A systematic review of contaminants in donor human milk.

Donor human milk (DHM) from a milk bank is the recommended feeding method for preterm infants when the mother's own milk (MOM) is not available. Despite this recommendation, information on the possible contamination of donor human milk and its impact on infant health outcomes is poorly characterised. The aim of this systematic review is to assess contaminants present in DHM samples that preterm and critically ill infants consume. The data sources used include PubMed, EMBASE, CINAHL and Web of Science. A search of the data sources targeting DHM and its potential contaminants yielded 426 publications. Two reviewers (S. T. and D. L.) conducted title/abstract screening through Covidence software, and predetermined inclusion/exclusion criteria yielded 26 manuscripts. Contaminant types (bacterial, chemical, fungal, viral) and study details (e.g., type of bacteria identified, study setting) were extracted from each included study during full-text review. Primary contaminants in donor human milk included bacterial species and environmental pollutants. We found that bacterial contaminants were identified in 100% of the papers in which bacterial contamination was sought (16 papers) and 61.5% of the full data set (26 papers), with the most frequently identified genera being Staphylococcus (e.g., Staphylococcus aureus and coagulase-negative Staphylococcus) and Bacillus (e.g., Bacillus cereus). Chemical pollutants were discovered in 100% of the papers in which chemical contamination was sought (eight papers) and 30.8% of the full data set (26 papers). The most frequently identified chemical pollutants included perfluoroalkyl substances (six papers), toxic metal (one paper) and caffeine (one paper). Viral and fungal contamination were identified in one paper each. Our results highlight the importance of establishing standardisation in assessing DHM contamination and future studies are needed to clarify the impact of DHM contaminants on health outcomes.

Associations of prenatal maternal depressive symptoms with cord blood glucocorticoids and child hair cortisol levels in the project viva and the generation R cohorts: a prospective cohort study.

BACKGROUND: Prior studies have reported conflicting results regarding the association of prenatal maternal depression with offspring cortisol levels. We examined associations of high levels of prenatal depressive symptoms with child cortisol biomarkers. METHODS: In Project Viva (n = 925, Massachusetts USA), mothers reported their depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS) during pregnancy, cord blood glucocorticoids were measured at delivery, and child hair cortisol levels were measured in mid-childhood (mean (SD) age: 7.8 (0.8) years) and early adolescence (mean (SD) age: 13.2 (0.9) years). In the Generation R Study (n = 1644, Rotterdam, The Netherlands), mothers reported depressive symptoms using the Brief Symptom Inventory (BSI) during pregnancy, and child hair cortisol was measured at a mean (SD) age of 6.0 (0.5) years. We used cutoffs of ≥ 13 for the EPDS and > 0.75 for the BSI to indicate high levels of prenatal depressive symptoms. We used multivariable linear regression models adjusted for child sex and age (at outcome), and maternal pre-pregnancy BMI, education, social support from friends/family, pregnancy smoking status, marital status, and household income to assess associations separately in each cohort. We also meta-analyzed childhood hair cortisol results from both cohorts. RESULTS: 8.0% and 5.1% of women respectively experienced high levels of prenatal depressive symptoms in Project Viva and the Generation R Study. We found no associations between high levels of maternal depressive symptoms during pregnancy and child cortisol biomarkers in either cohort. CONCLUSIONS: The present study does not find support for the direct link between high levels of maternal depressive symptoms and offspring cortisol levels.

Should we abandon annual physical examination? - A meta-analysis of annual physical examination and all-cause mortality in adults based on observational studies.

