Concentrations of plasma β-carotene and lutein declined in both the groups during the postpartum period but the decline was significantly less in the supplemented than in the control women at one month ; lutein -0.26 vs -0.49 μmol/L, p<0.05) and three months . Concentration of breastmilk retinol was also significantly greater in the supplemented group at three months postpartum than in the controls . Concentrations of infants’ plasma retinol, β-carotene, and lutein, measured at six months of age, did not differ between the groups. Fat supplementation during pregnancy and lactation in women with a very low intake of dietary fat has beneficial effects on maternal postpartum vitamin A status.Dietary fat intake is extremely low in most communities with vitamin A deficiency. However, its role in vitamin A status of pregnant and lactating women is poorly understood. The aim of the study was to examine the effect of supplementing women with fat from mid-/late pregnancy until six months postpartum on their vitamin A status and that of their infants. Women recruited at 5-7 months of gestation were supplemented daily with 20 mL of soybean-oil (n=248) until six months postpartum or received no supplement (n=251). Dietary fat intake was assessed by 24-hour dietary recall at enrollment and at 1, 3 and 6 months postpartum. Concentrations of maternal plasma retinol, β-carotene, and lutein were measured at enrollment and at 1, 3 and 6 months postpartum, and those of infants at six months postpartum. Concentration of breastmilk retinol was measured at 1, 3 and 6 months postpartum. The change in concentration of plasma retinol at three months postpartum compared to pregnancy was significantly higher in the supplemented compared to the control women  Vitamin A deficiency among pregnant and lactating women is widely prevalent in many developing countries –3 and poConventional approaches to combat vitamin A deficiency include periodic supplementation with vitamin A, fortification of foods, and a food-based approach with increased consumption of dark green-leafy vegetables. Among the intervention strategies, the dietary approach with an emphasis on increased consumption of provitamin A carotenoid-containing foods has been advocated as a preferable and sustainable strategy to eliminate vitamin A deficiency ,7. HowevStudies to date investigating the relationship between dietary fat and vitamin A status have been limited to investigations of efficacy in highly-controlled settings with a relatively-small number of subjects. Studies in children have shown that fat supplementation enhances the absorption of β-carotene and improves the vitamin A status . A studyThis community-based controlled trial was conducted from November 1995 to October 1997 in 16 villages in Matlab upazila (subdistrict) of Chandpur district, Bangladesh. The area, located approximately 55 km southeast of the capital city of Bangladesh—Dhaka, considered to be typical of rural and riverine delta areas . The usuSixteen socioeconomically-similar villages were grouped into two sets of eight each, separated by a distance of about 2 km. One set of villages was randomly selected for dietary intervention. It was felt that randomization of half of each selected area will have the same effect as would individual randomization in that both intervention and control groups will come from the same geographical area and community as each other. Therefore, any area-level effects are accounted for by the research design. The study participants were healthy pregnant women in their early or mid-pregnancy identified through menstrual history. A survey was conducted in the study villages to identify all currently-eligible women and also to list all married women of childbearing age, who could potentially become pregnant. A field team consisting of a health assistant, a community health worker (CHW), a dietary interviewer , and a porter visited each eligible subject at home and explained the study and meaning of their voluntary participation. A detailed interview on socioeconomic, demographic and household characteristics was conducted. Trained and experienced field workers measured body-weight, height, mid-upper arm circumference (MUAC) following standard procedures . Data onDuring the study period, 341 and 335 women were recruited from the intervention and control villages respectively . From thThe intervention consisted of unfortified soybean-oil supplied to the women in the intervention villages. The women in the control villages were not given any other dietary supplement or advice and maintained their usual diet. Each woman in the intervention villages was supplied with a weekly ration of 140 mL of soybean-oil and was asked to consume 10 mL of oil twice a day  with their main meals  as supplement. The community health worker (CHW) delivered the oil in a plastic bottle and a clearly-marked (at 10 mL) plastic dispenser to ensure the dose to each study woman in the home. Women were given several options to consume the supplement that included mixing of the oil with their foods, drinking during the meal, or frying their portion of the meal with the oil. However, pre-testing revealed that drinking during the meal was the most preferred choice of supplement intake, followed by mixing the oil directly with their meal portion. The study was, therefore, designed to supplement the diet in this way rather than instructing women to add oil during preparation of household food to ensure a measured ‘dose’ of oil for more accurate quantification of supplement intake. The total period of oil supplementation in an individual woman ranged from 8 to 10 months depending on the gestational ages of women at enrollment. The participants in the control group were not given any extra food to balance energy between the groups.Motivational efforts were continued throughout the study period to maximize high compliance to the intervention and to avoid any replacement of the usual diet by the supplement. Each subject was trained to maintain the daily record of oil intake using an easily-understandable record-keeping sheet supplied each time the oil was delivered. The CHWs collected the records of oil intake during their next weekly home-visits, and they supplied the participant with another bottle of oil for the ensuing week. They also interviewed the subject and obtained information about her attitudes towards and compliance to the oil during the previous one week.Fat intake from all sources was estimated by 24-hour dietary recall administered four times during the study period following standard guidelines . A surveData on nutrient intake were calculated using a computerized food-composition table for Bangladeshi foods, which used nutrient data from regional food-composition databases ,25. The Blood samples each of 0.5 mL were collected in lithium heparinized microtainers either by finger-prick or ante-cubital venipuncture, immediately put on ice, shielded from light in a cold carrier, and transported to the field laboratory within 3-6 hours of collection. Plasma was then separated by centrifugation  and transferred to labelled screw-top, amber-coloured cryovials and stored at -20 °C for 2-4 weeks in the field laboratory before being transferred to the central laboratory in Dhaka for storage at -7 °C until analysis 2-3 months later. Simultaneous determination of concentrations of serum retinol, lutein, and β-carotene was done by high-performance liquid chromatography (HPLC) in the Nutritional Biochemistry Laboratory of ICDDR,B . RetinolA nurse or a trained interviewer collected a casual breastmilk sample according to the method previously used in this population . Breastmt-test for statistical significance. Changes in each of the outcome variables from baseline (pregnancy) to different follow-up periods were calculated for each subject by subtraction. Paired t-test was used for comparing within-group differences from baseline to the respective time periods. Independent sample t-tests were used for comparing changes at respective study periods between the groups. Concentrations of breastmilk retinol were compared between the intervention group and the control group by independent sample t-test of means. In this case, the change was not examined or tested as the intervention had been continuing for a certain period before the first sample of breastmilk was collected. The mean concentrations of infants’ plasma retinol, β-carotene, and lutein were compared between the groups by the independent sample t-test. The p value of <0.05 was considered statistically significant.Numeric variables were examined for their distribution outliers, and extreme values were identified and excluded from the analyses. Such values did not exceed 3-4% of the observations. Results are presented as mean±standard deviation for the normally-distributed variables or median and interquartile range for the variables not normally distributed. The differences between the groups were examined by Student's The Ethical Review Committee of ICDDR,B approved the study. An informed written consent was obtained from each woman before enrollment into the study.The baseline characteristics of 248 supplemented and 251 control women are presented in As expected, the mean fat intake from all the sources (including supplement) was significantly higher in the intervention group at 1, 3 and 6 months postpartum than that of the control group . Fat intCompared to the pregnancy (baseline) level, concentrations of plasma retinol increased in the intervention women in all the three measurement periods during the postpartum period ; however, the change at one month postpartum reached statistical significance . In the During the postpartum months, the concentration of plasma β-carotene declined compared to the pregnancy level in both intervention and control groups . The decThe concentration of plasma lutein also declined during the postpartum measurements and followed the same trend as that observed in β-carotene . HoweverThe mean concentrations of breastmilk retinol were higher in the intervention group than those in the control group at one month and three months postpartum (0.06 and 0.13 μmol/L respectively), and the difference was significant at three months postpartum but not at six months postpartum . No signThe aim of this study was to examine the effect of supplementation of dietary fat on the vitamin A status of pregnant and lactating women and their infants in a population where vitamin A deficiency is prevalent and dietary fat intake is low. As indicated by the improvement in concentrations of blood retinol and carotenoids and the improvement in concentrations of breastmilk retinol in the supplemented group, these findings suggest that increasing the dietary fat intake may have beneficial effect on the vitamin A status of women during early lactation.In this study, we aimed at increasing the fat intake by 18 g per day in the intervention group but the actual increase was less in many individual women. This was not unexpected since administration of the supplement was ultimately controlled by the study subjects themselves and not by the study team. Further, consumption of oil in this way, i.e. in a medicinal dosing, is not a normal dietary practice. Nonetheless, supplementation resulted in a doubling or greater fat intake in the intervention group.The supplemented group increased concentrations of plasma retinol at 1, 3 and 6 months postpartum measurements  while an increase in the control group was observed only at one month postpartum measurement (5%) and a slightly declining tendency was noted at three and six months postpartum (-8 and -1%). The change compared to the baseline level at one month postpartum in the intervention was statistically significant, suggesting that dietary fat had a positive effect on plasma retinol concentration of the supplemented women. Both the groups showed lower concentrations of plasma β-carotene and lutein during postpartum; however, relatively less so in the supplemented group, indicating higher provitamin A bioavailability in the oil-supplemented women. These findings are consistent with earlier reports that fat supplementation in deficient population has beneficial effects on concentrations of retinol and carotenoids ,30,31.In the study population, dietary vitamin A is derived almost entirely from plant sources ,32. TherThe women in the supplemented group of our study had relatively higher concentrations of breastmilk retinol at one month and three months postpartum than those in the control group. The increase in concentration of breastmilk retinol in the supplemented group translates into 8-18 μg of daily additional preformed retinol delivery in their infants (assuming a breastmilk intake of 700 mL per day), an amount equivalent to 4-10% of the basal requirements for infants up to the age of six months ,36,37. AOur findings are consistent with those of other studies in developing countries where the breastmilk retinol level is either deficient or at the marginal range ,38. Of iWe have observed a substantial fluctuation in concentrations of breastmilk retinol. Such fluctuations in concentrations of breastmilk retinol have also been reported by others . It is aNo difference was observed in concentrations of the infants’ plasma retinol, β-carotene, or lutein. Possible reason might be that vitamin A status of the infants was measured at the end of six months of age when the difference in maternal vitamin A status between the supplemented and the control mothers did not exist. It might also be possible that the benefit to the infants of the intervention mothers, if it had occurred in early infancy, might not have been large enough to maintain a sustained higher concentration up to six months of age. Although the intervention mothers had a better concentration of breastmilk retinol during early lactation, it is notable that retinol concentration in most women of both the groups was always less than 1.05 μmol/L, the concentration considered to be just enough to meet the basal requirement of the infant but not enough to build good vitamin A stores . ICDDR,B acknowledges with gratitude the commitment of USAID/OMNI to the Centre's research efforts. Financial support from the Division of Human Nutrition and Epidemiology, Wageningen, is gratefully acknowledged. The authors thank all the mother-infant pairs for their valuable participation in the study.


