6-month Time Point Research Articles

SAT412 Effects Of Gender-Affirming Hormone Therapy On The Connectivity Of Intrinsic Brain Networks

Abstract Disclosure: C.C. Pedreira: None. S. Tchir-Bourgeois: None. S. Tuli: None. A. Giancola: None. C. Loxton: None. A.S. Keuroghlian: None. M. Misra: None. J.M. Andreano: None. Background: Previous research has indicated that both acute gonadal hormone treatments and fluctuations in ovarian hormone levels over the course of the menstrual cycle can significantly alter patterns of communication between brain regions, particularly regions involved in affective processing. However, the neural effects of prolonged exogenous gonadal hormone exposure, as in gender-affirming hormone therapy (GAHT), are not presently well-understood. A better understanding of the influence of GAHT on intrinsic network connectivity could point the way towards improved GAHT treatment regimens that minimize affective side effects.Objective: To characterize the effects of estradiol and testosterone treatments in GAH on patterns of connectivity within and between the brain’s intrinsic networks.Methods: 5 transgender individuals receiving GAHT (estradiol n =3, testosterone n = 2) were scanned using functional magnetic imaging (fMRI) at rest at two timepoints: baseline, prior to treatment, and 6 months into GAHT. The time course of neural activity was computed for each voxel in the brain, then tested for correlation with each other voxel to develop a whole-brain connectome for each participant. Connectomes were then analyzed in two ways: 1) maps of average connectivity to two regions of interest found in previous research to differ between cis and transgender people (the anterior insula and temporal pole) were generated for each participant. These maps were then compared between baseline and 6-month timepoints. 2) Overall network structure of the brain was generated a priori for each participant at each timepoint using a community detection algorithm. Network assignments were then compared between timepoints, noting regions whose connectivity shifted between networks after GAHT.Results: 2 of 3 participants treated with estradiol exhibited a significant reduction of connectivity to the anterior insula throughout the brain, most notably within the medial temporal lobe and cingulate cortex. Both participants receiving testosterone treatment showed reduced anterior insula connectivity, although connectivity to the cingulate cortex, particularly the mid-cingulate, was preserved. Estradiol did not significantly affect connectivity of the frontal pole, although testosterone produced a widespread reduction in frontal pole connectivity. Community detection analysis indicated a shift in connectivity to the salience network from the default mode network in the medial temporal lobe following estradiol treatment. Testosterone treatment was associated with greater connectivity in medial frontal regions to the frontoparietal network. Conclusions: Preliminary evidence indicates that both estradiol and testosterone treatment can produce significant changes in the connectivity of affective regions in the brain, as well as reorganization of the brain’s network structure. Presentation: Saturday, June 17, 2023

Preclinical In-Vivo Safety and Toxicokinetics of D-PLEX100 in an Abdominal Surgery Incision Model in Juvenile Miniature Swine.

D-PLEX100 (D-PLEX) is a novel product candidate made of a polymer-lipid-based matrix (PLEX platform) which contains doxycycline that is being released at a constant rate for 30days. D-PLEX was developed to prevent surgical site infections, which are a major global health challenge. Previous studies have shown its safety in adult humans, adult swine, and adult rabbits. The aim of this study was to assess the toxicity and safety of D-PLEX also in juvenile animals to support future clinical trials in pediatric patients. Yucatan miniature swine were selected as a model, primarily due to their relatively larger mass. D-PLEX or placebo (formulation without doxycycline) was administered locally to abdominal incisions, and the animal's safety parameters were followed for 9months and compared to sham-control swine. There was no evidence of any systemic safety concern or local toxicity at the incision site in D-PLEX-treated animals. D-PLEX was detected after 1month and was fully resorbed at the 3-month time point. The surgical incision sites were fully healed at the 6-month time point in all D-PLEX-treated animals. Toxicokinetic (TK) assessments revealed that doxycycline exhibited low Cmax and therefore minimal systemic exposure following a single dose of local administration. This study provides evidence for the safety of D-PLEX and PLEX-based formulation in juvenile miniature swine and supports its further testing in clinical pediatric population. In addition, it can be used as a reference for future preclinical studies aiming to evaluate the safety of other PLEX-based product candidates for the pediatric population.

Refractive errors in infants with retinopathy of prematurity treated using laser or anti-vascular endothelial growth factor monotherapy