Several meta-analyses based on randomized clinical trials data have failed to find an association between the annual physical examination (APE) and reduced mortality; however, no comparable meta-analysis based on observational data exists. We conducted a meta-analysis of observational studies comparing APE versus non-APE in adults for all-cause mortality. English-language searches of four databases (PubMed, CINAHL, EMBASE, and Google Scholar) between the years 2000 to 2019 yielded seven observational studies that investigated APE versus non-APE in healthy adults in relation to all-cause mortality. Random effects models were used to calculate pooled hazard ratios and 95% confidence intervals (CI), and to incorporate variation between studies. During follow-up periods that ranged from two to 25 years, there were 35,055 deaths among 633,957 participants. APE was significantly associated with a 45% lower hazard of all-cause mortality, with pooled hazard ratio of 0.55 (95% CI 0.48 to 0.64, P < 0.01) for all participants. This meta-analysis of seven observational studies in the past 20 years provides evidence of an association between APE and a lower hazard of all-cause mortality, a finding that contrasts with findings based on meta-analyses of randomized clinical trials data. Nonetheless, at present the evidence available about the effectiveness or ineffectiveness of APE on all-cause mortality still needs further study.

The effect of opioids on the cognitive function of older adults: results from the Personality and Total Health through life study.

BACKGROUND: chronic pain, a common complaint among older adults, affects physical and mental well-being. While opioid use for pain management has increased over the years, pain management in older adults remains challenging, due to potential severe adverse effects of opioids in this population. OBJECTIVE: we examined the association between opioid use, and changes in cognitive function of older adults. DESIGN: prospective study. SETTING: community dwelling older adults. SUBJECTS: study population consisted of 2,222 individuals aged 65-69 years at baseline from the Personality and Total Health Through Life Study in Australia. METHODS: medication data were obtained from the Pharmaceutical Benefits Scheme. Cognitive measures were obtained from neuropsychological battery assessment. Opioid exposure was quantified as Total Morphine Equivalent Dose (MED). The association between change in cognitive function between Wave 2 and Wave 3, and cumulative opioid use was assessed through generalized linear models. RESULTS: cumulative opioid exposure exceeding total MED of 2,940 was significantly associated with poorer performance in the Mini Mental State Examination (MMSE). Compared with those not on opioids, individuals exposed to opioids resulting in cumulative total MED of greater than 2,940 had significantly lower scores in the MMSE (Model 1: ß = -0.34, Model 2: ß = -0.35 and Model 3: ß = -0.39, P < 0.01). Performance in other cognitive assessments was not associated with opioid use. CONCLUSION: prolonged opioid use in older adults can affect cognitive function, further encouraging the need for alternative pain management strategies in this population. Pain management options should not adversely affect healthy ageing trajectories and cognitive health.

Factors associated with pediatric drowning admissions and outcomes at a trauma center, 2010-2017.

BACKGROUND: Drowning is a leading cause of preventable mortality and morbidity in children. Its high fatality rate and frequent severe sequelae (e.g. brain damage and permanent loss of functioning) place a premium on preventive efforts. METHODS: A retrospective analysis of patients ≤21 years of age admitted between 2010 and 2017 to a pediatric trauma center was conducted to identify factors associated with drowning admissions, fatal drowning, and severe outcome (ventilator use, ICU admission, or death). Outcomes were modeled and estimated by use of logistic regression and Poisson regression. RESULTS: Drowning accounted for 153/4931 (3.1%) trauma admissions between 2010 and 2017. The risk of death (13.1% vs. 1.5%, p < .01), and severe outcome (24.8% vs. 7.8%, p < .01) was significantly higher for drownings vs. other causes. All 20 drowning deaths occurred among children left unattended. In Poisson regression analysis, weekends, summer breaks, and hotter days were independently associated with a higher probability of drowning admissions. Additionally, in analyses excluding indicators of severity, the odds of severe outcome were higher for children age ≤ 2 years [adjusted odds ratio (AOR) = 3.88 95% CI (1.58, 9.53)], and injury downtime of >5 min or unknown length [AOR = 6.66 95% CI (2.74-16.15)]. Immediate intervention after the discovery was associated with ~70% lower odds of a severe outcome. CONCLUSIONS: Drowning admissions were both more severe and more often fatal compared to other pediatric injury causes of admission. Enhanced and targeted educational messages for parents of young children, focused on prevention behaviors on high-risk days and immediate bystander intervention, may reduce the occurrence and severity of these tragic accidents. TABLE OF CONTENTS SUMMARY: A retrospective multi-year cohort study to identify modifiable factors associated with drowning admissions, severe complications, and death from a large trauma registry database. WHAT'S KNOWN ON THIS SUBJECT: Drowning is a leading cause of unintentional injury that results in severe morbidity and a high rate of mortality. Children are disproportionately affected by drowning and have a higher risk of long term sequelae and death. WHAT THIS STUDY ADDS: This study identified high-risk populations and periods for drowning, the importance of supervision, and the effectiveness of immediate intervention in reducing unfavorable outcomes after drowning. It also highlights a need for heightened local intervention for drowning prevention.

