Faculty Bibliography

PURPOSE/OBJECTIVE:To describe the study protocol and baseline characteristics of the African Descent and Glaucoma Evaluation Study (ADAGES) III. DESIGN/METHODS:Cross-sectional, case-control study. PARTICIPANTS/METHODS:Three thousand two hundred sixty-six glaucoma patients and control participants without glaucoma of African or European descent were recruited from 5 study centers in different regions of the United States. METHODS:Individuals of African descent (AD) and European descent (ED) with primary open-angle glaucoma (POAG) and control participants completed a detailed demographic and medical history interview. Standardized height, weight, and blood pressure measurements were obtained. Saliva and blood samples to provide serum, plasma, DNA, and RNA were collected for standardized processing. Visual fields, stereoscopic disc photographs, and details of the ophthalmic examination were obtained and transferred to the University of California, San Diego, Data Coordinating Center for standardized processing and quality review. MAIN OUTCOME MEASURES/METHODS:Participant gender, age, race, body mass index, blood pressure, history of smoking and alcohol use in POAG patients and control participants were described. Ophthalmic measures included intraocular pressure, visual field mean deviation, central corneal thickness, glaucoma medication use, or past glaucoma surgery. Ocular conditions, including diabetic retinopathy, age-related macular degeneration, and past cataract surgery, were recorded. RESULTS:The 3266 ADAGES III study participants in this report include 2146 AD POAG patients, 695 ED POAG patients, 198 AD control participants, and 227 ED control participants. The AD POAG patients and control participants were significantly younger (both, 67.4 years) than ED POAG patients and control participants (73.4 and 70.2 years, respectively). After adjusting for age, AD POAG patients had different phenotypic characteristics compared with ED POAG patients, including higher intraocular pressure, worse visual acuity and visual field mean deviation, and thinner corneas (all P < 0.001). Family history of glaucoma did not differ between AD and ED POAG patients. CONCLUSIONS:With its large sample size, extensive specimen collection, and deep phenotyping of AD and ED glaucoma patients and control participants from different regions in the United States, the ADAGES III genomics study will address gaps in our knowledge of the genetics of POAG in this high-risk population.

OBJECTIVE:Find genetic contributions to glaucoma in African Americans. DESIGN/METHODS:Cross-sectional, case-control study. PARTICIPANTS/METHODS:1875 POAG cases and 1709 controls, self-identified as African Descent (AD), from the African Descent and Glaucoma Evaluation Study (ADAGESIII) and Wake Forest School of Medicine. METHODS:MegaChip genotypes were imputed to Thousand Genomes data. Association of SNPs with POAG and advanced POAG was tested by linear mixed model correcting for relatedness and population stratification. Genetic risk scores were tested by Receiver Operator Characteristics (ROC-AUC). MAIN OUTCOME/RESULTS:POAG defined by visual field loss without other non-ocular conditions (N=1875). Advanced POAG was defined by age-based mean deviation of visual field (N=946). RESULTS:) was observed, not in LD with the previously reported ED SNP. Additional previously identified loci associated with POAG in AD were: 8q22, AFAP1, TMCO1. An AUC of 0.62 was observed with an unweighted genetic risk score composed of 11 SNPs in candidate genes. Two additional risk scores were studied by using a penalized matrix decomposition with cross-validation; risk scores of 50 and 400 SNPs were identified with ROC of AUC=0.74 and AUC=0.94, respectively. CONCLUSIONS:A novel association with advanced POAG in the ENO4 locus was putatively identified in subjects of African descent. In addition to this finding, this GWAS in AD POAG subjects contributes to POAG genetics by identification of novel signals in prior loci (9p21), as well as advancing the fine-mapping of regions due to shorter average linkage disequilibrium (FNDC3B). While not useful without confirmation and clinical trials, the use of genetic risk scores demonstrated that considerable AD-specific genetic information remains in these data.

