Several previous epidemiological studies have shown a relation between drinking water quality and death in cardiovascular disease whereas others have not found such a relationship. An intervention study was undertaken to evaluate the effect of water with added magnesium and natural mineral water on blood pressure.A group of 70 subjects with borderline hypertension was recruited and consumed 1) a water low in minerals, 2) magnesium enriched water or 3) natural mineral water, in a random, double blind fashion during four weeks.Among persons with an initial low excretion of magnesium or calcium in the urine, the urinary excretion of magnesium was increased in the groups consuming the two waters containing magnesium after 4 weeks. A significant decrease in blood pressure was found in the group consuming mineral water at 2 and 4 weeks.The results suggest that minerals taken in water are significant for the body burden and that an intake of mineral water among persons with a low urinary excretion of magnesium or calcium may decrease the blood pressure. Further studies should investigate the extent of mineral deficiency in different populations and the efficiency of different vehicles for supplying minerals, particularly magnesium and calcium. A relation between mortality from ischaemic heart disease (IHD) and drinking water characteristics was first shown in Japan in 1957  and reviIn a case-control study, an inverse relation was found between the amount of magnesium in drinking water and death from acute myocardial infarction and for females also between the amount of calcium and death . Diets rRegarding individual minerals, several studies have been reported where hypertensive subjects were treated orally with nutritional doses of magnesium . The resEpidemiological studies on cardiovascular disease suggest that drinking water is an important vehicle for the supply of minerals . This isThe present intervention study was undertaken to determine the effect of minerals in water on one of the major risk factors for cardiovascular disease – blood pressure. Subjects with slightly elevated blood pressure consumed water with different levels of minerals. Serum and urinary levels of minerals were measured as a marker of intervention and blood pressure was measured before and after the intervention.Female and male subjects, aged 45 – 64 years (n = 70) were recruited by advertising in local newspapers. Inclusion criteria were living in an area with low magnesium content in the drinking water, systolic pressure 15 mm above normal values for their age, diastolic pressure above 90 mm Hg, and within 20% of ideal body weight. Exclusion criteria were hypertension target organ damage, chronic diseases , pregnancy, and taking oral contraceptives or regular intake of mineral supplements. Subjects with a diastolic pressure above 100 mm Hg were advised to consult a physician for treatment. A few persons decided not to seek a physician's advice and choose to participate anyway. The Ethical committee at the Medical faculty, University of Gothenburg, approved the study.Blood pressure was measured using standardized techniques before the intervention, at 2 weeks and at the end at 4 weeks. Two separate recordings were made (diastolic pressure as Korothoff phase 5) after 5 minutes of supine rest. The blood pressure is reported as the average of these recordings.idem). Magnesium and calcium levels in urine were expressed as the creatinine ratio.Blood samples were taken before and after the intervention to determine the serum concentration of magnesium, calcium, sodium, creatinine and potassium . Before and after the intervention period, 24 hours urine samples were collected and the amounts of magnesium, calcium, and creatinine were determined . Table Table In spite of the random allocation to the different waters, it was found that the group consuming water C comprised a larger number of persons with a high initial systolic pressure. In the groups receiving waters A and B, none of the subjects had systolic blood pressures above 170 before the intervention. The subjects drinking water C were divided into those with an initial systolic pressure above and below 170 mm. For the group with the higher pressure (n = 6), there was a decrease in the systolic pressure before and at 4 weeks p = 0.023) but no difference at 2 weeks or for diastolic pressure. The results from the remainder of the group are also shown in Table  but no dThe study is of exploratory character, based on a relatively small number of subjects and should be interpreted with care. There is also a lack of some data that retrospectively would have been of interest such as sodium in the urine and the effect of water with only calcium added. We do not think, however, that this has any influence on the major conclusions from the study.The intervention with the two waters with added magnesium influenced the body burden in terms of an increased excretion of magnesium in urine. This is consistent with findings from previous intervention studies ,17 althoThe intervention with water containing high amounts of several minerals decreased the blood pressure significantly in contrast to water with magnesium only where no significant effect was detected. This does not exclude that an effect could have been found with the latter water, had the intervention time been longer. On the other hand, the finding supports the concept that interventions should be performed under conditions similar to the ones present in normal environments, rather than with one specific agent. This could also explain the lack of an effect in previous studies where single minerals have been given as reviewed in the introduction.In summary, the results suggest that waterborne minerals constitute a supply for the body burden, that the urinary excretion can be used as a physiologically relevant indicator of the body burden of magnesium and calcium, and that the supplementation of magnesium together with other minerals may reduce blood pressure among persons with a low body burden of magnesium and calcium, either due to an insufficient intake through food or water, or through some metabolic/clinical disturbance. Additional studies are needed to explore this further.The study was supported by an unconditional grant to Gothenburg University from the Nestlé Water Institute, Vittel, France. The authors had full freedom for data analysis, manuscript preparation and submittance to a journal. RR has not received any fees or salaries for this work, including article processing charges, nor does he own any shares or has any other financial interest in the company. MA was an employee at the Water Institute at the time of the study.RR and MA jointly developed the research plan. RR conducted the field study. RR and MA jointly analyzed the data and wrote the manuscript.The pre-publication history for this paper can be accessed here:


This study was conceived to analyze how exercise and weight management psychosocial variables, derived from several health behavior change theories, predict weight change in a short-term intervention. The theories under analysis were the Social Cognitive Theory, the Transtheoretical Model, the Theory of Planned Behavior, and Self-Determination Theory.2; age = 38.3 ± 5.8y), participating in a 16-week University-based weight control program. Body weight and a comprehensive psychometric battery were assessed at baseline and at program's end.Subjects were 142 overweight and obese women  but with great individual variability. Both exercise and weight management psychosocial variables improved during the intervention, with exercise-related variables showing the greatest effect sizes. Weight change was significantly predicted by each of the models under analysis, particularly those including self-efficacy. Bivariate and multivariate analyses results showed that change in variables related to weight management had a stronger predictive power than exercise-specific predictors and that change in weight management self-efficacy was the strongest individual correlate (p < .05). Among exercise predictors, with the exception of self-efficacy, importance/effort and intrinsic motivation towards exercise were the stronger predictors of weight reduction (p < .05).The present models were able to predict 20–30% of variance in short-term weight loss and changes in weight management self-efficacy accounted for a large share of the predictive power. As expected from previous studies, exercise variables were only moderately associated with short-term outcomes; they are expected to play a larger explanatory role in longer-term results. Obesity and excessive weight are common concerns among people in industrialized countries. Scientific literature consistently reports the epidemic status of obesity e.g., -3], howe, howe3]]Albeit reported inconsistently in the literature, psychosocial variables are accepted as playing a key role in explaining weight management ,5. TheseThe SCT is the most frequently used paradigm in weight management interventions  and it iimplementation intentions) are also part of the behavior change intervention  and exercise ,28], witstages of change (SOC), which reflect the temporal dimension of the behavior, divided in six consecutive stages; and ii) a set of constructs that explain how people evolve along the SOC. These are named processes of change, i.e. cognitive and behavioral activities that individuals use to modify their experiences and environments to obtain the desired behavior. Also included in this model are the decisional balance, representing the pros and cons of engaging in the behavior, and self-efficacy, reflecting the person's confidence in performing the health behavior change  and exer change , e.g., [r change ], mainlyr change . Studiesr change . Weight r change . This str change . Suris ar change . In thisThe SDT is a motivation theory that highlights people's inherent need to evolve and to be integrated in a social scenario. Three primary needs that have been identified are competence, relatedness, and autonomy, which lead to different types of motivation to act, the most important and desirable being intrinsic motivation. This construct reflects our inherent tendency to seek out novelty and challenge, while feeling competent and autonomous in the process. Enjoyment, mastery, and positive feelings arise from this quest, reinforcing the continuation of the behavior. In opposition, extrinsic motivation is more externally driven, more controlled , and more disconnected from the behavior itself (more focused on its outcomes). Lastly, amotivation is a state where there is a lack of intention to act so that the outcome behavior has no personal value and feelings of competence are not present . The SDTThe previous theories constitute science' best effort to explain how peoples' decisions and choices toward exercise and healthy nutrition are built . They arBuilding on recent discussions on the usefulness of theory-based interventions in health behavior promotion -40 and f2, and be free from major disease to be eligible for the study. After the selection process 142 overweight and obese women  started the program. For this study, only the first four months are being analyzed, a period during which all participants received the same intervention; they were later randomized to two different long-term programs or to controls. Attrition was 6.3% from baseline to 4 months (133 completers). However, some