Social context and change in suicide ideation in a community sample of youths.

PURPOSE: Adolescent suicide ideation (SI) often portends more grievous suicidal behavior; yet, long-term studies of what risk factors predict SI are limited. We employ a multi-wave longitudinal design to investigate the impact of earlier social contexts on change in SI. METHOD: A community sample of 748 youths drawn from the Children in the Community (CIC) study was first assessed with the CIC Youth SI Scale at mean age 13.7 (range 9-18) (baseline) and in two follow-ups over 10 years. GEE Poisson Regression was used to estimate SI between ages 10 and 25 (intercept set at age midpoint of 17), and to examine associations between baseline measures of parent, peer, and school social contexts and subsequent change in SI. Analyses were controlled for demographic characteristics and known risks for SI: sexual or physical abuse before age 18 (obtained by official reports) and major depressive disorder (MDD, diagnosed by psychiatric interview at baseline and follow-ups). RESULTS: SI declined significantly by age 17 with greater mother affection (ß = - 0.091, SE = 0.037), peer friendship quality (ß = - 0.115, SE = 0.034), peer social support (ß = - 0.116, SE = 0.042), and school engagement (ß = - 0.083, SE = 0.045, trend), but increased significantly with more parent punishment (ß = 0.143, SE = 0.045) and school conflict (ß = 0.168, SE = 0.042). SI associations with sexual or physical abuse (ß = 0.299, SE = 0.137) and MDD (ß = 0.777, SE = 0.130) were independent of other effects. CONCLUSIONS: Earlier social contexts influence change in SI independent of each other and of known risks for SI in community youths, and may be a resource for intervention efforts to deter future SI.

Generalizability analysis for clinical trials: a simulation study.

Subjects are rarely selected on a random basis from a well-defined patient population of interest into a clinical trial, with women, children, the elderly, and those with common comorbidities who are frequently underrepresented. Decades of clinical experience have demonstrated that the application of trial findings to individual patients is permissible by using efficacy as a measure of effectiveness and assuming that the characteristics of patients are sufficiently similar. In order to investigate this issue in greater depth, we simulated a patient population with treatment effect size of 0.5 (Cohen's d) and five covariates that included gender, health insurance, comorbidity, age, and motivation. To demonstrate how selection of patients for a clinical trial can bias the results when treatment effect varies across individuals, we created 50 nonrandom clinical trials based on this patient population and showed relative bias to range from 1.68% to 99.70%. We calculated and evaluated three indexes: C-statistics, standardized mean difference (SMD), and Tipton's index (ß) of generalization for the 50 nonrandom trials. Findings indicated that (i) the ranges were 0.56-0.98, 0.23-11.17, and 0.99-0.73 for C-statistics, SMD, and ß, respectively, when treatment effect bias increased from 1.68% to 99.70% and (ii) C-statistics < 0.86, SMD < 1.95, and ß > 0.91 when treatment effect bias <50%. Recommendations are made using existing generalization indexes on the basis of our simulation results. An example from a real clinical trial is provided for illustration. Copyright © 2017 John Wiley & Sons, Ltd.

Impact of Adolescent Personality Disorders on Obesity 17 Years Later.

