Longitudinal Outcomes Research Articles

IMG-04. ASSOCIATION BETWEEN MICROSTRUCTURAL INTEGRITY OF BRAIN SUBSTRUCTURES AND NEUROCOGNITIVE OUTCOMES: A MULTI-TRAJECTORY ANALYSIS IN CHILDHOOD BRAIN TUMOR SURVIVORS

Abstract BACKGROUND The relationship between the brain’s microstructural integrity and neurocognitive outcomes is not well characterized in childhood brain tumor survivors. In healthy children, mean diffusivity (MD) generally decreases and fractional anisotropy (FA) increases with age as the brain progressively myelinates and develops. Increasing MD and decreasing FA is suggestive of microstructural injury. We investigate the association between longitudinal neurocognitive outcomes and change in MD and FA in childhood brain tumor survivors. METHODS Patients diagnosed with a brain tumor at < 20 years of age with ≥ 2 neurocognitive assessments and paired DTI at each neurocognitive timepoint were retrospectively identified and eligible for inclusion. Multi-trajectory modeling was applied to cluster patients into distinct neurocognitive trajectories based on intelligent quotient, processing speed and working memory. Linear mixed models were used to determine whether the clusters were associated with change in MD and FA over time. RESULTS A total of 61 patients were eligible with 151 neurocognitive assessments paired with DTI. Mean follow-up was 4.8 years. Multi-trajectory modeling identified two clusters of patients with distinct neurocognitive trajectories. Compared to the low-performance group, the high-performance group (45.5%) had higher baseline neurocognitive scores with less decline in all neurocognitive outcomes. The high-performance group was also associated with a greater decrease in MD and greater increase in FA of the hippocampus and several white matter tracts such as the corpus callosum, pontine crossing tract, anterior limb of the internal capsule and inferior cerebellar peduncle, after adjusting for age and sex (all p<0.05). Additionally, the high-performance group was associated with a greater increase in FA in the superior, middle and inferior frontal gyri (all p<0.05). CONCLUSIONS The high-performance neurocognitive group was associated with greater microstructural integrity over time in multiple brain substructures compared to the low-performance group, as measured by change in fractional anisotropy and mean diffusivity.

Identifying patterns of multidimensional self-compassion in Chinese young adults: implications for longitudinal mental health outcomes during the pandemic

Background Self-compassion (SC), reflecting self-attitude and self-connectedness, has proven to be a modifiable factor in promoting mental health outcomes. Increasingly, SC is recognized as a multidimensional construct consisting of six dimensions, rather than a single dimension. Objectives First, this study adopted a person-centered approach to explore profiles of SC dimensions in Chinese young adults. Second, the study examined the predictive effects of SC profiles on mental health outcomes. Methods In February 2020, young adults (N = 1164) were invited to complete the 26-item Neff’s Self-Compassion Scale online. Three months later, the same subjects (N = 1099) reported their levels of depressive symptoms, posttraumatic stress disorder (PTSD) symptoms, and posttraumatic growth (PTG). Results After controlling for retrospective ACEs, four classes best characterized the profiles: self-compassionate (26.7%, N = 294), self-uncompassionate (12.3%, N = 135), average (55.9%, N = 614), and detached groups (5.1%, N = 56). Young adults in the self-compassionate group adjusted the best (with the highest level of PTG and the lowest levels of depressive and PTSD symptoms). Adults in the self-uncompassionate group demonstrated the poorest mental health outcomes (with the lowest level of PTG and the highest levels of depressive and PTSD symptoms). Young adults in the average group obtained more PTG than adults in the detached group (p < .01), but did not differ significantly in depressive and PTSD symptoms (p > .05). Conclusion The compassionate profile is the most adaptable for young adults among all groups. This study highlights the limitations of representing the relative balance of SC with a composite score.

Intimate Partner Violence and HIV Outcomes Among Women Living with HIV in Durban, South Africa

We examined the impact of past-year intimate partner violence (IPV) on HIV outcomes among women living with HIV (WLHIV) in Durban, South Africa. We assessed past-year IPV using the WHO Violence Against Women Questionnaire. We conducted logistic regression to assess associations between demographic variables and IPV at baseline, and between IPV at baseline and longitudinal HIV outcomes. Among 235 WLHIV, 17% reported past-year emotional, physical, or sexual IPV. At baseline, HIV-disclosure to partner was associated with 4.35-fold odds of past-year IPV (95% CI 1.17–16.10) after controlling for children, education, and harmful alcohol use. In the prospective analysis, IPV was associated with not achieving the co-primary outcome of retention in care and viral suppression in univariate (OR = 2.32, 95% CI 1.04–5.18), but not in the multivariate model. In the context of rapid treatment scale-up, the high burden of IPV among WLHIV needs to be prioritized, with an emphasis on disclosure support.

