Latent Class Mixture Models Research Articles

Associations of Homeostatic Model Assessment for Insulin Resistance Trajectories With Cardiovascular Disease Incidence and Mortality.

Whether trends in insulin resistance changes are related to the risk of cardiovascular disease (CVD) incidence and mortality remains unclear. We aimed to examine the association of homeostatic model assessment for insulin resistance (HOMA-IR) trajectories with CVD incidence and mortality. Data from 6755 adults aged 40 to 69 years in the Korea Epidemiology and Genome Study were analyzed. During the exposure period (2001-2006), participants were classified into the increasing HOMA-IR trajectory group and the stable HOMA-IR trajectory group using a latent class mixture model. During the event accrual period (2007-2018), information about CVD and mortality were collected. During the median 9.83-year event accrual period, there were 379 (5.6%) new-onset CVD, 535 (7.9%) all-cause mortality, 102 (1.5%) CVD mortality, and 47 (0.7%) major adverse cardiovascular event mortality cases. Compared with the stable HOMA-IR trajectory group, the fully adjusted hazard ratios (95% CIs) for the increasing HOMA-IR trajectory group were 1.59 (1.04-2.44) for incident CVD, 1.87 (1.30-2.69) for all-cause mortality, 2.33 (1.11-4.89) for CVD mortality, and 3.67 (1.38-9.76) for major adverse cardiovascular event mortality. An increasing HOMA-IR appears to be independently and positively related to incident CVD, all-cause mortality, CVD mortality, and major adverse cardiovascular event mortality. Early lifestyle interventions for individuals with increasing HOMA-IR trend could be a practical strategy to prevent CVD and CVD mortality.

Are Physical and Depressive Symptoms Different Between Women and Men With Heart Failure?: An Exploration Using Two Analytic Techniques.

Adults with heart failure (HF) experience a constellation of symptoms; however, understanding of gender differences in HF symptoms remain elusive. The aim of this study was to determine whether there are gender differences in physical and depressive symptoms and symptom patterns in HF using 2 different analytic techniques. We performed a secondary analysis of combined data from 6 studies of adults with HF. Physical symptoms were measured with the HF Somatic Perception Scale, and depressive symptoms were measured with the Patient Health Questionnaire-9. First, we performed propensity matching with the nearest neighbor to examine the average treatment effect for HF Somatic Perception Scale and Patient Health Questionnaire-9 in the matched sample of women and men. Next, we used the entire data set in a latent class mixture model to determine patterns of symptoms. Finally, we calculated predictors of class membership with multinomial logistic regression. The sample (n = 524, 86.5% systolic HF) was 37% women with a mean age of 58.3 ± 13.9 years and mean number of years with HF of 6.9 ± 6.9. Three hundred sixty-six participants were matched on propensity scores; there were no significant gender differences in symptom scores between matched women (n = 183) and men (n = 183). Among all 524 participants, 4 distinct latent classes of symptom patterns indicate that many patients with HF are fatigued, some have more depressive symptoms, and others have significantly more edema or cough. Gender did not predict membership to any symptom pattern. There were significant gender differences in sociodemographics, health behaviors, and clinical characteristics, but not HF symptoms or symptom patterns, using either analytic technique.

Sociodemographic and clinical features of men and women with eating disorders: a diagnosis-matched, retrospective comparison among inpatients.

Eating disorders (EDs) are among the most severe mental disorders in women and men, often associated with high symptom burden and significant limitations in daily functioning, frequent comorbidities, chronic course of illness, and even high mortality rates. At the same time, differences between men and women with EDs remain poorly explored. In this study, we compared 104 men to 104 diagnosis-matched women with EDs regarding sociodemographic and clinical features. Using latent class mixture modelling, we identified four distinct patient subgroups based on their sociodemographic features. Men with EDs had significantly higher odds than women to belong to a "single-childfree-working" class. Moreover, while there were few overall differences in ED-related symptoms and general psychopathology between men and women, single-childfree-working men with EDs presented with higher general psychopathology symptoms than men in the other classes. We discuss how considering sex and gender along with further sociodemographic differences in EDs may help to improve ED diagnosis and treatment.