OBJECTIVES: To investigate associations between adolescent personality disorder (PD) and obesity 17 years later. METHODS: The Children in the Community is a longitudinal study based on a randomly sampled cohort of families, in effect since 1975. PDs were assessed in youths by self-report and mother report in 1985 to 1986, when participants were at an average age of 16 years. Obesity was assessed in 2001 to 2004 when participants were an average age of 33 years (n = 621). RESULTS: Prevalence of obesity was 16.59% (103/621) at an average age of 33 years. Prevalence of any adolescent PD was 17.55% (109/621) at an average age of 16 years. Adolescents who had any PD were 1.84 (95% confidence interval [CI] = 1.05-3.22) times as likely to be obese 17 years later after adjusting for demographic variables and known risk factors. Paranoid, histrionic, and obsessive-compulsive PDs in adolescence were significantly associated with obesity in adulthood, with odds ratios of 3.45 (95% CI = 1.46-8.17), 4.49 (95% CI = 1.91-10.53), and 6.80 (95% CI = 2.50-18.55), respectively. CONCLUSIONS: This is the first study to report a significant independent long-term association based on prospective data between adolescent PDs and adult obesity in a community-based sample. Findings will contribute to the design of preventive measures against the development of obesity.

Bayesian bivariate linear mixed-effects models with skew-normal/independent distributions, with application to AIDS clinical studies.

Bivariate correlated (clustered) data often encountered in epidemiological and clinical research are routinely analyzed under a linear mixed-effected (LME) model with normality assumptions for the random-effects and within-subject errors. However, those analyses might not provide robust inference when the normality assumptions are questionable if the data set particularly exhibits skewness and heavy tails. In this article, we develop a Bayesian approach to bivariate linear mixed-effects (BLME) models replacing the Gaussian assumptions for the random terms with skew-normal/independent (SNI) distributions. The SNI distribution is an attractive class of asymmetric heavy-tailed parametric structure which includes the skew-normal, skew-t, skew-slash, and skew-contaminated normal distributions as special cases. We assume that the random-effects and the within-subject (random) errors, respectively, follow multivariate SNI and normal/independent (NI) distributions, which provide an appealing robust alternative to the symmetric normal distribution in a BLME model framework. The method is exemplified through an application to an AIDS clinical data set to compare potential models with different distribution specifications, and clinically important findings are reported.

Jointly Modeling Event Time and Skewed-Longitudinal Data with Missing Response and Mismeasured Covariate for AIDS Studies.

In longitudinal studies it is often of interest to investigate how a repeatedly measured marker in time is associated with a time to an event of interest. This type of research question has given rise to a rapidly developing field of biostatistics research that deals with the joint modeling of longitudinal and time-to-event data. Normality of model errors in longitudinal model is a routine assumption, but it may be unrealistically obscuring important features of subject variations. Covariates are usually introduced in the models to partially explain between- and within-subject variations, but some covariates such as CD4 cell count may be often measured with substantial errors. Moreover, the responses may encounter nonignorable missing. Statistical analysis may be complicated dramatically based on longitudinal-survival joint models where longitudinal data with skewness, missing values, and measurement errors are observed. In this article, we relax the distributional assumptions for the longitudinal models using skewed (parametric) distribution and unspecified (nonparametric) distribution placed by a Dirichlet process prior, and address the simultaneous influence of skewness, missingness, covariate measurement error, and time-to-event process by jointly modeling three components (response process with missing values, covariate process with measurement errors, and time-to-event process) linked through the random-effects that characterize the underlying individual-specific longitudinal processes in Bayesian analysis. The method is illustrated with an AIDS study by jointly modeling HIV/CD4 dynamics and time to viral rebound in comparison with potential models with various scenarios and different distributional specifications.

Lingual traction to facilitate fiber-optic intubation of difficult airways: a single-anesthesiologist randomized trial.

