Recent Advances in Group-Based Trajectory Modeling for Clinical Research.

Group-based trajectory modeling (GBTM) identifies groups of individuals following similar trajectories of one or more repeated measures. The categorical nature of GBTM is particularly well suited to clinical psychology and medicine, where patients are often classified into discrete diagnostic categories. This review highlights recent advances in GBTM and key capabilities that remain underappreciated in clinical research. These include accounting for nonrandom subject attrition, joint trajectory and multitrajectory modeling, the addition of the beta distribution to modeling options, associating trajectories with future outcomes, and estimating the probability of future outcomes. Also discussed is an approach to selecting the number of trajectory groups.

Cohort bias in predictive risk assessments of future criminal justice system involvement.

Risk assessment instruments (RAIs) are widely used to aid high-stakes decision-making in criminal justice settings and other areas such as health care and child welfare. These tools, whether using machine learning or simpler algorithms, typically assume a time-invariant relationship between predictors and outcome. Because societies are themselves changing and not just individuals, this assumption may be violated in many behavioral settings, generating what we call cohort bias. Analyzing criminal histories in a cohort-sequential longitudinal study of children, we demonstrate that regardless of model type or predictor sets, a tool trained to predict the likelihood of arrest between the ages of 17 and 24 y on older birth cohorts systematically overpredicts the likelihood of arrest for younger birth cohorts over the period 1995 to 2020. Cohort bias is found for both relative and absolute risks, and it persists for all racial groups and within groups at highest risk for arrest. The results imply that cohort bias is an underappreciated mechanism generating inequality in contacts with the criminal legal system that is distinct from racial bias. Cohort bias is a challenge not only for predictive instruments with respect to crime and justice, but also for RAIs more broadly.

Behaviors in kindergarten are associated with trajectories of long-term welfare receipt: A 30-year population-based study.

This study examines the link between behavior in kindergarten and adult-life welfare receipt. Teacher-rated behavioral assessments were obtained for inattention, hyperactivity, aggression-opposition, anxiety, and prosociality when children (n=2960) were aged 5-6 years and linked to their tax return records from age 18-35 years. We used group-based based trajectory modeling to identify distinct trajectories of welfare receipt and multinomial logistic regression models to examine the association between behaviors and trajectory group membership. The child's sex, IQ, and family background were adjusted for. Four trajectories of welfare receipt were identified: low (n = 2,390, 80.7%), declining (n = 260, 8.8%), rising (n = 150, 5.2%), and chronic (n = 160, 5.4%). Relative to the low trajectory, inattention and aggression-opposition at age 6 years were associated with increased risk of following a declining, rising, and chronic trajectory of welfare receipt, independent of hyperactivity and anxiety. Prosocial behaviors were independently associated with a lower risk of following a chronic trajectory. This study shows that kindergarten children exhibiting high inattention and aggression-opposition and low prosocial behaviors may be at increased risk of long-term welfare receipt in adulthood. The implications for early screening, monitoring, and prevention are discussed.

Mortality Risk in Pediatric Sepsis Based on C-reactive Protein and Ferritin Levels.

