Faculty Bibliography

BACKGROUND:Benzodiazepine overdose rates have increased in the US, largely from concomitant use of other drugs such as opioids. Studies are needed to examine trends in prescription tranquilizer (e.g., benzodiazepine) use-with a particular focus on use of other drugs such as opioids-to continue to inform prevention efforts. METHODS:We conducted a secondary analysis of the 2005-2014 National Survey on Drug Use and Health, a repeated cross-sectional, nationally representative probability sample. Trends in past-year nonmedical tranquilizer use and trends in demographic and other past-year substance use characteristics among nonmedical users were examined (N = 560,099). RESULTS:Prevalence of nonmedical tranquilizer use remained stable from 2005/06 through 2013/14 at 2%. Prevalence of past-year heroin use and heroin use disorder both more than doubled among nonmedical tranquilizer users between 2005/06 and 2013/14 (Ps<.001). Nonmedical opioid use decreased between 2005/06 and 2013/14 (P < .001); however, opioid use disorder increased from 13.4% to 16.7% (P = .019). Prevalence doubled among those age >50 between 2005/06 and 2013/14 from 7.9% to 16.5% (P < .001), and nonmedical tranquilizer use among racial minorities also increased (Ps<.01). Prevalence of nonmedical use also increased among those with health insurance (P = .031), and this increase appeared to be driven by a 190.6% increase in nonmedical use among those with Medicare (from 2.6% to 7.4%; P = .002). CONCLUSIONS:Characteristics of nonmedical tranquilizer users are shifting, and many shifts are related to past-year nonmedical prescription opioid use and heroin use. Prevention needs to be geared in particular towards older individuals and to those who use opioids nonmedically.

BACKGROUND:Arsenic exposure through drinking water persists in many regions. Inorganic As (InAs) is methylated to monomethyl-arsenical species (MMAs) and dimethyl-arsenical species (DMAs), facilitating urinary excretion. Arsenic methylation is dependent on one-carbon metabolism, which is influenced by nutritional factors such as folate and creatine. OBJECTIVE:This study investigated the effects of folic acid (FA) and/or creatine supplementation on the proportion of As metabolites in urine. DESIGN:In a 24-wk randomized, double-blinded, placebo-controlled trial, 622 participants were assigned to receive FA (400 or 800 μg per day), 3 g creatine per day, 400 μg FA + 3 g creatine per day, or placebo. The majority of participants were folate sufficient; all received As-removal water filters. From wk 12-24, half of the participants receiving FA received placebo. RESULTS:Among groups receiving FA, the mean decrease in ln(%InAs) and %MMAs and increase in %DMAs exceeded those of the placebo group at wk 6 and 12 (P < 0.05). In the creatine group, the mean decrease in %MMAs exceeded that of the placebo group at wk 6 and 12 (P < 0.05); creatine supplementation did not affect change in %InAs or %DMAs. The decrease in %MMAs at wk 6 and 12 was larger in the 800 µg FA than in the 400 µg FA group (P = 0.034). There were no differences in treatment effects between the 400 µg FA and creatine + FA groups. Data suggest a rebound in As metabolite proportions after FA cessation; at wk 24, log(%InAs) and %DMAs were not significantly different than baseline levels among participants who discontinued FA supplementation. CONCLUSIONS:The results of this study confirm that FA supplementation rapidly and significantly increases methylation of InAs to DMAs. Further research is needed to understand the strong cross-sectional associations between urinary creatinine and As methylation in previous studies. This trial was registered at https://clinicaltrials.gov as NCT01050556.

Despite numerous international and national efforts, only 12 countries in the World Health Organization's African Region met the Millennium Development Goal #4 (MDG#4) to reduce under-five mortality by two-thirds by 2015. Given the variability across sub-Saharan Africa, a four-country study was undertaken to examine barriers and facilitators of child survival prior to 2015. Liberia and Zambia were chosen to represent countries making substantial progress towards MDG#4, while Kenya and Zimbabwe represented countries making less progress. Our individual case studies suggested that strong health governance and leadership (HGL) was a significant driver of the greater success in Liberia and Zambia compared with Kenya and Zimbabwe. To elucidate specific components of national HGL that may have substantially influenced the pace of reductions in child mortality, we conducted a cross-country analysis of national policies and strategies pertaining to maternal, neonatal and child health (MNCH) and qualitative interviews with individuals working in MNCH in each of the four study countries. The three aspects of HGL identified in this study which most consistently contributed to the different progress towards MDG#4 among the four study countries were (1) establishing child survival as a top national priority backed by a comprehensive policy and strategy framework and sufficient human, financial and material resources; (2) bringing together donors, strategic partners, health and non-health stakeholders and beneficiaries to collaborate in strategic planning, decision-making, resource-allocation and coordination of services; and (3) maintaining accountability through a 'monitor-review-act' approach to improve MNCH. Although child mortality in sub-Saharan Africa remains high, this comparative study suggests key health leadership and governance factors that can facilitate reduction of child mortality and may prove useful in tackling current Sustainable Development Goals.

