and non-public sectors.A cross-sectional in-person survey of all clinical laboratories in Kampala, Uganda was performed during the last quarter of 2011. Details of the methods have been described previously. Briefly,Laboratories were also classified according to affiliation as public, private, academic, or non-governmental organization (NGO)/religious laboratories. Academic laboratories were only those associated with Ugandan academia and not foreign academia. For example, a laboratory primarily doing research testing sponsored by western research universities would be classified as ‘private’, not academic. Surveyors also classified each laboratory as either a point-of-care (POC) laboratory or a moderate/high complexity laboratory (hereafter referred to simply as high complexity). Laboratories performing only single-step kit tests, single test instruments, or simple light microscope examinations of patient samples were classified as POC laboratories. Finally, laboratories were graded based on the Stepwise Laboratory Quality Improvement Process Toward Accreditation (SLIPTA) checklist, and graded on an ordinal system (0 to 5 stars). Further Test menus as well as laboratory-wide daily test volumes were documented in-person by the surveyors. For the purpose of this report, hard copies of test menus were requested from the 31 laboratories with greater than 20 tests performed daily. This specific request was made to minimize the impact of potential surveyor error. These additional data were successfully collected from 14 of the 31 larger laboratories in March, 2014. In addition, in April, 2015, prices for the most commonly offered tests were obtained from a sample of 20 private laboratories . Prices wtest types, hereafter referred to simply as tests. For example, rapid diagnostic tests for malaria and blood smear microscopy for malaria were combined under the heading Malaria. On the other hand, some tests used for the same disease were kept separate, e.g., HIV serology, CD4 cell count, and HIV PCR. Furthermore, multiple formats of a test were combined into the same heading. For example, HIV serology tests could have been performed as a rapid lateral flow diagnostic or on an automated instrument, and there was no discrimination of whether tests labeled HIV PCR measured RNA or DNA. Also, when a laboratory did offer a panel we assumed it offered all of the individual components as well. For example, a laboratory offering a basic metabolic panel was treated as though it also offered electrolytes, renal function tests, and glucose. Ambiguous test names, e.g., “micro other”, were included in the analyses concerning testing volumes of each laboratory, but excluded from other analyses.Test menus were not uniform in terms of what individual tests were called. Some test names were based on the analyte, others on the related disease. Thus, in order to combine the data from different laboratories individual tests were combined into diagnostic disease One estimate for availability of a test is simply the number (or percent) of laboratories offering the test. But it is reasonable to assume that not all laboratories contribute equally to availability. For instance, a larger laboratory will be more likely to have reagents in stock and more likely to receive samples in blood collection tubes from clinics in a larger geographic area, increasing the population of patients they serve. To account for this, in most analyses instead of using the percent of laboratories that offered a test, we used the Availability Index, which weights the percent of laboratories that offered a test by the laboratory-wide test volumes of those laboratories. This index was calculated as the aggregate laboratory-wide daily testing volume of all laboratories offering a given test, divided by the aggregate laboratory-wide daily testing volume of all laboratories in Kampala, expressed as a percentage. The total daily testing volume for individual laboratories was for all tests offered in that laboratory and not just the daily test volume of the test of interest. For example, urinalysis was offered in 496 laboratories that together performed 10,720 tests daily , and the total testing volume daily in Kampala  was 13,189, therefore the urinalysis Availability Index is equal to 100*, or roughly 81%. The weighted percent of laboratories can range between 0 and 100% for each test.K-means clustering was implemented in Stata 12. One-dimensional cluster analysis was performed on the Availability Index. To choose the number of clusters used in the K-means algorithm, we used the elbow method. Briefly, we plotted the sum of the within-group sum of squares as a function of the number of clusters used in the K-means algorithm . lgorithm . The finIn order to provide context to the price of tests in Kampala, we queried the Center of Medicare and Medicaid Service’s schedule of laboratory fees to compare the U.S. price of similar tests. Test priTest menus and daily laboratory-wide test volumes were obtained from 95% (907/954) of the laboratories identified in Kampala