OBJECTIVES: Interest in using bedside C-reactive protein (CRP) and ferritin levels to identify patients with hyperinflammatory sepsis who might benefit from anti-inflammatory therapies has piqued with the COVID-19 pandemic experience. Our first objective was to identify patterns in CRP and ferritin trajectory among critically ill pediatric sepsis patients. We then examined the association between these different groups of patients in their inflammatory cytokine responses, systemic inflammation, and mortality risks. DATA SOURCES: A prospective, observational cohort study. STUDY SELECTION: Children with sepsis and organ failure in nine pediatric intensive care units in the United States. DATA EXTRACTION: Two hundred and fifty-five children were enrolled. Five distinct clinical multi-trajectory groups were identified. Plasma CRP (mg/dL), ferritin (ng/mL), and 31 cytokine levels were measured at two timepoints during sepsis (median Day 2 and Day 5). Group-based multi-trajectory models (GBMTM) identified groups of children with distinct patterns of CRP and ferritin. DATA SYNTHESIS: Group 1 had normal CRP and ferritin levels ( n = 8; 0% mortality); Group 2 had high CRP levels that became normal, with normal ferritin levels throughout ( n = 80; 5% mortality); Group 3 had high ferritin levels alone ( n = 16; 6% mortality); Group 4 had very high CRP levels, and high ferritin levels ( n = 121; 11% mortality); and Group 5 had very high CRP and very high ferritin levels ( n = 30; 40% mortality). Cytokine responses differed across the five groups, with ferritin levels correlated with macrophage inflammatory protein 1α levels and CRP levels reflective of many cytokines. CONCLUSIONS: Bedside CRP and ferritin levels can be used together to distinguish groups of children with sepsis who have different systemic inflammation cytokine responses and mortality risks. These data suggest future potential value in personalized clinical trials with specific targets for anti-inflammatory therapies.

Bayesian Outcome Prediction After Resuscitation From Cardiac Arrest.

BACKGROUND AND OBJECTIVES: Postarrest prognostication research does not typically account for the sequential nature of real-life data acquisition and interpretation and reports nonintuitive estimates of uncertainty. Bayesian approaches offer advantages well suited to prognostication. We used Bayesian regression to explore the usefulness of sequential prognostic indicators in the context of prior knowledge and compared this with a guideline-concordant algorithm. METHODS: We included patients hospitalized at a single center after cardiac arrest. We extracted prospective data and assumed these data accrued over time as in routine practice. We considered predictors demographic and arrest characteristics, initial and daily neurologic examination, laboratory results, therapeutic interventions, brain imaging, and EEG. We fit Bayesian hierarchical generalized linear multivariate models predicting discharge Cerebral Performance Category (CPC) 4 or 5 (poor outcomes) vs 1-3 including sequential clinical and prognostic data. We explored outcome posterior probability distributions (PPDs) for individual patients and overall. As a comparator, we applied the 2021 European Resuscitation Council and European Society of Intensive Care Medicine (ERC/ESICM) guidelines. RESULTS: We included 2,692 patients of whom 864 (35%) were discharged with a CPC 1-3. Patients' outcome PPDs became narrow and shifted toward 0 or 1 as sequentially acquired information was added to models. These changes were largest after arrest characteristics and initial neurologic examination were included. Using information typically available at or before intensive care unit admission, sensitivity predicting poor outcome was 51% with a 0.6% false-positive rate. In our most comprehensive model, sensitivity for poor outcome prediction was 76% with 0.6% false-positive rate (FPR). The ERC/ESICM algorithm applied to 547 of 2,692 patients and yielded 36% sensitivity with 0% FPR. DISCUSSION: Bayesian models offer advantages well suited to prognostication research. On balance, our findings support the view that in expert hands, accurate neurologic prognostication is possible in many cases before 72 hours postarrest. Although we caution against early withdrawal of life-sustaining therapies, rapid outcome prediction can inform clinical decision making and future clinical trials.

A multi-trajectory analysis of commonly co-occurring mental health issues across childhood and adolescence.

