Multicenter Longitudinal Cohort Study Research Articles

Estimates and Predictors of Mortality, Stroke Recurrence, and Functional Dependency 1-Year after Ischemic Stroke: A Prospective Multicenter Longitudinal Cohort Study in Central Norway

Background. Stroke incidence and mortality have drastically decreased in high-income countries in the past twenty years. In this study, we provide updated estimates on mortality, recurrent stroke, and functional dependency among patients with first-ever ischemic stroke and assess predictors associated with poor outcomes with a focus on age, vascular factors, stroke severity, function, and comorbidity burden. Methods. MIDNOR STROKE is a multicenter prospective longitudinal study including patients with first-ever ischemic stroke admitted to stroke units in Central Norway during 2015-2017. Data on survival, stroke recurrence, and functional dependency were collected during hospital stay and follow-up. Multivariable Cox proportional hazard models and logistic regression models were used to analyze predictors of mortality, stroke recurrence, and functional dependency. Results. A total of 794 participants were included in the study. After a year, 7.6% of the participants had died, 5.8% had a recurrent stroke, and 13.6% experienced functional deterioration to dependency. Multivariable analysis revealed that age (HR: 1.07, 96% CI: 1.03, 1.10), stroke severity (HR: 1.10, 95% CI: 1.07, 1.13), comorbidity burden (low: HR: 4.05, 95% CI: 1.48, 11.10; moderate: HR: 5.44, 95% CI: 2.06, 14.40; and high: 7.72, 95% CI: 2.85, 21.00), and coronary artery disease (HR: 2.40, 95% CI: 1.32, 4.38) predicted all-cause death. Statin therapy predicted improved survival (HR: 0.39, 95% CI: 0.21, 0.75). High age (HR: 1.09, 95% CI: 1.05, 1.14) and increased stroke severity (OR: 1.26, 95% CI: 1.17, 1.38) predicted elevated risk of functional dependency at one year. Conclusions. In this study, we have demonstrated that 1-year survival following first-ever ischemic stroke was high compared to previous reports and that statin therapy predicted improved survival. The risk of recurrent stroke after one year was found to be low compared to previous studies. Approximately 14% of stroke survivors who were initially functionally independent experienced deterioration to functional dependency. In addition to older age and stroke severity, increased comorbidity burden and a history of coronary artery disease predicted poor stroke prognosis. Interventions aimed at reducing stroke severity may improve patient outcomes. Furthermore, prevention efforts targeting conditions such as CAD and reducing overall comorbidity burden in stroke patients may favorably improve survival. This trial is registered with NCT03962127.

Abstract PO1-04-12: Palbociclib versus ribociclib in first-line treatment of patients with hormone-receptor positive HER2 negative advanced breast cancer – real world outcome data from the German registry platform OPAL

Abstract Introduction CDK4/6 inhibitors (CDKi) plus endocrine therapy (ET) are standard of care in first-line (1L) treatment of hormone receptor-positive (HR+) HER2-negative (HER2-) advanced breast cancer (ABC). In the pivotal trials the three CDK4/6i (palbociclib, ribociclib and abemaciclib) + ET showed similar progression-free survival (PFS) benefit over ET alone. However, other than ribociclib, palbociclib failed to demonstrate overall survival (OS) benefit. As patient (pts) characteristics differed between the trials, especially in the number of pts with treatment-free interval (TFI) of < 12 months after end of adjuvant ET, head-to-head comparisons of the CDKi are of clinical interest. Here we analyze the outcome of pts treated with palbociclib + ET or ribociclib + ET with real-world data from OPAL. Methods OPAL (NCT03417115) is a prospective observational, open, longitudinal multicenter cohort study (clinical registry) in Germany. Pts with ABC and early breast cancer can be recruited at start of their first systemic treatment. There are no treatment restrictions. Sites from all medical sectors can participate in OPAL (medical and gynecologic oncologists from outpatient centers and hospitals). Details on all (sequential) treatments, patient and tumor characteristics, biomarker testing, clinical and patient-reported outcomes are collected. Follow-Up is until death or up to 5 years. Between 01/2018 and 07/2021 1049 pts with HR+ HER2- ABC were recruited by 143 sites. Database cut was on 31/08/2022. 384 pts received palbociclib + ET and 231 pts received ribociclib + ET as 1L treatment. All endocrine combination partners including switch of ET during first line therapy was allowed, whereas switch of CDK4/6i (n=25) were excluded. PFS in registries can differ from PFS in clinical trials, since the RECIST criteria are usually not applied in routine care. PFS in registries represents the time to clinically relevant progression in routine care. PFS and OS were estimated using the Kaplan-Meier method. To adjust for confounding, inverse probability of treatment weighting (IPTW) by propensity score analysis was used to compare PFS and OS between 1L palbociclib+ET and ribociclib+ET. IPTW was performed for the following variables: age, menopausal status, ECOG, any comorbidity, Charlson comorbidity index, metastatic stage, type of metastasis, number of metastatic sites, estrogen-/progesterone status, IHC status, previous chemo-/endocrine therapy, kind of endocrine combination partner, disease-free interval, and treatment-free interval. Results From 2018 to 2021, the proportion of CDK4/6i increased from 68% to 86% in 1L of HR+HER2- ABC. Overall, palbociclib was used in 44% and ribociclib in 26% of all first-line treatments in OPAL. Median age of pts receiving palbociclib/ribociclib was 66/68 years and for 77/81% of pts at least one comorbidity was documented. 37/35% of pts already had metastasis at diagnosis (M1) and 25/26% of pts had a TFI < 12 months. After IPTW, the two treatment groups were comparable for all tested characteristics. 42/46% of patients had a progression (palbociclib/ribociclib group). IPTW-adjusted median PFS was 25.1 months (95% Confidence interval (CI) 20.1 – 30.1) for the palbociclib and 27.0 months (95%-CI 21.1 – 31.6) for the ribociclib group. Hazard ratio was 0.91 (0.71 – 1.17) for palbociclib versus ribociclib. 26/29% of patients had an OS event (palbociclib/ribociclib group). IPTW-adjusted median OS was 36.7 months (95%-CI 33.0 – NA) for the palbociclib and 36.6 months (95%-CI 33.1 – NA) for the ribociclib group. Hazard ratio was 0.95 (0.69 - 1.30) for palbociclib versus ribociclib. Conclusions This analysis of real word data in the OPAL registry platform showed similar PFS and OS for palbociclib + ET compared to ribociclib + ET, when adjusted for a wide range of potential confounding variables. Further analyses will investigate whether one drug showed favorable results in certain subgroups of pts. Citation Format: Marc Thill, Mark-Oliver Zahn, Anja Welt, Arnd Nusch, Matthias Zaiss, Kathrin Engelken, Gabriele Kaltenecker, Kai Ringwald, Katja Gratzke, Lisa Kruggel, Martina Jänicke, Holger Schulz, Christoph Losem, Volker Hagen, Roland Fricker, Elmar Stickeler, Nadia Harbeck, Achim Wöckel, Thomas Decker. Palbociclib versus ribociclib in first-line treatment of patients with hormone-receptor positive HER2 negative advanced breast cancer – real world outcome data from the German registry platform OPAL [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-04-12.

