Characteristics that modify the effect of small-quantity lipid-based nutrient supplementation on child anemia and micronutrient status: an individual participant data meta-analysis of randomized controlled trials.

BACKGROUND: Small-quantity lipid-based nutrient supplements (SQ-LNSs) have been shown to reduce the prevalence of child anemia and iron deficiency, but effects on other micronutrients are less well known. Identifying subgroups who benefit most from SQ-LNSs could support improved program design. OBJECTIVES: We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child hemoglobin (Hb), anemia, and inflammation-adjusted micronutrient status outcomes. METHODS: We conducted a 2-stage meta-analysis of individual participant data from 13 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 15,946). We generated study-specific and subgroup estimates of SQ-LNSs compared with control, and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine potential study-level effect modifiers. RESULTS: SQ-LNS provision decreased the prevalence of anemia (Hb < 110 g/L) by 16% (relative reduction), iron deficiency (plasma ferritin < 12 µg/L) by 56%, and iron deficiency anemia (IDA; Hb < 110 g/L and plasma ferritin <12 µg/L) by 64%. We observed positive effects of SQ-LNSs on hematological and iron status outcomes within all subgroups of the study- and individual-level effect modifiers, but effects were larger in certain subgroups. For example, effects of SQ-LNSs on anemia and iron status were greater in trials that provided SQ-LNSs for >12 mo and provided 9 (as opposed to <9) mg Fe/d, and among later-born (than among first-born) children. There was no effect of SQ-LNSs on plasma zinc or retinol, but there was a 7% increase in plasma retinol-binding protein (RBP) and a 56% reduction in vitamin A deficiency (RBP < 0.70 µmol/L), with little evidence of effect modification by individual-level characteristics. CONCLUSIONS: SQ-LNSs can substantially reduce the prevalence of anemia, iron deficiency, and IDA among children across a range of individual, population, and study design characteristics. Policy-makers and program planners should consider SQ-LNSs within intervention packages to prevent anemia and iron deficiency.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020156663.

Small-quantity lipid-based nutrient supplements for children age 6-24 months: a systematic review and individual participant data meta-analysis of effects on developmental outcomes and effect modifiers.

BACKGROUND: Small-quantity (SQ) lipid-based nutrient supplements (LNSs) provide many nutrients needed for brain development. OBJECTIVES: We aimed to generate pooled estimates of the effect of SQ-LNSs on developmental outcomes (language, social-emotional, motor, and executive function), and to identify study-level and individual-level modifiers of these effects. METHODS: We conducted a 2-stage meta-analysis of individual participant data from 14 intervention against control group comparisons in 13 randomized trials of SQ-LNSs provided to children age 6-24 mo (total n = 30,024). RESULTS: In 11-13 intervention against control group comparisons (n = 23,588-24,561), SQ-LNSs increased mean language (mean difference: 0.07 SD; 95% CI: 0.04, 0.10 SD), social-emotional (0.08; 0.05, 0.11 SD), and motor scores (0.08; 95% CI: 0.05, 0.11 SD) and reduced the prevalence of children in the lowest decile of these scores by 16% (prevalence ratio: 0.84; 95% CI: 0.76, 0.92), 19% (0.81; 95% CI: 0.74, 0.89), and 16% (0.84; 95% CI: 0.76, 0.92), respectively. SQ-LNSs also increased the prevalence of children walking without support at 12 mo by 9% (1.09; 95% CI: 1.05, 1.14). Effects of SQ-LNSs on language, social-emotional, and motor outcomes were larger among study populations with a higher stunting burden (≥35%) (mean difference: 0.11-0.13 SD; 8-9 comparisons). At the individual level, greater effects of SQ-LNSs were found on language among children who were acutely malnourished (mean difference: 0.31) at baseline; on language (0.12), motor (0.11), and executive function (0.06) among children in households with lower socioeconomic status; and on motor development among later-born children (0.11), children of older mothers (0.10), and children of mothers with lower education (0.11). CONCLUSIONS: Child SQ-LNSs can be expected to result in modest developmental gains, which would be analogous to 1-1.5 IQ points on an IQ test, particularly in populations with a high child stunting burden. Certain groups of children who experience higher-risk environments have greater potential to benefit from SQ-LNSs in developmental outcomes.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020159971.