PURPOSE: Flexible fiber-optic bronchoscope-guided orotracheal intubation is a valuable technique with demonstrated benefits in the management of difficult airways. Despite its popularity with anesthesia providers, the technique is not fail-safe and airway-related complications secondary to failed intubation attempts remain an important problem. We sought to determine the effect of incorporating lingual traction on the success rate of fiber-optic bronchoscope-guided intubation in patients with anticipated difficult airways. METHODS: In this prospective, randomized, cohort study, we enrolled 91 adult patients with anticipated difficult airways scheduled for elective surgery to undergo fiber-optic bronchoscope-guided orotracheal intubation alone or with lingual traction by an individual anesthesiologist after induction of general anesthesia and neuromuscular blockade. A total of 78 patients were randomized: 39 patients to the fiber-optic bronchoscope-guided intubation with lingual traction group and 39 patients to the fiber-optic bronchoscope-guided intubation alone group. The primary endpoint was the rate of successful first attempt intubations. The secondary outcome was sore throat grade on post-operative day 1. RESULTS: Fiber-optic intubation with lingual traction compared to fiber-optic intubation alone resulted in a higher success rate (92.3 vs. 74.4 %, χ (2) = 4.523, p = 0.033) and greater odds for successful first attempt intubation (OR 4.138, 95 % CI 1.041-16.444, p = 0.044). Sore throat severity on post-operative day 1 was not significantly different but trended towards worsening grades with lingual traction. CONCLUSIONS: In this study, lingual traction was shown to be a valuable maneuver for facilitating fiber-optic bronchoscope-guided intubation in the management of patients with anticipated difficult airways.

The efficacy of religious service attendance in reducing depressive symptoms.

PURPOSE: To examine whether religiosity may help people ward off depression, we investigated the association between religious service attendance and depressive symptom scores in a community-based 30-year follow-up longitudinal study. METHODS: This study used data on 754 subjects followed over 30 years and evaluated at four time points. Linear mixed effects models were used to assess the association between religious service attendance and depressive symptoms development; frequency of attendance and age also were used as predictors. Demographic factors, life-time trauma, family socioeconomic status, and recent negative events were considered as control variables. RESULTS: Depressive symptom scores were reduced by an average of 0.518 units (95 % CI from -0.855 to -0.180, p < 0.005) each year in subjects who attended religious services as compared with subjects who did not. The more frequent the religious service attendance, the stronger the influence on depressive symptoms when compared with non-attendance. Yearly, monthly, and weekly religious service attendance reduced depression scores by 0.474 (95 % CI from -0.841 to -0.106, p < 0.01), 0.495 (95 % CI from -0.933 to -0.057, p < 0.05) and 0.634 (95 % CI from -1.056 to -0.212, p < 0.005) units on average, respectively, when compared with non-attendance after controlling for other covariates. CONCLUSION: Religious service attendance may reduce depressive symptoms significantly, with more frequent attendance having an increasingly greater impact on symptom reduction in this 30-year community-based longitudinal study.

Sex-specific effects of fetal exposure to the 1959-1961 Chinese famine on risk of adult hypertension.

Previous research is inconsistent about the effects of prenatal famine exposure on risk of adult hypertension. Follow-up of persons exposed to the 1959-1961 Chinese famine, the largest in human history, provides an opportunity to examine the long-term impact of prenatal famine exposure on adult cardiovascular disease (CVD). We investigated the effects of fetal-infant exposure to the famine on risk of hypertension in adulthood. We included 1,415 participants from the 2009 China Health and Nutrition Survey born September 1, 1956-December 31, 1964. Blood pressure (BP) measurements, self-reported previous diagnosis of hypertension and current anti-hypertension drug use were obtained from the survey. Differences in mean BP and risk of adult hypertension by famine exposure status were determined using linear and logistic regression analyses, after adjusting for confounders. Women with fetal-infant exposure to famine had higher mean systolic blood pressure (4.24 mmHg; 95% confidence interval (CI) 1.50-6.98) than those unexposed. They also had increased odds of a prior diagnosis of hypertension (odds ratio (OR) 2.16; 95% CI 1.16-4.02), and were more likely to be currently taking anti-hypertensive medications (OR 2.81; 95% CI 1.32-5.97) than unexposed women after adjusting for covariates. No statistically significant increases in mean BP or hypertension were seen among men. Exposure to famine during the fetal-infant period or early childhood has deleterious effects on adult health, but the effects may be greater for women. Gender-specific intervention strategies for CVD may be warranted for populations exposed to under-nutrition during critical time periods of fetal development.

