Faculty Bibliography

OBJECTIVE:Even though the early alliance has been shown to robustly predict posttreatment outcomes, the question whether alliance leads to symptom reduction or symptom reduction leads to a better alliance remains unresolved. To better understand the relation between alliance and symptoms early in therapy, we meta-analyzed the lagged session-by-session within-patient effects of alliance and symptoms from Sessions 1 to 7. METHOD/METHODS:We applied a 2-stage individual participant data meta-analytic approach. Based on the data sets of 17 primary studies from 9 countries that comprised 5,350 participants, we first calculated standardized session-by-session within-patient coefficients. Second, we meta-analyzed these coefficients by using random-effects models to calculate omnibus effects across the studies. RESULTS:In line with previous meta-analyses, we found that early alliance predicted posttreatment outcome. We identified significant reciprocal within-patient effects between alliance and symptoms within the first 7 sessions. Cross-level interactions indicated that higher alliances and lower symptoms positively impacted the relation between alliance and symptoms in the subsequent session. CONCLUSION/CONCLUSIONS:The findings provide empirical evidence that in the early phase of therapy, symptoms and alliance were reciprocally related to one other, often resulting in a positive upward spiral of higher alliance/lower symptoms that predicted higher alliances/lower symptoms in the subsequent sessions. Two-stage individual participant data meta-analyses have the potential to move the field forward by generating and interlinking well-replicable process-based knowledge. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Biobanks have the potential to be robust resource for understanding potential cancer risks associated with gender-affirming interventions. In this narrative review, we synthesized the current published literature regarding the inclusion of TGD health data in cancer biorepositories and cancer research conducted on biospecimens. Of the 6986 initial results, 153 (2.2%) assessed the biological effects of gender-affirming interventions on TGD tissues. Within that category, only one paper examined transgender tissues in relation to cancer biobanks. Strategies are offered to address the inequities in TGD tissue-based research and diversify the field of biobanking as a whole.

OBJECTIVE:Hypoglycemia has been postulated to contribute to falls risk in older adults with type 2 diabetes. However, few studies have prospectively examined the association between severe hypoglycemia and falls, both important causes of morbidity and mortality. RESEARCH DESIGN AND METHODS:We conducted a prospective cohort analysis of participants from the Atherosclerosis Risk in Communities (ARIC) study with diagnosed diabetes at visit 4 (1996-1998). Episodes of severe hypoglycemia requiring medical treatment were identified using ICD-9 codes from hospitalizations, emergency department visits, and ambulance calls; total falls were identified from medical claims using E-codes from 1996 to 2013. Secondary analyses examined hospitalized falls and falls with fracture. We calculated incidence rates and used Cox regression models to evaluate the independent association of severe hypoglycemia with falls occurring after visit 4 through 2013. RESULTS:Among 1,162 participants with diabetes, 149 ever had a severe hypoglycemic event before baseline or during the median of 13.1 years of follow-up. The crude incidence rate of falls among persons without severe hypoglycemia was 2.17 per 100 person-years (PY) (95% CI 1.93-2.44) compared with 8.81 per 100 PY (6.73-11.53) with severe hypoglycemia. After adjustment, severe hypoglycemia was associated with a more than twofold higher risk of falls (hazard ratio 2.23, 95% CI 1.61-3.07). Associations were consistent in subgroups defined by age, sex, race, BMI, duration of diabetes, or functional difficulty. CONCLUSIONS:Severe hypoglycemia was associated with a substantially higher risk of falls in this community-based population of adults with diabetes. Fall risk should be considered when individualizing glycemic treatment in older adults. Assessing hypoglycemia history and future hypoglycemia risk could also improve multifactorial fall prevention interventions for older adults with diabetes.

