Latent Class Mixed Models Research Articles

Characteristics and associated factors of blood lipid trajectories among HIV-infected patients receiving antiretroviral therapy

Objective: To examine characteristics and risk factors of the blood lipid trajectories among HIV-infected patients treated with antiviral therapy (ART). Methods: Based on the retrospective cohort study design, sociodemographic characteristics and baseline laboratory indicators of HIV-infected patients receiving ART from January 2004 to April 2021 in Taizhou, Zhejiang province. The blood lipid trajectories of the subjects was described and classified using the latent class mixed model (LCMM). Multivariate logistic regression was used to determine the risk factors of blood lipid trajectories. The data were analysized by R 3.5.0. software with lcmm package. Results: Among 2 079 HIV-infected patients, the median age (Q1, Q3) was 31 (43, 55) years, and the majority were being male (78.1%, 1 623/2 079) and married (58.7%, 1 221/2 079). BMI ≥24.0 kg/m2 accounted for 18.9% (393/2 079). Heterosexual transmission accounted for 67.7% (1 407/2 079). Three different blood lipid trajectories were classified: inverted U-shaped (2.3%, 48/2 079), progressive (31.3%, 650/2 079), and general trajectory (U-shaped) (66.4%, 1 381/2 079). The inverted U-shaped and progressive trajectory are identified as dangerous trajectories (33.6%). Multivariate logistic regression analysis indicated that compared with 3TC-TDF-EFV antiviral treatment regimen, baseline TC level <5.2 mmol/L, baseline TG level <1.7 mmol/L, BMI 18.5-23.9 kg/m2, baseline CD4+T lymphocytes (CD4) counts <200 cells/μl, antiviral treatment time <5 years,those who had been using 3TC-AZT-EFV antiviral therapy regimen (aOR=1.99,95%CI:1.44-2.77) and those who switched to LPV/r antiviral therapy regimen (aOR=3.17, 95%CI: 2.00-5.01), baseline TC levels were 5.2-6.1 mmol/L (aOR=2.55, 95%CI: 1.92-3.39) and ≥6.2 mmol/L (aOR=5.89,95%CI:3.76-9.25), and baseline TG levels were 1.7-2.2 mmol/L (aOR=2.00, 95%CI: 1.53-2.62) and ≥2.3 mmol/L (aOR=6.51,95%CI:4.97-8.54), respectively, BMI ≥24.0 kg/m2 (aOR=1.44, 95%CI: 1.11-1.88) were more likely to show the dangerous trajectories. BMI <18.5 kg/m2 (aOR=0.55, 95%CI: 0.35-0.86), baseline CD4 counts level was 200-349 cells/μl (aOR=0.67, 95%CI: 0.52-0.87) and baseline CD4 ≥350 cells/μl (aOR=0.71, 95%CI: 0.54-0.94). The duration of antiviral therapy was 5-9 years (aOR=0.74, 95%CI: 0.56-0.99), and ≥10 years (aOR=0.53, 95%CI: 0.22-0.67) were less likely to show the dangerous trajectories. Conclusions: HIV-infected patients showed a dangerous trajectory of blood lipids after ART, which was significantly associated with the use of specific antiviral drugs such as AZT and LPV/r, treatment duration, baseline CD4, TC, TG levels and BMI. It is recommended to strengthen blood lipid monitoring and targeted intervention measure when HIV infected persons start antiviral treatment.

Distinctive kidney function trajectories following left ventricular assist device implantation.

The aim of this study was to assess for distinct kidney function trajectories following left ventricular assist device (LVAD) placement. Cohort studies of LVAD recipients demonstrate that kidney function tends to increase early after LVAD placement, followed by decline and limited sustained improvement. Inter-individual differences in kidney function response may be obscured. We identified continuous flow LVAD implantations in US adults (2016-2017) from INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). Primary outcomes were estimated glomerular filtration rate (eGFR) trajectories pre-implantation to ∼12 months. Latent class mixed models were applied to primary and validation samples. Clinical differences among trajectory groups were investigated. Among 4,615 LVAD implantations, 5 eGFR trajectory groups were identified. The 2 largest groups (Groups 1 and 2) made up >80% of the cohort, and were similar to group average trajectories previously reported, with early eGFR rise followed by decline and stabilization. Three novel trajectory groups were found: worsening followed by sustained low kidney function (Group 3, 10.1%), sustained improvement (Group 4, 3.3%), and worsening followed by variation (Group 5, 1.7%). These groups differed in baseline characteristics and outcomes. Group 4 was younger and had more cardiogenic shock and pre-implantation dialysis; Group 3 had higher rates of pre-existing chronic kidney disease, along with older age. Novel eGFR trajectories were identified in a national cohort, possibly representing distinct cardiorenal processes. Type 1 cardiorenal syndrome may have been predominant in Group 4, and parenchymal kidney disease may have been predominant in Group 3.