Developmental trajectories of mental health issues can often be usefully summarised in a small number of clinically meaningful subtypes. Given the high levels of heterotypic and homotypic comorbidity in child and adolescent mental health symptoms, we explored whether it was possible to identify clinically meaningful developmental subtypes of multiple commonly co-occurring mental health issues. We evaluated the combined developmental trajectories of the most common and commonly co-occurring child and adolescent mental health issues: attention-deficit/hyperactivity disorder (ADHD), internalising, and externalising symptoms in a normative sample of youth with data (n = 1620) at ages 7, 8, 9, 10, 11, 12, 13 and 15 using group-based multi-trajectory modelling. Multinomial logistic regression was used to evaluate predictors of group membership. Our optimal model included six trajectory groups, labelled 'unaffected', 'normative maturing', 'internalising', 'multimorbid late onset', 'multimorbid remitting', and 'multimorbid with remitting externalising'. Examining covariates of group membership suggested that males and bully victims tend to have complex mental health profiles; academic achievement and smoking during pregnancy have general associations with mental health irrespective of symptom developmental trajectories or combination; and maternal post-natal depression is primarily related to symptoms that are already in evidence by the beginning of the school years. Results suggest that developmental trajectories of commonly co-occurring mental health issues can be usefully summarised in terms of a small number of developmental subtypes. These subtypes more often than not involve multiple co-occurring mental health issues. Their association with mental health covariates depends on the combination and developmental timing of symptoms in ways that suggest they can be clinically informative.

Young Adulthood Outcomes of Joint Mental Health Trajectories: A Group-Based Trajectory Model Analysis of a 13-Year Longitudinal Cohort Study.

Developmental trajectories of common mental health issues such as ADHD symptoms, internalising problems, and externalising problems can often be usefully summarised in terms of a small number of 'developmental subtypes' (e.g., 'childhood onset', 'adolescent onset') that may differ in their profiles or levels of clinically meaningful variables such as etiological risk factors. However, given the strong tendency for symptoms in these domains to co-occur, it is important to consider not only developmental subtypes in each domain individually, but also the joint developmental subtypes defined by symptoms trajectories in all three domains together (e.g., 'late onset multimorbid', 'pure internalising', 'early onset multimorbid'). Previous research has illuminated the joint developmental subtypes of ADHD symptoms, internalising problems, and externalising problems that emerge from normative longitudinal data using methods such as group-based trajectory modelling, as well as predictors of membership in these developmental subtypes. However, information on the long-term outcomes of developmental subtype membership is critical to illuminate the likely nature and intensity of support needs required for individuals whose trajectories fit different developmental subtypes. We, therefore, evaluated the relations between developmental subtypes previously derived using group-based trajectory modelling in the z-proso study (n = 1620 with trajectory data at ages 7, 8, 9, 10, 11, 12, 13, 15) and early adulthood outcomes. Individuals with multimorbid trajectories but not 'pure' internalising problem elevations showed higher levels of social exclusion and delinquency at age 20. These associations held irrespective of the specific developmental course of symptoms (e.g., early versus late onset versus remitting). There was also some evidence that intimate partner violence acts as a form of heterotypic continuity for earlier externalising problems. Results underline the need for early intervention to address the pathways that lead to social exclusion and delinquency among young people with multiple co-occurring mental health issues.

Trajectories of adolescent poly-substance use and their long-term social and economic outcomes for males from low-income backgrounds.

Substance abuse is a significant public health concern that disproportionately burdens males and low-income communities. This study examined (1) longitudinal profiles of male adolescent poly-substance use and (2) their association with social and economic participation across early adulthood. Drawing on a cohort of males (n = 890) from low-income neighborhoods, we used group-based multi-trajectory modeling to identify profiles of poly-substance use (alcohol, tobacco, cannabis, illicit drugs) from age 13-17 years. Regression models were used to link substance use profiles to high school graduation, criminal convictions, personal and household earnings, welfare receipt and partnership from age 19-37 years, obtained from administrative records. Child IQ, family adversity and behavioral problems were adjusted for. Four poly-substance use profiles were identified: abstinent (n = 128, 14.4%), late-onset (n = 412, 46.5%), mid-onset (n = 249, 28.1%), and early-onset (n = 98, 11.1%). Relative to the late-onset (reference) group, participants in the early-onset profile were 3.0 times (95%CI = 1.68-5.53) more likely to have left school without a diploma, 2.7 times (95% CI = 1.56-4.68) more likely to have a criminal conviction by age 24 years, earned 10,185 USD less (95% CI = - 15,225- - 5144) per year at age 33-37 years and had 15,790 USD lower (95% CI = - 23,378- - 8218) household income at age 33-37 years, a 1.3 times (95%CI = 1.15-1.57) higher incidence of annual welfare receipt and a 24% (95% CI = 5-40) lower incidence of marriage/cohabitation from age 18-35 years. We show that adolescent-onset poly-substance use by age 13 is associated with poor social and economic outcomes. Delaying the onset of substance use and reducing exposure to additional substance classes has potential for high societal cost savings.