Differential Effects of Genetic Polymorphism on Comorbid Disease in Metabolic Dysfunction–Associated Steatotic Liver Disease

PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 have been associated with an increased risk of liver-related events (LREs) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, we investigated the combined effects of these variants on LREs. The longitudinal multicenter cohort study enrolled 1178 patients with biopsy-proven MASLD. We calculated the genetic risk of hepatic fibrosis and LRE according to the impact of these variants. Patients with genetic fibrosis scores of 2, 3, and 4 or 5 were at greater risk than patients with scores of 0 or 1, with odds ratios of 2.45 (95% CI, 1.27-4.74), 2.14 (95% CI, 1.17-3.94), and 2.54 (95% CI, 1.35-4.77), respectively. Multivariate analysis revealed that PNPLA3 and TM6SF2, but not HSD17B13, were associated significantly with LRE development. The hazard ratio of the genetic high-risk group for LRE was 1.91 (95% CI, 1.20-3.04). The higher risk of LRE development in the genetic high-risk group also was seen in patients with F ≥ 3 or Fibrosis-4 index > 2.67. The hazard ratios of the genetic high-risk group for LRE were greater in patients without obesity, without diabetes, and of younger age compared with patients with obesity, with diabetes, or of older age, respectively. This combination of MASLD-related genetic variants is useful for predicting LREs in Japanese patients with MASLD. The genetic risk according to these variants is useful for LRE risk assessment, especially in patients without metabolic risk factors or in younger patients in Japan.

Response to psychotic experiences: Impact of personality traits on perceived levels of distress

BackgroundThis study examined the influence of personality traits on (subclinical) positive symptom distress in patients with a psychotic disorder, their unaffected siblings and healthy controls. MethodsData were obtained from the Genetic Risk and Outcome of Psychosis study (GROUP), a Dutch longitudinal multicenter cohort study. Data from 140 patients, 216 unaffected siblings and 102 healthy controls was available for baseline levels of Five Factor Model personality traits and frequency and distress due to psychotic experiences three years later, assessed with the Community Assessment of Psychic Experience questionnaire. Main effects of all five personality traits on symptom distress were investigated as well as moderating effects of Neuroticism, Extraversion and Openness on positive symptom frequency and positive symptom distress. Age, gender, symptom frequency and IQ were controlled for. ResultsIn both patients and siblings, the observed main effects of Neuroticism and Openness on (subclinical) positive symptom distress three years later either lost significance or had a very small effect size when controlling for covariates, mainly due to the correction for the effect of positive symptoms on personality traits at baseline. In both groups, levels of Openness at baseline moderated the association between positive symptom frequency and positive symptom distress three years later, in the direction that higher levels of Openness were associated with weaker associations between positive symptom frequency and - distress, even when covariates were controlled for. DiscussionThe level of Openness to Experiences influences the perceived distress from (subclinical) positive symptoms in both patients and siblings.