Life-Course Trajectories of Physical Activity and Melanoma Risk in a Large Cohort of Norwegian Women.

Physical activity (PA) is a cornerstone in disease prevention and varies throughout life. A pooled analysis of cohort studies and a meta-analysis of cohort studies found positive associations between PA and melanoma risk. However, previous studies focused on PA at specific ages and often lacked information on ultraviolet radiation (UVR) exposure. Using the population-based Norwegian Women and Cancer (NOWAC) cohort, including information on PA and UVR exposure, we estimated life-course PA trajectories from adolescence to adulthood and their associations with melanoma. Total PA across different domains (recreation, occupation, transport, household) was reported for ages 14 and 30 years, and when responding to the questionnaire (31-76 years) using a 10-point scale, validated to rank PA levels in Norwegian females. We estimated life-course PA trajectories using a latent class mixed model in 152,248 women divided into three subcohorts depending on age at questionnaire completion: 31-39 (n = 27,098), 40-49 (n = 52,515) and ≥50 years (n = 72,635). The unique 11-digit identity number of Norwegian citizens was used to link NOWAC to the Cancer Registry of Norway for information on cancer diagnoses, emigration and death. Associations between PA trajectories and melanoma risk were estimated in each subcohort using multivariable Cox regression. Five classes of individual life-course PA trajectories were identified in subcohort 31-39 years (low, moderate, high, decreasing, increasing PA) and four in subcohorts 40-49 and ≥50 years (low, moderate, high, decreasing PA). No significant association was found between life-course PA trajectories and melanoma risk in any subcohort. Hazard ratios (95% confidence intervals) for the high versus moderate trajectory were 0.92 (0.66-1.29), 1.15 (0.97-1.37) and 0.90 (0.78-1.05) for subcohorts 31-39, 40-49 and ≥50 years, respectively. Our results do not support a positive association between PA and melanoma risk found in previous studies, which is important for public health guidelines promoting regular PA.

Healthcare workers’ heterogeneous mental-health responses to prolonging COVID-19 pandemic: a full year of monthly follow up in Finland

BackgroundThe COVID-19 pandemic strained healthcare workers but the individual challenges varied in relation to actual work and changes in work. We investigated changes in healthcare workers’ mental health under prolonging COVID-19 pandemic conditions, and heterogeneity in the mental-health trajectories.MethodsA monthly survey over a full year was conducted for employees of the HUS Helsinki University Hospital (n = 4804) between 4th June 2020 to 28th May 2021. Pandemic-related potentially traumatic events (PTEs), work characteristics (e.g., contact to COVID-19 patients), local COVID-19 incidence, and demographic covariates were used to predict Mental Health Index-5 (MHI-5) and Insomnia Severity Index (ISI) in generalized multilevel and latent-class mixed model regressions.ResultsLocal COVID-19 log-incidence (odds ratio, OR = 1.21, with 95% CI = 1.10–1.60), directly caring for COVID-19 patients (OR = 1.33, CI = 1.10–1.60) and PTEs (OR = 4.57, CI = 3.85–5.43) were all independently associated with psychological distress, when (additionally) adjusting for age, sex, profession, and calendar time. Effects of COVID-19 incidence on mental health were dissociable from calendar time (i.e., evolved in time) whereas those on sleep were not. Latent mental-health trajectories were characterized by a large class of “stable mental health” (62% of employees) and minority classes for “early shock, improving” (14%) and “early resilience, deteriorating” mental health (24%). The minority classes, especially “early shock, improving”, were more likely to live alone and be exposed to PTEs than the others.ConclusionsHealthcare workers faced changing and heterogeneous mental-health challenges as the COVID-19 pandemic prolonged. Adversity and mental ill-being may have accumulated in some employees, and factors like living arrangements may have played a role. Knowledge on employees’ demographic and socioeconomic background, as well as further research on the factors affecting employees’ resilience, may help in maintaining healthy and efficient workforce in the face of a prolonging pandemic.