Trajectories of Follow-up Compliance in a Fracture Liaison Service and Their Predictors: A Longitudinal Group-Based Trajectory Analysis.

INTRODUCTION/OBJECTIVES: Identification of groups of patients following similar trajectories of time-varying patient characteristics are often of considerable clinical value. This study provides an example of how the identification of trajectory groups of patients can be useful. METHODS: Using clinical and administrative data of a prospective cohort study aiming to improve the secondary prevention of osteoporosis-related fractures with a Fracture Liaison Service (FLS), trajectory groups for visit compliance over time (2-year follow-up) were predicted using group-based trajectory modeling. Predictors of trajectory groups were identified using multinomial logistic regressions. RESULTS: Among 532 participants (86% women, mean age 63 years), three trajectories were identified and interpreted as high followers, intermediate followers, and low followers. The predicted probability for group-membership was: 48.4% high followers, 28.1% intermediate followers, 23.5% low followers. A lower femoral bone mineral density and polypharmacy were predictors of being in the high followers compared to the low followers group; predictors for being in the intermediate followers group were polypharmacy and referral to a bone specialist at baseline. CONCLUSIONS: Results provided information on visit compliance patterns and predictors for the patients undergoing the intervention. This information has important implications when implementing such health services and determining their effectiveness.

Social change and cohort differences in group-based arrest trajectories over the last quarter-century.

This article draws on official criminal histories for multiple birth cohorts spanning a 17-y difference in birth year to study how social change can alter our understanding of influential theories and policies about criminal offender groups. Arrest histories are linked to comprehensive longitudinal measurement on over 1,000 individuals originally from Chicago. Using group-based trajectory modeling, we investigated the magnitude and type of cohort differences in trajectories of arrest over the period 1995 to 2020. Our results show that trajectory group membership varies strongly by birth cohort. Membership in the nonoffender group is nearly 15 percentage points higher for cohorts born in the mid-1990s as compared to those born in the 1980s; conversely, older cohorts are more likely to be members of adolescent-limited and chronic-offender groups. Large cohort differences in trajectory group membership persist after controlling for a wide-ranging set of demographic characteristics and early-life risk factors that vary by cohort and that prior research has identified as important influences on crime. Not only does the effect of social change on cohort differentiation persist, but its magnitude is comparable to-indeed larger than-differences in trajectory group membership associated with varying levels of self-control or by whether individuals grew up in high-poverty households. These results suggest that changes in the broader social environment shared by members of the same birth cohort are as powerful in shaping their trajectory group membership as classic predictors identified in prior research, a finding that carries implications for crime-control policies that rely on prediction.

Behavior in childhood is associated with romantic partnering patterns in adulthood.