PURPOSE OF REVIEW:The presence of viruses in urine (urine virome) typically reflects infection in the kidneys and urinary tract. The urinary virome is associated with HIV-associated nephropathy and chronic glomerulosclerosis. There are many associations of this microbiome with human diseases that remain to be described. This manuscript reviews emerging data on relationships between kidney disease and urinary tract infection/colonization with JC polyomavirus (JCPyV). RECENT FINDINGS:Approximately 30% of the adult population sheds JCPyV in the urine. Further, urinary tract infection with one polyomavirus strain appears to inhibit secondary infections. The presence of urinary JCPyV and BK polyomavirus (BKPyV) replication were measured with polymerase chain reaction in African Americans to assess relationships with apolipoprotein L1 gene (APOL1)-associated nephropathy. Urinary JCPyV was associated with paradoxically lower rates of nephropathy in those with APOL1 high-risk genotypes. Subsequent studies revealed African Americans with JCPyV viruria had lower rates of nondiabetic nephropathy independent from APOL1. SUMMARY:Urinary tract JCPyV replication is common and associates with lower rates of nephropathy. This relationship is observed in diverse settings. Results support a host immune system that fails to eradicate nonnephropathic viruses and is also less likely to manifest renal parenchymal inflammation resulting in glomerulosclerosis.

BACKGROUND/OBJECTIVES/OBJECTIVE:Nonpharmacological interventions, such as biofeedback, cognitive behavioral therapy, and relaxation techniques are Level-A evidence-based treatments for headache. The impact of these interventions is often equivalent to or greater than pharmacological interventions, with fewer side effects. Despite such evidence, the rate of participation in nonpharmacological interventions for headache remains low. Once obstacles to optimizing use of behavioral interventions, such as local access to nonpharmacological treatment and primary headache providers are traversed, identification of barriers contributing to low adherence is imperative given the high levels of disability and cost associated with treating headache disorders. In this review of factors in adults associated with underuse of nonpharmacological interventions, we discuss psychological factors relevant to participation in nonpharmacological treatment, including attitudes and beliefs, motivation for change, awareness of triggers, locus of control, self-efficacy, acceptance, coping styles, personality traits, and psychiatric comorbidities associated with treatment adherence. Finally, future prospects and approaches to optimizing treatment matching and minimizing adherence issues are addressed. METHODS:An interdisciplinary team conducted this narrative review. Neuropsychologists conducted a literature search during the month of July 2017 using a combination of the keywords ("headache" or "migraine") and ("adherence" or "compliance") or "barriers to treatment" or various "psychological factors" discussed in this narrative review. Content experts, a psychiatrist, and a complementary and integrative health specialist provided additional commentary and input to this narrative review resulting in integration of additional noteworthy studies, book chapters and books. RESULTS:Various psychological factors, such as attitudes and beliefs, lack of motivation, poor awareness of triggers, external locus of control, poor self-efficacy, low levels of acceptance, and engagement in maladaptive coping styles can contribute to nonadherence. CONCLUSIONS:To maximize adherence, clinicians can assess and address an individual's level of treatment acceptance, beliefs that may present as barriers, readiness for change, locus of control, self-efficacy and psychiatric comorbidities. Identification of barriers to adherence as well as the application of relevant assessment and intervention techniques have the potential to facilitate adherence and ultimately improve treatment success.