Effectiveness of healthy relationships video-group-A videoconferencing group intervention for women living with HIV: preliminary findings from a randomized controlled trial.

INTRODUCTION: Expanded access to efficacious interventions is needed for women living with human immunodeficiency virus (WLH) in the United States. Availability of "prevention with (human immunodeficiency virus [HIV)] positives" interventions in rural/remote and low HIV prevalence areas remains limited, leaving WLH in these communities few options for receiving effective behavioral interventions such as Healthy Relationships (HR). Offering such programs via videoconferencing groups (VGs) may expand access. This analysis tests the effectiveness of HR-VG (versus wait-list control) for reducing sexual risk behavior among WLH and explores intervention satisfaction. SUBJECTS AND METHODS: In this randomized controlled trial unprotected vaginal/anal sex occasions over the prior 3 months reported at the 6-month follow-up were compared across randomization groups through zero-inflated Poisson regression modeling, controlling for unprotected sex at baseline. Seventy-one WLH were randomized and completed the baseline assessment (n=36 intervention and n=35 control); 59 (83% in each group) had follow-up data. RESULTS: Among those who engaged in unprotected sex at 6-month follow-up, intervention participants had approximately seven fewer unprotected occasions than control participants (95% confidence interval 5.43-7.43). Intervention participants reported high levels of satisfaction with HR-VG; 84% reported being "very satisfied" overall. CONCLUSIONS: This study found promising evidence for effective dissemination of HIV risk reduction interventions via VGs. Important next steps will be to determine whether VGs are effective with other subpopulations of people living with HIV (i.e., men and non-English speakers) and to assess cost-effectiveness. Possibilities for using VGs to expand access to other psychosocial and behavioral interventions and reduce stigma are discussed.

Breaking the silence of sharing data in medical research.

Data sharing is highly advocated in the scientific community, with numerous organizations, funding agencies, and journals promoting transparency and collaboration. However, limited research exists on actual data sharing practices. We conducted a comprehensive analysis of the intent to share individual participant data (IPD) in a total of 313,990 studies encompassing clinical trials and observational studies obtained from ClinicalTrials.gov, spanning the period from 2000 to 2023. Our study found that only 10.3% of principal investigators (PIs) expressed intent to share IPD. Clinical trials were more likely to share data than observational studies (odds ratio, OR = 1.98, 95% CI: 1.92-2.04). Large sample size studies were 1.69 times more likely to share data than small ones (95% CI: 1.65-1.73). Studies registered after 2018 were 1.6 times more likely to share data (95% CI: 1.57-1.64) than before 2019. NIH and other US Federal agency-funded studies had 1.49 times higher odds of sharing data (95% CI: 1.43-1.55) than other funders. USA-based studies were 1.53 times more likely to share data (95% CI: 1.49-1.57) than out of USA. Biological trials were 1.58 times more likely to share data than drug and other trials (95% CI: 1.51-1.66). Phase III trials had the highest odds, 2.47 times, of sharing data (95% CI: 2.38-2.56) than non-Phase III trials.

A data-driven approach to choosing privacy parameters for clinical trial data sharing under differential privacy.

OBJECTIVES: Clinical trial data sharing is crucial for promoting transparency and collaborative efforts in medical research. Differential privacy (DP) is a formal statistical technique for anonymizing shared data that balances privacy of individual records and accuracy of replicated results through a "privacy budget" parameter, ε. DP is considered the state of the art in privacy-protected data publication and is underutilized in clinical trial data sharing. This study is focused on identifying ε values for the sharing of clinical trial data. MATERIALS AND METHODS: We analyzed 2 clinical trial datasets with privacy budget ε ranging from 0.01 to 10. Smaller values of ε entail adding greater amounts of random noise, with better privacy as a result. Comparison of rates, odds ratios, means, and mean differences between the original clinical trial datasets and the empirical distribution of the DP estimator was performed. RESULTS: The DP rate closely approximated the original rate of 6.5% when ε > 1. The DP odds ratio closely aligned with the original odds ratio of 0.689 when ε ≥ 3. The DP mean closely approximated the original mean of 164.64 when ε ≥ 1. As ε increased to 5, both the minimum and maximum DP means converged toward the original mean. DISCUSSION: There is no consensus on how to choose the privacy budget ε. The definition of DP does not specify the required level of privacy, and there is no established formula for determining ε. CONCLUSION: Our findings suggest that the application of DP holds promise in the context of sharing clinical trial data.

