Faculty Bibliography

OBJECTIVE:To outline strategies for the treatment of migraine which do not require in-person visits to clinic or the emergency department, and to describe ways that health insurance companies can remove barriers to quality care for migraine. BACKGROUND:COVID-19 is a global pandemic causing widespread infections and death. To control the spread of infection we are called to observe "social distancing" and we have been asked to postpone any procedures which are not essential. Since procedural therapies are a mainstay of headache care, the inability to do procedures could negatively affect our patients with migraine. In this manuscript we review alternative therapies, with particular attention to those which may be contra-indicated in the setting of COVID-19 infection. DESIGN/RESULTS/UNASSIGNED:The manuscript reviews the use of telemedicine visits and acute, bridge, and preventive therapies for migraine. We focus on evidence-based treatment where possible, but also describe "real world" strategies which may be tried. In each section we call out areas where changes to rules from commercial health insurance companies would facilitate better migraine care. CONCLUSIONS:Our common goal as health care providers is to maximize the health and safety of our patients. Successful management of migraine with avoidance of in-person clinic and emergency department visits further benefits the current urgent societal goal of maintaining social distance to contain the COVID-19 pandemic.

Directed acyclic graphs (DAGs), a prominent tool for expressing assumptions in epidemiologic research, are most useful when the hypothetical data generating structure is correctly encoded. Understanding a study's data generating structure and translating that data structure into a DAG can be challenging, but these skills are often glossed over in training. Campbell and Stanley's framework for causal inference has been extraordinarily influential in social science training programs but has received less attention in epidemiology. Their work, along with subsequent revisions and enhancements based on practical experience conducting empirical studies, presents a catalog of 37 threats to validity describing reasons empirical studies may fail to deliver causal effects. We interpret most of these threats to study validity as suggestions for common causal structures. Threats are organized into issues of statistical conclusion validity, internal validity, construct validity, or external validity. To assist epidemiologists in drawing the correct DAG for their application, we map the correspondence between threats to validity and epidemiologic concepts that can be represented with DAGs. Representing these threats as DAGs makes them amenable to formal analysis with d-separation rules and breaks down cross-disciplinary language barriers in communicating methodologic issues.

BACKGROUND:Childhood anxiety prevents optimal diabetes management yet may be underrecognized by guardians. OBJECTIVE:We aimed to investigate associations among anxiety, diabetes treatment adherence, and diabetes symptom control through child and guardian report. METHODS:Cross-sectional pilot study surveying a convenience sample of children (ages 2-21) in a pediatric endocrinology clinic. Behavior Assessment System for Children, Second Edition 2, Self-Care Inventory Report, and Pediatric Quality of Life measured anxiety, diabetes treatment adherence, and diabetes symptom control. Analyses were performed with Spearman correlations. RESULTS: = -0.38, P = 0.02]). Child- and guardian-reported anxiety were positively correlated (rho = 0.426, P = 0.017)-particularly for children aged >12 (rho = 0.686, P = 0.003)-although not significantly for children ≤ 12 (rho = 0.201, P = 0.473). CONCLUSION:Anxiety in children with type 1 diabetes varies with the domain of diabetes management (treatment adherence vs. symptom control) and reporting source (child vs. guardian). Children aged ≤12 exhibited a stronger relationship between higher anxiety and worse diabetes management with worse treatment adherence and symptom control in the presence of higher anxiety. Guardians of younger children were less effective at recognizing symptoms. Challenges identifying anxiety and its detrimental effects on diabetes management suggest routine screening of anxiety in pediatric endocrinology clinics is especially salient.

Background: Primary care clinics often struggle to choose the approach to alcohol and drug screening that is best suited to their resources, workflows, and patient populations. We are conducting a multi-site study to inform the implementation and feasibility of electronic health record (EHR)-integrated screening.
Method(s): In two urban academic health systems, researchers worked with stakeholders from 6 clinics to define and implement their optimal screening approach. All clinics used single-item screening questions for alcohol/drugs followed by AUDIT-C/DAST-10. Clinics chose between: (a) screening at routine vs. annual visits; and (b) staff-administered vs computer self-administered screening. Results were recorded in the EHR, and data was extracted quarterly to describe implementation outcomes including screening rate and detected prevalence of unhealthy (moderate-high risk) use among those screened. Findings are from the first 3 to 12 months post-implementation at each clinic.
Result(s): Across sites, of 84 311 patients with primary care visits, 58 492 (69%) were screened. In the four clinics with mature (9-12 months) implementation, screening rates ranged from 42% to 95%. Rates were lower (10%-22%) in the two clinics that recently launched. Screening at routine encounters, in comparison to annual visits, achieved higher screening rates for alcohol (90%-95% vs 42%-62%) and drugs (90%-94% vs 38%-60%). Staff-administered screening, in comparison to patient self-administered screening, had lower rates of detection of unhealthy alcohol use (2% vs 15-37%). Detection of unhealthy drug use was low, ranging from 0.3% to 1.5%.
Conclusion(s): EHR-integrated screening was feasible to implement in at least four of the six clinics; 1-year results (available Fall 2019) will determine feasibility at all sites. Self-administered screening at routine primary care visits achieved the highest rates of screening and detection of unhealthy alcohol use. Although limited by differences among clinics and their patient populations, this study provides insight into outcomes that may be expected with commonly used screening strategies in primary care.
Summary: This multi-site study conducted in the NIDA Clinical Trials Network seeks to inform the implementation and feasibility of EHR-integrated screening for substance use in primary care. This study will provide insight into outcomes that may be expected with commonly used screening strategies in primary care and may assist in fine-tuning the most appropriate approach to alcohol and drug screening best suited for primary care clinics, based on their individual resources, workflows, and patient populations

