1-year Visit Research Articles

DOP006 Long term maintenance treatment with vedolizumab in pediatric IBD: a three-year follow-up of the prospective multicenter VEDOKIDS study

Abstract Background Long-term data on the use of vedolizumab in children with Crohn’s disease (CD) and ulcerative colitis (UC) are lacking and the drug is not yet approved in pediatrics. The VEDOKIDS prospective multicenter cohort study aimed to assess the effectiveness and safety of vedolizumab as maintenance therapy in children with CD and UC; this study reports the 3-year final visit outcomes (ClinicalTrials.gov, NCT02862132). Methods Children commenced on vedolizumab at any disease duration and with any degree of disease activity were enrolled in 17 pediatric centers in Europe, the USA and the Middle East and followed prospectively through 3 years. The primary outcome was complete remission at 3 years (i.e. steroid-free clinical remission and normal ESR/CRP with sustained vedolizumab treatment and without a surgery). Secondary outcome was loss of response (PUCAI ≥ 10 or wPCDAI ≥ 12.5 for children with UC and CD, respectively) in those achieving clinical remission at week 6. Results Altogether, 137 children were enrolled, of whom 53 (39%) continued vedolizumab treatment through three years. Sustainability rate was higher in UC (35/73 [48%]) than in CD (18/64 [28%]; OR 2.4 [95%CI 1.2-4.8]). Complete remission at three years was achieved in 19/73 (26%) children with UC vs. 9/64 (14%) with CD (OR 2.2 [95%CI 0.9-5.2]) using ITT analysis. The best predictor of complete remission at 3 years was clinical remission at week 6 measured in CD by wPCDAI ≤12.5 (AUROC 0.78 [95%CI 0.64-0.963]), and in UC by PUCAI<10 (AUROC 0.74 [0.63-0.85]). Similarly, in adjusted multivariable logistic regression, complete remission at 3 years was more likely in week-6 remitters or responders compared to non-responders (HR 2.6 [95%CI 1.1-7.2]). Of the 51 (37%) children who achieved clinical remission at week 6 (32 UC and 19 CD), the likelihood of achieving complete remission at 3 years was 41% for UC and 26% for CD (OR 1.9 [95%CI 0.6-6.6]). Of those achieving clinical remission at week 6, 22%, 28%, 31% and 38% lost response by 30, 54, 108 and 162 weeks, respectively, for UC, while for the fewer children with CD who achieved remission at week 6, 5%, 5%, 11% and 16%, respectively, lost response (Figure). Forty adverse events were recorded in 23 children (17%) as possibly related to vedolizumab, none were serious, with the most common being headache, myalgia and fever. Conclusion Vedolizumab was safe and effective for maintaining long-term remission in children with UC and CD. Remission rates were higher in UC compared to CD at the end of induction, but UC patients experienced a higher rate of loss of response over time. Achieving clinical remission by week 6 after initiation of the drug was the best predictor of long-term effectiveness in both UC and CD.

Exploring the potential mediating role of systemic antibiotics in the association between early-life lower respiratory tract infections and asthma at age 5 in the CHILD study.

Lower respiratory tract infections (LRTIs) in early life are one of the strongest risk factors for childhood asthma and are often treated with systemic antibiotics (IV or oral). We aimed to explore the association between early-life LRTIs and systemic antibiotics on asthma development and the potential mediating role of antibiotics in this relationship. Data were collected as part of the longitudinal, general Canadian population CHILD Study. LRTIs during the first 18 months of life were identified through parental symptom report at regular study visits. Systemic antibiotic use was defined as at least one dose of oral/intravenous antibiotics between birth and the 18-month visit and were further categorized by indication as either given for a respiratory indication (upper or lower respiratory symptoms) or non-respiratory indication. Asthma was diagnosed by in-study pediatricians at the 5-year study visit. Adjusted logistic regression models and mediation analyses via systemic antibiotics use were performed. Among 2,073 participants included in our analysis, 72 (4.9%) had asthma age 5, and 609 (29.3%) used systemic antibiotics before the 18-month visit. Among children who had taken antibiotics, 61.6% also had an LRTI in that period compared to 49.7% among children without exposure to systemic antibiotics (p < .001). Moderate-severe LRTIs before age 18 months were associated with higher odds of 5-year asthma [aOR 4.12 (95%CI 2.04-7.95) p < .001]. Antibiotics taken for respiratory indications were associated with higher odds of asthma at age 5 [aOR 2.36 (95%CI 1.59-3.48) p < .001]. Children who received systemic antibiotics for only non-respiratory indications during the first 18 months of life were not associated with increased odds of asthma [aOR 1.08 (95%CI 0.44-2.30) p = .851]. Using mediation analysis, 21.7% of the association between LRTI and asthma is estimated to be mediated through use of early-life systemic antibiotics. However, a significant direct effect of moderate-to-severe LRTIs on asthma risk remained in adjusted mediation models (p = .014). Through mediation modeling we estimate that the increased risk of asthma at age 5 that is associated with moderate-severe LRTIs in infancy may be partially mediated by systemic antibiotics taken during the first 18 months of life. This underscores the importance of public health strategies focused on antibiotic stewardship and reducing early life LRTIs to mitigate asthma risk.