Characteristics that modify the effect of small-quantity lipid-based nutrient supplementation on child growth: an individual participant data meta-analysis of randomized controlled trials.

BACKGROUND: Meta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child stunting and wasting. Identification of subgroups who benefit most from SQ-LNSs may facilitate program design. OBJECTIVES: We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child growth outcomes. METHODS: We conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 37,066). We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons. RESULTS: SQ-LNS provision decreased stunting (length-for-age z score < -2) by 12% (relative reduction), wasting [weight-for-length (WLZ) z score < -2] by 14%, low midupper arm circumference (MUAC) (<125 mm or MUAC-for-age z score < -2) by 18%, acute malnutrition (WLZ < -2 or MUAC < 125 mm) by 14%, underweight (weight-for-age z score < -2) by 13%, and small head size (head circumference-for-age z score < -2) by 9%. Effects of SQ-LNSs generally did not differ by study-level characteristics including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average compliance with SQ-LNS. Effects of SQ-LNSs on stunting, wasting, low MUAC, and small head size were greater among girls than among boys; effects on stunting, underweight, and low MUAC were greater among later-born (than among firstborn) children; and effects on wasting and acute malnutrition were greater among children in households with improved (as opposed to unimproved) sanitation. CONCLUSIONS: The positive impact of SQ-LNSs on growth is apparent across a variety of study-level contexts. Policy-makers and program planners should consider including SQ-LNSs in packages of interventions to prevent both stunting and wasting.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.

Impact of warning labels on reducing health halo effects of nutrient content claims on breakfast cereal packages: A mixed-measures experiment.

Chile recently implemented a food labeling law that requires packaged foods with sugar, saturated fats, sodium, and/or calorie content that exceeds government-defined thresholds to carry a front-of-package warning for each excessive nutrient. This law does not prohibit the use of nutrient content (NC) marketing claims on packages, as long as the claims do not directly contradict the warnings. Yet, having NC claims alongside nutrient warnings might send mixed messages confusing consumers about the overall healthiness of a product. The present study tests the co-occurrence of warning labels and NC claims in breakfast cereal packages on product perceptions and behavioral intentions of Chilean adults in a 3 (warnings: none, high calorie, high calorie/high sugar) × 3 (NC claims: none, fiber/wholegrain, low fat/cholesterol-free) mixed-measures experiment. Fiber-related claims had a main effect leading to more positive ratings of the product, compared to having no NC claims or fat-related claims. These positive ratings extended beyond perceptions of the fiber content to perceptions of overall healthiness, naturalness, quality, vitamin content, and intentions to purchase and recommend the product-a health halo effect. No significant interaction between warnings and NC claims was found. However, warnings had a main effect on perceptions irrespective of the presence of NC claims, with one warning significantly reducing ratings, dampening any halo effects, and two warnings further dampening any effects. These findings indicate that warning labels can mitigate, but not eliminate the influences of NC claims on consumer perceptions of product healthiness.

Moderators of the Association Between Serum Parathyroid Hormone and Metabolic Syndrome in Participants with Elevated Parathyroid Hormone: NHANES 2003-2006.