Sex-Specific Risk Factors and Clinical Dementia Outcomes for White Matter Hyperintensities in a large South Korean Cohort.

White matter hyperintensities (WMH) on brain MRI images are the most common feature of cerebral small vessel disease (CSVD). Studies have yielded divergent findings on the modifiable risk factors for WMH and WMH's impact on cognitive decline. Mounting evidence suggests sex differences in WMH burden and subsequent effects on cognition. Thus, we aimed to identify sex-specific modifiable risk factors for WMH. We then explored whether there were sex-specific associations of WMH to longitudinal clinical dementia outcomes. Participants aged 49-89 years were recruited at memory clinics and underwent a T2-weighted fluid-attenuated inversion recovery (FLAIR) 3T MRI scan to measure WMH volume. Participants were then recruited for two additional follow-up visits, 1-2 years apart, where clinical dementia rating sum of boxes (CDR-SB) scores were measured. We first explored which known modifiable risk factors for WMH were significant when tested for a sex-interaction effect. We additionally tested which risk factors were significant when stratified by sex. We then tested to see whether WMH is longitudinally associated with clinical dementia that is sex-specific. The study utilized data from 713 participants (241 males, 472 females) with a mean age of 72.3 years and 72.8 years for males and females, respectively. 57.3% and 59.5% of participants were diagnosed with mild cognitive impairment (MCI) for males and females, respectively. 40.7% and 39.4% were diagnosed with dementia for males and females, respectively. Of the 713 participants, 181 participants had CDR-SB scores available for three longitudinal time points. Compared to males, females showed stronger association of age to WMH volume. Type 2 Diabetes was associated with greater WMH burden in females but not males. Finally, baseline WMH burden was associated with worse clinical dementia outcomes longitudinally in females but not in males. Elderly females have an accelerated increase in cerebrovascular burden as they age, and subsequently are more vulnerable to clinical dementia decline due to CSVD. Additionally, females are more susceptible to the cerebrovascular consequences of diabetes. These findings emphasize the importance of considering sex when examining the consequences of CSVD. Future research should explore the underlying mechanisms driving these sex differences and personalized prevention and treatment strategies. The BICWALZS is registered in the Korean National Clinical Trial Registry (Clinical Research Information Service; identifier, KCT0003391). Registration Date 2018/12/14.

Bayesian transition models for ordinal longitudinal outcomes.

Ordinal longitudinal outcomes are becoming common in clinical research, particularly in the context of COVID-19 clinical trials. These outcomes are information-rich and can increase the statistical efficiency of a study when analyzed in a principled manner. We present Bayesian ordinal transition models as a flexible modeling framework to analyze ordinal longitudinal outcomes. We develop the theory from first principles and provide an application using data from the Adaptive COVID-19 Treatment Trial (ACTT-1) with code examples in R. We advocate that researchers use ordinal transition models to analyze ordinal longitudinal outcomes when appropriate alongside standard methods such as time-to-event modeling.

Serum and Urine Metabolites and Kidney Function.

Key Points We provide an atlas of cross-sectional and longitudinal serum and urine metabolite associations with eGFR and urine albumin-creatinine ratio in an older community-based cohort.Metabolic profiling in serum and urine provides distinct and complementary insights into disease. Background Metabolites represent a read-out of cellular processes underlying states of health and disease. Methods We evaluated cross-sectional and longitudinal associations between 1255 serum and 1398 urine known and unknown (denoted with “X” in name) metabolites (Metabolon HD4, 721 detected in both biofluids) and kidney function in 1612 participants of the Atherosclerosis Risk in Communities study. All analyses were adjusted for clinical and demographic covariates, including for baseline eGFR and urine albumin-creatinine ratio (UACR) in longitudinal analyses. Results At visit 5 of the Atherosclerosis Risk in Communities study, the mean age of participants was 76 years (SD 6); 56% were women, mean eGFR was 62 ml/min per 1.73 m2 (SD 20), and median UACR level was 13 mg/g (interquartile range, 25). In cross-sectional analysis, 675 serum and 542 urine metabolites were associated with eGFR (Bonferroni-corrected P &lt; 4.0E-5 for serum analyses and P &lt; 3.6E-5 for urine analyses), including 248 metabolites shared across biofluids. Fewer metabolites (75 serum and 91 urine metabolites, including seven metabolites shared across biofluids) were cross-sectionally associated with albuminuria. Guanidinosuccinate; N2,N2-dimethylguanosine; hydroxy-N6,N6,N6-trimethyllysine; X-13844; and X-25422 were significantly associated with both eGFR and albuminuria. Over a mean follow-up of 6.6 years, serum mannose (hazard ratio [HR], 2.3 [1.6–3.2], P = 2.7E-5) and urine X-12117 (HR, 1.7 [1.3–2.2], P = 1.9E-5) were risk factors of UACR doubling, whereas urine sebacate (HR, 0.86 [0.80–0.92], P = 1.9E-5) was inversely associated. Compared with clinical characteristics alone, including the top five endogenous metabolites in serum and urine associated with longitudinal outcomes improved the outcome prediction (area under the receiver operating characteristic curves for eGFR decline: clinical model=0.79, clinical+metabolites model=0.87, P = 8.1E-6; for UACR doubling: clinical model=0.66, clinical+metabolites model=0.73, P = 2.9E-5). Conclusions Metabolomic profiling in different biofluids provided distinct and potentially complementary insights into the biology and prognosis of kidney diseases.

