Predicting Poor Outcomes Among Individuals Seeking Care for Major Depressive Disorder

OBJECTIVE: To develop and validate algorithms to identify individuals with major depressive disorder (MDD) at elevated risk for suicidality or for an acute care event. METHODS: We conducted a retrospective cohort analysis among adults with MDD diagnosed between January 1, 2018 and February 28, 2019. Generalized estimating equation models were developed to predict emergency department (ED) visit, inpatient hospitalization, acute care visit (ED or inpatient), partial-day hospitalization, and suicidality in the year following diagnosis. Outcomes (per 1000 patients per month, PkPPM) were categorized as all-cause, psychiatric, or MDD-specific and combined into composite measures. Predictors included demographics, medical and pharmacy utilization, social determinants of health, and comorbid diagnoses as well as features indicative of clinically relevant changes in psychiatric health. Models were trained on data from 1.7M individuals, with sensitivity, positive predictive value, and area-under-the-curve (AUC) derived from a validation dataset of 0.7M. RESULTS: Event rates were 124.0 PkPPM (any outcome), 21.2 PkPPM (psychiatric utilization), and 7.6 PkPPM (suicidality). Among the composite models, the model predicting suicidality had the highest AUC (0.916) followed by any psychiatric acute care visit (0.891) and all-cause ED visit (0.790). Event-specific models all achieved an AUC \u3e0.87, with the highest AUC noted for partial-day hospitalization (AUC = 0.938). Select predictors of all three outcomes included younger age, Medicaid insurance, past psychiatric ED visits, past suicidal ideation, and alcohol use disorder diagnoses, among others. CONCLUSIONS: Analytical models derived from clinically-relevant features identify individuals with MDD at risk for poor outcomes and can be a practical tool for health care organizations to divert high-risk populations into comprehensive care models

Stalled scale-up of opioid agonist therapies for HIV prevention in Kazakhstan: history, policy, and recommendations for change

HIV incidence and mortality are increasing in Eastern Europe and Central Asia and are concentrated in people who inject drugs. Maintenance with opioid agonist therapies (OAT) like methadone or buprenorphine is the best treatment for opioid use disorder and a key HIV-prevention strategy in the region. In Kazakhstan, the scale-up of methadone has been minimal since methadone’s introduction in 2008 and has been supported through international charitable organizations. As the Republic of Kazakhstan is designated to assume financial and administrative oversight of OAT, legislative gains can ensure treatment continuity and scale-up. Here, we review legislative barriers to OAT scale-up in Kazakhstan using an implementation science lens. We review legislative, political, and cultural barriers that undermine the efficient distribution and allocation of medications and impose burdensome clinical and administrative demands on patients and clinicians. Legislative reform is required to support further OAT expansion. We therefore provide policy recommendations to overcome these barriers to increase access to this life-saving, life-prolonging, evidence-based medical treatment. Minimally, these include increased numbers of clinical sites and patients at these sites; re-engineering OAT delivery across the country and directly to patients; introducing newer formulations of OAT; and creating an open bidding process to procure treatment medications

Auditory Enhancement and Second Language Experience in Spanish and English Weighting of Secondary Voicing Cues

The role of secondary cues in voicing categorization was investigated in three listener groups: Monolingual English (n=20) and Spanish speakers (n=20), and Spanish speakers with significant English experience (n=16). Results showed that, in all three groups, participants used onset f0 in making voicing decisions only in the positive voice onset time (VOT) range (short lag and long lag tokens), while there was no effect of onset f0 on voicing categorization within the negative VOT range (voicing lead tokens) for any of the participant groups. These results support an auditory enhancement view of perceptual cue weighting: Onset f0 serves as a secondary cue to voicing only in the positive VOT range where it is not overshadowed by the presence of pre-voicing. Moreover, results showed that Spanish learners of English gave a significantly greater weight to onset f0 in their voicing decisions than did listeners in either of the other two groups. This result supports the view that learners may overweight secondary cues to distinguish between non-native categories that are assimilated to the same native category on the basis of a primary cue

DNA Sequence Analysis of SLC26A5, Encoding Prestin, in a Patient-Control Cohort: Identification of Fourteen Novel DNA Sequence Variations

Prestin, encoded by the gene SLC26A5, is a transmembrane protein of the cochlear outer hair cell (OHC). Prestin is required for the somatic electromotile activity of OHCs, which is absent in OHCs and causes severe hearing impairment in mice lacking prestin. In humans, the role of sequence variations in SLC26A5 in hearing loss is less clear. Although prestin is expected to be required for functional human OHCs, the clinical significance of reported putative mutant alleles in humans is uncertain.To explore the hypothesis that SLC26A5 may act as a modifier gene, affecting the severity of hearing loss caused by an independent etiology, a patient-control cohort was screened for DNA sequence variations in SLC26A5 using sequencing and allele specific methods. Patients in this study carried known pathogenic or controversial sequence variations in GJB2, encoding Connexin 26, or confirmed or suspected sequence variations in SLC26A5; controls included four ethnic populations. Twenty-three different DNA sequence variations in SLC26A5, 14 of which are novel, were observed: 4 novel sequence variations were found exclusively among patients; 7 novel sequence variations were found exclusively among controls; and, 12 sequence variations, 3 of which are novel, were found in both patients and controls. Twenty-one of the 23 DNA sequence variations were located in non-coding regions of SLC26A5. Two coding sequence variations, both novel, were observed only in patients and predict a silent change, p.S434S, and an amino acid substitution, p.I663V. In silico analysis of the p.I663V amino acid variation suggested this variant might be benign. Using Fisher's exact test, no statistically significant difference was observed between patients and controls in the frequency of the identified DNA sequence variations. Haplotype analysis using HaploView 4.0 software revealed the same predominant haplotype in patients and controls and derived haplotype blocks in the patient-control cohort similar to those generated from the International HapMap Project.Although these data fail to support a hypothesis that SLC26A5 acts as a modifier gene of GJB2-related hearing loss, the sample size is small and investigation of a larger population might be more informative. The 14 novel DNA sequence variations in SLC26A5 reported here will serve as useful research tools for future studies of prestin