The original and corrected Acknowledgements are shown in the accompanying Author Correction

Objective/UNASSIGNED:Scalable nonpharmacologic treatment options are needed for chronic pain conditions. Migraine is an ideal condition to test smartphone-based mind-body interventions (MBIs) because it is a very prevalent, costly, disabling condition. Progressive muscle relaxation (PMR) is a standardized, evidence-based MBI previously adapted for smartphone applications for other conditions. We sought to examine the usability of the RELAXaHEAD application (app), which has a headache diary and PMR capability. Methods/UNASSIGNED:Using the "Think Aloud" approach, we iteratively beta-tested RELAXaHEAD in people with migraine. Individual interviews were conducted, audio-recorded, and transcribed. Using Grounded Theory, we conducted thematic analysis. Participants also were asked Likert scale questions about satisfaction with the app and the PMR. Results/UNASSIGNED:Twelve subjects participated in the study. The mean duration of the interviews (SD, range) was 36 (11, 19-53) minutes. From the interviews, four main themes emerged. People were most interested in app utility/practicality, user interface, app functionality, and the potential utility of the PMR. Participants reported that the daily diary was easy to use (75%), was relevant for tracking headaches (75%), maintained their interest and attention (75%), and was easy to understand (83%). Ninety-two percent of the participants would be happy to use the app again. Participants reported that PMR maintained their interest and attention (75%) and improved their stress and low mood (75%). Conclusions/UNASSIGNED:The RELAXaHEAD app may be acceptable and useful to migraine participants. Future studies will examine the use of the RELAXaHEAD app to deliver PMR to people with migraine in a low-cost, scalable manner.

BACKGROUND:Cigarette smoking and chronic pain are prevalent, comorbid conditions with significant consequences for individuals and society. Despite overlap between smoking and chronic pain, and pain's role as a potential barrier to quitting, there are no validated interventions targeted for smokers with chronic pains (SWCPs). OBJECTIVE:To compare characteristics of urban inpatient smokers with and without chronic pain to inform the development of SWCP-targeted cessation interventions. METHODS:This study reports partial results from a randomized comparative effectiveness trial of two smoking cessation interventions (NCT01363245). Participants were enrolled at two safety net hospitals in New York, NY in 2011-2014. Data were collected from the electronic health record and an interviewer-administered survey. Participants were considered to have chronic pain if they affirmed having "long-lasting, persistent, or chronic pain in the last six months" on survey. RESULTS:Among smokers assessed for pain (n = 1093), the prevalence of chronic pain was 44%. SWCPs were more likely to report depressive symptoms and to have a history of psychiatric diagnosis (nonsubstance related) than smokers without pain. Severe problems with mobility and with performing usual activities were more common in SWCPs. No significant difference was observed in sex, race, education, nicotine dependence level, confidence in quit ability, or history of substance misuse. Conclusions/Importance: Chronic pain in smokers admitted to safety net hospitals is prevalent and associated with hindered mobility, history of psychiatric diagnosis, and prescription opioid use. Urban safety net hospitals are an appropriate setting in which to pilot SWCP-targeted cessation programs, which should be designed with consideration for patients' psychiatric history and mobility status.