Long-Term Clinical Course and Treatment Outcomes in Occult and Overt Acute Zonal Outer Retinopathy

ABSTRACT Purpose To report the longitudinal outcomes for AZOOR patients including treatment response, imaging evolution, and overlap with multiple evanescent white dot syndrome (MEWDS). Methods Visual acuity (VA) and visual field (VF) outcomes of occult and overt AZOOR patients were retrospectively compared between the first and final visits as well as between the two AZOOR subtypes. For treated patients, rates of VA change and fundus lesion area were compared before and after treatment. Analyses were performed using STATA 17. Results Seventeen eyes from 11 occult AZOOR patients and 45 eyes from 29 overt AZOOR patients were included. In a composite VA/VF primary outcome, clinical improvement was noted in five occult AZOOR and three overt AZOOR patients. The decline of logarithm of the Minimal Angle of Resolution (logMAR) VA was minimal in both groups: 0.00016 units/month in occult AZOOR patients and 0.009 units/month in overt AZOOR patients (p = 0.94). Occult AZOOR patients were more likely to have improved or stable VF than overt AZOOR patients (p = 0.04). One occult AZOOR and two overt AZOOR patients developed MEWDS at subsequent visits. Treatment with steroids or immunomodulatory therapy (IMT) was initiated in one occult AZOOR patient and nine overt AZOOR patients. Treated patients had overall VA stability. Fundus lesion area in treated patients changed by a mean of 0.2831 mm2/month, with 40% of patients showing decreased lesion area. Conclusion AZOOR patients generally maintained their VA. Overt AZOOR patients were more likely to receive steroids or IMT; treatment was associated with stabilization of VA.

Mean Affect Moderates the Association between Affect Variability and Mental Health

Increasing evidence suggests that within-person variation in affect is a dimension distinct from mean levels along which individuals can be characterized. This study investigated affect variability’s association with concurrent and longitudinal mental health and how mean affect levels moderate these associations. The mental health outcomes of depression, panic disorder, self-rated mental health, and mental health professional visits from the second and third waves of the Midlife in the United States Study were used for cross-sectional (n = 1,676) and longitudinal outcomes (n = 1,271), respectively. These participants took part in the National Study of Daily Experiences (NSDE II), where they self-reported their affect once a day for 8 days, and this was used to compute affect mean and variability. Greater positive affect variability cross-sectionally predicted a higher likelihood of depression, panic disorder, mental health professional use, and poorer self-rated mental health. Greater negative affect variability predicted higher panic disorder probability. Longitudinally, elevated positive and negative affect variability predicted higher depression likelihood and worse self-rated mental health over time, while greater positive affect variability also predicted increased panic disorder probability. Additionally, mean affect moderated associations between variability and health such that variability-mental health associations primarily took place when mean positive affect was high (for concurrent mental health professional use and longitudinal depression) and when mean negative affect was low (for concurrent depression, panic disorder, self-rated mental health, and longitudinal self-rated mental health). Taken together, affect variability may have implications for both short- and long-term health and mean levels should be considered.