Investigation of a targeted panel of gut microbiome-derived toxins in children with chronic kidney disease.

The gut-kidney axis is implicated in chronic kidney disease (CKD) morbidity. We describe how a panel of gut microbiome-derived toxins relates to kidney function and neurocognitive outcomes in children with CKD, consisting of indoleacetate, 3-indoxylsulfate, p-cresol glucuronide, p-cresol sulfate, and phenylacetylglutamine. The Chronic Kidney Disease in Children (CKiD) cohort is a North American multicenter prospective cohort that enrolled children aged 6months to 16years with estimated glomerular filtration rate (eGFR) 30-89ml/min/1.73 m2. Data from the 2-year study visit were used for this analysis. Toxin quantification (Metabolon Inc., Durham, NC) was performed with ultra-high performance liquid chromatography/tandem mass spectrometry. Executive function and echocardiograms were assessed. Regression analysis examined the association of toxin levels with eGFR, CKD etiology, and neurocognitive and cardiac assessments (adjusted for age, sex, and urine protein:creatinine [UPCR]). There were 150 CKiD participants included in this study. All toxins levels were significantly inversely correlated with eGFR (Spearman's rho - 0.45 to - 0.69). Children with non-glomerular CKD had significantly higher levels of 3-indoxylsulfate, phenylacetylglutamine, and p-cresol glucuronide. The toxin levels did not associate with neurocognitive outcomes. P-cresol glucuronide and phenylacetylglutamine negatively associated with left ventricular mass index z score, but did not associate with left ventricular hypertrophy. Children with CKD have high levels of circulating gut microbiome-derived toxins. The levels of these toxins are strongly correlated with eGFR. There appear to be differences in toxin level based on glomerular versus non-glomerular etiology, even when accounting for the differences in eGFR between these two subgroups. In this sample, we did not detect any associations between these toxin levels and neurocognitive or cardiac outcomes.

Ultraprocessed Food Consumption and Obesity Development in Canadian Children

Ultraprocessed foods (UPF), characterized as shelf-stable but nutritionally imbalanced foods, pose a public health crisis worldwide. In adults, UPF consumption is associated with increased obesity risk, but findings among children are inconsistent. To examine the associations among UPF intake, anthropometric adiposity indicators, and obesity status in Canadian children. In the CHILD Cohort Study, one of the largest prospective, multicenter, population-based pregnancy cohorts in Canada, diet was assessed during the 3-year visit (September 2011 to June 2016), and anthropometric measurements were assessed at the 5-year visit (December 2013 to April 2018). Data analysis was performed between July 1, 2023, and June 30, 2024. Diet intake was assessed using a semiquantitative food frequency questionnaire at 3 years of age. UPFs were identified using the NOVA classification system. Anthropometric adiposity indicators were measured at 5 years of age and used to calculate age- and sex-standardized z scores for body mass index (BMI), waist to height ratio, and subscapular and triceps skinfold thicknesses, and obesity, which was defined using BMI z score cutoffs. Multivariable-adjusted regression analyses were used to examine the associations of UPF with adiposity and obesity development, accounting for parental, birth, and early-childhood factors. Among 2217 participants included in this study, median age at the outcome assessment was 5.0 (IQR, 5.0-5.1) years, and 1175 (53.0%) were males. At 3 years of age, UPF contributed 45.0% of total daily energy intake. UPF energy contribution was higher in males vs females (46.0% vs 43.9%; P < .001). Among all participants, higher UPF intake at 3 years of age was associated with higher anthropometric adiposity indicators at 5 years of age, primarily driven by males. In males, every 10% UPF energy increase was associated with higher adiposity indicator z scores for BMI (β, 0.08; 95% CI, 0.03-0.14), waist to height ratio (β, 0.07; 95% CI, 0.01-0.12), and subscapular (β, 0.12; 95% CI, 0.06-0.18) and triceps (β, 0.09; 95% CI, 0.03-0.15) skinfold thickness and higher odds of living with overweight or obesity (odds ratio, 1.19; 95% CI, 1.03-1.36). No significant associations were observed among females. In this cohort study of Canadian children, high UPF consumption during early childhood was associated with obesity development, primarily in males. These findings can inform targeted public health initiatives for early childhood centers and caregiver education programs to reduce UPF intake and prevent obesity.

Clinical course and flare predictors in patients with rheumatoid arthritis in low disease activity and ultrasound remission monitored by ultrasound yearly and on-demand: A prospective 2-year observation study