This cross-sectional study extracted data of 392 NHANES participants with elevated serum parathyroid hormone (PTH) concentrations from 2 cycles of the US National Health and Nutrition Examination Survey (NHANES) 2003-2006 and evaluated the association between serum (PTH) concentration and metabolic syndrome (MetS) to identify dietary and lifestyle factors that may modify that association. The primary outcome was MetS severity scores. Results of univariate linear regression analyses revealed that serum PTH concentrations correlated positively and significantly with MetS severity scores (ß=0.399, p=0.030). After adjusting for gender, age, race, and alcohol consumption, results of multivariate analysis revealed that increased serum PTH concentration correlated significantly with higher MetS severity scores (ß=0.413, p=0.045) in participants with moderate physical activity over the past 30 days. Serum PTH concentration also correlated significantly with higher MetS severity scores in participants with serum 25-hydroxyvitamin D deficiency (ß=0.456 and p=0.014), those without vitamin D supplementation (ß=0.524, p=0.028) and with higher protein intake (ß=0.586 and p=0.030). In conclusion, increased serum PTH concentration is associated with higher MetS severity scores in participants with elevated serum PTH at baseline. The association between PTH concentration and MetS severity is moderated by participants' physical activity levels, status of serum vitamin D, vitamin D supplementation, and daily protein intake.

Predicting response to anti-TNFα therapy among patients with axial spondyloarthritis (axSpA): results from BSRBR-AS.

OBJECTIVES: While many axSpA patients, eligible to receive anti-TNFα therapy, derive benefit when prescribed them, some patients do not. The current study aims to identify modifiable targets to improve outcome as well as non-modifiable targets that identify groups less likely to derive benefit. METHODS: The BSRBR-AS is a prospective cohort study of axSpA patients who, at recruitment, were naïve to biologic therapy. Those in the 'biologic' sub-cohort commenced their first anti-TNFα therapy at recruitment or during follow-up. Prior to commencement, information was collected on socio-economic, clinical and patient-reported factors. Outcome was assessed according to ASAS20, ASAS40, ASDAS reduction and achieving a moderate/inactive ASDAS disease state. RESULTS: 335 participants commenced their first anti-TNFα therapy and were followed up at a median of 14 (inter-quartile range 12-17) weeks. Response varied between 33% and 52% according to criteria used. Adverse socio-economic factors, fewer years in education predicted lower likelihood of response across outcome measures as did not working full-time. Co-morbidities and poor mental health were clinical and patient-reported factors, respectively, associated with lack of response. The models, particularly those using ASDAS, were good at predicting those who did not respond (negative predictive value (NPV) 77%). CONCLUSION: Some factors predicting non-response (such as mental health) are modifiable but many (such as social/economic factors) are not modifiable in clinic. They do, however, identify patients who are unlikely to benefit from biologic therapy alone. Priority should focus on how these patients receive the benefits that many derive from such therapies.

Bayesian Methods for Exposure Misclassification Adjustment in a Mediation Analysis: Hemoglobin and Malnutrition in the Association Between Ascaris and IQ.

BACKGROUND: Soil-transmitted helminth infections have been found to be associated with child development. The objective was to investigate hemoglobin levels and malnutrition as mediators of the association between Ascaris infection and intelligence quotient (IQ) scores in children. METHODS: We conducted a longitudinal cohort study in Iquitos, Peru, between September 2011 and July 2016. A total of 1760 children were recruited at 1 year of age and followed up annually to 5 years. We measured Ascaris infection and malnutrition at each study visit, and hemoglobin levels were measured as of age 3. The exposure was defined as the number of detected Ascaris infections between age 1 and 5. We measured IQ scores at age 5 and used Bayesian models to correct exposure misclassification. RESULTS: We included a sample of 781 children in the analysis. In results adjusted for Ascaris misclassification, mean hemoglobin levels mediated the association between Ascaris infection and IQ scores. The natural direct effects (not mediated by hemoglobin) (95% CrI) and natural indirect effects (mediated by hemoglobin) (95% CrI) were compared with no or one infection: -0.9 (-4.6, 2.8) and -4.3 (-6.9, -1.6) for the effect of two infections; -1.4 (-3.8, 1.0) and -1.2 (-2.0, -0.4) for three infections; and -0.4 (-3.2, 2.4) and -2.7 (-4.3, -1.0) for four or five infections. CONCLUSION: Our results are consistent with the hypothesis that hemoglobin levels mediate the association between Ascaris infection and IQ scores. Additional research investigating the effect of including iron supplements in STH control programs is warranted.

Mental contrasting for health behaviour change: a systematic review and meta-analysis of effects and moderator variables.