Impact of improved air quality on lung function and blood pressure of middle-aged and older population in China

Long-term exposure to fine particulate matters (PM2.5) has been associated with respiratory and cardiovascular diseases and the burden are potentially higher in China experiencing heavy air pollution. In this study, we established the exposure-response association between long-term exposures to PM2.5 and lung function and blood pressure in Chinese middle-aged and older adults using linear mixed-effects and generalized additive mixed models based on 3 waves longitudinal health outcomes data by enrolling 19,988 participants from 121 cities across the mainland of China. We also assessed the effect of Clean Air Policy (CAP) based on a quasi-experimental difference-in-differences (DID) design. A 10 µg/m3 increase in PM2.5 concentration was associated with a 7.18 (95 % confidence interval [CI]: -8.35, -6.02) L/min decrease in PEF (peak expiratory flow) and a 0.72 (95 % [CI]: 0.53, 0.90) and a 0.30 (95 % [CI]: 0.18, 0.42) mmHg increase in systolic and diastolic blood pressure, respectively. The associations were more pronounced in males and rural areas for PEF, but similar across subgroups for blood pressure. DID results suggested that the effect of CAP on health outcomes were sensitive to magnitudes of reduction in PM2.5. A 5 µg/m3 reduction in PM2.5 or more generally led to 18.70 (95 % [CI]:0.79, 36.61) higher PEF and -2.05 (95 % [CI]: -3.87, -0.23) lower diastolic blood pressure, respectively, compared to no reduction or increase in exposure. However, the effects were significant only in rural areas. Our analysis support CAP aiming to benefit public health and provides insights to inform future control policy for efficiently decreasing air pollution exposure burden.

Helping ourselves, helping others: the Young Women’s Breast Cancer Study (YWS) – a multisite prospective cohort study to advance the understanding of breast cancer diagnosed in women aged 40 years and younger

PurposeCompared with older women diagnosed with breast cancer, younger women are more likely to die of breast cancer and more likely to suffer psychosocially in both the short-term and long...

Long-term Outcomes of Multiligament Knee Injuries in American Football Players

Background: Long-term outcomes for isolated anterior cruciate ligament (ACL) reconstructions in competitive American football athletes are well reported in the literature, but little data currently exist regarding multiligament knee injury (MLKI) reconstruction outcomes. Purpose: To examine patient-reported and return-to-sport outcomes of competitive American football athletes who underwent primary, single-staged, multiligament knee reconstruction. Study Design: Case series; Level of evidence, 4 Methods: We identified patients from our institution’s prospectively collected data repository between 2001 and 2020 who underwent single-staged surgical reconstruction of an MLKI sustained during competitive participation in American football. We assessed patient-reported outcomes at a minimum of 2 years after surgery using the International Knee Documentation Committee (IKDC) Subjective Knee Form and questions regarding surgical satisfaction and return to sport. Successful return to sport was defined as a return to preinjury level of competition. We summarized all outcome data and compared outcomes between 2-ligament and >2-ligament groups and between ACL-only MLKI injury and bicruciate MLKI injury groups using independent t test for IKDC scores and chi-square test for return to sport. Additionally, we evaluated predictors of postoperative IKDC scores using linear regression and predictors of return to sport using logistic regression. Results: Outcome data were successfully collected for 53 of 73 total eligible patients (73%; mean follow-up time, 7.7 ± 4.0 years; all male; mean age at surgery, 18.1 ± 2.7 years). The mean postoperative IKDC score was 84 ± 16. The most common level of preinjury competition was high school (n = 36; 68%), followed by college (n = 10; 19%). Seven patients did not return to sport competition at any level due to limitations from their knee surgery, and 82% of patients that attempted to return to preinjury level of sport were able to do so. A total of 50 patients (94%) were satisfied or very satisfied with their surgical outcome. The 2-ligament (n = 39) and >2-ligament (n = 14) groups did not significantly differ in IKDC scores (P = .96) or proportions with successful return to sport (P = .77). Similarly, the ACL-MLKI injury (n = 39) and bicruciate MLKI injury (n = 14) groups did not significantly differ in IKDC scores (P = .89) or proportions with successful return to sport (P = .77). Age and body mass index were not significantly associated with IKDC scores or successful return to sport at follow-up (all P > .05). Conclusion: This study may represent the largest cohort of competitive American football athletes evaluated for longitudinal outcomes after multiligament knee reconstruction. Despite the severity of these injuries, we found good knee-related function and that the large majority of athletes who attempted to return to sport were successful. The majority of athletes (94%) were satisfied with their operative treatment.