BACKGROUND AND PURPOSE/OBJECTIVE:Liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and gamma-glutamyl transpeptidase [GGT]) are glutamate-regulatory enzymes, and higher glutamate levels correlated with worse prognosis of patients with neurotrauma. However, less is known about the association between liver enzymes and incidence of stroke. We evaluated the association between serum levels of AST, ALT, and GGT and incidence of stroke in the Atherosclerosis Risk in Communities (ARIC) study cohort from 1990 to 1992 through December 31, 2016. METHODS:We included 12,588 ARIC participants without prevalent stroke and with data on liver enzymes ALT, AST, and GGT at baseline. We used multivariable Cox regression models to examine the associations between liver enzymes levels at baseline and stroke risk (overall, ischemic stroke, and intracerebral hemorrhage [ICH]) through December 31, 2016, adjusting for potential confounders. RESULTS:During a median follow-up time of 24.2 years, we observed 1,012 incident strokes (922ischemic strokes and 90 ICH). In age, sex, and race-center adjusted models, the hazard ratios (HRs; 95% confidence intervals [CIs]) for the highest compared to lowest GGT quartile were 1.94 (95% CI, 1.64 to 2.30) for all incident stroke and 2.01 (95% CI, 1.68 to 2.41) for ischemic stroke, with the results supporting a dose-response association (P for linear trend <0.001). Levels of AST were associated with increased risk of ICH, but the association was significant only when comparing the third quartile with the lowest quartile (adjusted HR, 1.82; 95% CI, 1.06 to 3.13). CONCLUSIONS:Elevated levels of GGT (within normal levels), independent of liver disease, are associated with higher risk of incident stroke overall and ischemic stroke, but not ICH.

The 2017 American College of Cardiology/American Heart Association guideline defines hypertension as a blood pressure ≥130/80 mm Hg, whereas the 2018 European Society of Cardiology (ESC) and 2019 National Institute for Health and Care Excellence (NICE) guidelines use a ≥140/90 mm Hg threshold. Our objective was to study the associations between isolated diastolic hypertension (IDH), diagnosed using these 2 blood pressure thresholds, and cardiovascular disease (CVD) in a large cohort of UK adults. We analyzed data from UK Biobank, which enrolled participants between 2006 and 2010 with follow-up through March 2019. We excluded persons with systolic hypertension or baseline CVD. We defined incident CVD as a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. We used Cox regression to quantify associations between IDH and CVD, as well as the individual outcomes included in the composite outcome. We studied 151 831 participants with normal systolic blood pressure (mean age 54 years, 40% male). Overall, 24.5% had IDH by the American College of Cardiology/American Heart Association definition compared with 6% by the ESC/NICE definition. Compared with normal diastolic blood pressure, IDH by the American College of Cardiology/American Heart Association definition was not significantly associated with CVD risk (hazard ratio, 1.08 [95% CI, 0.98-1.18]) whereas IDH by the ESC/NICE definition was significantly associated with a modest increase in CVD (hazard ratio, 1.15 [95% CI, 1.04-1.29]). Similar results were found by sex and among participants not taking baseline antihypertensives. Furthermore, neither IDH definition was associated with the individual outcomes of nonfatal myocardial infarction or stroke. In conclusion, the proportion of UK Biobank participants with IDH was significantly higher by the American College of Cardiology/American Heart Association definition compared with the ESC/NICE definitions; however, only the ESC/NICE definition was statistically associated with increased CVD risk.

We examine the causal link between proximity to fast food and the incidence of childhood obesity among low-income households in New York City. Using individual-level longitudinal data on students living in public housing linked to restaurant location data, we exploit the naturally occurring within-development variation in distance to fast food restaurants to estimate the impact of proximity on obesity. Since the assignment of households to specific buildings is based upon availability at the time of assignment to public housing, the distance between student residence and retail outlets-including fast food restaurants, wait-service restaurants, supermarkets, and corner stores-is plausibly random. Our credibly causal estimates suggest that childhood obesity increases with proximity to fast food, with larger effects for younger children who attend neighborhood schools.