High prevalence of associated injuries in anterior cruciate ligament tears: A detailed magnetic resonance imaging analysis of 254 patients

ObjectivesTo evaluate the type and prevalence of associated injuries by using magnetic resonance imaging (MRI) in patients with anterior cruciate ligament (ACL) tears.MethodsData from the Natural Corollaries and Recovery after ACL injury multicenter longitudinal cohort study were analyzed. Between May 2016 and October 2018, patients aged between 15 and 40 years, who had experienced an ACL tear within the last 6 weeks and sought medical attention at one of seven healthcare clinics in Sweden, were invited to participate. The mean time from injury to MRI was 19.6 ± 15.2 days. An orthopedic knee surgeon and a musculoskeletal radiologist reviewed all the MRI scans. The following structures were assessed: posterior cruciate ligament (PCL), medial collateral ligament (MCL) complex, lateral collateral ligament (LCL), popliteus tendon, medial meniscus (MM), lateral meniscus (LM), and cartilage. In addition, the presence of bone bruising, impaction fractures in the lateral femoral condyle (LFC) or posterolateral tibia (PLT), and Segond fractures were also assessed. ResultsA total of 254 patients (48.4% males) with a mean age of 25.4 ± 7.1 years were included. The prevalence of associated injuries was as follows: PCL (0.4%), MCL {41.3% [superficial MCL and deep MCL (dMCL) 16.5%; isolated dMCL 24.8%]}, LCL (2.4%), MM (57.4%), LM (25.2%), cartilage (15.0%), bone bruising (92.9%), impaction fracture in the LFC (45.7%) and PLT (4.7%), and Segond fracture (7.5%).ConclusionsThe prevalence of associated injuries in patients with ACL tears was high. The findings reported in this study may serve as a reference tool for orthopedic surgeons and radiologists in the diagnosis of associated injuries using MRI in patients with ACL tears.

Prevalence and trajectories of neuropsychological post-COVID-19 symptoms in initially hospitalized patients.

To investigate the prevalence and trajectories of post-COVID-19 neuropsychological symptoms. Prospective longitudinal multicentre cohort study. A total of 205 patients initially hospitalized with SARS-CoV-2 (COVID-19). Validated questionnaires were administered at 9 months (T1) and 15 months (T2) post-hospital discharge to assess fatigue, cognitive complaints, insomnia, anxiety, depression, and post-traumatic stress symptoms. Analyses included 184 out of 205 patients. Approximately 50% experienced high cognitive complaints at T1 and T2, while severe fatigue affected 52.5% at T1 and 55.6% at T2. Clinically relevant insomnia scores were observed in 25% of patients at both time-points. Clinically relevant anxiety scores were present in 18.3% at T1 and 16.7% at T2, depression in 15.0% at T1 and 18.9% at T2, and PTSD in 12.4% at T1 and 11.8% at T2. Most symptoms remained stable, with 59.2% of patients experiencing at least 1 persistent symptom. In addition, 31.5% of patients developed delayed-onset symptoms. Post-COVID-19 cognitive complaints and fatigue are highly prevalent and often persist. A subgroup develops delayed symptoms. Emotional distress is limited. Screening can help identify most patients experiencing long-term problems. Future research should determine risk factors for persistent and delayed onset symptoms.

COVID-19−Associated Acute Kidney Injury and Longitudinal Kidney Outcomes

COVID-19 infection is associated with a high incidence of acute kidney injury (AKI). Although rapid kidney function decline has been reported in the first few months after COVID-19-associated AKI (COVID-AKI), the longer-term association of COVID-AKI with kidney function remains unknown. To assess long-term kidney outcomes of patients who had COVID-19-associated AKI. This was a retrospective longitudinal multicenter cohort study conducted in a large hospital system using electronic health records data on adult hospitalized patients with AKI and COVID-19 or other illnesses. Included patients were hospitalized during the COVID-19 pandemic (March 2020-June 2022), were screened for SARS-CoV-2, had AKI, and survived to discharge, or had been hospitalized during the 5 years before the pandemic (October 2016-January 2020), had a positive influenza A or B test result, had AKI, and survived to discharge. Patients were followed up for a maximum of 2 years after hospital discharge. Data analyses were performed from December 2022 to November 2023. COVID-19 and influenza. The primary outcome was major adverse kidney events (MAKE), defined as a composite of mortality and worsened kidney function (estimated glomerular filtration rate [eGFR] decline by ≥25% from discharge eGFR or kidney failure requiring dialysis). Multivariable time-to-event analyses were performed to compare MAKE between individuals with COVID-AKI and those who had AKI associated with other illnesses hospitalized during the same period. For further comparison, this outcome was assessed for a historic cohort of patients with influenza-associated AKI. The study cohort included 9624 hospitalized patients (mean [SD] age, 69.0 [15.7] years; 4955 [51.5%] females) with AKI, including 987 patients with COVID-AKI, 276 with influenza-associated AKI, and 8361 with AKI associated with other illnesses (other-AKI). Compared with the other 2 groups, patients with COVID-19-associated AKI were slightly younger in age, had a higher baseline eGFR, worse baseline comorbidity scores, higher markers of illness severity, and longer hospital stay. Compared with the other-AKI group, the COVID-AKI group had lower MAKE (adjusted hazard ratio [aHR], 0.67; 95% CI, 0.59-0.75) due to lower all-cause mortality (aHR, 0.31; 95% CI, 0.24-0.39) and lower rates of worsened kidney function (aHR, 0.78; 95% CI, 0.69-0.88). The findings of this multicenter cohort study indicate that survivors of hospitalization with COVID-AKI experience lower rates of MAKE, long-term kidney function decline, and mortality compared with patients with AKI associated with other illnesses.