Introduction and objectivesUltrasound (US) remission in rheumatoid arthritis (RA) targets synovitis absence. Tenosynovitis triggers flares. Despite increased ultrasound use, flare patterns among patients with low disease activity (LDA) and ultrasound remission, especially in real-world settings, are poorly understood. This study examined flare rates and predictors of US remission in patients without synovitis or tenosynovitis. Materials and methodsIn a study of 88 patients achieving US remission and LDA, the focus was on the time to the first flare over a 2-year follow-up. US remission, indicated by the absence of active synovitis and tenosynovitis based on a power Doppler (US-PD) score of 0, was assessed on various joints. Flares are defined by the need for additional medication or encountering a US-PD flare. They were monitored at the baseline, 1-year, and 2-year visits with further US evaluation at clinical flare-ups. Baseline factors linked to a shorter time to flare were analyzed. ResultsAt 1 year, LDA and US remission rates were 75% and 92%, respectively, and at 2 years, 73% and 87% respectively. Over the 2 years, 40% experienced flare, occurring on average at 11.7±7.0 months. Notably, 5.7% have US-PD flares without clinical signs. Analysis revealed Stage III disease and CRP as factors linked to a shorter time to flare. Discussion and conclusionsIn patients with RA achieving LDA and US remission, frequent flares were observed with US remission over 2 years, but most maintained sustained remission. Baseline factors are essential for predicting flares, emphasizing continuous monitoring and personalized treatment to sustain remission and minimize flare risks in RA management.

Impact of cervical kyphosis on segmental motion and symptomatic adjacent segment degeneration: a long-term follow-up data of more than 5 years.

This study was performed to assess the impact of cervical kyphosis on the locations of average center of rotation (COR) of each level preoperatively and to investigate whether uncorrected cervical kyphosis increases the incidence of symptomatic adjacent segment degeneration (ASD) after anterior cervical decompression and fusion (ACDF). We retrospectively analyzed all patients surgically treated for cervical myelopathy, radiculopathy, or deformity at a single institution from 2012 to 2018. They were divided into cervical kyphosis and cervical lordosis cohorts. Propensity score matching was performed. Preoperative cervical segmental and postoperative adjacent segment CORs were measured. Development of symptomatic ASD in all patients was assessed after > 5 years of follow-up. Among 412 patients with cervical lordosis and 47 patients with S-type cervical kyphosis, we established 37 matched pairs before and after surgery. In total, 368 COR locations were measured. Uncorrected kyphosis was identified in seven patients. The CORs of the cervical spine were located farther forward and upward in the cervical kyphosis group than in the control group (p < 0.05). At 1-year visit after ACDF, the locations of the adjacent COR showed no significant differences between the cervical postoperative lordosis group and control group. The incidence of symptomatic ASD was significantly higher in the uncorrected kyphosis group than in the corrected kyphosis group (42.9% vs. 2.5%, p = 0.001) and lordosis group (42.9% vs. 1.9%, p < 0.001). Cervical kyphosis can impact the locations of COR and increase the incidence of symptomatic ASD. Kyphosis correction is needed during ACDF in patients with cervical kyphosis.

Prevalence and incidence of heart failure in patients with type 2 diabetes mellitus. Results of the prospective DIABET-IC study

Abstract Introduction Heart failure (HF) is one of the major health problems in our environment today. Type 2 diabetes mellitus (DM2) is an important cardiovascular risk factor and can increase the burden of HF through various mechanisms. The incidence of HF in DM2 has not been well studied. Purpose The aim of our study was to evaluate the prevalence and incidence of HF in patients with DM2 followed in hospital cardiology and endocrinology departments. Methods The DIABET-IC study is a longitudinal cohort, prospective, multicenter follow-up study that included 1,249 consecutive patients with DM2 in 2018-2019 in 30 Spanish centers in cardiology and endocrinology outpatient clinics. HF was diagnosed according to the clinical records and following the criteria of the European Society of Cardiology. The prevalence of HF at the inclusion visit was analyzed, as well as the incidence of HF (new diagnoses) during a 3-year follow-up. Results Mean age was 67.3±+9.9 years, with 31.7% of the patients being women. Cardiology clinics included 61.9% of patients and endocrinology clinics the remaining 38.1%. There was a previous history of coronary artery disease in 38.6%, hypertensive heart disease in 21% and atrial fibrillation in 31.9%. Cardiovascular and antidiabetic drugs prescribed at the baseline and 3-year visits are shown in figure 1. Figure 2 summarizes the results of the study. The prevalence of HF at the baseline visit was 39.2%, 490 cases (with reduced LVEF 17.3%, mildly reduced 8.1% and preserved 13.8%). After a follow-up of 1,935/100 persons-year of cases without baseline HF, 58 incident cases of HF were diagnosed, 7.6% (32 in the first year, 13 in the second and 13 in the third year of follow-up). The incidence rate was 3.01/100 person-years (95%CI: 2.30-3.92). Of these 58 cases, 23.7% were with reduced LVEF, 28.9% with slightly reduced LVEF and 47.4% preserved. The incidence was higher in patients followed by endocrinology (3.90 vs 2.90/100 persons-year; p=0.042). At the end of the 3-year follow-up, including baseline prevalence, 46.8% of all patients had HF. Conclusions The prevalence and incidence of HF in patients with DM2 are very high. The incidence of HF is around 3% per year, which is almost 8 times higher than the rate found in large studies in the general population. Approximately half of the new cases were HF with preserved LVEF, and the other half with LVEF &amp;lt; 50%. The use of new antidiabetic drugs, such as iSGLT2, which have been shown to reduce the incidence of HF, should be encouraged.

Subjective Memory Complaints and the Effect of a Multidomain Lifestyle Intervention on Cognition: The FINGER Trial.