Heart Failure–Type Symptom Score Trajectories in CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Quality of life in chronic kidney disease (CKD) is impaired by a large burden of symptoms including some that overlap with the symptoms of heart failure (HF). We studied a group of individuals with CKD to understand the patterns and trajectories of HF-type symptoms in this setting. Prospective cohort study. 3,044 participants in the Chronic Renal Insufficiency Cohort (CRIC) without prior diagnosis of HF. Sociodemographics, medical history, medications, vital signs, laboratory values, echocardiographic and electrocardiographic parameters. Trajectory over 5.5 years of a HF-type symptom score (modified Kansas City Cardiomyopathy Questionnaire [KCCQ] Overall Summary Score with a range of 0-100 where<75 reflects clinically significant symptoms). Latent class mixed models were used to model trajectories. Multinomial logistic regression was used to model relationships of predictors with trajectory group membership. Five trajectories of KCCQ score were identified in the cohort of 3,044 adults, 45% of whom were female, and whose median age was 61 years. Group 1 (41.7%) had a stable high score (minimal symptoms, average score of 96); groups 2 (35.6%) and 3 (15.6%) had stable but lower scores (mild symptoms [average of 81] and clinically significant symptoms [average of 52], respectively). Group 4 (4.9%) had a substantial worsening in symptoms over time (mean 31-point decline), and group 5 (2.2%) had a substantial improvement (mean 33-point increase) in KCCQ score. A majority of group 1 was male, without diabetes or obesity, and this group had higher baseline kidney function. A majority of groups 2 and 3 had diabetes and obesity. A majority of group 4 was male and had substantial proteinuria. Group 5 had the highest proportion of baseline cardiovascular disease (CVD). No validation cohort available, CKD management changes in recent years may alter trajectories, and latent class models depend on the missing at random assumption. Distinct HF-type symptom burden trajectories were identified in the setting of CKD, corresponding to different baseline characteristics. These results highlight the diversity of HF-type symptom experiences in individuals with CKD.

Modelling the impact of protein-kinase R allelic variant on HIV biomarkers trajectories by means of latent class mixed models

This paper is based on a retrospective longitudinal study on people living with HIV under antiretroviral treatment (ART) where allelic variants (either heterozygous CT genotype or homozygous CC genotype) have been evaluated at position −168 of the promoter region of the protein kinase R (−168/PKR). In general, antiviral effects of interferon are partially mediated by a RNA-dependent protein kinase (PKR) that, once activated, inhibits protein synthesis. Indeed, activation of PKR response can inhibit HIV replication. To explore the role of allelic variants in shaping dynamics of commonly monitored HIV biomarkers, CD4 cells, CD8 cells and HIV-load were modelled within a latent class mixed model (LCMM) to account for participants’ heterogeneity over time. The estimated models identified two sub-groups from CD4 and HIV-load dynamics, revealing better outcomes for subgroups of participants with the heterozygous CT genotype. Heterozygous CT subjects in one of the two identified subgroups exhibited higher increase of CD4 cells and more marked decrease of HIV-load, over time, with respect to the homozygous CC subjects assigned to the same group.

Five-Year Symptom Trajectories in Nondialysis-Dependent CKD Patients.

Late stages of CKD are characterized by significant symptom burden. This study aimed to identify subgroups within the 5-year trajectories of symptom evolution in patients with CKD and to describe associated patient characteristics and outcomes. Among 2787 participants (66% men) with eGFR <60 ml/min per 1.73 m2 enrolled in the CKD-Renal Epidemiology and Information Network (CKD-REIN) cohort study from July 2013 to May 2016, we assessed symptoms annually using the Kidney Disease Quality of Life-36 (KDQOL-36) questionnaire until December 2020. A total of 9121 measures were reported over follow-up; all participants had symptoms scored for at least one time point. We used a joint latent class-mixed model to distinguish profiles of symptom trajectories. Patient mean age (±SD) at baseline was 67±13 years, and mean eGFR was 33±13 ml/min per 1.73 m2. The prevalence of each symptom ranged from 24% (chest pain) to 83% (fatigue), and 98% of participants reported at least one symptom. After a median (interquartile range) follow-up of 5.3 (3.4-6.0) years, 690 participants initiated KRT, and 490 died before KRT. We identified two profiles of symptom trajectories: a "worse symptom score and worsening trajectory" in 31% of participants, characterized by a low initial symptom score that worsened more than ten points over time, and a "better symptom score and stable trajectory" in 69% of participants, characterized by a high initial score that remained stable. Participants in the worse symptom score and worsening trajectory group had more risk factors for CKD progression at baseline, worse quality of life, and a higher risk of KRT and death before KRT than other participants. This study highlights a significant worsening of symptoms in about one third of the participants, whereas the majority reported low symptom severity throughout the study.