Objectives Calls for pediatricians to tend to children's psychosocial concerns have existed for decades because they are known to negatively impact child health. Children with chronic illnesses frequently have child- and family-level psychosocial concerns that complicate the care provided by their pediatric subspecialists. This study compares pediatricians who exclusively practice general pediatrics with subspecialists regarding their inquiring/screening and referring for psychosocial concerns. Physician and practice characteristics associated with these behaviors were examined. Methods We conducted a cross-sectional study using the 2013 American Academy of Pediatrics Periodic Survey of Fellows. Respondents included 304 pediatricians who exclusively practice general pediatrics and 147 subspecialists. The primary analysis compared the current practices of generalists vs. subspecialists with regard to inquiring/screening and referring children with 10 different psychosocial concerns. Covariates included socio-demographics, practice characteristics, and training experiences. Weighted univariate, bivariate and multivariable analyses were performed. Results Less than half of all pediatricians in the sample reported routinely inquiring/screening for most psychosocial concerns, and 2/3 of subspecialists failed to routinely inquire/screen for most of these conditions. Pediatricians who practice general pediatrics exclusively were more likely to inquire/screen (incident rate ratio (IRR) 1.41, p < .05) and refer (IRR 1.59, p < .001) for a greater number of psychosocial concerns than subspecialists, after adjusting for provider and practice characteristics. Having attended a child or adolescent mental health (MH) lecture/conference in the past 2 years was also related to inquiring/screening (IRR 1.24, p < .05). Conclusions Pediatricians infrequently inquire/screen and refer psychosocial concerns, with subspecialists addressing these concerns even less frequently.

BACKGROUND:One in three adolescents and young adults with type 1 diabetes have at least one early diabetes-related complication or comorbidity. We aimed to examine the prevalence and pattern of co-occurring complications in this population, as well as the related risk factors. METHODS:This observational cohort study includes data from individuals diagnosed with type 1 diabetes before age 20 years who participated in the SEARCH for Diabetes in Youth Study across five sites in the USA. We assessed sociodemographic and metabolic risk factors at baseline and at follow-up, and diabetes complications at follow-up. A frequency analysis was done to examine the difference in observed versus expected prevalence (calculated using a contingency table assuming independence across cells) of co-occurring complications or comorbidities. A cluster analysis was done to identify unique clusters of participants based on demographic characteristics and metabolic risk factors. FINDINGS/RESULTS:1327 participants who completed the follow-up visit were included in the frequency analysis. The mean age was 10·1 (SD 3·9) years at the time of type 1 diabetes diagnosis and 18·0 (4·1) years at follow-up. At a mean diabetes duration of 7·8 [SD 1·9] years, co-occurrence of any two or more complications was observed in 78 (5·9%) participants, more frequently than expected by chance alone (58 [4·4%], p=0·015). Specifically, the complications that co-occurred more frequently than expected were retinopathy and diabetic kidney disease (11 [0·8%] vs three [0·2%]; p=0·0007), retinopathy and arterial stiffness (13 [1·0%] vs four [0·3%]; p=0·0016), and arterial stiffness and cardiovascular autonomic neuropathy (24 [1·8%] vs 13 [1·0%]; p=0·015). We identified four unique clusters characterised by progressively worsening metabolic risk factor profiles (longer duration of diabetes and higher glycated haemoglobin, non-HDL cholesterol, and waist-to-height ratio). The prevalence of at least two complications increased across the clusters (six [2·3%] of 261 in the low-risk cluster, 32 [6·3%] of 509 in the moderate-risk cluster, 28 [8%] of 348 in the high-risk cluster, and five [20·8%] of 24 in the highest-risk cluster). Compared with the low-risk and moderate-risk clusters, the high-risk and highest-risk clusters were characterised by a lower proportion of participants who were non-Hispanic white, and a higher proportion of participants who had a household income below US$50 000 and did not have private health insurance. INTERPRETATION/CONCLUSIONS:Early complications co-occur in adolescents and young adults with type 1 diabetes more frequently than expected. Identification of individuals with adverse risk factors could enable targeted behavioural or medical interventions that reduce the likelihood of early development of lifelong diabetes-related morbidity. FUNDING/BACKGROUND:US Centers for Disease Control and Prevention, US National Institutes of Health.

