Faculty Bibliography

PURPOSE OF REVIEW: Idiopathic intracranial hypertension (IIH) is a potentially blinding disorder of unknown cause, characterized by elevated intracranial pressure in the absence of a mass lesion, venous sinus thrombosis, or meningitis. This review summarizes recent developments and insights from leading treatment trials, emerging treatment options, and evolving ways to evaluate IIH. RECENT FINDINGS: The Idiopathic Intracranial Hypertension Treatment Trial is the first large-scale, randomized, prospective study to evaluate medical treatment of patients with mild vision loss. These data have facilitated our understanding of baseline clinical manifestations, including impact on quality of life and treatment outcomes. Recent hypotheses and studies evaluating the role of cerebral venous sinus stenosis and stenting are discussed. Technological advances in optical coherence tomography are emerging to provide novel ways of evaluating and tracking optic disc swelling in IIH. SUMMARY: Recent changes in defining IIH, understanding the impact and treatment of mild visual loss, and the roles that cerebral venous stenting and optical coherence tomography might have in clinical practice provide the framework to better treat patients with IIH.

BACKGROUND:People with end-stage renal disease are at high risk for bone fracture. Less is known about fracture risk in milder chronic kidney disease and whether chronic kidney disease-associated fracture risk varies by sex or assessment with alternative kidney markers. STUDY DESIGN/METHODS:Prospective cohort study. SETTING & PARTICIPANTS/METHODS:10,955 participants from the Atherosclerosis Risk in Communities (ARIC) Study followed up from 1996 to 2011. PREDICTOR/METHODS:Kidney function as assessed by creatinine-based estimated glomerular filtration rate (eGFRcr), urine albumin-creatinine ratio, and alternative filtration markers. OUTCOMES/RESULTS:Fracture-related hospitalizations determined by diagnostic code. MEASUREMENTS/METHODS:Baseline kidney markers; hospitalizations identified by self-report during annual telephone contact and active surveillance of local hospital discharge lists. RESULTS:Mean age of participants was 63 years, 56% were women, and 22% were black. During a median follow-up of 13 years, there were 722 incident fracture-related hospitalizations. Older age, female sex, and white race were associated with higher risk for fracture (P<0.001). The relationship between eGFRcr and fracture risk was nonlinear: <60mL/min/1.73m(2), lower eGFRcr was associated with higher fracture risk (adjusted HR per 10mL/min/1.73m(2) lower, 1.24; 95% CI, 1.05-1.47); there was no statistically significant association for ≥60mL/min/1.73m(2) in the primary analysis. In contrast, there was a graded association between other markers of kidney function and subsequent fracture, including albumin-creatinine ratio (HR per doubling, 1.10; 95% CI, 1.06-1.14), cystatin C-based eGFR (HR per 1-SD decrease, 1.15; 95% CI, 1.06-1.25), and 1/β2-microglobulin (HR per 1-SD decrease, 1.26, 95% CI, 1.15-1.37). LIMITATIONS/CONCLUSIONS:No bone mineral density assessment; one-time measurement of kidney function. CONCLUSIONS:Both low eGFR and higher albuminuria were significant risk factors for fracture in this community-based population. The shape of the association in the upper ranges of eGFR varied by the filtration marker used in estimation.

Hypertension is a very common disease, and office measurements of blood pressure are frequently inaccurate. Ambulatory Blood Pressure Monitoring (ABPM) offers a more accurate diagnosis, more detailed readings of average blood pressures, better blood pressure measurement during sleep, fewer false positives by detecting more white-coat hypertension, and fewer false negatives by detecting more masked hypertension. ABPM offers better management of clinical outcomes. For example, based on more accurate measurements of blood pressure variability, ABPM demonstrates that taking antihypertensive medication at night leads to better controlled nocturnal blood pressure, which translates into less end organ damage and fewer clinical complications of hypertension. For these reasons, albeit some shortcomings which were discussed, ABPM should be considered as a first-line tool for diagnosing and managing hypertension.

Academic preparedness, executive function abilities, and positive relationships with teachers have each been shown to be uniquely important for school readiness and success in the early elementary grades. Few studies, however, have examined the joint influence of these readiness variables on early school outcomes. Using data from a prospective longitudinal sample of 1292 children and families in predominantly low-income and rural communities, we found that executive function at child age 48 months and a higher quality relationship with the kindergarten teacher each uniquely moderated the effect of math ability in preschool on math ability at the end of kindergarten. This effect was seen for math ability as measured by the Early Childhood Longitudinal Study-Kindergarten (ECLS-K) mathematics assessment battery but not the Woodcock-Johnson III Tests of Achievement Applied Problems subtest. For children with lower math ability in preschool as assessed by the ECLS-K Math battery, higher executive function abilities and a more positive relationship with the kindergarten teacher were each associated with a higher than expected level of math ability in kindergarten. Conversely, lowest levels of math ability in kindergarten were observed among children with low math ability in preschool and poor executive function or a less positive relationship with the kindergarten teacher.

