24-month Follow-up Research Articles

Impact of recruitment strategies on individual participation practices in the Canadian National Vaccine Safety Network: prospective cohort study.

The Canadian National Vaccine Safety (CANVAS) network conducted a multi-center, prospective vaccine safety study to collect safety data after dose 1 and 2 of COVID-19 vaccines and follow up safety information 7 months after dose 1. This study aimed to describe and evaluate the recruitment methods used by CANVAS and the retention of participants by each modality. CANVAS deployed a multi-pronged recruitment approach to reach a larger sample, without in-person recruitment. Three primary recruitment strategies were used: passive recruitment, technology-assisted electronic invitation through the vaccine booking system (auto-invitation), or auto-registration through the vaccine registries (auto-enrollment). Between December 2020 and April 2022, approximately 1.3 million vaccinated adults either self-enrolled or were auto-enrolled in CANVAS, representing about 5% of the vaccinated adult Canadian population. Approximately 1 million participants were auto-enrolled, 300,000 were recruited by auto-invitation, and 5,000 via passive recruitment. Overall survey completion rates for dose 1, dose 2 and the 7-month follow-up surveys were 51.7% (681,198 of 1,318,838), 54.3% (369,552 of 681,198), and 66.4% (452,076 of 681,198), respectively. Completion rates were lower among auto-enrolled participants compared to passively recruited or auto-invited participants who self-enrolled. However, auto-enrolled samples were much larger, which offset the lower completion rates. Our data suggest that auto-enrollment provided an opportunity to reach and retain a larger number of individuals in the study compared to other recruitment modalities.

Efficacy of escalating therapy with brentuximab vedotin-AVD in advanced stage Hodgkin lymphoma patients with positive interim positron emission tomography after ABVD.

Patients with advanced-stage Hodgkin lymphoma treated with ABVD who have a positive interim FDG-PET (iPET) have a poor prognosis. Escalation to BEACOPP has been shown to improve progression-free survival (PFS). However, randomized trials are lacking to determine the best strategy for intensification. We report on A-AVD escalation treatment outcomes for 15 iPET-positive patients post-ABVD. Overall response and complete response rates were 80% and 60%, respectively. Four patients underwent salvage therapy followed by autologous stem cell transplantation. At a median 17-month follow-up, all patients are alive, 87% in complete remission, and 1-year PFS was 57.8%. For patients ineligible for BEACOPP due to age, comorbidities, or preference, A-AVD escalation may be a viable alternative.

Clinical comparison of lateral supine position mini-percutaneous nephrolithotomy and anatrophic nephrolithotomy in the treatment of complete staghorn renal calculi

BackgroundAt present, the guidelines for urology recommend percutaneous nephrolithotomy (PCNL) as the preferred treatment for staghorn renal calculi (SRC). However, for complete SRC, it has been questioned by clinicians and patients due to high residual stone rate, complications, repeated hospitalizations and high treatment cost. Anatrophic nephrolithotomy (ANL) is a traditional and classic method for the treatment of SRC. Due to its high trauma and high technical requirements, it is difficult to carry out in primary hospitals, and gradually replaced by PCNL. The purpose of this study is to compare the efficacy of PCNL and ANL in the treatment of complete SRC.MethodsOverall, 238 patients with complete SRC were divided into mini-PCNL in lateral supine position group, (n = 190) and ANL group (n = 94) according to treatment for a retrospective cohort study. The calculi parameters, renal function index, comorbidities of calculi, surgical complications, length and frequency of hospitalization, treatment costs, results of postoperative satisfaction survey were compared between the two groups.ResultsThe risk of the residual stone rate after mini-PCNL in lateral supine position was 239 times (OR = 238.667, P < 0.0001), the number of residual stone 1.3 times (OR = 1.326, P < 0.0001), the amount of residual stone 2.2 times (OR = 2.224, P < 0.0001) that of ANL. The risk of the cost of initial treatment after mini-PCNL in lateral supine position was 3.3 times (OR = 3.273, P < 0.0001), the total cost of treatment 4 times (OR = 4.051, P < 0.0001), the total length of hospital stays 1.4 times (OR = 1.44, P < 0.0001) that of ANL, the incidence of postoperative renal atrophy was 2.2 times (OR = 2.171, P = 0.008) higher in the ANL than in the mini-PCNL in lateral supine position. Glomerular filtration rate (GFR) reduction after ANL was 1.4 times (OR = 1.381, P = 0.037) greater than that after mini-PCNL in lateral supine position at 24-month follow-up. The risk of the overall satisfaction of ANL was 58 times (OR = 57.857, P < 0.0001) higher than that of mini-PCNL in lateral supine position, the number of branches of staghorn greater than 8 is a high risk factor for the occurrence of residual stone after mini-PCNL in lateral supine position (OR = 353.137, P < 0.0001).ConclusionAlthough the risk of renal atrophy and decreased GFR after ANL is higher than that of mini-PCNL in lateral supine position, the efficacy of traditional ANL in the treatment of complete SRC was generally superior to that of mini-PCNL in lateral supine position. Moreover, number of branches of staghorn greater than 8 are the preferred ANL for complete SRC.Trial registrationChiCTR2100047462. The trial was registered in the Chinese Clinical Trial Registry; registration date: 19/06/2021.