OBJECTIVES/OBJECTIVE:To assess relations of prepregnancy maternal and paternal obesity with offspring behavioral problems and psychiatric symptoms at 7-8 years in the Upstate KIDS study, a prospective cohort study. STUDY DESIGN/METHODS:Maternal body mass index (BMI) was calculated from prepregnancy height and weight provided in vital records or self-report at 4 months postpartum. Mothers reported paternal height and weight. At 7-8 years, mothers indicated if their children had been diagnosed with ADHD or anxiety (n = 1915). Additionally, children's behavior was measured with the Strengths and Difficulties Questionnaire at 7 years of age (n = 1386) and the Vanderbilt ADHD Diagnostic Parent Rating Scale at 8 years of age (n = 1484). Based on Strengths and Difficulties Questionnaire scores, we identified children with borderline behavioral problems. Adjusted risk ratios (aRR) and 95% CIs were estimated with robust multivariable Poisson regression. RESULTS:had higher risks of reported ADHD (aRR, 1.14, 95% CI, 0.78-1.69; aRR, 1.96, 95% CI, 1.29-2.98; and aRR, 1.82, 95% CI,1.21-2.74, respectively). Risks of hyperactivity problems identified by the Strengths and Difficulties Questionnaire and a positive screen for inattentive or hyperactive/impulsive behavior with the Vanderbilt ADHD Diagnostic Parent Rating Scale were also higher with increasing maternal prepregnancy BMI. Paternal BMI was not associated with child outcomes. CONCLUSIONS:Our findings suggest that maternal, rather than paternal, obesity is associated with maternal report of child ADHD diagnosis and inattentive or hyperactivity problems. Further research is needed to understand how maternal obesity might influence these behavioral changes during or after pregnancy.

Rationale & Objectives/UNASSIGNED:Recent data demonstrate that center volume is not a factor in the outcomes of adult kidney transplant recipients. This study assessed whether center volume affects graft survival in pediatric patients who received a kidney transplant. Study Design/UNASSIGNED:Case-cohort study. Setting & Participants/UNASSIGNED:Kidney transplantation centers, recipients younger than 18 years. Results/UNASSIGNED: = 0.02. Although outcomes for deceased donor kidney recipients were similar in the 3 volume categories, outcomes in patients who received a living kidney donation were better in the high-volume centers. Low household income was associated with poorer outcomes. However, 3-year graft survival was similar in the 3 center volume categories in high and low mean household income states. Limitations/UNASSIGNED:Lack of information for complications and individual family household income of recipients. Conclusions/UNASSIGNED:Transplantation outcomes are worse in pediatric patients treated at lower-volume centers. The difference was more pronounced for patients receiving living versus deceased donor kidneys. The distribution of household income in pediatric transplant recipients may also be a factor that contributes to lower 3-year graft survival in low-volume centers.