A multi-year longitudinal study exploring the impact of the COVID-19 pandemic on students’ familiarity and perceptions of active learning

The COVID-19 pandemic caused nearly ubiquitous emergency remote teaching in both secondary and post-secondary education. While there has been a plethora of work examining how instructors adjusted classes to incorporate active learning during emergency remote teaching, there has only been minimal work examining how such emergency remote teaching may have influenced students’ perceptions of active learning. Here, we conduct a longitudinal multi-cohort study at one institution across nine semesters before, during, and after emergency remote teaching due to the pandemic to explore how college students’ familiarity and perceptions of active learning have shifted over time because of the pandemic. Our results reveal decreases in familiarity with active learning during emergency remote teaching, with familiarity remaining lower than pre-COVID even after the end of emergency remote teaching. In addition, our results indicate shifts in students’ perceptions of active learning, leading to potentially higher student resistance to active learning following emergency remote teaching. We conclude by discussing implications for instructors to better support active learning and promote engagement in active learning classes following the end of emergency remote teaching.

Investigation of the Associations of Smoking With Hip Osteoarthritis: A Baseline Cross-Sectional and Four- to Five-Year Longitudinal Multicohort Study.

This study aimed to investigate the effect of smoking on the prevalence, incidence, and progression of hip osteoarthritis (OA). We used data from the Osteoarthritis Initiative (OAI) and the Cohort Hip and Cohort Knee (CHECK) studies. We analyzed 9,386 hips from 4,716 participants (OAI cohort) and 1,954 hips from 977 participants (CHECK cohort). The primary exposure was smoking status at baseline, categorized as current, former, or never smoker. Outcomes of radiographic hip OA (RHOA) and symptomatic hip OA were evaluated both cross-sectionally at baseline and longitudinally over a 4- to 5-year follow-up, with adjustments for major covariates. No significant differences were observed between current or former smokers and never smokers for any of the outcomes examined, either at baseline or at the 4- to 5-year follow-up. In the cross-sectional analysis, the odds ratios with 95% confidence intervals for the prevalence of RHOA for current and former smokers were 1.29 (0.68-2.46) and 0.99 (0.70-1.40) in the OAI cohort and 1.38 (0.78-2.44) and 0.85 (0.54-1.32) in the CHECK cohort, respectively. In the longitudinal analysis, odds ratio with 95% confidence intervals for the incidence of RHOA were 1.03 (0.23-4.50) and 0.92 (0.46-1.85) in the OAI cohort and 0.61 (0.34-1.11) and 1.00 (0.69-1.44) in the CHECK cohort, respectively. Our study found no clear association between smoking and the prevalence, incidence, or progression of RHOA or symptomatic hip OA, either at baseline or over a 4- to 5-year period.

PLASMA BIOMARKERS FOR ALZHEIMER’S DISEASE AND RELATED NEUROPATHOLOGY IN RELATION TO MCI AND DEMENTIA: THE ARIC STUDY

Abstract Blood-biomarkers for Alzheimer’s Disease and related neuropathological processes, including amyloidosis, tau deposition, and neurodegeneration, may revolutionize the monitoring of risk and progression of neurocognitive outcomes in older adults. At visit 5 (2011-13) of the ARIC study, a multi-center longitudinal cohort study, amyloid-beta (Aβ42:Aβ40), ptau-181, glial fibrillary acidic protein (GFAP), and neurofilament light (NFL) were measured in plasma using an ultrasensitive single-molecule array (Simoa; Quanterix N4PE + p-tau-181 single-plex) in a sample of 1,711 participants (Age=76±5 years, 60% Female, 28% Black). Neurocognitive outcomes included adjudicated dementia and mild cognitive impairment (MCI) through 2019 for a median follow-up of 5.6 years. Multinomial logistic regressions estimated Relative Risk Ratios (RRR) of the four-category outcome of MCI (n=543), dementia (n=371), and death (n=59) vs. cognitively unimpaired (n=736) for each base(2) log-transformed biomarker, adjusted for age, sex, education, site-race, hypertension, diabetes, BMI, APOE, and eGFR. When estimates appeared similar for MCI and dementia, an additional analysis modeled RRR of a three-category outcome of combined MCI/dementia, death, and cognitively unimpaired. Higher plasma Aβ42:Aβ40 ratio was associated with lower MCI/dementia risk (RRR=0.48, 95%CI: 0.32,0.73). Higher levels of all other biomarkers were associated with higher risk of MCI [p-tau181 (RRR=1.57, 95%CI: 1.23,2.00); GFAP (RRR=1.31, 95%CI: 1.03,1.67); NFL (RRR=1.64, 95%CI: 1.26,2.13)] and dementia [p-tau181 (RRR=3.16, 95%CI: 2.43,4.11); GFAP (RRR=2.40, 95%CI: 1.80,3.20); NFL (RRR=3.62, 95%CI: 2.58,5.09)]. These results indicate blood-biomarkers representative of multiple neuropathological processes were strongly associated with both MCI and all-cause dementia outcomes, emphasizing their potential role as tools in risk identification, early diagnosis, and possibly guiding interventions.