The Association Between Trajectories of Self-reported Psychotic Experiences and Continuity of Mental Health Care in a Longitudinal Cohort of Adolescents and Young Adults.

Young people (YP) with psychotic experiences (PE) have an increased risk of developing a psychiatric disorder. Therefore, knowledge on continuity of care from child and adolescent (CAMHS) to adult mental health services (AMHS) in relation to PE is important. Here, we investigated whether the self-reported trajectories of persistent PE were associated with likelihood of transition to AMHS and mental health outcomes. In this prospective cohort study, interviews and questionnaires were used to assess PE, mental health, and service use in 763 child and adolescent mental health service users reaching their service's upper age limit in 8 European countries. Trajectories of self-reported PE (3 items) from baseline to 24-month follow-up were determined using growth mixture modeling (GMM). Associations were assessed with auxiliary variables and using mixed models. Study results. At baseline, 56.7% of YP reported PE. GMM identified 5 trajectories over 24 months: medium increasing (5.2%), medium stable (11.7%), medium decreasing (6.5%), high decreasing (4.2%), and low stable (72.4%). PE trajectories were not associated with continuity of specialist care or transition to AMHS. Overall, YP with PE reported more mental health problems at baseline. Persistence of PE or an increase was associated with poorer outcomes at follow-up. PE are common among CAMHS users when reaching the upper age limit of CAMHS. Persistence or an increase of PE was associated with poorer mental health outcomes, poorer prognosis, and impaired functioning, but were less discriminative for continuity of care.

A Vaping Cessation Text Message Program for Adolescent E-Cigarette Users

E-cigarettes are the most commonly used tobacco product among adolescents. Despite known harms of nicotine exposure among teens, there are no empirically tested vaping cessation interventions. To compare the effectiveness of a text message program for nicotine vaping cessation among adolescents with assessment-only control. A parallel, 2-group, double-blind, individually randomized clinical trial with follow-ups at 1 and 7 months after randomization was conducted from October 1, 2021, to October 18, 2023. Participants were recruited via social media ads; the intervention was delivered via text message; and assessments were completed online or by telephone. Eligible individuals were US residents aged 13 to 17 years who reported past 30-day e-cigarette use, were interested in quitting within 30 days, and owned a mobile phone with an active text message plan. To optimize study retention, all participants received monthly assessments via text message about e-cigarette use. Assessment-only controls (n = 744) received only study retention text messages. Intervention participants (n = 759) also received an automated, interactive text message program for vaping cessation that delivers cognitive and behavioral coping skills training and social support. The primary outcome was self-reported 30-day point-prevalence abstinence from vaping at 7 months analyzed as intention-to-treat, with missingness coded as vaping. Among n = 1503 adolescents randomized, average age was 16.4 (SD, 0.8) years. The sample was 50.6% female, 42.1% male, and 7.4% nonbinary/other; 10.2% Black/African American, 62.6% White, 18.5% multiracial, and 8.7% another race; 16.2% Hispanic; 42.5% sexual minority; and 76.2% vaped within 30 minutes of waking. The 7-month follow-up rate was 70.8%. Point-prevalence abstinence rates were 37.8% (95% CI, 34.4%-41.3%) among intervention participants and 28.0% (95% CI, 24.9%-31.3%) among control participants (relative risk, 1.35 [95% CI, 1.17-1.57]; P < .001). No baseline variables moderated the treatment-outcome relationship. There was no evidence that adolescents who quit vaping transitioned to combustible tobacco products. A tailored, interactive text message intervention increased self-reported vaping cessation rates among adolescents recruited via social media channels. ClinicalTrials.gov Identifier: NCT04919590.

Effectiveness and safety of istent inject as an interventional glaucoma approach for uncontrolled open-angle glaucoma.

To describe the results of iStent inject implantation as a standalone procedure in early-stage uncontrolled glaucoma, with results up to 24 months. A retrospective, single-center case series that recruited patients with open-angle glaucoma (OAG), uncontrolled IOP (defined as ≥18 mmHg), and who are receiving 1-4 glaucoma medications were implanted the iStent inject as a standalone procedure. Exclusion criteria were the contraindications of iStent inject implantation. Primary outcome measures were IOP at 6, 12, 18, and 24 months compared to baseline, and the number of medications at baseline and 24 months. Eighty-eight eyes from 88 patients, aged 57.6 ± 9.8 years, were included. Ten eyes underwent a subsequent glaucoma procedure during follow-up and were excluded from the analysis. The mean IOP (mmHg) was reduced from 20.54 ± 1.42 at baseline to 15.99 ± 1.98 and 16.15 ± 2.21 (n = 78, p < 0.001) at the 12- and 24-month follow-up, respectively, and the mean number of medications was reduced from 2.35 ± 0.70 to 1.31 ± 0.80 (p < 0.001) at 24 months. Of those eyes, 59% had ≥20% reduction in IOP at 24 months, 91% had an IOP ≤18 mmHg at 24 months, and 71.8% were receiving fewer medications. At 24 months, 14.1% of eyes were medication-free, compared to none at baseline. No serious intraoperative or postoperative adverse events occurred. iStent inject can effectively control intraocular pressure in mild glaucoma, reducing medication reliance and improving patient quality of life.

Minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) in treatment of degenerative diseases of lumbosacral spine compared to modified open TLIF: a prospective randomised controlled study.

The aim of this study was to determine the clinical and radiological outcomes of minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) compared to modified open TLIF via the Wiltse approach for treatment of degenerative diseases of the lumbosacral region. The results were evaluated over a post-operative period of 48 months. Radiological data and medical records of patients who underwent MIS TLIF and modified open TLIF between May 2017 and May 2021 were reviewed. Parameters monitored to evaluate the surgical results were: clinical status, operation time, blood loss, radiation dose to patient, day of discharge, analgesic consumption, fusion, and complications rate. For functional assessment, the Visual Analogue Scale for back pain (VAS-BP), VAS for leg pain (VAS-LP), Oswestry Disability Index (ODI), Patient Satisfaction Rate (PSR), and the complication rate were used. This study included 57 patients randomly divided into two groups: 30 operated on using the MIS TLIF technique, and 27 operated on using the modified open TLIF technique via the Wiltse approach. 48-month follow-up rates were similar for the two cohorts. Patients did not differ significantly at baseline in terms of ODI, VAS-BP, or VAS-LP. Perioperatively, MIS TLIF was associated with significantly less blood loss (167.3 ± 80.0 vs. 297.9 ± 81.5 ml, p = 1.1E-05), slightly longer procedures (185.7 ± 45.2 vs. 183.1 ± 66.4 minutes, p = 0.76), a lower radiation dose (MIS 16.9 ± 7.1 vs. 22.0 ± 9.7 mGy OPEN p = 0.012), and shorter hospitalisations (MIS 5.9 ± 1.8 vs. 7.7 ± 1.6 days OPEN). The most common complication was radiculitis, which accounted for 33% and 37% in the MIS and the TLIF groups, respectively. The second most common complication was malposition of the fixation material, which accounted for 18.5% in the TLIF group and 20% in the MIS group. The level of fusion achieved was 92.6% in the MIS group versus 92.3% in the TLIF group. There was lower consumption of analgesics in MIS. Patient Satisfaction Rate (PSR) was 90%. Clinical and radiological outcomes after MIS TLIF in patients with degenerative disease of the lumbosacral region are generally favourable. MIS TLIF was associated with decreased blood loss perioperatively, a lower radiation dose and an earlier discharge, but there was no difference between MIS TLIF and modified open TLIF in 48-month outcomes in terms of disability, back pain, leg pain, quality of life, or patient satisfaction rate or complication rate. Although the differences taper off over time, MIS TLIF has undeniable advantages in the perioperative and early postoperative periods.

Cell-free biomimetic osteochondral scaffold for the treatment of knee articular surface lesions: Clinical outcomes differ based on patient and lesion characteristics.

A cell-free biomimetic osteochondral scaffold was developed to treat cartilage knee lesions, with positive clinical results documented in small case series. However, clear evidence on patient and lesion characteristics that might affect the outcome is still lacking. The aim of this study isto analyse a large cohort of patients treated with this scaffold to investigate factors that could influence the clinical outcome. Two hundred and three patients (mean age 30.7 ± 10.9 years) treated with this scaffold were prospectively evaluated at baseline, 6-, 12-and 24-month follow-up. The clinical outcome was analysed using the International Knee Documentation Committee (IKDC) score, and the activity level was assessed with the Tegner score. The influence of patient and lesion characteristics on clinical outcomes was analysed. Mild and severe adverse reactions were found in 39.0% and 1.5% of patients, respectively. The failure rate was 2.0%, increasing to 12.3% when including also clinical failures. The IKDC subjective score increased from 43.3 ± 15.9 to 61.0 ± 16.2 at 6 months, 68.3 ± 18.5 at 12 monthsand 73.8 ± 18.3 at 24 months (p < 0.0005). The Tegner improved from 2.5 ± 1.7 to 4.2 ± 1.7 at 24 months (p < 0.0005), without reaching the pre-injury level (6.0 ± 2.2) (p < 0.0005). The IKDC objective score changed from 68.5% normal and nearly normal knees before the treatment to 90.1% at 24 months. At 24 months, age showed a correlation with the IKDC subjective score (ρ = -0.247; p < 0.0005), women had a lower score (p < 0.0005), as well as patients with patellar lesions (p = 0.002). Previous surgery correlated with lower results (p = 0.003), while better results were found in osteochondritis dissecans (OCD) compared to degenerative lesions (p = 0.001). This cell-free biomimetic scaffold is a safe and effective treatment for cartilage knee lesions, offering positive clinical results at 2 years with a low failure rate. Better outcomes were observed in younger patients, in lesions of the femoral condylesand in OCD, while joints affected by patellar lesions, patients who underwent previous knee surgery, and women may expect lower results. III, Cohort study.