BACKGROUND: Most people will partner at some point during their lives. Yet little is known about the association between childhood behavior and patterns of long-term romantic partnering in adulthood. METHODS: In this population-based cohort study, behavioral ratings were prospectively obtained from teachers when children (n = 2,960) were aged 10-12 years - for inattention, hyperactivity, aggression-opposition, anxiety, and prosociality - and linked to their tax return records from age 18 to 35 years (1998-2015). We used group-based based trajectory modeling to estimate the probability of partnership (marriage/cohabitation) over time and multinomial logistic regression models to examine the association between childhood behavior and trajectory group membership. The child's sex and family socioeconomic background were adjusted for. RESULTS: Five distinct trajectories of partnering were identified: early-partnered (n = 420, 14.4%), mid-partnered (n = 620, 21.3%), late-partnered (n = 570, 19.2%), early-partnered-separated (n = 460, 15.5%), and delayed-or-unpartnered (n = 890, 30.0%). Participants in the early-partnered-separated and delayed-or-unpartnered trajectories were more likely to have left high school without a diploma and to have lower earnings and higher welfare receipt from age 18 to 35 years. After adjustment for sex and family background, inattention and aggression-opposition were uniquely and additively associated with increased likelihood of following an early-partnered-separated trajectory, while inattention and anxiety were associated with an increased likelihood of following a delayed-or-unpartnered trajectory. Childhood prosocial behaviors were consistently associated with earlier and more sustained patterns of partnership. CONCLUSIONS: Children with behavioral problems are more likely to separate or to be unpartnered across early adulthood. This may have consequences for their psychological health and wellbeing and that of their families.

Adolescent internalizing symptoms: The importance of multi-informant assessments in childhood.

BACKGROUND: Childhood internalizing symptoms can be associated with adolescent internalizing symptoms, but only a small proportion of symptomatic children are at long-term risk. Our objectives were to (1) distinguish between typical and atypical levels of internalizing symptoms using mother- and teacher-assessments and (2) test the association between childhood internalizing symptoms and adolescent generalized anxiety, depression, and social phobia symptoms in boys and girls. METHODS: Multi-trajectory models were used to estimate the evolution of mother- and teacher-reported internalizing symptoms across childhood (1.5 to 12 years) in a large population-based cohort (n = 1431). Multiple linear regression models were implemented to estimate the association between childhood group membership of internalizing symptoms and self-reported specific internalizing symptoms at 15 years by sex. RESULTS: Five groups of childhood internalizing symptoms were identified: Mother & teacher low (22.6%), Mother moderate/teacher low (37.9%), Mother moderate/teacher high (18.3%), Mother high/teacher low (11.8%) and Mother & teacher high (9.5%). Multiple linear regression models showed that compared to the low group, (1) boys in the high group reported higher social phobia symptoms (p = 0.04), (2) girls in the high group reported higher depression (p = 0.01) and generalized anxiety (p < 0.01) symptoms, and (3) girls in the moderate/high group reported higher generalized anxiety symptoms (p = 0.02) in adolescence. LIMITATIONS: The main limitation is that mothers' and teachers' assessments mostly covered different developmental periods. CONCLUSIONS: A multi-informant assessment of childhood internalizing symptoms improves adolescent specific internalizing symptoms identification in a general population sample over reliance on a single informant.

Comparison of parametric and nonparametric methods for outcome prediction using longitudinal data after cardiac arrest.

INTRODUCTION: Predicting outcome after cardiac arrest is challenging. We previously tested group-based trajectory modeling (GBTM) for prognostication based on baseline characteristics and quantitative electroencephalographic (EEG) trajectories. Here, we describe implementation of this method in a freely available software package and test its performance against alternative options. METHODS: We included comatose patients admitted to a single center after resuscitation from cardiac arrest from April 2010 to April 2019 who underwent ≥6 h of EEG monitoring. We abstracted clinical information from our prospective registry and summarized suppression ratio in 48 hourly epochs. We tested three classes of longitudinal models: frequentist, statistically based GBTMs; non-parametric (i.e. machine learning) k-means models; and Bayesian regression. Our primary outcome of interest was discharge CPC 1-3 (vs unconsciousness or death). We compared sensitivity for detecting poor outcome at a false positive rate (FPR) <1%. RESULTS: Of 1,010 included subjects, 250 (25%) were awake and alive at hospital discharge. GBTM and k-means derived trajectories, group sizes and group-specific outcomes were comparable. Conditional on an FPR < 1%, GBTMs yielded optimal sensitivity (38%) over 48 h. More sensitive methods had 2-3 % FPRs. CONCLUSION: We explored fundamentally different tools for patient-level predictions based on longitudinal and time-invariant patient data. Of the evaluated methods, GBTM resulted in optimal sensitivity while maintaining a false positive rate <1%. The provided code and software of this method provides an easy-to-use implementation for outcome prediction based on GBTMs.

