Functional Trajectories Research Articles

Societal recovery trajectories in people with a psychotic disorder in long term care: a latent class growth analysis.

For many individuals with a psychotic disorder societal recovery is not accomplished. Research on societal recovery trajectories is mostly focussed on patients with a first episode psychosis. The present study aims to identify distinct societal trajectories in those with long duration of illness, through the identification of patient subgroups that are characterized by homogeneous trajectories. Longitudinal data were used from an ongoing dynamic cohort in which people with a psychotic disorder receive yearly measurements to perform a latent class growth analysis. Societal functioning was assessed with the Functional Recovery tool, consisting of three items (1) daily living and self-care, (2) work, study and housekeeping, and (3) social contacts. Furthermore, logistic regression was used to compare subgroups with similar societal recovery at baseline, but distinct trajectories. A total of 1476 people were included with a mean treatment time of 19 years (SD 10.1). Five trajectories of functioning were identified, a high stable (24.5%), a medium stable (28.3%), a low stable (12.7%), a high declining (11.2%) and a medium increasing subgroup (23.3%). Predictors for not deteriorating included happiness, recent hospitalisation, being physically active, middle or higher education and fewer negative symptoms. Predictors for improving included fewer positive and negative symptoms, fewer behavioural problems and fewer physical and cognitive impairments. While the majority of individuals show a stable trajectory over four years, there were more patients achieving societal recovery than patients deteriorating. Predictors for improvement are mainly related to symptoms and behavioural problems, while predictors for deteriorating are related to non-symptomatic aspects such as physical activity, happiness and level of education.

Recovery Trajectories of Patient-reported Outcomes After Surgery for Degenerative Cervical Myelopathy: A Bayesian Latent Class Modeling Approach.

Retrospective study. The aim of this study was to identify recovery trajectory clusters after surgery for degenerative cervical myelopathy (DCM), as well as to determine clinical and imaging characteristics associated with functional recovery trajectories. Accurate prediction of postsurgical neurological recovery for the individual patient with DCM is challenging due to varying patterns of functional recovery. Latent class Bayesian models can model individual patient patterns and identify groups of patients with similar phenotypes for personalized prognostication. A prospective single-center study of 70 consecutive patients with DCM undergoing elective cervical spine decompression for DCM between 2010 and 2017 was performed. Outcomes were recorded using the modified Japanese Orthopedic Association (mJOA), Neck Disability Index (NDI), and the Short Form-36 Physical Component Score (SF-36 PCS) at 3, 6, 12, and 24 months. Recovery trajectories were constructed based on unsupervised Bayesian latent class modeling. Clinical and imaging predictors of recovery trajectories were also determined. Recovery after surgery for DCM showed 3 distinct recovery trajectory clusters for each outcome. The commonest recovery trajectory was sustained improvement for the mJOA (41.1%), stagnation for the NDI (60.3%), and stability for the SF-36 PCS (46.6%). Age, duration of symptoms, and baseline disability were the strongest predictors of each recovery trajectory. Degree of cord compression, neck pain, and intramedullary T2-hyperintensity were predictive of NDI and SF-36 PCS but not mJOA recovery trajectory. Sex was associated with the NDI recovery trajectory but not SF-36 PCS and mJOA recovery trajectories. Using prospective data and a data-driven approach, we identified 3 distinct recovery trajectory clusters and associated factors for mJOA, NDI, and SF-36 PCS in the first 24 months after surgery for DCM. Our results can enhance personalized clinical prognostication and guide patient expectations at different time points after surgery for DCM.

