Publications

Abstract

Objective To evaluate the association between newborn acylcarnitine profiles and the subsequent development of necrotizing enterocolitis (NEC) with the use of routinely collected newborn screening data in infants born preterm. Study design A retrospective cohort study was conducted with the use of discharge records for infants born preterm admitted to neonatal intensive care units in California from 2005 to 2009 who had linked state newborn screening results. A model-development cohort of 94 110 preterm births from 2005 to 2008 was used to develop a risk-stratification model that was then applied to a validation cohort of 22 992 births from 2009. Results Fourteen acylcarnitine levels and acylcarnitine ratios were associated with increased risk of developing NEC. Each log unit increase in C5 and free carnitine /(C16 + 18:1) was associated with a 78% and a 76% increased risk for developing NEC, respectively (OR 1.78, 95% CI 1.53-2.02, and OR 1.76, 95% CI 1.51-2.06). Six acylcarnitine levels, along with birth weight and total parenteral nutrition, identified 89.8% of newborns with NEC in the model-development cohort (area under the curve 0.898, 95% CI 0.889-0.907) and 90.8% of the newborns with NEC in the validation cohort (area under the curve 0.908, 95% CI 0.901-0.930). Conclusions Abnormal fatty acid metabolism was associated with prematurity and the development of NEC. Metabolic profiling through newborn screening may serve as an objective biologic surrogate of risk for the development of disease and thus facilitate disease-prevention strategies.

Abstract

Widespread pain and anxiety are commonly reported in cancer patients. We hypothesize that cancer is accompanied by attenuation of endogenous opioid-mediated inhibition, which subsequently causes widespread pain and anxiety. To test this hypothesis we used a mouse model of oral squamous cell carcinoma (SCC) in the tongue. We found that mice with tongue SCC exhibited widespread nociceptive behaviors in addition to behaviors associated with local nociception that we reported previously. Tongue SCC mice exhibited a pattern of reduced opioid receptor expression in the spinal cord; intrathecal administration of respective mu (MOR), delta (DOR), and kappa (KOR) opioid receptor agonists reduced widespread nociception in mice, except for the fail flick assay following administration of the MOR agonist. We infer from these findings that opioid receptors contribute to widespread nociception in oral cancer mice. Despite significant nociception, mice with tongue SCC did not differ from sham mice in anxiety-like behaviors as measured by the open field assay and elevated maze. No significant differences in c-Fos staining were found in anxiety-associated brain regions in cancer relative to control mice. No correlation was found between nociceptive and anxiety-like behaviors. Moreover, opioid receptor agonists did not yield a statistically significant effect on behaviors measured in the open field and elevated maze in cancer mice. Lastly, we used an acute cancer pain model (injection of cancer supernatant into the mouse tongue) to test whether adaptation to chronic pain is responsible for the absence of greater anxiety-like behavior in cancer mice. No changes in anxiety-like behavior were observed in mice with acute cancer pain.

Abstract

CONCLUSIONS: In this study, CFIR provided a valuable framework for evaluating factors that may influence implementation of a systems-level intervention for tobacco control in a LMIC and understand what adaptations may be needed to translate a model of care delivery from a HIC to a LMIC.TRIAL REGISTRATION: NCT02564653 . Registered September 2015.BACKGROUND: Services to treat tobacco dependence are not readily available to smokers in low-middle income countries (LMICs) where smoking prevalence remains high. We are conducting a cluster randomized controlled trial comparing the effectiveness of two strategies for implementing tobacco use treatment guidelines in 26 community health centers (CHCs) in Viet Nam. Guided by the Consolidated Framework for Implementation Research (CFIR), prior to implementing the trial, we conducted formative research to (1) identify factors that may influence guideline implementation and (2) inform further modifications to the intervention that may be necessary to translate a model of care delivery from a high-income country (HIC) to the local context of a LMIC.METHODS: We conducted semi-structured qualitative interviews with CHC medical directors, health care providers, and village health workers (VHWs) in eight CHCs (n = 40). Interviews were transcribed verbatim and translated into English. Two qualitative researchers used both deductive (CFIR theory driven) and inductive (open coding) approaches to analysis developed codes and themes relevant to the aims of this study.RESULTS: The interviews explored four out of five CFIR domains (i.e., intervention characteristics, outer setting, inner setting, and individual characteristics) that were relevant to the analysis. Potential facilitators of the intervention included the relative advantage of the intervention compared with current practice (intervention characteristics), awareness of the burden of tobacco use in the population (outer setting), tension for change due to a lack of training and need for skill building and leadership engagement (inner setting), and a strong sense of collective efficacy to provide tobacco cessation services (individual characteristics). Potential barriers included the perception that the intervention was more complex (intervention characteristic) and not necessarily compatible (inner setting) with current workflows and staffing historically designed to address infectious disease prevention and control rather than chronic disease prevention and competing priorities that are determined by the MOH (outer setting).