Patterns of PrEP continuation and coverage in the first year of use: a latent class analysis of a programmatic PrEP trial in Kenya.

Effective PrEP use is critical for impact, but data are limited on common patterns of continuation and coverage among persons using PrEP in real-world settings. Data are from the Partners Scale-Up Project, a programmatic stepped-wedge cluster-randomized trial to integrate PrEP delivery in 25 Kenyan public health facilities conducted between February 2017 and December 2021. We evaluated PrEP continuation using visit attendance and pharmacy refill records, and computed medication possession ratio to define coverage during the first year of use. Latent class mixture models were used to identify and characterize membership to different PrEP continuation patterns. Multinomial logistic regression was used to examine the association between group trajectories and demographic and behaviour characteristics. Overall, 4898 persons initiated PrEP, 54% (2640) were female, mean age was 33 years (standard deviation 11) and 84% (4092) had partners living with HIV. PrEP continuation was 57%, 44%, and 34% at 1, 3, and 6 months, respectively. Four unique trajectories of PrEP coverage were identified: (1) one-fourth (1154) exhibited consistent high coverage throughout the year with 93%, 94%, 96%, and 67% continuing PrEP at months 1, 3, 6, and 12, respectively; (2) 13% (682) showed high coverage trajectory throughout 6 months but coverage rapidly declined thereafter (94%, 93%, 63%, and 10% continued at months 1, 3, 6, and 12, respectively); (3) 18.9% (918) exhibited moderate coverage trajectory with 91% of clients refilling PrEP at month 1 but nearly all dropped-off thereafter (37%, 5%, and 4% continued at months 3, 6, and 12, respectively); and (4) 43.8% (2144) exhibited immediate discontinuation trajectory, in which nearly all did not have any subsequent PrEP refill. Overall, being female, older age, having partners living with HIV or of unknown HIV status were statistically associated with better PrEP continuation trajectories compared to the immediate discontinuation trajectory (p <0.05 for all). In this analysis of a real-world PrEP implementation programme in Kenya, we found four distinct patterns of PrEP continuation, with one-third of users exhibiting consistent high continuation throughout 12 months and two-fifths with immediate discontinuation patterns. These data may help guide tailored interventions to support PrEP continuation in this setting.

Trajectories of glycated hemoglobin of T2DM and progress of arterial stiffness: a prospective study

AimThis study aimed to describe the different trajectories groups of HbA1c during the long-term treatment of diabetes and explore the effect of glycemic control on the progression of arterial stiffness.MethodThe study participants registered at the National Metabolic Management Center (MMC) of Beijing Luhe hospital. The latent class mixture model (LCMM) was used to identify distinct trajectories of HbA1c. We calculated the change value of baPWV (ΔbaPWV) of each participant between the whole follow-up time as the primary outcome. Then we examined the associations between each HbA1c trajectory pattern and ΔbaPWV using covariate-adjusted means (SE) of ΔbaPWV, which were calculated by multiple linear regression analyses adjusted for the covariates.ResultsAfter data cleaning, a total of 940 type 2 diabetes patients aged 20–80 years were included in this study. According to the BIC, we identified four discrete trajectories of HbA1c: Low-stable, U-shape, Moderate-decrease, High-increase, respectively. Compared with the low-stable group of HbA1c, the adjusted mean values of baPWV were significantly higher in U-shape, Moderate-decrease, and High-increase groups (all P < 0.05, and P for trend < 0.001), the mean values (SE) were 82.73 (0.08), 91.19 (0.96), 116.00 (0.81) and 223.19 (11.54), respectively.ConclusionWe found four different trajectories groups of HbA1c during the long-term treatment of diabetes. In addition, the result proves the causal relationship between long-term glycemic control and arterial stiffness on a time scale.