Recovery from severe cardio-respiratory failure: the trajectory of muscle mass, strength, function and health related quality of life

Abstract Background The impact of intensive care unit acquired weakness (ICUAW) is associated with reduced muscle mass, strength, function and health related quality of life (HRQoL). Patients suffering from severe cardio-respiratory failure are known to lose considerable muscle mass and strength in the first 7 days of admission to the intensive care unit (ICU). Furthermore, patients surviving critical illness have a considerable less HRQoL and physical function with long term outcomes such as inability to return to work being reported. However, more information regarding muscle loss and recovery is required when patients leave hospital. Currently there are no treatments for ICUAW as once the process is established management is supportive, such as physical therapy. Purpose We Sought to investigate the effects of severe cardio-respiratory failure, in patients receiving extra corporeal membrane oxygenation (ECMO), on ICUAW (including muscle mass, strength, function and HRQoL). Researching a real life model of ICUAW allows the observation of the loss of muscle mass and strength in the first stages of critical illness and severe cardio-respiratory failure. Methods Adults receiving ECMO for severe cardiorespiratory failure were included. Muscle mass was measured using ultrasound of the rectus femoris cross sectional area (RFcsa). Muscle strength was measured using hand held dynamometry for both hand held grip strength and isometric leg extension. HRQoL was measured using the EQ-5D-5L. Function was measured using the short physical performance battery (SPPB). Measurements were taken on day 0, day 7, ICU discharge, hospital discharge and at out-patient follow up. Results 17 patients were recruited with 10 patients completing follow up. Patients lost 24% muscle mass in the first 7 days of ICU admission and ECMO initiation, with muscle loss continuing up until ICU discharge. Contrary to the hypothesis only 50% of the patients were seen to recover muscle mass at follow up. Strength and function all considerably improved between ICU discharge and out patient follow up. The EQ5D crosswalk index supported this suggesting considerable functional improvement. Conclusion Patients in severe cardio-respiratory failure lose considerable muscle mass in the first 7 days of admission, with only 50% of these patients recovering the initial muscle loss at follow up. However, strength, function and HRQoL all improve following ICU discharge suggesting an element of functional recovery. Strength and function have shown to improve regardless of the status of the muscle mass. Therefore, given the advantages of the real-life model and novel findings, this could serve as a platform to assess muscle loss and recovery over a longer time frame continuing to build the understanding of the patients recovery trajectory from critical illness.Rectus Femoris Muscle MassHand-Held Grip Strength

Neurocognition in adolescents and young adults at clinical high risk for psychosis: Predictive stability for social and role functioning

The prodromal phase of schizophrenia provides an optimal opportunity to mitigate the profound functional disability that is often associated with fully expressed psychosis. Considerable evidence supports the importance of neurocognition in the development of interpersonal (social) and academic (role) skills. Further findings from adolescents and young adults at clinical high risk for developing psychosis (CHRP) suggest that treatment for functioning might be most effective when targeting early and specific neurocognitive deficits. The current study addresses this critical intervention issue by examining the potential of neurocognitive deficits at intake for predicting social and role functioning over time in CHR-P youth. The study included 345 CHR-P participants from the second phase of the North American Prodrome Longitudinal Study (NAPLS2) with baseline neurocognition and 2-year follow-up data on social and role functioning. Slower baseline processing speed consistently predicted poor social functioning over time, while attention deficits predicted poor role functioning at baseline and follow-up. In addition, the impact of processing speed and attention impairments on social and role functioning, respectively, persisted even when adjusting the regression models for attenuated positive, negative, and disorganized symptoms, and transition status. The current study demonstrates for, arguably the first time, that processing speed and attention are strongly predictive of social and role functioning over time, respectively, above and beyond the impact of symptoms and those CHR-P individuals that develop psychosis over the course of the study. These findings imply that early neurocognition is a critical treatment target linked to the developmental trajectory of social and role functioning.