Refugee women have a high risk of coronary heart disease with low physical activity as one possible mediator. Furthermore, cultural and environmental barriers to increasing physical activity have been demonstrated. The aim of the study was to evaluate the combined effect of an approximate 6-month primary health care- and community-based exercise intervention versus an individual written prescription for exercise on objectively assessed cardiorespiratory fitness in low-active refugee women.Relative aerobic capacity and fitness level were assessed as the two main outcome measures.A controlled clinical trial, named "Support for Increased Physical Activity", was executed among 243 refugee women recruited between November 2006 and April 2008 from two deprived geographic areas in southern Stockholm, Sweden. One geographic area provided the intervention group and the other area the control group. The control group was on a higher activity level at both baseline and follow-up, which was taken into consideration in the analysis by applying statistical models that accounted for this. relative aerobic capacity and the percentage with an acceptable fitness level (relative aerobic capacity > 23 O2ml·kg·min-1) to a greater extent than the control group between baseline and the 6-month follow-up, after adjusting for possible confounders (P = 0.020).The intervention group increased their A combined primary health-care and community-based exercise programme (involving non-profit organizations) can be an effective strategy to increase cardiorespiratory fitness among low-active refugee women.ClinicalTrials.gov ID: NCT00747942 Demographic and economic changes have resulted in a more diverse population with greater social disparities in Sweden during the last few decades because of the large influx of refugees mainly from Latin America in the 1970 s, Iran in the 1980 s, Bosnia and the Balkans in the 1990 s, and Iraq and the Middle East in the 2000 s. Refugee status has previously been defined by the United Nations as a person who is outside the protection of his or hers country owing to a well-founded fear of being persecuted for reasons of race, religion, nationality, membership of a particular social group, or political opinion [New York Times Magazine provided data documenting the growing ethnic minority and socioeconomic segregation in urban and suburban Sweden [The large influx of refugees has changed Swedish society. A 2005 article in the Many of these refugees have an increased risk of coronary heart disease (CHD) in both men and women. Female refugees born in Turkey, Iran, and Iraq and settled in Sweden had an age-adjusted excess risk of CHD compared with Swedish-born controls ranging from 110% to 130% -7. Femal2max below the 50th percentile and were also obese [Although it is convenient to assess changes in physical activity with questionnaires, cardiovascular fitness is a more reliable and objective measure. For example, data from the longitudinal CARDIA study showed that a change in individual cardiorespiratory fitness is strongly associated with a corresponding change in habitual energy expenditure and leisure time physical activity . Furtherso obese .largest increase in physical activity levels can be found among the least active at baseline; minority groups were, however, not included in that study [Physical inactivity and obesity are potential mediators of accelerating arteriosclerosis and the development of CHD seen among refugee women. According to the World Health Organization (WHO), it is important to target these risk factors in order to decrease the global burden of CHD. In addition, previous research has shown that the at study . Therefoat study . The finBoth individual and environmental factors are associated with physical activity in minority women. For example, a qualitative study from the United States showed that a lack of time due to caregiving duties, health worries, and lack of motivation were important barriers to women from ethnic minorities and refugee women becoming more physically active . The womThe real life situation of many refugee women in Sweden, such as low socioeconomic status, low educational status, and residing in a deprived and unsafe neighbourhood, has been associated with low levels of physical activity and exercise . In thisThe purpose of the present study was to investigate whether appropriate physical activities and social support can increase cardiorespiratory fitness in refugee women in Sweden. This purpose was implemented by evaluating the effect of an approximate 6-month primary health-care- and community-based exercise intervention versus an individual written prescription for exercise on objectively assessed cardiorespiratory fitness in low-active and overweight refugee women.Stöd till Aktivare Motion or STAM in Swedish).This controlled clinical trial was named Support for Increased Physical Activity , to identify the two deprived and immigrant-dense geographic areas (including large populations of Middle East refugees). The CNI scores ranged from-76.4 (most affluent neighbourhood) to 53.5 (most deprived neighbourhood) . The CNIEligible for inclusion were women aged 25 through 64 who were first-generation refugees in Sweden from either the Middle East or Latin America, were overweight and reported low levels of physical activity during their leisure time  ,23. We eWe appealed to the community to obtain access to physical activity facilities for the intervention. Nine primary health care centres located in the two immigrant-dense areas were partly used in the recruitment processes. This process included information brochures in the waiting room but the women were also informed about the study by the personnel at the primary health care centres. We also recruited women through local advertising and via community organizations such as women's associations, child welfare centres, pre-schools, churches/mosques and courses in Swedish for immigrants.The women who were willing to participate filled in a first screening protocol. All women who filled in the screening protocol were contacted by research staff who could speak their native language. The participants were further informed about the study and those who agreed to participate and were eligible for inclusion were enrolled for a baseline assessment. Eligible for inclusion included 131 women in the intervention group and 112 women in the control group. All written material  was translated to Spanish or Arabic by two independent professional translators and backwards translated by two other professional translators.2(m) (according to WHO's recommendations) and comprised three categories: (1) normal weight (BMI < 25.0), (2) overweight (BMI 25.0-29.9) and (3) obesity (BMI ≥ 30).In total three questions were included in the screening protocol to assess physical activity, overweight/obesity, and pre-existing ill health. Physical activity was assessed by asking the participants how often they exercise during their leisure-time. The response alternatives were the following: (1) I get practically no exercise at all, (2) I exercise occasionally, (3) I exercise regularly, about once a week, (4) I exercise regularly, about twice a week and (5) I exercise regularly, quite vigorously at least twice a week. Overweight and obesity were assessed on the basis of self-reported data on weight and height. Body mass index (BMI) was calculated as weight(kg)/heightOur intention was to include only those who were inactive  and overweight/obese. However, around 10% in the intervention group and 50% in the control group were found to have a normal weight at the baseline measurements. They were not excluded from the study but we took BMI into account in the analyses.n = 114 women in the intervention group and 98 women in the control group) were assessed at baseline. Most women came from the Middle East: 96% and 80% in the intervention and control group, respectively. The women mainly came from the following countries: Iraq, Syria, Turkey, Lebanon and Chile. The largest groups in the intervention group came from Syria (26%) and Lebanon (10%) and the largest groups in the control group came from Turkey (26%) and Iraq (24%).Background information  was assessed at baseline. Height, weight and cardiorespiratory fitness were assessed at baseline and at 6 months. In total, 212 women  was given during the summer break. The women attended 16 sessions in average (range 1-32). An initial session of individual counselling with the purpose to strengthen self-efficacy, empowerment and personal motivation was given by a female physiotherapist who guided the women concerning how to start doing regular physical activities at a health-enhancing level and informed them about the benefits associated with physical activity. This initial session also addressed possible barriers to physical activity based on findings of a previous qualitative study, e.g. worries about palpitations, tiredness and sweating (15). The women received information about different levels of health-enhancing physical activity, such as moderate and vigorous physical activity and how they are related to perceived exertion . The womThe participants in the control group received an individual written prescription for exercise that was partly based on the results from the cardiorespiratory fitness together with an initial session of individual counselling. In general, the written prescription was based on the recommendation of regular health-enhancing physical activity, i.e. 30 minutes per day at a moderate intensity level ,30. The 2 l·min-1) were calculated by the bicycle computer, using the Åstrand-Rhyming nomogram (24). The data collectors in the present study were not blinded because we recruited the intervention and control groups from two different geographic areas.The Åstrand-Rhyming submaximal bicycle ergometer test was used to assess cardiorespiratory fitness . The MonOut of the 212 women who were assessed at baseline, 179 (84%) had at least one measurement either at baseline or at the six-month follow-up and they were included in the analysis (n = 91 in the intervention group and n = 88 in the control group). Most of the 33 excluded women were either not able to perform the test due to poor bicycling skills, or not able to bike at the correct speed, or had inadequate muscular strength to perform the test. A standardized walking test might have been an option; still, we believe that many of the women had too low a capacity to fit within any standardized protocol. The 33 excluded women did not differ with regard to age or BMI from those included.To sum up, 243 women (131 women in the intervention group and 112 women in the control group) showed an initial interest to take part in the study and were considered eligible. Of these women, 212 came to the baseline assessments (114 women in the intervention group and 98 women in the control group) and 179 had at least one measurement either at baseline or at the six-month follow-up (91 women in the intervention group and 88 women in the control group). All women in the intervention group took part in at least one session with a leader/instructor.relative aerobic capacity, defined as oxygen uptake per kilo body weight (O2ml·kg·min-1). The second outcome variable, fitness level, was dichotomized at a relative aerobic capacity larger than or equal to 23 O2ml·kg·min-1 (1) and (0) otherwise. According to Blair, a relative aerobic capacity below 23 O2ml·kg·min-1 is regarded as a high risk value for cardiovascular disease in women [Two outcome variables were used. The first was in women .age was categorized into 3 groups based upon tertiles of the data, 24-39, 40-44, and 45-64 years.Self-reported BMI (kg·m-2) was calculated from the objectively measured height and weight. BMI is categorized into 3 groups by the WHO  and otherwise as (0).Height was measured to the nearest 0.5 cm using a stadiometer (Seca 214), and weight was measured using a bioimpedance analysis  to the nearest 0.1 kg, subtracting 2.0 kg for clothes.  