#5510 CKD-ASSOCIATED PRURITUS SEVERITY AND ITS ASSOCIATION WITH BODY DISTRIBUTION AND EQ-5D HEALTH-RELATED QUALITY OF LIFE IN HAEMODIALYSIS PATIENTS

Abstract Background and Aims Chronic Kidney Disease associated pruritus (CKD-aP) is common affecting 40% of people with kidney disease receiving dialysis. It is associated with decreased health-related quality of life (HRQoL) as assessed using disease-specific instruments. A better understanding of how the severity of CKD-aP is related to the distribution of affected body parts and generic of HRQoL assessed using the EQ-5D instrument could improve the identification, assessment, and treatment of CKD-aP including advocating for access to new therapies. Method Prevalent in-centre haemodialysis patients from five centres prospectively completed the EQ-5D-5L HRQoL questionnaires, the severity-based worst itch numeric rating scale (WI-NRS) and multi-dimensional 5-D itch pruritus disease specific quality of life instruments. Latent class mixture models were used to identify clusters of patients with similarly affected body parts as assessed through the 5-D itch and map the pruritus measures to the EQ-5D utility value (1 being perfect health and 0 being dead, heavily skewed). Patient demographics, comorbidities, dialysis prescription and anti-pruritus medications were collected. Results Pruritus data on 485 respondents were obtained. No pruritus was reported in 164 (33.8%), with 117 (24.1%) reporting mild, 123 (25.4%) reporting moderate and 81 (16.7%) reporting severe pruritus. Commonly affected body parts included groin (22%), upper arms (21%), forearms (11%), and back (10%). Anti-pruritus medication use across CKD-aP severity (none to severe) was 40.6%, 38.5%, 36.6% and 55.6%, and varied by body part with 38.8%, 21.0% and 14.5% use in those affected in the upper limbs, groin and lower legs respectively. Latent class analysis identified three groups of patients who had progressively worsening severity and number of body parts affected, but the distribution of affected body parts was relatively constant (left-hand figure) and reduction in EQ-5D by affected body part was similar. Although the WI-NRS and 5-D itch instruments correlated with each other, only the 5-D itch had a strong relationship with EQ-5D-3L: Controlling for age, sex, diabetes, and years receiving dialysis, predicted EQ-5D utility dropped linearly from 0.69 to 0.41 (right-hand figure). Conclusion Contemporary UK data shows CKD-aP remains highly prevalent amongst people with kidney failure on dialysis. Severe CKD-aP was commonly reported despite half of the patients with severe CKD-aP receiving antipruritic medication, illustrating a high unmet need and likely undertreated. Although there were similar reductions in HRQoL, medication use varied by body part and those whose groin is affected may be reporting other body parts to access therapies. High use of CKD-aP medications in none or mild severity may represent more severely affected individuals benefiting from these drugs as the cross-sectional nature of the study means those who reported no pruritus may have had pruritus in the past which resolved in response to the medications prescribed and reported in these analyses. Overall, as it worsens CKD-aP appears to affect a similar distribution of body parts. Pruritus instruments that include domains that are broader than just pruritus severity more closely approximate the EQ-5D generic HRQoL measure and therefore more strongly advocate for the value of treating this unpleasant condition. Funded by CSL Vifor.

Associations of alcohol and cannabis use with change in posttraumatic stress disorder and depression symptoms over time in recently trauma-exposed individuals.

Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians. In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance. Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12. Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.

Microvascular Cerebral Blood Flow Monitoring Detects Response to Intrathecal Nicardipine Treatment for Vasospasm (S4.005)

