Faculty Bibliography

OBJECTIVES/OBJECTIVE:Usable tools to support individual primary care clinicians in their diagnostic processes could help to reduce preventable harm from diagnostic errors. We conducted a formative study with primary care providers to identify key requisites to optimize the acceptability of 1 online collective intelligence platform (Human Diagnosis Project; Human Dx). MATERIALS AND METHODS/METHODS:We conducted semistructured interviews with practicing primary care clinicians in a sample of the US community-based clinics to examine the acceptability and early usability of the collective intelligence online platform using standardized clinical cases and real-world clinical cases from the participants' own practice. We used an integrated inductive-deductive qualitative analysis approach to analyze the interview transcripts. RESULTS AND DISCUSSION/CONCLUSIONS:Perceived usefulness, perceived accuracy, quality assurance, trust, and ease of use emerged as essential domains of acceptability required for providers to use a collective intelligence tool in clinical practice. Participants conveyed that the collective opinion should: (1) contribute to their clinical reasoning, (2) boost their confidence, (3) be generated in a timely manner, and (4) be relevant to their clinical settings and use cases. Trust in the technology platform and the clinical accuracy of its collective intelligence output emerged as an incontrovertible requirement for user acceptance and engagement. CONCLUSION/CONCLUSIONS:We documented key requisites to building a collective intelligence technology platform that is trustworthy, useful, and acceptable to target end users for assistance in the diagnostic process. These key lessons may be applicable to other provider-facing decision support platforms.

BACKGROUND:Full-term pregnancy (FTP) at an early age confers long-term protection against breast cancer. Previously, we reported that a FTP imprints a specific gene expression profile in the breast of postmenopausal women. Herein, we evaluated gene expression changes induced by parity in the breast of premenopausal women. METHODS:Gene expression profiling of normal breast tissue from 30 nulliparous (NP) and 79 parous (P) premenopausal volunteers was performed using Affymetrix microarrays. In addition to a discovery/validation analysis, we conducted an analysis of gene expression differences in P vs. NP women as a function of time since last FTP. Finally, a laser capture microdissection substudy was performed to compare the gene expression profile in the whole breast biopsy with that in the epithelial and stromal tissues. RESULTS:Discovery/validation analysis identified 43 differentially expressed genes in P vs. NP breast. Analysis of expression as a function of time since FTP revealed 286 differentially expressed genes (238 up- and 48 downregulated) comparing all P vs. all NP, and/or P women whose last FTP was less than 5 years before biopsy vs. all NP women. The upregulated genes showed three expression patterns: (1) transient: genes upregulated after FTP but whose expression levels returned to NP levels. These genes were mainly related to immune response, specifically activation of T cells. (2) Long-term changing: genes upregulated following FTP, whose expression levels decreased with increasing time since FTP but did not return to NP levels. These were related to immune response and development. (3) Long-term constant: genes that remained upregulated in parous compared to nulliparous breast, independently of time since FTP. These were mainly involved in development/cell differentiation processes, and also chromatin remodeling. Lastly, we found that the gene expression in whole tissue was a weighted average of the expression in epithelial and stromal tissues. CONCLUSIONS:Genes transiently activated by FTP may have a role in protecting the mammary gland against neoplastically transformed cells through activation of T cells. Furthermore, chromatin remodeling and cell differentiation, represented by the genes that are maintained upregulated long after the FTP, may be responsible for the lasting preventive effect against breast cancer.

OBJECTIVE:/UNASSIGNED:Despite the potential benefits of mobile mental health apps, real-world results indicate engagement issues because of low uptake and sustained use. This review examined how studies have measured and reported on user engagement indicators (UEIs) for mental health apps. METHODS:/UNASSIGNED:A systematic review of multiple databases was performed in July 2018 for studies of mental health apps for depression, bipolar disorder, schizophrenia, and anxiety that reported on UEIs, namely usability, user satisfaction, acceptability, and feasibility. The subjective and objective criteria used to assess UEIs, among other data, were extracted from each study. RESULTS:/UNASSIGNED:Of 925 results, 40 studies were eligible. Every study reported positive results for the usability, satisfaction, acceptability, or feasibility of the app. Of the 40 studies, 36 (90%) employed 371 indistinct subjective criteria that were assessed with surveys, interviews, or both, and 23 studies used custom subjective scales, rather than preexisting standardized assessment tools. A total of 25 studies (63%) used objective criteria-with 71 indistinct measures. No two studies used the same combination of subjective or objective criteria to assess UEIs of the app. CONCLUSIONS:/UNASSIGNED:The high heterogeneity and use of custom criteria to assess mental health apps in terms of usability, user satisfaction, acceptability, or feasibility present a challenge for understanding real-world low uptake of these apps. Every study reviewed claimed that UEIs for the app were rated highly, which suggests a need for the field to focus on engagement by creating reporting standards and more carefully considering claims.