Mental contrasting is a self-regulation imagery strategy that involves imagining a desired future and mentally contrasting it with the present reality, which is assumed to prompt the individual to realise that action is required to achieve the desired future. Research has combined mental contrasting with implementation intentions (MCII) ('if-then' plans), which is hypothesised to strengthen the effects. A systematic review was conducted to evaluate the effectiveness of mental contrasting for improving health-related behaviours. A meta-analysis (N = 1528) using random effects modelling found a main effect of mental contrasting on health outcomes, adjusted Hedges' g = 0.28 (SE = .07), 95% CI [0.13-0.43], p < .001 at up to four weeks, and an increased effect at up to three months (k = 5), g = 0.38 (SE = 0.6), CI [0.20-0.55], p < .001. The combination of mental contrasting with implementation intentions (MCII; k = 7) showed a similar effect, g = 0.28, CI [0.14-0.42], p < .001. Mental contrasting shows promise as a brief behaviour change strategy with a significant small to moderate-sized effect on changing health behaviour in the short-term. Analysis on a small subset of studies suggested that the addition of implementation intentions (MCII) did not further strengthen the effects of mental contrasting on health behaviours, although additional studies are needed.

Who should conduct ethnobotanical studies? Effects of different interviewers in the case of the Chácobo Ethnobotany project, Beni, Bolivia.

BACKGROUND: That the answers elicited through interviews may be influenced by the knowledge of the interviewer is accepted across disciplines. However, in ethnobotany, there is little evidence to quantitatively assess what impact this effect may have. We use the results of a large study of traditional ecological knowledge (TEK) of plant use of the Chácobo and Pacahuara of Beni, Bolivia, to explore the effects of interviewer identity and knowledge upon the elicited plant species and uses. METHODS: The Chácobo are a Panoan speaking tribe of about 1000 members (300+ adults) in Beni, Bolivia. Researchers have collected anthropological and ethnobotanical data from the Chácobo for more than a century. Here, we present a complete ethnobotanical inventory of the entire adult Chácobo population, with interviews and plant collection conducted directly by Chácobo counterparts, with a focus on the effects caused by external interviewers. RESULTS: Within this large study, with a unified training for interviewers, we did find that different interviewers did elicit different knowledge sets, that some interviewers were more likely to elicit knowledge similar to their own, and that participants interviewed multiple times often gave information as different as that from two randomly chosen participants. CONCLUSIONS: Despite this, we did not find this effect to be overwhelming-the amount of knowledge an interviewer reported on the research subject had comparatively little effect on the amount of knowledge that interviewer recorded from others, and even those interviewers who tended to elicit similar answers from participants also elicited a large percentage of novel information.

Vitamin E and the risk of pneumonia: using the I 2 statistic to quantify heterogeneity within a controlled trial.

Analyses in nutritional epidemiology usually assume a uniform effect of a nutrient. Previously, four subgroups of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of Finnish male smokers aged 50-69 years were identified in which vitamin E supplementation either significantly increased or decreased the risk of pneumonia. The purpose of this present study was to quantify the level of true heterogeneity in the effect of vitamin E on pneumonia incidence using the I 2 statistic. The I 2 value estimates the percentage of total variation across studies that is explained by true differences in the treatment effect rather than by chance, with a range from 0 to 100 %. The I 2 statistic for the effect of vitamin E supplementation on pneumonia risk for five subgroups of the ATBC population was 89 % (95 % CI 78, 95 %), indicating that essentially all heterogeneity was true variation in vitamin E effect instead of chance variation. The I 2 statistic for heterogeneity in vitamin E effects on pneumonia risk was 92 % (95 % CI 80, 97 %) for three other ATBC subgroups defined by smoking level and leisure-time exercise level. Vitamin E decreased pneumonia risk by 69 % among participants who had the least exposure to smoking and exercised during leisure time (7·6 % of the ATBC participants), and vitamin E increased pneumonia risk by 68 % among those who had the highest exposure to smoking and did not exercise (22 % of the ATBC participants). These findings refute there being a uniform effect of vitamin E supplementation on the risk of pneumonia.