Heterogeneity in Response to MCT and Psychoeducation: A Feasibility Study Using Latent Class Mixed Models in First-Episode Psychosis.

Metacognitive training (MCT) is an effective treatment for psychosis. Longitudinal trajectories of treatment response are unknown but could point to strategies to maximize treatment efficacy during the first episodes. This work aims to explore the possible benefit of using latent class mixed models (LCMMs) to understand how treatment response differs between metacognitive training and psychoeducation. We conducted LCMMs in 28 patients that received MCT and 34 patients that received psychoeducation. We found that MCT is effective in improving cognitive insight in all patients but that these effects wane at follow-up. In contrast, psychoeducation does not improve cognitive insight, and may increase self-certainty in a group of patients. These results suggest that LCMMs are valuable tools that can aid in treatment prescription and in predicting response to specific treatments.

Insight trajectories and their impact on psychosocial functioning: A 10-year follow-up study in first episode psychosis patients.

Insight has been considered a core symptom of psychosis and closely related to functional outcome. However, little is known regarding the role of insight and its progression in different long-term functioning subdomains among First Episode Psychosis (FEP) patients. A total of 209 participants were followed up over a 10-year period. Latent class mixed models were used to identify trajectory classes in each of the three different insight dimensions. Multivariate analyses were performed to explore predictive value of insight dimensions and its long-term trajectories in psychosocial functioning over a 10-year follow-up period including in the analyses a complete set of baseline and follow-up measures. Three different trajectories (improvement, continued awareness, and worsening) were differentiated in each of the insight dimensions, resulting continued awareness the most common trajectory. Awareness into mental illness at baseline represented one of the main predictors of very long-term instrumental and global functioning. Moreover, enhancement/maintenance of illness awareness was significantly related to better interpersonal functioning. Early intervention programs that promote the acquisition of awareness in the very early stages of the psychotic disorder could have a relevant impact on long-term functioning in FEP patients. Insight dimensions showed mostly trait-like properties although a considerable proportion of FEP patients experienced changes in insight dimensions over the follow-up period. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A longitudinal evaluation of alcohol intake throughout adulthood and colorectal cancer risk.

Alcohol intake is an established risk factor for colorectal cancer (CRC); however, there is limited knowledge on whether changing alcohol drinking habits during adulthood modifies CRC risk. Leveraging longitudinal exposure assessments on alcohol intake at different ages, we examined the relationship between change in alcohol intake and subsequent CRC risk. Within the European Prospective Investigation into Cancer and Nutrition, changes in alcohol intake comparing follow-up with baseline assessments were investigated in relation to CRC risk. The analysis included 191,180, participants and 1530 incident CRC cases, with exclusion of the first three years of follow-up to minimize reverse causation. Trajectory profiles of alcohol intake, assessed at ages 20, 30, 40, 50years, at baseline and during follow-up, were estimated using latent class mixed models and related to CRC risk, including 407,605 participants and 5,008 incident CRC cases. Mean age at baseline was 50.2years and the follow-up assessment occurred on average 7.1years later. Compared to stable intake, a 12g/day increase in alcohol intake during follow-up was positively associated with CRC risk (HR = 1.15, 95%CI 1.04, 1.25), while a 12g/day reduction was inversely associated with CRC risk (HR = 0.86, 95%CI 0.78, 0.95). Trajectory analysis showed that compared to low alcohol intake, men who increased their alcohol intake from early- to mid- and late-adulthood by up to 30g/day on average had significantly increased CRC risk (HR = 1.24; 95%CI 1.08, 1.42), while no associations were observed in women. Results were consistent by anatomical subsite. Increasing alcohol intake during mid-to-late adulthood raised CRC risk, while reduction lowered risk.

Exploring trajectories of depressive symptoms in North Korean defectors: A latent class mixed analysis.