Pulmonary function trajectories in COVID-19 survivors with and without pre-existing respiratory disease

A significant proportion of COVID-19 survivors still experience a reduced diffusion capacity three and twelve months after discharge. We aimed to compare pulmonary function trajectories between hospitalized COVID-19 patients with pre-existing respiratory disease (PRD) and patients without pre-existing respiratory disease (Non-PRD) at three and twelve months after hospital discharge. This single-centre retrospective cohort study included COVID-19 patients admitted to the VieCuri Medical Centre (Venlo, the Netherlands) between February and December 2020 that were invited to the outpatient clinic at three and twelve months after discharge. During this visit, pulmonary function tests were performed and impairments were based on lower limit of normal. Data of 239 patients were analysed (65% male, 66 ± 10 years, and 26% with a history of respiratory disease). Three months after discharge, 49% and 64% of the Non-PRD patients (n = 177) and PRD patients (n = 62) had a low diffusion capacity, respectively. This improved over time in Non-PRD patients (p = 0.003), but not in PRD patients (p = 0.250). A low diffusion capacity was still observed in 34% and 57% of the Non-PRD and PRD group, respectively, twelve months after discharge. Pulmonary function impairments, mainly a reduced diffusion capacity, are observed among hospitalized COVID-19 patients with PRD and Non-PRD, at three and twelve months follow-up. Although diffusion capacity impairments restore over time in Non-PRD patients, poor recovery was observed among PRD patients.

The trajectory of functional status of patients with kidney failure choosing conservative kidney management.

In older patients with kidney failure (KF) starting dialysis, there is a high rate of functional decline. Not much is known about the functional trajectory of patients receiving conservative kidney management (CKM). Therefore, the aim of this study is to assess this functional trajectory and explore clinical parameters associated with functional decline. The functional trajectory of patients choosing CKM was evaluated using data from the Geriatric Assessment in Older Patients Starting Dialysis (GOLD) study, which included patients aged ≥ 65years with KF at the moment of decision-making. Functional status was assessed using a combined score for activities of daily living (ADL) and instrumental activities of daily living (iADL) dependency at baseline and after six months of follow-up. Change in functional status was divided into improvement (gain of one or more domains in functional status), stable (no change), decline (loss of one or more domains in functional status), and death at follow-up. The association between functional status at baseline and functional decline after six months was assessed with chi-squared test or Fisher's exact test. Furthermore, caregiver experiences were explored using self perceived pressure of informal care (SPPIC) at baseline and 6-month follow-up. Follow-up data were available for 86 patients. Mean age was 82 ± 6years and 43% were women. At baseline, 12% of the patients were independent, 55% were mild/moderately dependent, and 34% severely dependent. After 6 months of follow-up, 9% of all patients had improved, 35% remained stable, 41% had declined, and 15% had died. No significant associations were found between baseline characteristics and the composite outcomes. In patients aged ≥ 65years receiving CKM, functional decline and death are highly prevalent. No association was found between poor outcome ("decline/death") and different potential risk factors.

Intrinsic Infant Hippocampal Function Supports Inhibitory Processing.

Impaired cerebral inhibition is commonly observed in neurodevelopmental disorders and may represent a vulnerability factor for their development. The hippocampus plays a key role in inhibition among adults and undergoes significant and rapid changes during early brain development. Therefore, the structure represents an important candidate region for early identification of pathology that is relevant to inhibitory dysfunction. To determine whether hippocampal function corresponds to inhibition in the early postnatal period, the present study evaluated relationships between hippocampal activity and sensory gating in infants 4-20 weeks of age (N=18). Resting-state functional magnetic resonance imaging was used to measure hippocampal activity, including the amplitude of low-frequency fluctuations (ALFFs) and fractional ALFF. Electroencephalography during a paired-stimulus paradigm was used to measure sensory gating (P50). Higher activity of the right hippocampus was associated with better sensory gating (P50 ratio), driven by a reduction in response to the second stimulus. These findings suggest that meaningful effects of hippocampal function can be detected early in infancy. Specifically, higher intrinsic hippocampal activity in the early postnatal period may support effective inhibitory processing. Future work will benefit from longitudinal analysis to clarify the trajectory of hippocampal function, alterations of which may contribute to the risk of neurodevelopmental disorders and represent an intervention target.