obesity . In the Educational status was classified into three categories: less than 10 years, 10-12 years, and more than 12 years.Employment status was dichotomized as being employed or unemployed. Unemployed also included those on sick- or parental leave, retirees, students, and housewives.Acculturation was assessed on the basis of language skills. The acculturation variable has been used previously by the Swedish government-owned statistics bureau to study integration and health in a random sample of Swedish immigrants from Chile, Iran, Poland and Turkey.The participants in the present study answered to the following questions concerning: (1) knowledge of how to appeal against authorities, (2) ability to understand news reports, (3) speaking Swedish at meetings, (4) communicating with authorities over the telephone, (5) reading books in Swedish, and (6) being able to complete a written application for employment. The 1st question had two response alternatives (yes or no). The other five questions had four possible response alternatives, with 1 characterizing the highest degree and 4 the lowest degree of knowledge in Swedish. The answers to each question were dichotomized as one point for alternatives 1 and 2 (or 1 for question 1) and with zero points for alternatives 3 and 4 (or 2 for question 1). The dichotomy variables were summed up and categorized at two levels, with a low level of knowledge of Swedish/acculturation if the score was less than 4 and a high level of knowledge of Swedish/acculturation for a score of 4 or more.Years in Sweden was assessed as a continuous variable.n) and percentage (%) for categorical data (Table Baseline characteristics are shown as the median and interquartile range (IQR) for continuous data and number  × 2 (time: baseline and 6-month follow-up) design, we analysed the treatment effect in relative aerobic capacity by applying a mixed linear model with random intercepts and slopes. Mixed model analyses allowed inclusion of subjects with missing data and differences between groups at baseline . The resWe used a generalized estimating equations (GEE) model (with an exchangeable correlation matrix and robust standard errors) when analysing the dichotomized outcome, fitness level . The resThe statistical package used was STATA Release 10 .2ml·kg·min-1) between groups with a power of 90% and a significance level α = 0.05 (based upon data from a pilot study with a mean of 24 O2ml·kg·min-1 and a standard deviation of 7 and a correlation of 0.7 between occasions), 69 individuals per group were needed. An increase of 3 units for a person with very low aerobic capacity is important from a cardiovascular health perspective [To find a difference of 3 units in Δ for relative aerobic capacity .P < 0.05). The control group had a significantly better relative aerobic capacity and a higher percentage with an acceptable fitness level (relative aerobic capacity > 23 O2ml·kg·min-1) at baseline than the intervention group.The characteristics of the study population are shown by group in Table relative aerobic capacity as outcome, while educational level, employment status, and acculturation did not. Table P = 0.02). This indicates that there is a treatment effect, i.e. the intervention group improved their relative aerobic capacity significantly more than the control group.We found that age and BMI significantly influenced the mixed model for P = 0.00001) larger increase over the 6-month follow-up in relative aerobic capacity than the control group (P = 0.02). However, the control group had a higher relative aerobic capacity than the intervention group at both baseline (P = 0.0001) and the 6-month follow-up (P = 0.01).The β-coefficients with 95% confidence intervals are shown in Table P = 0.02), also including age and BMI, when analysing the dichotomized outcome fitness level (relative aerobic capacity > 23 O2ml·kg·min-1). Table The GEE model showed results similar to those of the mixed model with a significant interaction between treatment and time (relative aerobic capacity and the percentage with an acceptable fitness level (relative aerobic capacity > 23 O2ml·kg·min-1) to a greater extent than the control group from baseline to the 6-month follow-up, after adjustments for age and BMI. However, the control group was on a higher level at both baseline and follow-up, which was taken into consideration by employing a mixed linear model with random intercepts and slopes and, for fitness level, a GEE model.The main finding of this controlled clinical trial was that the intervention group increased their 2max), determined during submaximal exercise testing, has been shown to provide a good estimate of cardiorespiratory capacity, which is an independent marker of the early atherosclerotic cardiovascular diseases [The finding that a combined primary health care- and community-based exercise intervention increased the relative aerobic capacity and the percentage with an acceptable fitness level is important because such an intervention may have the potential to decrease lifestyle-related disease risks such as coronary heart disease, cancer, and diabetes mellitus in low-active refugee women. Cardiorespiratory fitness, which we measured as maximum oxygen consumption  in comparison with standard care in a primary care setting of sedentary ethnic minority and low-income women . Their rA protocol for an ongoing randomized controlled trial in primary health care recently reported on the effectiveness of an exercise referral scheme in the short and long term among women from ethnic minority groups . SeveralOne limitation in the design of the study is the use of a controlled clinical trial instead of a randomized controlled trial (RCT). Conducting a study in a real-life setting that can be implemented in the society at large is difficult. Although an RCT would have been optimal from a study design perspective, bias may be present in an RCT . For exaThis study also has several strengths. One is that it was conducted using existing community institutions, such as primary health care centres, which means that the model can be readily implemented. There are challenges in recruiting minority groups to prevention programmes with the aim to reduce cardiovascular risk factors ,52.A recent systematic review was able to identify only 13 intervention studies among immigrants of which three focused on cardiovascular risk factors . Most ofAnother strength is the use of a group-based intervention to be used in a country with a large and diverse immigrant population, particularly from the Middle Eastern countries. Besides the fact that the women can support one another, it is also cost-effective for the community compared to programmes for individuals or single immigrant groups. Finally, this study was evaluated using an objective measure of fitness, not just the self-reported level of physical activity, which is subject to measuring errors .This controlled clinical trial showed that a combined primary-health-care and community-based exercise programme can constitute an effective strategy to increase fitness among low-active overweight refugee women who are at risk of future coronary heart disease.The authors declare that they have no competing interests.JS, KS and SEJ contributed to the design of the study. All authors contributed to the analysis and interpretation of data. MH drafted the first manuscript. All authors revised the manuscript for important intellectual content and gave their final approval of the version to be submitted.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2296/11/55/prepub


Physicians are often unable to eat and drink properly during their work day. Nutrition has been linked to cognition. We aimed to examine the effect of a nutrition based intervention, that of scheduled nutrition breaks during the work day, upon physician cognition, glucose, and hypoglycemic symptoms.A volunteer sample of twenty staff physicians from a large urban teaching hospital were recruited from the doctors' lounge. During both the baseline and the intervention day, we measured subjects' cognitive function, capillary blood glucose, "hypoglycemic" nutrition-related symptoms, fluid and nutrient intake, level of physical activity, weight, and urinary output.Cognition scores as measured by a composite score of speed and accuracy (Tput statistic) were superior on the intervention day on simple  and complex  reaction time tests. Group mean glucose was 0.3 mmol/L lower (p = 0.03) and less variable (coefficient of variation 12.2% vs. 18.0%) on the intervention day. Although not statistically significant, there was also a trend toward the reporting of fewer hypoglycemic type symptoms. There was higher nutrient intake on intervention versus baseline days as measured by mean caloric intake , and improved hydration as measured by mean change in body mass .Our study provides evidence in support of adequate workplace nutrition as a contributor to improved physician cognition, adding to the body of research suggesting that physician wellness may ultimately benefit not only the physicians themselves but also their patients and the health care systems in which they work. The typical work day of a hospital based physician is not only cognitively demanding, requiring complex decision-making in a fast-paced environment, it is also physically demanding, with extended hours and frequent on call periods. During their work time, physicians may be far removed from areas that provide access to nutrition (fluids and nutrients). As a result, physicians are often unable to eat and drink properly or at all during their work day -4.Previous studies have demonstrated that the impairment of neurological functions such as fine motor skills, information processing, and memory, is linked to hypoglycemia and under-nutrition and may contribute to motor vehicle collisions and air crashes -9. ConvePhysician performance has been increasingly linked to lifestyle and wellness factors such as sleep deprivation and stress and, in turn, to the quality of patient care -18. HoweTwenty consecutive staff physician volunteers were recruited from the doctors' lounge of a large urban teaching hospital during the first week of May 2008 following a hospital wide poster campaign advertising study recruitment location and timing. The physicians selected two typical, similar work days to be scheduled as the baseline and intervention study periods during May and/or June 2008. All data were collected on site at the hospital. Ethics approval was obtained from the Conjoint Ethics Review Board of the University of Calgary. Written consent was obtained from participants.This prospective study compared physicians' nutritional intake and cognitive function during work hours on two separate work days, a baseline day and an intervention day. A before and after study design was chosen rather than assigning participants to intervention or control days in random order, given