BackgroundNorth Korean defectors (NKDs) are known to be vulnerable to depression due to the influence of various psychosocial factors during their settlement process. Therefore, this study aimed to explore different trajectories of depressive symptoms in NKDs and identify predictors of the worsening of depressive symptoms. In particular, the focus was on whether posttraumatic stress disorder (PTSD) functions as a significant predictor.MethodsParticipants consisted of 300 NKDs who settled in South Korea within 3 years of entering in the country. Five waves of longitudinal data collected from 2016 to 2019 were used. In this study, the North Korean Composite International Diagnostic Interview (NK-CIDI), a diagnostic interview tool, was conducted at baseline and depressive symptoms were measured at each wave. Trajectory identification was based on latent class mixed modeling. Logistic regression was used to extract the significant factors predicting a high/increasing depressive symptom trajectory.ResultsTwo trajectories of depressive symptoms were identified: “low/stable symptom” (76.7% of participants) and “high/increasing symptom” (23.3% of participants). Predictors of the high/increasing symptom group were being female and a low use of mental health services. Generalized anxiety disorder, social phobia, and alcohol dependence acted as significant predictors. Although PTSD was not a significant predictor, self-reported PTSD symptom scores were high in the high/increasing symptom group.ConclusionsIdentifying the trajectories of depressive symptoms in NKDs helps identify the risk factors of clinically vulnerable groups. In the process of establishing government-level interventions, it may be helpful to create a therapeutic environment. In addition, when evaluating initial psychiatric problems, it is important to primarily consider NKDs' anxiety levels and alcohol problems. There should also be an appropriate consideration of PTSD symptoms.

Machine learning prediction of posttraumatic stress disorder trajectories following traumatic injury: Identification and validation in two independent samples.

Due to its heterogeneity, the prediction of posttraumatic stress disorder (PTSD) development after traumtic injury is difficult. Recent machine learning approaches have yielded insight into predicting PTSD symptom trajectories. Using data collected within 1 month of traumatic injury, we applied eXtreme Gradient Boosting (XGB) to classify admitted and discharged patients (hospitalized, n = 192; nonhospitalized, n = 214), recruited from a Level 1 trauma center, according to PTSD symptom trajectories. Trajectories were identified using latent class mixed models on PCL-5 scores collected at baseline, 1-3 months posttrauma, and 6 months posttrauma. In both samples, nonremitting, remitting, and resilient PTSD symptom trajectories were identified. In the admitted patient sample, a unique delayed trajectory emerged. Machine learning classifiers (i.e., XGB) were developed and tested on the admitted patient sample and externally validated on the discharged sample with biological and clinical self-report baseline variables as predictors. For external validation sets, prediction was fair for nonremitting versus other trajectories, areas under the curve (AUC = .70); good for nonremitting versus resilient trajectories, AUCs = .73-.76; and prediction failed for nonremitting versus remitting trajectories, AUCs = .46-.48. However, poor precision (< .57) across all models suggests limited generalizability of nonremitting symptom trajectory prediction from admitted to discharged patient samples. Consistency in symptom trajectory identification across samples supports prior studies on the stability of PTSD symptom trajectories following trauma exposure; however, continued work and replication with larger samples are warranted to understand overlapping and unique predictive features of PTSD in different traumatic injury populations.

Changes in blood pressure and cardiovascular disease in middle-aged to older Chinese: the Guangzhou Biobank Cohort Study.

Most studies on the associations of blood pressure (BP) with cardiovascular disease (CVD) risk were based on single or average BP levels. Knowledge on the association between BP trajectories and CVD in middle-aged individuals who are not on antihypertensive medication may inform the care of individuals in this group whose BPs are not controlled. Eight thousand nine hundred and sixty-nine participants aged 50-70 years, without CVD at baseline and not taking antihypertensive medication throughout the study, were included. Four time-points data from the Guangzhou Biobank Cohort Study were used to identify BP trajectories using latent class mixed model. Cox regression was used to investigate the association of BP trajectories with fatal and nonfatal CVD till April 2021. Three SBP trajectories were identified: 'low-slow-increase' characterized by SBP from 110 to 125 mmHg (86.5%); 'low-increase' from 110 to 150 mmHg (8.1%) and 'moderate-increase' from 125 to 155 mmHg (5.4%). Compared with the low-slow-increase group, the moderate-increase had the highest risk of CVD (hazard ratio = 1.76, 95% confidence interval = 1.34-2.29), ischemic heart disease (1.77, 1.01-3.09), myocardial infarction (3.52, 1.58-7.85), all strokes (1.88, 1.37-2.60), ischemic stroke (1.65, 1.10-2.49), haemorrhagic stroke (3.98, 1.30-12.12) and CVD mortality (2.41, 1.55-3.76). Higher risks of CVD (1.27, 1.01-1.61) and ischemic stroke (1.49, 1.07-2.09) in the low-increase group were also found. Most people between 50 and 70 years of age and not taking antihypertensive medication maintained a slow increase SBP trajectory over a follow-up period of approximately 7 years. However, those whose SBPs increased from low and moderate levels were associated with higher CVD risks.