Abstract

Healthy People 2020 established a national objective to increase the proportion of 9th-to-12th-grade students reporting sufficient sleep. A salient approach for achieving this objective is to delay middle and high school start times. Despite decades of research supporting the benefits of delayed school start times on adolescent sleep, health, and well-being, progress has been slow. Accelerating progress will require new approaches incorporating strategies that influence how school policy decisions are made. In this commentary, we introduce four strategies that influence decision-making processes and demonstrate how they can be applied to efforts aimed at changing school start time policies.

Abstract

In recent years, the Chinese government began expanding access to social services to older adults. This study examined whether older adults have increasing expectations that psychological consulting services will be provided by their communities. We analyzed the responses of participants in a prospective cohort study at 2 time points: 2005 and 2008. We utilized logistic regression with survey weights to determine whether there were any changes in attitudes toward community mental health services during the study period, and to determine the correlates of this change. The study participants had a higher expectation that their government would provide psychological consulting services in 2008 than 2005. The multiple logistic regressions conducted indicated that there was a statistically significant relationship between expectations for community-provided psychological consulting services and being a rural resident (odds ratio [OR] = 0.553, 95% confidence interval [CI] [0.353, 0.865]), change in gross regional product per capita (OR = 0.967, 95% CI [0.937, 0.997]), the interaction of those 2 variables (OR = 1.07, 95% CI [1.03, 1.11]), and increase in psychological well-being (OR = 0.971, 95% CI [0.954, 0.988]). Our study highlights the role that economic development can play in changing attitudes toward communityprovided psychological consulting services. It suggests that as economic development occurs, expectations for local communities to provide mental health services will increase.

Abstract

Purpose The purpose of the study was to determine the extent to which arthritis-related limitations are salient in predicting less than the recommended amount of time for adults with prediabetes to spend on moderate or vigorous physical activity. Methods Data from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) in the United States were used to identify the predictors of insufficient physical activity in a large sample of adults with prediabetes 20 years of age and older (n = 2536). Results When extrapolated to more than 45 million adults in the United States at least 20 years of age with prediabetes, 42.7% had insufficient physical activity. Having arthritis- related functional limitations was a significant predictor of insufficient physical activity, even after accounting for the statistically significant contributions of female sex, older age, lower education level, higher body mass index, and depression. Conclusion When educating and counseling adults with prediabetes, diabetes educators should assess for arthritis-related functional limitations when examining factors that may affect prediabetes progression. Recommendations for physical activity for those with mobility and other limitations need to be individualized within a tailored exercise program to accommodate their specific limitations.

Abstract

Objective: To assess variation in genes that regulate cholesterol metabolism in relation to the natural history of HIV infection. Design: Cross-sectional and longitudinal analysis of the Women's Interagency HIV Study. Methods: We examined 2050 single nucleotide polymorphisms (SNPs) in 19 genes known to regulate cholesterol metabolism in relation to HIV viral load and CD4 + T-cell levels in a multiracial cohort of 1066 antiretroviral therapy-naive women. Results: Six SNPs were associated with both HIV viral load and CD4 + T-cell levels at a false discovery rate of 0.01. Bioinformatics tools did not predict functional activity for five SNPs, located in introns of nuclear receptor corepressor 2, retinoid X receptor alpha (RXRA), and tetratricopeptide repeat domain 39B. Rs17111557 located in the 3′ untranslated region of proprotein convertase subtilisin/kexin type 9 (PCSK9) putatively affects binding of hsa-miR-548t-5p and hsa-miR-4796-3p, which could regulate PCSK9 expression levels. Interrogation of rs17111557 revealed stronger associations in the subset of women with HIV/hepatitis C virus (HCV) coinfection (n=408, 38% of women). Rs17111557 was also associated with low-density lipoprotein cholesterol levels in HIV/HCV coinfected (β: -10.4; 95% confidence interval: -17.9, -2.9; P=0.007), but not in HIV monoinfected (β:1.2; 95% confidence interval: -6.3, 8.6; P=0.76) women in adjusted analysis. Conclusion: PCSK9 polymorphism may affect HIV pathogenesis, particularly in HIV/HCV coinfected women. A likely mechanism for this effect is PCSK9-mediated regulation of cholesterol metabolism. Replication in independent cohorts is needed to clarify the generalizability of the observed associations.