Inattention in boys from low-income backgrounds predicts welfare receipt: a 30-year prospective study.

BACKGROUND: Childhood disruptive behaviors are highly prevalent and associated with adverse long-term social and economic outcomes. Trajectories of welfare receipt in early adulthood and the association of childhood behaviors with high welfare receipt trajectories have not been examined. METHODS: Boys (n = 1000) from low socioeconomic backgrounds were assessed by kindergarten teachers for inattention, hyperactivity, aggression, opposition, and prosociality, and prospectively followed up for 30 years. We used group-base trajectory modeling to estimate trajectories of welfare receipt from age 19-36 years using government tax return records, then examined the association between teacher-rated behaviors and trajectory group membership using mixed effects multinomial regression models. RESULTS: Three trajectories of welfare receipt were identified: low (70.8%), declining (19.9%), and chronic (9.3%). The mean annual personal employment earnings (US$) for the three groups at age 35/36 years was $36 500 (s.d. = $24 000), $15 600 (s.d. = $16 275), and $1700 (s.d. = $4800), respectively. Relative to the low welfare receipt group, a unit increase in inattention (mean = 2.64; s.d. = 2.32, range = 0-8) at age 6 was associated with an increased risk of being in the chronic group (relative risk ratio; RRR = 1.16, 95% CI 1.03-1.31) and in the declining group (RRR = 1.13, 95% CI 1.03-1.23), after adjustment for child IQ and family adversity, and independent of other behaviors. Family adversity was more strongly associated with trajectories of welfare receipt than any behavior. CONCLUSIONS: Boys from disadvantaged backgrounds exhibiting high inattention in kindergarten are at elevated risk of chronic welfare receipt during adulthood. Screening and support for inattentive behaviors beginning in kindergarten could have long-term social and economic benefits for individuals and society.

Trajectories of prescription opioids filled over time.

We performed a retrospective cohort study that aimed to identify one or more groups that followed a pattern of chronic, high prescription use and quantify individuals' time-dependent probabilities of belonging to a high-utilizer group. We analyzed data from 52,456 adults age 18-45 who enrolled in Medicaid from 2009-2017 in Allegheny County, Pennsylvania who filled at least one prescription for an opioid analgesic. We used group-based trajectory modeling to identify groups of individuals with distinct patterns of prescription opioid use over time. We found the population to be comprised of three distinct trajectory groups. The first group comprised 83% of the population and filled few, if any, opioid prescriptions after their index prescription. The second group (12%) initially filled an average of one prescription per month, but declined over two years to near-zero. The third group (6%) demonstrated sustained high opioid prescriptions utilization. Using individual patients' posterior probability of membership in the high utilization group, which can be updated iteratively over time as new information become available, we defined a sensitive threshold predictive of sustained future opioid utilization. We conclude that individuals at risk of sustained opioid utilization can be identified early in their clinical course from limited observational data.

Association Between Childhood Behaviors and Adult Employment Earnings in Canada.