Evidence suggests that relations between child care and children's development-behaviorally and physiologically-likely differ between children from high-versus low-risk contexts. Using data from the Family Life Project (N = 1,155), the authors tested (a) whether within- and between-child differences in children's child care experiences (i.e., quantity, type, caregiver responsivity, and peer exposure) were predictive of their cortisol levels across infancy and toddlerhood and (b) whether these relations differed for children experiencing different levels of environmental risk. They found some evidence of such interactive effects. For children from high-risk contexts, within-child increases in child care hours were predictive of cortisol decreases. The inverse was evident for children from low-risk contexts. This relation grew across toddlerhood. Whereas a history of greater center-based child care was predictive of heightened cortisol levels for low-risk families, this was not the case for children from high-risk families. Irrespective of risk, greater peer exposure (between children) was associated with lower cortisol levels.

BACKGROUND:Disordered mineral metabolism is characteristic of decreased kidney function. However, the prospective associations between circulating levels of vitamin D binding protein, vitamin D, and end-stage renal disease (ESRD) have not been extensively evaluated in epidemiologic studies. STUDY DESIGN/METHODS:Nested case-control study. SETTING & PARTICIPANTS/METHODS:Middle-aged black and white men and women from 4 US communities. PREDICTORS/METHODS:Baseline levels of vitamin D binding protein, 25-hydroxyvitamin D (25[OH]D), and 1,25-dihydroxyvitamin D (1,25[OH]2D) were measured in blood samples collected at study visit 4 (1996-1998) of the ARIC (Atherosclerosis Risk in Communities) Study. OUTCOME/RESULTS:ESRD cases (n=184) were identified through hospitalization diagnostic codes from 1996 to 2008 and were frequency matched to controls (n=251) on categories of estimated glomerular filtration rate, albuminuria, diabetes mellitus, sex, and race. MEASUREMENTS/METHODS:Logistic regression was used to estimate the association between mineral metabolism biomarkers (vitamin D binding protein, 25(OH)D, and 1,25(OH)2D) and incident ESRD, adjusting for age, sex, race, estimated glomerular filtration rate, albuminuria, diabetes mellitus, hypertension, education, specimen type, and serum levels of calcium, phosphate, and parathyroid hormone. RESULTS:Higher vitamin D binding protein levels were associated with elevated risk for incident ESRD (OR, 1.76; 95% CI, 1.22-2.54; P=0.003). Higher free and bioavailable 25(OH)D levels were associated with reduced risk for incident ESRD (ORs of 0.65 [95% CI, 0.46-0.92; P=0.02] and 0.63 [95% CI, 0.43-0.91; P=0.02] for free and bioavailable 25[OH]D, respectively). There was no association between ESRD and overall levels of 25(OH)D (OR, 0.83; 95% CI, 0.58-1.19; P=0.3) or 1,25(OH)2D (OR, 0.73; 95% CI, 0.48-1.13; P=0.2). LIMITATIONS/CONCLUSIONS:Lack of direct measurement of free and bioavailable vitamin D. CONCLUSIONS:In the general population, blood levels of vitamin D binding protein were positively associated and blood levels of free and bioavailable 25(OH)D were inversely associated with new-onset ESRD during follow-up.