NTproBNP values for the diagnosis of congestive heart failure in dyspneic old patients regarding age

Abstract Background The diagnosis of heart failure (HF) in elderly patients is often difficult, due to overlap of typical signs and symptoms with those of comorbidities. Plasma N-Terminal Pro-Brain Natriuretic Peptide(NTproBNP) is known to increase with age and according to comorbidities. However, the diagnostic performance of this biomarker is unclear in those patients. Aims This study sought to define the diagnostic accuracy of plasma NTproBNP in patients over 75 yo in a large population referred for acute dyspnea in the Assistance Publique-Hôpitaux de Paris. Methods and Results In this retrospective, longitudinal multicenter cohort study, we collected data from 12,974 patients aged 75 years or older who were hospitalized for acute dyspnea with NTproBNP measurement in the 48 hours after admission between 2011 and 2021 in geriatrics, cardiology and pulmonology departments. The final diagnosis was classified with the International Classification of Diseases, 10th Revision (ICD 10) as either "AHF" or "other acute respiratory failure" (OARF), represented by pulmonary embolism, COPD and pneumonia. The Mean (SD) age of our population was 84.4 (6.1) years old, and 52.7% of patients were women. 8,385 (64.6%) patients had an AHF diagnosis at discharge. Regarding age of patients, NT-proBNP threshold values was higher in patients over 85 yo, 2530 ng/L, compared to that of patients < 85 yo, 1680 ng/L. The NTproBNP threshold for ‘ruling-out’ AHF had a 79% sensitivity in patient > 85 YO and 82% sensitivity in patient 75- 85 YO. In patients > 85 compared with patient 75-85 yo, predictive positive value was 85 and 86 %, specificity was 65% and 75% and AUC was 0.77 and 0.84. Finally, despite the consideration of other clinical and biological parameters, NTproBNP level remain more discriminating for the diagnosis of AHF in old patients with comorbidities. Conclusion In patients 75-85 and over 85 years of age referred for acute dyspnea with NTproBNP dosage at admission, a cutoff of 1680 and 2530 ng/L respectively allow for an accurate diagnosis of AHF.

NTproBNP values for diagnosis of congestive heart failure in old patients regarding kidney failure

Abstract Background The diagnosis of heart failure (HF) in old patients is often difficult, due to overlap of typical symptoms and comorbidities. Plasma N-Terminal Pro-Brain Natriuretic Peptide(NTproBNP) is known to increase with age and according to comorbidities particularly in chronic kidney failure. However, the diagnostic performance of this biomarker is unclear in those patients with kidney failure. Aims This study sought to define the diagnostic accuracy of plasma NTproBNP in patients over 75 yo in a large population referred for acute dyspnea in the Assistance Publique-Hôpitaux de Paris. Methods and Results In this retrospective, longitudinal multicenter cohort study, we collected data from 12,974 patients aged 75 years or older who were hospitalized for acute dyspnea with NTproBNP measurement in the 48 hours after admission between 2011 and 2021 in geriatrics, cardiology and pulmonology departments. The final diagnosis was classified with the International Classification of Diseases, 10th Revision (ICD 10) as either "AHF" or "other acute respiratory failure" (OARF), represented by pulmonary embolism, COPD and pneumonia. The Mean (SD) age of our population was 84.4 (6.1) years old, and 52.7% of patients were women. 8,385 (64.6%) patients had an AHF diagnosis at discharge. Regarding creatinine clearance (CrCl) of patients, NT-proBNP threshold values was lower in patients with CrCl ≥40 ml/min compared to that of patients CrCl <40 ml/min, 1681 and 2238 ng/L respectively. The NTproBNP threshold for ‘ruling-out’ AHF had 81% sensitivity in patient with CrCl ≥40 ml/min and 87% sensitivity in patient with CrCl <40 ml/min. In patients with CrCl ≥40 ml/min compared with patient with CrCl <40 ml/min, predictive positive value was 82 and 89 %, specificity was 70% and 45% and AUC was 0.81 and 0.69. The other comorbidities that statistically change NTproBNP cutpoint diagnostic value were atrial fibrillation, age and sex. Conclusion In old patients referred for acute dyspnea with NTproBNP dosage at admission with kidney failure, cutpoint values of 1681 and 2238 ng/L according to CrCl allow for an accurate diagnosis of AHF.