Importance: Specifying the association between childhood behaviors and adult earnings can inform the development of screening tools and preventive interventions to enhance social integration and economic participation. Objective: To test the association between behaviors at age 6 years and employment earnings at age 33 to 35 years. Design, Setting, and Participants: This study obtained data from the Quebec Longitudinal Study of Kindergarten Children, a population-based sample of boys and girls (n = 3020) born in 1980 or 1981 in Quebec, Canada, and followed up from January 1, 1985, to December 31, 2015. The data included behavioral ratings by kindergarten teachers when the children were aged 5 or 6 years and 2013 to 2015 government tax returns of those same participants at age 33 to 35 years. Data were analyzed from September 2017 to December 2018. Main Outcomes and Measures: Mixed-effects linear regression models were used to test the associations between teacher-rated inattention, hyperactivity, aggression, opposition, anxiety, and prosociality at age 6 years and reported annual earnings on income tax returns at age 33 to 35 years. Participant IQ and family adversity were adjusted for in the analysis. Results: The study included 2850 participants, with a mean (SD) age of 35.9 (0.29) years, of whom 1470 (51.6%) were male and 2740 (96.2%) were white. The mean (SD) personal earnings at follow-up were US $33 300 ($27 500) for men and $19 400 ($15 200) for women. A 1-unit increase in inattention score at age 6 years (males mean [SD], 2.47 [2.42] vs females mean [SD], 1.67 [2.07]) was associated with a decrease in annual earnings of $1271.49 (95% CI, -1908.67 to -634.30) for male participants and $924.25 (95% CI, -1424.44 to -425.46) for female participants. A combined aggression-opposition score (males mean [SD] 2.22 [2.52] vs females mean [SD], 1.05 [1.73]) was associated with a reduction in earnings of $699.83 (95% CI, -1262.49 to -137.17) for males only, albeit with an effect size roughly half that of inattention. A 1-unit increase in prosociality score (males mean [SD], 6.12 [4.30] vs females mean [SD], 7.90 [4.56]) was associated with an increase in earnings of $476.75 (95% CI, 181.53-771.96) for male participants only. A 1-SD reduction in inattention score at age 6 years would theoretically restore $3077 in annual earnings for male participants and $1915 for female participants. Conclusions and Relevance: In this large population-based sample of kindergarten children, behavioral ratings at 5-6 years were associated with employment earnings 3 decades later, independent of a person's IQ and family background. Inattention and aggression-opposition were associated with lower annual employment earnings, and prosociality with higher earnings but only among male participants; inattention was the only behavioral predictor of income among girls. Early monitoring and support for children demonstrating high inattention and for boys exhibiting high aggression-opposition and low prosocial behaviors could have long-term advantages for those individuals and society.

A novel methodological framework for multimodality, trajectory model-based prognostication.

INTRODUCTION: Prognostic tools typically combine several time-invariant clinical predictors using regression models that yield a single, time-invariant outcome prediction. This results in considerable information loss as repeatedly or continuously sampled data are aggregated into single summary measures. We describe a method for real-time multivariate outcome prediction that accommodates both longitudinal data and time-invariant clinical characteristics. METHODS: We included comatose patients treated after resuscitation from cardiac arrest who underwent ≥6 h of electroencephalographic (EEG) monitoring. We used Persyst v13 (Persyst Development Corp, Prescott AZ) to generate quantitative EEG (qEEG) features and calculated hourly summaries of whole brain suppression ratio and amplitude-integrated EEG. We randomly selected half of subjects as a training sample and used the other half as a test sample. We applied group-based trajectory modeling (GBTM) to the training sample to group patients based on qEEG evolution, then estimated the relationship of group membership and clinical covariates with awakening from coma and surviving to hospital discharge using logistic regression. We used these parameters to calculate posterior probabilities of group membership (PPGMs) in the test sample, and built three prognostic models: adjusted logistic regression (no GBTM), unadjusted GBTM (no clinical covariates) and adjusted GBTM (all data). We compared these models performance characteristics. RESULTS: We included 723 patients. Group-specific outcome estimates from a 7-group GBTM ranged from 0 to 75%. Compared to unadjusted GBTM, adjusted GBTM calibration was significantly improved at 6 and 12 h, and time to an outcome estimate <10% and <5% were significantly shortened. Compared to simple logistic regression, adjusted GBTM identified a substantially larger proportion of subjects with outcome probability <1%. CONCLUSIONS: We describe a novel methodology for combining GBTM output and clinical covariates to estimate patient-specific prognosis over time. Refinement of such methods should form the basis for new avenues of prognostication research that minimize loss of clinically important information.