psychometric data were incomplete due to errors in the completion of some questionnaires either on baseline or after the intervention, leading to smaller sample sizes in some analyses.Participants were recruited from the community for a 2-year weight management program through newspaper ads, a website, email messages on listservs, and announcement flyers. Subjects were required to be older than 24 years, be premenopausal and not currently pregnant, have a BMI higher than 24.9 kg/mThe intervention was composed of fifteen weekly meetings, which lasted 120 minutes, and where both educational and practical components were scheduled. Attendance averaged 83% and groups were composed of 32–35 women, who entered the study in two cohorts. The intervention has been described before  and was In short, content included exercise, nutrition, and behavior modification components. Exercise topics ranged from the caloric expenditure of some common physical activities to choosing the right apparel to exercise. Exercise behavioral contents involved a motivational setup to increase walking and lifestyle physical activity, in which a pedometer was distributed and planning and log techniques were taught. Nutrition topics dealt, for example, with macronutrient and micronutrient content of the most common foods, energy density, and meal frequency. Behavioral nutrition contents comprised planning for special occasions, using the hunger scale, emotional eating, and preventing lapses, among others.These contents were expected to have effects on several constructs of the health behavior theories studied in the present investigation. For example the planning techniques should have an effect on intentions, on expected outcomes and in behavioral POC, while the more instructional activities should have interfered with attitudes, perceived barriers and in cognitive POC. In the beginning of each session participants were asked to share with the group their program-related experiences in the previous week. This discussion should have impacted on social support, social norms and self-efficacy, by vicarious learning and also by verbal and social persuasion from both staff and group members. Lastly, the intervention had the underlying goals of improving autonomy and that the participants should choose the tasks that were more enjoyable to them. These are highly motivational factors that have an effect on SDT constructs, accounting specifically for intrinsic motivation.The sessions were conducted by a team composed by two Ph.D.- and six M.S.-level exercise physiologists, psychologists, or dietitians. Participants were provided with individualized dietary plan and specific physical activity goals, aiming to induce an energy deficit of 300–500 kcal/d, by comparison with baseline values. Participants were informed that weight loss should be understood as a long-term goal, and that 5% weight loss after six months was an appropriate goal.A large battery of psychometric instruments was used in this study and participants were requested to attend two sessions for their completion, in each evaluation period. The instruments were Portuguese validated versions of some of the most used instruments for the constructs under analysis. In this section and throughout the manuscript, variables were divided and are presented in two separate categories: "weight management" and "exercise".The SCT weight management-related variables included self-efficacy and outcome expectancy measures. The Weight Efficacy Lifestyle Questionnaire WEL – ,44] is a is a44]]The TTM weight management constructs were i) self-efficacy ,44, ii) The TPB weight management constructs were assessed by a set of 18 items ,48 measuSocial-cognitive theory exercise-related variables comprise self-efficacy, perceived barriers, and social support. Exercise self-efficacy was measured with the Self-Efficacy for Exercise Behaviors Scale SEEB – ,50], ass, ass50]]The TTM exercise related variables were self-efficacy ,50, SOC,The TPB exercise-related variables were assessed through 17 items ,56 measuWe used the Intrinsic Motivation Inventory IMI – ,58], to , to 58]]Weight was measured at baseline and four months. A standardized procedure was used where weight was measured twice, to the nearest 0.1 kg (average was used), using an electronic scale .For correlational analyses, all variables were expressed by the residuals of the 4-month variable value regressed on baseline data. This procedure is recommended by Cohen and Cohen  as it crThe impact of the intervention on weight and psychosocial variables was assessed by paired t-test procedures. Effect size' were calculated, and the criteria to designate its magnitude was the following: < .30 small effect size; .30 to .80 medium effect size; >.80 large effect size .The linear bivariate association between changes in weight and psychosocial variables were assessed by Pearson correlations. Multiple regression models were created to evaluate the multivariate estimates for the associations between psychosocial variables and weight change. The health behavior models' variables were entered separately in seven regression designs (three for the weight management related models and four for the exercise related models). The squared semi-part correlation was calculated to reflect the unique contribution of each predictor to the variance in the outcome variables .Weight change (WC) showed a large individual variability , contemplation (35.5%) and preparation (37.5%). After the 4-month intervention, these numbers were inverted, as participants were mostly in the action (58.6%) or maintenance (18.0%) stages. Further analysis of the exercise-related psychosocial variables , while maintenance was reached by 11.7% of the women. Weight management psychosocial variables did not change as markedly as exercise constructs and different variables emerged as significant, with intentions, subjective norms and outcome expectancies showing no change, while behavioral POC , self-efficacy , cognitive POC , attitude , and PBC  reflected the desired intervention changes.Pearson correlation was used to analyze associations between predictors and WC Table . The firTo look further at the predictive power of constructs from behavior change models on WC, we designed a set of multiple regressions, with separate models for the constructs within each theory Tables  and 4. T2 = 26.8%, p < .001), mostly due to changes in self-efficacy, which independently explained 19.4% of WC variance, seconded by behavioral POC with 3.1%. The SCT represented the next strongest model , with changes in self-efficacy alone contributing 20.5% to the explained variance. The model for TPB explained 17.6% (p < .001) of the variance in weight change, with attitude and PBC showing similar semi-part correlation values . All other weight management psychosocial constructs did not contribute significantly to the models.Weight management variables presented the stronger models, particularly the TTM , seconded by TTM . Change in self-efficacy was the only variable that significantly added predictive power to these models . The other models did not account significantly to weight change, although the importance/effort dimension in the SDT model independently contributed with 4.8% of the explained variance (p = .015).Table 2) scores; c) Theories that included self-efficacy (TTM and SCT) presented the stronger regression models, and d) Change in variables and models related to weight management had higher predictive power than those from exercise-related models.This study was conceived to analyze how changes in key psychosocial exercise- and weight management-related variables, derived from four important health behavior theories, would predict weight change during a behavioral obesity treatment short-term intervention. Weight change was significantly predicted by several single variables and by health behavior change theories/models as a whole. The following were this study's primary findings: a) Change in eating/weight management self-efficacy was the single best correlate of weight reduction, though several other variables were also associated with weight outcomes  ; b) About 20–30% of the variance in weight change was explained by the best prediction models and most showed statistically significant prediction  [The stronger models, TTM and SCT, were weight management-related and both included self-efficacy. We found few studies that have analyzed  losses) ,64. In t losses) . It coul losses)  reviewed losses) ,66. Inte losses) , raisingExercise processes seemed to be substantially influenced by the intervention, which included information on how to cope with common barriers, recommended exercises , scheduling techniques, physiologic and psychological benefits of exercise, and how to use/find available resources. Nevertheless, exercise-related variables and models were only moderately associated with weight outcomes with self-efficacy again showing the highest bivariate and multivariate associations. It is interesting to note that despite its association with weight loss, mean exercise self-efficacy scores did not change significantly during the intervention. As pointed out before , it is pSelf-Determination Theory was only evaluated regarding exercise constructs and represented a stronger model than the TPB, with the importance/effort dimension emerging as a single predictor from SDT. The intervention sessions repeatedly reinforced the importance of exercise for the success in weight management, especially for long-term outcomes, for instance by citing results from the National Weight Control Registry results . As a coLimitations of this investigation include self-reported data, the absence of a control group, a relatively small sample, and the lack of complete evaluation for some models , mostly due to the absence of validated Portuguese questionnaires for these constructs. Also, some of the constructs were analyzed with less than ideal measures, such as outcome expectancies. Finally, multiple measures collected during the 4-month program, instead of only pre and post results, would have improved our assessment of the psychosocial variables by better describing changes in each construct throughout the program.In sum, we observed that theories that comprise self-efficacy are the most predictive of weight change and that weight management- and eating-related constructs and theories better explain the variance in short-term outcomes, compared to exercise models. To a lesser extent, exercise theories were also predictive. However, their predictive power is expected to increase in longer-term analyses, especially for variables related to intrinsic motivation and SDT. This is in line with recent results in a very similar intervention, where psychosocial eating variables better predicted 4-months results while exercise motivation constructs were superior correlates of 16-month weight loss . In the The author(s) declare that they have no competing interests.ALP and PJT conceived the study and drafted the manuscript. ALP performed the statistical analysis, was responsible for psychometric assessments and participated in the study's implementation. TLB, SSM, CSM, and JTB actively participated in the study implementation and in data collection. SOS participated in the study design and in the selection of psychosocial predictors. LBS is a principal investigator in the research trial. All authors read and approved the final manuscript.