Abstract

BACKGROUND: Reliable non-invasive markers to characterize inflammation, hepatocellular ballooning, and fibrosis in nonalcoholic fatty liver disease (NAFLD) are lacking. We investigated the relationship between plasma cytokine levels and features of NAFLD histology to gain insight into cellular pathways driving NASH and to identify potential non-invasive discriminators of NAFLD severity and pattern.METHODS: Cytokines were measured from plasma obtained at enrollment in pediatric participants in NASH Clinical Research Network studies with liver biopsy-proven NAFLD. Cytokines were chosen a priori as possible discriminators of NASH and its components. Minimization of Akaike Information Criterion (AIC) was used to determine cytokines retained in multivariable models. RESULTS: Of 235 subjects, 31% had "Definite NASH" on liver histology, 43% had "Borderline NASH", and 25% had NAFLD but not NASH. Total plasminogen activator inhibitor 1 (PAI1) and activated PAI1 levels were higher in pediatric participants with Definite NASH and with lobular inflammation. Interleukin-8 (IL-8) was higher in those with stage 3-4 fibrosis and lobular inflammation. sIL-2rα was higher in children with stage 3-4 fibrosis and portal inflammation. In multivariable analysis, PAI1 variables were discriminators of Borderline/Definite NASH, definite NASH, lobular inflammation and ballooning. IL-8 increased with steatosis and fibrosis severity; sIL-2rα increased with fibrosis severity and portal inflammation. IL-7 decreased with portal inflammation and fibrosis severity.CONCLUSIONS: Plasma cytokines associated with histology varied considerably among NASH features, suggesting promising avenues for investigation. Future, more targeted analysis is needed to identify the role of these markers in NAFLD and to evaluate their potential as non-invasive discriminators of disease severity.

Abstract

Background: This study aimed to synthesize the current literature examining the association between migration and cognitive function among middle-aged and older adults. Methods: We used the PRISMA as a guideline for this systematic review and searched the following databases: PubMed, CINAHL, EMBASE, and Global Health. Results: Twenty-five published studies were included. Twenty-two studies were focused on international migrants, while only 3 studied internal migrants. Fourteen studies were conducted in the United States, followed by UK (n = 2), Israel (n = 2), India (n = 2) and other countries like Canada and Australia. Some studies showed that middle-aged and older migrants demonstrated poorer cognitive function comparing to non-migrants in hosting places; while other studies indicated no association between migration and cognitive function. A higher level of acculturation was associated with better performance on cognitive function tests among migrants. Conclusion: It is unclear how or whether migration and cognitive function are related. The quality of current literature suffered from methodological deficiencies. Additional research is needed to examine the linkages using more comprehensive measures of migration and cognitive function.

Abstract

Objectives To examine the association between the number of teeth remaining and cognitive decline among Chinese older adults over a 13-year period. Design A large national longitudinal survey of Chinese older adults Setting The Chinese Longitudinal Healthy Longevity Survey (CLHLS) (1998-2011). Participants A total of 8,153 eligible participants aged 60+ interviewed in up to six waves. Measurements Cognitive function and teeth number were measured at each interview. Cognitive function was measured by the Mini-Mental Status Examination (MMSE). Number of natural teeth was self-reported. Individuals with severe cognitive impairment were excluded. Covariates included demographic characteristics, adult socioeconomic status characteristics, childhood socioeconomic status, health conditions, and health behaviors. Linear mixed models were applied in the analysis. Results The mean teeth number at baseline was 17.5(SD = 0.1), and the mean of baseline cognitive function was 27.3(SD = 0.0). Cognitive function declined over time (β = -0.19, P < .001) after controlling covariates. But, regardless of time, more teeth were associated with better cognitive function (β = 0.01, P < .001). The interaction of teeth number and time was significant (β = 0.01, P < .001), suggesting that the participants who had more teeth showed a slower pace of cognitive decline over time than those with fewer teeth after controlling for other covariates. Conclusion This study showed that tooth loss was associated with cognitive decline among Chinese older adults. Further studies are needed to examine the linkages between cognitive decline and oral health status using clinical examination data.