Longitudinal lung function trajectories in response to azithromycin therapy for chronic lung disease in children with HIV infection: a secondary analysis of the BREATHE trial

BackgroundChronic lung disease (CLD) is common among children with HIV (CWH) including in those taking antiretroviral therapy (ART). Azithromycin has both antimicrobial and anti-inflammatory effects and has been effective in improving lung function in a variety of lung diseases. We investigated lung function trajectories among CWH with CLD on ART enrolled in a randomized controlled trial of adjuvant azithromycin. We also investigated factors that modified the effect of azithromycin on lung function.MethodsThe study used data from a double-blinded placebo-controlled trial conducted in Malawi and Zimbabwe of 48 weeks on azithromycin (BREATHE: ClinicalTrials.gov NCT02426112) among CWH aged 6 to 19 years taking ART for at least six months who had a forced expiratory volume in one second (FEV1) z-score <-1.0. Participants had a further follow-up period of 24 weeks after intervention cessation. FEV1, forced vital capacity (FVC) and FEV1/FVC were measured at baseline, 24, 48 and 72-weeks and z-scores values calculated. Generalized estimating equations (GEE) models were used to determine the mean effect of azithromycin on lung-function z-scores at each follow-up time point.ResultsOverall, 347 adolescents (51% male, median age 15 years) were randomized to azithromycin or placebo. The median duration on ART was 6.2 (interquartile range: 3.8–8.6) years and 56.2% had an HIV viral load < 1000copies/ml at baseline. At baseline, the mean FEV1 z-score was − 2.0 (0.7) with 44.7% (n = 155) having an FEV1 z-score <-2, and 10.1% had microbiological evidence of azithromycin resistance. In both trial arms, FEV1 and FVC z-scores improved by 24 weeks but appeared to decline thereafter. The adjusted overall mean difference in FEV1 z-score between the azithromycin and placebo arms was 0.004 [-0.08, 0.09] suggesting no azithromycin effect and this was similar for other lung function parameters. There was no evidence of interaction between azithromycin effect and baseline age, lung function, azithromycin resistance or HIV viral load.ConclusionThere was no observed azithromycin effect on lung function z-scores at any time point suggesting no therapeutic effect on lung function.Trial registrationClinicalTrials.gov NCT02426112. First registered on 24/04/2015.

Meeting complex multidimensional needs in older patients and their families during and beyond critical illness.

To highlight the emerging crisis of critically ill elderly patients and review the unique burden of multidimensional morbidity faced by these patients and caregivers and potential interventions. Physical, psychological, and cognitive sequelae after critical illness are frequent, durable, and robust across the international ICU outcome literature. Elderly patients are more vulnerable to the multisystem sequelae of critical illness and its treatment and the resultant multidimensional morbidity may be profound, chronic, and significantly affect functional independence, transition to the community, and quality of life for patients and families. Recent data reinforce the importance of baseline functional status, health trajectory, and chronic illness as key determinants of long-term functional disability after ICU. These risks are even more pronounced in older patients. The current article is an overview of the outcomes of older survivors of critical illness, putative interventions to mitigate the long-term morbidity of patients, and the consequences for families and caregivers. A multimodal longitudinal approach designed to follow patients for one or more years may foster a better understanding of multidimensional morbidity faced by vulnerable older patients and families and provides a detailed understanding of recovery trajectories in this unique population to optimize outcome, goals of care directives, and ongoing informed consent to ICU treatment.

State-Level Education Quality and Trajectories of Cognitive Function by Race and Educational Attainment.

Although educational attainment is consistently associated with better cognitive function among older adults, we know little about how education quality is related to cognitive function. This is a key gap in the literature given that the quality of US education improved considerably during the early to mid-20th century as state and federal investment increased. We posit that growing up in states with higher-quality education systems may protect against poor cognitive function, particularly among Black adults and adults who completed fewer years of school. We used prospective data on cognitive function from the Health and Retirement Study linked to historical data on state investment in public schools, restricting our sample to non-Hispanic White and Black adults born between 1914 and 1959 (19,096 White adults and 4,625 Black adults). Using race-stratified linear mixed models, we considered if state-level education quality was associated with level and decline in cognitive function and if these patterns differed by years of schooling and race. Residing in states with higher-resourced education systems during childhood was associated with better cognitive function, particularly among those who completed less than 12 years of schooling, regardless of race. For White adults, higher-resourced state education systems were associated with higher scores of total cognitive function and episodic memory, but there were diminishing returns as resources increased to very high levels. For Black adults, the relationship between state education resources and cognitive function varied by age with positive associations in midlife and generally null or negative associations at the oldest ages. Federal and state investment in public schools may provide students with opportunities to develop important cognitive resources during schooling that translate into better cognitive function in later life, especially among marginalized populations.