Older people reporting subjective memory complaints (SMCs) may have a greater risk of cognitive decline. Multidomain lifestyle interventions are a promising strategy for the prevention of cognitive decline. The aim of this study was to investigate whether the presence of SMCs affects the efficacy of a 2-year multidomain lifestyle intervention on cognition. This study is part of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) project. Participants (a subsample of 568 individuals, baseline age 60-77 years) were randomized (1:1) to receive a 2-year multidomain lifestyle intervention group including dietary advice, exercise, cognitive training, and vascular risk management, or regular health advice control group. Cognitive performance was assessed at baseline and at 1- and 2-year visits, using a neuropsychological test battery, including tests assessing memory, executive functions, and processing speed. Participants rated the frequency of SMCs using the Prospective and Retrospective Memory Questionnaire. Having more retrospective SMCs was linked to a less favorable cognitive trajectory over 2 years. The difference between the intervention and control groups in annual change in tested memory performance was 0.077 (95% CI, 0.008-0.146) among those reporting more retrospective SMCs and -0.011 (-0.074 to 0.053) among those with less SMCs; interaction effect p = .019. No other interactions between SMCs and intervention allocation were observed. A lifestyle intervention may be beneficial for older adults with and without SMCs. Persons having more retrospective SMCs may benefit more from the intervention regarding memory functioning. Clinical Trials Registration Number: NCT01041989.

Machine Learning For Risk Prediction After Heart Failure Emergency Department Visit or Hospital Admission Using Administrative Health Data.

Patients visiting the emergency department (ED) or hospitalized for heart failure (HF) are at increased risk for subsequent adverse outcomes, however effective risk stratification remains challenging. We utilized a machine-learning (ML)-based approach to identify HF patients at risk of adverse outcomes after an ED visit or hospitalization using a large regional administrative healthcare data system. Patients visiting the ED or hospitalized with HF between 2002-2016 in Alberta, Canada were included. Outcomes of interest were 30-day and 1-year HF-related ED visits, HF hospital readmission or all-cause mortality. We applied a feature extraction method using deep feature synthesis from multiple sources of health data and compared performance of a gradient boosting algorithm (CatBoost) with logistic regression modelling. The area under receiver operating characteristic curve (AUC-ROC) was used to assess model performance. We included 50,630 patients with 93,552 HF ED visits/hospitalizations. At 30-day follow-up in the holdout validation cohort, the AUC-ROC for the combined endpoint of HF ED visit, HF hospital readmission or death for the Catboost and logistic regression models was 74.16 (73.18-75.11) versus 62.25 (61.25-63.18), respectively. At 1-year follow-up corresponding values were 76.80 (76.1-77.47) versus 69.52 (68.77-70.26), respectively. AUC-ROC values for the endpoint of all-cause death alone at 30-days and 1-year follow-up were 83.21 (81.83-84.41) versus 69.53 (67.98-71.18), and 85.73 (85.14-86.29) versus 69.40 (68.57-70.26), for the CatBoost and logistic regression models, respectively. ML-based modelling with deep feature synthesis provided superior risk stratification for HF patients at 30-days and 1-year follow-up after an ED visit or hospitalization using data from a large administrative regional healthcare system.

MINISTOP 3.0: Implementation of a mHealth obesity prevention program within Swedish child healthcare – study protocol for a cluster randomized controlled trial

BackgroundPreviously, we have reported on the efficacy and real-world effectiveness of a parent-oriented mobile health intervention (MINISTOP 1.0 and 2.0), which have shown improvements in pre-school children’s lifestyle behaviours. However, there is a need for implementation evidence. The overall aims of this study are to: (i) compare two different implementation strategies for MINISTOP 3.0 (Basic vs. Enhanced) on: acceptability, appropriateness, feasibility, organizational readiness to implement MINISTOP 3.0 within Swedish child healthcare (primary outcomes) as well as reach, costs, and adoption of MINISTOP 3.0 (secondary outcomes); (ii) evaluate cost-effectiveness of MINISTOP 3.0; (iii) explore the sustainability of MINISTOP 3.0; (iv) evaluate the determinants of effectiveness of MINISTOP 3.0 on children’s key lifestyle behaviours; and (v) investigate the long-term effects of MINISTOP 3.0 on children’s body mass index.MethodsA hybrid type III implementation-effectiveness design will be used. A cluster randomized controlled trial will be conducted to compare the effects of basic versus enhanced implementation strategies on the outcomes at the child healthcare level. A minimum of 50 child healthcare centers across Sweden will participate and we aim to recruit 120 nurses. Child healthcare nurses in both groups will offer the MINISTOP 3.0 app to the families at the 2.5/3-year routine visit. Basic implementation strategies include educational meeting with nurses, formal implementation blueprint, develop/distribute educational materials and enhanced implementation includes all aforementioned strategies plus auditing/providing feedback and ongoing training for nurses. All outcomes will be assessed at baseline and 12 months post-implementation. Implementation outcomes will be assessed quantitatively using questionnaires and sustainability will be assessed qualitatively at 12 months. Children’s key lifestyle behaviours will be collected through a parental questionnaire within the MINISTOP app at baseline and 6 months after they have received the app. Children’s weight/height will be measured at routine visits at 2.5/3 (baseline), 4 and 5 years of age.DiscussionThis study will provide important implementation evidence with regards to implementing mHealth interventions within Swedish child healthcare at scale and these results have the potential to be generalized to other digital interventions being implemented in child healthcare.Trial registrationClinicalTrials.gov, NCT05667753. Registered December 29, 2022.