the possibility that physicians assigned to first receive the intervention may be influenced to alter their typical nutritional habits. On the baseline day, the physicians followed their usual eating and drinking habits. On the intervention day, they were fed nutritious meals, snacks and fluids at scheduled intervals. Participants chose two typical and similar work days  within a two week period to serve as baseline and intervention days. Most physicians chose daytime work hours as the study period (17/20) while three chose evening and overnight work hours.The intervention, that of ensuring that physicians consumed nutrients and fluids at regular intervals throughout their work day, was designed based on previous research where physicians and other health care professionals described barriers to achieving adequate nutritional intake during work hours -4, unpub, unpub4,The primary outcome was cognition. Secondary outcomes were blood glucose levels and "hypoglycemic" nutrition-related symptoms. Baseline demographic characteristics were recorded at study enrolment. Fluid and nutrient intake and physical activity were measured on both days. At the beginning of each day, participants were weighed and fitted with an activity and heart rate monitor. At that time and at approximately two hour intervals on both days, measures of cognitive function, capillary blood glucose, "hypoglycemic" nutrition-related symptoms, food and fluid intake, and volume of urine excreted over the previous two hours were captured. Participants were weighed again at the end of each day. On the baseline day, the physicians maintained their usual eating and drinking habits. On the intervention day, the physicians reported to the study center fasting, and all nutrition for the day was delivered to the physician and recorded. The participants were blinded to their glucose and cognitive function test results at the time of testing.Cognition was measured using Brain Checkers software, Version 3.01  run on Palm Tungsten E2, . Two software programs were used. The simple reaction test was designed to measure the speed of motor response to a visual cue with repeated testing over thirty seconds. The complex reaction test, a choice reaction time and continuous performance task, was designed to measure running memory, attention and visual information processing with repeated testing over two minutes. This task requires the subject to indicate whether the current number (1 through 9 appearing randomly on a screen) matches the previously displayed number (with random time delay between the two) by tapping on the appropriate text box (labelled "same" or "different") located below the number. For both tests, the reaction times of each unique response as well as the mean reaction time for the session were recorded for each participant. Accuracy was documented in terms of percent correct responses, lapses (the subject did not respond to the stimulus) and impulses (the subject anticipated and acted before the prompt). A Tput statistic was calculated that captures the correct responses per minute of time available to respond. It represents a combination of speed and accuracy with a higher Tput statistic indicating a superior performance. Based on the manufacturer's recommendation, subjects completed three practice tests prior to baseline data collection. This approach eliminates any learning effect during the study period and prevents learning effects from confounding actual study measurements -22.Capillary blood glucose samples were collected from participants' fingertip and analyzed immediately using the Precision Xtra Blood Glucose Monitoring System (glucose measured in millimoles per liter). Participants were asked to report from a checklist of "hypoglycemic" nutrition-related symptoms, including those produced by falling glucose and counterregulatory hormones and by reduced brain glucose. The seventeen symptoms covered manifestations of adrenergic responses , glucagon responses , and neuroglycopenic responses  ,24. The Body mass was measured using SR Model SR241 scales . The measure of weight, performed by either of the two research assistants at the beginning and end of each study period, was standardized by using a single digital scale at the same location and ensuring participants' equivalent post urinary void state and clothing status . Volume of fluid consumed and urine voided were quantified. Dietary analyses were performed using individual physicians' recorded diet history . Two-hour diet recall was also taken at each blood glucose sampling in order to enhance the validity of the dietary record. Only nutritional intake during the study period was analyzed using Diet Analysis+, Canadian version 4.0 . Nutritional requirements were based upon the Dietary Reference Intakes (DRI 2002) , which rA triaxial accelerometer that records acceleration in three planes  recorded activity level and heart rate simultaneously every fifteen seconds. Physicians were asked to rate both days on scales of 0 (low) to 10 (high) for workload, stress and general well being.After determining the appropriateness of parametric analytical methods, the statistical significance of mean differences in blood glucose levels and cognitive test scores were calculated using a generalized estimating equation to take into account the repeated measurements taken during each study day; change in body mass, and fluid and nutrient intake on baseline and intervention days were assessed for normalcy and means were compared using paired two sided t-tests; where the assumption of normalcy was not met, results were presented as medians plus interquartile range, and compared using a Wilcoxon signed rank test. Variability in glucose values was calculated using the coefficient of variation (CV), which describes variability relative to the mean [CV = (standard deviation/mean)*100%]. Analysis of variance (ANOVA) was used to assess within-day differences in mean cognitive test scores across the sampling times. A Fisher's exact test was used to compare proportion of physicians reporting "hypoglycemic" nutrition-related symptoms on baseline and intervention days.This study was originally conceived as a pilot study for preliminary testing of a nutrition based intervention, and for determination of multiple physiological and nutritional measurements in twenty working physicians. Given this, there were no a priori sample size considerations. However, based on mean glucose and cognition (Tput) values obtained, and corresponding standard deviations, we determined post-hoc that we had 96% power to detect a difference of 0.28 mmol/L in glucose values, and 97% power to detect a difference of 5 in Tput scores from the complex cognition test for the intervention day versus the baseline day.All statistical analyses were performed using Stata 10 .2 and ranged from 20.3 to 38.3 kg/m2. All participants were non-smokers and 15/20 (75%) reported exercising at moderate or high intensity for 30 minutes or longer at least 2-4 days per week. All twenty subjects completed both days with full data and follow-up for all study measures. No adverse effects of the intervention were reported.Twenty physicians from various medical specialties participated, with 10/20 participants (50%) from a medical specialty , 8/20 (40%) from a surgical specialty , and the remaining two (10%) from a primary care specialty . The mean duration of medical practice was 16.5 years, ranging from 5 to 36 years. The mean age was 46.8 years, and ranged from 36 to 64 years, and 85% were male. The mean Body Mass Index was 25.5 kg/mGroup mean glucose was slightly lower and considerably less variable on the intervention day compared to the baseline day Figure . The groStudy participants often reported symptoms associated with "hypoglycemia" despite few glucose results in the hypoglycemic range. On the baseline day, the symptoms most commonly reported were hunger (15/20 participants), fatigue (9/20), sweating (6/20), sensation of warmth (6/20), and drowsiness (5/20). On the intervention day, the symptoms most commonly reported were hunger (12/20), fatigue (7/20), sweating (3/20), sensation of warmth (3/20), or inability to concentrate (3/20). Supplementary analysis of the number of individual symptoms reported by each participant was also undertaken. Although the results were not statistically significant (p = 0.36), there was a trend toward fewer symptoms during the intervention day relative to the baseline day  participants showed a mean loss of body mass on the baseline day compared with a mean gain during the intervention day . Mean fluid intake was significantly greater on the intervention day  . The group mean average heart rate  and physical workload  were also similar. Physicians' self reports on a scale of 0 (low) to 10 (high) comparing the baseline to the intervention day showed no difference for perceived workload , stress , or general well being .The scheduled healthy food and fluids consumed during the intervention day were associated with improved physician cognition and less glucose variability. Although not statistically significant, there was also a trend toward the reporting of fewer hypoglycemic type symptoms. The change in cognitive function associated with the intervention appears notable relative to both population norms and age-related differences. For the simple reaction time test, the expected normal performance for ages 34-49 is a Tput score of 207, and a mean reaction time of 294 msec, and for ages 50-59, scores of 197 and 309 msec respectively. For the complex reaction time test, the expected normal performance for ages 34-49 is a Tput score of 100, and a mean reaction time of 547 msec and for ages 50-59, scores of 80 and 618 msec respectively . Our stuThe intervention was well received by participating physicians and its success may have been due to a number of factors. Nutrition was enforced through a scheduled regimen of food and fluid intake, readily available either at the centrally located doctors' lounge or at the physician's practice location. Physicians have previously indicated that they are often too busy to stop and eat and that limited access to nutrition during the work day, due to factors such as location, hours of operation, and cafeteria line ups, is a significant barrier . They haOn a practical level, implementing a nutritional intervention in a health care system is feasible. Health care organizations are increasingly evaluating the quality of food and drink made available to patients and staff, recognizing the benefits of quality nutrition to overall health. Making time for nutrition can be encouraged by developing educational campaigns that promote the benefits of nutrition breaks, by carefully scheduling nutrition opportunities during work hours, and through peer support of nutrition as a necessary component of a physician's ability to deliver quality health care. While food and drink are already available at defined locations in most hospitals, improved access can be achieved through placement of nutrition stations in high workload areas. For example, healthy food stations may be set up near operating rooms and on acute care wards via mobile carts, or where physicians tend to gather most, such as in the doctors' lounge. Although the nutritional intervention in this study was cost free, qualitative interview data from the study participants (results available from authors) support that physicians are willing to pay for good quality