Breast multiparametric ultrasound: a single-center experience.

To evaluate the role of multiparametric ultrasound (mpUS) in the characterization of focal breast lesions (FBLs). This prospective study enrolled patients undergoing multiparametric breast ultrasound for FBLs. An experienced breast radiologist evaluated the following ultrasound features: US BI-RADS category, vascularization pattern (internal, vessels in rim and combined) and presence of penetrating vessels with each Doppler method (Color-Doppler, Power-Doppler, Microvascular imaging), strain ratio (SR) and Tsukuba score (TS) with Strain Elastography (SE), Emax, Emean, Emin and Eratio with 2D-shear wave elastography (2D-SWE). Core biopsy for all BI-RADS 4-5 FBLs and 24-month follow-up for all BI-RADS 2-3 FBLs were considered for standard of reference. The diagnostic performance was assessed with the area under curve (AUCs) and cut-off values were determined according to the Youden's index. A total of 139 FBLs were included with 75/139 (53.9%) benign and 64/139 (46.1%) malignant FBLs. Internal vascularization patterns (p < 0.001), penetrating vessels (p < 0.001), TS 4-5 (p < 0.001) and all 2D-SWE parameters (p < 0.001) were significantly different between benign and malignant FBLs. The BI-RADS score provided an AUC of 0.876 (95% CI 0.810-0.926) for the diagnosis of malignant FBLs. Among the 2D-SWE measurements, an excellent diagnostic performance was observed for Emax with an AUC of 0.915 (95% CI 0.856-0.956) and Emean of 0.908 (95% CI 0.847-0.951). Optimal cutoff for the diagnosis of malignant FBLs were US BI-RADS > 3, Strain Ratio > 2.52, Tsukuba Score > 3, Emax > 82.6kPa, Emean > 66.0kPa, Emin > 54.4kPa and Eratio > 330.8. Multiparametric ultrasound, particularly SWE, can improve specificity in the characterization of FBLs.

Two universal school-based prevention programs for depression and anxiety: 24-Month follow-up of an RCT

Background and objectivesTransdiagnostic approaches have been promoted as a means of maximising preventative effects across multiple problems with depression and anxiety suitable targets as they appear to have highly interconnected systems in pathology development and maintenance. This study investigated long-term effects of two universal school-based programs, Emotion Regulation (ER) and Behavioral Activation (BA), that sought to prevent depression and anxiety by targeting worry (a transdiagnostic feature) to promote resilience. MethodsThis follow-up study captured data from 162 of 316 initial students (aged 8–13; 52.2% female), from six Australian schools. The original study design cluster randomised students by school into BA, ER, or a usual class control. Intervention conditions consisted of 8 × 50-min weekly sessions. This study measured the effects of these interventions after 24 months on resilience, worry, depression, and anxiety. Resilience was also examined as a potential mediator. ResultsAt 24-month follow-up, there was no significant effect of either intervention on depression, anxiety, worry, or resilience levels. Significantly fewer participants in ER and BA met clinical thresholds for separation anxiety disorder (SAD) and obsessive-compulsive disorder (OCD) in the 24-month follow-up compared with baseline. No mediation effects were found. LimitationsAlthough self-report measures are common in universal, school-based research, this represents a study limitation. ConclusionsBoth interventions may provide limited long-term protective effects on SAD and OCD symptoms, which appear to have a shelf-life shorter than 24 months. To maintain program effects, refresher sessions at shorter intervals may be a consideration for future research.

Abstract Mo033: Circulating Long Noncoding RNA Expression Signature Predicts Adverse Cardiovascular Outcomes in Patients with Coronary Artery Disease