<h3>Objective:</h3> Determining the effect of intrathecal nicardipine on microvascular cerebral blood flow <h3>Background:</h3> A common complication of subarachnoid hemorrhage is cerebral vasospasm, which is associated with delayed cerebral ischemia (DCI), a predictor of poor functional outcome. Intrathecal administration of nicardipine (ITn) upon detection of vasospasm holds promise as a treatment that reduces the incidence of secondary stroke. Herein, we utilize a novel non-invasive optical measurement of regional microvascular perfusion to determine the effect of ITn on microvascular cerebral blood flow (CBF). <h3>Design/Methods:</h3> In this observational study, we prospectively studied 20 patients with non-traumatic subarachnoid hemorrhage who were treated with ITn as part of usual care for evolving cerebral vasospasm. Regional microvascular CBF in the frontal cortex was measured with diffuse correlation spectroscopy for up to 90 min after the first treatment dose, and for a subset of patients, on days 2 and 3 of treatment as well. Outcome was assessed as the presence of DCI on imaging. <h3>Results:</h3> CBF increased significantly over the 90 min of monitoring after the first and subsequent doses (p&lt;0.001) in the absence of systemic hemodynamic changes. In general, the CBF response was heterogeneous across subjects. Using data from the first dose, a latent class mixture model was used to classify 19/20 patients into two distinct classes of cerebral blood flow response: patients in class 1 (n=6) showed a decrease or no change in CBF, while patients in class 2 (n=13) showed a pronounced increase in CBF in response to nicardipine. The incidence of DCI was 5/6 in class 1 and 0/13 in class 2 (p&lt;0.001). Similar significant differences in CBF response in patients with and without DCI were also observed on days 2 and 3 (both p&lt;0.001). <h3>Conclusions:</h3> Microvascular CBF monitoring is feasible in critically ill subarachnoid hemorrhage patients. CBF response may provide a valuable biomarker for treatment responsiveness. <b>Disclosure:</b> Dr. Sathialingam has nothing to disclose. Mr. Cowdrick has nothing to disclose. Ms. Urner has nothing to disclose. Ms. Liew has nothing to disclose. Dr. Sigman has nothing to disclose. Dr. Akbik has nothing to disclose. Dr. Samuels has received publishing royalties from a publication relating to health care. Dr. Kandiah has nothing to disclose. Dr. Buckley has received research support from Global Blood Therapeutics. Dr. Buckley has received research support from NIH. Ofer Sadan has received intellectual property interests from a discovery or technology relating to health care.

Microvascular cerebral blood flow response to intrathecal nicardipine is associated with delayed cerebral ischemia.

One of the common complications of non-traumatic subarachnoid hemorrhage (SAH) is delayed cerebral ischemia (DCI). Intrathecal (IT) administration of nicardipine, a calcium channel blocker (CCB), upon detection of large-artery cerebral vasospasm holds promise as a treatment that reduces the incidence of DCI. In this observational study, we prospectively employed a non-invasive optical modality called diffuse correlation spectroscopy (DCS) to quantify the acute microvascular cerebral blood flow (CBF) response to IT nicardipine (up to 90 min) in 20 patients with medium-high grade non-traumatic SAH. On average, CBF increased significantly with time post-administration. However, the CBF response was heterogeneous across subjects. A latent class mixture model was able to classify 19 out of 20 patients into two distinct classes of CBF response: patients in Class 1 (n = 6) showed no significant change in CBF, while patients in Class 2 (n = 13) showed a pronounced increase in CBF in response to nicardipine. The incidence of DCI was 5 out of 6 in Class 1 and 1 out of 13 in Class 2 (p < 0.001). These results suggest that the acute (<90 min) DCS-measured CBF response to IT nicardipine is associated with intermediate-term (up to 3 weeks) development of DCI.

Abstract P6-03-02: Social determinants, food deserts, and their combined contribution to breast cancer mortality

Abstract Recent studies have found that both food deserts (FD) and lower socio-economic status (SES) are individually associated with increased breast cancer mortality in the US. However, further work is needed to investigate their combined contribution to breast cancer mortality. Furthermore, valid inference for area-level disease mapping requires careful consideration of spatial clustering. In our study, we utilize data from the USDA Food Access Research Atlas and the American Community Survey. Breast cancer mortality data come from the National Center of Health Statistics 2014 report. We consider a latent class mixture model to determine deprivation categories which incorporate six SES proportion variables (no car, poverty, no HS graduation, crowded housing, unemployment, crowded housing), two FD (Low income and &amp;gt; 1 mile from supermarket and receiving snap benefits and &amp;gt; 1 mile from supermarket) variables. Our latent class model has three levels: Low, Moderate, and High, making up 36.6%, 45.6%, and 17.8% of US counties, respectively. We then incorporated these levels as a fixed effect in a Bayesian hierarchical spatial negative binomial model using R-INLA. In this model, we account for both spatially structured and unstructured effects. Counties classified as “High” on our deprivation categories were associated with a 50% increase in breast cancer mortality rates (95% CrI: [1.12, 2.02]). Also, the county proportion of women &amp;gt;65 was significantly associated with 1.42 times higher breast cancer mortality (95% CrI [1.37, 1.42]). Policies that allow for access in the face of deprivation may contribute to lower overall breast cancer mortality. Citation Format: Kara McCormack. Social determinants, food deserts, and their combined contribution to breast cancer mortality [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-03-02.