Anxiety Trajectories the First 10 Years After a Traumatic Brain Injury (TBI): A TBI Model Systems Study

ObjectiveDetermine anxiety trajectories and predictors up to 10 years posttraumatic brain injury (TBI). DesignProspective longitudinal, observational study. SettingInpatient rehabilitation centers. Participants2836 participants with moderate to severe TBI enrolled in the TBI Model Systems National Database who had ≥2 anxiety data collection points (N=2836). Main Outcome MeasureGeneralized Anxiety Disorder-7 (GAD-7) at 1, 2, 5, and 10-year follow-ups. ResultsLinear mixed models showed higher GAD-7 scores were associated with Black race (P<.001), public insurance (P<.001), pre-injury mental health treatment (P<.001), 2 additional TBIs with loss of consciousness (P=.003), violent injury (P=.047), and more years post-TBI (P=.023). An interaction between follow-up year and age was also related to GAD-7 scores (P=.006). A latent class mixed model identified 3 anxiety trajectories: low-stable (n=2195), high-increasing (n=289), and high-decreasing (n=352). The high-increasing and high-decreasing groups had mild or higher GAD-7 scores up to 10 years. Compared to the low-stable group, the high-decreasing group was more likely to be Black (OR=2.25), have public insurance (OR=2.13), have had pre-injury mental health treatment (OR=1.77), and have had 2 prior TBIs (OR=3.16). ConclusionsA substantial minority of participants had anxiety symptoms that either increased (10%) or decreased (13%) over 10 years but never decreased below mild anxiety. Risk factors of anxiety included indicators of socioeconomic disadvantage (public insurance) and racial inequities (Black race) as well as having had pre-injury mental health treatment and 2 prior TBIs. Awareness of these risk factors may lead to identifying and proactively referring susceptible individuals to mental health services.

Differential trajectories of tobacco smoking in people at ultra-high risk for psychosis: Associations with clinical outcomes.

ObjectivePeople at ultra-high risk (UHR) for psychosis have a high prevalence of tobacco smoking, and rates are even higher among the subgroup that later develop a psychotic disorder. However, the longitudinal relationship between the course of tobacco smoking and clinical outcomes in UHR subjects is unknown.MethodsWe investigated associations between tobacco smoking and clinical outcomes in a prospective study of UHR individuals (n = 324). Latent class mixed model analyses were used to identify trajectories of smoking severity. Mixed effects models were applied to investigate associations between smoking trajectory class and the course of attenuated psychotic symptoms (APS) and affective symptoms, as assessed using the CAARMS.ResultsWe identified four different classes of smoking trajectory: (i) Persistently High (n = 110), (ii) Decreasing (n = 29), (iii) Persistently Low (n = 165) and (iv) Increasing (n = 20). At two-year follow-up, there had been a greater increase in APS in the Persistently High class than for both the Persistently Low (ES = 9.77, SE = 4.87, p = 0.046) and Decreasing (ES = 18.18, SE = 7.61, p = 0.018) classes. There were no differences between smoking classes in the incidence of psychosis. There was a greater reduction in the severity of emotional disturbance and general symptoms in the Decreasing class than in the High (ES = −10.40, SE = 3.41, p = 0.003; ES = −22.36, SE = 10.07, p = 0.027), Increasing (ES = −11.35, SE = 4.55, p = 0.014; ES = −25.58, SE = 13.17, p = 0.050) and Low (ES = −11.38, SE = 3.29, p = 0.001; ES = −27.55, SE = 9.78, p = 0.005) classes, respectively.ConclusionsThese findings suggests that in UHR subjects persistent tobacco smoking is associated with an unfavorable course of psychotic symptoms, whereas decrease in the number of cigarettes smoked is associated with improvement in affective symptoms. Future research into smoking cessation interventions in the early stages of psychoses is required to shine light on the potential of modifying smoking behavior and its relation to clinical outcomes.