Objectives: To study the health-related quality of life (HRQoL) of persons with opioid use disorder (OUD) initiating medication treatment.
Method(s): We conducted a secondary analysis of data collected from a clinical trial funded by the National Drug Abuse Treatment Clinical Trials Network, where participants (N=570) in residential treatment were randomized to initiating extended-release naltrexone (XR-NTX) or buprenorphine-naloxone (BUP-NX) for the prevention of opioid relapse. A generalized structural equation latent-class model was used to identify associations and describe HRQoL trajectories over the 24-week trial and subsequent 28- and 36-week follow-ups for all participants regardless of success initiating treatment.
Result(s): Two latent classes were identified and defined: HRQoL "pharmacotherapy responsive" (82.3%), and HRQoL "baseline sensitive" (17.7%). The pharmacotherapy responsive class was characterized by HRQoL that tended to increase over time and a significant positive association between HRQoL and whether BUP-NX or XR-NTX was received in the past 30 days. The baseline sensitive class was characterized by lower average receipt of pharmacotherapy, initial increase in HRQoL with gradual decrease over time, and no significant HRQoL response to pharmacotherapy. HRQoL changes over time among patients in this class were sensitive to age, race, marital status, and motivation at baseline. Compared to the pharmacotherapy responsive class, the baseline sensitive class included higher proportions of participants who were female, white, married, less educated, and less motivated at baseline. The pharmacotherapy responsive class participants had, on average, less severe medical, drug, legal, and psychiatric problems at baseline.
Conclusion(s): The majority of persons with OUD enrolled in this trial experienced improvements in HRQoL that were associated with pharmacotherapy, while a smaller sub-group with lower average receipt of pharmacotherapy had HRQoL changes that were associated with baseline characteristics but not pharmacotherapy. Our analysis provides insights for improved person-centered care for OUD patients receiving pharmacotherapy who are not adherent to treatment.
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OBJECTIVES/OBJECTIVE:Fetal exposure to phthalates and bisphenols may lead to vascular developmental adaptations, which program later cardiovascular disease. We examined the associations of fetal exposure to phthalates and bisphenols with childhood blood pressure. METHODS:In a population-based, prospective cohort study among 1,064 mother-child pairs, we measured maternal urine phthalate and bisphenol concentrations in first, second and third trimester of pregnancy. We measured childhood blood pressure at the mean age of 9.7 years (standard deviation 0.2 years) old. Analyses were performed for the total group, and for boys and girls separately. RESULTS:Maternal urine phthalate concentrations were not associated with childhood blood pressure among boys. Higher third trimester maternal urine concentrations of high molecular weight phthalates (HMWP), di-2-ehtylhexylphthalate (DEHP) and di-n-octylphthalate (DNOP) were associated with lower systolic and diastolic blood pressure among girls (p-values < 0.01). Also, higher second trimester maternal urine total bisphenol and bisphenol A concentrations were associated with higher systolic blood pressure among boys (p values < 0.01), but tended to be associated with a lower diastolic blood pressure among girls. CONCLUSIONS:Our results suggest sex-dependent associations of maternal urine phthalate and bisphenol concentrations during pregnancy with childhood blood pressure. Further studies are needed to explore the underlying mechanisms and long term consequences.

PURPOSE:Cohort participants usually have lower mortality rates than nonparticipants, but it is unclear if this survival advantage decreases or increases as cohort studies age. METHODS:We used a 1975 private census of Washington County, Maryland, to compare mortality among cohort participants to nonparticipants for three cohorts, Campaign Against Cancer and Stroke (CLUE I), Campaign Against Cancer and Heart Disease (CLUE II), and Atherosclerosis Risk In Communities (ARIC) initiated in 1974, 1989, and 1986, respectively. We analyzed mortality risk using time-truncated Cox regression models. RESULTS:Participants had lower mortality risk in the first 10 years of follow-up compared with nonparticipants (fully adjusted average hazard ratio [95% confidence intervals] were 0.72 [0.68, 0.77] in CLUE I, 0.69 [0.65, 0.73] in CLUE II, and 0.74 [0.63, 0.86] in ARIC), which persisted over 20 years of follow-up (0.81 [0.78, 0.84] in CLUE I, 0.87 [0.84, 0.91] in CLUE II, and 0.90 [0.83, 0.97] in ARIC). This lower average hazard for mortality among participants compared with nonparticipants attenuated with longer follow-up (0.99 [0.96, 1.01] after 30+ years in CLUE I, 1.02 [0.99, 1.05] after 30 years in CLUE II, and 0.95 [0.89, 1.00] after 30+ years in ARIC). In ARIC, participants who did not attend visits had higher mortality, but those who did attend visits had similar mortality to the community. CONCLUSIONS:Our results suggest the volunteer selection for mortality in long-standing epidemiologic cohort studies often diminishes as the cohort ages.

Beta amyloid (Aβ) accumulation is the earliest pathological marker of Alzheimer's disease (AD), but early AD pathology also affects white matter (WM) integrity. We performed a cross-sectional study including 44 subjects (23 healthy controls and 21 mild cognitive impairment or early AD patients) who underwent simultaneous PET-MR using 18F-Florbetapir, and were categorized into 3 groups based on Aβ burden: Aβ- [mean mSUVr ≤1.00], Aβi [1.00 < mSUVr <1.17], Aβ+ [mSUVr ≥1.17]. Intergroup comparisons of diffusion MRI metrics revealed significant differences across multiple WM tracts. Aβi group displayed more restricted diffusion (higher fractional anisotropy, radial kurtosis, axonal water fraction, and lower radial diffusivity) than both Aβ- and Aβ+ groups. This nonmonotonic trend was confirmed by significant continuous correlations between mSUVr and diffusion metrics going in opposite direction for 2 cohorts: pooled Aβ-/Aβi and pooled Aβi/Aβ+. The transient period of increased diffusion restriction may be due to inflammation that accompanies rising Aβ burden. In the later stages of Aβ accumulation, neurodegeneration is the predominant factor affecting diffusion.