BACKGROUND:Apolipoprotein L1 gene (APOL1) G1 and G2 kidney-risk variants (KRVs) cause CKD in African Americans, inducing mitochondrial dysfunction. Modifying factors are required, because a minority of individuals with APOL1 high-risk genotypes develop nephropathy. Given that APOL1 function is pH-sensitive and the pH of the kidney interstitium is <7, we hypothesized the acidic kidney interstitium may facilitate APOL1 KRV-induced mitochondrial dysfunction. METHODS:Human embryonic kidney (HEK293) cells conditionally expressing empty vector (EV), APOL1-reference G0, and G1 or G2 KRVs were incubated in media pH 6.8 or 7.4 for 4, 6, or 8 h. Genotype-specific pH effects on mitochondrial length (µm) were assessed using confocal microscopy in live cells and Fiji derivative of ImageJ software with MiNA plug-in. Lower mitochondrial length indicated fragmentation and early dysfunction. RESULTS:After 6 h doxycycline (Dox) induction in pH 6.8 media, G2-expressing cells had shorter mitochondria (6.54 ± 0.40) than cells expressing EV (7.65 ± 0.72, p = 0.02) or G0 (7.46 ± 0.31, p = 0.003). After 8 h Dox induction in pH 6.8 media, both G1- (6.21 ± 0.26) and G2-expressing cells had shorter mitochondria (6.46 ± 0.34) than cells expressing EV (7.13 ± 0.32, p = 0.002 and p = 0.008, respectively) or G0 (7.22 ± 0.45, p = 0.003 and p = 0.01, respectively). Mitochondrial length in cells incubated in pH 7.4 media were comparable after 8 h Dox induction regardless of genotype. APOL1 mRNA expression and cell viability were comparable regardless of pH or genotype after 8 h Dox induction. CONCLUSION/CONCLUSIONS:Acidic pH facilitates early mitochondrial dysfunction induced by APOL1 G1 and G2 KRVs in HEK293 cells. We propose that the acidic kidney interstitium may play a role in APOL1-mediated mitochondrial pathophysiology and nephropathy.

BACKGROUND:Most hookah use studies have not included racial and ethnic minorities which limits our understanding of its use among these growing populations. This study aimed to investigate the individual characteristics of hookah use patterns and associated risk behaviors among an ethnically diverse sample of college students. METHODS:A cross-sectional survey of 2460 students (aged 18-25) was conducted in 2015, and data was analyzed in 2017. Descriptive statistics were used to present the sociodemographic characteristics, hookah use-related behavior, and binge drinking and marijuana use according to the current hookah use group, including never, exclusive, dual/poly hookah use. Multivariate logistic regression was conducted to examine how hookah related behavior and other risk behaviors varied by sociodemographics and hookah use patterns. RESULTS:Among current hookah users (n = 312), 70% were exclusive hookah users and 30% were dual/poly hookah users. There were no statistically significant differences in sociodemographic characteristics except for race/ethnicity (p < 0.05). Almost half (44%) of the exclusive hookah users reported having at least five friends who also used hookah, compared to 30% in the dual/poly use group. Exclusive users were less likely to report past year binge drinking (17%) and past year marijuana use (25%) compared to those in the dual/poly use group (44 and 48% respectively); p < 0.001. CONCLUSIONS:The socialization aspects of hookah smoking seem to be associated with its use patterns. Our study calls for multicomponent interventions designed to target poly tobacco use as well as other substance use that appears to be relatively common among hookah users.

BACKGROUND:Sublingual buprenorphine-naloxone (BUP-NX), an FDA-approved treatment for opioid use disorder (OUD), combines buprenorphine (a partial mu/kappa agonist) with naloxone (a mu/ kappa antagonist). Extended-release injection naltrexone (XR-NTX; a mu receptor antagonist and kappa receptor partial agonist) is also an FDA-approved treatment for OUD. However, while some patients respond well to these medications, many others leave treatment and relapse. OBJECTIVES/OBJECTIVE:Determine whether gene variants in the opioid gene system are associated with better or worse treatment response. METHODS:= 334), two outcomes measures were assessed: received first dose (yes/no) and received last dose (yes/no). Separate logistic regressions were used to each model outcome measure as a function of treatment (XR-NTX vs BUP-NX), each gene variant, and their interaction. RESULTS:There were no significant main effects of gene variant on receiving first dose or last dose. There were also no significant gene variant by treatment interactions. CONCLUSIONS:The outcome of treatment of OUD with medications is likely a complex function of multiple factors, including environmental, psychosocial, and possibly genetic, such that major effects of genetic variants may be unlikely.

Using objectively-measured height and weight data from academic years 2009-2013 (n = 1,114,010 student-year observations), we estimated the association between the food outlet in closest proximity to schools and the likelihood of obesity among New York City public high school students. Obesity risk was higher for students with a corner store as the nearest option to schools, regardless of whether other food outlet types were located within a quarter mile or a half mile of schools (i.e., benchmarks for zoning policies). Policymakers may want to consider introducing healthier food options near schools, in conjunction with programs to support changes within corner stores.