Abstract 57: Distinct Gestational Blood Pressure Trajectories Predict Pregnancy, Birth, and Postpartum Health in a Low-Income Hispanic Population

Objective: Blood pressure (BP) typically drops to a nadir around 20 to 24 gestation weeks in a normal pregnancy. Distinct BP trajectories over pregnancy could reveal underlying cardiovascular function and predict future cardiovascular risk, but little is known about BP trajectories in Hispanic women. We aim to identify BP trajectories during pregnancy among low-income, Hispanic women. Methods: In the prospective Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort, we abstracted clinic BP measures of 732 participants who had an average of 12 BP measures over pregnancy, ranging from 4 to 41 weeks. We used latent class mixture modeling to identify BP trajectories. We examined associations of population characteristics, pregnancy and birth outcomes, and 1-year postpartum BP with the identified trajectories. Results: We identified three distinct BP trajectories ( Figure ). Compared to the majority (class 1, n=569), the consistently high class 2 (14.8%, 108) was characterized by a higher pre-pregnancy BMI (ppBMI, 32.3±7.6 vs. 27.6 ±6.1 Kg/m 2 ) and a higher proportion of having college or above education (21.3% vs. 14.9%), while the high-low-high U-shape class 3 (7.5%, 55) had a higher ppBMI (32.0±7.9 Kg/m 2 ) but lower proportion of having college or above education (9.1%). Risk of preeclampsia was the highest in class 3 (43.6%), followed by class 2 (10.2%) and class 1 (6.0%), while the risk of gestational diabetes was the highest in class 2 (14.8%), followed by class 1 (7.9%) and class 3 (7.3%). Birthweight and gestational duration were both significantly lower in class 3 than classes 1 and 2. One-year postpartum systolic BP was significantly higher in class 2 (120.2±16.0 mmHg) and class 3 (122.4±16.0 mmHg) than class 1 (111.7±26.2 mmHg) after adjusting for maternal age, pre-pregnancy BMI, parity, and education. Conclusion: Elevated blood pressure may develop into district trajectories in pregnancy that further predict pregnancy and birth outcomes, as well as postpartum blood pressure.

Latent Trajectories of Haematological, Hepatic, and Renal Profiles after Oil Spill Exposure: A Longitudinal Analysis.

Exposure to polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) in crude oil has carcinogenic effects on various organ systems. This longitudinal cohort study examined the effects of oil spill exposure on the haematological, hepatic, and renal profiles of Rayong oil spill clean-up workers. The sample included 869 clean-up workers from the Rayong oil spill. Latent class mixture models were used to investigate and classify the longitudinal trajectories and trends of the haematological, hepatic, and renal indices. Subgroup analysis was used to evaluate the association between the urinary metabolites of PAHs and VOCs and haematological, hepatic, and renal parameters. Most clean-up workers (97.6%) had increasing levels of white blood cells (WBCs) (0.03 × 103 cells/µL), 94.90% of the workers had a significantly increasing trend of blood urea nitrogen (0.31 mg/dL per year), and 87.20% had a significantly increasing trend of serum creatinine (0.01 mg/dL per year). A high-decreasing trend of WBCs was seen in 2.42% (-0.73 × 103 per year). Post-exposure changes in haematological, renal, and hepatic profiles are present in workers exposed to the Rayong oil spill. This indicates possible long-term health complications and worsening renal function after exposure to PAHs and VOCs in crude oil.