Free-water: A promising structural biomarker for cognitive decline in aging and mild cognitive impairment.

Diffusion MRI derived free-water (FW) metrics show promise in predicting cognitive impairment and decline in aging and Alzheimer's disease (AD). FW is sensitive to subtle changes in brain microstructure, so it is possible these measures may be more sensitive than traditional structural neuroimaging biomarkers. In this study, we examined the associations among FW metrics (measured in the hippocampus and two AD signature meta-ROIs) with cognitive performance, and compared FW findings to those from more traditional neuroimaging biomarkers of AD. We leveraged data from a longitudinal cohort (nparticipants = 296, nobservations = 870, age at baseline: 73 ± 7 years, 40% mild cognitive impairment [MCI]) of older adults who underwent serial neuropsychological assessment (episodic memory, information processing speed, executive function, language, and visuospatial skills) and brain MRI over a maximum of four time points, including baseline (n = 284), 18-month (n = 246), 3-year (n = 215), and 5-year (n = 125) visits. The mean follow-up period was 2.8 ± 1.3 years. Structural MRI was used to quantify hippocampal volume, in addition to Schwarz and McEvoy AD Signatures. FW and FW-corrected fractional anisotropy (FAFWcorr) were quantified in the hippocampus (hippocampal FW) and the AD signature areas (SchwarzFW, McEvoyFW) from diffusion-weighted (dMRI) images using bi-tensor modeling (FW elimination and mapping method). Linear regression assessed the association of each biomarker with baseline cognitive performance. Additionally, linear mixed-effects regression assessed the association between baseline biomarker values and longitudinal cognitive performance. A subsequent competitive model analysis was conducted on both baseline and longitudinal data to determine how much additional variance in cognitive performance was explained by each biomarker compared to the covariate only model, which included age, sex, race/ethnicity, apolipoprotein-ε4 status, cognitive status, and modified Framingham Stroke Risk Profile scores. All analyses were corrected for multiple comparisons using an FDR procedure. Cross-sectional results indicate that hippocampal volume, hippocampal FW, Schwarz and McEvoy AD Signatures, and the SchwarzFW and McEvoyFW metrics are all significantly associated with memory performance. Baseline competitive model analyses showed that the McEvoy AD Signature and SchwarzFW explain the most unique variance beyond covariates for memory (ΔRadj 2 = 3.47 ± 1.65%) and executive function (ΔRadj 2 = 2.43 ± 1.63%), respectively. Longitudinal models revealed that hippocampal FW explained substantial unique variance for memory performance (ΔRadj 2 = 8.13 ± 1.25%), and outperformed all other biomarkers examined in predicting memory decline (pFDR = 1.95 x 10-11). This study shows that hippocampal FW is a sensitive biomarker for cognitive impairment and decline, and provides strong evidence for further exploration of this measure in aging and AD.

One-year follow-up of clinical convergence measures in children enrolled in the Convergence Insufficiency Treatment Trial-Attention and Reading Trial.

To assess the long-term stability of clinical measures of convergence (near point of convergence [NPC] and positive fusional vergence [PFV]) in participants enrolled in the Convergence Insufficiency Treatment Trial-Attention and Reading Trial (CITT-ART) who received 16 weeks of office-based vergence/accommodative therapy. A total of 310 children, 9-14 years old, with symptomatic convergence insufficiency were enrolled in CITT-ART. Some 270 completed both their 16-week primary outcome visit followed by a 1-year follow-up visit. Of those 270, 181 (67%) were randomised to the vergence/accommodative therapy. Of the 181 in the vergence/accommodative group, 121 (67%) reported not receiving any additional treatment after the 16-week primary outcome visit. The mean change in NPC, PFV and percentages of children classified by the predetermined success criteria of convergence (normal NPC [<6 cm] and/or improved by ≥4 cm; normal PFV [passing Sheard's criterion and base-out break >15Δ] and/or improved by ≥10Δ) were compared at the 16-week primary outcome visit and 1 year later. Of the 121 who returned for their 1-year follow-up visit, there was no significant change in mean adjusted NPC (reduction of -0.2 cm; 95% CI: -1.0 to 0.5 cm) at 1 year. There was a statistically significant decrease in mean-adjusted PFV (-4.7∆; 95% CI: -6.5 to -2.8Δ) at 1 year. There were similar percentages of participants classified as 'normal' (p = 0.30), 'normal and/or improved' (p > 0.50) and 'normal and improved' (p > 0.14) based on NPC and PFV at the 1-year visit compared with the 16-week primary outcome visit. The improvements in NPC and PFV following 16 weeks of vergence/accommodative therapy (with no reported additional treatment thereafter) in children with symptomatic convergence insufficiency persisted 1-year post-treatment.