Men who have sex with men (MSM) who use smartphone applications (apps) to meet sexual partners represent a high-risk subset of MSM. As such, the use of pre-exposure prophylaxis (PrEP) may be highly suitable. The purpose of the study was to evaluate awareness of and willingness to use PrEP among 179 HIV-uninfected MSM recruited in London who use these apps. Regression models were fit to assess the associations between perceived barriers and willingness to use PrEP in the future. Most (84.9%) had heard of PrEP and more than half (57.1%) were willing to use PrEP in the future if it were to become available. Low perceived risk for acquiring HIV (prevalence ratio (PR): 0.11; 95% confidence interval (CI): 0.04, 0.33) and concerns about PrEP-related side effects (PR: 0.01; 95% CI: 0.00, 0.04) were associated with being unwilling to use PrEP. Efforts to make PrEP widely available should be continued. Uptake interventions should focus on correcting self-perceptions of HIV risk and educate MSM about the potential side effects of PrEP use so that MSM can make more informed decisions about prevention options.

INTRODUCTION/BACKGROUND:The opioid epidemic in the U.S. continues to increase in severity, and misuse of prescription opioids is of particular concern since it commonly precedes heroin use. This study examined whether sexual orientation (i.e., sexual identity and sexual attraction) is a risk factor for prescription opioid misuse and use disorder among a nationally representative sample of adults in the U.S. METHODS:This study used data from adult participants (ages ≥18 years) in the 2015 National Survey on Drug Use and Health. Chi-square tests and logistic regression examined how sexual identity and sexual attraction relate to past-year and past-month prescription opioid misuse and past-year prescription opioid use disorder. Multivariable models examined associations controlling for demographic characteristics and other drug use. Gender-stratified analyses were also conducted. Data were analyzed in 2018. RESULTS:In multivariable analyses, compared with those identifying as heterosexual, bisexual individuals were at 1.53 (95% CI=1.20, 1.97) and 1.66 (95% CI=1.14, 2.42) higher odds of reporting past-year and past-month misuse, respectively. In stratified analyses, female bisexuals remained at high risk. Regarding sexual attraction, compared with being attracted to only the opposite sex, being attracted to mostly the opposite sex (AOR=2.15, 95% CI=1.77, 2.63) or being equally attracted to both sexes (AOR=1.78, 95% CI=1.38, 2.30) were associated with higher odds for past-year opioid misuse. In stratified analyses, these associations were limited to females. CONCLUSIONS:Sexual orientation disparities in opioid misuse and use disorder among a nationally representative sample of U.S. adults was found.

OBJECTIVE:Although patient-therapist collaboration (working alliance) has been studied extensively in Europe and America, it is unknown to what extent the importance of working alliance for psychotherapy outcome generalizes to lower- and middle-income countries. Additionally, there is a need for more studies on the alliance using methods that are robust to confounders of its effect on outcome. METHOD/METHODS:In this study, 345 outpatients seeking care at the 2 public psychiatric hospitals in Nairobi, Kenya, filled out the Session Alliance Inventory (SAI) and the Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) during each session. The effect of alliance on next-session psychological distress was modeled using the random intercept cross-lagged panel model, which estimates a cross-lagged panel model on within- and between-subjects disaggregated data. RESULTS:Changes in the working alliance from session to session significantly predicted change in psychological distress by the next session, with an increase of 1 point of the SAI in a given session resulting in a decrease of 1.27 points on the CORE-OM by the next session (SE = .60, 95% confidence interval [-2.44, -.10]). This finding represents a medium-sized standardized regression coefficient of between .16 and .21. Results were generally robust to sensitivity tests for stationarity, missing data assumptions, and measurement error. CONCLUSION/CONCLUSIONS:Results affirm cross-cultural stability of the session-by-session reciprocal effects model of alliance and psychological distress-symptoms as seen in a Kenyan psychiatric outpatient sample, using the latest developments in cross-lagged panel modeling. A limitation of the study is its naturalistic design and lack of control over several variables. (PsycINFO Database Record (c) 2018 APA, all rights reserved).