Background: Infants treated for retinopathy of prematurity (ROP) could develop visually significant refractive errors. In this study, we report pre-treatment refractive errors in premature infants with treatment-requiring ROP treated using laser or anti-VEGF monotherapy and compare the components of post-treatment refractive error values between the two treatment groups at different follow-up timepoints.
 Methods: In this retrospective cohort study, we analyzed 360 eyes of 181 premature infants with treatment-requiring ROP who were referred to Farabi Eye Hospital, Tehran, Iran between March 2020 and April 2021. Of the 360 eyes, 195 received laser monotherapy (laser treatment group) and 165 received an intravitreal anti-VEGF injection (anti-VEGF therapy group). All included eyes underwent pre- and post-treatment cycloplegic refraction. Cycloplegia was induced for each infant by instilling a mixed eye drop containing 1% tropicamide, 2.5% phenylephrine, and 0.5% tetracaine (in equal volumes) in each eye three times at five-minute intervals. Cycloplegic refraction was performed 30 minutes after the third instillation.
 Results: The mean (standard deviation [SD]) gestational age (GA) and birth weight (BW) of the infants were 29.0 (2.0) weeks and 1241.0 (403.0) g, respectively. The male-to-female ratio in the entire study cohort was 107 (59.1%) / 74 (40.9%), whereas the ratios in the anti-VEGF therapy group and laser treatment group were 47 (56.6%) / 36 (43.4%) and 60 (61.2%) / 38 (38.8%), respectively. The pre-treatment assessment revealed that 218 (60.6%) eyes were hyperopic, 112 (31.1%) were myopic, and 30 (8.3%) were emmetropic. In the anti-VEGF therapy group, 87 (52.7%) eyes were hyperopic, 63 (38.2%) were myopic, and 15 (9.1%) were emmetropic. In the laser treatment group, 131 (67.2%) eyes were hyperopic, 49 (25.1%) were myopic, and 15 (7.7%) were emmetropic. The mean (SD) spherical refractive error and spherical equivalent of refractive error (SEQ) at the 1-week, 1-month, and > 6-month post-treatment follow-up timepoints; the mean cylindrical refractive error at the 3-month post-treatment timepoint; and the mean SEQ at the time of ROP regression were significantly different between the treatment groups (all P < 0.05). The rate of anisometropia increased significantly from 3.4% at baseline to 9.2% at the 6-month post-treatment follow-up timepoint (P < 0.05).
 Conclusions: In this study, the most common pre-treatment refractive status of all included eyes with treatment-requiring ROP and eyes in each treatment group was hyperopia, followed by myopia and emmetropia. At the more than 6-month post-treatment follow-up, cycloplegic refraction revealed that the laser-treated eyes were significantly more hyperopic than the anti-VEGF-treated eyes, a finding similar to the pre-treatment refraction results. Further studies of same cohort with a longer follow-up period and a control group are needed to determine the real-world effect of each treatment modality on the refractive statuses of children treated for ROP.

Recovery Capital Gains May Precede Craving Reduction in Opioid Use Disorder.

Cravings for drugs and alcohol have been significantly associated with worse treatment outcomes. We investigated if improvements in recovery capital (RC) (eg, a measure of social capital/network, financial resources, education, and cultural factors) over time were associated with decreased reported cravings. The original cohort consisted of 133 participants (63 females) with opioid use disorder seeking outpatient treatment, who completed the Assessment of Recovery Capital (ARC) (range 0 to 50) and the Brief Addiction Monitor (BAM) thrice over the 6-month study. Intervention was medication and case management. Analysis included one-way mixed models testing change over time for ARC total scores and single question craving rating (5-point Likert scale). Cross-lagged panel estimates used structural equation models with variables z-scored, allowing for path coefficient evaluation as standard deviations (sd). Total ARC significantly increased over the study (χ2 = 33.77, df = 2, p < 0.0001), with baseline of 36.6 (n = 114, sd = 11.1) and 6-month of 41.2 (n = 107, sd = 9.5). Craving also changed significantly (χ2 = 8.51, df = 2, p < 0.015), with baseline of 1.1 (n = 101, sd = 1.2) and 6-month of 0.9 (n = 107, sd = 1.1). The cross-lag from baseline RC to 3-month craving was significant (β = -0.28, SE = 0.11, z = -2.53, p < 0.011). The converse was not true; baseline craving did not affect later RC. Results were similarly significant when comparing 3-month to 6-month. The majority of sample was on buprenorphine. As RC improves, the reported cravings at both 3- and 6-month study time points are significantly reduced. When evaluated inversely, there was not a significant association with baseline cravings and follow-up RC. Significant path coefficients provide an estimation of a directional effect from increased RC towards craving reduction.

Longitudinal Radiomics-Based Prediction of Local Recurrence after Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