food and drink, suggesting that most of these proposals would be cost neutral. Lastly, there may be a number of secondary benefits to health care systems that are staffed by physicians who are cognitively improved as a result of adequate nutrition.As noted above, the literature provides evidence of the negative consequences of suboptimal nutrition for workers in a variety of work settings, in particular as they relate to cognitive function. Studies have also shown an association between the personal dietary habits of physicians and medical students and their nutrition counseling behaviors and attitudes ,29. FurtThe main limitation of this study is the relatively small number of participants. However, our paired study design and richness of measures nonetheless permitted sufficient statistical power to detect several significant differences on key measures between the two study days. A second limitation is the predominantly male and hospital based physician study sample, with a potential lack of sampling across the different types of workdays physicians may experience. For further generalization of results, these variables, and others such as age and weight would also need to be taken into account in future research. A third potential limitation is the non-randomized study design. However, the study is not necessarily weakened by lack of randomization between the intervention and non-intervention control groups given we ensured comparability in our pair wise comparison within individuals. A fourth limitation is that the study was not designed to evaluate whether the differences found between the study days translate into improved patient care. Lastly, the manufacturers of the cognitive function tests cite research to support that the learner effect is attenuated after three practice trials. Although it is still possible that a learner effect influenced the study results, each participant did undergo three practice trials before starting the study, and the ANOVA analyses across sampling times within each study day did not suggest a learner effect for same days responses. Weighing against these limitations is the strength of the full participation of twenty physicians over both study days despite interruptions in their work day due to the extensive collection of physiological measures and the added time commitments.Future studies might consider the development and randomized evaluation of an intervention that is more feasible in the acute care setting and that is based on a sustainable business model . Our study provides evidence in support of adequate workplace nutrition as a contributor to improved physician cognition, adding to the body of research suggesting that physician wellness may ultimately benefit not only the physicians themselves but also their patients and the health care systems in which they work .The authors declare that they have no competing interests.All authors had access to the data, had a role in writing the manuscript, and approved the final manuscript. JL contributed to the study conception and design, acquisition of data, analysis and interpretation of data, drafting and critical revision of the manuscript, statistical analysis, obtaining funding, and administrative support. JW contributed to the study conception and design, analysis and interpretation of data, critical revision of the manuscript, statistical analysis, obtaining funding. KD contributed to the study design, acquisition of data, analysis and interpretation of data, critical revision of the manuscript and technical support. WG contributed to the analysis and interpretation of the data, critical revision of the manuscript, statistical analysis, and administrative and material support. AL contributed to statistical analysis and interpretation of data, drafting of the manuscript and critical revision of the manuscript. DR contributed to the conception and design of the study, acquisition of data, analysis and interpretation of data, critical revision of the manuscript, statistical analysis, and technical and material support. JL had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis, and had final responsibility for the decision to submit the manuscript for publication.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/10/241/prepub


Objective To determine whether integration of nutritional supplementation with other public health programmes in early life reduces the risk of cardiovascular disease in undernourished populations.Design Approximately 15 years’ follow-up of participants born within an earlier controlled, community trial of nutritional supplementation integrated with other public health programmes.Setting 29 villages  near Hyderabad city, south India.Participants 1165 adolescents aged 13-18 years.Intervention Balanced protein-calorie supplementation  offered daily to pregnant women and preschool children aged under 6 years, coupled with integrated delivery of vertical public health programmes.Main outcome measures Height, adiposity, blood pressures, lipids, insulin resistance (homoeostasis model assessment (HOMA) score), and arterial stiffness (augmentation index).Results The participants from the intervention villages were 14 mm  taller than controls but had similar body composition. The participants from the intervention villages had more favourable measures of insulin resistance and arterial stiffness: 20%  lower HOMA score and 3.3%  lower augmentation index. No strong evidence existed for differences in blood pressures and serum lipids.Conclusions In this undernourished population, integrated delivery of supplemental nutrition with other public health programmes in pregnancy and early childhood was associated with a more favourable profile of cardiovascular disease risk factors in adolescence. This pragmatic study provides the most robust evidence to date on this important hypothesis for which classic trials are unlikely. Improved maternal and child nutrition may have a role in reducing the burden of cardiovascular disease in low income and middle income countries. Some authors have suggested that the risk of cardiovascular diseases can be “programmed” in early life through the persistence of endocrine, physiological, and metabolic adaptations made in the face of undernutrition.3The evidence in support of this hypothesis is largely circumstantial: animal experiments and observational studies in humans showing associations between anthropometric measures (as proxies for undernutrition) and risk of cardiovascular disease.10Integrated Child Development Services is a national community based programme aimed at improving the health, nutrition, and development of children in India.13Using the opportunity afforded by the stepwise expansion of this programme during the 1980s and 1990s, the National Institute of Nutrition in India ran a trial to assess (among other things) the impact of food supplementation in pregnancy on the birth weight of offspring. A cluster of villages with a total population of 30 000 was chosen from each of the two adjacent administrative areas , one of which already had the Integrated Child Development Services programme in place (intervention arm), whereas the other was awaiting implementation (control arm). As the 100 or more villages in each of the two blocks were spread over an unfeasibly large area, villages were chosen geographically for random selection: contiguous villages falling within a 10 km radius of a prominent central village  in each block were selected. This process resulted in 15 villages from the intervention arm and 14 villages from the control arm being recruited to the study.A 12 member team of investigators resided full time in the field for the duration of the study. Following a lead-in period of six months , the trial included all births in the area between 1 January 1987 and 31 December 1990. The “at risk” (of pregnancy) women were monitored monthly to detect missing of menstruation, and those identified as pregnant were followed closely during pregnancy until delivery . The field team attempted to visit the home as soon as possible after delivery to collect data on the outcome of the pregnancy and to weigh the newborn within 48 hours. An infant beam balance with a 20 g accuracy  was used to measure weight.The supplement given in this trial was “upma,” a local preparation made from corn-soya blend (120 g) and soybean oil (16 g), providing 2.51 MJ and 20 g protein to the women and half this amount to the children. No other nutrients  were added to the supplement. The other universal programmes—immunisation, anaemia control in pregnancy through distribution of iron  and folic acid (500 μg) tablets, and the provision of basic health care—existed to a similar extent in both the intervention and control areas, although their uptake may be presumed to have been higher in the intervention area. Crossover of supplements from intervention to control villages was not a problem because of their separation by a large number of villages not involved in the study; in addition, supplements were offered only to the named residents of the village. A preliminary abstract reported the ongoing study,We designed this follow-up study to establish the status of women and their offspring who took part in the trial and to clinically examine offspring who were still resident in the area. The parents and children gave written informed consent.We did two parallel surveys on a village to village basis—the first to identify the study participants and the second to do clinical examinations. The identification survey preceded the clinical survey by three months, and we interchanged the survey area between intervention and control villages every couple of months to even out any variations arising from seasons and experience of the study team. In the identification survey, we first identified women who took part in the baseline trial by using their own and their husband’s name. We interviewed each woman thus identified to collect details on children she had previously borne. All children born in these villages during the initial trial period (1987-90) were potential study participants. However, owing to limited resources and to make maximal use of the baseline data, we invited only those children who could be successfully matched to the previous records to have clinical examinations. We used date of birth and sex for matching, as infants’ names were not recorded in the baseline study . Where multiple children of the same woman were eligible, we invited them all and made appropriate adjustments in the analyses.We used a single clinic site at each village  to reduce measurement error arising from differences in clinic conditions. We held clinics in the morning, and invited 10-15 children to come fasting each day. We completed a full interviewer administered questionnaire and clinical examination on the children and a brief questionnaire on the mothers (who were asked to accompany the child).We measured height with a portable stadiometer . The participant stood erect with his or her head in the Frankfort plane, and a gentle upward pressure was applied under the mastoid. We used a digital weighing machine  to measure weight. We measured skinfold thickness at four sites  in triplicate with the Holtain calliper . We used a validated oscillometric device  to measure blood pressure in the supine position with appropriate cuff sizes; we took two measurements and averaged them for analyses. We measured ambient room temperature