The Association between Longitudinal BMI Patterns in Children and their Parents

ObjectivesParental (maternal and paternal) weight before and after pregnancy has been associated with an increased risk of obesity in the offspring. However, less is known on the longitudinal association between parental and child growth trajectories across early childhood. This work aims to describe parental and child body mass index (BMI) trajectory patterns from birth until adolescence and assess their association.MethodsWe analyzed 1537 single-child families participating in the Applied Research Group for Kids (TARGet Kids! ) cohort (ON, Canada). Children and their parents had repeated measurements of weight and length or height from child's birth to 13 years during scheduled visits with their primary care physician. These measurements were used to calculate BMI for parents and age and sex adjusted BMI z-scores (zBMI) for children based on the World Health Organization. Latent class mixed modeling was used to identify children and parental growth patterns. A loglinear analysis was conducted to study the tri-party interaction between child, maternal, paternal longitudinal patterns. Jaccard distance was used to assess cluster similarity.ResultsWe identified two distinct patterns in children (normal, increasing obesity), mothers (normal, increasing obesity), and fathers (overweight, obesity). The three-way loglinear analysis indicated that the tri-party interaction between children, maternal and paternal growth patterns interaction was significant (χ2 (1) = 15.1, p < .001). 92.1% of children in the normal pattern had mothers in the normal pattern and fathers in the overweight pattern. Cluster similarity was 63% for mothers and children, but 12.5% between fathers and children, with most children from the increasing obesity group with a father in the overweight group.ConclusionsThere is a significant tri-party association between children, maternal and paternal BMI patterns from birth to adolescence. Future studies should aim in studying eating and other health behaviors associated with these relationships at the family level.Funding SourcesJoannah and Brian Lawson Center for Child Nutrition, Ontario Graduate Scholarship, Canadian Institutes of Health Research.

148-LB: Glomerular Filtration Rate Trajectories in Children with Type 1 Diabetes

Background: While children with type 1 diabetes (T1D) may be at risk for chronic kidney disease (CKD) , data describing changes in kidney function from diagnosis is lacking. Currently, Canadian guidelines do not recommend routine monitoring of serum creatinine in these children. As part of a quality improvement initiative, we implemented routine serum creatinine monitoring. In this study, we describe estimated glomerular filtration rate (eGFR) trajectories in children with T1D. Methods: This longitudinal cohort study involved children with T1D followed in the Diabetes Clinic, who had ≥2 eGFR measurements. Data was collected from health records from 2016 to 2021. Annualized change in eGFR was calculated using the Bedside Schwartz equation, and a declining trajectory was defined a priori as &amp;lt;-3 ml/min/1.73m2 per year. Latent class mixed models were used to categorize eGFR trajectories, and patient characteristics were compared between trajectories. Results: Of the 307 participants, 46% were male; the median age at diagnosis and duration of T1D was 6.2 years and 6.9 years, respectively. Three eGFR trajectories were identified: stable-declining from normal baseline (93.8%) , rapidly declining from high baseline (4.5%) , and rapidly inclining from normal baseline (1.6%) . During their follow-up, 68 (22%) patients had an eGFR &amp;lt;90 ml/min/1.73 m2. Increasing BMI and blood pressure were observed in patients with a declining trajectory (46.9% of all patients) . Conclusion: Nearly half of children with T1D in this cohort had a declining eGFR trajectory. Notably, 22% of these children are at risk for CKD (eGFR &amp;lt;90 ml/min/1.73 m2) early in their T1D course. These findings, along with the steady rise in blood pressure, are concerning given the increased risk of CKD and end-stage renal disease in adults with T1D. These data suggest that careful monitoring of serum creatinine and blood pressure at baseline and regular intervals is warranted in children with T1D. Disclosure K. Favel: None. C. Mammen: None. C. Panagiotopoulos: Speaker's Bureau; Eli Lilly and Company. Funding BC Children's Hospital Research Institute, Canucks for Kids Fund Diabetes Legacy Grant (FAS #: F21-02506)

1201-P: Glycemic Response Phenotypes on Metformin Monotherapy in Real-World Diabetes Care

Metformin is the most prescribed initial treatment for type 2 diabetes in many parts of the world. Glycemic response to metformin has been described based on glycemic change - a measure that ignores potential differences in glycemic trajectories or paths between the start and end of metformin monotherapy. We examined HbA1c trajectories over two years in adults treated with metformin and developed prediction models for treatment response. We studied adults treated with metformin alone for &amp;gt;30 days after diabetes diagnosis in the US VA Health System from 20to 2016 who had a minimum of two HbA1c measurements from 90 days prior to two years after the first metformin prescription (N=140,413) . We included all HbA1c measurements (487,6total) during two years after metformin initiation, censoring at addition of a 2nd diabetes medication, metformin discontinuation, nursing home admission, death, or 90-day metformin non-adherence (medication possession ratio &amp;lt;80%) . We used latent class mixed models to identify HbA1c trajectory classes, then used random forests machine learning to predict trajectory class membership based on demographic, laboratory, vital sign, and comorbidity data at the time of diabetes diagnosis. We found three HbA1c trajectories: stably low (89.7% of sample, mean HbA1c decrease from 7.2% to 6.6%) , brisk response (7.1% of sample, mean HbA1c decrease from 11.4% to 7.0%) , and non-response (3.1% of sample, mean HbA1c increase from 8.9% to 10.8%) . Of those in the stably low and brisk response classes at 2 years, 91% maintained HbA1c at ∼7% on metformin alone for 5 years after drug initiation. Random forests yielded prediction models that accurately predicted brisk response (91% accuracy) but not non-response (59% accuracy) . CONCLUSION: Three glycemic response phenotypes were evident by 6 months after metformin monotherapy initiation in real world data and persisted in the vast majority out to 5 years. Early HbA1c surveillance can inform diabetes treatment optimization with durable impact. Disclosure S.Raghavan: None. W.Liu: None. T.Warsavage: None. L.S.Phillips: Other Relationship; Cystic Fibrosis Foundation, Diasyst Inc., Research Support; Abbott Diabetes, AbbVie Inc., Janssen Pharmaceuticals, Inc., Janssen Scientific Affairs, LLC, Pfizer Inc. J.E.Reusch: Advisory Panel; Medtronic. L.Caplan: None. Funding US Department of Veterans Affairs (IK2-CX001907)