BACKGROUND:African American youth (aged 8-14 years) do not adhere to national dietary and physical activity guidelines. Nonadherence to these recommendations contributes to disproportionate rates of obesity compared with their white counterparts. Culturally tailored electronic health (eHealth) solutions are needed to communicate nutrition and physical activity messages that resonate with this target population. OBJECTIVE:This study aimed to identify the impact of exposure to a website hosting culturally tailored cartoons to inspire fruit and vegetable uptake and physical activity levels in African American mother-child dyads. METHODS:Statistical analysis included paired sample t tests to evaluate knowledge gains, self-efficacy, and readiness to change. Adapted items from Prochaska's Stages of Change toward the following 4 behaviors were assessed with pre- and posttest surveys: (1) fruit and vegetable selection on my plate, (2) meal preparation, (3) fruit and vegetable selection outside of home, and (4) physical activity. Open-ended comments on videos from mother-child dyads were used to determine user acceptance. Observations of repeated responses during content analysis informed coding and development of key themes. RESULTS:A final sample size of 93 mother-child dyads completed the study. Mothers reported significant improvement from precontemplation or contemplation stages to preparation or action stages for (1) fruit and vegetable selection on her plate (P=.03), (2) meal preparation for her family (P=.01), (3) fruit and vegetable selection outside the home (P<.001), and (4) physical activity (P<.001). Significant improvements were found in knowledge, stage of change, and self-efficacy for the 4 target behaviors of interest (P<.001). Children's open-ended commentary reported vicarious learning and positive character identification with brown-skinned cartoons exhibiting healthful food and exercise behaviors. Mothers commented on the lack of accessible produce in their neighborhoods not depicted in the cartoon videos. CONCLUSIONS:Culturally adapted cartoons that incorporate tailored preferences by African American families, such as race or demography, may help increase adherence to target health behaviors when developing eHealth behavior solutions.

UNLABELLED:Several recent papers have reported strong signals of selection on European polygenic height scores. These analyses used height effect estimates from the GIANT consortium and replication studies. Here, we describe a new analysis based on the the UK Biobank (UKB), a large, independent dataset. We find that the signals of selection using UKB effect estimates are strongly attenuated or absent. We also provide evidence that previous analyses were confounded by population stratification. Therefore, the conclusion of strong polygenic adaptation now lacks support. Moreover, these discrepancies highlight (1) that methods for correcting for population stratification in GWAS may not always be sufficient for polygenic trait analyses, and (2) that claims of differences in polygenic scores between populations should be treated with caution until these issues are better understood. EDITORIAL NOTE:This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

BACKGROUND:The adverse consequences of major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) affect a significant portion of the US population every year (i.e., 15 million for MDD; 8 million for PTSD) and are of public health concern. The current study examines tobacco, alcohol, and marijuana use as possible longitudinal predictors of MDD and/or PTSD. METHODS:A community sample of 674 participants (53% African Americans and 47% Puerto Ricans; 405 females and 269 males) were recruited from the Harlem Longitudinal Development Study. We used Mplus software to obtain the triple trajectories of tobacco, alcohol, and marijuana use from mean age 14 to 36. Logistic regression analyses were then conducted to examine the associations between those triple trajectory groups and a single diagnosis of MDD or PTSD as well as a dual diagnosis of MDD with PTSD at age 36. RESULTS:The observed percentages of MDD, PTSD, and the comorbidity of MDD and PTSD were 17%, 8%, and 5%, respectively. The heavy use of all 3 substances group was associated with an increased likelihood of having MDD (adjusted odds ratio [AOR] = 3.14, P < .01), PTSD (AOR = 3.91, P < .05), and MDD with PTSD (AOR = 6.64, P < .01), as compared with the tobacco and alcohol use group. CONCLUSIONS:Treatment programs to quit or reduce the use of tobacco, alcohol, and marijuana may help decrease the prevalence of MDD and PTSD. This could lead to improvements in individualized treatments for patients who use tobacco, alcohol, and marijuana and who have both MDD and PTSD.