Tricuspid valve surgery for acute infective endocarditis can be performed with very low operative mortality

ObjectiveTricuspid valve surgery historically has been perceived as having elevated operative risk, prompting the recent development of transcatheter therapies including aspiration vegetectomy for endocarditis. The opioid epidemic has exacerbated tricuspid valve endocarditis, particularly in people who inject drugs. We sought to evaluate contemporary outcomes of tricuspid valve surgery in real-world practice. MethodsAn institutional multidisciplinary endocarditis database inclusive of clinical, microbiologic, and echocardiographic data was analyzed for those undergoing isolated or concomitant tricuspid valve surgery for acute active endocarditis. Consecutive patients between 2016 and 2021 were followed for longitudinal outcomes. ResultsA total of 283 patients with tricuspid valve endocarditis underwent tricuspid valve repair (n = 137, 48.4%) or replacement (n = 146, 51.6%). Median age was 31 (27-37) years, 63.1% were female, and 257 (90.8%) were active people who inject drugs. The leading indications for surgery were severe valvular insufficiency (71.2%), vegetation size greater than 2 cm (51.3%), or septic shock (23.3%). Concomitant procedures were performed in 44 patients (15.5%). In patients who underwent isolated tricuspid valve surgery (n = 239), no patient required permanent pacemaker after tricuspid valve repair, whereas 13.3% required permanent pacemaker after tricuspid valve replacement. Overall and isolated tricuspid valve surgery operative mortality were 1.8% and 1.3%, respectively. Overall and isolated tricuspid valve surgery 1-year survivals were 89.3% and 89.7%, respectively. ConclusionsTricuspid valve surgery for endocarditis has low operative mortality. When feasible, repair is preferred over replacement. In an era of promulgation of investigational therapies, heart teams should note that tricuspid valve surgery is low risk and remains the first-line beyond antibiotics.

Comparison of children and adults in deep brain stimulation for Tourette Syndrome: a large-scale multicenter study of 102 cases with long-term follow-up

BackgroundDeep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories.MethodsThis retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged < 18 years; n = 34) and adults (aged ≥ 18 years; n = 68). The longitudinal outcomes as tic symptoms were assessed by the YGTSS, and the YBOCS, BDI, and GTS-QOL were evaluated for symptoms of obsessive–compulsive disorder (OCD), depression, and quality of life, respectively.ResultsOverall, these included patients who finished a median 60-month follow-up, with no significant difference between children and adults (p = 0.44). Overall, the YGTSS total score showed significant postoperative improvements and further improved with time (improved 45.2%, 51.6%, 55.5%, 55.6%, 57.8%, 61.4% after 6, 12, 24, 36, 48, and ≥ 60 months of follow-up compared to baseline, respectively) in all included patients (all p < 0.05). A significantly higher improvement was revealed in children than adults at ≥ 60 months of follow-up in the YGTSS scores (70.1% vs 55.9%, p = 0.043), and the time to achieve 60% improvement was significantly shorter in the children group (median 6 months vs 12 months, p = 0.013). At the last follow-up, the mean improvements were 45.4%, 48.9%, and 55.9% and 40.3%, 45.4%, and 47.9% in YBOCS, BDI, and GTS-QOL scores for children and adults, respectively, which all significantly improved compared to baseline (all p < 0.05) but without significant differences between these two groups (all p > 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p = 0.049).ConclusionsDBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.

Trend in prevalence, associated risk factors, and longitudinal outcomes of sarcopenia in China: A national cohort study.

To estimate the contemporary trend in the prevalence of sarcopenia and evaluate its risk factors and the longitudinal associations with multiple chronic conditions and mortality among Chinese middle-aged and older adults. This was a nationwide, prospective cohort study using data from the China Health and Retirement Longitudinal Study. The definition of sarcopenia was based on the Asian Working Group for Sarcopenia 2019 algorithm. In the cross-sectional analysis, we estimated the trend in the weighted prevalence of sarcopenia from 2011 to 2015 and examined the associated risk factors for sarcopenia severity in 2011. In the longitudinal analysis, we assessed the longitudinal associations between sarcopenia and 14 chronic conditions and mortality during a 9-year follow-up. The weighted prevalence of sarcopenia remained consistently high in the overall population from 2011 (15.9%, 95% confidence intervals [CI]: 15.1, 16.6) to 2015 (15.0%, 95% CI: 14.3, 15.6; p for trend=0.075). A range of risk factors were independently associated with the severity of sarcopenia, including older age, female sex, lower socioeconomic status, smoking status, malnutrition, and several chronic conditions. Possible sarcopenic and sarcopenic individuals had higher odds of several chronic conditions (i.e., heart disease, chronic lung disease, and memory-related disease) and increased risks of mortality (possible sarcopenia: odds ratios (OR): 1.66, 95% CI: 1.37, 2.00; sarcopenia: OR: 1.69, 95% CI: 1.36, 2.11) in 9 years of follow-up. The prevalence of sarcopenia remained consistently high in the investigated population. Various risk factors were significantly associated with a higher prevalence of sarcopenia. Sarcopenic individuals had higher odds of several chronic conditions and increased risks of mortality, highlighting that the urgent need for dedicated efforts to improve the management of sarcopenic patients.