The relationship between BMI and leptin has been studied extensively in the past, but previous reports in postmenopausal women have not been conducted under carefully controlled dietary conditions of weight maintenance using precise measures of body fat distribution. The aim of the present study was to examine the association between serum leptin concentration and adiposity as estimated by BMI and dual energy x-ray absorptiometry (DEXA) measures  in postmenopausal women.This study was conducted as a cross-sectional analysis within the control segment of a randomized, crossover trial in which postmenopausal women (n = 51) consumed 0 (control), 15 (one drink), and 30 (two drinks) g alcohol (ethanol)/d for 8 weeks as part of a controlled diet. BMIs were determined and DEXA scans were administered to the women during the 0 g alcohol treatment, and a blood sample was collected at baseline and week 8 of each study period for leptin analysis.2) had a 2-fold increase, and obese women (BMI > 30 kg/m2) had more than a 3-fold increase in serum leptin concentrations compared to normal weight (BMI ≤25 kg/m2) women. When the models for the different measures of adiposity were assessed by multiple R2, models which included percent body fat explained the highest proportion (approximately 80%) of the serum leptin variance.In multivariate analysis, women who were overweight (BMI > 25 to ≤ 30 kg/mUnder carefully controlled dietary conditions, we confirm that higher levels of adiposity were associated with higher concentrations of serum leptin. It appears that percent body fat in postmenopausal women may be the best adiposity-related predictor of serum leptin. Natural menopause, a normal aspect of aging, may influence risk of breast cancer , the leain vitro models, leptin acts as a growth factor and stimulates cellular proliferation, angiogenesis, motility, and invasion [In various invasion -20. Leptinvasion ,20 and cinvasion . Leptin invasion . In thisstudy periods; each study period was separated by two-five week washout periods. Total and regional adiposity measurements were assessed during the fourth week of the control treatment . DEXA  whole body scans were used for adiposity assessments; measures of BMI were taken on the same day.This study was part of a randomized, crossover, intervention trial of moderate alcohol supplementation in postmenopausal women (n = 51). Details of the study design and procedures have been published previously ,24. Brie(1) women ≥ 50 y of age, (2) postmenopausal , (3) not receiving hormone replacement therapy (HRT), (4) not taking prescription medications that might interfere with the study, (5) willing and able to consume the diet prepared or approved by the Center and no other foods or beverages, and (6) without personal or parental history of alcohol abuse. The subjects were evaluated by a physician and determined to be in good health with no signs or symptoms of any disease or endocrine disorders.Postmenopausal women were recruited by advertisement from the communities surrounding the Beltsville Human Nutrition Research Center, Beltsville, MD. The eligibility criteria were: This study was approved by the National Cancer Institute's Institutional Review Board and the Committee on Human Research of the Johns Hopkins University Bloomberg School of Hygiene and Public Health. All subjects were fully informed of the study requirements and were required to read and sign a consent form detailing the objectives, risks, and benefits of the study. The subjects were compensated for their participation.All meals were prepared at the Beltsville Human Nutrition Research Center from typical U.S. foods and served in a seven-day menu cycle. Each day's diet provided 15% energy as protein, 50% energy as carbohydrate, and 35% energy as fat, with a polyunsaturated/monounsaturated/saturated fat ratio of 0.6:1:1. Daily fiber intake was 10 g/1,000 kcal, and daily cholesterol intake was 150 mg/1,000 kcal. Diets provided 100% of the U.S. recommended dietary allowances for vitamins and minerals . The stuBody composition was determined by pencil beam dual energy x-ray absorptiometry . Subjects were placed in a supine position with arms and legs close to their body for a whole body scan following the manufacturer's recommended protocol. Whole body and regional lean mass (mass of bone and nonfat soft tissue) and fat mass were determined using the manufacturer's algorithm (software version 1.33).During the last week of the control treatment, blood samples for leptin analysis were collected from fasting (> 12 hours) subjects before breakfast (6:30 AM to 9:00 AM) on each of three non-consecutive days in each study period. An equal volume of serum from each day's blood draw was pooled for analysis. Serum was separated and aliquots were frozen at -70°C. The laboratory methods for the serum leptin measurements were described previously . BrieflySerum leptin concentrations were log transformed using the natural log. All estimates of means and the differences between means were made using the log transformed leptin values. In tables we report means and regression coefficients returned to the original (arithmetic) scale.2 calculated from measured weight and height) were determined. Mean serum leptin concentrations for BMI categories were estimated using linear regression models that included a series of indicator variables for three standard BMI categories . BMI categories were also modeled as ordinal variables with values 0, 1, and 2. Additional models estimated percent changes in serum leptin concentrations per one-unit change in BMI, one-percent change in total body fat (measured as percent body fat), and 1000 g change in central, peripheral, or lean mass modeled as continuous variables. All models included age (continuous), parity (continuous), race , age of menarche , and family history of breast cancer . One woman's breast cancer information was missing and she was excluded from models that included breast cancer history. Sensitivity models including her as having or not having a family history of breast cancer did not change analysis conclusions. In a second series of models (Model 2), we added BMI to Model 1 as a covariate The addition of alcohol group assignment order, study period, hysterectomy, duration of menses, years since last menses, nulliparity, and age at first birth (for those with children) did not improve the precision of the estimates and these terms were not included in the final models. There was no evidence of effect modification as assessed by likelihood ratio tests of model fit after the addition of cross-product terms to models that included main effects. Throughout the paper all P-values are two-sided nominal (unadjusted) P-values. P-values for BMI and DEXA measurements were determined using likelihood ratio tests comparing models with the BMI or DEXA term of interest to models without that term. Multiple R2 and F-tests were calculated from the linear regression models. Statistical analyses were performed using S-PLUS .Pearson and Spearman correlations between the different DEXA measurements and BMI (kg/m2 to 42.5 kg/m2 (median 26.9); and total body fat ranged from 7,942 g to 55,756 g , while trunk, leg, and arm fat were of progressively lesser magnitude. Descriptive statistics for serum leptin concentrations are also presented in Table Fifty-one women successfully completed the entire study and are included in the present analysis. The physical characteristics and reproductive history of the subjects at baseline are provided in Table P < 0.0001). Among obese subjects, serum leptin concentrations were more than three-fold those seen in the normal weight subjects.Table Table 2 was used to assess the strength of the linear associations of the overall models to leptin , all adjusted for the covariates, so that they can be compared. Looking at the multiple R2 values, we found the percent body fat model explains a largest proportion (more than 80%) of the variance associated with serum leptin concentrations, and thus appear to be very strongly associated with serum leptin concentrations. However, all of the R2 values in Table Our adiposity measures are on different scales and it is difficult for example, to compare changes of one percent in body fat versus one kg body fat versus one BMI unit, thus we also used multiple RIn addition to the previous studies which suffer from inadequate control of diet and energy balance (known confounders of leptin levels) -14, in pSince increased BMI  and centAlthough our study is limited by its cross-sectional design and modest sample size, the strengths of this study include a homogeneous study population  and measurement stability, which resulted from the use of a carefully controlled diet adjusted to maintain body weight. The DEXA scans employed are considered a reference method for body composition analysis . AlthougIn conclusion, our study demonstrated that serum leptin concentrations showed striking differences by adiposity levels. Increased exposure to leptin was observed for increased adiposity determined by BMI, percent body fat, central and peripheral fat as well as lean body mass. Although BMI and DEXA adiposity  are highly correlated in this cross-sectional study, it remains for further studies to confirm and refine our observations regarding: (i) percent body fat as the best adiposity-related predictor of serum leptin, and (ii) the independent value of central body fat in this prediction even after adjustment for BMI. Because of the well-known arguments for limitations in the use of BMI , such asThe author(s) declare that they have no competing interests.


African American women exhibit a higher mortality rate from breast cancer than do white women. African American women are more likely to gain weight at diagnosis, which may increase their risk of cancer recurrence and comorbidities. Physical activity has been shown to decrease body mass index and improve quality of life in cancer survivors. This study was designed to evaluate the feasibility and impact of a community-based exercise intervention in African American breast cancer survivors.A theory-based eight-week community intervention using pedometers with scheduling, goal setting, and self-assessment was tested in a convenience sample of African American breast cancer survivors (n = 24). Data were collected at three time points to examine changes in steps walked per day, body mass index, and other anthropometric measures, attitudes, and demographic variables.Statistically significant increases in steps walked per day and attitude toward exercise as well as significant decreases in body mass index, body weight, percentage of body fat, and waist, hip, and forearm circumferences, as well as blood pressure, were reported from baseline to immediate post-intervention. Positive changes were retained or improved further at three-month follow-up except for attitude toward exercise. Participant retention rate during eight-week intervention was 92%.Increasing walking for exercise, without making other changes, can improve body mass index, anthropometric measures, and attitudes, which are associated with improved quality of life and reduced risk of cancer recurrence. The high participant retention rate, along with significant study outcomes, demonstrate that among this sample of African American breast cancer survivors, participants were motivated to improve their exercise habits. African American women exhibit a higher rate of breast cancer mortality when compared with white women ,2. BeingUntil recently, women who have completed cancer therapy have been offered little to improve survival or decrease risk of new disease. Yet studies show that as a group, breast cancer survivors are interested in improving their health behaviors and quality of life ,7. Two rTo address weight gain in African American breast cancer survivors, we designed a theory-based cognitive-behavioral walking program to test its feasibility and impact on steps per day and BMI. The study was pilot tested among African American breast cancer survivors, using a community education model in an urban inner-city setting.We pilot tested an eight-week community-based walking program in a convenience sample of African American breast cancer survivors (n = 24) to investigate feasibility and impact on outcome measures over three time points: 1) baseline, 2) immediate post-intervention, and 3) three-month follow-up. African American women who 1) had been diagnosed with breast cancer, 2) had completed treatment at least three months before recruitment, 3) were mobile, and 4) were less than 70 years of age were eligible for the study.Using a broad, organized effort, participants were recruited from Massey Cancer Center