city. Based on these 907 laboratories, 100 different types of tests were offered in the city .Tests varied widely in their availability. The 10 most commonly offered tests were offered in a median of 528 laboratories each, while the bottom 80 tests were offered in a median of 6 laboratories each. The 100 tests offered in Kampala clustered into 3 groups based on their Availability Indices . The fulPrivate laboratories offered 99 different types of tests, public laboratories offered 56 types of tests, religious/NGO laboratories offered 66 types of tests, and academic laboratories offered 19 types of tests.As the vast majority of laboratories in Kampala are private laboratories, the avaiLaboratories in the survey were also categorized based on whether they performed only simple POC tests, or also high complexity tests . POC labThe average price of a test in Kampala was $2.62  and the This report, based on a comprehensive survey of laboratories in Kampala, Uganda (population ~ 1.72 million), presents data on test availability and price in this sub-Saharan African city. It also describes the relationship of test availability to laboratory affiliation, such as private, public, NGO/religious, or academic, as well as laboratory complexity. There were 100 distinct test types offered in Kampala. These tests fell into three groups in terms of their relative Availability Index  and the average prices of the 10 most commonly offered tests ranged from $1.83-$3.46.and non-public laboratories. Compared to prior studies, this more comprehensive approach helped unearth unique information. For example we found 100 different types of tests in use in Kampala city, where the DHS Program Service Provision Assessment (SPA) typically surveys for roughly 25 tests.[This survey included all tests from both public 25 tests. Clearly,25 tests. However,However, this conclusion assumes that all 100 tests are available at a level needed for clinical care. Although disease burdens do vary between Kampalan and U.S. populations, overall testing per person in Kampala is 2 tests per person per year, contrasted with 20 to 30 tests per person per year in the United States. FurthermTest availability appears to follow burden of disease. For example, HIV and malaria rapid testing are highly available, while testing for prostate-specific antigen and testosterone are minimally available. Still, there are some peculiarities that deserve discussion.First, although tuberculosis represents a major burden of disease, tuberculosis testing does not appear in the high availability group. There are likely explanations for this. For example tuberculin skin testing (TST), an inexpensive screen for TB, is minimally available. While this may not seem rational at first, Uganda recommends use of BCG vaccination; thus reducing the utility of TST. Likewise, tuberculosis serological testing is in the minimal availability group, but this test has not proven to be useful for tuberculosis testing and as discussed below, the World Health Organization has recommended against its use. Acid fast bacilli staining and microscopy is an appropriate testing strategy for Kampala, but is only found in the moderate availability group. This is likely because it is a complex test while the high availability testing group consists nearly exclusively of tests that are available in easy to use, point of care formats see . This gaSecond, tests for non-communicable diseases, with the exception of glucose, were found in the moderately available group. This is likely because all these tests (except glucose) are offered nearly exclusively in complex laboratories while glucose testing is offered in POC labs as well as complex labs .Finally, some tests addressing relatively low burdens of disease are much more available than many tests addressing high burdens of disease. This can be understood in part by realizing that the ideal availability of a test depends on many factors beyond the burden of disease it addresses: cost of the test, accuracy of the test, clinical impact of the test , and use of the test in diseases that mimic more common diseases with higher burdens. For example, several accurate, inexpensive, and easy to use tests are available for syphilis testing , which may explain why syphilis testing is the 2nd most available test although it addresses a relatively low burden of disease. Likewise, brucellosis testing is relatively highly available while addressing a relatively low burden of disease. This could be due to availability of inexpensive lateral flow testing formats, high prevalence of brucellosis in Uganda with occasional outbreaks, and the fact that brucellosis is on the differential with more common non-specific febrile disease like malaria.Only public and private laboratories contributed significantly to the availability of high and moderate availability tests. Private and NGO/religious sectors were the primary contributors of the minimal availability tests, thus providing low volume, niche tests like Hb A1c, C-reactive protein, and HIV PCR. For example, contributions to