On the relation between school and residential location choice: Evidence of heterogeneous strategies from Santiago de Chile

Voucher systems have been vastly discussed on their ability to provide better quality education and more efficient school systems, but also on the role they play on segregation mechanisms through education markets. With free school choice, parents' preferences and the trade-offs they take into account become relevant, as they are free to decide between educational alternatives and are not restricted to their geographical location's school assignment. In this context, the Chilean case is a singular one due to its nationwide, unrestricted, system implementation. Chilean household's preferences have shown to be complex, heterogeneous, and tightly bound to socioeconomic attributes, as well as deeply intertwined with residential location, especially in Santiago, being a source for social and spatial inequities distributed around the city. Comprehending household's sensitivities on both of these choices and their interactions is essential for understanding the city's complex urban and social structure.This paper seeks to understand the existing bond between school and residential location choices through discrete choice models. By constructing a dataset based on Santiago's 2012 travel survey, a latent class mixed logit model was estimated, capturing observed and unobserved factors that determine household's preferences on both choices. The latent class approach defines two different choice strategies: households that prioritize residential location, and households that prioritize school choice. This enables characterization of households' preferences and choice structures.Main findings suggest both strategies are identifiable through household's characteristics, capturing heterogeneity in household's preferences. In addition, unobserved factors linked to access to office opportunities and neighborhood's socioeconomic level in both school and residential locations explain the correlation binding both choices, capturing heterogeneity. Results suggest that, for both segments, distance tends to be a relevant attribute when choosing. Also, households that prioritize school over residential location tend to be more elastic to socioeconomic characteristics in comparison to households that prioritize residence over school. These ‘school first’ decision-makers are characterized by higher incomes, possession of cars, and more residential mobility due to not being homeowners. Understanding this bond, and household's behavior regarding it, should allow policymakers to better plan for the reduction of social and spatial urban inequalities.

Trajectory patterns of SARS-CoV-2 neutralising antibody response in convalescent COVID-19 patients

BackgroundThe adaptive immune responses of COVID-19 patients contributes to virus clearance, restoration of health and protection from re-infection. The patterns of and the associated characteristics with longitudinal neutralising antibody (NAb) response following SARS-CoV-2 infection are important in their potential association with the population risks of re-infection.MethodsThis is a longitudinal study with blood samples and clinical data collected in adults aged 18 or above following diagnosis of SARS-CoV-2 infection. NAb levels were measured by the SARS-CoV-2 surrogate virus neutralisation test (sVNT). Anonymous clinical and laboratory data were matched with surveillance data for each subject for enabling analyses and applying latent class mixed models for trajectory delineation. Logistic regression models were performed to compare the characteristics between the identified classes.ResultsIn 2020–2021, 368 convalescent patients in Hong Kong are tested for NAb. Their seroconversion occur within 3 months in 97% symptomatic patients, the level of which are maintained at 97% after 9 months. The NAb trajectories of 200 symptomatic patients are classified by the initial response and subsequent trend into high-persistent and waning classes in latent class mixed models. High-persistent (15.5%) class patients are older and most have chronic illnesses. Waning class patients (84.5%) are largely young adults who are mildly symptomatic including 2 who serorevert after 10 months.ConclusionsCharacteristic sub-class variabilities in clinical pattern are noted especially among patients with waning NAb. The heterogeneity of the NAb trajectory patterns and their clinical association can be important for informing vaccination strategy to prevent re-infection.