Caution regarding the choice of standard deviations to guide sample size calculations in clinical trials.

BACKGROUND: The method used to determine choice of standard deviation (SD) is inadequately reported in clinical trials. Underestimations of the population SD may result in underpowered clinical trials. PURPOSE: This study demonstrates how using the wrong method to determine population SD can lead to inaccurate sample sizes and underpowered studies, and offers recommendations to maximize the likelihood of achieving adequate statistical power. METHODS: We review the practice of reporting sample size and its effect on the power of trials published in major journals. Simulated clinical trials were used to compare the effects of different methods of determining SD on power and sample size calculations. RESULTS: Prior to 1996, sample size calculations were reported in just 1%-42% of clinical trials. This proportion increased from 38% to 54% after the initial Consolidated Standards of Reporting Trials (CONSORT) was published in 1996, and from 64% to 95% after the revised CONSORT was published in 2001. Nevertheless, underpowered clinical trials are still common. Our simulated data showed that all minimal and 25th-percentile SDs fell below 44 (the population SD), regardless of sample size (from 5 to 50). For sample sizes 5 and 50, the minimum sample SDs underestimated the population SD by 90.7% and 29.3%, respectively. If only one sample was available, there was less than 50% chance that the actual power equaled or exceeded the planned power of 80% for detecting a median effect size (Cohen's d = 0.5) when using the sample SD to calculate the sample size. The proportions of studies with actual power of at least 80% were about 95%, 90%, 85%, and 80% when we used the larger SD, 80% upper confidence limit (UCL) of SD, 70% UCL of SD, and 60% UCL of SD to calculate the sample size, respectively. When more than one sample was available, the weighted average SD resulted in about 50% of trials being underpowered; the proportion of trials with power of 80% increased from 90% to 100% when the 75th percentile and the maximum SD from 10 samples were used. Greater sample size is needed to achieve a higher proportion of studies having actual power of 80%. LIMITATIONS: This study only addressed sample size calculation for continuous outcome variables. CONCLUSIONS: We recommend using the 60% UCL of SD, maximum SD, 80th-percentile SD, and 75th-percentile SD to calculate sample size when 1 or 2 samples, 3 samples, 4-5 samples, and more than 5 samples of data are available, respectively. Using the sample SD or average SD to calculate sample size should be avoided.

Associations of maternal glucose markers in pregnancy with cord blood glucocorticoids and child hair cortisol levels.

Exposure to maternal hyperglycemia in utero has been associated with adverse metabolic outcomes in offspring. However, few studies have investigated the relationship between maternal hyperglycemia and offspring cortisol levels. We assessed associations of gestational diabetes mellitus (GDM) with cortisol biomarkers in two longitudinal prebirth cohorts: Project Viva included 928 mother-child pairs and Gen3G included 313 mother-child pairs. In Project Viva, GDM was diagnosed in N = 48 (5.2%) women using a two-step procedure (50 g glucose challenge test, if abnormal followed by 100 g oral glucose tolerance test [OGTT]), and in N = 29 (9.3%) women participating in Gen3G using one-step 75 g OGTT. In Project Viva, we measured cord blood glucocorticoids and child hair cortisol levels during mid-childhood (mean (SD) age: 7.8 (0.8) years) and early adolescence (mean (SD) age: 13.2 (0.9) years). In Gen3G, we measured hair cortisol at 5.4 (0.3) years. We used multivariable linear regression to examine associations of GDM with offspring cortisol, adjusting for child age and sex, maternal prepregnancy body mass index, education, and socioeconomic status. We additionally adjusted for child race/ethnicity in the cord blood analyses. In both Project Viva and Gen3G, we observed null associations of GDM and maternal glucose markers in pregnancy with cortisol biomarkers in cord blood at birth (ß = 16.6 nmol/L, 95% CI -60.7, 94.0 in Project Viva) and in hair samples during childhood (ß = -0.56 pg/mg, 95% CI -1.16, 0.04 in Project Viva; ß = 0.09 pg/mg, 95% CI -0.38, 0.57 in Gen3G). Our findings do not support the hypothesis that maternal hyperglycemia is related to hypothalamic-pituitary-adrenal axis activity.