Association of Behavior in Boys From Low Socioeconomic Neighborhoods With Employment Earnings in Adulthood.

Importance: Identifying early childhood behavioral problems associated with economic success/failure is essential for the development of targeted interventions that enhance economic prosperity through improved educational attainment and social integration. Objective: To test the association between kindergarten teacher-rated assessments of inattention, hyperactivity, opposition, aggression, and prosociality in boys with their employment earnings at age 35 to 36 years as measured by government tax return data. Design, Setting, and Participants: A 30-year prospective follow-up study analyzing low socioeconomic neighborhoods in Montreal, Quebec, Canada. Boys aged 5 to 6 years attending kindergarten in low socioeconomic neighborhoods were recruited. Teacher-rated behavioral assessments were obtained for 1040 boys. Data were collected from April 1984 to December 2015. Analysis began January 2017. Main Outcomes and Measures: Mixed-effects linear regression models were used to examine the association between teacher ratings of inattention, hyperactivity, opposition, aggression, and prosociality at age 6 years and individual earnings obtained from government tax returns at age 35 to 36 years. The IQ of the child and family adversity were adjusted for in the analysis. Results: Complete data were available for 920 study participants (mean age at follow-up was 36.3 years). Mean (SD) personal earnings at follow-up were $28 865.53 ($24 103.45) (range, $0-$142 267.84). A 1-unit increase in inattention (mean [SD], 2.66 [2.34]; range, 0-8) at age 6 years was associated with decrease in earnings at age 35 to 36 years of $1295.13 (95% CI, -$2051.65 to -$538.62), while a unit increase in prosociality (mean [SD], 8.0 [4.96]; range, 0-20) was associated with an increase in earnings of $406.15 (95% CI, $172.54-$639.77). Hyperactivity, opposition, and aggression were not significantly associated with earnings. Child IQ was associated with higher earnings and family adversity with lower earnings in all models. A 1-SD reduction in inattention at age 6 years was associated with a theoretical increase in annual earnings of $3040.41, a similar magnitude to an equivalent increase in IQ. Conclusions and Relevance: Teacher ratings of inattention and prosociality in kindergarten boys from low socioeconomic neighborhoods are associated with earnings in adulthood after adjustment for hyperactivity, aggression, and opposition, which were not associated with earnings. Interventions beginning in kindergarten that target boys' inattention and enhance prosociality could positively impact workforce integration and earnings.

Development of Aggression Subtypes from Childhood to Adolescence: a Group-Based Multi-Trajectory Modelling Perspective.

The persistence of elevated subtypes of aggression beginning in childhood have been associated with long-term maladaptive outcomes. Yet it remains unclear to what extent there are clusters of individuals following similar developmental trajectories across forms (i.e., physical and indirect) and functions (i.e., proactive and reactive) of aggression. We aimed to identify groups of children with distinct profiles of the joint development of forms and functions of aggression and to identify risk factors for group membership. A sample of 787 children was followed from birth to adolescence. Parent and teacher reports, and standardised assessments were used to measure two forms and two functions of aggressive behaviour, between six and 13 years of age along with preceding child, maternal, and family-level risk-factors. Analyses were conducted using a group-based multi-trajectory modelling approach. Five trajectory groups emerged: non-aggressors, low-stable, moderate-engagers, high-desisting, and high-chronic. Coercive parenting increased membership risk in the moderate-engagers and high-chronic groups. Lower maternal IQ increased membership risk in both high-desisting and high-chronic groups, whereas maternal depression increased membership risk in the high-desisting group only. Never being breastfed increased membership risk in the moderate-engagers group. Boys were at greater risk for belonging to groups displaying elevated aggression. Individuals with chronic aggression problems use all subtypes of aggression. Risk factors suggest that prevention programs should start early in life and target mothers with lower IQ. Strategies to deal with maternal depression and enhance positive parenting while replacing coercive parenting tactics should be highlighted in programming efforts.