A comprehensive CMR analysis improves risk stratification in left ventricular noncompaction

Abstract Background Left ventricular noncompaction (LVNC) is a heterogeneous and controversial entity. Risk assessment by cardiovascular magnetic resonance (CMR) remains poorly defined. Purpose To develop a CMR prediction model of major adverse cardiovascular events (MACE) in LVNC. Methods We conducted a retrospective longitudinal multicentre cohort study of LVNC patients with core-lab CMR analysis. The endpoint was a composite of MACE: heart failure, ventricular arrhythmias, systemic embolisms and all-cause death. The effect of variables on the endpoint was analysed by Cox regression and variables were dichotomized according to their association with the outcome. Three sequential prediction models were developed: a "traditional model" based on LV ejection fraction (LVEF); a "clinical model" based on daily-practice CMR variables (e.g.: LVEF, right ventricular (RV) EF, and late gadolinium enhancement (LGE)); and a "research model" including advanced parameters (e.g.: global longitudinal strain (GLS) and hemodynamic forces (HDF)). The best prediction models were chosen based on C-statistic and Akaike information criterion (AIC). A risk score was developed based on the third model, and according to proportional hazard ratios. Results A total of 348 patients were included, age was 46 (19) years and 150 (43%) were female. LVEF was 48 (14) % and 32 (10%) had LGE. During a median follow-up of 3.9 (1.8-6.1) years, 54 (16%) patients developed MACE: 27 (8%) heart failure, 32 (9%) ventricular arrhythmias, 2 (1%) systemic embolisms and 6 (2%) deaths. Figure 1 shows the association of the main CMR variables with the endpoint. The "traditional model" (dichotomic LVEF with cut-off point at 40%) had an AUC of 0.71 (95% CI: 0.64-0.78). The best "clinical model" was a combination of LVEF, RVEF (cut-off point 35%), left atrium (LA) volume index (cut-off point 53 mL/m2) and percentage of LGE mass (LGE%, cut-off point 5%), with an AUC of 0.77 (95% CI: 0.70-0.85; p=0.006 compared to the first model). The best "research model" included LVEF, RVEF, LGE%, LA GLS (two cut-off points 17% and 28%), and lateral-septal HDF (cut-off point 3%), with an AUC of 0.85 (95% CI: 0.80-0.90; p=0.007 compared to the second model) (Figure 2a). Subsequently, a risk score was developed: 1 point was assigned to LVEF<40%, RVEF<35%, LGE% >5% and LA-GLS <28%, 2 points to LA-GLS <17% and 4 points to HDF<3%. The score was accurate at identifying both low- (0-4 points), intermediate- (5-7 points) and high-risk (8-9 points) patients (Figure 2b). Conclusions A comprehensive CMR evaluation in LVNC allows for precise risk stratification. Our proposed prediction model could be used to individualise patients’ management, which might improve long-term outcomes.CMR characteristics according to MACEPrediction models of MACE and risk score

Risk determination of COVID-19 among unvaccinated nonpregnant women in Metro Manila, Philippines: A multicenter longitudinal cohort study

BACKGROUND: While the COVID-19 pandemic’s impact on the general population is well studied, less attention has been given to preexisting socioeconomic, lifestyle, and obstetric-gynecologic factors affecting baseline risks for unvaccinated nonpregnant women in early pandemic days in the Philippines. MATERIALS AND METHODS: This prospective multicenter cohort study assessed COVID-19 status and used a validated questionnaire to identify potential disease risks. Generalized linear models with a Poisson distribution were employed to examine the relationship between determinants and COVID-19 status, adjusting for confounding factors. RESULTS: Risk factors include Manila residency, Muslim faith, smoking history, at least one familial comorbidity, and local government hospital admission. Conversely, postgraduate education and contraceptive use seem protective. CONCLUSION: Sociodemographic and lifestyle factors may be linked to COVID-19 infection in unvaccinated nonpregnant women. Further exploration of sociocultural pressures on women during the pandemic is warranted.

The severity of the recurrent preeclampsia compared with prior preeclampsia: A multicenter retrospective longitudinal cohort study

The severity of the recurrent preeclampsia compared with prior preeclampsia: A multicenter retrospective longitudinal cohort study

UNICORNS: Uveitis in childhood prospective national cohort study protocol.

Background: Childhood uveitis is a rare inflammatory eye disease which is typically chronic, relapsing-remitting in nature, with an uncertain aetiology (idiopathic). Visual loss occurs due to structural damage caused by uncontrolled inflammation. Understanding of the determinants of long term outcome is lacking, including the predictors of therapeutic response or how to define disease control. Aims: To describe disease natural history and outcomes amongst a nationally representative group of children with non-infectious uveitis, describe the impact of disease course on quality of life for both child and family, and identify determinants of adverse visual, structural and developmental outcomes. Methods: UNICORNS is a prospective longitudinal multicentre cohort study of children newly diagnosed with uveitis about whom a core minimum clinical dataset will be collected systematically. Participants and their families will also complete patient-reported outcome measures annually from recruitment. The association of patient (child- and treatment- dependent) characteristics with outcome will be investigated using logistic and ordinal regression models which incorporate adjustment for within-child correspondence between eyes for those with bilateral disease and repeated outcomes measurement. Discussion: Through this population based, prospective longitudinal study of childhood uveitis, we will describe the characteristics of childhood onset disease. Early (1-2 years following diagnosis) outcomes will be described in the first instance, and through the creation of a national inception cohort, longer term studies will be enabled of outcome for affected children and families.