Computed tomography (CT)-based radiomic analysis is an emerging tool that can help predict recurrence after radiation in non-small cell lung cancer (NSCLC). Most studies have focused on using radiomic features obtained from pre-treatment CT scans but not on post-treatment CTs. Our goal was to determine if radiomic features derived from post-treatment CTs perform better than those from pre-treatment CTs in predicting local recurrence after stereotactic body radiation therapy (SBRT) in patients with early-stage NSCLC. Patients with T1/T2 N0 early-stage NSCLC were retrospectively reviewed. Criteria for selection included patients with biopsy-proven NSCLC, non-ground glass solid lesions, 4-5 fraction SBRT treatments, and non-contrast thin-slice CTs available at pre-treatment baseline and at 3 and 6 months post-SBRT. Clinical and tumor characteristics were compared using Chi-square and Student's t-tests. CT image pre-processing was performed and 107 radiomic features were extracted using 3D Slicer and open-source software. Univariate analysis for local recurrence was determined by Cox regression with death as a competing risk. The Benjamini-Hochberg Procedure was applied to control the false discovery rate. Pearson correlation analysis was used to exclude redundant features (r > 0.8), and multivariate analysis was conducted with Random Forest on the top-performing features found on univariate logistic regression. Models were trained on a class-balanced loss to account for class imbalance. Twenty iterations of stratified 3 k-fold cross-validation were used to select the best model by the area under the receiver operating characteristic curve (AUC). We identified and analyzed 86 patient tumors, including 76 non-local recurrences and 10 local recurrences (49 males, 37 females; age, median 72, range 52-91 years). No differences in age, histology, standardized uptake values on positron emission tomography scans, gross tumor volume, and radiation dose were found between patients with and without local recurrence (all p >0.05). The median time to local recurrence was 18.9 months (range 5.5-45.6 months). At the baseline, 3-month, and 6-month timepoints, 2, 10, and 10 radiomic features predicted local recurrence on Cox regression univariate analysis, respectively (all q <0.01). On multivariate analysis of top-performing radiomic features, the 3-month timepoint performed the best with a mean (±standard deviation) AUC score of 0.82 (±0.13) compared to a mean AUC of 0.73 (±0.086) at baseline and a mean AUC of 0.74 (±0.10) at 6 months. Post-treatment radiomic features at 3 months outperformed pre-treatment radiomic features in predicting local recurrence after SBRT for NSCLC. These results suggest radiomic data from follow-up CTs may be helpful when developing radiomic models to predict local recurrence in patients with NSCLC.

Medications for opioid use disorder prescribed at hospital discharge associated with decreased opioid agonist dispensing in patients with opioid use disorder requiring critical care: A retrospective study

IntroductionBuprenorphine is highly effective for the treatment of opioid use disorder (OUD), and, in recent years, the rates of patients maintained on buprenorphine requiring critical care have been steadily increasing. Currently, no unified guidance exists for buprenorphine management during critical illness. Likewise, we do not know if patients maintained on buprenorphine for OUD are prescribed medications for OUD (MOUD) following hospital discharge or if buprenorphine management influences mu opioid agonist dispensing. MethodsIn our cohort of adults over the age of 18 with OUD, receiving buprenorphine formulations in the 3 months preceding their ICU admission, we sought to investigate the relationship between receipt of MOUD and non-MOUD opioid prescribing up to 12 months following hospital discharge. This was a single-center, retrospective cohort study approved by the MaineHealth institutional review board. The study analyzed differences in prescription rates between discharge and subsequent time points using chi square or Fisher's exact test, as appropriate. We performed analyses using SPSS Statistical Software version 28 (IBM SPSS Inc., Armonk, NY) with significance set at p < 0.05. ResultsWe identified a statistically significant increase in MOUD prescribing 3 months posthospital discharge in patients who received MOUD at time of discharge (87.9 % vs 40 % p = 0.002.) The study found a significant increase in nonbuprenorphine opioid prescribing in patients who did not receive an MOUD prescription at time of discharge (24.2 % vs 70 % p = 0.007). This trend persisted at the 6-month and 12-month time points; however, it did not reach statistical significance. Additionally, the study identified a significant reduction in the incidence of non-MOUD opioid dispensing in patients prescribed MOUD at each time point measured (p = 0.007, p < 0.001. p < 0.001 and p = 0.008 at discharge, 3, 6, and 12 months, respectively). ConclusionsThese findings support continuing buprenorphine dispensing following hospital discharge.

Memantine for Pediatric Patients Receiving Cranial Irradiation: A Pilot Study

While memantine has become standard in certain adults receiving brain RT to decrease the cognitive impacts of RT, it is unknown whether pediatric patients can take and tolerate memantine or experience benefit. In this prospective single-arm feasibility study, we hypothesized pediatric patients receiving brain RT would tolerate memantine with good treatment adherence. Patients aged 4-18 years with a primary CNS malignancy (excluding WHO Grade IV astrocytoma and glioblastoma) receiving intracranial RT were eligible. A 6-month course of memantine was given during and after RT. Dosing began once daily at 5 mg with up-titration in 5 mg increments over 4 weeks to a weight-based maximum (0.4 mg/kg to the closest 5 mg), not to exceed 10 mg BID. To reduce patient and clinical research associate (CRA) burden, medication adherence was tracked via the Medisafe Pill and Reminder application which study staff helped install on the patient or parent's smart phone. A paper pill diary was provided for those unable to use the app. The primary endpoint was to achieve 80% adherence rate to memantine in 80% of patients measured 1-month post-RT. Eighteen patients (14 male and 4 female, median age 11.5 years (range: 4-18)) were enrolled from 2020-2022. The study closed early after enrolling 18 of 20 planned patients to avoid competing with the phase III randomized Children's Oncology Group (COG) study AACL2031. One patient withdrew for cognition-altering substance-use, leaving 17 patients with data available for analysis. Histologies included germ cell tumor (n = 6), craniopharyngioma (n = 3), choroid plexus papilloma (n = 2), ependymoma (n = 2), glial/astrocytoma (n = 2), medulloblastoma (n = 1), and meningioma (n = 1). Thirteen had surgery, and 9 received chemotherapy. Eight received craniospinal irradiation (CSI). Median RT dose was 54 Gy (range 36-59.4) in 30 fractions (range: 20-33). At data freeze, all 17 had passed the 1-month post-RT time point. One patient discontinued memantine after a single dose due to nausea. Pill-reports were available for 14 of the remaining 16; two patients did not complete digital pill logs. For those with complete logs, all adherence rates were above 80%, with a median of 99.32% pill completion rate (range: 92.67-100). Seven (50%) took 100% of prescribed doses. Irrespective of adherence for the 2 unavailable for evaluation, the primary endpoint was still achieved. Grade 1 toxicities included headache (n = 6, 35%) and constipation (n = 1, 6%); there were no grade 2+ toxicities. At last follow-up, 15/16 have completed the full 6-month memantine course. Secondary endpoints including neurocognitive evaluations have not yet been met and will be the subject of future reports. Memantine is a feasible and well-tolerated addition to multi-modality treatment for pediatric brain tumors. Secondary endpoints of this study and results of the ongoing COG study are awaited to define the value of memantine in this population.