clinics, outreach sites, contacts with local churches, community leaders, and breast cancer organizations including breast cancer support groups. A city council member, along with other breast cancer survivors, was also instrumental in communicating study information throughout the community. Flyers, television announcements, and personal communication were used during the three-month recruitment effort. We contacted approximately 230 potentially eligible women. Recruitment rate was approximately 10%. Reasons for nonparticipation included having cancer treatment within the prior three months, not being able to attend community meetings because of work or family commitments, or having comorbid conditions that decreased mobility.The theory-driven intervention was designed with the primary study goal of integrating walking into one's daily routine. The Health Belief Model was used as the theoretical framework for the intervention . This weStudy variables were assessed at three time points: baseline, immediate post-intervention, and at three-month follow-up. The study goal was the integration of walking into the participant's daily routine. The primary study outcomes were changes in number of steps and BMI. Steps per day were measured using a steps-only pedometer. Participants were instructed to wear the pedometer upon rising in the morning until bedtime and to record the number of steps walked. BMI was calculated from weight and height using a calibrated scale. Waist, hip, and upper arm circumferences were measured using a tape measure, and blood pressure was measured with a standard blood pressure cuff. Body-fat percentage was measured using Futrex, a portable near-infrared sensor system . All cliParticipant demographic information, cancer history, and attitudinal measures were assessed using standardized survey items from other study instruments. The instrument was pilot tested in a comparable age group of African American women. Attitudes toward exercise were measured using the Exercise Decisional Balance instrument , a 16-itt tests were used to determine differences in mean anthropometric and attitudinal measures between the three time points. In addition, based on frequency distribution of time since diagnosis, all study variables were tested among those diagnosed three years or less prior to start of the intervention (1999–2002) (n = 10) and those diagnosed earlier (1978–1998) (n = 12), using independent samples t tests.Data were entered into a database using SPSS statistical software . Descriptive statistics were determined for all study variables. Analysis of variance was performed to test for differences in measures collected at baseline, immediately after intervention, and at three-month follow-up. Paired Twenty-four women were enrolled in the intervention study. One participant dropped out because of scheduling conflicts. One experienced a cancer recurrence, resulting in 22 eligible women completing the intervention.Feasibility was determined by examining attendance at weekly sessions, study retention, and receptivity to pedometer use. Attendance at weekly sessions was excellent, with 70% of the participants attending seven or more intervention sessions. Study retention to the eight-week study was also excellent, with 22 of 24 women completing the intervention and immediate post-assessment. Participants had positive experiences using the pedometers and recording steps per day. Broken or lost pedometers were reported by approximately 25% of the study sample, and they were replaced to ensure continuous data collection. Additional data showed that 95% responded "about right" to a survey item asking whether number of study sessions were too many, too few, or about right.P < .001), hip circumference (P = .009), forearm circumference (P < .001), systolic blood pressure (P = .002), diastolic blood pressure (P = .001), and attitude toward exercise (P = .005).Results of ANOVA analyses of repeated measures  showed statistically significant differences in steps per day . Other significant decreases included the following: BMI (P = .004), body weight (P = .005), percentage body fat (P = .003), and forearm circumference (P = .007). Increased positive perception of exercise was also reported (P = .03).P = .04), forearm circumference (P = .04), and diastolic blood pressure (P = .02). Thus, all anthropometric measures either stayed the same or showed further improvement by further reduction in measures from immediate post-intervention to three-month follow-up. Of all study variables, only attitude toward exercise significantly changed direction (P < .001), with women showing a more negative opinion of exercise by three-month follow-up compared with immediate post-intervention. There were no differences in mean study outcomes in the participants who did not attend three-month follow-up assessment sessions (n = 5) compared with participants who did attend and had measurements (n = 17).P = .02) when compared to earlier diagnosed women. The same effect was true at immediate post-intervention for both diastolic blood pressure (P = .02) and systolic blood pressure (P = .003). At three-month follow-up, recently diagnosed women were significantly more likely to have higher waist measures (P = .048), with trends toward larger hip (P = .06) and body fat (P = .05) measures than earlier diagnosed women.More recently diagnosed women tended to have higher body measures at all three time points, but only diastolic blood pressure was significantly higher at baseline (We found statistically significant changes in the main study outcomes of steps per day, BMI, and virtually all of the anthropometric changes measured in the study population after an eight-week intervention, with most results remaining at three-month follow-up. The breast cancer survivor participants were motivated and compliant with the intervention, which likely enhanced their success. Having had cancer and understanding their risk of recurrence may account for the strong motivation we found in this population, as suggested by the constructs of the Health Belief Model. It is also important to note that the sample participants all had more than a high school education, which may also have contributed to their success.Although we found only a few statistically significant differences in mean body measures in relationship to time since diagnosis, we may have detected more evidence of this pattern had we had a larger study sample. While not significant, the more recently diagnosed women had larger body measures and lower mean steps per day than earlier diagnosed women at both immediately post and at three-month follow-up.The goal of the study was to have women integrate walking into their daily routines on their own. They attended sessions for education, motivation, and self-assessment; walking did not take place during the study sessions. This was an important feature of the study design because research shows that compliance is likely to decline significantly after an intervention is completed . Thus, oThe mean change in body weight was modest but significantly less than baseline. This level of weight loss supports what similar interventions have reported . We wereWomen in the study improved their attitude toward exercise from baseline to post-intervention by reporting fewer barriers to exercise over the study period. This was not surprising given the focus of the intervention sessions on overcoming personal obstacles to exercise. However, the attitudinal improvement did not hold at three-month follow-up. Although steps per day did not significantly change at three-month follow-up, one might wonder if the decline in exercise attitude might eventually negatively influence exercise behavior after a longer time interval. Cancer stress scores did not change significantly over the course of the intervention. However, scores for this variable were not particularly high even at the start of the intervention. This could be related to the fact that only 18% of participants were diagnosed during the 12 months prior to the start of the study. Cancer stress may subside as time passes after a woman's diagnosis. Had we studied a group of more recently diagnosed women, we may have found more evidence of cancer stress at baseline and potential for impact after the exercise intervention than we did the with this study population.and physical activity — are modified. Overall, the study objectives were realized, and the study provides interesting pilot data for testing a more comprehensive lifestyle intervention in a similar population. However, the sample does not constitute a representative sample, and the study findings may not be applicable to other breast cancer survivors.This study was limited by the study size and lack of control group. For a pilot study, however, the sample size was adequate to study feasibility and study outcomes. In addition, the study reflects the common limitations for relying on self-report data. Anthropometric variables were included in the study in addition to self-reported data to provide measured data for evaluating results. The intervention tested exercise only; thus, even more significant changes among this population are possible if both energy balance components — food intake Steps walked per day, BMI, body circumferences, blood pressure, and attitudinal variables all showed improved mean statistically significant changes in this population of African American breast cancer survivors after a theory-based cognitive-behavioral community intervention. The study showed strong feasibility measures in positive response to using pedometers, high participant retention, social support, and excellent compliance after eight weeks. Given data indicating obesity is associated with shorter breast cancer survival time, these study results may position breast cancer survivors to have both improved quality of life and reduced risk of cancer recurrence. Further study is needed to test a randomized comprehensive diet and exercise intervention in African American breast cancer survivors against controls in a longer, larger randomized trial with additional study variables.


Asthma and allergic diseases are becoming increasingly frequent in children in urban centres of Latin America although the prevalence of allergic disease is still low in rural areas. Understanding better why the prevalence of asthma is greater in urban migrant populations and the role of risk factors such as life style and environmental exposures, may be key to understand what is behind this trend.The Esmeraldas-SCAALA  study consists of cross-sectional and nested case-control studies of school children in rural and urban areas of Esmeraldas Province in Ecuador. The cross-sectional study will investigate risk factors for atopy and allergic disease in rural and migrant urban Afro-Ecuadorian school children and the nested case-control study will examine environmental, biologic and social risk factors for asthma among asthma cases and non-asthmatic controls from the cross-sectional study. Data will be collected through standardised questionnaires, skin prick testing to relevant aeroallergen extracts, stool examinations for parasites, blood sampling , anthropometric measurements for assessment of nutritional status, exercise testing for assessment of exercise-induced bronchospasm and dust sampling for measurement of household endotoxin and allergen levels.The information will be used to identify the factors associated with an increased risk of asthma and allergies in migrant and urbanizing populations, to improve the understanding of the causes of the increase in asthma prevalence and to identify potentially modifiable factors to inform the design of prevention programmes to reduce the risk of allergy in urban populations in Latin America. Large increases in the prevalence of asthma and allergic diseases have been reported in industrialized countries during the last twenty to thirty years ,2, althoAllergic diseases are caused by a complex interaction between host genetics and environmental exposures. Temporal trends in allergy prevalence in developed countries , and theRural residence is consistently identified as the strongest protective factor against asthma in epidemiological studies ,9 and isChanges in exposures to many different environmental and life style factors are likely to occur in populations that migrate from rural to urban areas, and studies of migrants to urban areas and comparisons of environmental exposures with the original rural and with more established urban populations should allow the effects of environmental exposures in early life (e.g. causing immune programming) on allergy risk to be distinguished from the effects of current