On the Origins of Disorganized Attachment and Internal Working Models: Paper II. An Empirical Microanalysis of 4-Month Mother-Infant Interaction.

A microanalysis of 4-month mother-infant face-to-face communication predicted 12-month infant disorganized (vs. secure) attachment outcomes in an urban community sample. We documented a dyadic systems view of the roles of both partners, the roles of both self- and interactive contingency, and the importance of attention, orientation and touch, and as well as facial and vocal affect, in the co-construction of attachment disorganization. The analysis of different communication modalities identified striking intrapersonal and interpersonal intermodal discordance or conflict, in the context of intensely distressed infants, as the central feature of future disorganized dyads at 4 months. Lowered maternal contingent coordination, and failures of maternal affective correspondence, constituted maternal emotional withdrawal from distressed infants. This maternal withdrawal compromises infant interactive agency and emotional coherence. We characterize of the nature of emerging internal working models of future disorganized infants as follows: Future disorganized infants represent states of not being sensed and known by their mothers, particularly in moments of distress; they represent confusion about both their own and their mothers' basic emotional organization, and about their mothers' response to their distress. This internal working model sets a trajectory in development which may disturb the fundamental integration of the person. The remarkable specificity of our findings has the potential to lead to more finely-focused clinical interventions.

How Community and Individual Risk Factors Mutually Impact Youth's Perceived Safety: A Syndemic Analysis Using Structural Equation Modeling.

The purpose of this study was to evaluate the mutual impact of community and individual factors on youth's perceptions of community safety, using structural equation modeling (SEM) conceptualized by syndemic theory. This study used survey data collected from a county wide sample of middle and high school students (N=25,147) in West Central Florida in 2015. The outcome variable was youth's perceptions of community safety. Predictors were latent individual and community factors constructed from 14 observed variables including gun accessibility, substance use, depressive symptoms, and multiple neighborhood disadvantage questions. Three structural equation models were conceptualized based on syndemic theory and analyzed in Mplus 8 using weighted least squares (WLS) estimation. Each model's goodness of fit was assessed. Approximately seven percent of youth reported feeling unsafe in their community. After model modifications, the final model showed a good fit of the data and adhered to the theoretical assumption. In the final SEM model, an individual latent factor was implied by individual predictors measuring gun accessibility without adult's permission (ß=0.70), sadness and hopelessness (ß=0.52), alcohol use (ß=0.79), marijuana use (ß=0.94), and illegal drug use (ß=0.77). Meanwhile, a community latent factor was indicated by multiple community problems including public drinking (ß=0.88), drug addiction (ß=0.96), drug selling (ß=0.97), lack of money (ß=0.83), gang activities (ß=0.90), litter and trash (ß=0.79), graffiti (ß=0.91), deserted houses (ß=0.86), and shootings (ß=0.93). A second-order syndemic factor that represented the individual and community factors showed a very strong negative association with youth's safe perception (ß=-0.98). This study indicates that individual risk factors and disadvantaged community conditions interacted with each other and mutually affected youth's perceptions of community safety. To reduce these co-occurring effects and improve safe perceptions among youth, researchers and practitioners should develop and implement comprehensive strategies targeting both individual and community factors.