Colorectal cancer screening participation in First Nations populations worldwide: a systematic review and data synthesis

First Nations populations have poorer colorectal cancer (CRC) survival compared to non-First Nations populations. Whilst First Nations populations across the world are distinct, shared experiences of discrimination and oppression contribute to persistent health inequities. CRC screening improves survival, however screening rates in First Nations populations are poorly described. This study seeks to define participation rates in CRC screening in First Nations populations worldwide. A systematic literature search was conducted of PubMed, Embase, Cochrane Library, CINAHL, MEDLINE, grey literature, national registries and ClinicalTrials.gov. All sources were searched from their inception date to 18 February 2024. Studies were included if they reported CRC screening rates in adult (≥18 years) First Nations populations. We aimed to undertake a meta-analysis if there were sufficient data. Quality of papers were assessed using the Joanna Briggs Institute (JBI) appraisal tool. The study was registered with PROSPERO, CRD42020210181. The literature search identified 1723 potentially eligible published studies. After review, 57 studies were included, 50 from the United States (US), with the remaining studies from Australia, Aotearoa New Zealand (NZ), Canada, Dominica and Guatemala. Additionally, eleven non-indexed reports from national programs in Australia and NZ were included. There were insufficient data to undertake meta-analysis, therefore a systematic review and narrative synthesis were conducted. CRC screening definitions varied, and included stool-based screening, sigmoidoscopy and colonoscopy. US First Nations screening rates ranged between 4.0 and 79.2%, Australia reported 10.6-35.2%, NZ 18.4-49%, Canada 22.4-53.4%, Guatemala 2.2% and Dominica 4.2%. Fifty-five studies were assessed as moderate or high quality and two as low quality. Our findings suggested that there is wide variation in CRC screening participation rates across First Nations populations. Screening data are lacking in direct comparator groups and longitudinal outcomes. Disaggregation of screening data are required to better understand and address First Nations CRC outcome inequities. None.

P.039 Informing treatment advancement and innovation in a tertiary care neurocritical care (NCC)) program

Background: Children with neurological injuries/insults carry the highest risk of death and disability in Pediatric and Neonatal ICUs. These patients comprise 25-30% of admissions and have a myriad of diagnoses. Longitudinal outcome data is required to inform treatment effects and innovation strategies. NCC at the Alberta Children’s Hospital (ACH) participates in acute, subacute, and long-term/outpatient management with an aim to use comprehensive clinical data to improve outcomes. Methods: A prospective, longitudinal, population-based observational cohort study of NCC patients from local NICUs, PICU, and a NCC follow-up program, with comprehensive data from clinical records, development scores and QoL assessments. Results: Since 2019, 929 patients have been enrolled including: 407 neonates, 167 infants, 106 preschool-age and 100 school-age children, and 152 adolescents. The most common reasons for NCC consult were paroxysmal events (36%), encephalopathy (27%) and neonatal HIE (20%). Conclusions: Our database encapsulates the diverse nature of NCC patients and has enabled cohort-specific studies (e.g., neonatal HIE and ECLS outcomes). Program evolution will further facilitate higher powered research studies through large enrollment, comprehensive data capture (with a provincial EHR), and longitudinal outcomes. Engagement with staff and families will also inform treatment and afford evidence-based counseling to families.

Characterising paroxysmal supraventricular tachycardia episodes by patient-perceived episode duration, symptoms, and severity: longitudinal patient-reported outcomes