exposures. Clarification of the dynamics behind the causation of allergy and asthma in urban migrant populations will further improve our understanding of what is behind the increase of frequency of these diseases with urbanization and westernization. The identification of modifiable risk factors could lead to new public health initiatives to reduce the burden of allergic disease among urbanizing populations.Latin American countries are undergoing a rapid process of population change that includes urbanization, migration, economic development and adoption of a "modern" lifestyle. Among the burgeoning urban populations of Ecuador and other Latin American countries, asthma and allergic diseases are perceived to be an increasingly important public health problem of children , althougThe study described here is part of the Programme "Social Change, Asthma and Allergy in Latin America" (SCAALA), a research programme being conducted in Ecuador and Brazil , funded by The Wellcome Trust as part of the programme of Major Awards to Centres of Excellence in Latin America. The SCAALA collaboration aims to clarify the social and biological mechanisms that mediate the effect of population and lifestyle changes on the frequency of atopic diseases. This paper deals with the methodological aspects of the study being conducted in Ecuador.The study in Ecuador aims to study changes in the prevalence and risk factors for asthma and allergy in populations that migrate from rural to urban areas and examine how such changes may relate to changes in the risk of atopic disease. The study will measure the frequency of symptoms of asthma, allergic rhinitis and atopic dermatitis in school children in urban and rural areas, and will collect detailed information on life style factors and environmental exposures that may affect the frequency of atopic diseases in the urban and rural environments. The study will investigate also changes in key immunologic factors (i.e. cytokines) and environmental exposures  that may be associated with altered asthma risk in the rural and urban study groups. On the other hand, the SCAALA study in Brazil aims to investigate the associations between the prevalence and incidence of allergic diseases, environmental exposures, particularly hygiene-related exposures, and immunological parameters in a cohort of children in the city of Salvador in the State of Bahia, and has been described elsewhere .Ecuador is among the poorest of South American countries, with an estimated per capita GDP of US$4,300 in 2005 and industrialization that is far less advanced compared to richer countries in the region, such as Chile  . In Ecua2 and has a population of approximately 429,000. The main economic activities are oil industry, tourism, timber extraction, and African palm oil. The principal city in the Province is Esmeraldas, with a population of 250,566 that is home to approximately 80% of the Ecuador's Afro-Ecuadorian population [The study is based in Ecuador's northern coastal province, Esmeraldas Province. The Province covers an area of 15,237 kmpulation . Esmeralpulation . Over thThe study will be conducted among school children attending rural schools in Afro-Ecuadorian communities in the District of Eloy Alfaro, in a tropical coastal area of Esmeraldas Province, and in marginal Afro-Ecuadorian 'barrios' in an urban centre, where migrants from the rural area  congregate.The study forms two parts: (i) a cross-sectional study of environmental factors associated with atopy and allergic symptoms in school-age children in the rural District of Eloy Alfaro in Esmeraldas Province and in 'barrios' of the city of Esmeraldas where rural migrants congregate; and (ii) a nested case-control study of environmental risk factors for asthma using asthma cases identified from the cross-sectional study in urban and rural school children and a random sample of non-asthmatic controls.A total of 4,000 school children, aged 7 to 15 years, living in the District of Eloy Alfaro and 2,500 children of the same age range, living in the city of Esmeraldas, will be assessed to estimate the frequency of atopy and allergic diseases, including asthma, rhinitis and eczema, and identify and compare risk factors associated with these outcomes in urban and rural study populations. School children in urban areas will be defined by place of birth, period of residence in urban area and at what age, and whether their parents are migrants  or not. The cross-sectional study will examine the relationship between atopy and allergic symptoms in urban and rural school children and the environmental factors that modify this relationship.Asthma cases  and non-asthmatic controls , respectively, will be identified from the results of an allergy symptom questionnaire performed in the cross-sectional study by the questions – "Have you had wheezing or whistling in the chest in the last 12 months? " and "Have you ever had wheezing or whistling in the chest at any time in the past?" Non-asthmatic controls will be randomly selected from all children in each of the urban and rural areas that respond negatively to the second question. Nested case-control studies in the urban and rural areas will identify risk factors associated with symptoms of recent wheeze using both quantitative and qualitative epidemiological methods, investigations of immunological function and measurements of allergens and endotoxin in the environment.Data are available for the prevalence of recent wheeze in urban and rural study areas, from pilot surveys of 245 and 536 school children, respectively. These surveys estimate the prevalence of recent wheeze to be greater in the urban area . The prevalence of atopy was similar in urban and rural school children . A sample of 4,000 children in the rural area and 2,500 children in the urban area will provide approximately 820 cases of atopy for the cross-sectional study, and 292 and 335 cases of asthma for the case-control study in the rural and urban areas, respectively. Two hundred asthma cases from each area will be recruited into case-control studies . The study will have a case-control ratio of 1:4 . With a study power of 80% and P < 0.05, the nested case-control studies combined  will be able to detect significant effects on asthma of common exposures  with OR<0.7 and rare exposures  with OR<0.5. Likewise, the individual case-control studies  with the same power and level of significance will be able to detect an effect of OR<0.6 for common exposures , and OR<0.4 for rare exposures (10%).Asthma, rhinitis and eczema will be defined according to the core allergy symptom questions of the International Study of Allergy and Asthma in Childhood (ISAAC) . Atopy wA. Cross-sectional study: The questionnaire has been modified from the ISAAC Phase II study questionnaire [ionnaire , and hasionnaire ,25). TheB. Case-control study: A questionnaire for a more detailed history of asthma, rhinitis and eczema symptoms, based on the ISAAC phase II supplementary questionnaires [onnaires , will beonnaires  and of rThe presence of exercise-induced bronchospasm (EIB) will be assessed in all children in the case-control as described previously ,26. Briez-scores for weight-for-age, weight-for-height and height-for-age will be calculated using the EPINUT program .Finger prick blood samples will be collected from all subjects in the cross-sectional study to estimate hemoglobin level using standard procedures. Anthropometric measurements will be performed using standardised methodology and will include weight (kg), height (cm) and triceps skin fold thickness (mm). Entamoeba histolytica (with ingested red cells) and Giardia intestinalis will be offered appropriate doses of tinidazole.Single stool samples will be collected from all children and examined using the modified Kato-Katz and formol-ether concentration methods . IntestiDermatophagoides pteronyssinus mite and the American cockroach, Periplaneta americana. Dust samples will be analyzed for endotoxin and fungal β-glucans  and allergens from D. pteronyssinus (Der p 1) and P. americana (Per a 1) .Dust samples will be collected from the homes of the children in the case-control study using a ~ 1200 W vacuum cleaner, weighed and stored as described previously . SurveysD. pteronyssinus, American cockroach, and Ascaris lumbricoides using the Pharmacia CAP system ; IgG antibodies specific for hepatitis A virus, Helicobacter pylori, herpes simplex virus, herpes zoster virus, Epstein-Barr virus, and Toxoplasma gondii using commercially available assays; and for whole blood cultures stimulated with mitogen and relevant allergens for the measurement of the regulatory cytokines, IFN-γ, IL-13, and IL-10, as described elsewhere [Blood samples (7 mL) will be collected by venipuncture from participants in the case-control study and will be used for obtaining serum for the measurement of: polyclonal IgE ; IgE antlsewhere . A wholelsewhere .D. pteronyssinus/D. farinae mix, American cockroach, Alternaria tenuis, cat, dog, '9 Southern grass mix', and 'New stock fungi mix' .All children in the cross-sectional study will be tested for immediate hypersensitivity responses to relevant aeroallergens as described previously ,28. A poThe analysis will be designed to address five principal study questions: 1) What is the frequency of atopy and asthma in school children from the rural and urban study areas? 2) What environmental exposures are associated with atopy and asthma and how do these interact with area of residence  to affect the relationship between atopy and wheeze symptoms? 3) Do environmental exposures associated with wheeze differ between migrant and established urban populations and, if so, are they potentially modifiable through intervention programmes? 4) Are place of birth  and/or period of residence in rural and urban areas associated with risk of allergy? 5) How do complex inter-relationships between factors at different levels  interact to affect the risk of asthma in urban and rural populations? Statistical analysis will be conducted according to a conceptual framework that defines a proposed causal pathway and the complex analytic approach to be used has been described in detail in a companion paper . MethodsEthical approval for the study has been obtained from the Hospital Pedro Vicente Maldonado, Provincia de Pichincha, Ecuador. Written informed consent to participate in the study will be obtained from the parent of each child and signed minor assent will be obtained from each child. The parent or guardian of each child will be provided with a copy of all laboratory results and if, appropriate, treatment recommendations will be made by a trained clinician that will review each case.Atopic asthma and other allergic diseases are becoming increasingly important public health problems in Latin American cities and there is little published information on the causes of this disease epidemic. The SCAALA  research initiative includes two epidemiological studies being conducted in urbanizing populations  that are investigating the environmental causes of allergy in urban Latin America and the biological and social mechanisms that underlie these epidemiological trends. While the SCAALA-Salvador aims to investigate the associations between the prevalence of asthma and other allergic diseases  and potential risk factors that includes living conditions and early life and current exposures to infections , the SCAThe Esmeraldas-SCAALA study in Ecuador includes cross-sectional and nested case-control studies conducted in rural and urban contexts. The studies are investigating the impact of urban migration on asthma risk and the environmental exposures that are associated with an increased risk of asthma in populations that migrate from rural to urban areas. The study will focus on a single ethnic cultural group, Afro-Ecuadorians, that traditionally has lived in the remote rural North Eastern region of Esmeraldas Province, but that has migrated in significant numbers over the past 30 years to cities such as the provincial capital, Esmeraldas. The study of a single and easily identifiable group that presumably shares the same genetic 'stock' and that has migrated locally (within the same Province) should allow important environmental risk factors to be identified more easily and should not suffer from the biases that limit the interpretation of studies that have investigated populations that have migrated between countries. Specifically, the study, by investigating a migrant population, will distinguish between the effects of early life exposures (inducing immune programming) and current exposures in determining allergy risk.The knowledge generated from this study will help to define the size of the public health