Longer ICU stay and invasive mechanical ventilation accelerate telomere shortening in COVID-19 patients 1 year after recovery

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes virus-induced-senescence. There is an association between shorter telomere length (TL) in coronavirus disease 2019 (COVID-19) patients and hospitalization, severity, or even death. However, it remains unknown whether virus-induced-senescence is reversible. We aim to evaluate the dynamics of TL in COVID-19 patients 1 year after recovery from intensive care units (ICU). Longitudinal study enrolling 49 patients admitted to ICU due to COVID-19 (August 2020 to April 2021). Relative telomere length (RTL) quantification was carried out in whole blood by monochromatic multiplex real-time quantitative PCR (MMqPCR) assay at hospitalization (baseline) and 1 year after discharge (1-year visit). The association between RTL and ICU length of stay (LOS), invasive mechanical ventilation (IMV), prone position, and pulmonary fibrosis development at 1-year visit was evaluated. The median age was 60 years, 71.4% were males, median ICU-LOS was 12 days, 73.5% required IMV, and 38.8% required a prone position. Patients with longer ICU-LOS or who required IMV showed greater RTL shortening during follow-up. Patients who required pronation had a greater RTL shortening during follow-up. IMV patients who developed pulmonary fibrosis showed greater RTL reduction and shorter RTL at the 1-year visit. Patients with longer ICU-LOS and those who required IMV had a shorter RTL in peripheral blood, as observed 1 year after hospital discharge. Additionally, patients who required IMV and developed pulmonary fibrosis had greater telomere shortening, showing shorter telomeres at the 1-year visit. These patients may be more prone to develop cellular senescence and lung-related complications; therefore, closer monitoring may be needed.

Long-Term Safety and Immunogenicity of AZD1222 (ChAdOx1 nCoV-19): 2-Year Follow-Up from a Phase 3 Study.

A better understanding of the long-term safety, efficacy, and immunogenicity of COVID-19 vaccines is needed. This phase 3, randomized, placebo-controlled study for AZD1222 (ChAdOx1 nCoV-19) primary-series vaccination enrolled 32,450 participants in the USA, Chile, and Peru between August 2020 and January 2021 (NCT04516746). Endpoints included the 2-year follow-up assessment of safety, efficacy, and immunogenicity. After 2 years, no emergent safety signals were observed for AZD1222, and no cases of thrombotic thrombocytopenia syndrome were reported. The assessment of anti-SARS-CoV-2 nucleocapsid antibody titers confirmed the durability of AZD1222 efficacy for up to 6 months, after which infection rates in the AZD1222 group increased over time. Despite this, all-cause and COVID-19-related mortality remained low through the study end, potentially reflecting the post-Omicron decoupling of SARS-CoV-2 infection rates and severe COVID-19 outcomes. Geometric mean titers were elevated for anti-SARS-CoV-2 neutralizing antibodies at the 1-year study visit and the anti-spike antibodies were elevated at year 2, providing further evidence of increasing SARS-CoV-2 infections over long-term follow-up. Overall, this 2-year follow-up of the AZD1222 phase 3 study confirms that the long-term safety profile remains consistent with previous findings and supports the continued need for COVID-19 booster vaccinations due to waning efficacy and humoral immunity.

One-Year Results of Ear Reconstruction with 3D Printed Implants.

External ear reconstruction has been a challenging subject for plastic surgeons for decades. Popular methods using autologous costal cartilage or polyethylene still have their drawbacks. With the advance of three-dimensional (3D) printing technique, bioscaffold engineering using synthetic polymer draws attention as an alternative. This is a clinical trial of ear reconstruction using 3D printed scaffold, presented with clinical results after 1 year. From 2021 to 2022, five adult patients with unilateral microtia underwent two-staged total ear reconstruction using 3D printed implants. For each patient, a patient-specific 3D printed scaffold was designed and produced with polycaprolactone (PCL) based on computed tomography images, using fused deposition modeling. Computed tomography scan was obtained preoperatively, within 2 weeks following the surgery and after 1 year, to compare the volume of the normal side and the reconstructed ear. At 1-year visit, clinical photo was taken for scoring by two surgeons and patients themselves. All five patients had completely healed reconstructed ear at 1-year follow-up. On average, the volume of reconstructed ear was 161.54% of that of the normal side ear. In a range of 0 to 10, objective assessors gave scores 3 to 6, whereas patients gave scores 8 to 10. External ear reconstruction using 3D printed PCL implant showed durable, safe results reflected by excellent volume restoration and patient satisfaction at 1 year postoperatively. Further clinical follow-up with more cases and refinement of scaffold with advancing bioprinting technique is anticipated. The study's plan and results have been registered with the Clinical Research Information Service (CRIS No. 3-2019-0306) and the Ministry of Food and Drug Safety (MFDS No. 1182).

Laparoscopic Lateral Hysteropexy versus Hysterosacropexy in Women with Stage III Uterine Prolapse.