Viral suppression and retention in HIV care during the postpartum period among women living with HIV: a longitudinal multicenter cohort study.

Low rates of postnatal retention in HIV care and viral suppression have been reported in women living with HIV (WLWH) despite viral suppression at delivery. At the same time, postpartum follow-up is of crucial importance in light of the increasing support offered in many resource-rich countries including Switzerland to WLWH choosing to breastfeed their infant, if optimal scenario criteria are met. We longitudinally investigated retention in HIV care, viral suppression, and infant follow-up in a prospective multicentre HIV cohort study of WLWH in the optimal scenario who had a live birth between January 2000 and December 2018. Risk factors for adverse outcomes in the first year postpartum were assessed using logistic and proportional hazard models. Overall, WLWH were retained in HIV care for at least six months after 94.2% of the deliveries (694/737). Late start of combination antiretroviral therapy (cART) during the third trimester was found to be the main risk factor for failure of retention in HIV care (crude odds ratio [OR] 3.91; 95% confidence interval [CI], 1.50-10.22; p=0.005). Among mothers on cART until at least one year after delivery, 4.4% (26/591) experienced viral failure, with illicit drugs use being the most important risk factor (hazard ratio [HR], 13.2; 95% CI, 2.35-73.6; p=0.003). The main risk factors for not following the recommendations regarding infant follow-up was maternal depression (OR, 3.52; 95% CI, 1.18-10.52; p=0.024). Although the results are reassuring, several modifiable risk factors for adverse postpartum outcome, such as late treatment initiation and depression, were identified. These factors should be addressed in HIV care of all WLWH, especially those opting to breastfeed in resource-rich countries. This study has been financed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #201369), by SHCS project 850 and by the SHCS research foundation.

High Prevalence of Superficial and Deep Medial Collateral Ligament Injuries on Magnetic Resonance Imaging in Patients With Anterior Cruciate Ligament Tears

To assess the prevalence of and factors associated with medial collateral ligament (MCL) complex injuries on magnetic resonance imaging (MRI) in patients with anterior cruciate ligament (ACL) tears. Data were extracted from the Natural Corollaries and Recovery After ACL Injury (NACOX) multicenter longitudinal cohort study. Between May 2016 and October 2018, patients who presented to 1 of 7 health care clinics across Sweden with an ACL tear sustained no more than 6 weeks earlier and who were aged between 15 and 40 years at the time of injury were invited to participate. All the patients included in this study underwent MRI. The mean time from injury to MRI was 19.6 ± 15.2 days. An orthopaedic surgeon specializing in knee surgery and a musculoskeletal radiologist reviewed all MRI scans. Injuries to the superficial MCL (sMCL), deep MCL (dMCL), and posterior oblique ligament were identified. Stepwise forward multiple binary logistic regression analyses were used to evaluate patient characteristics (age, sex, body mass index, preinjury Tegner activity level, and activity at injury) and injuries on MRI (lateral meniscus [LM] injury, medial meniscus [MM] injury, pivot shift-type bone bruising, medial femoral condyle [MFC] bone bruising, and lateral femoral condyle [LFC] impaction) associated with the presence of MCL complex tears. In total, 254 patients (48.4% male patients) with a mean age of 25.4 ± 7.1 years were included. The overall prevalence of MCL (sMCL and dMCL) injuries and isolated dMCL injuries was 16.5% (42 of 254) and 24.8% (63 of 254), respectively. No isolated sMCL injuries were found. Posterior oblique ligament injuries were found in 12 patients (4.7%) with MCL (sMCL and dMCL) injuries. An LM injury (odds ratio [OR], 3.94; 95% confidence interval [CI], 1.73-8.94; P= .001) and LFC impaction (OR, 2.37; 95% CI, 1.11-5.07; P= .02) increased the odds of having an MCL injury, whereas an MM injury (OR, 0.26; 95% CI, 0.12-0.59; P= .001) reduced the odds. Isolated dMCL injuries were significantly associated with MFC bone bruising (OR, 4.21; 95% CI, 1.92-9.25; P < .001) and LFC impaction (OR, 3.86; 95% CI, 1.99-7.49; P < .001). The overall combined prevalence of MCL (sMCL and dMCL) injuries and isolated dMCL injuries in patients with ACL tears was high (16.5%+ 24.8%= 41.3%). The presence of an LM injury and LFC impaction increased the odds of having an MCL injury, whereas the presence of an MM injury reduced the odds. MFC bone bruising and LFC impaction were associated with the presence of isolated dMCL injuries. Level III, retrospective cohort study.