Background: Patients with coronary artery disease (CAD) have increased risks of subsequent major adverse cardiovascular events (MACE). Currently, there are no reliable tools to predict recurrent MACE in CAD patients. Objective: To determine if circulating long noncoding RNA (lncRNA) expression signature predicts recurrent MACE in CAD patients. Methods: As part of the Taiwan Biosignature Study, this prospective nested case-control study included 168 CAD patients who experienced MACE during the follow-up and another 108 CAD patients who remained free of MACE after a≥24-month follow-up. Plasma lncRNAs were profiled to determine their prognostic values for MACE in CAD patients. Results: Initially, RNA sequencing in 59 CAD patients (41 with recurrent MACE) revealed that a total of 124 plasma lncRNAs were dysregulated in CAD patients with recurrent MACE. Subsequent analyses showed that the expression signature of these lncRNAs classified CAD patients with vs. without recurrent MACE with an accuracy of 93%. Elevated levels of plasma lnc-NCF1-1, BRE-AS1, lnc-ZFAT-6, lnc-SLC46A3-5, lnc-CXCL3-2 and lnc-EBF3-4 were associated with increased risks of recurrent MACE. Additional studies in the remaining 217 CAD patients (127 with recurrent MACE) validated that increased plasma levels of lnc- NCF1-1, BRE-AS1, lnc-ZFAT-6, and lnc-EBF3-4 were significant predictors of recurrent MACE. In addition, lnc-SCORE, an index calculated from MACE-associated plasma lncRNA levels, was shown to be a strong independent predictor (adjusted HR, 2.70 [95% CI 1.78-4.09]) of recurrent MACE in CAD patients. BRE-AS1 and lnc-ZFAT-6 , two endothelium-enriched MACE-associated lncRNAs, were specifically dysregulated in cardiomyopathy of ischemic, but not of non-ischemic, origin, suggesting their potential contribution to the development of myocardial ischemia. Moreover, knocking BRE-AS1 reversed hypoxia-induced upregulation of VCAM-1 in human aortic endothelial cells, suggesting its functional contribution to vascular inflammation upon ischemia. Conclusions: This study shows the prognostic roles of circulating lncRNAs in predicting recurrent MACE in CAD patients. Endothelium-enriched lncRNA BRE-AS1 is involved in ischemia-induced vascular inflammation.

Treating Aortic Valve Stenosis for Vitality Improvement: The TAVI Study.

Degenerative aortic valve stenosis (AS) is the most common valvular heart disease among the elderly. Once cardiac symptoms occur, current guidelines recommend aortic valve replacement. Progressive degeneration/calcification reduces leaflet mobility with gradual cardiac output (CO) impairment. Low CO might induce abnormal brain-aging with cognitive impairment and increased risk of dementia, such as Alzheimer's disease or vascular dementia. On the contrary, cognitive improvement has been reported in patients in whom CO was restored. Transcatheter aortic valve implantation (TAVI) has proven to be a safe alternative to conventional surgery, with a similar mid-term survival and stroke risk even in low-risk patients. TAVI is associated with an immediate CO improvement, also effecting the cerebrovascular system, leading to an increased cerebral blood flow. The correlation between TAVI and cognitive improvement is still debated. The present study aims at evaluating this relationship in a cohort of AS patients where cognitive assessment before and after TAVI was available. a total of 47 patients were retrospectively selected. A transcranial Doppler ultrasound (TCD) before and after TAVI, a quality of life (QoL) score, as well as a mini-mental state examination (MMSE) at baseline and up to 36 months, were available. TAVI was associated with immediate increase in mean cerebral flow at TCD. MMSE slowly increase at 36-months follow-up with improved QoL mainly for symptoms, emotions and social interactions. this proof-of-concept study indicates that TAVI might induce cognitive improvement in the long-term as a result of multiple factors, such as cerebral flow restoration and a better QoL.

Macular thickness and visual acuity are characterized by a quadratic nonlinear relation in previously treated neovascular AMD eyes.

To assess the associations between visual acuity (VA) and retinal thickness in age-related macular degeneration (AMD) eyes treated with anti-vascular endothelial growth factor (VEGF) therapy. Sixty-eight patients with neovascular AMD (68 eyes) undergoing anti-VEGF therapy with two years of follow-up imaging data after the initiation of treatment were retrospectively included. Linear and nonlinear regression analyses with curve fitting estimation were performed to explore the relationship between visual acuity and OCT-based parameters at the 3-month and 24-month follow-up visits. Regression analyses were also performed between visual acuity and the retinal thickness deviation which was calculated as the absolute value of the difference between measured and normative retinal thickness values. The VA was not associated with either foveal (R2 = 0.011 and p = .401 at 3 months; R2 = 0.032 and p = .142 at 24 months) or parafoveal (R2 = 0.045 and p = .081 at 3 months; R2 = 0.050 and p = .055 at 24 months) retinal thicknesses. Compared with the linear models, a quadratic function yielded a relative increase in the R2 coefficients. Conversely, the VA was linearly associated with foveal retinal thickness deviation (R2 = 0.041 and p = .037 at 24 months) and parafoveal retinal thickness deviation (R2 = 0.062 and p = .040 at 3 months; R2 = 0.088 and p = .014 at 24 months) values. Although there was no linear relationship between retinal thickness and VA, a weak but statistically significant linear relationship could be observed when a retinal thickness deviation was considered. This suggests that deviation-based parameters may be beneficial for structure-function correlations in the context of anti-VEGF therapy for neovascular AMD.

Health care resource utilization and direct costs incurred over 24 months after initiating galcanezumab or standard-of-care preventive migraine treatments in the United States.