Abstract

The objective ot this study was to investigate whether lymphatic markers measured in women during the second trimester are associated with critical congenital heart defects (CCHDs) in offspring. This is a retrospective cohort study of pregnant women who participated in the California Prenatal Screening Program. CCHD data in the offspring was captured by linking birth certificate data with hospital patient discharge records. Second trimester samples were assayed for vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF) AA/BB, and PDGF AB. Logistic models were used to evaluate the association between lymphatic biomarkers and CCHD. Models were adjusted for other serum biomarkers and maternal characteristics. Results are presented in odds ratios (OR) with 95% confidence intervals (CI). We identified 93 cases with CCHDs and 194 controls without CCHDs. The crude and adjusted OR for log (ln) VEGF was 1.07 (95%CI 0.94–1.22) and 1.08 (95%CI 0.94–1.24), respectively; for ln PDGF AB/BB was 0.93 (95%CI 0.6–1.35) and 0.58 (95%CI 0.32–1.05), respectively. There was a significant association between ln PDFG AA and CCHDs (crude OR 1.83 (95%CI 1.05–3.2); adjusted OR 2.41 (95%CI 1.06–5.44)). Levels of circulating PDGF AA were highest in cases with hypoplastic left heart syndrome (HLHS) (mean 8.78 +/− 1.54 pg/ml). In this study, increased mid-pregnancy maternal serum levels of PDGF AA were associated with CCHDs in offspring. The highest PDGF AA levels were found in mothers of fetuses with HLHS. These findings may be useful in screening for CCHDs and offer insight into their association with nuchal translucency.

Abstract

Persistent pain following breast cancer surgery is a significant problem. Both inherited and acquired mechanisms of inflammation appear to play a role in the development and maintenance of persistent pain. In this longitudinal study, growth mixture modeling was used to identify persistent breast pain phenotypes based on pain assessments obtained prior to and monthly for 6 months following breast cancer surgery. Associations between the “no pain” and “mild pain” phenotypes and single nucleotide polymorphisms (SNPs) spanning 15 cytokine genes were evaluated. The methylation status of the CpG sites found in the promoters of genes associated with pain group membership was determined using bisulfite sequencing. In the multivariate analysis, three SNPs (i.e., interleukin 6 (IL6) rs2069840, C-X-C motif chemokine ligand 8 (CXCL8) rs4073, tumor necrosis factor (TNF) rs1800610) and two TNF CpG sites (i.e., c.−350C, c.−344C) were associated with pain group membership. These findings suggest that variations in IL6, CXCL8, and TNF are associated with the development and maintenance of mild persistent breast pain. CpG methylation within the TNF promoter may provide an additional mechanism through which TNF alters the risk for mild persistent breast pain after breast cancer surgery. These genetic and epigenetic variations may help to identify individuals who are predisposed to the development of mild levels of persistent breast pain following breast cancer surgery.

Abstract

Background: Recent methodological advancements should catalyze the evaluation of measurement invariance across groups, which is required for conducting meaningful cross-group comparisons. Objective: The aim of this study was to apply a state-of-the-art statistical method for comparing latent mean scores and evaluating measurement invariance across managers' and frontline workers' ratings of the organization of hospital care. Methods: On the 87 nursing units in a single institution, French-speaking and Dutch-speaking nursing unit managers' and staff nurses' ratings of their work environment were measured using the multidimensional 32-item practice environment scale of the nursing work index (PES-NWI). Measurement invariance and latent mean scores were evaluated in the form of a Bayesian 2-level multiple indicators multiple causes model with covariates at the individual nurse and nursing unit level. Role (manager, staff nurse) and language (French, Dutch) are of primary interest. Results: Language group membership accounted for 7 of 11 PES-NWI items showing measurement noninvariance. Cross-group comparisons also showed that covariates at both within-level and between-level had significant effects on PES-NWI latent mean scores. Most notably, nursing unit managers, when compared with staff nurses, hold more positive views of several PES-NWI dimensions. Conclusions: Using a widely used instrument for measuring nurses' work environment, this study shows that precautions for the potential threat of measurement noninvariance are necessary in all stages of a study that relies on survey data to compare groups, particularly in multilingual settings. A Bayesian multilevel multiple indicators multiple causes approach can accommodate for detecting all possible instances of noninvariance for multiple covariates of interest at the within-level and between-level jointly.