AFFECTIVE TRAJECTORIES: RISK OF DEMENTIA AND UNDERLYING STRUCTURAL BRAIN VARIABLES IN OLDER WOMEN

Abstract Understanding how trajectories of positive and negative affect relate to dementia risk and underlying structural brain variables is important for dementia prevention. We examined associations between annually assessed Positive and Negative Affect Scale subscales and dementia risk (2000-18) among cognitively-intact community-dwelling women (N=948; aged 72.9±3.7) from the Women’s Health Initiative Study of Cognitive Aging (years 2000-2010) and Magnetic Resonance Imaging Study (2005-2006). Joint latent class mixture models were constructed to identify latent classes of women with similar trajectories of affect and dementia risk over time. Multinomial and logistic regressions examined whether structural MRI measures predicted latent class membership (adjusted for sociodemographic, lifestyle, clinical characteristics, and intracranial volume). Two latent classes of positive affect (high stable:88% and decreasing:12%) and four classes of negative affect (Minimal stable:75%; high stable:4%; emerging:12%; moderate decreasing:9%) were identified. With the high stable trajectory as referent, women with decreasing positive affect were more likely to develop dementia (HR=4.33;p&amp;lt;.001). The odds of being classified as this high-dementia risk group were increased among women with more (per SD) global small vessel ischemic disease (SVID;OR=1.42;p&amp;lt;.001), deep white matter SVID (OR=1.93;p&amp;lt;.001), and smaller parahippocampal volumes (OR=1.41;p=.016). For negative affect, with minimal stable negative affect as referent, women with smaller hippocampal volumes were more likely to be classified as having moderate decreasing negative affect (OR=1.45;p=.024) while emerging negative affect was associated with higher dementia risk (HR=2.00;p=.014). These findings highlight the importance of changes in affect in later-life with dementia risk and potential underlying role of cerebrovascular disease and medial temporal lobe structures.

528: CEREBRAL BLOOD FLOW MONITORING PREDICTS RESPONSE TO INTRATHECAL NICARDIPINE TREATMENT FOR VASOSPASM

Introduction: A common complication of subarachnoid hemorrhage is cerebral vasospasm, which is associated with delayed cerebral ischemia, a predictor of poor functional outcome. Intrathecal administration of nicardipine upon detection of vasospasm holds promise as a treatment that reduces the incidence of secondary stroke. Herein, we utilize a novel non-invasive optical measurement of regional microvascular perfusion to determine the effect of intrathecal nicardipine on microvascular cerebral blood flow (CBF). Methods: In this observational study, we prospectively studied 20 patients with non-traumatic subarachnoid hemorrhage who required an external ventricular drain to treat obstructive hydrocephalus and who were treated with intrathecal nicardipine as part of usual care for evolving cerebral vasospasm. Regional microvascular CBF in the frontal cortex was measured with diffuse correlation spectroscopy for up to 90 min after the first treatment dose, and for a subset of patients, on days 2 and 3 of treatment as well. Outcome was assessed as the presence of delayed cerebral ischemia on imaging. Results: CBF increased significantly over the 90 min of monitoring after the first dose (p< 0.001) in the absence of systemic hemodynamic changes. CBF also increased on average in response to repeated doses on days 2 and 3, although the magnitude of this response decreased with successive treatment day. In general, the CBF response was heterogeneous across subjects. Using data from the first dose, a latent class mixture model was used to classify 19/20 patients into two distinct classes of cerebral blood flow response: patients in class 1 (n=6) showed a decrease or no change in CBF, while patients in class 2 (n=13) showed a pronounced increase in CBF in response to nicardipine. The incidence of delayed cerebral ischemia was 5/6 in class 1 and 0/13 in class 2 (p< 0.001). Similar significant differences in CBF response in patients with and without delayed cerebral ischemia were also observed on days 2 and 3 (both p< 0.001). Conclusions: These results suggest that the CBF response to intrathecal nicardipine reaches a therapeutic steady state with successive treatment days. Moreover, the CBF response may provide a valuable biomarker for treatment responsiveness.

Defining the ATN framework using longitudinal biomarker trajectories reveals an emerging amyloid accumulation group