Associations of Epigenetic Age Estimators With Cognitive Function Trajectories in the Women's Health Initiative Memory Study.

Epigenetic age estimators indicating faster/slower biological aging vs chronological age independently associate with several age-related outcomes; however, longitudinal associations with cognitive function are understudied. We examined associations of epigenetic age estimators with cognitive function measured annually. This longitudinal study consisted of older women enrolled in the Women's Health Initiative Memory Study with DNA methylation (DNAm) collected at baseline (1995-1998) from 3 ancillary studies and were followed up to 13 years. Global cognitive function was measured annually by Modified Mini-Mental State Examination (3MS; baseline-2007) and by modified Telephone Interview for Cognitive Status (TICS-m, 2008-2021). We calculated 5 epigenetic age estimators: extrinsic AgeAccel, intrinsic AgeAccel, AgeAccelPheno, AgeAccelGrim2, Dunedin Pace of Aging Calculated From the Epigenome (DunedinPACE), and AgeAccelGrim2 components (DNA-based plasma protein surrogates). We estimated longitudinal epigenetic age estimator-cognitive function associations using linear mixed-effects models containing age, education, race or ethnicity, and subsequently alcohol, smoking, body mass index, and comorbidities. We examined effect modification by APOE ε4 carriage. A total of 795 participants were enrolled. The mean baseline age was 70.8 ± 4 years (10.7% Black, 3.9% Hispanic or Latina, 85.4% White), A 1-SD (0.12) increment in DunedinPACE associated with faster annual declines in TICS-m scores in minimally adjusted (β = -0.118, 95% CI -0.202 to -0.034; p = 0.0006) and fully adjusted (β = -0.123, 95% CI -0.211 to -0.036; p = 0.006) models. AgeAccelPheno associated with faster annual declines in TICS-m with minimal adjustment (β = -0.091, 95% CI -0.176 to -0.006; p = 0.035) but not with full adjustment. No other epigenetic age estimators associated with changes in 3MS or TICS-m. Higher values of DNAm-based surrogates of growth differentiation factor 15, beta-2 microglobulin, Cystatin C, tissue inhibitor metalloproteinase 1, and adrenomedullin associated with faster annual declines in 3MS and TICS-m. Higher DNAm log A1c associated with faster annual declines in TICS-m only. DunedinPACE associated with faster annual declines in 3MS among APOE ε4 carriers but not among noncarriers (p-interaction = 0.020). Higher DunedinPACE associated with faster declines in TICS-m and 3MS scores among APOE ε4 carriers. DunedinPACE may help identify older women at risk of future cognitive decline. Limitations include the ancillary studies that collected epigenetic data not designed to study epigenetics and cognitive function. We examined epigenetic age estimators with global cognitive function and not specific cognitive domains. Findings may not generalize to men and more diverse populations.

Historic Cognitive Function Trajectories as Predictors of Sedentary Behavior and Physical Activity in Older Adults.