Disclosure of sensitive behaviors across self-administered survey modes: a meta-analysis.

In surveys, individuals tend to misreport behaviors that are in contrast to prevalent social norms or regulations. Several design features of the survey procedure have been suggested to counteract this problem; particularly, computerized surveys are supposed to elicit more truthful responding. This assumption was tested in a meta-analysis of survey experiments reporting 460 effect sizes (total N =125,672). Self-reported prevalence rates of several sensitive behaviors for which motivated misreporting has been frequently observed were compared across self-administered paper-and-pencil versus computerized surveys. The results revealed that computerized surveys led to significantly more reporting of socially undesirable behaviors than comparable surveys administered on paper. This effect was strongest for highly sensitive behaviors and surveys administered individually to respondents. Moderator analyses did not identify interviewer effects or benefits of audio-enhanced computer surveys. The meta-analysis highlighted the advantages of computerized survey modes for the assessment of sensitive topics.

Serum phosphorus and mortality in the Third National Health and Nutrition Examination Survey (NHANES III): effect modification by fasting.

BACKGROUND: Serum phosphorus levels have been associated with mortality in some but not all studies. Because dietary intake prior to measurement can affect serum phosphorus levels, we hypothesized that the association between serum phosphorus level and mortality is strongest in those who have fasted longer. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Nationally representative sample of 12,984 participants 20 years or older in the Third National Health and Nutrition Examination Survey (1988-1994). FACTORS: Serum phosphorus level, fasting duration (dichotomized as ≥ 12 or < 12 hours). OUTCOMES: All-cause and cardiovascular mortality determined by death certificate data from the National Death Index. MEASUREMENTS: Serum phosphorus measured in a central laboratory and fasting duration recorded as time since food or drink other than water was consumed. RESULTS: Individuals fasting 12 or more hours had lower serum phosphorus levels than those fasting less than 12 hours (3.34 vs 3.55 mg/dL; P < 0.001) and higher correlation with repeat measurement (0.66 vs 0.53; P = 0.002). In multivariable-adjusted Cox regression models, the highest quartile of serum phosphorus was associated with increased mortality in participants fasting 12 or more hours (adjusted HR, 1.74; 95% CI, 1.38-2.20; reference, lowest quartile) but not in participants fasting less than 12 hours (adjusted HR, 1.08; 95% CI, 0.89-1.32; P for interaction = 0.002). Relationships were consistent using 8 hours as the fasting cutoff point or cardiovascular mortality as the outcome. LIMITATIONS: Observational study, lack of fibroblast growth factor 23 or intact parathyroid hormone measurements. CONCLUSIONS: Fasting but not nonfasting serum phosphorus levels were associated with increased mortality. Risk prognostication based on serum phosphorus may be improved using fasting levels.

Influence of control group on effect size in trials of acupuncture for chronic pain: a secondary analysis of an individual patient data meta-analysis.

BACKGROUND: In a recent individual patient data meta-analysis, acupuncture was found to be superior to both sham and non-sham controls in patients with chronic pain. In this paper we identify variations in types of sham and non-sham controls used and analyze their impact on the effect size of acupuncture. METHODS: Based on literature searches of acupuncture trials involving patients with headache and migraine, osteoarthritis, and back, neck and shoulder pain, 29 trials met inclusion criteria, 20 involving sham controls (n = 5,230) and 18 non-sham controls (n = 14,597). For sham controls, we analysed non-needle sham, penetrating sham needles and non-penetrating sham needles. For non-sham controls, we analysed non-specified routine care and protocol-guided care. Using meta-regression we explored impact of choice of control on effect of acupuncture. FINDINGS: Acupuncture was significantly superior to all categories of control group. For trials that used penetrating needles for sham control, acupuncture had smaller effect sizes than for trials with non-penetrating sham or sham control without needles. The difference in effect size was -0.45 (95% C.I. -0.78, -0.12; p = 0.007), or -0.19 (95% C.I. -0.39, 0.01; p = 0.058) after exclusion of outlying studies showing very large effects of acupuncture. In trials with non-sham controls, larger effect sizes associated with acupuncture vs. non-specified routine care than vs. protocol-guided care. Although the difference in effect size was large (0.26), it was not significant with a wide confidence interval (95% C.I. -0.05, 0.57, p = 0.1). CONCLUSION: Acupuncture is significantly superior to control irrespective of the subtype of control. While the choice of control should be driven by the study question, our findings can help inform study design in acupuncture, particularly with respect to sample size. Penetrating needles appear to have important physiologic activity. We recommend that this type of sham be avoided.