AbstractBackgroundThe ATN framework is defined by cross‐sectional biomarkers of β‐amyloid (Aβ), tau and neurodegeneration. Given that prevention trials, e.g., AHEAD 3‐45, are focused on individuals who have lower Aβ than established thresholds, we investigated whether defining the ATN framework using longitudinal biomarker trajectories might better identify an at‐risk sample within this boundary. Here, we applied a data‐driven method to re‐define the ATN with longitudinal biomarker data from the Harvard Aging Brain Study (HABS) and we then replicated this longitudinal framework in ADNI.Method157 HABS participants were clinically‐normal at baseline and underwent at least two Pittsburgh Compound‐B [PiB]‐PET, Flortaucipir‐PET, and T1‐weighted MRI scans. To define longitudinal ATN, we applied latent class mixture models (LCMM) to each biomarker (global Aβ DVR, entorhinal tau SUVr, ICV‐adjusted hippocampal volume) separately, adjusting for age, and including random intercept and slopes. Akaike information criteria (AIC) determined the best‐fitting models out of two‐group or three‐group solutions with linear or spline‐link functions. We compared longitudinal ATN profiles on demographics and an optimized estimate of cognitive change (derived from longitudinal Preclinical Alzheimer Cognitive Composite (PACC) data).ResultAβ trajectories (Fig.1a) were best categorized by one stable (A→) and two accumulating subgroups, a predominantly amyloid‐negative at baseline subgroup (A‐↑) and an entirely amyloid positive at baseline subgroup (A+↑). Tau (Fig.1b) and neurodegeneration (Fig.1c) were optimally defined by stable (T→/N→) vs accumulating/atrophying (T↑/N↑) groups, respectively. These groups were replicated in ADNI (Fig.2). The entire A‐↑ subgroup were stable on T and N (A‐↑/T→/N→) and were predominantly A‐/T‐/N‐ at baseline (86%; Table 1). By contrast, 38% of A+↑ individuals changed on T, or T&amp;N. A‐↑/T→/N→ demographically most closely resembled the longitudinally‐stable ATN group (A→/T→/N→), but were older, more likely to carry e4+ and exhibited higher baseline Aβ (Table 2). Although demonstrating Aβ accumulation, A‐↑/T→/N→ did not exhibit greater cognitive decline versus the stable group (A→/T→/N→; Fig. 3).ConclusionOur findings suggest that a longitudinal biomarker run‐in of Aβ‐PET may be useful for the identification of early‐risk groups for prevention trials. Future work will establish whether other features (e.g. genetics, neuroinflammatory markers, functional imaging) can help to distinguish this cohort.

Consistent trajectories of rhinitis control and treatment in 16,177 weeks: The MASK-air® longitudinal study.

Data from mHealth apps can provide valuable information on rhinitis control and treatment patterns. However, in MASK-air®, these data have only been analyzed cross-sectionally, without considering the changes of symptoms over time. We analyzed data from MASK-air® longitudinally, clustering weeks according to reported rhinitis symptoms. We analyzed MASK-air® data, assessing the weeks for which patients had answered a rhinitis daily questionnaire on all 7 days. We firstly used k-means clustering algorithms for longitudinal data to define clusters of weeks according to the trajectories of reported daily rhinitis symptoms. Clustering was applied separately for weeks when medication was reported or not. We compared obtained clusters on symptoms and rhinitis medication patterns. We then used the latent class mixture model to assess the robustness of results. We analyzed 113,239 days (16,177 complete weeks) from 2590 patients (mean age ± SD=39.1 ± 13.7 years). The first clustering algorithm identified ten clusters among weeks with medication use: seven with low variability in rhinitis control during the week and three with highly-variable control. Clusters with poorly-controlled rhinitis displayed a higher frequency of rhinitis co-medication, a more frequent change of medication schemes and more pronounced seasonal patterns. Six clusters were identified in weeks when no rhinitis medication was used, displaying similar control patterns. The second clustering method provided similar results. Moreover, patients displayed consistent levels of rhinitis control, reporting several weeks with similar levels of control. We identified 16 patterns of weekly rhinitis control. Co-medication and medication change schemes were common in uncontrolled weeks, reinforcing the hypothesis that patients treat themselves according to their symptoms.