with a digital thermometer.We assessed the augmentation index, a measure of global arterial stiffness, by using an applanation tonometry technique with the Sphygmocor apparatus  Medical, Sydney, Australia).We classified sexual maturation into four stages  on the basis of time since the onset of menstruation (girls) and testicular volume (boys).We collected fasting blood samples (at least eight hours) in appropriate vacutainers, transferred them within one to two hours (in icebox at 4-8° C), and processed them within four hours. We did assays for glucose, triglycerides, total cholesterol, and high density lipoprotein cholesterol on the same day with an autoanalyser  and the recommended kits . We estimated insulin concentrations by radioimmunoassay in batches within four to six weeks.18We produced detailed protocols and used them regularly to standardise the work of the fieldwork team. “Blinding” of the fieldworkers to the group assignment was not an option; however, all measurements except anthropometry were to a large extent automated , thus reducing the possibility of bias. Only one observer made each measurement , to eliminate interobserver bias. We assessed reproducibility of clinic measurements by repeating the measurements on a random subsample (5%) of participants after one to three weeks and found it to be consistently high (intraclass correlation coefficients of >0.98 for anthropometric measures and >0.85 for blood pressures and augmentation index). We put in place internal and external quality control arrangements  for biochemical assays, and split assays were done on a 5% subsample (intraclass correlation coefficients >0.94). We validated testicular self assessment technique against a trained observer in a separate substudy and found it to be highly accurate (mean difference in model ranks (self reported minus directly observed)—0.07 —with no evidence of systematic bias on a Bland-Altman plot).We used the log of the sum of four skinfolds to calculate the percentage of body fat23We applied suitable transformations to outcome variables that deviated markedly from a normal distribution . We used linear regression models to investigate association of supplemental nutrition with cardiovascular disease risk factors. Analysis was on an intention to treat basis, using area of birth as proxy (irrespective of whether the participant took the supplement or not). We fitted four predefined models to adjust incrementally for the main domains of potential confounding or intermediary variables: model 1 ; model 2 ; model 3 (stature—height); and model 4 . We additionally adjusted blood pressure for ambient room temperature and augmentation index for heart rate, as these factors can artefactually affect their values.26Data could be clustered at the level of the village and the household (in case of multiple children). To take account of village level clustering, we used robust standard errors in all the models, with village as the level of cluster. This technique uses the cluster level residuals to derive the standard errors, so that the resulting standard errors are larger and valid in the presence of clustering but the parameter estimate remains unchanged. This technique was inappropriate for household level clustering, as very few households had multiple children taking part in the study. We therefore examined the impact of household level clustering on the results by excluding the second of the two children from the same household (no household contained more than two children). We similarly estimated the impact of a few migrant children  on the results by excluding these children from the final models. We examined interaction between the intervention and the sex of the participant, as evidence exists of preferential feeding of male children in this setting,Sample size calculations done before the start of the study suggested that the anticipated sample  was going to be adequate to detect important differences in most outcomes .Of the 4338 pregnancies recorded in the trial, birth weights (recorded within 48 hours) were available for 2964 (68%) children. The mean birth weight of children born in the intervention area (2655 (SD 424) g) was higher than that of controls (2594 (SD 430) g); the mean difference was 61 g . Adjustment for sex of the child made no difference to the results; however, we deemed data on gestational age to be of insufficient quality (strong digit preference) to be included in the analyses. Personal information (necessary to trace families) was available for 2756 women, of which 1963 (71%) could be contacted successfully  children for at least one outcome, with slightly fewer for blood pressure , lipid profile , glucose-insulin , and arterial stiffness . The lower number with glucose-insulin data was due to a failure to obtain insulin assay reagent in time for the last batch of assays (n=48), and that for arterial stiffness data was due to an inability to complete all assessments during the course of a clinic day, as most villages lacked the continuous electricity supply needed to run the apparatus. Some, but not all, of the participants returned subsequently to have their assessments completed.Table 2Children in the intervention and control arms were not different in their sexual maturation (data not shown). Table 4The study included 36 sibling pairs, of which five pairs were twins; all other households contributed only one child to the study. Thirty two participants had migrated away from their place of birth, of which nine had migrated within the study area . Exclusion of the migrant children or the second child (in the case of sibling pairs) made no material difference to the results.This is the first intervention study to show that modest improvements in the protein-calorie intake of pregnant women and young children may result in a more favourable cardiovascular disease risk factor profile among populations with prevalent undernutrition. These findings may indicate potential life course pathways underlying the causes of cardiovascular diseases in general.The importance of balanced protein-calorie malnutrition in early life has been studied in two natural experiments based on the starvation experience of populations under siege in the second world war (Dutch and Leningrad studies) and one small randomised controlled trial of supplemental nutrition from Guatemala.The main strength of this study is its setting: a nutritional intervention in a population with high background levels of chronic undernutrition, so we could realistically expect to find programming effects of inadequate diet, if they exist. The controlled design of the original evaluation would have reduced the chances of confounding; furthermore, the crucial confounders were either completely absent  or severely restricted .The study also has some important limitations that need to be acknowledged, chief among them the potential for bias owing to non-randomisation of villages in the baseline study, losses to follow-up, and lack of data on current diet and patterns of physical activity. In the baseline study, all villages within a radius of the central village were selected in both intervention and control areas, making selection bias unlikely. Bias could arise, however, if the intervention area urbanised at a different rate from the control area, thus influencing the prevalence of risk factors for cardiovascular disease. Data on urbanisation  collected from the village heads showed little variation between the villages (data not shown), and adjustment for urbanisation (population size) did not materially alter any of the results. Areas considered deprived are prioritised for the introduction of the Integrated Child Development Services programme in phases; however, the staggered introduction of the programme in similarly deprived and adjacent areas (such as those in the study) is mainly due to financial and operational constraints associated with the introduction of a public programme in a large country .12The response rate among children invited to the clinic was high 78%), although it was somewhat lower in the control areas, which in all probability arose from lack of interest in participation in the study shown by heads of some of the control villages . Loss to follow-up resulting from this is likely to be non-systematic. The participating children represented 45% of all eligible births in the area from that time, which compares favourably with the overall follow-up rates in other relevant studies .8%, althoDifferences in current diet and patterns of physical activity could account for the differences seen in risk of cardiovascular disease. Although it is theoretically possible, we see no obvious reason to believe that children from these neighbouring villages had marked differences in lifestyle. The villages are still fairly homogeneous in their diet (limited range of foods eaten mostly at home) and activity patterns . Furthermore, no differences in body composition existed; as adiposity reflects the net energy balance between intake (diet) and expenditure , the low fat mass in this population and its narrow distribution range, argues against any important lifestyle differences between the two areas. Finally, despite the relative automation of most of the outcome measures used in this study , the possibility of bias arising from the lack of blinding of the fieldworkers cannot be ruled out completely.Insulin resistance is believed to be central to many of the changes attributed to the thrifty phenotype.42The relative importance of nutrition in various stages , sources of nutrition, or indeed the rate of growth in early versus late postnatal life cannot be delineated from this study, as the intervention was given throughout.45We need to contextualise our observations and consider what public health benefits may accrue if this intervention was translated into primary prevention of disease burden. The Anglo-Cardiff collaborative study suggested that a 3% lower augmentation index equates to a three year less aged vascular phenotype.34The intervention in this study was given within the framework of a public welfare programme.Observational studies suggest that early undernutrition predisposes to cardiovascular disease in later life, but robust evidence from intervention trials is lackingIntegration of supplemental nutrition with public health programmes in pregnancy and early childhood was associated with a reduction in cardiovascular riskImproved maternal and child nutrition may have a role in reducing the burden of cardiovascular disease in low income and middle income countries