We examined whether trajectories of cognitive function over 10 years predict later-life physical activity (PA), sedentary time (ST), and sleep. Participants were from the Adult Changes in Thought (ACT) cohort study. We included 611 ACT participants who wore accelerometers and had 3+ measures of cognition in the 10 years prior to accelerometer wear. The Cognitive Assessment Screening Instrument (CASI) measured cognition and was scored using item-response theory (IRT). activPAL and ActiGraph accelerometers worn over 7 days measured ST and PA outcomes. Self-reported time in bed and sleep quality measured sleep outcomes. Analyses used growth mixture modeling to classify CASI-IRT scores into latent groups and examine associations with PA, ST, and sleep including demographic and health covariates. Participants (Mean age = 80.3 (6.5) years, 90.3% White, 57.1% female, 29.3% had less than 16 years of education) fell into 3 latent trajectory groups: average stable CASI (56.1%), high stable CASI (34.0%), and declining CASI (9.8%). The declining group had 16 minutes less stepping time (95% confidence interval [95% CI]: 0.6, 31.4), 1517 fewer steps per day (95% CI: 138, 2896), and 16.3 minutes per day less moderate-to-vigorous PA (95% CI: 1.3, 31.3) compared to the average stable group. There were no associations between CASI trajectory and sedentary or sleep outcomes. Declining cognition predicted lower PA providing some evidence of a reverse relationship between PA and cognition in older adults. However, this conclusion is limited by having outcomes at only one time point, a nonrepresentative sample, self-reported sleep outcomes, and using a global cognition measure.

Associations between IL-1β, IL-6, and TNFα polymorphisms and longitudinal trajectories of cognitive function in non-demented older adults

Inflammation is implicated in Alzheimer's disease (AD), and specific single nucleotide polymorphisms (SNPs) in inflammatory cytokine genes are associated with increased AD risk. Whether the same polymorphisms also predict domain-specific cognitive change in cognitively healthy older adults is unclear. Specific SNPs in three cytokine genes, IL-1β (rs16944), IL-6 (rs1800795), and TNFα (rs1800629) were assessed for association with longitudinal trajectories spanning up to 16 years of global cognitive function, episodic memory, attention and working memory, and executive function in a sample of 324 non-demented older adults. Only rs1800629 (TNFα) was associated with significant change in global cognitive function over time [γ = 5.22; 95% CI: 0.61, 9.83; p = 0.027]. Despite an association with AD risk, rs16944 and rs1800795 may not predict cognitive decline in cognitively healthy older adults. The presence of an A at rs1800629 (TNFα) may have broad, protective effects on cognitive function, over time. More validation studies are needed to determine whether specific cytokine SNPs are associated with respective serum levels to further understanding of AD biomarkers that may also serve as markers of cognitive decline.

Clinical characteristics associated with functioning trajectories following admission to a psychiatric institution: A prospective cohort study of individuals with psychosis

Psychotic disorders can be severely enabling, and functional recovery is often difficult to achieve. Admission to a psychiatric unit represents a key opportunity to implement strategies that will improve functional outcomes. In the current literature, there is a lack of consensus on which factors influence functional recovery. Therefore, the present longitudinal cohort study aimed to identify factors associated with functional trajectories following hospital admission for acute psychosis. A sample of 453 individuals with acute psychosis was extracted from the Signature Biobank database. Participants were followed for up to a year following admission. Various clinical indicators were documented over time. Functional trajectories were calculated based on the World Health Organization Disability Assessment Schedule 2.0. Three groups were identified: "improving", "stable", and "worsening" function. Individuals with a more severe symptomatic presentation at baseline were found to have better functional improve more over time. Over time, individuals in the "improving" and "stable" groups had significant improvements in their psychiatric symptoms. Finally, individuals following a "worsening" functional trajectory initially improved in terms of psychotic symptoms, but it did not persist over time. These results highlight the importance of studying function as a key component of recovery rather than solely focusing on relapse prevention.

Risk and protective factors for cognitive decline in Brazilian lower educated older adults: A 15-year follow-up study using group-based trajectory modelling