Clinical and Radiographic Outcomes for Patients with Cervical Adjacent Segment Disease Treated with Anterior Cervical Discectomy and Fusion with Integrated Interbody Spacers

Anterior cervical discectomy and fusion (ACDF) is among the most common spine procedures. Adjacent segment disease (ASD), characterized by degenerative disease at an adjacent spinal level to a prior fusion, is a well-recognized and significant sequela following ACDF. Adjacent segment ACDF may be considered after the failure of non-surgical options for patients with symptomatic ASD. This study aimed to assess the incidence of dysphagia and other complications as well as radiographic outcomes in adult patients who have undergone ACDF with an integrated interbody spacer device for symptomatic ASD. This was a retrospective review of patients who underwent ACDF for symptomatic ASD with commercially available integrated interbody spacers by three spine surgeons at an academic institution from March 2018 to April 2022. Demographic, radiographic, and postoperative data were collected, including dysphagia, device-related complications, and the need for revision surgery. There were 48 patients (26 male, 22 female) who met inclusion criteria (mean age 59.7 years, mean body mass index 19.5 kg/m2) who underwent ACDF for symptomatic ASD (1one-level, n= 44; 2-level, n= 4). Overall, 12 patients (25%) experienced dysphagia postoperatively before the first follow-up appointment. Nine of 44 (20.4%) of 1-level ACDF patients experienced dysphagia, and 3 of 4 (75%) of 2-level ACDF patients experienced dysphagia. Three patients had severe dysphagia which prompted an otolaryngology referral. Two of those patients remained symptomatic at 6 weeks postoperatively. Of 43 patients with prior plate cage systems, none required hardware removal at the time of surgery. Preoperative global and segmental lordosis were 9.07° ± 8.36° (P= 0.22) and 3.58° ± 4.57° (P= 0.14), respectively. At 6 weeks postoperatively, global and segmental lordosis were 11.44° ± 9.06° (P= 0.54) and 5.11° ± 4.44° (P= 0.44), respectively. This constitutes a change of+2.37° and+1.53° in global and segmental lordosis, respectively. The mean anterior disc height change between preoperative and immediate postoperative time points was 6.3 ± 3.1 mm. Between the immediate postoperative and 6-week postoperative time points, the mean anterior disc height change was -1.5 ± 2.7 mm. Between the immediate postoperative and 3-month postoperative time points, the mean anterior disc height change was -3.7 ± 5.0 mm. The posterior disc height changes at the same time points were 2.5 ± 1.7 mm, -0.4 ± 1.8. and -0.5 ± 1.4 mm, respectively. This fusion rate was 50% and 70% at 6 months and 1 year post-surgery, respectively. ACDF with integrated spacer is a viable alternative to traditional plate-cage systems for symptomatic ASD. An advantage over traditional plate-cage systems is that the removal of prior instrumentation is not needed in order to place implants. Based on a review of the literature, these standalone systems allowed for a shorter operative time and had less incidence of dysphagia than plate-cage systems for ASD after ACDF. The different standalone and plate-cage systems used in treating ASD after ACDF surgeries should be compared in prospective studies.

Real-world clinical outcomes in patients with relapsed and refractory multiple myeloma receiving VTD-PACE treatment in the era of monoclonal antibodies.