Abstract Background/Information Paroxysmal supraventricular tachycardia (PSVT) encompasses a range of heart rhythms that are often associated with clinical symptoms. The duration and symptoms a patient experiences during a PSVT episode are variable. The impact of episode duration and symptom type on a patient’s perceived severity of an episode of PSVT has not been well defined. Purpose To characterise the relationship between duration, symptom type, and patient-perceived episode severity in a longitudinal study of patient-reported outcomes in the US and UK. Methods The survey included patients &amp;gt;18 years of age with a self-reported diagnosis of PSVT, without a history of ablation. Surveys included a 30-minute baseline survey (Mar 2019), 5-minute weekly tracking surveys (Mar 2019 to Dec 2019), and a 15-minute closing survey (Dec 2019). Patients were asked during the baseline survey to rate the severity of their PSVT (mild/moderate/severe). Weekly episode surveys assessed patient-reported episode duration, symptoms, severity, and interventions. If multiple episodes occurred, characteristics of the most recent episode were assessed. Results Among 117,252 patients screened, 368 met the inclusion criteria and completed the baseline survey, while 247 patients in the final cohort met the quality control checks. Most patients were White (92%), female (70%), and from the US (80%) and had a mean age of 52 years. At baseline, 47% of patients described their PSVT as moderate severity, while 39% reported mild and 14% reported severe. Overall, 5277 longitudinal weekly surveys were completed, of which 48% captured a PSVT episode (n=2518). Median reported duration of an episode was 15 minutes, with severe episodes having numerically longer duration (71 minutes) than moderate (20 minutes) or mild (6 minutes) episodes. Among severe episodes, 57% lasted 1 hour or longer; only 9% of mild episodes lasted 1 hour or longer (Figure 1). Among all assessed episodes of PSVT, 89% had palpitations, 35% shortness of breath, 26% dizziness, and 17% chest pain; mean number of symptoms per episode was 3.1, while numerically more symptoms were reported with severe episodes (mean 6.0) than with moderate (mean 3.5) or mild (mean 2.1) episodes. Shortness of breath was more frequently reported with severe episodes (81%) than with moderate (43%) or mild (17%) episodes. Similar findings were seen with dizziness and chest pain (Figure 2). Overall, approximately half of the reported episodes during follow-up were classified as moderate severity (47%), followed by mild (44%) and severe (9%). Conclusions Episodes of PSVT of longer duration and/or accompanied by a greater number of symptoms are reported by patients to be more severe. However, heterogeneity of symptoms and episode duration is substantial within a given classification of PSVT severity. Additional studies are needed to better understand how the optimal treatment of patients with PSVT may vary by duration, symptoms, and severity.

Assessing sleep in primary brain tumor patients using smart wearables and patient-reported data: Feasibility and interim analysis of an observational study.

Sleep-wake disturbances are common and disabling in primary brain tumor (PBT) patients but studies exploring longitudinal data are limited. This study investigates the feasibility and relationship between longitudinal patient-reported outcomes (PROs) and physiologic data collected via smart wearables. Fifty-four PBT patients ≥ 18 years wore Fitbit smart-wearable devices for 4 weeks, which captured physiologic sleep measures (eg, total sleep time, wake after sleep onset [WASO]). They completed PROs (sleep hygiene index, PROMIS sleep-related impairment [SRI] and Sleep Disturbance [SD], Morningness-Eveningness Questionnaire [MEQ]) at baseline and 4 weeks. Smart wearable use feasibility (enrollment/attrition, data missingness), clinical characteristics, test consistency, PROs severity, and relationships between PROs and physiologic sleep measures were assessed. The majority (72%) wore their Fitbit for the entire study duration with 89% missing < 3 days, no participant withdrawals, and 100% PRO completion. PROMIS SRI/SD and MEQ were all consistent/reliable (Cronbach's alpha 0.74-0.92). Chronotype breakdown showed 39% morning, 56% intermediate, and only 6% evening types. Moderate-severe SD and SRI were reported in 13% and 17% at baseline, and with significant improvement in SD at 4 weeks (P = .014). Fitbit-recorded measures showed a correlation at week 4 between WASO and SD (r = 0.35, P = .009) but not with SRI (r = 0.24, P = .08). Collecting sleep data with Fitbits is feasible, PROs are consistent/reliable, > 10% of participants had SD and SRI that improved with smart wearable use, and SD was associated with WASO. The skewed chronotype distribution, risk and impact of sleep fragmentation mechanisms warrant further investigation. NCT04 669 574.

Factorial structure of the Comprehensive Assessment of At-Risk Mental States in help-seeking individuals: mapping the structure and the prediction of subsequent transition to psychosis

ObjectivesThe aim of the current study was 3-fold: 1) to examine the factorial structure of the Comprehensive Assessment of At-Risk Mental States (CAARMS) in help-seeking individuals undergoing an assessment on suspicion of psychosis risk; 2) to investigate the association of CAARMS factors with functioning; 3) and to test the association of any derived factors with the longitudinal outcome of transition to psychosis.MethodsThe study included 101 patients. First, a principal component analysis (PCA) was conducted using the Varimax rotation method. A minimum initial eigenvalues of greater than or equal to 1.0, analysis of Scree plots, percentage of variance explained by each component, reliability (Cronbach’s alpha) of factors above 0.7 and Parallel Analysis were the criteria used to determine the appropriate number of factors Second, Spearman correlations were run to analyze the relationship between CAARMS factors and sociodemographic and functional variables (i.e. age, schooling, Social and Occupational Functioning Assessment Scale-SOFAS- and Health of the Nation Outcome Scales-HoNOS- scores). Third, we performed a Logistic regression analysis to evaluate the association between baseline CAARMS factors and the risk of transition to psychosis at the 6-month follow-up.ResultsA total of 101 consecutive patiens were recruited. We found that: 1) a 6 factor model solution as the most appropriate, jointly accounting for 65% of the variance; 2) factors 1 (“negative-interpersonal”), 2 (“cognitive-disorganization”), 3 (“positive”), and 4 (“motor-physical changes”) were negatively correlated with SOFAS total score; factors 1, 2, and 3 showed positive correlations with HoNOS total score; factors 2 and 3 present similar patterns of correlations, factor 3 manifesting the strongest association with HoNOS symptoms, HONOS and SOFAS total score. Both factors 5 and 6 show significant associations with HoNOS behavioral impairment; 3) after 6 months 28 participants (30.1%) converted to psychosis. Factors 2 and 3 were positively associated with the risk of transition to psychosis; whereas, the factor 5 (“affective factor”) was negatively associated with the outcome variable.ConclusionsIt is thus crucial to recognize the type and severity of psychopathology in help-seeking individuals in order to intensive clinical monitoring of subclinical psychopathology risk profiles, and design specific care pathways.