Intervention to improve social and family support for caregivers of dependent patients: ICIAS study protocol.

BACKGROUND: Despite the existence of formal professional support services, informal support (mainly family members) continues to be the main source of eldercare, especially for those who are dependent or disabled. Professionals on the primary health care are the ideal choice to educate, provide psychological support, and help to mobilize social resources available to the informal caregiver.Controversy remains concerning the efficiency of multiple interventions, taking a holistic approach to both the patient and caregiver, and optimum utilization of the available community resources. .For this reason our goal is to assess whether an intervention designed to improve the social support for caregivers effectively decreases caregivers burden and improves their quality of life. DESIGN: CONTROLled, multicentre, community intervention trial, with patients and their caregivers randomized to the intervention or control group according to their assigned Primary Health Care Team (PHCT). STUDY AREA: Primary Health Care network (9 PHCTs). STUDY PARTICIPANTS: Primary informal caregivers of patients receiving home health care from participating PHCTs. SAMPLE: Required sample size is 282 caregivers (141 from PHCTs randomized to the intervention group and 141 from PHCTs randomized to the control group. INTERVENTION: a) PHCT professionals: standardized training to implement caregivers intervention. b) Caregivers: 1 individualized counselling session, 1 family session, and 4 educational group sessions conducted by participating PHCT professionals; in addition to usual home health care visits, periodic telephone follow-up contact and unlimited telephone support. CONTROL: Caregivers and dependent patients: usual home health care, consisting of bimonthly scheduled visits, follow-up as needed, and additional attention upon request.Data analysisDependent variables: Caregiver burden (short-form Zarit test), caregivers' social support (Medical Outcomes Study), and caregivers' reported quality of life (SF-12)INDEPENDENT VARIABLES: a) Caregiver: sociodemographic data, Goldberg Scale, Apgar family questionnaire, Holmes and Rahe Psychosocial Stress Scale, number of chronic diseases. b) Dependent patient: sociodemographic data, level of dependency (Barthel Index), cognitive impairment (Pfeiffer test). DISCUSSION: If the intervention intended to improve social and family support is effective in reducing the burden on primary informal caregivers of dependent patients, this model can be readily applied throughout usual PHCT clinical practice. TRIAL REGISTRATION: Clinical trials registrar: NCT02065427.

In search of synergy: strategies for combining interventions at multiple levels.

The social ecological perspective provides a compelling justification for multilevel intervention. Yet, it offers little guidance for selecting interventions that work together in complementary or synergistic ways. Using a causal modeling framework, we describe five strategies for increasing potential complementarity or synergy among interventions that operate at different levels of influence: accumulation, amplification, facilitation, cascade, and convergence. We illustrate these strategies with examples of multilevel interventions to improve the quality of cancer treatment.

The epidemiology of thyroid disease.

INTRODUCTION: Thyroid disorders are prevalent and their manifestations are determined by the dietary iodine availability. SOURCES OF DATA: Data from screening large population samples from USA and Europe. AREAS OF AGREEMENT: The most common cause of thyroid disorders worldwide is iodine deficiency, leading to goitre formation and hypothyroidism. In iodine-replete areas, most persons with thyroid disorders have autoimmune disease. AREAS OF CONTROVERSY: Definition of thyroid disorders, selection criteria used, influence of age and sex, environmental factors and the different techniques used for assessment of thyroid function. GROWING POINTS: Increasing incidence of well-differentiated thyroid cancer. Environmental iodine influences the epidemiology of non-malignant thyroid disease. AREAS TIMELY FOR DEVELOPING RESEARCH: Iodine supplementation of populations with mild-to-moderate iodine deficiency. An evidence-based strategy for the risk stratification, treatment and follow-up of benign nodular thyroid disease. Is there any benefit in screening adults for thyroid dysfunction?