Bortezomib (Velcade), thalidomide, dexamethasone, platinum (cisplatin), adriamycin (doxorubicin), cyclophosphamide, and etoposide (VTD-PACE) are commonly used as salvage treatment for patients with relapsed/refractory multiple myeloma (RRMM). However, its outcomes in the era of monoclonal antibodies remain unclear. Therefore, this retrospective cohort study assessed the clinical outcomes of 60 patients with RRMM (median four prior treatment lines) administered VTD-PACE. The median follow-up period was 11.1months, during which they received a median of two cycles of VTD-PACE. The overall response rate (ORR) was 66.7%; ORRs of 53.1 and 82.1% were noted in patients with ≥ 4 and ≤ 3 prior lines (P = 0.027), respectively. The median overall survival (OS) was 17months, with a median progression-free survival (PFS) of 9.8months. Using the 3-month time point after VTD-PACE treatment as a landmark, 54 patients were still alive. Landmark analysis was conducted for PFS and OS of patients who received or did not receive HSCT or CART after VTD-PACE treatment. Patients who underwent subsequent hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T-cell therapy (CART) following VTD-PACE showed a trend of longer PFS and OS than those who did not undergo subsequent HSCT or CART. The median OS in patients with and without renal dysfunction was 10.7months and 21.5months, respectively (P = 0.0091). Therefore, VTD-PACE is useful as a bridging therapy for HSCT or CART, as a response can be expected regardless of organ damage, disease risk, or history of anti-CD38 antibody use.

Feasibility and Effects of Namaste Care for Persons with Advanced Dementia in Canadian Long-Term Care Homes.

To evaluate the feasibility and effects of the Namaste Care intervention for persons with advanced dementia (ie, moderate and late-stage) in long-term care (LTC) and their family carers. A pre-posttest study design. Staff carers delivered Namaste Care for residents with the support of volunteers in a small group setting. Activities provided included aromatherapy, music, and snacks/beverages. Residents with advanced dementia and family carers from 2 Canadian LTC homes, located in a midsize metropolitan area, were included. Feasibility was evaluated using a research activity log. Outcome data for residents (ie, quality of life, neuropsychiatric symptoms, pain) and family carers (ie, role stress, quality of family visits) were collected at baseline and 3 and 6months of the intervention. Descriptive analyses and generalized estimating equations were used for quantitative data. A total of 53 residents with advanced dementia and 42 family carers participated in the study. Mixed findings were found for feasibility as not all intervention targets were met. There was a significant improvement in resident neuropsychiatric symptoms at the 3-month time point only (95% CI-9.39,-0.39; P= .033) and family carer role stress at both time points (3-month 95% CI-37.40,-1.80; P= .031; 6-month 95% CI-48.90,-2.09; P= .033). Namaste Care is an intervention with preliminary evidence of impact. Feasibility findings revealed that not all targets were met as the intended number of sessions were not delivered. Future research should explore how many sessions per week are required to lead to an impact. It is important to assess outcomes for both residents and family carers, and to consider enhancing family engagement in delivering the intervention. Given the promise of this intervention, a large-scale randomized controlled trial with a longer follow-up should be conducted to further evaluate its outcomes.

Advanced Messaging Intervention for Medication Adherence and Clinical Outcomes Among Patients With Cancer: Randomized Controlled Trial.

Medication adherence is crucial for improving clinical outcomes in the treatment of patients with cancer. The lack of adherence and adverse drug reactions can reduce the effectiveness of cancer therapy including the quality of life. The commonly used intervention methods for medication adherence continue to evolve, and the age of fifth-generation (5G) messaging has arrived. In this study, we conducted a prospective, pilot randomized controlled trial to evaluate the effect of 5G messaging on medication adherence and clinical outcomes among patients with cancer in China. The research population was patients with nonsmall cell lung cancer undergoing pemetrexed chemotherapy who require regular folic acid (FA) and vitamin B12 supplements. The intervention and control groups were assigned to 5G messaging and second-generation (2G) messaging, respectively. The patients' medication adherence and quality of life were assessed at baseline and 1-month and 3-month time points. Moreover, the chemotherapy-related hematologic or nonhematologic toxicities, as well as the serum levels of FA and vitamin B12, were measured. Of the 567 patients assessed for eligibility between January and May 2021, a total of 154 (27.2%) patients were included. Overall, 80 were randomized to the control group and 74 to the intervention group. The odds of adherence in the 5G messaging intervention group were significantly higher than the control group at the 1-month (62/69, 90% vs 56/74, 76%; adjusted odds ratio 2.67, 95% CI 1.02-7.71) and 3-month (50/60, 83% vs 48/64, 75%; adjusted odds ratio 2.36, 95% CI 1.00-5.23) time points. Correspondingly, the FA and vitamin B12 serum levels of patients in the 5G messaging group were higher than those of the control group. Regarding hematologic toxicities, only the incidence of leukopenia in the intervention group was lower than that in the control group (25/80, 31% in the control group vs 12/74, 16% in the intervention group; P=.04). There were no differences in nonhematologic toxicities and quality of life between the 2 groups. In summary, we conclude that compared with conventional 2G text-based messaging, a 5G messaging intervention can better improve medication adherence and clinical outcome among patients with cancer. Chinese Clinical Trial Registry ChiCTR2200058188; https://www.chictr.org.cn/showproj.html?proj=164489.

Shifting Mindsets: The Impact of a Patient Portal on Functioning and Recovery in a Mental Health Setting.