BackgroundPatterns of cognitive change and modifiable factors for cognitive decline versus stable cognitive trajectories have rarely been described in lower-educated older adults. ObjectivesWe aimed to identify long-term trajectories of cognitive functioning and possible factors associated with cognitive decline. Design and participantsWe used data from 1,042 adults aged ≥ 60 participating in the Health, Welfare and Aging Study (SABE), São Paulo, Brazil, without cognitive impairment at baseline. Data were collected across four waves (2000–2015). Group-based trajectory modelling was used to identify cognitive trajectories. Associations with socioeconomic variables, childhood background, lifestyle, and cardiovascular risk factors were explored using weighted multinomial logistic regressions. MeasurementsThe abbreviated Mini-Mental State Examination was used to measure cognition. ResultsThree cognitive trajectories were identified: stable (n= 754, 68.6%), mild-decline (n= 183, 20.8%), and strong-decline (n= 105, 10.7%). At baseline, respondents in the strong-decline group were more likely to be older than those with stable and mild-decline trajectories. Furthermore, participants in both the mild and strong-decline groups were more likely to have no schooling, be divorced/separated, receive less than 4 monthly wages, and be underweight (BMI < 18.5) compared to the stable group. Finally, the mild-decline group was more likely to have lived in rural areas during childhood than participants located in a stable trajectory. ConclusionsOur findings suggest that interventions to reduce cognitive decline for low-educated older adults might include strategies addressing inequalities and improving modifiable risk factor burden.

Kidney Outcomes and Trajectories of Tubular Injury and Function in Critically Ill Patients With and Without COVID-19.

COVID-19 may injure the kidney tubules via activation of inflammatory host responses and/or direct viral infiltration. Most studies of kidney injury in COVID-19 lacked contemporaneous controls or measured kidney biomarkers at a single time point. To better understand mechanisms of acute kidney injury in COVID-19, we compared kidney outcomes and trajectories of tubular injury, viability, and function in prospectively enrolled critically ill adults with and without COVID-19. The COVID-19 Host Response and Outcomes study prospectively enrolled patients admitted to ICUs in Washington State with symptoms of lower respiratory tract infection, determining COVID-19 status by nucleic acid amplification on arrival. We evaluated major adverse kidney events (MAKE) defined as a doubling of serum creatinine, kidney replacement therapy, or death, in 330 patients after inverse probability weighting. In the 181 patients with available biosamples, we determined trajectories of urine kidney injury molecule-1 (KIM-1) and epithelial growth factor (EGF), and urine:plasma ratios of endogenous markers of tubular secretory clearance. At ICU admission, the mean age was 55 ± 16 years; 45% required mechanical ventilation; and the mean serum creatinine concentration was 1.1 mg/dL. COVID-19 was associated with a 70% greater occurrence of MAKE (relative risk 1.70; 95% CI, 1.05-2.74) and a 741% greater occurrence of KRT (relative risk 7.41; 95% CI, 1.69-32.41). The biomarker cohort had a median of three follow-up measurements. Urine EGF, secretory clearance ratios, and estimated glomerular filtration rate (eGFR) increased over time in the COVID-19 negative group but remained unchanged in the COVID-19 positive group. In contrast, urine KIM-1 concentrations did not significantly change over the course of the study in either group. Among critically ill adults, COVID-19 is associated with a more protracted course of proximal tubular dysfunction and reduced eGFR despite similar degrees of kidney injury.

A Dynamic Entropy Approach Reveals Reduced Functional Network Connectivity Trajectory Complexity in Schizophrenia.

Over the past decade and a half, dynamic functional imaging has revealed low-dimensional brain connectivity measures, identified potential common human spatial connectivity states, tracked the transition patterns of these states, and demonstrated meaningful transition alterations in disorders and over the course of development. Recently, researchers have begun to analyze these data from the perspective of dynamic systems and information theory in the hopes of understanding how these dynamics support less easily quantified processes, such as information processing, cortical hierarchy, and consciousness. Little attention has been paid to the effects of psychiatric disease on these measures, however. We begin to rectify this by examining the complexity of subject trajectories in state space through the lens of information theory. Specifically, we identify a basis for the dynamic functional connectivity state space and track subject trajectories through this space over the course of the scan. The dynamic complexity of these trajectories is assessed along each dimension of the proposed basis space. Using these estimates, we demonstrate that schizophrenia patients display substantially simpler trajectories than demographically matched healthy controls and that this drop in complexity concentrates along specific dimensions. We also demonstrate that entropy generation in at least one of these dimensions is linked to cognitive performance. Overall, the results suggest great value in applying dynamic systems theory to problems of neuroimaging and reveal a substantial drop in the complexity of schizophrenia patients' brain function.