Mindfulness as a moderator in expressive writing.

Randomized, controlled studies have documented positive physical and psychological effects of writing about traumatic stress. Some of these studies have shown that individual differences play an important role, with participants responding differently to the intervention based on their personal characteristics. In the present expressive writing experiment, the trait of mindfulness was examined as a potential moderator. Seventy-six undergraduates were randomly assigned to either expressive writing (n = 37) or a control group (n = 39). Main effects favoring expressive writing were found, and these were qualified by significant interactions with mindfulness. Specifically, individuals with higher mindfulness scores responded better to expressive writing, experiencing greater physical and psychological benefits than individuals with lower mindfulness scores.

Mercury exposure and risk of cardiovascular disease in two U.S. cohorts.

BACKGROUND: Exposure to methylmercury from fish consumption has been linked to a potentially increased risk of cardiovascular disease, but evidence from prior studies is equivocal. Beneficial effects of the ingestion of fish and selenium may also modify such effects. METHODS: Among subjects from two U.S. cohorts (a total of 51,529 men and 121,700 women) whose toenail clippings had been stored, we prospectively identified incident cases of cardiovascular disease (coronary heart disease and stroke) in 3427 participants and matched them to risk-set-sampled controls according to age, sex, race, and smoking status. Toenail mercury and selenium concentrations were assessed with the use of neutron-activation analysis. Other demographic characteristics, cardiovascular risk factors, fish consumption, and lifestyle habits were assessed by means of validated questionnaires. Associations between mercury exposure and incident cardiovascular disease were evaluated with the use of conditional logistic regression. RESULTS: Median toenail mercury concentrations were 0.23 µg per gram (interdecile range, 0.06 to 0.94) in the case participants and 0.25 µg per gram (interdecile range, 0.07 to 0.97) in the controls. In multivariate analyses, participants with higher mercury exposures did not have a higher risk of cardiovascular disease. For comparisons of the fifth quintile of mercury exposure with the first quintile, the relative risks were as follows: coronary heart disease, 0.85 (95% confidence interval [CI], 0.69 to 1.04; P=0.10 for trend); stroke, 0.84 (95% CI, 0.62 to 1.14; P=0.27 for trend); and total cardiovascular disease, 0.85 (95% CI, 0.72 to 1.01; P=0.06 for trend). Findings were similar in analyses of participants with low selenium concentrations or low overall fish consumption and in several additional sensitivity analyses. CONCLUSIONS: We found no evidence of any clinically relevant adverse effects of mercury exposure on coronary heart disease, stroke, or total cardiovascular disease in U.S. adults at the exposure levels seen in this study. (Funded by the National Institutes of Health.).

Two new covariate adjustment methods for non-inferiority assessment of binary clinical trials data.

In clinical trials, examining the adjusted treatment difference has become the preferred way to establish non-inferiority (NI) in cases involving a binary endpoint. However, current methods are inadequate in the area of covariate adjustment. In this paper, we introduce two new methods, nonparametric and parametric, of using the probability and probability (P-P) curve to address the issue of unadjusted categorical covariates in the traditional assessment of NI in clinical trials. We also show that the area under the P-P curve is a valid alternative for assessing NI using the adjusted treatment difference, and we compute this area using Mann-Whitney nonparametric statistics. Our simulation studies demonstrate that our proposed methods can not only control type I error at a predefined significance level but also achieve higher statistical power than those of traditional parametric and nonparametric methods that overlook covariate adjustment, especially when covariates are unbalanced in the two treatment groups. We illustrate the effectiveness of our methodology with data from clinical trials of a therapy for coronary heart disease.