Health care resource utilization (HCRU) and direct costs incurred over 12 months following initiation of galcanezumab (GMB) or standard-of-care (SOC) preventive migraine treatments have been evaluated. However, a gap in knowledge exists in understanding longer-term HCRU and direct costs. To compare all-cause and migraine-related HCRU and direct costs in patients with migraine initiating GMB or SOC preventive migraine treatments over a 24-month follow-up. This retrospective study used Optum deidentified Market Clarity Data. The study included adults diagnosed with migraine, with at least 1 claim for GMB or SOC preventive migraine therapy (September 2018 to March 2020), with continuous enrollment for 12 months before and 24 months after (follow-up) the index date (date of first GMB or SOC claim). Propensity score (PS) matching (1:1) was used to balance cohorts. All-cause and migraine-related HCRU and direct costs for GMB vs SOC cohorts were reported as mean (SD) per patient per year (PPPY) over a 24-month follow-up and compared using a Z-test. Costs were inflated to 2022 US$. After PS matching, 2,307 patient pairs (mean age: 44.4 years; female sex: 87.3%) were identified. Compared with the SOC cohort, the GMB cohort had lower mean (SD) PPPY all-cause office visits (17.9 [17.7] vs 19.1 [18.7]; P = 0.023) and migraine-related office visits (2.6 [3.3] vs 3.0 [4.7]; P = 0.002) at follow-up. No significant differences were observed between cohorts in other all-cause and migraine-related events assessed including outpatient visits, emergency department (ED) visits, inpatient stays, and other medical visits. The mean (SD) costs PPPY were lower in the GMB cohort compared with the SOC cohort for all-cause office visits ($4,321 [7,518] vs $5,033 [7,211]; P < 0.001) at follow-up. However, the GMB cohort had higher mean (SD) PPPY all-cause total costs ($24,704 [30,705] vs $21,902 [28,213]; P = 0.001) and pharmacy costs ($9,507 [12,659] vs $5,623 [12,605]; P < 0.001) compared with the SOC cohort. Mean (SD) costs PPPY were lower in the GMB cohort for migraine-related office visits ($806 [1,690] vs $1,353 [2,805]; P < 0.001) compared with the SOC cohort. However, the GMB cohort had higher mean (SD) PPPY migraine-related total costs ($8,248 [11,486] vs $5,047 [9,749]; P < 0.001) and migraine-related pharmacy costs ($5,394 [3,986] vs $1,761 [4,133]; P < 0.001) compared with the SOC cohort. There were no significant differences between cohorts in all-cause and migraine-related costs for outpatient visits, ED visits, inpatient stays, and other medical visits. Although total costs were greater for GMB vs SOC following initiation, changes in a few categories of all-cause and migraine-related HCRU and direct costs were lower for GMB over a 24-month follow-up. Additional analysis evaluating indirect health care costs may offer insights into further cost savings incurred with preventive migraine treatment.

Tocilizumab Prophylaxis Following Axicabtagene Ciloleucel in Relapsed or Refractory Large B-Cell Lymphoma

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Most patients treated with axi-cel experience cytokine release syndrome (CRS) and/or adverse neurologic events (NEs). To explore potential approaches for reducing CAR T-cell-related toxicities with axi-cel, several safety expansion cohorts were added to the pivotal ZUMA-1 trial. ZUMA-1 Cohort 3 was an exploratory safety cohort that investigated the use of the IL-6 receptor-blocking antibody tocilizumab and anticonvulsant levetiracetam as prophylaxis against CRS and NEs in patients treated with axi-cel. Patients with R/R LBCL were enrolled in Cohort 3 and received conditioning chemotherapy on d -5 through -3 followed by a single infusion of axi-cel (2 × 106 cells/kg) on d 0. Prophylactic tocilizumab (8 mg/kg) was administered 48 h after axi-cel infusion. Primary endpoints were incidence and severity of CRS and NEs. Key secondary endpoints included the incidence of adverse events, objective response rate (ORR), duration of response, progression-free survival, overall survival (OS), and biomarker analyses (eg, circulating CAR T cells, cytokines, chemokines). Forty-two patients were enrolled in Cohort 3, 38 of whom received axi-cel. In the 24-month analysis, any-grade CRS and NEs occurred in 92% and 87% of patients, and Grade ≥3 CRS and NEs occurred in 3% and 42% of patients, respectively. One Grade 5 NE (cerebral edema) occurred. With 24-mo minimum follow-up, the ORR was 63%, and 39.5% of patients had ongoing response. With 48-month follow-up, median OS was 34.8 mo (95% CI, 5.4-not estimable). CAR T-cell expansion in ZUMA-1 Cohort 3 was comparable with pivotal Cohorts 1 and 2. Consistent with tocilizumab-mediated inhibition of IL-6R, serum IL-6 levels were increased relative to Cohorts 1 and 2. Grade ≥3 NEs were associated with elevated IL-6 levels, proinflammatory cytokines, and myeloid cells in the cerebrospinal fluid. Based on these findings, prophylactic tocilizumab is not recommended to prevent CAR T-cell-related adverse events, and beneficial effects of prophylactic levetiracetam remain uncertain in patients with R/R LBCL.