IMPORTANCE/OBJECTIVE:Proton pump inhibitors (PPIs) are among the most commonly used drugs worldwide and have been linked to acute interstitial nephritis. Less is known about the association between PPI use and chronic kidney disease (CKD). OBJECTIVE:To quantify the association between PPI use and incident CKD in a population-based cohort. DESIGN, SETTING, AND PARTICIPANTS/METHODS:In total, 10,482 participants in the Atherosclerosis Risk in Communities study with an estimated glomerular filtration rate of at least 60 mL/min/1.73 m(2) were followed from a baseline visit between February 1, 1996, and January 30, 1999, to December 31, 2011. The data was analyzed from May 2015 to October 2015. The findings were replicated in an administrative cohort of 248,751 patients with an estimated glomerular filtration rate of at least 60 mL/min/1.73 m(2) from the Geisinger Health System. EXPOSURES/METHODS:Self-reported PPI use in the Atherosclerosis Risk in Communities study or an outpatient PPI prescription in the Geisinger Health System replication cohort. Histamine2 (H2) receptor antagonist use was considered a negative control and active comparator. MAIN OUTCOMES AND MEASURES/METHODS:Incident CKD was defined using diagnostic codes at hospital discharge or death in the Atherosclerosis Risk in Communities Study, and by a sustained outpatient estimated glomerular filtration rate of less than 60 mL/min/1.73 m(2) in the Geisinger Health System replication cohort. RESULTS:Among 10,482 participants in the Atherosclerosis Risk in Communities study, the mean (SD) age was 63.0 (5.6) years, and 43.9% were male. Compared with nonusers, PPI users were more often of white race, obese, and taking antihypertensive medication. Proton pump inhibitor use was associated with incident CKD in unadjusted analysis (hazard ratio [HR], 1.45; 95% CI, 1.11-1.90); in analysis adjusted for demographic, socioeconomic, and clinical variables (HR, 1.50; 95% CI, 1.14-1.96); and in analysis with PPI ever use modeled as a time-varying variable (adjusted HR, 1.35; 95% CI, 1.17-1.55). The association persisted when baseline PPI users were compared directly with H2 receptor antagonist users (adjusted HR, 1.39; 95% CI, 1.01-1.91) and with propensity score-matched nonusers (HR, 1.76; 95% CI, 1.13-2.74). In the Geisinger Health System replication cohort, PPI use was associated with CKD in all analyses, including a time-varying new-user design (adjusted HR, 1.24; 95% CI, 1.20-1.28). Twice-daily PPI dosing (adjusted HR, 1.46; 95% CI, 1.28-1.67) was associated with a higher risk than once-daily dosing (adjusted HR, 1.15; 95% CI, 1.09-1.21). CONCLUSIONS AND RELEVANCE/CONCLUSIONS:Proton pump inhibitor use is associated with a higher risk of incident CKD. Future research should evaluate whether limiting PPI use reduces the incidence of CKD.

OBJECTIVES: To determine what effect driving cessation may have on subsequent health and well-being in older adults. DESIGN: Systematic review of the evidence in the research literature on the consequences of driving cessation in older adults. SETTING: Community. PARTICIPANTS: Drivers aged 55 and older. MEASUREMENTS: Studies pertinent to the health consequences of driving cessation were identified through a comprehensive search of bibliographic databases. Studies that presented quantitative data for drivers aged 55 and older; used a cross-sectional, cohort, or case-control design; and had a comparison group of current drivers were included in the review. RESULTS: Sixteen studies met the inclusion criteria. Driving cessation was reported to be associated with declines in general health and physical, social, and cognitive function and with greater risks of admission to long-term care facilities and mortality. A meta-analysis based on pooled data from five studies examining the association between driving cessation and depression revealed that driving cessation almost doubled the risk of depressive symptoms in older adults (summary odds ratio = 1.91, 95% confidence interval = 1.61-2.27). CONCLUSION: Driving cessation in older adults appears to contribute to a variety of health problems, particularly depression. These adverse health consequences should be considered in making the decision to cease driving. Intervention programs ensuring mobility and social functions may be needed to mitigate the potential adverse effects of driving cessation on health and well-being in older adults.

BACKGROUND: Our knowledge about the impact of coping behavior styles in people exposed to stressful disaster events is limited. Effective coping behavior has been shown to be a psychosocial stress modifier in both occupational and nonoccupational settings. METHODS: Data were collected by using a web-based survey that administered the Post-Traumatic Stress Disorder (PTSD) Checklist-Civilian, General Coping Questionnaire-30, and a supplementary questionnaire assessing various risk factors. Logistic regression models were used to test for the association of the 3 coping styles with probable PTSD following disaster exposure among federal disaster responders. RESULTS: In this sample of 549 study subjects, avoidant coping behavior was most associated with probable PTSD. In tested regression models, the odds ratios ranged from 1.19 to 1.26 and 95% confidence intervals ranged from 1.08 to 1.35. With control for various predictors, emotion-based coping behavior was also found to be associated with probable PTSD (odds ratio=1.11; 95% confidence interval: 1.01-1.22). CONCLUSION: This study found that in disaster responders exposed to traumatic disaster events, the likelihood of probable PTSD can be influenced by individual coping behavior style and other covariates. The continued probability of disasters underscores the critical importance of these findings both in terms of guiding mental health practitioners in treating exposed disaster responders and in stimulating future research. (Disaster Med Public Health Preparedness. 2016;10:108-117).