Think fast! The relationship between goal prediction speed and social competence in infants

Skilled social interactions require knowledge about others' intentions and the ability to implement this knowledge in real-time to generate appropriate responses to one's partner. Young infants demonstrate an understanding of other people's intentions (e.g. Woodward, Sommerville, Gerson, Henderson & Buresh, 2009), yet it is not until the second year that infants seem to master the real-time implementation of their knowledge during social interactions (e.g. Warneken & Tomasello, 2007). The current study investigates the possibility that developments in social competence during the second year are related to increases in the speed with which infants can employ their understanding of others' intentions. Twenty- to 22-month-old infants (N = 23) viewed videos of goal-directed actions on a Tobii eye-tracker and then engaged in an interactive perspective-taking task. Infants who quickly and accurately anticipated another person's future behavior in the eye-tracking task were more successful at taking their partner's perspective in the social interaction. Success on the perspective-taking task was specifically related to the ability to correctly predict another person's intentions. These findings highlight the importance of not only being a 'smart' social partner but also a 'fast' social thinker

The early social significance of shared ritual actions

Many rituals are socially stipulated such that engaging in a group's rituals can fundamentally signal membership in that group. Here, we asked whether infants infer information about people's social affiliation based on whether those people perform the same ritualistic action versus different actions. We presented 16-month-old infants with two people who used the same object to achieve the same goal: turning on a light. In a first study, the actions that the actors used to turn on the light had key properties of ritual: they were not causally necessary to reach the overall goal, and there were no features of the situation that required doing the particular actions. We varied whether the two actors performed the same action or performed different actions to turn on the light. Infants expected people who used the same ritualistic action to be more likely to affiliate than people who used different actions. A second study indicated that these results were not due to perceptual similarity: when the differences in the actors' actions were not marked by properties of ritual, but were instead due to situational constraints, infants expected the actors to affiliate. Thus, infants understand the social significance of people engaging in common, potentially ritualistic actions, and expect these actions to provide information about third-party social relationships

The Origins of Social Categorization

Forming conceptually-rich social categories helps people to navigate the complex social world by allowing them to reason about the likely thoughts, beliefs, actions, and interactions of others, as guided by group membership. Nevertheless, social categorization often has nefarious consequences. We suggest that the foundation of the human ability to form useful social categories is in place in infancy: social categories guide the inferences infants make about the shared characteristics and social relationships of other people. We also suggest that the ability to form abstract social categories may be separable from the eventual negative downstream consequences of social categorization, including prejudice, discrimination, and stereotyping. Although a tendency to form inductively-rich social categories appears early in ontogeny, prejudice based on each particular category dimension may not be inevitable

Friends or foes: Infants use shared evaluations to infer others’ social relationships.

Predicting others’ affiliative relationships is critical to social cognition, but there is little evidence of how this ability develops. We examined 9-month-old infants’ inferences about third-party affiliation based on shared and opposing evaluations. Infants expected two people who expressed shared evaluations to interact positively, whereas they expected two people who expressed opposing evaluations to interact negatively. A control condition revealed that infants’ expectations could not be due to mere perceptual repetition. Thus, an abstract understanding that third-party affiliation can be based on shared intentions has roots in the first year of life. These findings have implications for understanding humans’ earliest representations of the social world

Preverbal Infants Infer Third‐Party Social Relationships Based on Language

Language provides rich social information about its speakers. For instance, adults and children make inferences about a speaker's social identity, geographic origins, and group membership based on her language and accent. Although infants prefer speakers of familiar languages (Kinzler, Dupoux, & Spelke, 2007), little is known about the developmental origins of humans' sensitivity to language as marker of social identity. We investigated whether 9-month-olds use the language a person speaks as an indicator of that person's likely social relationships. Infants were familiarized with videos of two people who spoke the same or different languages, and then viewed test videos of those two individuals affiliating or disengaging. Results suggest that infants expected two people who spoke the same language to be more likely to affiliate than two people who spoke different languages. Thus, infants view language as a meaningful social marker and use language to make inferences about third-party social relationships

Friends or Foes: Infants Use Shared Evaluations to Infer Others’ Social Relationships

Predicting others' affiliative relationships is critical to social cognition, but there is little evidence of how this ability develops. We examined 9-month-old infants' inferences about 3rd-party affiliation based on shared and opposing evaluations. Infants expected 2 people who expressed shared evaluations to interact positively, whereas they expected 2 people who expressed opposing evaluations to interact negatively. A control condition revealed that infants' expectations could not be due to mere perceptual repetition. Thus, an abstract understanding that 3rd-party affiliation can be based on shared intentions has roots in the 1st year of life. These findings have implications for understanding humans' earliest representations of the social world