Treatment comparison of hydroxyurea versus ruxolitinib in essential thrombocythaemia: A matched-cohort analysis.

Hydroxyurea is the preferred first-line cytoreductive treatment for high-risk essential thrombocythaemia (ET), but many patients are intolerant or refractory to hydroxyurea. Ruxolitinib has been shown to improve symptoms in patients with ET. This post hoc analysis compared the clinical outcomes of patients with ET who received hydroxyurea only with those who switched from hydroxyurea to ruxolitinib due to intolerance/resistance to hydroxyurea. Patients with ET refractory/intolerant to hydroxyurea treated with ruxolitinib in a completed phase 2 study (HU-RUX) were propensity score matched with patients who received hydroxyurea only in an observational study (HU). Changes in leukocyte and platelet counts were reported at 6-month intervals during the 48-month follow-up. Following propensity score matching, 37 patients were included for analysis in each cohort. Mean (standard deviation [SD]) leukocyte and platelet counts at index were higher for HU-RUX versus HU (leukocyte: 9.3 [5.1] vs. 6.8 [3.1]×109/L; platelet: 1027.4 [497.8] vs. 513.9 [154.7]×109/L), both of which decreased significantly from index to 6 months through to 48 months in HU-RUX (mean [SD] change from index at 6 months-leukocyte: -1.8 [4.6]×109/L; platelet: -391.7 [472.9]×109/L; at 48 months-leukocyte: -3.8 [5.3]×109/L; platelet: -539.0 [521.8]×109/L), but remained relatively stable in HU (mean [SD] change from index at 6 months-leukocyte: 0 [1.8]×109/L; platelet: -5.7 [175.3]×109/L; at 48 months-leukocyte: -0.1 [2.7]×109/L; platelet: -6.9 [105.1]×109/L). In conclusion, these results demonstrate that switching from hydroxyurea to ruxolitinib in patients with ET who are intolerant or refractory to hydroxyurea could improve abnormal haematologic values similar to those who receive first-line hydroxyurea.

Improved Health Outcomes in Patients with Systemic Lupus Erythematosus Following Early Belimumab Initiation Without Prior Immunosuppressant Use: A Real-World Descriptive Study.

Patients with systemic lupus erythematosus (SLE) have variable treatment pathways, including antimalarials, glucocorticoids, immunosuppressants, and/or biologics. This study describes differences in clinical outcomes when initiating belimumab (BEL) before and after immunosuppressant use. This real-world, retrospective cohort study (GSK Study 217536) used de-identified administrative claims data from January 2015 to December 2022 in the Komodo Health Database. Adults with moderate/severe SLE initiating BEL (index date) were identified from January 2017 to May2022, allowing a ≥ 24-month baseline period. Patients were stratified into those initiating BEL before immunosuppressant use (no immunosuppressant use within 24months before index) and those initiating BEL after immunosuppressant use (one immunosuppressant used within 24months before index). Oral glucocorticoid (OGC) use, SLE flares, new organ damage, and all-cause healthcare resource utilization (HCRU) were analyzed descriptively over a 24-month follow-up. Baseline SLE severity was similar for patients initiating BEL before (n = 2295) versus after (n = 4114) immunosuppressant use (moderate, 83.1% vs 79.0%; severe, 16.8% vs 21.0%). Patients initiating BEL before versus after immunosuppressant use had lower SLE flare rates and OGC use. Post-index, patients initiating BEL before versus after immunosuppressant use discontinued their OGC sooner (moderate baseline SLE, 4.5 vs 8.9months; severe baseline SLE, 6.2 vs 11.6months). Patients initiating BEL before versus after immunosuppressant use had lower SLE flare rates per person-year at all time points (especially severe flare rates in patients with severe baseline SLE, 0.70 vs 1.48 through 24months post-index). Median time to new organ damage occurrence was longer in patients initiating BEL before versus after immunosuppressant use (moderate baseline SLE, 32.1 vs 26.7months; severe baseline SLE, 22.7 vs 21.6months). All-cause HCRU was similar between cohorts. These results suggest that patients initiating BEL before versus after immunosuppressant use had more favorable outcomes.