Ingestion of glucosinolates has previously been reported to improve endothelial function in spontaneously hypertensive rats, possibly because of an increase in NO availability in the endothelium due to an attenuation of oxidative stress; in our study we tried to see if this also would be the case in humans suffering from essential hypertension.in vitro antioxidative potential, for a 4 week period or to continue their ordinary diet and act as controls. Blood pressure, endothelial function measured by flow mediated dilation (FMD) and blood samples were obtained from the participants every other week and the content of glucosinolates was measured before and after the study. Measurements were blinded to treatment allocation.40 hypertensive individuals without diabetes and with normal levels of cholesterol were examined. The participants were randomized either to ingest 10 g dried broccoli sprouts, a natural donor of glucosinolates with high In the interventional group overall FMD increased from 4% to 5.8% in the interventional group whereas in the control group FMD was stable (4% at baseline and 3.9% at the end of the study). The change in FMD in the interventional group was mainly due to a marked change in FMD in two participants while the other participants did not have marked changes in FMD. The observed differences were not statistically significant. Likewise significant changes in blood pressure or blood samples were not detected between or within groups. Diastolic blood pressure stayed essentially unchanged in both groups, while the systolic blood pressure showed a small non significant decrease (9 mm Hg) in the interventional group from a value of 153 mm Hg at start.Daily ingestion of 10 g dried broccoli sprouts does not improve endothelial function in the presence of hypertension in humans.NCT00252018Clinicaltrials.gov  Oxidative stress is considered to play a important role in the processes of cellular injury which ultimately leads to the development of atherosclerosis.A group of substances which might have this effect are the glucosinolates, substances naturally occurring in cruciferous plants; the glucosinolates are precursors to isothiocyanates, of which sulphoraphane is one of the most potent inducers of the expression of phase-2-enzymes, in mammalian cells.Among the enzymes induced in vitro the gluthation-S-reductase may be of particular interest since it is instrumental in recycling gluthathion to its reduced state in the cell. In broccoli sprouts younger than 4 days glucoraphaninWe therefore decided to study whether the administration of dried broccoli sprouts in patients with essential hypertension could decrease blood pressure and increase flow mediated vasodilation(FMD). We have focused on endothelial function since this parameter previously has been demonstrated to be influenced by the level of oxidative stress, and because it is a sensitive predictor for oxidative stress as well as for the future development of atherosclerosis.We hypothesized that an increase in flow mediated vasodilation shooud be detectable in the interventonal group after four weeks of treatment both if we used the participants as their own controls and if we compared them to a control group. This was our primary outcome.Secondary outcomes in our study were measurement of blood pressure and lipoproteins where we were interested in seeing if the blood pressure would decrease during treatment and if lipoproteins would show an increase in HDL as well as a decrease in LDL.The protocol for this trial and supporting CONSORT checklist are available as supporting information; see Volunteers were enrolled in the study after advertising in local newspapers for non smoking hypertensive individuals without known diabetes or hypercholesterolemia. In- and Exclusion criteria are listed in The study was approved of the ethics committee for Copenhagen and Frederiksberg municipalities (no 01-257/04). Written informed consent was obtained from all participants.Endothelial function was measured on each individual three times, at start of treatment and twice during the four weeks of treatment with an interval of two weeks. Blood samples for erythrocyte content and inflammation, samples for lipids, blood glucose and inflammation were taken at each visit. Furthermore samples were obtained for analyzing the blood content of glucosinolates and their metabolites. The purpose for measuring the erythrocyte content blood glucose and inflammatory status was to insure that the stimulus for measuring FMD was as uniform as possible for each visit since a change in blood viscosity could influence the shear stress of the vessel wall and therefore increase the measured FMD, likewise elevated blood glucose has been showed to decrease FMD response. Endothelial function was measured using Flow Mediated Dilation (FMD) using a protocol following current guidelines.The broccoli sprouts were obtained from a commercial grower  and were sprouted for 3 days. Immediately after harvesting they were refrigerated and subsequently dried at 40°C.The dried sprouts were afterwards packaged in airtight plastic bags each containing 10 grams of dried sprouts, equivalent to 100 g fresh sprouts. The dried sprouts had the glucosinolate content measured using previously described methodsPatients were randomised to treatment with broccoli sprouts or control in a 1∶1 ratio. Treatment consisted in a daily ingestion of 10 g dried broccoli sprouts. The block size for randomization was 4. Randomization was performed by an assistant in sealed envelopes and group allocation was blinded to the investigator. The participants were thus unblinded with regards to their allocation but the investigator was blinded throughout the study to the status of the participants. Since broccoli sprouts are not commercially available and have a much larger content of glucoraphanin than mature broccoli, we were confident that the control group would not ingest glucoraphanin in substantial amounts during the study. Pre-study antihypertensive medications were maintained during the study for all participants. The participants were given a package containing 28 bags with 10 g dried broccoli sprouts in each, instructions were to eat the content with one of the meals of the day, they were also instructed to avoid eating or drinking for at least 8 hours prior to each day of study. As part of our efforts to determine compliance we took blood samples from the participants at each session and the participants were informed that this also was done in order to estimate the content of the active substances in their blood stream. The investigator was blinded during the study and the preliminary statistical analys, During the study the analysis of blood samples and measurement of FMD was done immediately after each session and the data were entered into the study database. The investigator was unaware of the allocation of the participants during the study. After conclusion of the study the allocation of each participant into two groups was given the investigator, but during this part it was still not revealed which group had been the control and which had been the interventional group.Following the hypothesis outlined in the introduction our primary outcome was if we would observe an increase in FMD in the interventional group during the intervention.Secondary outcomes were changes in blood pressure and changes in levels of blood cholesterol during the study in the interventional group.The results were analyzed using SAS software (version 9.10). Comparisons between intervention and control group were analysed by non-paired Student's t-test and comparison of changes over time for the intervention and the control group were performed using a paired students test. Results were presented with calculated mean values and confidence intervals for the measurements at the different session as well as for the differences between values in the two groups.It was assumed that a detectable effect would produce at least a 3% difference in FMD, on this assumption it was calculated that our study would have a power of 90% with 20 individuals in each group.The study enrolled 41 participants, 20 in the control group and 21 in the interventional group. In all 53 persons were screened prior to enrollment, of these10 did not meet the enrollment criteria and 2 decided not to participate. The reason for including one more in the interventional group was that one participant dropped out one day after receiving the sprouts owing to the disagreeable taste of the sprouts. One participant in the interventional group missed one visit because of hospitalization (leg fracture). All other participants received treatment as allocated and participated in examinations as planned. The baseline characteristics for the participants are listed in The FMD values with 95% confidence interval and p values calculated using students test for the intervention and control group are displayed in For the blood test taken simultaneously with the FMD measurements, we have not been able to detect any differences in these samples in the course of our study. The results for are shown in Systolic, diastolic as well as mean blood pressure did not change significantly during the study. Differences detected in the study were related to gender and age.Results are shown in The glucosinolate content of the sprouts was determined before and after the drying and packaging had taken place in order to ensure that the content of glucosinolates in the dried sprouts was known and to asses the possible deterioration of the glucosinolates due to the drying.Measurements of the concentration in the sprouts at the end of the study were similar to those prior to the study . The sprAs stated in the Apart from one participant leaving the study because of the taste of the sprouts which made her very uncomfortable, no adverse effects were observed during the study.In the current study we have tested whether dietary glucosinolates can improve endothelial function in patients with hypertension as it has been demonstrated in animal models.During this period, we have not been able to demonstrate any change in blood pressure, or blood samples reflecting blood lipids or inflammatory status. This finding is at odds with experiments carried out on spontaneously hypertensive stroke prone rats (SHSP), which may be due to a variety of factors. The animal study was designed to investigate if a daily dose of sprouts would protect against the development of hypertension, while we only studied endothelial function in patients with established hypertension. Furthermore, dosage as well as duration of treatment was also different, as the rats were given dried sprouts from weaning and until termination of the experiment after fourteen weeks, which translated to a human lifespan would imply treatment form early childhood into adolescence. Finally, hypertension is not a well described disease entity in humans whereas the SHSP are a distinct breed of rats characterized by their tendency to develop hypertension and stroke.Our study has some limitations that need to be addressed. The dose we gave was, if related to body mass, approximately 7 times smaller than the dosage given to the rats in the study discussed aboveThe fact that we were not able to detect glucosinolates in the blood of the participants raises the question if lack of compliance could be a reason for the lack of observed effect. Other studies does indicate that the glucosinolates in the precense of myrosinase will be transformed to isothocyanates at an early stage of digestionAs stated in the result section we did not find any changes in blood lipids measured during the intervention period. This is at odds with other experiments carried out in humans and with similar doses of sprouts, since Murashima et al demonstrated a decrease in total and LDL cholesterol in humans after one week of treatment with 50 g of fresh broccoli sprouts given daily, our daily dose had twice the glucosinolate content, comparable to 100 g fresh sprouts. We used dried broccoli sprouts as opposed to fresh sprouts, since other studies have shown a rather fast deterioration of the glucosinolate content in fresh broccoliChecklist S1CONSORT Checklist.(0.19 MB DOC)Click here for additional data file.Protocol S1Trial Protocol, in Danish.(0.10 MB DOC)Click here for additional data file.


