Prospective Longitudinal Multicenter Study Research Articles

SARS-CoV-2 seroprevalence among people living with HIV in the German HIV-1 Seroconverter Cohort, 2020–2022

ObjectivesPeople living with HIV (PLWH) are a risk group for severe symptoms and higher mortality during COVID-19. We analyzed the dynamic rise of SARS-CoV-2 seroprevalence induced by coinfections and vaccinations in PLWH in the first three years of the pandemic in Germany and compared it with corresponding data available for the general population.MethodsEach month on average 93 blood samples from the German HIV-1 Seroconverter Cohort, a prospective longitudinal multicenter study that includes PLWH whose date of seroconversion is well defined, were received. The samples from 1569 PLWH were tested for the presence of anti-S1 and if positive, also for anti-N antibodies.ResultsIn 2020 the number of anti-S1 positive cases/month was between 0.0 and 6.9% (average 1.6%). Since then the anti-S1 prevalence increased reaching already 35% (33/94) in May 2021. At that time 3.2% of the cases were also anti-N positive. In 2022 the average anti-S1 seroprevalence reached 97.5%. In the vaccination era a positive anti-N response was associated with a younger age and females were overrepresented among anti-S1/anti-N negative samples (assuming no vaccination or infection).ConclusionsThe average 1.6% anti-S1 seroprevalence in the cohort in 2020 was comparable to that in the general population (1.3%). The increase in anti-S1 seroprevalence in the first half of 2021 occurred slightly earlier. This increase was likely caused by the prioritization of PLWH at the early stage of the vaccination campaign and by infections during the third wave of the pandemic.

Association between the cumulative excessive systolic blood pressure and left ventricular mass index

Abstract Background Ambulatory blood pressure (ABP) has been increasingly adopted in day-to-day clinical practices. Although clinicians can access an enormous amount of information regarding an individual’s blood pressures (BPs) through the ABP monitoring (ABPM), to date, only the mean BP is utilized as the diagnostic threshold of hypertension and the therapeutic target for BP control and no other indices were widely used to assess the burdens of high BP in the ABPM. Because elevated systolic BPs (SBPs) cumulatively damage the myocardium and induce hypertrophy and fibrosis, we hypothesized that the summated value of BP readings beyond a target level may be the better indicator of the overall BP loads than the mean BP value. Methods The Korean ABP registry is a multicenter prospective longitudinal cohort study performed in outpatients with hypertension. Among 5,965 patients enrolled in the registry, 951 patients with valid ABPM records and appropriate echocardiography measurements included in the study. The left ventricular mass (LVM) was normalized using the height2.7(m) (LVM index [LVMIH2.7] = LVM/Height2.7). The cumulative excessive SBP CE-SBP) was defined as the summation of the products of excessive SBPs (≥135 mmHg during wake, ≥10 mmHg during sleep) and the durations of the excessive SBP (Figure 1). Results The CE-SBP was non-linearly associated with both the office SBP and the mean SBP, but the association strength was much greater with the mean SBP than with the office SBP (R2=0.902 vs. R2=0.430). In linear regression models, the association of the CE-SBP with the LVMIH2.7 (R2=0.112 [0.074-0.149]) was greater than that of the office SBP (R2=0.072 [0.040-0.103]), the mean SBP (R2=0.082 [0.049-0.116]) or the mean SBP during sleep (R2=0.99 [0.063-0.134]). Non-linear regression models using restrictive cubic spline fits also showed that the association strength was greater with the CE-SBP (R2=0.117 [0.078-0.155]) than with the office SBP, mean SBP or mean SBP during sleep (Figure 2). Left ventricular hypertrophy (LVH) defined as the LVMIH27 ≥54 g/m2.7 was better predicted with the CE-SBP than with the other SBPs. The association between the CE-SBP and LVMIH27 was stronger in the patients not taking antihypertensive medications (R2=0.121) and strongest in those with the non-dipper pattern (R2=0.125). Combination with the variability indices (successive variation and average real variability) during sleep or the maximum SBP during sleep significantly improved the association strength of CE-SBP with LMMIH27, whereas the combination with the mean SBP or the variability indices during the entire period did not, in the linear models. Conclusion The CE-SBP was more strongly associated with the LVMIH27 than the office SBP and the mean SBP in the ABPM. This result suggests that the CE-SBP may be the better indicator of overall BP loads than the office SBP or the mean SBP in the ABPM, in patients with hypertension.Figure 1Figure 2