Hip Arthroscopy Versus Physical Therapy for the Treatment of Symptomatic Acetabular Labral Tears in Patients Older Than 40 Years: 24-Month Results From a Randomized Controlled Trial

Background: The indications for hip arthroscopy in patients aged ≥40 years remain controversial, as observational studies have suggested that advanced age portends poor functional outcomes, poor durability of improvement, and high rates of conversion to total hip arthroplasty. Purpose: To compare hip arthroscopy versus nonoperative management for symptomatic labral tears in patients aged ≥40 years with limited radiographic osteoarthritis. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: This single-surgeon, parallel randomized controlled trial included patients aged ≥40 years with limited osteoarthritis (Tönnis grades 0-2) who were randomized 1:1 to arthroscopic surgery with postoperative physical therapy (SPT) or physical therapy alone (PTA). Patients who received PTA and achieved unsatisfactory improvement were permitted to cross over to SPT after completing ≥14 weeks of physical therapy (CO). The primary outcomes were the International Hip Outcome Tool-33 score and modified Harris Hip Score at 24 months after surgery, and secondary outcomes included other patient-reported outcome measures and the visual analog scale for pain. The primary analysis was performed on an intention-to-treat basis using linear mixed-effects models. Sensitivity analyses included modified as-treated and treatment-failure analyses. Results: A total of 97 patients were included, with 52 (53.6%) patients in the SPT group and 45 (46.4%) patients in the PTA group. Of the patients who underwent PTA, 32 (71.1%) patients crossed over to arthroscopy at a mean of 5.10 months (SD, 3.3 months) after physical therapy initiation. In both intention-to-treat and modified as-treated analyses, the SPT group displayed superior mean patient-reported outcome measure and pain scores across the study period for nearly all metrics relative to the PTA group. In the treatment-failure analysis, the SPT and CO groups showed greater improvement across all metrics compared with PTA; however, post hoc analyses revealed no significant differences in improvement between the SPT and CO groups. No significant differences were observed between groups in rates of total hip arthroplasty conversion. Conclusion: In patients ≥40 years of age with limited osteoarthritis, hip arthroscopy with postoperative physical therapy led to better outcomes than PTA at a 24-month follow-up. However, additional preoperative physical therapy did not compromise surgical outcomes and allowed some patients to avoid surgery. When surgery is indicated, age ≥40 years should not be considered an independent contraindication to arthroscopic acetabular labral repair. Registration: NCT03909178 (ClinicalTrials.gov identifier).

Comparative analysis of VenaBlock and VenaSeal Systems for catheter-guided endovenous cyanoacrylate closure in treating chronic venous insufficiency of the lower extremity: effectiveness and feasibility.

Cyanoacrylate adhesive closure (CAC) systems are widely used to treat varicose veins. In terms of efficacy and safety, these nonthermal, non-tumescent methods are noninferior to endovenous thermal ablation techniques. However, no published studies have compared products that use CAC systems. VenaSeal® (Medtronic, Santa Rosa, CA, USA) and VenaBlock® (Invamed) are the most commonly used CAC-based products worldwide. This study aimed to focus on the efficacy of these two commonly used products, with little emphasis on safety. Published full-text articles on the VenaBlock® and VenaSeal® systems were searched. Data for each product were evaluated by comparing them with each other in terms of effectiveness. In total, 1882 extremities from 11 studies using VenaBlock® and 524 extremities from eight studies using VenaSeal® were included and compared. Both devices were effective, and their cumulative recanalization-free survival rates were similar (P=0.188) at the 6-, 12-, 24-, 36-, and 60-month follow-ups. Both products improved the venous clinical severity score (VCSS) and quality of life (QoL) scores. VenaBlock® and VenaSeal® are effective in terms of cumulative recanalization-free survival rates, and no significant difference was found between the two groups (P=0.188). Both significantly improve the VCSS and QoL scores. CAC is feasible for the treatment of varicose veins.

Long-term effects on growth in preterm and small for gestational age infants: A national birth cohort study

BackgroundPremature and small-for-gestational-age (SGA) infants tend to have long-term growth morbidities such as short stature, failure to thrive, and obesity. Although most of these infants show catch-up growth at 2–4 years of age, they are still more susceptible to childhood obesity and related metabolic disorders. Those who fail to achieve catch-up will suffer from pathological short stature and neurodevelopmental impairment through adulthood. This study aims to depict the growth pattern of premature or SGA infants and their growth morbidities in Taiwan. MethodsData were obtained from a nationally representative cohort of 24,200 pairs of postpartum women and newborns in the Taiwan Birth Cohort Study (TBCS), using structured questionnaire interviews. A total of 16,358 infants were included and three follow-up surveys were completed at 6, 18, and 36 months after the deliveries. We constructed growth curves to conduct an in-depth investigation into anthropometric data, applying a linear mixed model. Logistic regression was used to model the relevant outcomes, with adjustment for various potential confounding factors. ResultsDespite being born shorter and lighter, preterm and SGA infants generally showed catch-up growth and had no higher odds ratios (ORs) of developing short stature or failure to thrive compared to appropriate-for-gestational-age (AGA) term infants before 3 years of age. Preterm SGA infants, particularly females, had higher ORs for obesity at the 36-month follow-up. ConclusionThis is the first nationwide population-based study depicting the growth of SGA infants in Taiwan. The growth patterns of preterm and term SGA infants are different from those of preterm and term AGA infants. Further research is necessary to understand the growth trajectories of preterm and SGA infants and their associations with later diseases.