This study aims to understand whether higher use of a patient portal can have an impact on mental health functioning and recovery. A mixed methods approach was used for this study. In 2019-2021, patients with mental health diagnoses at outpatient clinics in an academic centre were invited to complete World Health Organization Disability Assessment Scale 12 (WHODAS-12) and Mental Health Recovery Measure surveys at baseline, 3 months, and 6 months after signing up for the portal. At the 3-month time point, patients were invited to a semistructured interview with a member of the team to contextualize the findings obtained from the surveys. Analytics data was also collected from the platform to understand usage patterns on the portal. Overall, 113 participants were included in the analysis. There was no significant change in mental health functioning and recovery scores over the 6-month period. However, suboptimal usage was observed as 46% of participants did not complete any tasks within the portal. Thirty-five participants had low use of the portal (1-9 interactions) and 18 participants had high usage (10+ interactions). There were also no differences in mental health functioning and recovery scores between low and high users of the portal. Qualitative interviews highlighted many opportunities where the portal can support overall functioning and mental health recovery. Collectively, this study suggests that higher use of a portal had no impact, either positive or negative, on mental health outcomes. While it may offer convenience and improved patient satisfaction, adequate support is needed to fully enable these opportunities for patient care. As the type of interaction with the portal was not specifically addressed, future work should focus on looking at ways to support patient engagement and portal usage throughout their care journey.

Corticosteroid implants for chronic non-infectious uveitis.

Corticosteroid implants for chronic non-infectious uveitis.

Elimination of senescent cells by treatment with Navitoclax/ABT263 reverses whole brain irradiation-induced blood-brain barrier disruption in the mouse brain.

Whole brain irradiation (WBI), a commonly employed therapy for multiple brain metastases and as a prophylactic measure after cerebral metastasis resection, is associated with a progressive decline in neurocognitive function, significantly impacting the quality of life for approximately half of the surviving patients. Recent preclinical investigations have shed light on the multifaceted cerebrovascular injury mechanisms underlying this side effect of WBI. In this study, we aimed to test the hypothesis that WBI induces endothelial senescence, contributing to chronic disruption of the blood-brain barrier (BBB) and microvascular rarefaction. To accomplish this, we utilized transgenic p16-3MR mice, which enable the identification and selective elimination of senescent cells. These mice were subjected to a clinically relevant fractionated WBI protocol (5 Gy twice weekly for 4 weeks), and cranial windows were applied to both WBI-treated and control mice. Quantitative assessment of BBB permeability and capillary density was performed using two-photon microscopy at the 6-month post-irradiation time point. The presence of senescent microvascular endothelial cells was assessed by imaging flow cytometry, immunolabeling, and single-cell RNA-sequencing (scRNA-seq). WBI induced endothelial senescence, which associated with chronic BBB disruption and a trend for decreased microvascular density in the mouse cortex. In order to investigate the cause-and-effect relationship between WBI-induced senescence and microvascular injury, senescent cells were selectively removed from animals subjected to WBI treatment using Navitoclax/ABT263, a well-known senolytic drug. This intervention was carried out at the 3-month post-WBI time point. In WBI-treated mice, Navitoclax/ABT263 effectively eliminated senescent endothelial cells, which was associated with decreased BBB permeability and a trend for increased cortical capillarization. Our findings provide additional preclinical evidence that senolytic treatment approaches may be developed for prevention of the side effects of WBI.

Comparison of Oral Health-Related Quality of Life scores in children treated for early childhood caries under general and local anesthesia: a quasi-experimental study.

The purpose of this study was to compare the changes in oral health-related quality of life (OHRQoL) scores in children treated for Early Childhood Caries (ECC) under general (GA) and local anesthesia (LA). A quasi-experimental study was carried out on 73 children, with 37 in the GA group and 36 in the LA group. The early childhood oral health impact scale (ECOHIS) was used to measure OHRQoL, with the type of anesthesia (LA or GA) serving as the explanatory variable. A Friedman test was used to assess the difference between the LA and GA groups at baseline, one-week, and one-month follow-up points. The results showed a significant difference in the overall mean ECOHIS scores between the LA and GA groups at 1-week (LAmean ± SD = 6.12 ± 1.11, GAmean ± SD = 5.50 ± 0.88; P = 0.01) and 1-month (LAmean ± SD = 5.87 ± 1.12, GAmean ± SD = 4.96 ± 0.99; P < 0.001) follow-up points. Irrespective of the administered anesthesia, a significant (P < 0.001) reduction in the mean score for dental pain was observed at both 1-week (mean ± SD = 1.30 ± 1.16) and 1-month (mean ± SD = 0.81 ± 0.89) timepoints after the treatment, as compared to the baseline assessment (mean ± SD = 2.02 ± 1.02). Early treatment for ECC reduces pain, restore normal activities, and improves the quality of life of affected children. Specifically, GA was found to be more beneficial for both children and parents. However, further studies using more robust study designs and carefully considering related factors are necessary to confirm these findings.

Selective Prevention of Depression in Workers Using a Smartphone App: Randomized Controlled Trial.