Personalized prediction of mortality in patients with acute ischemic stroke using explainable artificial intelligence

BackgroundResearch into the acute kidney disease (AKD) after acute ischemic stroke (AIS) is rare, and how clinical features influence its prognosis remain unknown. We aim to employ interpretable machine learning (ML) models to study AIS and clarify its decision-making process in identifying the risk of mortality.MethodsWe conducted a retrospective cohort study involving AIS patients from January 2020 to June 2021. Patient data were randomly divided into training and test sets. Eight ML algorithms were employed to construct predictive models for mortality. The performance of the best model was evaluated using various metrics. Furthermore, we created an artificial intelligence (AI)-driven web application that leveraged the top ten most crucial features for mortality prediction.ResultsThe study cohort consisted of 1633 AIS patients, among whom 257 (15.74%) developed subacute AKD, 173 (10.59%) experienced AKI recovery, and 65 (3.98%) met criteria for both AKI and AKD. The mortality rate stood at 4.84%. The LightGBM model displayed superior performance, boasting an AUROC of 0.96 for mortality prediction. The top five features linked to mortality were ACEI/ARE, renal function trajectories, neutrophil count, diuretics, and serum creatinine. Moreover, we designed a web application using the LightGBM model to estimate mortality risk.ConclusionsComplete renal function trajectories, including AKI and AKD, are vital for fitting mortality in AIS patients. An interpretable ML model effectively clarified its decision-making process for identifying AIS patients at risk of mortality. The AI-driven web application has the potential to contribute to the development of personalized early mortality prevention.

Household Environments and Cognitive Decline Among Middle-Aged and Older Adults in China: Exploring Gender, Age, and Residential Variations

This study examined the relationship between household environments and trajectories of cognitive function among middle-aged and older adults in China and its urban/rural, gender, and age variations. We estimated multi-level linear growth curve models using a representative sample of 16,111 respondents aged 45 years and over from the China Health and Retirement Longitudinal Study (2011–2018). Older people who lived with a spouse, but not with children, and those with higher living expenditures, better housing quality, and indoor clean fuels for cooking had a slower cognitive decline. Living arrangement more strongly predicted men's cognitive decline, while living expenditure, solid fuel use, and housing quality significantly predicted only women's cognitive decline. Only for older adults and rural residents, those living alone had significantly faster cognitive decline than those living with a spouse only. These findings underscore the importance of improving the living conditions of older adults to help alleviate their cognitive decline.

Treatable traits in pre-COPD: Time to extend the treatable traits paradigm beyond established disease.

To date, the treatable traits (TTs) approach has been applied in the context of managing diagnosed diseases. TTs are clinical characteristics and risk factors that can be identified clinically and/or biologically, and that merit treatment if present. There has been an exponential increase in the uptake of this approach by both researchers and clinicians. Realizing the potential of the TTs approach to pre-clinical disease, this expert review proposes that it is timely to consider acting on TTs present before a clinical diagnosis is made, which might help to prevent development of the full disease. Such an approach is ideal for diseases where there is a long pre-clinical phase, such as in chronic obstructive pulmonary disease (COPD). The term 'pre-COPD' has been recently proposed to identify patients with respiratory symptoms and/or structural or functional abnormalities without airflow limitation. They may eventually develop airflow limitation with time but patients with pre-COPD are likely to have traits that are already treatable. This review first outlines the contribution of recently generated knowledge into lifetime lung function trajectories and the conceptual framework of 'GETomics' to the field of pre-COPD. GETomics is a dynamic and cumulative model of interactions between genes and the environment throughout the lifetime that integrates information from multi-omics to understand aetiology and mechanisms of diseases. This review then discusses the current evidence on potential TTs in pre-COPD patients and makes recommendations for practice and future research. At a broader level, this review proposes that introducing the TTs in pre-COPD may help reenergize the preventive approaches to health and diseases.