Differential impact of clinic BP target on the prevalence and predictors of the masked uncontrolled hypertension and white-coat uncontrolled hypertension

Abstract Background Although intensive blood pressure (BP) control have been advocated, major clinical practices guidelines still recommend clinic BP (cBP) < 149/90 mmHg as the target for antihypertensive therapy. But, cBP targets could influence the prevalence and predictors of any hypertension phenotype. We investigated how different cBP targets impacted on the prevalence and predictors of masked uncontrolled hypertension (MUCH) and white-coat uncontrolled hypertension (WUCH) using the Korean Ambulatory Blood Pressure (KorABP) registry. Methods A multicenter prospective longitudinal cohort study was performed in outpatients with hypertension. Among 5,965 patients enrolled in the KorABP registry, 1,601 patients on antihypertensive medications with a valid ambulatory BP monitoring record were included in this study. Two different cBP targets, <130/80mmHg (intensive) and <140/90 mmHg (conventional) were investigated. Results Controlled ambulatory BP (aBP; <130/80 mmHg) was observed in 472 patients (29.5%). Controlled cBP was shown in 348 patients (21.7%) with the intensive cBP target and in 697 patients (43.5%) with the conventional cBP target. Controlled hypertension, WUCH, MUCH and uncontrolled hypertension were found in 294, 174, 54, and 1,075 patients with the intensive target and in 378, 94, 319 and 810 patients with the conventional target, respectively. Among the patients with controlled cBP, the prevalence of MUCH markedly decreased with the intensive target (15.5%), compared to the conventional target (45.8%). In contrast, among the patients with uncontrolled cBP, the prevalence of WUCH had only 3.8% increase with the intensive target (10.4%), compared to the conventional target (14.2%) (Figure 1). With the conventional target, 75.9% of patients with MUCH had cBP between 130/80 mmHg and 139/89 mmHg. The concordance between the controlled aBP and controlled cBP was higher with the intensive target than with the conventional target (Cohen’s κ 0.62 [0.58-0.67] vs. 0.46 [0.41-0.50]). The logistic models for MUCH included the left ventricular mass index and underuse of antihypertensive drugs (<2 types of drugs) as the common predictors of the both targets. With the conventional target, clinic systolic BP and diastolic BP were the strongest predictors of MUCH, but the cBP was not a predictor of MUCH with the intensive target. The logistic models for WUCH included beta-blocker use, increased heart rate and lower waist circumference and clinic systolic BP as the common predictors of WUCH with the both target. The logistic model for MUCH performed better with the conventional target, whereas the logistic model for WUCH performed better with the intensive target (Figure 2). Conclusion The use of the intensive cBP target (<130/80 mmHg) could reduce the prevalence of MUCH with minimal increase in the prevalence of WUCH and would provide the better assessment for the BP control status than the use of the conventional cBP target (<140/90 mmHg).Figure 1Figure 2

Faecal Volatile Organic Compounds to Detect Colorectal Neoplasia in Lynch Syndrome-A Prospective Longitudinal Multicentre Study.

Non-invasive biomarkers may reduce post-colonoscopy colorectal cancer (CRC) rates and colonoscopy overuse in Lynch syndrome. Unlike faecal immunochemical test (FIT), faecal volatile organic compounds (VOCs) may accurately detect both advanced and non-advanced colorectal neoplasia. The aim of this study was to evaluate the potential of faecal VOCs-separately and with FIT-to guide optimal colonoscopy intervals in Lynch syndrome. Prospective longitudinal multicentre study in which individuals with Lynch syndrome collected faeces before and after high-quality surveillance colonoscopy. VOC-patterns were analysed using field asymmetric ion mobility spectrometry (FAIMS) and gas chromatography-ion mobility spectrometry (GC-IMS) followed by machine learning pipelines, and combined with FIT at 2.55 μg Hb/g faeces. Gas chromatography time-of-flight mass spectrometry analysed individual VOC abundance. Among 200 included individuals (57% female, median 51 years), 62 had relevant neoplasia at colonoscopy: 3 CRC, 6 advanced adenoma (AA), 3 advanced serrated lesion (ASL), and 50 non-advanced adenoma (NAA). Respective sensitivity and negative predictive value for CRC and AA (and also ASL in case of FAIMS) were 100% and 100% using FAIMS (54% specificity), and 89% and 99% using GC-IMS (58% specificity). Respective sensitivity and specificity for any relevant neoplasia were 88% and 44% (FAIMS) and 84% and 28% (GC-IMS); accuracy did not significantly improve upon VOC-FIT. VOC-patterns differed before and after polypectomy (AUC 0.70). NAA showed decreased faecal abundance of butanal, 2-oxohexane, dimethyldisulphide and dimethyltrisulphide. In Lynch syndrome, faecal VOCs may be a promising strategy for postponing colonoscopy and for follow-up after polypectomy. Our results serve as a stepping stone for large validation studies. NL8749.

Prospective Multi-Center Longitudinal Study to Validate Accuracy of the Global Anatomic Staging System (GLASS) Score in Predicting Major Acute Limb Events in Patients With Chronic Limb Threatening Ischemia Undergoing Endovascular Intervention: The PROMOTE-GLASS Study Protocol.

Developed by the Global Vascular Guidelines committee, the Global Limb Anatomic Staging System (GLASS) is an angiographic scoring system used for quantifying infrainguinal disease extent and predicting treatment success with endovascular techniques (EVT). Currently, no other risk prediction model is available for patients with chronic limb threatening ischemia (CLTI) undergoing EVT. GLASS' validation and adoption outside academic institutions for research are limited. Thus, this longitudinal multicenter prospective study aims to examine GLASS' validity and reliability in predicting major acute limb events and overall survival (OS) in patients with CLTI undergoing EVT. This prospective, international, multicenter, observational study will include patients with CLTI undergoing EVT (PROMOTE-GLASS) (ClinicalTrials.gov; ID: NCT06186544) identified through routine clinical referrals and emergency visits to vascular units in participating centers. Only patients who are referred for EVT will be recruited. The primary outcomes are immediate technical success, immediate technical failure, and 1-year limb base patency. The secondary outcomes are major adverse limb events, major lower limb amputation, and OS in patients presenting with CLTI who undergo EVT up to 1 year after the procedure. Clinical and imaging data will be analyzed at the end of follow-up to validate risk prediction. This protocol outlines our approach for identifying cases, GLASS score calculation, outcome measures assessment, and a statistical analysis plan. PROMOTE-GLASS holds significant implications and can potentially revolutionize clinical decision-making by assisting clinicians in identifying patients who are likely to benefit from EVT. Ultimately, reduce the need for more invasive procedures and improve patient outcomes. Furthermore, PROMOTE-GLASS can provide useful information, including patient selection, for future randomized controlled trials (RCTs) investigating EVT for CLTI. PROMOTE-GLASS anticipated implications on the vascular community are rooted in its potential to improve patient care, inform future research, and address limitations in existing literature regarding CLTI treatment outcomes.

Recruitment and retention of pediatric participants for pandemic preparedness research: Experience from the PREMISE EV-D68 Pilot Study

Recruitment and retention are challenges for prospective pediatric cohort studies, particularly those involving serial venipunctures. We investigated factors underlying enrollment and retention in the Pandemic Response Repository through Microbial and Immune Surveillance and Epidemiology (PREMISE) Enterovirus D68 (EV-D68) Pilot Study, a multicenter prospective longitudinal cohort study assessing the utility of immunologic surveillance for pandemic preparedness. This study enrolls children ≤10 years for two blood draws, pre- and post-EV-D68 season, separated by 6–18 months. Overall, 174 children were enrolled in Cohort 1 of the study and 120 (69 %) of children completed the study, with follow-up blood samples obtained from 101 (58 %) of participants. Families were primarily motivated to participate by a desire to help other children, advance science, and better prepare for the next pandemic. Adding research blood draws to clinically indicated blood draws improved enrollment, and multiple study touch points facilitated retention. These findings can be applied to improve recruitment and retention in future pandemic preparedness efforts and longitudinal pediatric cohort studies.

Associations between readmission and patient-reported measures in acute psychiatric inpatients: a multicenter prospective longitudinal study.

This study examined whether patient-reported measures (PRMs) addressing quality of life, personal agency, functional impairment, and treatment satisfaction at hospital discharge were associated with future readmission during a 12-month follow-up period. The study also examined whether readmission influenced changes in the same measures. A multicenter prospective cohort study was conducted at 21 psychiatric hospitals in Japan. Participants completed the EuroQol-five-dimensions-five-level (EQ-5D), the Five-item Subjective Personal Agency Scale, and the Sheehan Disability Scale (SDS) at the time of index admission (T1), discharge from index admission (T2), and 6months (T3) and 12months (T4) after discharge. Inpatient treatment satisfaction was assessed at T2. Readmission and variables potentially associated with hospitalization and PRMs were evaluated using mixed-effects logistic regression models and mixed models for repeated measures. A total of 491 participants were followed for 12months (attrition rate: 19.4%), and 480 were included in the EQ-5D analysis. The most common diagnoses were schizophrenia (59%), depression (14%), and bipolar disorder (13%). No patient-reported measures were significantly associated with readmission over the follow-up period. Interaction of readmission and time did not significantly affect changes in EQ-5D. Readmission did significantly influence SDS score changes between T2 and T3 (B = 1.78, 95% CI = 0.30-3.25, p = 0.018) and between T3 and T4 (B = 1.43, 95% CI = 0.14-2.72, p = 0.029).The same influence of readmission on SDS score changes was not observed in the model which adjusted for all potential covariates. Readmission was potentially associated with changes in self-reported functional impairment. Findings highlight the potential role of intensive post-discharge services in preventing readmission, rather than relying on time-of-discharge PRMs in order to predict readmission risk. This study was registered in UMIN Clinical Trials Registry (UMIN000034220).

Development and External Validation of a Motor Intention–Integrated Prediction Model for Upper Extremity Motor Recovery After Intention-Driven Robotic Hand Training for Chronic Stroke

ObjectiveTo derive and validate a prediction model for minimal clinically important differences (MCIDs) in upper extremity (UE) motor function after intention-driven robotic hand training using residual voluntary electromyography (EMG) signals from affected UE. DesignA prospective longitudinal multicenter cohort study. We collected preintervention candidate predictors: demographics, clinical characteristics, Fugl-Meyer assessment of UE (FMAUE), Action Research Arm Test scores, and motor intention of flexor digitorum and extensor digitorum (ED) measured by EMG during maximal voluntary contraction (MVC). For EMG measures, recognizing challenges for stroke survivors to move paralyzed hand, peak signals were extracted from 8 time windows during MVC-EMG (0.1-5s) to identify subjects’ motor intention. Classification and regression tree algorithm was employed to predict survivors with MCID of FMAUE. Relationship between predictors and motor improvements was further investigated. SettingNine rehabilitation centers. ParticipantsChronic stroke survivors (N=131), including 87 for derivation sample, and 44 for validation sample. InterventionsAll participants underwent 20-session robotic hand training (40min/session, 3-5sessions/wk). Main Outcome MeasuresPrediction efficacies of models were assessed by area under the receiver operating characteristic curve (AUC). The best effective model was final model and validated using AUC and overall accuracy. ResultsThe best model comprised FMAUE (cutoff score, 46) and peak activity of ED from 1-second MVC-EMG (MVC-EMG 4.604 times higher than resting EMG), which demonstrated significantly higher prediction accuracy (AUC, 0.807) than other time windows or solely using clinical scores (AUC, 0.595). In external validation, this model displayed robust prediction (AUC, 0.916). Significant quadratic relationship was observed between ED-EMG and FMAUE increases. ConclusionsThis study presents a prediction model for intention-driven robotic hand training in chronic stroke survivors. It highlights significance of capturing motor intention through 1-second EMG window as a predictor for MCID improvement in UE motor function after 20-session robotic training. Survivors in 2 conditions showed high percentage of clinical motor improvement: moderate-to-high motor intention and low-to-moderate function; as well as high intention and high function.

The Impact of Non-Pain Factors on Pain Interference Among U.S. Service Members and Veterans with Symptoms of Mild Traumatic Brain Injury.

U.S. Service members and Veterans (SM/V) experience elevated rates of traumatic brain injury (TBI), chronic pain, and other non-pain symptoms. However, the role of non-pain factors on pain interference levels remains unclear among SM/Vs, particularly those with a history of TBI. The primary objective of this study was to identify factors that differentiate high/low pain interference, given equivalent pain intensity among U.S. SM/V participating in the ongoing Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC) national multi-center prospective longitudinal observational study. An explainable machine learning was used to identify key predictors of pain interference conditioned on equivalent pain intensity. The final sample consisted of n = 1,577 SM/Vs who were predominantly male (87%), and 83.6% had a history of mild TBI(s) (mTBI), while 16.4% were TBI negative controls. The sample was categorized according to pain interference level (Low: 19.9%, Moderate: 52.5%, and High: 27.6%). Both pain intensity scores and pain interference scores increased with the number of mTBIs (p < 0.001), and there was evidence of a dose response between the number of injuries and pain scores. Machine learning models identified fatigue and anxiety as the most important predictors of pain interference, whereas emotional control was protective. Partial dependence plots identified that marginal effects of fatigue and anxiety were associated with pain interference (p < 0.001), but the marginal effect of mTBI was not significant in models considering all variables (p > 0.05). Non-pain factors are associated with functional limitations and disability experience among SM/V with an mTBI history. The functional effects of pain may be mediated through multiple other factors. Pain is a multi-dimensional experience that may benefit most from holistic treatment approaches that target comorbidities and build supports that promote recovery.

Association of nutritional intake with clinical and imaging activity in pediatric multiple sclerosis

Background: Understanding nutrition’s role in multiple sclerosis (MS) can guide recommendations and intervention-based studies. Objective: Evaluate the association between nutrition and pediatric-onset MS outcomes. Methods: Prospective longitudinal multicenter study conducted as part of the US Network of Pediatric MS centers. Predictors were collected using a food screener estimating intake of various dietary food groups (e.g. dairy and fruits) and additional calculated indices (e.g. Healthy Eating Index (HEI)). Outcomes included time-from-enrollment to clinical relapse, new magnetic resonance imaging (MRI) T2 lesions, and Expanded Disability Status Scale (EDSS) increase. Results: 353 children with MS were enrolled (mean ± SD age 15.4 ± 2.9, follow-up 3.9 ± 2.6 years). Multivariable analysis demonstrated that increased dairy by 50% of recommended intake was associated with increased relapse risk by 41% (adjusted hazard ratio (HR) 1.41, 95% CI 1.07–1.86), and risk of T2 progression by 40% (1.40, 1.12–1.74). Increased intake of fruit or vegetable above recommended, and every five-point HEI increase decreased relapse risk by 25% (0.75, 0.60–0.95), 45% (0.55, 0.32–0.96), and 15% (0.84, 0.74–0.96), respectively. No associations were found with EDSS. Conclusion: This work supports the influence of dietary intake on MS course, particularly with dairy intake. Future prospective study is required to establish causation.

Resting state EEG relates to short- and long-term cognitive functioning after cardiac arrest

BackgroundApproximately half of cardiac arrest survivors have persistent cognitive impairment. Guidelines recommend early screening to identify patients at risk for cognitive impairment, but there is no consensus on the best screening method. We aimed to identify quantitative EEG measures relating with short- and long-term cognitive function after cardiac arrest for potential to cognitive outcome prediction. MethodsWe analyzed data from a prospective longitudinal multicenter cohort study designed to develop a prediction model for cognitive outcome after cardiac arrest. For the current analysis, we used twenty-minute EEG registrations from 80 patients around one week after cardiac arrest. We calculated power spectral density, normalized alpha-to-theta ratio (nATR), peak frequency, and center of gravity (CoG) of this peak frequency. We related these with global cognitive functioning (scores on the Montreal Cognitive Assessment (MoCA)) at one week, three and twelve months follow-up with multivariate mixed effect models, and with performance on standard neuropsychological examination at twelve months using Pearson correlation coefficients. ResultsEach individual EEG parameter related to MoCA at one week (βnATR = 7.36; P < 0.01; βpeak frequency = 1.73, P < 0.01; βCoG = -9.88, P < 0.01). The nATR also related with the MoCA at three months ((βnATR = 2.49; P 0.01). No EEG metrics significantly related to the MoCA score at twelve months. nATR and peak frequency related with memory performance at twelve months. Results were consistent in sensitivity analyses. ConclusionEarly resting-state EEG parameters relate with short-term global cognitive functioning and with memory function at one year after cardiac arrest. Additional predictive values in multimodal prediction models need further study.

Investigating incidence of and factors associated with SARS-CoV-2 infection over a nine-month period in a highly-vaccinated healthcare worker cohort.

Healthcare workers (HCWs) are at increased risk of SARS-CoV-2 infection. This risk persists despite the implementation of mitigating factors, including vaccination. The ongoing impact of incident SARS-CoV-2 infection and symptomatic COVID-19 disease in vaccinated healthcare workers is poorly understood. We aimed to describe the epidemiology of incident SARS-CoV-2 infections, as well as investigating the serological, clinical and demographic factors associated with developing infection. This was a multi-centre prospective longitudinal study followed a HCW cohort over a nine-month period. Spike and nucleocapsid SARS-CoV-2 antibodies were measured at enrolment. Vaccination status, demographics, and medical history were collated. Incident infection over the study period was recorded. Multivariable regression models investigated factors associated with nucleocapsid antibody status, incident infection, and symptomatic infection. 1,260 participants took part, of whom n = 1,006 were anti-nucleocapsid antibody positive. Negative anti-nucleocapsid antibody was associated with older age and having a known SARS-CoV-2 acquisition risk. There were n = 274 (22%) incident infections, with n = 225 (87%) diagnosed using antigen tests. Incident infections were associated with lower anti-nucleocapsid titres, increased time since previous SARS-CoV-2 infection, and having a known acquisition risk, but were not associated with vaccination status. This study demonstrates a high rate of incident SARS-CoV-2 infection amongst healthcare workers, despite broad vaccine coverage. There is a shift in diagnostics, from PCR to antigen testing. We identify at-risk groups for incident infection, and these should continue be targeted as part of risk reduction campaigns. Vaccination status and prior infection status alone are not surrogates for protection.

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.

Cardio-ankle vascular index for predicting cardiovascular morbimortality and determinants for its progression in the prospective advanced approach to arterial stiffness (TRIPLE-A-Stiffness) study

BackgroundThe cardio-ankle vascular index (CAVI) measure of arterial stiffness is associated with prevalent cardiovascular risk factors, while its predictive value cardiovascular events remains to be established. The aim was to determine associations of CAVI with cardiovascular morbimortality (primary outcome) and all-cause mortality (secondary outcome), and to establish the determinants of CAVI progression. Methods TRIPLE-A-Stiffness, an international multicentre prospective longitudinal study, enrolled >2000 subjects ≥40 years old at 32 centres from 18 European countries. Of these, 1250 subjects (55% women) were followed for a median of 3.82 (2.81 – 4.69) years. Findings Unadjusted cumulative incidence rates of outcomes according to CAVI stratification were higher in highest stratum (CAVI >9). Cox regression with adjustment for age, sex, and cardiovascular risk factors revealed that CAVI was associated with increased cardiovascular morbimortality (HR 1.25 per 1 increase; 95% confidence interval, CI: 1.03‒1.51) and all-cause mortality (HR 1.37 per 1 increase; 95%CI: 1.10-1.70) risk in subjects ≥60 years. In ROC analyses, CAVI optimal threshold was 9.25 (c-index 0.598; 0.542-0.654) and 8.30 (c-index 0.565; 0.512-0.618) in subjects ≥ or <60 years, respectively, to predict increased CV morbimortality. Finally, age, mean arterial blood pressure, anti-diabetic and lipid-lowering treatment were independent predictors of yearly CAVI progression adjusted for baseline CAVI. Interpretation The present study identified additional value for CAVI to predict outcomes after adjustment for CV risk factors, in particular for subjects ≥60 years. CAVI progression may represent a modifiable risk factor by treatments. Funding International Society of Vascular Health (ISVH) and Fukuda Denshi Co Ltd., Japan

Health and sociodemographic determinants of excess mortality in Spanish nursing homes during the COVID-19 pandemic: a2-year prospective longitudinal study.

Age, multimorbidity, immunodeficiency and frailty of older people living in nursing homes make them vulnerable to COVID-19 and overall mortality. To estimate overall and COVID-19 mortality parameters and analyse their predictive factors in older people living in nursing homes over a2-year period. Design: A2-year prospective longitudinal multicentre study was conducted between 2020 and 2022. This study involved five nursing homes in Central Catalonia (Spain). Residents aged 65years or older who lived in the nursing homes on apermanent basis. Date and causes of deaths were recorded. In addition, sociodemographic and health data were collected. For the effect on mortality, survival curves were performed using the Kaplan-Meier method and multivariate analysis using Cox regression. The total sample of 125 subjects had amean age of 85.10 years (standard deviation = 7.3 years). There were 59 (47.2%) deaths at 24months (95% confidence interval, CI, 38.6-55.9) and 25 (20.0%) were due to COVID-19, mostly in the first 3months. In multivariate analysis, functional impairment (hazard ratio, HR 2.40; 95% CI 1.33-4.32) was asignificant risk factor for mortality independent of age (HR 1.17; 95% CI 0.69-2.00) and risk of sarcopenia (HR 1.40; 95% CI 0.63-3.12). Almost half of this sample of nursing home residents died in the 2‑year period, and one fifth were attributed to COVID-19. Functional impairment was arisk factor for overall mortality and COVID-19 mortality, independent of age and risk of sarcopenia.

Length of hospital stay and its predictors among burn patients in a resource limited setting: a multicenter prospective longitudinal study

Introduction: There is a paucity of data relating to length of hospital stay (LOS) among burn patients managed in hospitals with no burn units, yet this constitute a big percentage of hospitals in low-income countries. This study was aimed at determining the predictors of length of stay at three hospitals in a resource limited setting. Methods: This was a prospective longitudinal multicentre study that enrolled burn patients with moderate and severe burns according to the American Burn Association (ABA) admitted at three tertiary hospitals in western Uganda. Follow up was done till discharge. LOS and its predictors were determined using logistic regression in SPSS version 26. The cut off for prolonged hospital stay was a length of stay above the median which was 8 days. Results: This study included 101 patients with majority in the age bracket of 18–55 (56.4%). Majority were males (69.3%) from a rural setting (61.4%) and were accidentally burnt (95.0%) at home (75.2%). The median LOS was 8 days. The variables that independently predicted increased LOS were receiving medical attention after 12 h (P=0.002), burn severity according to the ABA (P=0.017), and type of procedure done (P&lt;0.001). Conclusion: The factors independently associated with increased LOS were; time to medical attention, burn severity, and type of procedure done. Measures to ensure timely medical attention can reduce the length of stay among patients with burns even in the absence of a burn unit.

Patients undergoing double J substitution with a pigtail suture stent report a significant decrease of stent-related symptoms. Results from a prospective multicenter longitudinal trial

PurposeTo compare stent-related symptoms (SRS) in patients with double J (DJ) undergoing substitution with a pigtail suture stent (PSS) after ureteroscopy (URS), through the Ureteral Stent Symptom Questionnaire (USSQ).Materials and methodsPatients with DJ undergoing URS for stone treatment were enrolled in this prospective multicenter longitudinal study. The USSQ was submitted thrice: 2 weeks after DJ, 2 weeks after PSS and 4 weeks after PSS removal (baseline). Primary endpoint: to compare Urinary Symptom Index Score and the rate of patients with pain 2 weeks after DJ and PSS. Secondary endpoints: to compare other USSQ scores and single answers 2 weeks after DJ and PSS, and DJ and PSS USSQ scores with baseline.Results93 patients were enrolled. 2 weeks Urinary Symptom Index Score (p < 0.001) and the percentage of patients complaining of pain (60.2% vs 88.2%, p < 0.001) were significantly in favour of PSS compared to DJ. 2 weeks scores were significantly improved with PSS compared to DJ: Pain Index (p < 0.001), VAS (p < 0.001), General Health Index (p < 0.001) and Work Performance Index (p < 0.001). All urinary symptoms were significantly decreased with PSS, including renal pain during micturition and pain interfering with life. Pain Index Score (p = 0.622) and VAS (p = 0.169) were comparable to baseline with PSS, while differed with DJ.ConclusionsPatients undergoing DJ substitution with PSS after URS report a significant decrease of SRS. Urologists may consider positioning PSS after URS in pre-stented patients to reduce the impact of SRS.

Depression and anxiety among nurses during the COVID-19 pandemic: Longitudinal results over 2 years from the multicentre VOICE-EgePan study.

To examine symptoms of depression and generalised anxiety among nurses over 2 years during the pandemic and compare them to the general population. The COVID-19 pandemic has led to a significant increase in mental stress among the population worldwide. Nursing staff have been identified as being under remarkable strain. A multicentre prospective longitudinal study. Symptoms of depression and generalised anxiety in 507 nurses were examined at four different time points (T1: April-July 2020, T2: November 2020-January 2021, T3: May-July 2021, T4: February-May 2022). Results were compared with values of the German general population, presence of gender-specific differences was analysed and frequencies of clinically relevant levels of depression and anxiety were determined. Throughout the study (T1-T4), a significant increase in depressive and anxiety symptoms was observed. At all four measurement time points, nurses showed significantly higher prevalence for depression and anxiety compared to the German general population. No significant gender differences were found. Frequencies for probable depression and generalised anxiety disorder among nurses were: 21.6% and 18.5% (T1), 31.4% and 29.2% (T2), 29.5% and 26.2% (T3), 33.7% and 26.4% (T4). During the pandemic, symptoms of depression and generalised anxiety among nurses increased significantly and remained elevated. Their symptom levels were permanently higher than in the general population. These findings strongly suggest that the circumstances of the pandemic severely affected nurses´ mental health. The COVID-19 pandemic caused a great mental strain on caregivers. This study was able to demonstrate the significant increase in depression and anxiety among nurses during the pandemic. It highlights the urgent need for prevention, screening and support systems in hospitals. Supportive programmes and preventive services should be developed, not least to prevent the growing shortage of nurses in the health care systems. The study adhered to relevant EQUATOR guidelines. The STROBE checklist for cohort study was used as the reporting method. Five hundred and seven nurses completed the questionnaire and provided data for analysis. The study was registered with the German Clinical Trials Register (https://drks.de/search/en) under the following ID: DRKS00021268.

Social determinants of health rather than race impact health-related quality of life in 10-year-old children born extremely preterm.

Reducing healthcare disparities among children is extremely important given the potential impact of these disparities on long-term health-related quality of life (HRQL). Race and parental socioeconomic status (SES) are associated with child HRQL, but these associations have not been studied in infants born extremely preterm (EP), a population at increased risk for physical, cognitive, and psychosocial impairments. Achieving health equity for infants born EP across their life course requires identifying the impact of racism and SES on HRQL. We aimed to evaluate the association between self-reported maternal race, SES factors, and HRQL among 10-year-old children born EP. Participants were identified from an ongoing multicenter prospective longitudinal study of Extremely Low Gestational Age Newborns (ELGAN Study), born between 2002 and 2004, and evaluated at 10 years of age using the Pediatric quality of life (QoL) Inventory completed by their parent or guardian, assessing physical, emotional, social, school, and total (composite) QoL domains. Multivariable regression models were used to evaluate the relationship between QoL scores and self-identified maternal race, adjusting for SES factors (education level, marital status, and public insurance). Of 1,198 study participants who were alive at 10 years of age, 863 (72.0%) were evaluated at 10 years of age. Differences in mean 10-year QoL scores across racial groups were observed and were significant on univariate analysis. However, these associations attenuated when adjusted for the marital status, public insurance status, and education status of mothers. A comparison of children with English as the primary language spoken at home vs. any other language revealed a significant difference only in school QoL, in which non-English language was associated with more favorable school QoL scores. Among 10-year-old children born EP, differences in parent-reported QoL were associated with maternal SES factors but not with race. Our results suggest that interventions designed to improve the SES of mothers may enhance the QoL of children born EP. Furthermore, these results underscore that race is a social construct, rather than a biological variable, as we work toward greater equity in care provision.

The Swedish initiative for the study of Primary sclerosing cholangitis (SUPRIM)

Despite more than 50 years of research and parallel improvements in hepatology and oncology, there is still today neither a treatment to prevent disease progression in primary sclerosing cholangitis (PSC), nor reliable early diagnostic tools for the associated hepatobiliary cancers. Importantly, the limited understanding of the underlying biological mechanisms in PSC and its natural history not only affects the identification of new drug targets but implies a lack of surrogate markers that hampers the design of clinical trials and the evaluation of drug efficacy. The lack of easy access to large representative well-characterised prospective resources is an important contributing factor to the current situation. We here present the SUPRIM cohort, a national multicentre prospective longitudinal study of unselected PSC patients capturing the representative diversity of PSC phenotypes. We describe the 10-year effort of inclusion and follow-up, an intermediate analysis report including original results, and the associated research resource. All included patients gave written informed consent (recruitment: November 2011-April 2016). Out of 512 included patients, 452 patients completed the five-year follow-up without endpoint outcomes. Liver transplantation was performed in 54 patients (10%) and hepatobiliary malignancy was diagnosed in 15 patients (3%). We draw a comprehensive landscape of the multidimensional clinical and biological heterogeneity of PSC illustrating the diversity of PSC phenotypes. Performances of available predictive scores are compared and perspectives on the continuation of the SUPRIM cohort are provided. We envision the SUPRIM cohort as an open-access collaborative resource to accelerate the generation of new knowledge and independent validations of promising ones with the aim to uncover reliable diagnostics, prognostic tools, surrogate markers, and new treatment targets by2040. This work was supported by the Swedish Cancer Society, Stockholm County Council, and the Cancer Research Funds of Radiumhemmet.