There is increasing evidence that depression can be prevented; however, universal approaches have had limited success. Appropriate targeting of interventions to at-risk populations has been shown to have potential, but how to selectively determine at-risk individuals remains unclear. Workplace stress is a risk factor for depression and a target for intervention, but few interventions exist to prevent depression among workers at risk due to heightened stress. This trial aimed to evaluate the efficacy of a smartphone-based intervention in reducing the onset of depression and improving related outcomes in workers experiencing at least moderate levels of stress. A randomized controlled trial was conducted with participants who were currently employed and reported no clinically significant depression and at least moderate stress. The intervention group (n=1053) were assigned Anchored, a 30-day self-directed smartphone app-based cognitive behavioral- and mindfulness-based intervention. The attention-control group (n=1031) were assigned a psychoeducation website. Assessment was performed via web-based self-report questionnaires at baseline and at 1-, 3-, and 6-month postbaseline time points. The primary outcome was new depression caseness aggregated over the follow-up period. The secondary outcomes included depressive and anxiety symptoms, stress, well-being, resilience, work performance, work-related burnout, and quality of life. Analyses were conducted within an intention-to-treat framework using mixed modeling. There was no significant between-group difference in new depression caseness (z score=0.69; P=.49); however, those in the Anchored arm had significantly greater depressive symptom reduction at 1 month (Cohen d=0.02; P=.049) and 6 months (Cohen d=0.08; P=.03). Anchored participants also showed significantly greater reduction in anxiety symptoms at 1 month (Cohen d=0.07; P=.04) and increased work performance at 1 month (Cohen d=0.07; P=.008) and 6 months (Cohen d=0.13; P=.01), compared with controls. Notably, for Anchored participants completing at least two-thirds of the intervention, there was a significantly lower rate of depression onset (1.1%, 95% CI 0.0%-3.7%) compared with controls (9.0%, 95% CI 6.8%-12.3%) at 1 month (z score=4.50; P<.001). Significant small to medium effect sizes for most secondary outcomes were seen in the highly engaged Anchored users compared with controls, with effects maintained at the 6-month follow-up for depressive symptoms, well-being, stress, and quality of life. Anchored was associated with a small comparative reduction in depressive symptoms compared with controls, although selective prevention of case-level depression was not observed in the intention-to-treat analysis. When users adequately engaged with the app, significant findings pertaining to depression prevention, overall symptom reduction, and functional improvement were found, compared with controls. There is a need for a greater focus on engagement techniques in future research. Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000178943; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378592.

Long-term outcomes of therapeutic corneal transplants performed in a tertiary eye care hospital in South India.

This study aimed to review the demographics, clinical characteristics, and long-term outcomes of therapeutic penetrating keratoplasty (TPK) performed in a tertiary eye care hospital. Case records of 149 therapeutic transplants (135 patients) that were performed during the calendar year 2016 were retrospectively analyzed, and outcomes were measured until 3 years of follow-up. Information on demographics, presentation characteristics, keratoplasty indications, offending microbe, and secondary surgical interventions was studied. The final outcome was classified in terms of therapeutic, anatomical, and functional outcomes. The median age of the recipients was 55 years with 61% men. The most common indications for TPK were perforated infectious ulcer (45.9%), nonhealing ulcers (29.9%), and graft infections (17.4%). Fungal etiology was noted in 61.2% and bacterial etiology in 17.4% of the eyes. Therapeutic success was achieved in 130 eyes (89%) at the end of 1 month. Anatomical success was achieved in 130 (98.5%) and 88 patients (86.3%) at the end of 1 and 6 months, respectively. At the 6-month time point, 78 patients (76.5%) attained functional success with vision better than light perception. Three-year follow-up data were available for 23.7% of recipients, of which only 12 patients (37.5%) retained a clear graft either after a primary therapeutic or secondary optical keratoplasty. Therapeutic keratoplasty is highly effective in eradicating infection and providing anatomical integrity. However, timely intervention can aid in achieving the best functional outcome.

Cardiovascular Safety in Postmenopausal Women and Men With Osteoporosis Treated With Denosumab and Zoledronic Acid: A Post-Authorization Safety Study.

Osteoporosis and cardiovascular disease are common in older adults. Treatment of osteoporosis reduces the burden of debilitating fractures; however, it is important to understand the benefit versus risk of treatment. This study evaluates the risk of stroke (ischemic or hemorrhagic) and myocardial infarction (MI) among postmenopausal women and men initiating osteoporosis treatment with denosumab (receptor activator of nuclear factor κB ligand [RANKL] inhibitor) or zoledronic acid (bisphosphonate) between October 2010 and June 2019. A retrospective cohort study employing the new user/active comparator design was conducted. Analyses were conducted separately in two national US commercial databases, MarketScan® and Optum® for reproducibility. Inverse probability of treatment and censoring weighting was employed to control for confounding and informative censoring. Cumulative risks at 6-month, 12-month, and 36-month time points were calculated and adjusted risk ratios and differences (with 95% confidence intervals [CIs]) were estimated. In MarketScan® and Optum® databases, 96,611 and 73,127 patients met all study eligibility criteria, respectively. At 36 months, the risk ratio estimates (zoledronic acid referent group) were 1.22 (95% CI, 0.77-1.66) and 0.97 (95% CI, 0.63-1.32) for MI and 1.00 (95% CI, 0.61-1.40) and 0.87 (95% CI, 0.56-1.17) for stroke in MarketScan and Optum, respectively. Most of the treatment associations across the other time periods and outcomes also had 95% CIs including the null value. In these large samples of real-world US patients, no increased risk in MI and stroke were identified for up to 36 months of treatment in denosumab users compared with zoledronic acid users. © 2023 Amgen. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Long-Term Outcomes in Early versus Limited Response to Anti-VEGF Treatment for Retinal Vein Occlusion