the HIV PCR Availability Index were 58% from private laboratories, 26% from NGO/religious laboratories, and 16% from public laboratories. This pattern is consistent with recent literature demonstrating the significant impact the private sector has on health care in resource limited settings. For instance, The World Bank estimates that 74% of health care dollars spent in Uganda are spent in the private sector, and 50.5% of health care dollars spent in sub-Saharan Africa are spent in the private sector.However, the impact of private sector health care delivery is not always positive. The World Bank reported that the private health sector was regulated as intended in only 6 of 45 countries. To illusRegarding POC vs high complexity laboratory testing, our data are consistent with the prevailing idea that implementation of POC diagnostics can increase test access in resource-limited settings.,29 In ouet al. survey found that 704 out of 718 POC laboratories did not meet the lowest quality standards defined by the WHO/AFRO-derived laboratory strengthening tool (1–5 stars).[But a key concern of promoting additional POC testing is quality. Although there are very few laboratories of any type in sub-Saharan Africa that are accredited to international standards, smaller 5 stars). Thus theFinally, our data show that the most commonly offered tests are priced between $1.83 and $3.46. We estimate that a similar fraction of the household healthcare budgets in Kampala is spent on laboratory testing compared to levels in the US market. At a population level of 1.72 million and a daily testing volume of 13,189, citizens of Kampala, Uganda consume an average of 1.9 tests per year. In the United States this number is estimated at 20 to 30 tests per person per year, which isThis analysis had several limitations. First, the survey was conducted in 2011 and there may have been significant changes in the laboratory landscape since that time. For example, if more automated analyzers are being employed in Kampala, it would be likely that testing for non-communicable diseases—which are more commonly performed on automated analyzers—has increased. Second, the original survey only collected up to 18 tests per laboratory. Although this was sufficient for the majority of laboratories some didS1 Data Availability(ZIP)Click here for additional data file.S1 Fig(DOCX)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


The rising popularity of electronic cigarettes (e-cigarettes) has been accompanied by the proliferation of vape shops in the United States. Vape shops are devoted to the sale of e-cigarettes and e-juices. This study aimed to describe the age, gender, and ethnicity of customers who frequent these shops, determine whether conversations transpire between retailers and customers, as well as identify the types of activities taking place while customers are inside the store.A naturalistic observation study of 186 customers in 59 vape shops in Southern California was completed in locations that were relatively high in Korean, Non-Hispanic white, Hispanic, or African American ethnicity.Across all shops, the average estimated age of customers was 30.29 years old (SD = 9.70), 53 % were estimated to be non-Hispanic white, and 79 % were males; few minors entered the shops. Conversations about vaping related topics were prevalent . Purchases were commonly observed as well as customers lounging in the shop.Vape shops provide consumers a place to purchase and discuss e-cigarettes and offer an environment that serves as a place of recreation with customers lounging once inside. Findings should inform local tobacco control efforts and regulatory policies in the future. The recent and rising popularity of electronic cigarettes (e-cigarettes) has been accompanied by the proliferation of vape shops in the United States (U.S.) and elsewhere. Vape shops are devoted to the sale of e-cigarettes, providing a setting for customers to learn about different hardware from retailers, sample flavors, and socialize , 2. VapeWhat is missing from this literature is a description of the customers who frequent these shops , if conversations transpire between retailers and customers , as well as a description of types of activities that take place while customers are inside the store . The present study aimed to document vape shops in Southern California. Because tobacco-related behaviors vary by ethnicity , the preNaturalistic observation, developed in ethology, zoology, and anthropology , has beeThe locations (communities) of interest  were selected because each of these racial/ethnic groups has a unique tobacco use profile , and togObservation forms were used to code the approximate age of customers, gender, ethnicity, purchases made, and activities and conversations that took place. There was room to code two customers on each page of the form, and all customers observed in the shops during the data collection period were coded.r = .95, indicating high accuracy of the estimates made. These results converge with a previous age estimation study   16] and