Abstract 13549: Plasma Metabolomics Identify Major Differences in Symptoms and Quality of Life Among Patients With Heart Failure

BACKGROUND: Plasma metabolites predict survival among patients with heart failure (HF), but symptom burden is critical, underpinning functional status and quality of life (QOL). The relationship of plasma metabolome and symptom or QOL phenotypes is not established. AIM: We conducted a latent class analysis to identify plasma metabolite patterns in relation to symptoms and QOL among HF patients. METHOD: A prospective HF registry collected baseline plasma for metabolomics and health status. A total of 13 metabolites (organic acids, amino acids, acylcarnitines) previously shown to predict survival were used in analyses. QOL and symptoms were quantified using the Kansas City Cardiomyopathy Questionnaire. Distinct metabolite patterns were identified using latent class mixture modeling. Linear regression tested the association of metabolite profile with QOL and total symptom scores controlling for age, gender, and NYHA class. One-way ANOVA characterized group differences. Results: A total of 1192 patient participants had complete metabolite and health status data for analysis. Among these patients, 62% were male, 48.5% self-identified as African-American and average age was 68 years (± 12). The majority (58%) were non-ischemic, 56% were NYHA Class I and comorbid conditions were common (90% hypertension, 72% hyperlipidemia, 43% diabetes). Three metabolite latent profiles (MLPs) were identified. MLP 1 had significantly higher NT-proBNP, worse functional class (72% NYHA 3-4) and lower ejection fractions (0.30 vs 0.35) compared with MLP 2 and 3. MLP class predicted symptoms (R 2 =0.39, F(7,1182)=F 107, p=0.006) and total QOL scores (R 2 =0.31, F(7, 1182)=F77.3, p=&lt;0.001) controlling for age, gender and NYHA class. The magnitude of difference was high; among MLP 2 and 3 compared to MLP1, total symptom scores ranged 7-9 points better and QOL 12-15 points better. No differences in age, gender or race were found across MLPs. Conclusion: Three latent metabolite profiles were identified that independently associated with significant differences in symptoms and QOL. Considering a minimal clinically important difference in KCCQ scores is 5 points, our results demonstrated large differences in patient reported outcomes related to plasma metabolite profile.

Clustering longitudinal data using R: A Monte Carlo Study

The analysis of change within subjects over time is an ever more important research topic. Besides modelling the individual trajectories, a related aim is to identify clusters of subjects within these trajectories. Various methods for analyzing these longitudinal trajectories have been proposed. In this paper we investigate the performance of three different methods under various conditions in a Monte Carlo study. The first method is based on the non-parametric k-means algorithm. The second is a latent class mixture model, and the third a method based on the analysis of change indices. All methods are available in R. Results show that the k-means method performs consistently well in recovering the known clustering structure. The mixture model method performs reasonably well, but the change indices method has problems with smaller data sets.

Functional Improvement Trajectories After Surgery (FIT After Surgery) study: protocol for a multicentre prospective cohort study to evaluate significant new disability after major surgery in older adults

IntroductionOlder adults prioritise surviving surgery, but also preservation of their functional status and quality of life. Current approaches to measure postoperative recovery, which focus on death, complications and length of...

Dynamics of circulating calprotectin accurately predict the outcome of moderate COVID-19 patients.

SummaryBackgroundSevere COVID-19 is associated with a high circulating level of calprotectin, the S100A8/S100A9 alarmin heterodimer. Baseline calprotectin amount measured in peripheral blood at diagnosis correlates with disease severity. The optimal use of this biomarker along COVID-19 course remains to be delineated.MethodsWe focused on patients with a WHO-defined moderate COVID-19 requiring hospitalization in a medical ward. We collected plasma and serum from three independent cohorts (N = 626 patients) and measured calprotectin amount at admission. We performed longitudinal measures of calprotectin in 457 of these patients (1461 samples) and used a joint latent class mixture model in which classes were defined by age, body mass index and comorbidities to identify calprotectin trajectories predicting the risk of transfer into an intensive care unit or death.FindingsAfter adjustment for age, sex, body mass index and comorbidities, the predictive value of baseline calprotectin in patients with moderate COVID19 could be refined by serial monitoring of the biomarker. We discriminated three calprotectin trajectories associated with low, moderate, and high risk of poor outcome, and we designed an algorithm available as online software (https://calpla.gustaveroussy.fr:8443/) to monitor the probability of a poor outcome in individual patients with moderate COVID-19.InterpretationThese results emphasize the clinical interest of serial monitoring of calprotectin amount in the peripheral blood to anticipate the risk of poor outcomes in patients with moderate COVID-19 hospitalized in a standard care unit.FundingThe study received support (research grants) from ThermoFisher immunodiagnostics (France) and Gustave Roussy Foundation.