#2285 Potentially modifiable factors influencing longitudinal health-related quality of life for those with chronic kidney disease in the NURTuRE-CKD cohort

Abstract Background and Aims Factors affecting poor health-related quality of life (HRQoL) for people with chronic kidney disease (CKD) have been previously described in literature, and worse HRQoL is associated with CKD progression and death. Little emphasis has been placed on which factors may be potentially modifiable, and longitudinal HRQoL outcome analyses in non-dialysis dependent CKD cohorts are few in number. Baseline analysis of the NURTuRE-CKD cohort identified several associations between these factors and HRQoL and these associations can now be examined with longitudinal data. Method The NURTuRE-CKD cohort study recruited 2996 participants with non-dialysis dependent CKD between 2017-2019, collecting biochemical, anthropometric, sociodemographic, medical history and patient reported outcome measure (PROM) data. Face-to-face follow-up repeated these measures. Longitudinal worsening overall HRQoL was the main outcome of interest, represented by mapped EQ-5D-3L index value and visual analogue score (VAS). Multivariable linear mixed effects models were fitted in R using the lmer and lmerTest packages. Models for index value were fit separately for each independent variable of interest and collated, as well as fitting models with all variables of interest. Models were adjusted for available confounders, repeated measures and follow-up time. P-values were adjusted for multiple testing using false discovery rate correction. Results 2054/2996 (68.6%) had complete HRQoL data at follow-up, of whom most had CKD stage G3a-G4 (n = 1597, 77.8%). 1817 (88.5%) were white and 1196 (58.2%) were male. Mean age was 63.7 (SD ±14.5) years and the mean number of comorbidities was 3.7 (SD ±2.2). Median (IQR) time between baseline and follow-up was 518 (410) days. At follow-up, mean mapped EQ-5D-3L index value was 0.72 (SD ±0.3) and mean VAS score was 70.4/100 (SD ±20.6). 1595 (77.7%) reported problems in at least one EQ-5D-5L dimension, with 255 (12.4%) developing issues since baseline. 1203 (58.6%) reported worse HRQoL index values at follow up and 910 (44.3%) reported worse VAS. The dimension with the highest number of newly reported issues at follow-up was ‘usual activities’ with 301 (14.7%). Multivariable linear mixed methods models showed independent associations with worse HRQoL (Figs 1 and 2) for those on ten or more medications (β −0.118, CI −0.137 to −0.100, p &amp;lt; 0.001), current smokers (β −0.036, CI −0.067 to −0.006, p = 0.0.012), obesity (β-0.059, CI −0.080 to-0.039, p &amp;lt; 0.001), haemoglobin of &amp;lt;100g/L (β-0.044, CI −0.073 to-0.016, p = 0.014), hospital anxiety and depression scale scores of 8 or above for anxiety (β-0.146, CI −0.161 to-0.130, p &amp;lt; 0.001) and depression (β-0.202, CI-0.219 to −0.186, p &amp;lt; 0.001), worse health literacy (β −0.099, CI −0.136 to −0.063, p &amp;lt; 0.001), and pain (β −0.148, CI −0.161 to −0.135, p ≤ 0.001), weakness (β −0.106, CI −0.120 to −0.092, p &amp;lt; 0.001) and shortness of breath symptoms (β −0.074, CI −0.087 to −0.060, p &amp;lt; 0.001). Conclusion Potentially modifiable factors influencing longitudinal worsening of HRQoL for people with CKD include polypharmacy, smoking, obesity, anaemia, depression and anxiety, limited health literacy, pain, weakness and shortness of breath symptoms. This highlights the need for high quality randomised controlled trials to test interventions addressing these factors with reported HRQoL outcomes. Further work in this cohort is required, examining a third timepoint for HRQoL and linked clinical outcome data.