STUDY QUESTION/OBJECTIVE:Are early-pregnancy urinary bisphenol and phthalate metabolite concentrations associated with placental function markers, blood pressure (BP) trajectories during pregnancy and risk of gestational hypertensive disorders? SUMMARY ANSWER/UNASSIGNED:Early-pregnancy bisphenols and phthalate metabolites were not consistently associated with maternal BP changes or gestational hypertensive disorders, but subclinical, statistically significant associations with placental angiogenic markers and placental hemodynamics were identified. WHAT IS KNOWN ALREADY/UNASSIGNED:In vitro studies suggest that bisphenols and phthalate metabolites may disrupt early placental development and affect the risk of gestational hypertensive disorders. Previous studies investigating effects of bisphenols and phthalate metabolites on gestational hypertensive disorders reported inconsistent results and did not examine placental function or BP throughout pregnancy. STUDY DESIGN, SIZE, DURATION/UNASSIGNED:In a population-based prospective cohort study, bisphenol and phthalate metabolite concentrations were measured in a spot urine sample in early pregnancy among 1396 women whose children participated in postnatal follow-up measurements. PARTICIPANTS/MATERIALS, SETTING, METHODS/UNASSIGNED:After exclusion of women without any BP measurement or with pre-existing hypertension, 1233 women were included in the analysis. Urinary bisphenol and phthalate metabolite concentrations were measured in early-pregnancy [median gestational age 13.1 weeks, inter-quartile range 12.1-14.5]. Molar sums of total bisphenols and of low molecular weight phthalate, high molecular weight (HMW) phthalate, di-2-ethylhexylphthalate, and di-n-octylphthalate metabolites were calculated. Placental angiogenic markers (placental growth factor (PlGF), soluble fms-like tyrosine kinase (sFlt)-1), placental hemodynamic function measures (umbilical artery pulsatility index (PI), uterine artery resistance index (RI), notching and placental weight), and maternal BP were measured in different trimesters. Information on gestational hypertensive disorders was obtained from medical records. MAIN RESULTS AND THE ROLE OF CHANCE/UNASSIGNED:Each log unit increase in HMW phthalate metabolites was associated with a 141.72 (95% CI: 29.13, 373.21) higher early pregnancy sFlt-1/PlGF ratio (range in total sample 9-900). This association was driven by mono-[(2-carboxymethyl)hexyl]phthalate. In the repeated measurements regression models, each log unit increase in bisphenol A was associated with a 0.15 SD (95% CI: 0.03, 0.26) higher intercept and -0.01 SD (95% CI: -0.01, -0.00) decreasing slope of the umbilical artery PI Z-score and a -1.28 SD (95% CI: -2.24, -0.33) lower intercept and 0.06 SD (95% CI: 0.02, 0.11) increasing slope of the uterine artery RI Z-score. These associations remained significant after Bonferroni correction. Early-pregnancy bisphenols or phthalate metabolites showed no consistent associations with any other outcome. LIMITATIONS, REASONS FOR CAUTION/UNASSIGNED:Information on a large number of potential confounders was available but was partly self-reported. Bisphenols and phthalate metabolites, which typically have a half-life of 24-48 h, were measured via single spot urine samples in early-pregnancy. In addition, at the current sample size, the study was powered to detect an odds ratio of 1.57 for gestational hypertension and 1.78 for pre-eclampsia, but was underpowered to perform multivariable analyses for these outcomes. Further studies combining data from different cohorts may be necessary to increase power. These limitations are possible sources of non-differential misclassification leading to bias toward the null. WIDER IMPLICATIONS OF THE FINDINGS/UNASSIGNED:Bisphenols and phthalate metabolites were not associated with longitudinal changes in BP in pregnancy in our low-risk population. The observed subclinical associations of phthalates with the sFlt-1/PlGF ratio and of bisphenol A with placental hemodynamics may contribute to adverse pregnancy outcomes. Our results are therefore more supportive of an association of early pregnancy bisphenols and phthalate metabolites with risk for pre-eclampsia than with gestational hypertension. STUDY FUNDING/COMPETING INTEREST(S)/UNASSIGNED:This analysis was supported by Grant (ES022972) from the National Institutes of Health, USA. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health. The authors report no conflicts of interest.

PURPOSE/OBJECTIVE:As many as two-thirds of male childhood cancer survivors are at risk for fertility impairment as a consequence of treatment. Despite this, survivorship guidelines lack concrete recommendations as to when fertility status conversations should happen between patients and providers and what should be discussed. Thus, conversations may be inconsistent, or do not occur at all in survivorship. To inform recommendations for fertility-related conversations in survivorship, this pilot study aimed to better understand background (e.g., age, diagnosis and treatment intensity) and psychosocial factors (i.e., perceived barriers and perceived susceptibility) associated with survivor interest in learning about fertility status. METHODS:Male survivors (N = 45) 15-25 years of age were recruited within 1-8 years of completing treatment. Survivors completed questionnaires based on the Health Belief Model (HBM) to assess perception of infertility risk and attitudes toward testing. RESULTS:Most survivors (n = 31; 69%) reported they were informed of their risk for infertility by a healthcare provider before treatment, but only 31% (n = 14) of the sample banked sperm. Nearly two-thirds of survivors (n = 29; 64%) were interested in learning more about their fertility post-treatment. This interest was significantly correlated with greater perceived susceptibility to infertility by survivors, but it was not associated with other psychosocial or background factors. CONCLUSION/CONCLUSIONS:Informing survivors of their personal infertility risk may increase interest in pursuing testing. Offering opportunities for fertility testing and family planning alternatives may mitigate potential psychological distress and unplanned pregnancy. While additional research is needed, future survivorship guidelines should encourage regular communication about fertility status and offer fertility testing for male survivors.