BACKGROUND:Models that accurately predict risk of breast cancer are needed to help younger women make decisions about when to begin screening. Premenopausal concentrations of circulating anti-Müllerian hormone (AMH), a biomarker of ovarian reserve, and testosterone have been positively associated with breast cancer risk in prospective studies. We assessed whether adding AMH and/or testosterone to the Gail model improves its prediction performance for women aged 35-50. METHODS:In a nested case-control study including ten prospective cohorts (1762 invasive cases/1890 matched controls) with pre-diagnostic serum/plasma samples, we estimated relative risks (RR) for the biomarkers and Gail risk factors using conditional logistic regression and random-effects meta-analysis. Absolute risk models were developed using these RR estimates, attributable risk fractions calculated using the distributions of the risk factors in the cases from the consortium, and population-based incidence and mortality rates. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminatory accuracy of the models with and without biomarkers. RESULTS:The AUC for invasive breast cancer including only the Gail risk factor variables was 55.3 (95% CI 53.4, 57.1). The AUC increased moderately with the addition of AMH (AUC 57.6, 95% CI 55.7, 59.5), testosterone (AUC 56.2, 95% CI 54.4, 58.1), or both (AUC 58.1, 95% CI 56.2, 59.9). The largest AUC improvement (4.0) was among women without a family history of breast cancer. CONCLUSIONS:AMH and testosterone moderately increase the discriminatory accuracy of the Gail model among women aged 35-50. We observed the largest AUC increase for women without a family history of breast cancer, the group that would benefit most from improved risk prediction because early screening is already recommended for women with a family history.

Awareness of the human health impacts of exposure to air pollution is growing rapidly. For example, it has become evident that the adverse health effects of air pollution are more pronounced in disadvantaged populations. Policymakers in many jurisdictions have responded to this evidence by enacting initiatives that lead to lower concentrations of air pollutants, such as urban traffic restrictions. In this review, we focus on the interplay between advances in environmental exposure assessment and developments in policy. We highlight recent progress in the granular measurement of air pollutants and individual-level exposures, and how this has enabled focused local policy actions. Finally, we detail an illustrative study designed to link individual-level health-relevant exposures with economic, behavioral, biological, familial, and environmental variables.

BACKGROUND:Cocaine is commonly involved in unintentional drug poisoning (overdose) deaths, accounting for 46% of overdose deaths in New York City (NYC) in 2016. However, little research exists regarding cocaine use by middle-aged and older adults, who are more likely than younger individuals to have underlying cardiovascular disease (CVD) and therefore, may be at increased risk for the adverse health consequences of cocaine. METHODS:We conducted a retrospective analysis of unintentional drug overdose deaths of middle-aged and older NYC residents age 45-84 from 2000 to 2016 using two linked sources, NYC death certificates and toxicology results from the Office of the Chief Medical Examiner. RESULTS:From 2000 to 2016, there were 6061 unintentional drug overdose deaths among New Yorkers age 45-84. Of those, cocaine was involved in 53% (n = 3183). Co-occurring opioid involvement (fentanyl, heroin, methadone, or opioid analgesics) among deaths involving cocaine was common (58%). Compared to decedents of non-cocaine involved overdose, decedents of cocaine-involved overdose were more likely to be male and non-Latino Black. Multivariable analysis showed that adults age 45-54 (adjusted odds ratio [AOR] = 1.34, 95% 1.05, 1.70), males (AOR = 1.30, 95% CI 1.15, 1.46), Bronx residence (AOR = 1.29, 95% CI 1.08, 1.54), and non-Latino black race/ethnicity (AOR = 2.37, 95% CI 2.07, 2.72) were independently associated with cocaine-involved overdose. CONCLUSION/CONCLUSIONS:Characteristics of decedents of cocaine-involved overdose overlap with populations with high CVD burden in NYC. Studies are needed to better understand the risks of cocaine among adults with underlying CVD.

BACKGROUND AND OBJECTIVES:Data are scarce on blood metabolite associations with proteinuria, a strong risk factor for adverse kidney outcomes. We sought to investigate associations of proteinuria with serum metabolites identified using untargeted profiling in populations with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:=620), two rigorously conducted clinical trials with per-protocol measures of 24-hour proteinuria and GFR, we evaluated cross-sectional associations between urine protein-to-creatinine ratio and 637 known, nondrug metabolites, adjusting for key clinical covariables. Metabolites significantly associated with proteinuria were tested for associations with CKD progression. RESULTS:) were 4-hydroxychlorthalonil and 1,5-anhydroglucitol; all six quantified metabolites in the phosphatidylethanolamine pathway were also significant. Of the 58 metabolites associated with proteinuria, four were associated with ESKD in both the AASK and the MDRD study. CONCLUSIONS:We identified 58 serum metabolites with cross-sectional associations with proteinuria, some of which were also associated with CKD progression. PODCAST:This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_02_07_CJASNPodcast_19_03_.mp3.