Objective To assess whether non-polluting, more effective home heating  has a positive effect on the health of children with asthma.Design Randomised controlled trial.Setting Households in five communities in New Zealand.Participants 409 children aged 6-12 years with doctor diagnosed asthma.Interventions Installation of a non-polluting, more effective home heater before winter. The control group received a replacement heater at the end of the trial.Main outcome measures The primary outcome was change in lung function . Secondary outcomes were child reported respiratory tract symptoms and daily use of preventer and reliever drugs. At the end of winter 2005 (baseline) and winter 2006 (follow-up) parents reported their child’s general health, use of health services, overall respiratory health, and housing conditions. Nitrogen dioxide levels were measured monthly for four months and temperatures in the living room and child’s bedroom were recorded hourly.Results Improvements in lung function were not significant . Compared with children in the control group, however, children in the intervention group had 1.80 fewer days off school , 0.40 fewer visits to a doctor for asthma (0.11 to 0.62), and 0.25 fewer visits to a pharmacist for asthma (0.09 to 0.32). Children in the intervention group also had fewer reports of poor health , less sleep disturbed by wheezing , less dry cough at night , and reduced scores for lower respiratory tract symptoms  than children in the control group. The intervention was associated with a mean temperature rise in the living room of 1.10°C  and in the child’s bedroom of 0.57°C (0.05°C to 1.08°C). Lower levels of nitrogen dioxide were measured in the living rooms of the intervention households than in those of the control households . A similar effect was found in the children’s bedrooms .Conclusion Installing non-polluting, more effective heating in the homes of children with asthma did not significantly improve lung function but did significantly reduce symptoms of asthma, days off school, healthcare utilisation, and visits to a pharmacist.Trial registration Clinical Trials NCT00489762. Asthma is one of the most prevalent chronic diseases in childhood. In New Zealand about 25% of children report symptoms of asthma, and asthma is the second most common reason for children being admitted to hospital.4Evidence is growing that symptoms of asthma can be aggravated or triggered by adverse aspects of the indoor environment.9As well as cold temperatures, factors such as damp, mould, and pollutants  have been implicated in aggravating the symptoms of asthma.12Infants and elderly people spend proportionally more time indoors15Nitrogen dioxide has been widely used as a marker for outdoor air quality in studies of pollution related to vehicle emissions, but the most important source of personal exposure to nitrogen dioxide is unflued gas appliances.23Nitrogen dioxide is a proinflammatory gas and can exacerbate respiratory symptoms such as wheeze or cough. It can reduce immunity to lung infections and increase the severity and duration of an episode of flu.32Relatively few intervention studies have examined the effects of housing improvements on health and fewer still have shown an impact on symptoms of asthma.37We previously carried out a randomised controlled trial of the effects on respiratory health of insulating homes.We carried out a randomised controlled trial in which baseline measures were collected in winter (June to September) 2005. Households in the intervention group were allocated a non-polluting, more effective replacement heater  before the follow-up winter of 2006. The control group received a similar heater in 2007, after the final data collection in 2006.The study was carried out in five areas in New Zealand—Porirua and the Hutt Valley in the North Island and Christchurch, Dunedin, and Bluff in the South Island. Households were recruited from December 2004 to May 2005. We identified community coordinators in nine local asthma societies and primary health organisations . The community coordinators invited families who had a child with asthma to participate in the study. The study was also publicised in radio interviews. Overall, 899 applications were received of which 422 (47%) met the inclusion criteria: the family lived in a study area and had a child aged between 6 and 12 years with doctor diagnosed asthma and symptoms in the past 12 months; the child slept at least four nights a week in the house; the house contained a less effective form of heating (unflued gas or plug-in electric heaters); the family intended to live in the house over the two winter periods; and the homeowner agreed that the household could take part in the study. If more than one child in a household met the study criteria then the child whose birthday occurred first after 1 June became the index child.After enrolment and before winter 2005 participating houses were insulated to the current New Zealand building code standard, as our previous study had shown positive effects from insulation alone.1), and correct placement of temperature loggers and nitrogen dioxide diffusion tubes. At the end of winter 2005 the community coordinators assisted households in completing the questionnaires. To check for reporting bias we included three outcomes for which we hypothesised no association with the intervention: diarrhoea, vomiting, and ear infections. The questionnaires are available at www.wnmeds.ac.nz/healthyhousing.html.The research team trained the community coordinators in the informed consent procedures, completion of questionnaires and symptom diaries, use of Piko meters  for measuring peak expiratory flow rate and forced expiratory volume in one second  were explained at community meetings and described on the research group’s website. The homeowners chose a replacement for their existing heaters. Landlords were encouraged to consider their tenants’ preferences. An independent statistician then randomised the households to intervention or control groups, stratified by area and heater choice. The heaters were installed in the intervention houses before winter 2006. The control group were told that they would receive a replacement heater at the end of the study.Baseline measures were repeated after the intervention at follow-up in winter 2006. In 2006 we changed the format of the questionnaire, eliminating the instruction that if people answered no to the question on wheeze they were to skip related questions, and we added a question on twisted ankles to check for reporting bias. We changed the method of recording the data from the Piko meter to recording readings in the symptom diary, as the downloaded data from 2005 were unsatisfactory. The temperature loggers were reprogrammed to record temperature every hour instead of every 20 minutes and to remain in place for the whole winter. We re-emphasised to the community coordinators the need for accuracy and timely retrieval of data.Participants signed informed consent forms. Parents signed on behalf of their children. Households were told that the heaters were the property of the homeowner.The primary outcome measure was changes to lung function. The study was powered to show a reduction in the amplitude of diurnal changes, expressed as a percentage of their mean peak expiratory flow rate over winter (amplitude % mean). A total of 430 children were required to detect a 15% reduction in the intervention group compared with the control group, assuming a correlation with the previous year’s measurement of 0.4, with 90% power, α at 0.05, and a 15% non-response rate. Secondary outcomes were reported asthma symptoms, scores for lower respiratory tract symptoms from the diaries, asthma drug use, healthcare utilisation, and days off school. Intermediate outcomes were temperature and nitrogen dioxide levels in the living room and child’s bedroom.www.r-project.org/). The binary information  was analysed using both standard generalised linear models and analysis of covariance (adjusting for outcome at baseline) generalised linear models with the logistic link function. From these models we derived unadjusted odds ratios  as measures of effect size and adjusted odds ratios  as measures for precision of estimates. We similarly analysed the numerical counts  but with a Poisson link function. For these models we present the change for the intervention group compared with the control group as mean number of events, with 95% confidence intervals.Epi-Info version 3.4.1  was used to double enter the responses to the questionnaire and data from the diaries. We cleaned and analysed the data using the statistical package R version 2.4.1 , we used the overall mean and validated the results using the complete data. Results for the interpolated data were predominantly within 5% of the results for the non-interpolated data.1 and peak expiratory flow rate from three good forced expiratory manoeuvres, measured each morning and evening. The three outcomes presented are the best blow in the morning, in the evening, and that day.In the daily diaries individual respiratory symptoms were recorded on a nominal scale (0 to 3) as used previously.1.For all daily records we used a linear mixed modelWe tested model distributions by examining the dispersion variable in the Poisson models and QQ plots for the normal models. Ethnicity was collected using the standardised self identity question of Statistics New Zealand. When multiple ethnicities were reported we used prioritised Māori and then Pacific ethnicities.41Overall, 409 households were randomised. After exclusions and withdrawals 349 (85%) households remained  and daily peak expiratory flow rate .Table 2v good, very good, excellent) by their parents . Parental reports showed a reduction in sleep disturbed by wheeze  and dry cough at night .The other three symptoms  improved but not significantly. Of the four outcomes used to test for reporting bias  only twisted ankles showed a significant effect.Table 3Results from the daily symptom diaries are presented as mean ratios—the average score for the intervention group divided by the average score for the control group , 0.4 fewer visits to the doctor for asthma , 0.25 fewer visits to a pharmacist for asthma , and 0.27 fewer visits to the doctor for non-asthma related conditions .After the intervention, during the winter of 2006, the average living room temperature of intervention households was 17.07°C compared with 15.97°C for control households: a difference of 1.10°C . Similarly, the average temperature in the child’s bedroom for intervention households was 14.84°C compared with 14.26°C for control households: a mean difference of 0.57°C .Exposure to low temperatures, measured as degree hours—that is, hours per day, multiplied by number of degrees less than 10°C—was over 50% less in the intervention group than control group. In the living room the exposure was 1.13 degree hours in the intervention group compared with 2.31 degree hours in the control group, a difference of 1.18 degree hours . Exposure in the child’s bedroom was 2.03 degree hours in the intervention group compared with 4.29 degree hours in the control group, a difference of 2.26 degree hours .3v 15.7 μg/m3, P<0.001). A similar significant effect was found in the child’s bedroom .42Ambient outdoor nitrogen dioxide levels were the same in both groups, but indoor levels were significantly reduced in the intervention group. In 2006 the intervention group had significantly (P<0.001) lower geometric mean nitrogen dioxide levels in the living room than the control group  compared with the average cost of the unflued gas or portable electric heater ($NZ100 per house).The major limitation in randomised trials of this sort is the impossibility of implementing blinding of the participants or field workers, once they visited the home. This could have resulted in a reporting bias, although as all participants knew at the outset of the study that they would receive new heaters it is unclear in which direction this would be. However, the outcome measurements included both self report and blinded measures and when both were available, as with days off school, the blinded measures showed a greater effect, suggesting any reporting bias was in the direction of minimising the intervention effect. In addition, three of the four questions that tested for reporting bias were not significantly affected by the intervention. The other outcome (twisted ankles) showed increased reporting in the intervention group, also suggesting that any bias was in the direction of minimising the effect of the intervention.Another important issue is the choice of primary outcome measure; we chose lung function because it was more objective and because the study could not be double blinded. It may be that lung function is less important to the daily life of children with asthma than are the frequency and severity of symptoms. In addition symptoms may be more sensitive to change and more reliable than laboratory based measures carried out by children in a community setting.As highlighted by one study, managing a community trial with community organisations as partners is challenging for all parties.The results suggest that improving both the type and amount of heating in the homes of children with asthma does not significantly affect measured lung function but does have several beneficial effects. Houses in this study included all forms of tenure, and the households had a range of incomes, so apportioning the relative benefits to the participants and to the public good is an important policy issue. In the United Kingdom, Scotland has made the policy decision that installing central heating in all social and pensioner housing, regardless of tenure, is largely for the good of the public and will pay more health dividends than focusing on clinical waiting lists, as is done in England.47Although the improvement in lung function was not statistically significant, large improvements were found in the symptoms of asthma. These patient centred measures are arguably as important to the daily life of children with asthma as more objective measures, and adopting this environmental intervention is an effective adjunct to the pharmaceutical treatment of asthma symptoms.Observational, but few intervention, studies have shown associations between asthma symptoms and dampness and cold in poorly heated homesNon-polluting, effective heating did not significantly affect measured lung function of children with asthma but it improved wellbeing and reduced symptoms of asthma and days off school