Abstract

Background and objective: Adiposity in pre- and postnatal life may influence menarcheal age. Existing evidence is primarily cross-sectional, failing to address temporality, for which the role of adiposity in early life remains unclear. The current study sought to systematically review longitudinal studies evaluating the associations between birth weight and infant/childhood weight status/weight gain in relation to menarcheal age. Methods: PubMed, EMBASE, Web of Science, Global Health (Ovid) and CINAHL were systematically searched. Selected studies were limited to English-language articles presenting multi-variable analyses. Seventeen studies reporting risk estimates for birth weight (n = 3), infant/childhood weight gain/weight status (n = 4) or both (n = 10), in relation to menarcheal age were included. Results: Lower vs. higher birth weight was associated with earlier menarche in nine studies and later menarche in one study, while three studies reported a null association. Greater BMI or weight gain over time and greater childhood weight were significantly associated with earlier menarche in nine of nine and six of seven studies, respectively. Conclusions: Studies suggested that lower birth weight and higher body weight and weight gain in infancy and childhood may increase the risk of early menarche. The pre- and postnatal period may thus be an opportune time for weight control interventions to prevent early menarche, and its subsequent consequences.

Abstract

Building clinical education training capacity in nurse practitioner programs is critical to build the primary care workforce and to address the access to care problem in the country. Challenges related to obtaining clinical sites and qualified preceptors are well reported, but few practical solutions are presented. Clinical sites and qualified preceptors willing to serve can be found, but nurse practitioner faculty must remove obstacles and strengthen resources by discovering untapped capacity. Nurse practitioner faculty can design, implement, and test innovative clinical models to maximize clinical training capacity. Clinical capacity development in geriatrics and long-term care, convenience care, distance immersions, correctional nursing, occupational health, and through interprofessional collaborations and faculty practice partnerships can be expanded.

Abstract

Background/Objectives: Frailty, characterized by low physiological reserves, is strongly associated with vulnerability to adverse outcomes. Features of frailty overlap with those of advanced heart failure, making a distinction between them difficult. We sought to determine whether implantation of a left ventricular assist device (LVAD) would decrease frailty. Design: Prospective, cohort study. Setting: Five academic medical centers. Participants: Frail individuals (N = 29; mean age 70.6 ± 5.5, 72.4% male). Measurements: Frailty, defined as having 3 or more of the Fried frailty criteria, was assessed before LVAD implantation and 1, 3, and 6 months after implantation. Other domains assessed included quality of life, using the Kansas City Cardiomyopathy Questionnaire; mood, using the Patient Health Questionnaire; and cognitive function, using the Trail-Making Test Part B. Results: After 6 months, three subjects had died, and one had undergone a heart transplant; of 19 subjects with serial frailty measures, the average number of frailty criteria decreased from 3.9 ± 0.9 at baseline to 2.8 ± 1.4 at 6 months (P =.003). Improvements were observed after 3 to 6 months of LVAD support, although 10 (52.6%) participants still had 3 or more Fried criteria, and all subjects had at least one at 6 months. Changes in frailty were associated with improvement in QOL but not with changes in mood or cognition. Higher estimated glomerular filtration rate at baseline was independently associated with a decrease in frailty. Conclusion: Frailty decreased in approximately half of older adults with advanced heart failure after 6 months of LVAD support. Strategies to enhance frailty reversal in this population are worthy of additional study.

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Higher carbohydrate intake, glycaemic index (GI), and glycaemic load (GL) are hypothesised to increase cancer risk through metabolic dysregulation of the glucose-insulin axis and adiposity-related mechanisms, but epidemiological evidence is inconsistent. This prospective cohort study investigates carbohydrate quantity and quality in relation to risk of adiposity-related cancers, which represent the most commonly diagnosed preventable cancers in the USA. In exploratory analyses, associations with three site-specific cancers: breast, prostate and colorectal cancers were also examined. The study sample consisted of 3184 adults from the Framingham Offspring cohort. Dietary data were collected in 1991-1995 using a FFQ along with lifestyle and medical information. From 1991 to 2013, 565 incident adiposity-related cancers, including 124 breast, 157 prostate and sixty-eight colorectal cancers, were identified. Cox proportional hazards models were used to evaluate the role of carbohydrate nutrition in cancer risk. GI and GL were not associated with risk of adiposity-related cancers or any of the site-specific cancers. Total carbohydrate intake was not associated with risk of adiposity-related cancers combined or prostate and colorectal cancers. However, carbohydrate consumption in the highest v. lowest quintile was associated with 41 % lower breast cancer risk (hazard ratio (HR) 0·59; 95 % CI 0·36, 0·97). High-, medium- and low-GI foods were not associated with risk of adiposity-related cancers or prostate and colorectal cancers. In exploratory analyses, low-GI foods, were associated with 49 % lower breast cancer risk (HR 0·51; 95 % CI 0·32, 0·83). In this cohort of Caucasian American adults, associations between carbohydrate nutrition and cancer varied by cancer site. Healthier low-GI carbohydrate foods may prevent adiposity-related cancers among women, but these findings require confirmation in a larger sample.