Macular edema secondary to retinal vein occlusion (RVO) is a sight-threatening condition. Previous studies showed that early responders (ERs) who respond well to anti-VEGF injections within 3 months of treatment have better outcomes, as measured by best visual acuity (BVA) and central subfield thickness (CST) at 12 months postinjection initiation compared with limited early responders (LERs). This study analyzed whether ER eyes continue to respond better than LER eyes over longer periods. This study also aimed to identify baseline comorbidities associated with response status. Retrospective cohort study. Patients aged > 18 years with RVO-related macular edema treated with anti-VEGF injections. Patients were categorized as ERs or LERs. Limited early responder eyes were defined as having CST reduction < 10%, BVA gain < 5 ETDRS letters, or both at 3 months after anti-VEGF initiation. Best visual acuity and CST changes over the 24- and 36-month period after the first anti-VEGF treatment were compared between ERs and LERs. Patient characteristics and systemic comorbidities were identified by chart review. Statistical analysis involved the Levene test, Welch t test, and Welch analysis of variance. Best visual acuity and CST changes over the initial 24-month and 36-month periods after treatment. The 24-month cohort included 68 ERs and 39 LERs, and the 36-month cohort included 58 ERs and 33 LERs. At the 24-month time point, there were significant differences in BVA and CST gains between ERs (+19.8 letters,-221.2 um) and LERs (-2.4 letters,-90.1 um; P < 0.001, P < 0.01). Similarly, at 36 months, there were significant differences in BVA and CST gains between ERs (+17.7 letters,-229.3 um) and LERs (+1.3letters,-128 um; P < 0.001, P < 0.05). After controlling for differences in baseline BVA and CST, only the 24-month change in BVA remained significant (P < 0.001). There were no significant associations between response status and cardiopulmonary, endocrine, and oncologic comorbidities. Early responder eyes with branched retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) have better functional responses to anti-VEGF injections at 24 months compared with LER eyes, even after controlling for baseline differences. Early identification of eyes as ERs or LERs in BRVO and CRVO may predict long-term functional prognoses. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

What predicts durable symptom relief of uterine fibroids treated with MRI-guided focused ultrasound? A multicenter trial in 8 academic centers.

To identify variables predictive of durable clinical success after MRI-guided focused ultrasound (MRgFUS) treatment of uterine fibroids. In this prospective, multicenter trial, 99 women with symptomatic uterine fibroids were treated using MRgFUS. Pelvic MRI was obtained at baseline and treatment day. The Uterine Fibroid Symptom-Quality of Life questionnaire was used to calculate a symptom severity score (SSS) at baseline and 6, 12, 24, and 36months following treatment. Clinical, imaging, and treatment variables were correlated with symptom reduction sustained through the 12- and 24-month time points using univariable and multivariable logistic regression analyses. A novel parameter, the ratio of non-perfused volume to total fibroid load (NPV/TFL), was developed to determine association with durable outcomes. Post-treatment, mean symptom severity decreased at the 6-, 12-, 24-, and 36-month follow-ups (p < 0.001, all time points). In univariable analysis, three variables predicted treatment success (defined by ≥ 30-point improvement in SSS) sustained at both the 12-month and 24-month time points: increasing ratio of NPV/TFL (p = 0.002), decreasing total fibroid load (p = 0.04), and the absence of T2-weighted Funaki type 2 fibroids (p = 0.02). In multivariable analysis, the NPV/TFL was the sole predictor of durable clinical success (p = 0.01). Patients with ratios below 30% had less improvement in SSS and lacked durable clinical response compared with those between 30-79 (p = 0.03) and ≥ 80% (p = 0.01). Increased non-perfused volume relative to total fibroid volume was significantly associated with durable reduction of symptoms of abnormal uterine bleeding and bulk bother. Patient selection for sustained clinical benefit should emphasize those with likelihood of achieving high ablation ratios, as determined by imaging (e.g., device access, Funaki type) and by considering the total fibroid load, not just the primary symptomatic fibroid. Clinical trial ID: NCT01285960. • Patient selection/treatment approach associated with durable symptom relief in MRI-guided focused ultrasound ablation of uterine fibroids remains unclear. • The ablation ratio, non-perfused volume/total fibroid volume, was positively associated with sustained symptom relief in both bleeding and bulk bother at 1- and 2-year follow-ups. • Selecting patients with imaging features that favor a high ratio of ablation to total fibroid load (including non-targeted fibroids) is the main factor in predicting durability of symptom relief after uterine fibroid treatment.