problem of allergy in Ecuador and may identify possible environmental exposures that could be considered for primary prevention public health strategies. The study in Brazil is a prospective study investigating the effects of early life exposures to environmental factors, and the potential effects of these on the immune system and the risk of allergy and has been described in detail in a separate paper .The causes of the allergy epidemic in Latin America are assumed to be multifactorial and an important strength of the SCAALA studies is the use of similar causal frameworks and the sharing of methodology and expertise in a wide range of scientific disciplines . The two studies are complementary and are likely to yield important information on the underlying causes of the allergy epidemic in urban Latin America.st century, and allergic diseases are likely to emerge as the most prevalent of chronic diseases of childhood in Latin America during this century. Latin America urbanization has its roots on the intense process of displacement of the poor rural population that move to the urban centres looking for work and other improvements in their life conditions. It is expected that the knowledge generated from the SCAALA studies will help identify public health interventions that may ameliorate the adverse effects of urbanization on the prevalence and severity of asthma and allergic diseases.In summary, the aim of the proposed programme is to investigate the biological and social mechanisms that underlie the epidemic of allergic diseases in urban Latin America. Urbanization and the health problems associated with this phenomenon probably represent the single most important challenge for health researchers working in developing countries in the 21ISAAC: International Study of Asthma and Allergies in ChildhoodSCAALA: Social Change, Asthma and Allergy in Latin AmericaThe author(s) declare that they have no competing interests.PJC and LCR had the original idea for the study. PJC designed the study and drafted the manuscript. MC, MV were involved in study design and co-ordination. NAN and LPC were responsible for the immunological methods. BG was responsible for the statistical analysis plan. LR, AR, AC, RS and MB were involved in study design. All authors helped draft the manuscript, and read and approved the final version of the manuscript.The pre-publication history for this paper can be accessed here:


Evaluation of an Internet-based smoking cessation program: lessons learned from a pilot study [http://www.qsn.ori.org/), and the efforts to recruit participants and conduct a study through the Internet.It is estimated that more than 4 million people die annually from tobacco-related illnesses globally . Well-deot study  represenThe authors of this paper have considerable experience in medical computing and in the burgeoning area of behavioural eHealth, having published several recent papers on Internet-based interventions for diabetes -6. AlthoThe aim of the study is to evaluate a strategy for online study recruitment and retention, to evaluate the influence of incentives on follow-up response, and to assess the impact of the Quit Smoking Network site on smoking behaviour.Feil and colleagues  describea structured intervention that guides development of a cessation quit plan, interpersonal support , and a library of a wide variety of cessation resources .The intervention was also described as "based on theoretically grounded and empirically validated intervention approaches" citing an earlier paper by Lichenstein and Glasgow . DespiteThe research design is a single-condition study with a randomized follow-up component. Participants were recruited largely through magazine ads, local media coverage of the study and through the website itself . All participants were exposed to the website intervention and then randomly assigned to 1 of 4 follow-up conditions  afterwards. Participants completed a pretest survey online prior to the intervention and were contacted at 3 months postintervention to complete the follow-up online. Participants who did not complete the 3-month follow-up were randomly assigned to receive further follow-up notifications by email or regular US mail after 3 weeks. No description of the randomization process was provided.Two hundred and nine participants (56%) completed the 3-month follow-up, mostly through the Internet . Both the mode of communication  and incentive amount  provided similar rates of follow-up. With regard to the impact of the intervention, 38% (67) of participants reported abstinence  at 3-month follow-up . Such results are comparable to many other non-Internet smoking cessation trials .Although there was a reported cessation rate of 18% at 3 months, it is unclear whether this effect can be attributed to the intervention as no method of accounting for alternative explanations was provided. Since participants were self-selected based on an expressed interest in smoking cessation it seems reasonable that participants also sought other treatment options at the time of their participation. Another limitation of the study is the absence of the reported mean time to response after the second 3-month reminder was sent to participants.From a tobacco control perspective, there are additional concerns. An absence of a detailed description of instruments used to assess smoking variables is unfortunate. With a large body of literature in tobacco control, a number of acceptable measures or items have emerged to assess smoking behaviours and tobacco use. However no details of the items, item source, or scale reliability were provided and, in the case of cessation self-efficacy, were not even defined. Outside the effect on cigarette abstinence, the study's effects on outcome variables such as cessation self-efficacy were not reported.This study introduces a number of innovations for advancing knowledge of eHealth. The implementation and evaluation of an intervention completely at a distance represents a significant step forward in advancing eHealth research. Another innovation is the study of both incentive value and mode of contact on follow-up participation rates--issues that clearly require further study.Although the study design was innovative, the study as reported was problematic in a number of areas. With respect to eHealth issues, many of the evaluation reporting guidelines recommended by the Science Panel on Interactive Health Communication  were notDespite its limitations, many of which could have been reduced by more complete reporting, this is an important study for eHealth and tobacco control. As with many pioneering studies, this work offers more questions for eHealth research than answers; but the answers it does provide are nonetheless important. Furthermore, the findings of the study have great clinical significance for tobacco control given that the intervention was delivered in absentia and the potential for widespread, population-based translation of the intervention is high. Building on the results of this pilot test it is hoped that the authors will soon offer a more extensive evaluation of the Quit Smoking Network, one that has addressed some of the concerns stated here and that furthers this study's unique contribution to the literature.What method or process was used to randomize participants into each condition?Among those participants who did not respond to the initial follow-up request, what was the mean time to follow-up?What are the theoretical model(s) guiding the Quit Smoking Network site and how are they applied?How was intervention exposure (dose) assessed or measured for each participant?What other smoking strategies did participants report engaging in? If not measured, why?How was cessation self-efficacy measured?What were the levels of reported social support at baseline and how were such measures correlated with smoking cessation at 3-month follow-up?How do you propose researchers address the issue of validating smoking self-report using remotely-delivered interventions?


RESPIRE, a randomized trial of an improved cookstove, was conducted in Guatemala to assess health effects of long-term reductions in wood smoke exposure. Given the evidence that ambient particles increase blood pressure, we hypothesized that the intervention would lower blood pressure.a) between-group comparisons based on randomized stove assignment, and b) before-and-after comparisons within subjects before and after they received improved stoves. From 2003 to 2005, we measured personal fine particle  exposures and systolic (SBP) and diastolic blood pressure (DBP) among women > 38 years of age from the chimney woodstove intervention group (49 subjects) and traditional open wood fire control group (71 subjects). Measures were repeated up to three occasions.Two study designs were used: 2.5 exposures were 264 and 102 μg/m3 in the control and intervention groups, respectively. After adjusting for age, body mass index, an asset index, smoking, secondhand tobacco smoke, apparent temperature, season, day of week, time of day, and a random subject intercept, the improved stove intervention was associated with 3.7 mm Hg lower SBP  and 3.0 mm Hg lower DBP  compared with controls. In the second study design, among 55 control subjects measured both before and after receiving chimney stoves, similar associations were observed.Daily average PMThe between-group comparisons provide evidence, particularly for DBP, that the chimney stove reduces blood pressure, and the before-and-after comparisons are consistent with this evidence. Approximately half of the world’s households depend on biomass  and coal for cooking and heating . Most ofAlthough numerous epidemiologic investigations have concluded that fine ambient particles and secondhand tobacco smoke (SHS) are associated with cardiovascular morbidity and mortality , the WHO3 in homes where open fires were used for cooking  < 3.5 μm in aerodynamic diameter] were 1,930 μg/m cooking . Howeverxposures .plancha to conduct the first randomized intervention to reduce long-term air pollution exposures (We participated in RESPIRE (Randomized Exposure Study of Pollution Indoors and Respiratory Effects), which used the xposures . This trElevated blood pressure (BP) predicts cardiovascular morbidity and mortality, and reductions in BP have been shown to reduce risk , 2003. Splancha improved woodstove would be associated with long-term reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) among healthy adults. As supporting evidence, we also aimed to determine whether the stove intervention was associated with reduced personal exposures to fine particulate air pollution.We hypothesized that the The protocols for the stove intervention trial were approved by the human subjects committees at the University of California-Berkeley, the U.S. Centers for Disease Control and Prevention, Liverpool University (UK), and the Universidad del Valle in Guatemala. The cardiovascular substudy was approved by the human subjects committees of the Harvard School of Public Health and Universidad del Valle, and all participants gave informed consent before data collection.San Marcos, Guatemala, borders the Pacific Ocean to the west and Chiapas, Mexico, to the north. From the rural area within this district, near the towns of San Lorenzo and Comitancillo, 23 villages were chosen based on a rapid assessment showing high prevalence (> 90%) of cooking with open wood fires. The study villages lie at 2,200–3,000 m elevation, creating a cool climate that necessitates enclosed homes, leading to high indoor air pollution concentrations.n = 537) were recruited and randomized from October 2002 through May 2003.Household eligibility criteria for the randomized trial, which focused on acute lower respiratory infections in infants, included exclusive use of an open biomass fire for cooking and having a pregnant woman or infant < 4 months of age. Households , among whom 208  were living and found at home during the substudy recruitment visit. The additional eligibility criteria, which were met by 185  of these women, were that they cooked daily and resided in a study house at the time of recruitment. Among the 185 eligible women invited to participate, the response rates were 75% among the control households and 54% among the intervention households, resulting in 120  participants overall. None of these women were pregnant, had given birth during the previous three months, nor were breast-feeding at the time of the study. Most were grandmothers of a child in the main study.2.5 (suspended PM < 2.5 μm in diameter) with gravimetric samplers during the 24 hr before blood pressure measurements. Each air sampler setup included an Apex pump , a Triplex Sharp-Cut