Background: Minimally invasive techniques in gynecological pathology have well-known benefits, the "gold standard" of uterine prolapse being currently managed laparoscopically. Laparoscopic lateral hysteropexy and hysterosacropexy are surgical techniques that can be performed for uterine prolapse. Laparoscopic management of such cases is recommended, but requires well-trained teams in laparoscopic surgery. Methods: This study is a prospective analysis of patients who required surgical treatment for stage III uterine prolapse, hospitalized in the Surgery Department of Constanta County Hospital, for which laparoscopic lateral hysteropexy or laparoscopic hysterosacropexy was performed. Results: Between 2016-2020, 61 patients were hospitalized with stage III uterine prolapse that required surgery. All patients underwent laparoscopic surgery. Symptomatology was dominated by urinary incontinence (50%, 44.89%) and obstructive defecation (16.66%, 18.36%). Intraoperative complications were encountered in 33.3% of cases undergoing laparoscopic hysterosacropexy and in 8.16% undergoing laparoscopic lateral hysteropexy. At one year, the recurrence rate was 2.04% for patients who underwent lateral hysteropexy and 8.33% for patients who underwent hysterosacropexy. No patient had a recurrence at the 3-year visit. Conclusions: Laparoscopic lateral hysteropexy is emerging as an appropriate, safe, and effective procedure to treat advanced apical prolapse that requires further clinical attention and development to fully understand its surgical place in the treatment of pelvic defects.

Choroidal Changes During and After Discontinuing Long-Term 0.01% Atropine Treatment for Myopia Control.

Few studies have explored choroidal changes after cessation of myopia control. This study evaluated the choroidal thickness (ChT) and choroidal vascularity index (CVI) during and after discontinuing long-term low-concentration atropine eye drops use for myopia control. Children with progressive myopia (6-16years; n = 153) were randomized to receive 0.01% atropine eye drops or a placebo (2:1 ratio) instilled daily over 2years, followed by a 1-year washout (no eye drop use). Optical coherence tomography imaging of the choroid was conducted at the baseline, 2-year (end of treatment phase), and 3-year (end of washout phase) visits. The main outcome measure was the subfoveal ChT. Secondary measures include the CVI. During the treatment phase, the subfoveal choroids in both treatment and control groups thickened by 12-14 µm (group difference P = 0.56). During the washout phase, the subfoveal choroids in the placebo group continued to thicken by 6.6 µm (95% confidence interval [CI] = 1.7 to 11.6), but those in the atropine group did not change (estimate = -0.04 µm; 95% CI = -3.2 to 3.1). Participants with good axial eye growth control had greater choroidal thickening than the fast-progressors during the treatment phase regardless of the treatment group (P < 0.001), but choroidal thickening in the atropine group's fast-progressors was not sustained after stopping eye drops. CVI decreased in both groups during the treatment phase, but increased in the placebo group after treatment cessation. On average, compared to placebo, 0.01% atropine eye drop treatment did not cause a differential rate of change in ChT during treatment, but abrupt cessation of long-term 0.01% atropine eye drops may disrupt normal choroidal thickening in children.

Three-year analysis of results, safety and progression in patients with open-angle glaucoma or ocular hypertension, undertaking trabecular microsurgery

AimTo evaluate the efficacy, safety, structural and functional progression following the insertion of iStent inject ® implants in patients with open-angle glaucoma or ocular hypertension at a tertiary-level hospital. Materials and methodsA retrospective study included 98 eyes (57 males and 41 females) with open-angle glaucoma or ocular hypertension, which underwent iStent inject W® implantation (Glaukos, Corporation, CA) between December 2018 and December 2022. Differences in intraocular pressure (IOP), the number of hypotensive eye drops used, and structural and functional tests were assessed between preoperative values and subsequent reviews during a follow-up period of one (n = 98), two (n = 55), and three years (n = 15) after surgery. ResultsAmong the 98 eyes studied, 85% were diagnosed with open-angle glaucoma (50% mild, 32% moderate, and 18% severe) and 15% with ocular hypertension. There was a statistically significant reduction in IOP compared to preoperative values for all visits except the 1-month (p = 0.36) and 3-year (p = 0.39) visits. Visual acuity increased from 0.39 ± 0.25 to 0.72 ± 0.24 (p < 0.01), considering that a significant portion of the interventions included cataract surgery. Before surgery, 66% of the sample used 2 or more hypotensive medications. Post-surgery, the number of hypotensive medications decreased (from 1.88 ± 0.84 to 0.21 ± 0.59 at 3 years) (p < 0.01), with an 88.9% reduction in the number of medications over three years. After surgery, 75% of cases did not require any medication.Regarding structural and functional tests, thickness of retinal nerve fiber layers (RNFL (p = 0.35), excavation / papilla ratio E/P (p = 0.31), visual function index(VFI (p = 0.06), and deviation mean (MD (p = 0.06) showed no statistically significant differences post-intervention. However, standard deviation of the pattern (DSM) did exhibit differences, decreasing from 5.46 ± 4.03 dB to 5.34 ± 3.48 dB (p = 0.02). ConclusionThe results of this study suggest that the iStent inject W® technique constitutes an effective and safe option for tension control and glaucoma treatment.