#2599 LONG-TERM LONGITUDINAL CHANGES OF PULSE WAVE VELOCITY AND THEIR ASSOCIATION TO CARDIOVASCULAR RISK FACTORS IN MAINTENANCE HEMODIALYSIS PATIENTS

Abstract Background and Aims The incidence of end-stage renal disease (ESRD) is increasing worldwide. The mortality rate in this patient cohort remains unacceptably high. The WHO estimates ESRD as one of the ten global causes of premature death. Approximately half of all death cases are due to cardiovascular complications. A main cardiovascular risk factor is enhanced arterial stiffness. The measurement of pulse wave velocity (PWV) for evaluation of progressive atherosclerosis is known to be an independent risk predictor for cardiovascular and all-cause mortality in chronic dialysis patients. Method The study cohort contains patients from the “Risk stratification in end-stage renal disease - the ISAR study”, a multicenter prospective longitudinal observatory cohort study. A total of 105 patients on maintenance hemodialysis were examined and followed-up for up to 72 months. Pulse wave velocity was obtained by the Mobil-O-Graph 24h PWA Monitor device at baseline and follow-up. We assessed the PWV change over time and correlated PWV with known cardiovascular risk factors using Pearson correlation coefficient adjusting for age. Longitudinal changes were examined using t-tests for paired and independent samples. Results Patients had a median age of 61,2 years (IQR 23,2), 36 (34%) were female. Median baseline dialysis vintage was 105 months (IQR 71), and median adapted Charlson Comorbidity Index 2 (IQR 3). During a median follow-up of 74,1 months there was a significant increase in PWV from baseline (9,25 m/s) to 6YFU (10,18 m/s, p = &amp;lt;0,001), a delta-PWV of 0,92 m/s, appropriate to a yearly change of 0,15 m/s. Patients with hypertension had a significant higher PWV (10,47 m/s) than those with normal blood pressure (8,91 m/s, p = 0,034). The Pearson correlation coefficient analysis showed after adjustment for age a significant correlation between blood pressure and both 6YFU-PWV (systolic r = 0,89 diastolic r = 0,62, p = &amp;lt;0,001) and delta-PWV (systolic r = 0,71 diastolic 0,48, p = &amp;lt;0,001). Additionally, after adjustment for age delta-PWV correlated with LDL-cholesterol (r = 0,27, p = 0,023). Neither 6YFU-PWV nor delta-PWV showed significant associations to other traditional cardiovascular risk factors such as diabetes, high cholesterol or obesity. Conclusion In this cohort, we found a longitudinal increase of pulse wave velocity over 6 years. However, the average change in PWV per year was significantly lower in our cohort compared to other studies with a shorter observation period. A main reason might be the long follow-up time, with the occurrence of several deaths in the primary cohort of the ISAR-Study before reaching the follow-up point and therefore including more younger and possibly healthier patients. Nevertheless, in this cohort blood pressure in contrast to diabetes, high cholesterol or obesity was a primary factor in the change of PWV. The reasons for the deceleration of cardiovascular and mortality risk after a long term in this sub cohort remains unclear and requires further investigation.

Migrating a Well-Established Longitudinal Cohort Database From Oracle SQL to Research Electronic Data Entry (REDCap): Data Management Research and Design Study.

Providing user-friendly electronic data collection tools for large multicenter studies is key for obtaining high-quality research data. Research Electronic Data Capture (REDCap) is a software solution developed for setting up research databases with integrated graphical user interfaces for electronic data entry. The Swiss Mother and Child HIV Cohort Study (MoCHiV) is a longitudinal cohort study with around 2 million data entries dating back to the early 1980s. Until 2022, data collection in MoCHiV was paper-based. The objective of this study was to provide a user-friendly graphical interface for electronic data entry for physicians and study nurses reporting MoCHiV data. MoCHiV collects information on obstetric events among women living with HIV and children born to mothers living with HIV. Until 2022, MoCHiV data were stored in an Oracle SQL relational database. In this project, R and REDCap were used to develop an electronic data entry platform for MoCHiV with migration of already collected data. The key steps for providing an electronic data entry option for MoCHiV were (1) design, (2) data cleaning and formatting, (3) migration and compliance, and (4) add-on features. In the first step, the database structure was defined in REDCap, including the specification of primary and foreign keys, definition of study variables, and the hierarchy of questions (termed "branching logic"). In the second step, data stored in Oracle were cleaned and formatted to adhere to the defined database structure. Systematic data checks ensured compliance to all branching logic and levels of categorical variables. REDCap-specific variables and numbering of repeated events for enabling a relational data structure in REDCap were generated using R. In the third step, data were imported to REDCap and then systematically compared to the original data. In the last step, add-on features, such as data access groups, redirections, and summary reports, were integrated to facilitate data entry in the multicenter MoCHiV study. By combining different software tools-Oracle SQL, R, and REDCap-and building a systematic pipeline for data cleaning, formatting, and comparing, we were able to migrate a multicenter longitudinal cohort study from Oracle SQL to REDCap. REDCap offers a flexible way for developing customized study designs, even in the case of longitudinal studies with different study arms (ie, obstetric events, women, and mother-child pairs). However, REDCap does not offer built-in tools for preprocessing large data sets before data import. Additional software is needed (eg, R) for data formatting and cleaning to achieve the predefined REDCap data structure.