Cyclone , and a 37-mm Teflon filter placed on top of a drain disc and inside a metal filter holder. The flow rate was set to 1.5 L/min and measured at the start and end of sampling with a soap bubble flow meter . The air sampler, weighing about 0.5 kg, was carried in a shoulder bag with the inlet clipped to the strap above waist height. The participants were instructed to carry the bags everywhere they went and place them near their bed when sleeping. The filters were weighed with a micro-balance  under atmosphere-controlled conditions before and after sampling.We measured average personal PMParticipants were transported in project vehicles from their homes to the San Lorenzo Health Center, where all BP measures were taken between 1400 and 1800 hr. An automatic blood pressure monitor  was used to measure SBP and DBP in the supported right arm of the seated subject after 10-min rest. Three repeat measures were taken within a 10-min period of continued rest.plancha for 293 days . After control households received the echo-intervention, an additional 65 measures were taken among 55 control subjects from March 2004 through March 2005. On average, the post–echo-intervention measures were taken 63 days  after control households started using the improved stoves.Although 10 control subjects and 7 intervention subjects dropped out of the study or moved away from the study site after one measurement round, the protocol was repeated on two or three occasions for most participants. The trial period, from July 2003 through December 2005, included 111 measures among 71 women in the control group cooking over open fires and 115 measures among 49 women in the intervention group using the improved stoves. On average, the intervention participants had been cooking with the t-tests for continuous variables and chi-square tests for binary variables in SAS version 9.1 .We tested the baseline characteristics of the BP study intervention and control groups for comparability using We used the average of the second and third of three consecutive BP measures taken during each visit as the estimate for that day. SBP and DBP were the dependent variables in separate regression analyses. We estimated the intervention effects using two different study designs: between-group comparisons based on randomized stove assignment, and before-and-after echo-intervention comparisons among the control group.2.5 exposure and BP by study group, we plotted smoothed probability densities with spans determined by the default rule of thumb (nrd0) using R 2.4.0 software .The between-group study design compares BP between control and intervention groups during the trial period, when control homes had open fires for cooking and intervention homes had improved stoves. To illustrate the distributions of personal PMMixed models were run using the linear mixed effects (lme) function in R software. The model for the between-group estimates of the effect of improved stoves on BP isi denotes subject and j denotes the repeated measures within subjects. BMI is body mass index. β̂1 is the effect estimate for the randomly assigned improved stove (Group), which has only the subscript i because it varies between people but not temporally. β̂2, β̂3, and so on represent the effects of covariates, the boi term is a random intercept for the ith subject, and ɛij are the residuals. The random intercept accounts for correlation among repeated measures and therefore provides appropriate weighting of information from each subject, even though the number of measures per subject may vary.where temascal (wood-heated sauna), having household electricity, and an asset index as a measure of socioeconomic status. Age and BMI were fit as linear terms. We used binary indicator variables for smoking, SHS exposure, temascal use, and household electricity. The asset index is the sum of binary indicators for having a bicycle, a radio, and a television, and was entered as categorical variable. To increase precision, we also considered time-varying covariates, such as apparent temperature, season, day of the week, and time of day. We used linear terms to control for daily average apparent temperature and time of day and dummy variables for each day of the week and for rainy (1 May–31 October) versus dry season (1 November –30 April).Although randomization made the two groups similar according to all baseline covariates measured, because of the small sample size and potential for differential selection by intervention status and predictors of BP, we adjusted for covariates that may predict BP between subjects, such as age, BMI, ever smoking, SHS exposure, use of a 2.5 and BP among the control group during the trial and echo-intervention periods were illustrated using smoothed probability densities as described above. Only control subjects who had echo-intervention measures are included in these analyses, which were based on the following mixed model:The before-and-after study design estimates the within-subject effect of the stove intervention on BP by comparing the same people before and after adoption of the chimney stove. Distributions of personal PMPeriod), an indicator for the echo-intervention period, now also has a subscript j to denote that it varies across measurements within subjects. Temp refers to daily average apparent temperature. Again, a random intercept for subject is included.where the stove variable , −8.1 to 0.6] and 3.0 mm Hg lower DBP , both similar to the unadjusted associations. Excluding smokers did not alter the results, and there was no significant interaction between intervention and ever smoking nor intervention and SHS exposure for either BP measure .The crude and adjusted mixed-model estimates of between-group differences in mean SBP and DBP are shown in p < 0.001), and the association of SBP with the chimney stove in the between-group model increased in magnitude and precision to a reduction of 4.0 mm Hg . DBP did not have a significant nonlinear relationship with age (p = 0.62), and the estimate of the stove effect on DBP was unchanged by adjustment for age using the penalized spline model.Using penalized splines to adjust for age, we found a significant nonlinear relationship between SBP and age .The crude and adjusted mixed-model estimates of before-and-after differences in mean SBP and DBP are shown in In the before-and-after study design, adjustment for nonlinear associations between BP and age using penalized splines did not alter the associations of stove with either BP measure.plancha improved stove instead of the traditional open fire. After adjustment, the 95% CI for the mean difference in DBP did not overlap zero, and the 95% CI for the mean difference in SBP only barely overlapped zero. A few subjects from both groups were measured each week during the trial period, making any unmeasured time-varying covariates unlikely to be strong confounders. Adjustment for predictors of BP in the between-group model moved the effect estimates further away from the null. Similar estimates from the between-group and before-and-after analyses greatly strengthen the evidence because these are not susceptible to the same sources of bias. That participants and research assistants were not blinded to exposure status is unlikely to induce bias, because automatic blood pressure monitors were used. BP differences associated with stove type were estimated with greater precision in the before-and-after than in the between-group analyses, despite the larger sample size in the latter. This is attributed to lower random variability in BP within-subjects than in between-subjects.SBP and DBP were lower among women randomly assigned to cook with the 2.5 exposure associated with plancha compared with open fire use strengthens the evidence that the observed BP differences may have been caused by reduced wood smoke exposure. These personal exposures among both open fire and plancha users were much lower than average kitchen levels found in similar populations with the same stove types . If participation was also associated with BP, selection bias may have produced study groups that were not comparable. Although the original study design included baseline BP measures, ethical approval was given after the intervention group received improved stoves. Adjustment for age, socioeconomic indicators, and BMI is likely to have at least partially attenuated the potential selection bias. Furthermore, we did not find any meaningful difference between the groups out of all available baseline covariates. n = 23) were higher than the trial period BP among the 55 subjects measured both before and after . Thus, there is no evidence of spurious findings due to selection of subjects for the echo-intervention follow-up who happened to have higher blood pressure when measured during the trial period.The before-and-after comparisons rely on the assumption that BP would not have changed in the control group in the absence of the echo-intervention. There may be unmeasured time-varying covariates that influence BP and were associated with the echo-intervention. In addition, because not all control subjects measured during the trial period were also measured during the echo-intervention period, it is possible that we unintentionally selected people for the before-and-after comparisons who happened to have higher than usual BP before the echo-intervention. The trial period BP among the 16 control subjects excluded from the before-and-after comparisons due to missing post-echo-intervention measures  for cooking and heating , but woo


Whether lower frequency, moderate intensity exercise alters cardiovascular disease (CVD) risk has received little attention. This study examined the effects of 45 minutes self-paced walking, 2 d· wk37 subjects (24 women) aged 41.5 ± 9.3 years were randomly assigned to either two 45 minute walks per week  or no training (control group). Aerobic fitness, body composition, blood pressure (BP), CRP and lipoprotein variables were measured at baseline and following 8 weeks. Steps counts were measured at baseline and during weeks 4 and 8 of the intervention.P < 0.05). There were no changes other risk factors. Subjects took significantly more steps on the days when prescribed walking was performed (9303 ± 2665) compared to rest days .Compared to the control group, the walking group showed a significant reduction in systolic BP and maintained body fat levels (max, improves activity levels, reduces systolic BP and prevents an increase in body fat in previously sedentary adults. This walking prescription, however, failed to induce significant improvements in other markers of cardiovascular disease risk following eight weeks of training.These findings suggest that walking twice per week for 45 minutes at ~ 62% HR It has become increasingly clear that many of the chronic diseases we face today are associated fundamentally with the pervasive sedentariness of modern lifestyle. In Northern Ireland at least 2000 people die each year due to an inactive lifestyle and the avoidable cost of inactivity to the health service is estimated at £0.62 million each year . DespiteIn the past decade, physical activity research has been characterised by the development of exercise prescriptions that are palatable to sedentary populations in the western world. First advocated by the American College of Sports Medicine  and subs-1 for six months, improved fitness in 79–91 year old females [Walking is eminently suited to population exercise prescription as it is easy to do, requires no special skills or facilities, and is achievable by virtually all age groups with little risk of injury . There i females . However females . Recentl-1 on fitness, BP, body composition, lipids and CRP.The present study evaluates the efficacy of a workplace walking intervention on physical activity levels and cardiovascular risk factors. An examination of the effects of self-paced walking twice per week will reveal whether individuals can achieve health benefits from outdoor walking performed with minimal investment in time. The purpose of the present study was to examine the effects of 45 minutes walking, 2 d· wkThis study was a randomised controlled trial, with subjects assigned to a walking or control group. The Research Ethics Committee at Queen's University, Belfast approved the study. Measurements were made at baseline (pre-intervention) and following eight weeks (post-intervention).