A holistic lifestyle mobile health intervention for the prevention of type 2 diabetes and common mental disorders in Asian women with a history of gestational diabetes: a randomised control trial with 3-year follow-up protocol

BackgroundWomen with a history of gestational diabetes mellitus (GDM) are 12-fold more likely to develop type 2 diabetes (T2D) 4–6 years after delivery than women without GDM. Similarly, GDM is associated with the development of common mental disorders (CMDs) (e.g. anxiety and depression). Evidence shows that holistic lifestyle interventions focusing on physical activity (PA), dietary intake, sleep, and mental well-being strategies can prevent T2D and CMDs. This study aims to assess the effectiveness of a holistic lifestyle mobile health intervention (mHealth) with post-GDM women in preventing T2D and CMDs in a community setting in Singapore.MethodsThe study consists of a 1-year randomised controlled trial (RCT) with a 3-year follow-up period. Post-GDM women with no current diabetes diagnosis and not planning to become pregnant will be eligible for the study. In addition, participants will complete mental well-being questionnaires (e.g. depression, anxiety, sleep) and their child’s socio-emotional and cognitive development. The participants will be randomised to either Group 1 (Intervention) or Group 2 (comparison). The intervention group will receive the “LVL UP App”, a smartphone-based, conversational agent-delivered holistic lifestyle intervention focused on three pillars: Move More (PA), Eat Well (Diet), and Stress Less (mental wellbeing). The intervention consists of health literacy and psychoeducational coaching sessions, daily “Life Hacks” (healthy activity suggestions), slow-paced breathing exercises, a step tracker (including brisk steps), a low-burden food diary, and a journaling tool. Women from both groups will be provided with an Oura ring for tracking physical activity, sleep, and heart rate variability (a proxy for stress), and the “HAPPY App”, a mHealth app which provides health promotion information about PA, diet, sleep, and mental wellbeing, as well as display body mass index, blood pressure, and results from the oral glucose tolerance tests. Short-term aggregate effects will be assessed at 26/27 weeks (midpoint) and a 1-year visit, followed by a 2, 3, and 4-year follow-up period.DiscussionHigh rates of progression of T2D and CMDs in women with post-GDM suggest an urgent need to promote a healthy lifestyle, including diet, PA, sleep, and mental well-being. Preventive interventions through a holistic, healthy lifestyle may be the solution, considering the inextricable relationship between physical and psychological health. We expect that holistic lifestyle mHealth may effectively support behavioural changes among women with a history of GDM to prevent T2D and CMDs.Trial statusThe protocol study was approved by the National Healthcare Group in Singapore, Domain Specific Review Board (DSRB) [2023/00178]; June 2023. Recruitment began on October 18, 2023.Trial registrationClinicalTrials.gov NCT05949957. The first submission date is June 08, 2023.

Socioeconomic Disadvantage and Youth Mental Health During the COVID-19 Pandemic Lockdown

Adolescence is a period in which mental health problems emerge. Research suggests that the COVID-19 lockdown may have worsened emotional and behavioral health. To examine whether socioeconomic status was associated with mental health outcomes among youths during the COVID-19 pandemic. The Adolescent Brain Cognitive Development (ABCD) Study is a multisite 10-year longitudinal study of youth neurocognitive development in the US. Recruitment was staggered where the baseline visit (ages 9 to 10 years) occurred from 2016 to 2018, and visits occurred yearly. The COVID-19 lockdown halted research collection during the 2-year follow-up visits (ages 11 to 12 years), but eventually resumed. As some youths already underwent their 2-year visits prior to lockdown, this allowed for a natural experiment-like design to compare prepandemic and intrapandemic groups. Thus, data were gathered from the 1-year follow-up (pre-COVID-19 lockdown for all youths) and the 2-year follow-up, of which a portion of youths had data collected after the lockdown began, to compare whether a period of near social isolation was associated with mental health symptoms in youths. The prepandemic group consisted of youths with a 2-year follow-up visit collected prior to March 11, 2020, and the intrapandemic group had their 2-year follow-up visit after lockdown restrictions were lifted. Assessments included measures on income-to-needs ratio (INR; derived from total household income), the Child Behavior Checklist (a measure of mental health symptomology), and the Family Environmental Scale. The final sample included 10 399 youths; 3947 (52.3%) were male; 2084 (20.3%) were Latinx/Hispanic; 6765 (66.0%) were White; 4600 (44.2%) reported caregiver education levels below a 4-year college degree; and 2475 (26.2%) had INR either below 100% (indicating poverty) or between 100% and less than 200% (near poverty). Among youths in the intrapandemic group, worse mental health symptoms (eg, more total problems, greater depression, and greater anxiety) over time were associated with being from a household with higher socioeconomic status (eg, when comparing individuals who differed by 1 unit on INR between prepandemic and intrapandemic groups from 1-year to 2-year follow-up, their expected difference in total problems score was 0.79 [95% CI, 0.37-1.22]; false discovery rate-corrected P < .001). This cohort study found that the COVID-19 lockdown was associated with disproportionately negative mental health outcomes among youths from higher socioeconomic status backgrounds. Although this study does not shed light on the direct mechanisms driving these associations, it does provide some support for positive outcomes for youths. Future studies are needed to understand whether these associations persist over longer periods of time.