Multicenter Longitudinal Study Research Articles

Reducing administrative burden by implementing a core set of quality indicators in the ICU: a multicentre longitudinal intervention study

BackgroundThe number of quality indicators for which clinicians need to record data is increasing. For many indicators, there are concerns about their efficacy. This study aimed to determine whether working...

Development and External Validation of Motor-intention Integrated Prediction Model for Upper Extremity Motor Recovery After Intention-driven Robotic-hand Training for Chronic Stroke.

To derive and validate a prediction model for minimal clinically important differences (MCID) in upper extremity (UE) motor function after intention-driven robotic-hand training using residual voluntary EMG signals from affected UE. A prospective longitudinal multicenter cohort study. We collected pre-intervention 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 eight time-windows during MVC-EMG (0.1s-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. Nine rehabilitation centers. Chronic stroke survivors (N=131), including 87 for Derivation-sample, and 44 for Validation-sample. All participants underwent 20-session robotic-hand training (40min/session, 3-5sessions/week). Prediction 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. The best model comprised FMAUE (cut-off score: 46) and peak activity of ED from one-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. This 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 two 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.

Self-care in patients affected by inflammatory bowel disease and caregiver contribution to self-care (IBD-SELF): a protocol for a longitudinal observational study

IntroductionSupporting patient self-care and the contribution of their caregivers is crucial in chronic illness care. Inflammatory bowel disease (IBD) is a chronic condition whose prevalence is expected to double, especially...

Autoantibodies and damage in patients with idiopathic inflammatory myopathies: A longitudinal multicenter study from the MYONET international network

ObjectiveTo study the trajectories of changes in damage over time and explore associations with autoantibody defined subgroups using a large international cohort of patients with idiopathic inflammatory myopathies (IIM). MethodsData from the MYONET registry, including patients who were tested for autoantibodies and had at least one assessment of damage using the Myositis Damage Index (MDI), were analyzed. Patients were sub-grouped according to their autoantibody profiles (myositis-specific, myositis-associated, or seronegative). The index date was defined as the time point for the first registered MDI assessment. The longitudinal trajectories of damage with autoantibody status as the main predictor were analyzed using linear mixed models. ResultsA total of 757 adult patients were included in this study. Each year of disease duration since diagnosis had an estimated MDI score increase of 0.16 units for the seronegative group (reference). Compared with the seronegative group as reference, patients with dermatomyositis-specific autoantibodies developed less damage per year of follow-up since diagnosis (average 0.08 less score, P = 0.04), whereas patients with anti-PM/Scl autoantibodies developed more damage per year of follow-up since diagnosis (average 0.28 higher score, P = 0.03) independent of sex and age at diagnosis. The seronegative subgroup and the immune-mediated necrotizing myopathy autoantibody subgroup had the strongest correlation between severity of muscle damage and HAQ-DI scores at five years of follow-up, rho=0.84, P < 0.001 and rho=0.72, P < 0.001, respectively. ConclusionOur study is the first to describe patterns and trajectories of change in damage over time in relation to autoantibody defined subgroups in a large international multicenter cohort of patients with IIM. Patients with anti-PM/Scl scored a greater extent of damage, whereas patients with dermatomyositis-specific antibodies had less damage than seronegative patients. Severity in muscle damage had moderate to strong correlation with functional disability among the IMNM and seronegative subgroups with lower correlations for the other subgroups. These findings suggest that autoantibodies may be useful predictors of long-term damage.

Kidney transplantation in children and adolescents with C3 glomerulopathy or immune complex membranoproliferative glomerulonephritis: a real-world study within the CERTAIN research network.

Complement 3 glomerulopathy (C3G) and immune complex membranoproliferative glomerulonephritis (IC-MPGN) are ultra-rare chronic kidney diseases with an overall poor prognosis, with approximately 40-50% of patients progressing to kidney failure within 10years of diagnosis. C3G is characterized by a high rate of disease recurrence in the transplanted kidney. However, there is a lack of published data on clinical outcomes in the pediatric population following transplantation. In this multicenter longitudinal cohort study of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, we compared the post-transplant outcomes of pediatric patients with C3G (n = 17) or IC-MPGN (n = 3) with a matched case-control group (n = 20). Eleven of 20 children (55%) with C3G or IC-MPGN experienced a recurrence within 5years post-transplant. Patients with C3G or IC-MPGN had a 5-year graft survival of 61.4%, which was significantly (P = 0.029) lower than the 5-year graft survival of 90% in controls; five patients with C3G or IC-MPGN lost their graft due to recurrence during this observation period. Both the 1-year (20%) and the 5-year (42%) rates of biopsy-proven acute rejection episodes were comparable between patients and controls. Complement-targeted therapy with eculizumab, either as prophylaxis or treatment, did not appear to be effective. These data in pediatric patients with C3G or IC-MPGN show a high risk of post-transplant disease recurrence (55%) and a significantly lower 5-year graft survival compared to matched controls with other primary kidney diseases. These data underscore the need for post-transplant patients for effective and specific therapies that target the underlying disease mechanism.

Sudden cardiac death after early-onset myocardial infarction. A multicentre longitudinal cohort study with 20 years' follow-up.

Sudden cardiac death (SCD) is a serious consequence of a myocardial infarction (MI), but identifying patients at risk of developing SCD remains a major clinical challenge especially in the case of juvenile MI. The aim of this study was to identify predictors of SCD after early-onset MI using long-term follow-up data relating to a large nationwide patient cohort. The Italian Genetic Study on Early-onset MI enrolled 2,000 patients experiencing a first MI before the age of 45 years, who were followed up for a median of 19.9 years. Fine-Gray proportional hazard models were used to assess the associations between their clinical, demographic and index event data and the occurrence of SCD. SCD occurred in 195 patients, who were more frequently males, hypertensive and/or diabetic; had a history of previous thromboembolic events with a greater atherosclerotic burden; and had a lower left ventricular ejection fraction (LVEF) after the index event. Multivariable analysis showed that the independent predictors of SCD were diabetes, hypertension, previous thromboembolic events, higher Syntax score, and a lower LVEF. There was no clear evidence of the clustering of SCD events during follow-up. SCD was the first post-MI clinical event in 101 patients; the remaining 94 experienced SCD after a non-fatal MI or hospitalisation for coronary revascularisation. SCD frequently occurs during the 20 years after early-onset MI. The nature of the identified predictors and the absence of clustering suggests that the pathophysiological basis of SCD may be related to progressive coronary atherosclerosis.

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).

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.

Personality, Social Factors, Brain Functioning, Familial Risk, and Trajectories of Alcohol Misuse in Adolescence

The development of an alcohol use disorder in adolescence is associated with increased risk of future alcohol dependence. The differential associations of risk factors with alcohol use over the course of 8 years are important for preventive measures. To determine the differential associations of risk-taking aspects of personality, social factors, brain functioning, and familial risk with hazardous alcohol use in adolescents over the course of 8 years. The IMAGEN multicenter longitudinal cohort study included adolescents recruited from European schools in Germany, the UK, France, and Ireland from January 2008 to January 2019. Eligible participants included those with available neuropsychological, self-report, imaging, and genetic data at baseline. Adolescents who were ineligible for magnetic resonance imaging or had serious medical conditions were excluded. Data analysis was conducted from July 2021 to September 2022. Personality testing, psychosocial factors, brain functioning, and familial risk of alcohol misuse. Hazardous alcohol use as measured with the Alcohol Use Disorders Identification Test scores, a main planned outcome of the IMAGEN study. Alcohol misuse trajectories at ages 14, 16, 19, and 22 years were modeled using latent growth curve models. A total of 2240 adolescents (1110 female [49.6%] and 1130 male [50.4%]) were included in the study. There was a significant negative association of psychosocial resources (β = -0.29; SE = 0.03; P < .001) with the general risk of alcohol misuse as well as a significant positive association of the risk-taking aspects of personality with the intercept (β = 0.19; SE = 0.04; P < .001). Furthermore, there were significant positive associations of the social domain (β = 0.13; SE = 0.02; P < .001) and the personality domain (β = 0.07; SE = 0.02; P < .001) with trajectories of alcohol misuse development over time (slope). Family history of substance misuse was negatively associated with general risk of alcohol misuse (β = -0.04; SE = 0.02; P = .045) and its development over time (β = -0.03; SE = 0.01; P = .01). Brain functioning showed no significant association with intercept or slope of alcohol misuse in the model. The findings of this cohort study suggest known risk factors of adolescent drinking may contribute differentially to future alcohol misuse. This approach may inform more individualized preventive interventions.

Monocyte/lymphocyte ratio as a risk factor of cardiovascular and all-cause mortality in coronary artery disease with low-density lipoprotein cholesterol levels below 1.4 mmol/L: a large longitudinal multicenter study

Background and aimsThe monocyte/lymphocyte ratio (MLR), an inflammatory marker, has an unclear relationship with the risk of residual inflammation in patients with coronary artery disease (CAD) and low-density lipoprotein cholesterol (LDL-C) below 1.4 mmol/L. This study aimed to assess the association between the MLR and cardiovascular and all-cause mortalities in these patients. MethodsA total of 2747 patients diagnosed with CAD via coronary angiography (CAG) and presenting with LDL-C levels < 1.4 mmol/L were enrolled in this observational study conducted from January 2007 to December 2020. Patients were categorized into four groups based on the MLR quartiles. We used Kaplan-Meier analysis and Cox regression models to evaluate the relationship between baseline MLR and cardiovascular and all-cause mortalities. ResultsAmong the 2747 participants followed up for a median duration of 6 years, there were 184 cardiovascular and 462 all-cause deaths. Elevated MLR levels were found to be associated with an increased risk of both cardiovascular and all-cause mortalities according to the Kaplan-Meier analysis. Multivariate Cox regression analysis demonstrated a significant association between higher MLR and an elevated risk of cardiovascular and all-cause mortality. Compared to the older group, with an increase in MLR levels, the younger group showed a higher hazard ratio for cardiovascular death. Similar results were obtained in the single-vessel disease group. ConclusionsIn patients with CAD and LDL-C levels < 1.4 mmol/L, MLR can serve as a risk factor for both cardiovascular and all-cause mortalities owing to the risk of residual inflammation.

COVID-19 Across Pandemic Variant Periods: The Severe Acute Respiratory Infection-Preparedness (SARI-PREP) Study.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has evolved through multiple phases in the United States, with significant differences in patient centered outcomes with improvements in hospital strain, medical countermeasures, and overall understanding of the disease. We describe how patient characteristics changed and care progressed over the various pandemic phases; we also emphasize the need for an ongoing clinical network to improve the understanding of known and novel respiratory viral diseases. To describe how patient characteristics and care evolved across the various COVID-19 pandemic periods in those hospitalized with viral severe acute respiratory infection (SARI). Severe Acute Respiratory Infection-Preparedness (SARI-PREP) is a Centers for Disease Control and Prevention Foundation-funded, Society of Critical Care Medicine Discovery-housed, longitudinal multicenter cohort study of viral pneumonia. We defined SARI patients as those hospitalized with laboratory-confirmed respiratory viral infection and an acute syndrome of fever, cough, and radiographic infiltrates or hypoxemia. We collected patient-level data including demographic characteristics, comorbidities, acute physiologic measures, serum and respiratory specimens, therapeutics, and outcomes. Outcomes were described across four pandemic variant periods based on a SARS-CoV-2 sequenced subsample: pre-Delta, Delta, Omicron BA.1, and Omicron post-BA.1. Multicenter cohort of adult patients admitted to an acute care ward or ICU from seven hospitals representing diverse geographic regions across the United States. Patients with SARI caused by infection with respiratory viruses. Eight hundred seventy-four adult patients with SARI were enrolled at seven study hospitals between March 2020 and April 2023. Most patients (780, 89%) had SARS-CoV-2 infection. Across the COVID-19 cohort, median age was 60 years (interquartile range, 48.0-71.0 yr) and 66% were male. Almost half (430, 49%) of the study population belonged to underserved communities. Most patients (76.5%) were admitted to the ICU, 52.5% received mechanical ventilation, and observed hospital mortality was 25.5%. As the pandemic progressed, we observed decreases in ICU utilization (94% to 58%), hospital length of stay (median, 26.0 to 8.5 d), and hospital mortality (32% to 12%), while the number of comorbid conditions increased. We describe increasing comorbidities but improved outcomes across pandemic variant periods, in the setting of multiple factors, including evolving care delivery, countermeasures, and viral variants. An understanding of patient-level factors may inform treatment options for subsequent variants and future novel pathogens.

A longitudinal multi-centric cohort study assessing infant neurodevelopment delay among women with persistent postpartum depression in Nepal

BackgroundInfant neurodevelopment in the first years after birth is determined by multiple factors, including parental care and maternal mental wellbeing. In this study, we aim to assess the impact of persistent maternal depressive symptoms during the first 3 months postpartum on infant neurodevelopment at 6 months.MethodsUsing a longitudinal cohort design, 1253 mother-infant pairs were followed up at 7, 45, and 90 days to assess postpartum depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS); infants were followed up at 6 months to assess neuro-developmental status using the WHO’s Infant and Young Child Development (IYCD) tool. A generalized linear regression model was used to assess the association between persistent postpartum depressive symptoms and infant neurodevelopmental delay at 6 months. A generalized linear mixed model (GLMM) with a hospital as a random intercept was used to assess the persistent postpartum depressive symptoms with an IYCD score. Linear regression was used to compare the IYCD scores between exposure groups.ResultsIn the study population, 7.5% of mothers had persistent depressive symptoms, and 7.5% of infants had neurodevelopmental delay. Infants born to mothers with persistent depressive symptoms had a higher proportion of neurodevelopmental delay than infants born to women without persistent symptoms (48.6% vs 5.1%; p < 0.001). In the adjusted regression model, infants whose mothers had persistent depressive symptoms at 7, 45, and 90 days had a 5.21-fold increased risk of neurodevelopmental delay (aRR, 5.21; 95% CI, 3.17, 8.55). Mean scores in the motor domain (12.7 vs 15.2; p < 0.001) and language domain (6.4 vs 8.5; p < 0.001) were significant when a mother had persistent depression vs. no depression. Mean scores in the general behavioral domain (5.9 vs 10.4, p < 0.001) and the socio-emotional domain (15.4 vs 17.7; p < 0.001) were significantly different when a mother had persistent depression vs no persistent depression.ConclusionsOur results suggest that 6-month-old infants are at higher risk for neurodevelopment delays if their mother reports persistent symptoms of depression from 7 to 90 days postpartum. The neurodevelopmental delay can be observed in all functional domains. Preventive intervention to reduce maternal postpartum depression may reduce the impact on infant developmental delay.

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.

Baseline levels and longitudinal changes in plasma Aβ42/40 among Black and white individuals

Blood-based biomarkers of Alzheimer disease (AD) may facilitate testing of historically under-represented groups. The Study of Race to Understand Alzheimer Biomarkers (SORTOUT-AB) is a multi-center longitudinal study to compare AD biomarkers in participants who identify their race as either Black or white. Plasma samples from 324 Black and 1,547 white participants underwent analysis with C2N Diagnostics’ PrecivityAD test for Aβ42 and Aβ40. Compared to white individuals, Black individuals had higher average plasma Aβ42/40 levels at baseline, consistent with a lower average level of amyloid pathology. Interestingly, this difference resulted from lower average levels of plasma Aβ40 in Black participants. Despite the differences, Black and white individuals had similar longitudinal rates of change in Aβ42/40, consistent with a similar rate of amyloid accumulation. Our results agree with multiple recent studies demonstrating a lower prevalence of amyloid pathology in Black individuals, and additionally suggest that amyloid accumulates consistently across both groups.

Occurrence and trends of Clostridioides difficile infections in hospitalized patients: a prospective multi-centre cohort study in six German university hospitals, 2016–2020

For Clostridioides difficile infections (CDI) in Germany no longitudinal multicentre studies with standardized protocols for diagnosing CDI are available. Recent evaluations of general surveillance databases in Germany indicate a downward trend in CDI rates. We aimed to describe the actual burden and trends of CDI in German university hospitals from 2016 to 2020. Our study is a prospective multicentre study covering six German university hospitals. We report the data in total, stratified by year, by medical specialty as well as by CDI severity. Multivariable regression analyses were performed to assess risk factors for severe CDI. We registered 3,780 CDI cases among 1,436,352 patients. The median length of stay (LOS) of CDI cases was 20 days (IQR 11-37) compared with a general LOS of 4.2 days. In-hospital all-cause mortality in CDI patients was 11.7% (n=444/3780), while mortality attributed to CDI was 0.4% (n=16/3761). CDI recurrence rate was comparatively low at 7.2%. The incidence density of severe healthcare-associated healthcare onset (HAHO)-CDI showed a significant decrease from 2.25/10,000 patient days (pd) in 2016 to 1.49/10,000 pd in 2020 (trend calculation p = 0.032). Compared with a European point-prevalence study in 2013/2014, where overall CDI incidence density was 11.2 cases/10,000 pd in Germany (EUCLID), we see in our study halved overall CDI rates of 5.6 cases/10,000 pd in 2020. Our study shows current data on the distribution of CDI cases in German university hospitals and thus provides international comparative data on the key indicators of CDI.

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.

A multi-centre longitudinal study analysing multiple sclerosis disease-modifying therapy prescribing patterns during the COVID-19 pandemic.

The COVID-19 pandemic raised concern amongst clinicians that disease-modifying therapies (DMT), particularly anti-CD20 monoclonal antibodies (mAb) and fingolimod, could worsen COVID-19 in people with multiple sclerosis (pwMS). This study aimed to examine DMT prescribing trends pre- and post-pandemic onset. A multi-centre longitudinal study with 8,771 participants from MSBase was conducted. Two time periods were defined: pre-pandemic (March 11 2018-March 10 2020) and post-pandemic onset (March 11 2020-11 March 2022). The association between time and prescribing trends was analysed using multivariable mixed-effects logistic regression. DMT initiation refers to first initiation of any DMT, whilst DMT switches indicate changing regimen within 6months of last use. Post-pandemic onset, there was a significant increase in DMT initiation/switching to natalizumab and cladribine [(Natalizumab-initiation: OR 1.72, 95% CI 1.39-2.13; switching: OR 1.66, 95% CI 1.40-1.98), (Cladribine-initiation: OR 1.43, 95% CI 1.09-1.87; switching: OR 1.67, 95% CI 1.41-1.98)]. Anti-CD20mAb initiation/switching decreased in the year of the pandemic, but recovered in the second year, such that overall odds increased slightly post-pandemic (initiation: OR 1.26, 95% CI 1.06-1.49; Switching: OR 1.15, 95% CI 1.02-1.29. Initiation/switching of fingolimod, interferon-beta, and alemtuzumab significantly decreased [(Fingolimod-initiation: OR 0.55, 95% CI 0.41-0.73; switching: OR 0.49, 95% CI 0.41-0.58), (Interferon-gamma-initiation: OR 0.48, 95% CI 0.41-0.57; switching: OR 0.78, 95% CI 0.62-0.99), (Alemtuzumab-initiation: OR 0.27, 95% CI 0.15-0.48; switching: OR 0.27, 95% CI 0.17-0.44)]. Post-pandemic onset, clinicians preferentially prescribed natalizumab and cladribine over anti-CD20 mAbs and fingolimod, likely to preserve efficacy but reduce perceived immunosuppressive risks. This could have implications for disease progression in pwMS. Our findings highlight the significance of equitable DMT access globally, and the importance of evidence-based decision-making in global health challenges.

Intereye Asymmetry as a Predictor of Progression in Patients With Untreated Keratoconus: Findings From a Longitudinal Study.

The purpose of this study was to evaluate interocular predictors of progression in patients with untreated keratoconus. This is a multicenter longitudinal observational study with real-world data collected through the Save Sight Keratoconus Registry. Patients between the period of June 2000 and September 2022 were included in this study. Parameters such as patient age, sex, ocular history, visual acuity, K2, Max-K, and thinnest corneal thickness pachymetry (TCT) were analyzed. There were 4342 untreated eyes from 2171 patients with keratoconus. A total of 333 patients showed progression of either Max-K, TCT, or both, whereas 1838 patients showed stable parameters. Factors associated with a higher incidence of progression in Max-K were younger baseline age (HR 0.96 per year older; 95% CI 0.95-0.98, P < 0.0001) and a higher baseline intereye asymmetry in Max-K (HR 1.02 per higher diopter; 95% CI 1.00-1.04, P = 0.04). A younger baseline age was the only predictor of progression in TCT (HR 0.97 per year older; 95% CI 0.95-0.99, P = 0.001). Age is the most significant predictor of progression for both corneal thinning and progression of Max-K. Interocular asymmetry in Max-K at baseline could be used as part of an algorithm for determining the risk of keratoconus progression. It is recommended that patients with higher interocular asymmetry in Max-K have a closer follow-up of both eyes as they are at a higher risk of progression.

Setting the optimal threshold of NT-proBNP and BNP for the diagnosis of heart failure in patients over 75years.

Diagnosing acute heart failure (AHF) remains particularly challenging in older patients. Natriuretic peptides are recommended as valuable diagnostic tools in this context. This study aims to establish the diagnostic thresholds of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for AHF in patients aged over 75years, both with and without co-morbidities. In this retrospective longitudinal multicentre cohort study, data were gathered from 12071 hospitalized patients aged 75years or older, presenting with acute dyspnoea and undergoing BNP or NT-proBNP measurement within 48h of admission across 10 Assistance Publique-Hôpitaux de Paris facilities between 2011 and 2022, encompassing geriatrics, cardiology, and pulmonology departments. Final diagnoses were categorized using ICD-10 criteria as either AHF or other acute respiratory conditions such as COPD exacerbation, pulmonary embolism, and pneumonia. The mean (SD) age of the population was 84.0 (80.0, 89.0) years, with 52.7% being female. Out of these, 7946 (65.8%) were diagnosed with AHF upon discharge. For NT-proBNP, the identified 'optimal' threshold for diagnosing AHF was 1748ng/L, with a positive predictive value (PPV) of 84%. Among patients aged over 85years, a threshold of 2235pg/mL for NT-proBNP was associated with an 84% PPV. In patients with atrial fibrillation (AF), a threshold of 2332pg/mL for NT-proBNP demonstrated a PPV of 90% for AHF diagnosis. Additionally, in patients with an estimated glomerular filtration rate (eGFR)<30mL/min, a threshold of 3474pg/mL for NT-proBNP yielded a 90% PPV for AHF diagnosis. In male patients, a threshold of 1800pg/mL showed an 85% PPV for AHF diagnosis, while in patients with obesity, a threshold of 1375pg/mL demonstrated an 85% PPV for AHF diagnosis. In older patients, we found significant effects of co-morbidities on natriuretic peptides results, particularly in patients over 85years old, older patients with abnormal renal function, obesity, and atrial fibrillation. Despite the consideration of those co-morbid conditions, NT-proBNP and BNP level continue to demonstrate utility in the diagnosis of AHF in older patients.

Multicentric Longitudinal Prospective Study in a European Cohort of MYO7A Patients: Disease Course and Implications for Gene Therapy.

We investigated the natural history of retinal dystrophy owing to variants in the MYO7A gene. Fifty-three patients (mean age, 33.6 ± 16.7years) with Usher syndrome owing to biallelic, mostly pathogenic, variants in MYO7A underwent baseline and two annual follow-up visits. Best-corrected visual acuity (BCVA), semiautomatic kinetic visual field, full-field electroretinogram, color fundus imaging, microperimetry, spectral-domain optical coherence tomography, and fundus autofluorescence were assessed. At baseline, all patients presented with decreased BCVA (66.4 ± 17.9 Early Treatment Diabetic Retinopathy score and 59.5 ± 21.7 Early Treatment Diabetic Retinopathy score, in the better- and worse-seeing eyes, respectively), restricted semiautomatic kinetic visual field (III4e area, 3365.8 ± 4142.1°2; 4176.4 ± 4400.3°2) and decreased macular sensitivity (9.7 ± 9.9dB; 9.0 ± 10.2dB). Spectral-domain optical coherence tomography revealed reduced central macular thickness (259.6 ± 63.0µm; 250.7 ± 63.3µm) and narrowed ellipsoid zone band width (2807.5 ± 2374.6µm; 2615.5 ± 2370.4µm). Longitudinal analyses (50 patients) showed a significant decrease of BCVA in better-seeing eyes, whereas no changes were observed in worse-seeing eyes for any parameter. BCVA, semiautomatic kinetic visual field (III4e and V4e) and macular sensitivity were related significantly to age at baseline. Hyperautofluorescent foveal patch (16 eyes [31.4%]) and abnormal central hypoautofluorescence (9 eyes [17.6%]) were significantly associated with worse morphological and functional read-outs compared with the hyperautofluorescent ring pattern (22 eyes [43.1%]). Our European multicentric study offers the first prospective longitudinal analysis in one of the largest cohorts of MYO7A patients described to date, confirming the slow disease progression. More important, this study emphasizes the key role of fundus autofluorescence patterns in retinal impairment staging and advocates its adoption as an objective biomarker in patient selection for future gene therapy clinical trials.