-1, fasting blood glucose > 7.0 mmol· L-1, body mass index (BMI) > 34.9 kg· m-2, current cigarette smokers, individuals with cardiovascular, pulmonary or metabolic disease, pain or discomfort in the chest, dizziness or heart murmur. In addition, individuals taking medication known to interfere with lipid metabolism, and females who were pregnant or planning to become pregnant in the following five months were excluded from taking part in the study. Thirty seven subjects (24 women) aged 41.5 ± 9.3 years were randomised to either a walking  or control group  on a 3 to 2 basis . All subjects gave their written informed consent.Subjects were recruited from staff at the Northern Ireland Civil Service via internal email. All subjects completed a Health History questionnaire. Exclusionary criteria were a physically active lifestyle , age > 65 years, resting BP > 159/99 mm Hg, total cholesterol > 6.2 mmol· L2). Waist measurements were made at the level of the trunk where the girth is minimal, i.e. the location where there was a noticeable indentation of the trunk. If there was no noticeable indentation the tape was located at the umbilicus. Hip girth was the horizontal circumference at the broadest part of the lower body, usually at the level of the trochanters [Height and body mass were recorded using a stadiometer  and scales  respectively. BMI was calculated by dividing body mass (kg) by height  after the subject had rested in a seated position for five minutes. The average of the readings was used. If the first two readings differed by more than 5 mm Hg, an additional reading was obtained and all three readings averaged.max). They were encouraged to complete all four stages, but the test was terminated if heart rate (HR) reached 85% HRmax. HR was measured continually by short-range telemetry. During the last 30 seconds of each test stage, a capillary sample of blood was obtained and immediately analysed for lactate using a Lactate Pro Test Meter . Ratings of perceived exertion (RPE) using the Borg 15-grade scale  were obtained during the last minute of each test stage, in accordance with scripted instructions [To monitor cardiovascular adaptations to training, a submaximal, graded exercise test was conducted pre- and post-intervention. In the week prior to the treadmill test, subjects were familiarised with walking on the treadmill  at various speeds and slopes. Following a three minute warm-up, subjects were instructed to walk on the treadmill for four minutes at each of four gradients selected to elicit 40, 50, 60, and 70% of age-predicted (220 – age) maximum heart rate (HRructions -1) a value of 0.5 mg.L-1 was recorded. All samples for each given assay were analysed on the same day in a single batch at the Institute of Clinical Science at Queen's University, Belfast.Whole blood glucose and total cholesterol were determined from a fresh sample of capillary blood using dry chemistry methods  for the purpose of initial screening criteria. Blood samples were obtained by venepuncture after a 10 hour fast and with subjects in a seated position. Subjects were instructed to refrain from physical activity on the previous day. Samples were separated, frozen at -20°C, and analysed within 8 months. Total cholesterol, HDL and triglycerides were determined by automated enzyme assay using a Cobas FARA bioanalyser . Commercial enzyme assay kits were purchased from Randox Laboratories Ltd. . The concentration of LDL cholesterol was calculated using the Friedewald formula . CRP wasA sample of whole blood was analysed within 12 hours for haematocrit and haemoglobin. Haematocrit was corrected by 1.5% to account for plasma trapped between erythrocytes. Haematocrit and haemoglobin values were subsequently used to correct for changes in plasma volume . As femaIt has previously been reported that adults intuitively self-select a pace concordant with cardiorespiratory benefits when walking for exercise . TherefoTwelve walkers and all of the controls wore a pedometer during weeks 0, 4 and 8 of the intervention . They were instructed to wear the pedometer during all waking hours and record the number of steps taken at the end of each day. In addition, during weeks 4 and 8, those assigned to the walking group recorded their step count before and after each walking session in their training diary. Each subject was trained in the correct use of the pedometer and given written guidelines to follow.t-tests. Non-parametric Kruskall-Wallis tests were used to compare the step counts of groups at baseline. Non-parametric Wilcoxon tests were used to compare paired step count data of the walking group . Physiological data were analysed using a 2-way ANOVA with repeated measures, with one factor between subjects  and one factor within subjects (pre- vs. post-intervention).Physiological differences between groups at baseline were compared using independent -1, was excluded from the analysis as CRP values of this order may be indicative of infection or trauma . CRP data is therefore presented for 11 walkers and 8 controls. For all other parameters measured data are presented for the 21 walkers and 12 controls who completed the study. Physiological characteristics of the participants at baseline are shown in Table P > 0.05).Four individuals dropped out of the study due to: illness 1 control), moving job (1 control), family circumstances  and lack of interest . Due to equipment error at the end of the walking intervention, body fat measurement was only possible in 12 walkers and 12 controls. Due to problems in blood sampling we were only able to determine blood lipids  in 11 walkers and 9 controls. In addition one control subject, who had CRP values > 10 mg· L control,P > 0.05). Daily step counts for the walking group on days when prescribed walking was performed , on days when no prescribed walking was performed (Rest-days) and all days during the programme are shown in Table P < 0.001). Walkers undertook more voluntary steps  on Rest-days (5803 ± 2749) than on Walk-days (4567 ± 2639) (P < 0.05). During the intervention, mean step counts for the control group averaged 6470 ± 1709.During week 0 (i.e. the week prior to commencing the intervention) daily step counts for the walking and control groups averaged 6437 ± 2285 and 6831 ± 2727 respectively. There was no significant difference in the week 0 step counts between groups . Systolic BP for the walking group decreased from 120.4 ± 19.7 mm Hg at baseline to 115.4 ± 17.7 mm Hg at post intervention. Body fat percentage of the walking group was 28.0 ± 5.8 and 27.9 ± 5.6 at pre- and post-intervention respectively. No significant changes were observed in body mass, waist and hip circumference, diastolic BP or lipid variables.Table -1 respectively (n = 11). Corresponding values for controls were 1.5 ± 1.5 and 1.5 ± 1.3 mg· L-1 at pre- and post-intervention respectively (n = 8). There were no significant effects observed. One subject, who had CRP values > 10 mg· L-1, was excluded from the analysis as CRP values of this order may be indicative of infection or trauma .Mean values for CRP in the walking group at pre- and post-intervention were 1.9 ± 1.7 and 1.6 ± 1.5 mg· L-1 and 112.0 ± 9.3 beats· min-1 at pre- and post-intervention respectively. Corresponding values for the control group were 121.2 ± 14.7 and 118.1 ± 13.0 beats· min-1 at pre- and post-intervention respectively. Blood lactate values for walkers at pre-and post-intervention were 1.6 ± 0.5 and 1.5 ± 0.5 mmol· L-1 respectively. Pre- and post-intervention values for the control group were 1.5 ± 0.5 and 1.7 ± 0.5 mmol· L-1. Following training RPE during the treadmill test reduced from 11.2 ± 1.4 to 10.8 ± 1.4 in the walking group. A similar reduction was observed in controls, who demonstrated RPE values of 11.3 ± 2.1 and 10.8 ± 1.8 at pre- and post-intervention respectively. No significant differences were observed between groups in HR, blood lactate or RPE.Mean HR for the walking group during the treadmill test was 116.5 ± 8.5 beats· minThe main finding of the present study is that 45 minutes self-paced walking, two days per week, decreases systolic BP, but has no discernable effects on fitness, body mass, waist/hip circumferences, diastolic BP, CRP or lipoproteins, in previously sedentary employees. The novel aspect of this investigation is that it is the first to use a low frequency walking programme with adults < 60 years of age, and the first to examine the effects of walking, without dietary intervention, on CRP levels. The study augments the limited body of evidence on the efficacy of worksite physical activity interventions.A significant effect was observed between groups for the change in systolic BP from pre- to post-intervention. Systolic BP was reduced by 5.0 ± 7.9 mm Hg in the walking group following eight weeks of training. A reduction of this magnitude is in general agreement with the findings of a meta-analysis on the effect of aerobic exercise on BP in normotensive adults . In suchFew other studies ,26 have A significant effect was observed between groups for change in body fat percentage from pre- to post-intervention. Relative to an increase in controls, the body fat percentage of walkers remained stable. The increases in body fat percentage of the control group may, however, be the result of over-cautious control subjects. It is possible that a desire 'not to be active' may have resulted in marginally lower than normal physical activity levels thus contributing to worsened adiposity.-1 vs. 150–420 min· wk-1). Given the varied training regimes in the aforementioned studies, and the paucity of data in the area, comparisons are difficult to draw. Further research is required to elucidate the relationship between exercise levels  and changes in CRP, and the effects of training in various population groups. The present study augments the very limited body of evidence on the effects of training on resting CRP concentrations.Participants in the present study are classified as being at moderate risk of future cardiovascular events according to their baseline CRP levels . In the -1 [max, heart rate during a submaximal exercise test was reduced. Failure to evoke changes in aerobic fitness in the present study, despite the same volume of exercise, may be due to differences in training intensity (67–78% HRmax vs. ~ 62% HRmax) or differences in the length of the intervention (26 weeks vs. 8 weeks) [max for lower-fit subjects [Heart rate and blood lactate responses to submaximal workloads were used in the present study to monitor changes in aerobic fitness. No significant effects were observed for changes in heart rate or lactate response to submaximal workloads. The authors know of one other study in the published literature that has used the same walking prescription as the present investigation. Eighty women, aged 60–70 years progressed to walking 45 minutes 2 d· wk-1 . Followi8 weeks) . It has subjects . The facA systematic review of 32 cross-sectional, prospective observational and intervention studies, suggested that for adults, 7000 – 13,000 steps per day can be expected . BaselinThe walking intervention was well tolerated by the employees in the present study. No injuries were reported during the programme, most likely due to the mode of exercise and that fact that low injury rates are associated with moderate intensity activity . This fi-1. However, apart from one subject, the same individuals were below detectable limits at both sampling times, thus limiting the resulting effect on observed changes over time.The limitations of this study need to be considered when interpreting findings. The CRP assay used in the present study did not detect CRP in the blood samples of 6 subject  as they were below the detectable level of < 0.5 mg· L-1 for eight weeks at ~ 62% HRmax, reduces systolic BP and prevents an increase in body fat, in previously sedentary employees. This walking prescription, however, failed to induce significant improvements in fitness, diastolic BP, body mass, serum lipids and CRP levels. The walking programme was associated with high adherence. These findings support the use of a twice-weekly, self-paced, worksite based, walking programme, to improve activity levels and systolic BP in previously sedentary employees. There is little evidence however to support the use of this exercise prescription for improvements in other markers of CVD risk. This walking prescription may therefore be useful as a stepping-stone to further increase levels of exercise, which may then provide greater benefits.In summary, the findings of the present study suggest that self-paced walking 45 min, 2 d· wkThe author(s) declare that they have no competing interests.MHM, EMM and CAGB were responsible for the design of the studyEMM was responsible for data collectionLGH was responsible for blood profilingAMN was responsible for statistical analysisMHM and EMM were responsible for preparing the manuscriptAll authors read and approved the final manuscriptThe pre-publication history for this paper can be accessed here: