6-month Time Point Research Articles

IMG-01. LONGITUDINAL SIGNAL CHANGES IN THE DENTATE AND INFERIOR OLIVARY NUCLEI IN PATIENTS WITH CEREBELLAR MUTISM SYNDROME

Abstract BACKGROUND Cerebellar mutism syndrome (CMS) is a complication of posterior fossa surgery with an acute impairment in speech, and long-term neurocognitive deficits. Lesion mapping studies suggest the cognitive symptoms are associated with dentatorubrolivary damage1. We hypothesize that CMS patients will demonstrate more longitudinal MRI signal abnormalities in the dentate and inferior olivary nuclei as compared to non-CMS patients. METHODS MRI brains on 40 pediatric medulloblastoma patients between 2013-2015 were retrospectively reviewed by a neuroradiologist blinded to the diagnosis at pre-operative and immediate, 6-month, 12 month and most recent post-operative time points. The dentate and inferior olivary nuclei were scored for restricted diffusion, T1 and T2 hypo-and hyperintensity. A linear regression with different scores on CMS status (YES vs NO) was applied, after adjusting for age. RESULTS In the dentate nuclei, there was significantly higher T2 hypointensity in the CMS group on immediate (difference is 0.4084, p=0.0467) and most recent (difference is 0.7190, p=0.0386) post-operative MRIs. The CMS group had significantly higher T1 hyperintensity on the 1-year (difference is 0.9254, p=0.0108) and most recent (difference is 1.3291, p<0.001) post-operative MRIs. In the inferior olivary nuclei, there was significantly higher T2 hyperintensity on the 6-month (difference is 0.71, p=0.0045) and 1-year (difference is 0.6356, p=0.0162) post-operative MRIs. CONCLUSION The immediate post-operative findings are suggestive of a hemorrhagic, rather than an ischemic process in the dentate nuclei. On long-term follow up, the signal changes in the dentate and the inferior olivary nuclei represent dystrophic mineralization and hypertrophic degeneration, due to inflammation and axonal degeneration within the dentatorubroolivary tract2

(113) PRACTICAL DISTRESS AT DIAGNOSIS PORTENDS WORSE SEXUAL WELL-BEING DURING BREAST CANCER TREATMENT

Abstract Introduction A breast cancer diagnosis and subsequent treatment can have profound impacts on patients' body image and sexual health. Sexual health and well-being are an unmet concern for many and declines in sexual function have been associated with higher distress and anxiety. Objective Our study aims to evaluate how distress at diagnosis is related to sexual well-being and referral to ancillary resources during breast cancer treatment at a comprehensive cancer center. Methods All patients with newly diagnosed breast cancer were offered a distress screening tool which measures distress in the emotional (I.e. worry, nervousness), physical (I.e. nausea, sexual intimacy, fatigue), social (I.e. relating with others), and practical domains (I.e. bills, housing, transportation). High distress in a domain was defined as a score greater than 5. Patients were then invited to complete the Breast-Q module, a validated patient reported outcome (PRO) scale that quantifies outcomes related to sexual well-being (SW). Participants who had at least one distress measure at baseline and at least one PRO at either baseline or 6-months post-operatively were eligible for inclusion. Chart review was conducted for referral to and utilization of ancillary services including sexual health consultation. Multivariable linear mixed models were used to compare high and low distress with an interaction between distress and time. Results 227 patients were included in the study population. The median baseline SW score was 55.4 (standard deviation = 22.9). High practical distress was found in 18.4% of patients, however, those with high practical distress at baseline were more likely to have greater decline in their SW scores between the pre-operative and 6-month post-operative time points (p = 0.03) (Figure 1). After adjusting for age, stage, and treatment received, this relationship remained significant. Of the available ancillary resources, social work and care management services were the most common referrals with 135 patients seen. Only 4 patients attended a sexual health consultation based on clinician discretion. Change in pre-operative and 6-month post operative SW was not related to emotional, physical, or social distress. Conclusions Sexual well-being trajectories are related to practical distress at diagnosis. This suggests that patients who are already struggling with the logistics of a new breast cancer diagnosis may suffer the most when it comes to their sexual health. Most patients here received some ancillary support however it is clear something is still missing given the observed declines in sexual well-being. Further study is necessary to understand the drivers of this relationship and how these patients can receive early intervention to prevent worsening of their sexual well-being during breast cancer treatment. Disclosure No.

Building a baby-friendly community: Development, strategy, implementation and evaluation of a BFCI program.

The aim of the study was to investigate the impact of the use of baby-friendly community initiative (BFCI) model on various stakeholders in the community. Quasi-experimental research design. The study was conducted in public premises and online workshops from April 2019 to September 2022. Participants were followed up for a period of 1 month, except for those employed at public premises. The program involved training based on an accredited BFCI framework to cultivate a breastfeeding-friendly attitude and knowledge. A paired sample t-test was used to examine breastfeeding attitude and knowledge scores before and after BFCI training among staff employed from public premises. An analysis of variance was conducted to examine the breastfeeding self-efficacy and attitude scores, measured repeatedly at different timepoints over 1-month timepoint (T0, T1 and T2) among pregnant and postpartum women. A total of 2340 perinatal women and 1339 staff from public premises were recruited. For staff, there was an increase in the mean score of breastfeeding knowledge and attitude by 5.8 and 6.1, respectively, at T1. Similarly, for perinatal women, there was an increase in the mean score of breastfeeding self-efficacy and attitude by 6.6 and 3.3, respectively, at T1. In summary, a BFCI model, with active community participation, accreditation and an award system, has been effective in promoting breastfeeding. Adapting the baby-friendly hospital initiative to local contexts and employing a social theory model can enhance breastfeeding promotion and improve infant health outcomes. Prioritizing culturally sensitive breastfeeding education is crucial for successful BFCI implementation. Healthcare professionals should consider clients' culture and socio-economic backgrounds when providing breastfeeding education to maximize effectiveness. The target audience for breastfeeding education should be expanded to include various community stakeholders beyond families. What problem did the study address? This study addressed the problem of knowledge gaps among stakeholders in building a breastfeeding-friendly community, particularly in implementing a baby-friendly community initiative (BFCI) as part of a baby-friendly hospital initiative (BFHI). The research filled a service gap by providing effective interventions targeting community stakeholders and assessing the impact of a BFCI program on their knowledge and attitudes towards breastfeeding. What were the main findings? The findings highlighted the effectiveness of a BFCI program in enhancing breastfeeding knowledge and attitudes among frontline staff and increasing breastfeeding confidence among mothers. These findings contribute to the understanding of the program's impact on different stakeholders in the community. Where and on whom will the research have an impact? It impacts on global policymakers by providing insights for developing comprehensive guidelines for future BFCI implementations. It also contributes to the creation of a more baby-friendly community, benefiting breastfeeding families and their infants by promoting and supporting breastfeeding families. This study has adhered to relevant EQUATOR guidelines using the TREND reporting guideline. No patient or public contribution. WHAT DOES THIS PAPER CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: This study provides an overview of the establishment of a localized BFCI program. It also opens up a new direction for the community to investigate BFCI strategies for community stakeholders. It also provides evidence to support other countries in following a similar process, as each country approaches becoming breastfeeding-friendly in its own unique way. No protocol.

Three-Dimensional Changes of Condylar Position After Bimaxillary Surgery to Correct Skeletal III Malocclusion: Cone Beam Computed Tomography Voxel-Based Superimposition Analysis

BackgroundThe stability of the condylar position within the first three months after orthognathic surgery in patients with skeletal Class III malocclusion is crucial for subsequent orthodontic treatment. PurposeThe purpose was to compare condylar positional changes three months after bimaxillary surgery to correct skeletal Class III deformities, utilizing the conventional two-dimensional (2D) combined with the cone beam computed tomography (CBCT) voxel-based superimposition analysis. Study design, setting, sampleThis retrospective cohort study included skeletal Class III patients undergoing bimaxillary orthognathic surgery at Khon Kaen University, Thailand in 2020. Exclusion criteria were patients with temporomandibular disorder (TMD) symptoms, facial asymmetry prior to the surgery, or surgical complications. Exposure variableThe exposure variable was the timing, both preoperatively and 3 months postoperatively. This 3-month postoperative time point was chosen because complete healing of the bimaxillary surgery is expected by then, without any potential influence of condylar changes resulting from subsequent orthodontic treatment. Main outcome variablesThe outcome variable is condylar position measurement, joint space (mm) and axial condylar angle (degrees). CovariatesDemographics (age, sex), and surgical details (direction and amount of movement) were collected as covariates. AnalysesStatistical analysis of condylar positional changes and correlations was performed using paired t-test and linear correlation (P-value < 0.05), respectively. ResultsThe sample included 11 subjects (22 condyles), with a mean age of 24±5.24 years. Both 2D measurements and voxel-based 3D superimposition showed significant changes in condylar position three months after bimaxillary surgery: inferior (0.45±0.26 mm, P < 0.001), posterior (0.46±0.39 mm, P = 0.003), lateral (0.38±0.42 mm, P = 0.01) displacement, and inward rotation (5.21±2.54°, P < 0.001). No significant correlation was found between jaw movement distance and condylar changes. Conclusions and relevanceTo our knowledge, this is the first study to report measures of condylar changes at 3 months, when complete healing of the osteotomies would be expected, using Le Fort I osteotomy for maxillary advancement combined with bilateral sagittal split ramus osteotomy (BSSRO) for mandibular setback. These changes are small in magnitude and may be of little relevance to patient care.

Piloting “From the Inside Out” — a toolkit addressing tuberculosis-related self-stigma

BackgroundSelf-stigma among people who have tuberculosis (TB) can contribute to non-adherence to medication and disengagement from care. It can manifest in feelings of worthlessness, shame, and guilt, leading to social withdrawal and disengagement from life opportunities. Self-stigma may also affect families of those who have TB, or healthcare workers who treat them. However, few interventions addressing TB self-stigma exist to date.MethodsWe piloted the delivery of a toolkit of psychosocial interventions using a “training-of-trainers” approach with six staff members of a TB-focused NGO (Non-Governmental Organisation) and partner organisations in Jakarta, Indonesia. These trainers could then disseminate the toolkit among community partner organisations. Local staff involvement throughout the study supported translation and adaptation to enhance cultural and language appropriateness. Over a 2-day training-of-trainers workshop, the NGO staff were familiarised with the mode of delivery of the toolkit, which they then delivered via a four-day participatory workshop with 22 people who have TB/TB survivors, who were representatives of partner organisations working among communities affected by TB.ResultsThe newly-trained local facilitators delivered the toolkit to the participants, who self-reported significant increases in knowledge and efficacy around TB self-stigma post-intervention compared to baseline (Z = 1.991, p = 0.047, Wilcoxon signed-rank test). The participants’ levels of self-compassion were also significantly higher post-workshop (Z = 2.096, p = 0.036, Wilcoxon signed-rank test); however, these effects were not maintained at 3-month timepoint. There was also a significant increase post-workshop in one of the participants’ Ryff dimensions of psychological wellbeing, that of positive relationships with others (Z = 2.509, p = 0.012, Wilcoxon signed-rank test) but this was also not maintained at the 3-month timepoint.ConclusionsThe observed changes in recipients’ self-reported levels of knowledge and efficacy, self-compassion, and psychological wellbeing may warrant further investigation into the best modalities for toolkit delivery (frequency, dose, duration) and support for individuals as they progress through the TB treatment journey.

Financial toxicity (FT), quality of life (QoL), and medication adherence patient-reported outcomes (PROs) in CLL on first-line (1L) oral oncolytics.

e23157 Background: While oral oncolytics have transformed CLL treatment, high costs may cause significant FT adversely impacting patients beyond direct out-of-pocket (OOP) costs. The association of FT with QoL and medication adherence has not been characterized with oral oncolytics in CLL. Methods: Electronic PRO surveys were longitudinally administered to patients initiating any 1L oral oncolytic therapy for CLL within the last 6 months at two academic centers. PROs included FACIT-COST (significant FT: score &lt; 26), FACT-LEU QoL, MARS-5 (suboptimal adherence: score &lt; 25) and PROMIS PMAS to assess medication adherence. PROs were administered at baseline, 3 months, and 6 months after enrollment. Pearson’s correlation ( r) was calculated between PRO domains. Semi-structured, qualitative interviews were conducted after 3-month timepoints and analyzed. Results: 34 patients were enrolled: median age 65 yrs (range 33-80), 59% male, 6% Black, 9% Hispanic. Majority received BTK inhibitors (56%, acalabrutinib/zanubrutinib) followed by venetoclax (44%); 50% received concurrent obinutuzumab. Most had private insurance (50%) followed by Medicare (44%). Median time from 1L initiation to study enrollment: 1.5 months. PRO completion rates: 100% (baseline), 85% (3 mo) and 74% (6 mo). Summarized PRO and interview outcomes are displayed below. Conclusions: Patients with CLL on 1L oral oncolytics experienced worsening FT associated with poor medication adherence and worse QoL over time. PROs were discordant with qualitative interviews and suggested that FT may be driven by factors other than OOP costs. Although funding and patient assistance programs were beneficial, uncertainty over losing funding may be a long-term driver of FT and merits further study. [Table: see text]

Time dependency for HPV ctDNA detection as a prognostic biomarker for anal cancer.

3513 Background: Prior HPV infection is associated with &gt; 90% of anal cancers, a malignancy with rising incidence in the United States. Standard treatment for localized anal cancer is concurrent chemoradiation (cRT). While detection of circulating tumor DNA (ctDNA) within weeks after surgery is linked to recurrence in other solid tumors, the optimal time point for ctDNA detection as a prognostic biomarker following cRT for HPV-associated anogenital cancers is not well characterized. We utilized a novel, highly sensitive HPV ctDNA assay to evaluate clinical outcomes according to HPV ctDNA status among patients with localized anal cancer treated with cRT. Methods: ctDNA was isolated from patients with stages I-III anal cancer treated at our institution with cRT prior to treatment, at the end of treatment (week 5), and at months 3, 6, 9, and 12 after treatment under an IRB-approved protocol. A droplet digital HPV ctDNA PCR assay evaluating HPV E6 and E7 oncogenes for 13 oncogenic HPV types was utilized for quantification of HPV ctDNA. A limit of quantification at 16 HPV copies/mL plasma was set for “HPV ctDNA detection.” Median recurrence-free survival (RFS) according to HPV ctDNA status was estimated via Kaplan-Meier and compared using a log-rank test. Associations between selected clinical factors and recurrence were evaluated with a Chi-square test, with a one-sided p &lt; .05 considered significant. Results: Following cRT, HPV ctDNA was detected in 9/41 (22%), 4/30 (13%), 2/20 (10%), and 0/12 (0%) patients at week 5 and months 3, 6, and 12, respectively. Detection of HPV ctDNA 3 months after cRT was associated with clinical recurrence (100% versus 8%; odds ratio 88, 95% CI 4-2000; p = .006) and inferior RFS (5.9 months vs not reached (NR); hazard ratio (HR) 24, 95% CI 1.2-475; p &lt; .001) relative to HPV ctDNA-negative status. Differences in RFS according to HPV ctDNA status were not observed at week 5/end of treatment (median RFS NR for both; HR 2.4, 95% CI .5-10; p = .15). At month 3, sensitivity and specificity for recurrence according to HPV ctDNA detection were 57% and 100%, respectively, with a PPV and NPV of 100% and 89%, respectively. Baseline clinical stage, T stage, N stage, age, and gender were not associated with clinical recurrence after cRT (p &gt; .25 for all). Conclusions: With a novel, highly sensitive assay, detection of HPV ctDNA at 3 months after cRT was associated with RFS. Further, an HPV ctDNA-positive status outperformed baseline clinical features for prognosticating anal cancer recurrence after cRT in this retrospective series. Future clinical trials should incorporate the 3-month post-treatment time point for identification of patients with HPV-positive anal cancer at elevated risk for recurrence according to HPV ctDNA status. A clinical trial evaluating anti-PD-L1 + anti-TIGIT immunotherapy for patients with HPV-associated cancers with detected HPV ctDNA after cRT is forthcoming at our institution.

Which North American spine society disc herniation morphology descriptors are most associated with improvements in clinical outcomes after microdiscectomy?

The North American Spine Society (NASS) assembled the first ever comprehensive naming system for describing lumbar disc disease, including lumbar disc herniation. The objectives of this study were (1) to determine which NASS descriptors are most predictive of independent patient-reported outcomes after microdiscectomy and (2) to identify the inter-rater reliability of each NASS descriptor. Adult patients (≥18 years) who underwent a lumbar microdiscectomy from 2014-2021 were retrospectively identified. Patient-reported outcome measures (PROMs) were collected at preoperative, 3-month, and 1-year postoperative time points. Lumbar disc herniations were evaluated and classified on preoperative MRI using the NASS lumbar disc nomenclature specific to disc herniation. About 213 microdiscectomy patients were included in the final analysis. Herniation descriptors exhibiting the greatest reliability included sequestration status (κ=0.83), axial disc herniation area (κ=0.83), and laterality (κ=0.83). The descriptor with the lowest inter-rater reliability was direction of migration (κ=0.53). At 3 months, a sequestered herniation was associated with lower odds of achieving the minimal clinically important difference (MCID) for ODI (p=.004) and MCS (p=.032). At 12 months, a similar trend was observed for Oswestry Disability Index (ODI) MCID achievement (p=.001). At 3 months, a herniation with larger axial area was a predictor of MCID achievement in ODI (p=.004) and the mental component summary (MCS) (p=.009). Neither association persisted at 12 months; however, larger axial disc herniation area was able to predict MCID achievement in the Visual Analogue Scale (VAS) leg (p=.031) at 12 months. The utility of the NASS nomenclature system in predicting postoperative outcomes after microdiscectomy has yet to be studied. We showed that sequestration status and disc area are both reliable and able to predict the odds of achieving MCID in certain clinical outcomes at 3 months and 12 months after surgery. Hence, preoperative imaging analysis of lumbar disc herniations may be useful in accurately setting patient expectations.

Ground-based adaptive horsemanship lessons for veterans with post-traumatic stress disorder: a randomized controlled pilot study.

Equine-assisted services (EAS) has received attention as a potential treatment strategy for post-traumatic stress disorder (PTSD), as existing literature indicates that symptoms may decrease following EAS. Relatively little is known about the mechanisms at play during lessons and if physiological measures are impacted. The objectives of this pilot study were to 1) explore the effects of adaptive horsemanship (AH) lessons on symptoms of PTSD, hormone concentrations, and social motor synchrony; 2) determine if physiological changes occur as veterans interact with horses; and 3) explore if the interaction between veteran and horse changes over the 8-week session. Veterans with PTSD were randomly assigned to control (CON, n = 3) or AH (n = 6) groups for an 8-week period (clinical trial; NCT04850573; clinicaltrials.gov). Veterans completed the PTSD Checklist (PCL-5) and Brief Symptom Inventory (BSI) at pre-, post-, and 2- and 6-month follow-up time points. They also completed a social motor synchrony test (pendulum swinging) and blood draw at pre- and post-time points. In weeks 1, 4, and 8, blood samples were drawn at 0 min, 3 min, 5 min, 25 min, and 30 min during the 30-min AH lessons. Veterans completed the Human-Animal Interaction Scale (HAIS) after each lesson. Blood samples were assayed for plasma cortisol, epinephrine, norepinephrine, and oxytocin. Data were analyzed with repeated measure ANOVAs. Changes in PTSD symptoms from pre- to post-time point were analyzed with paired t-tests. Changes in PCL-5 scores tended to differ (p = 0.0989), and global BSI scores differed (p = 0.0266) between AH (-11.5 ± 5.5, mean ± SE; -0.5 ± 0.2) and CON (5.3 ± 5.4; 0.4 ± 0.2) groups. Social motor synchrony and hormone concentrations did not differ between groups or time points (p > 0.05). Cortisol, norepinephrine, and oxytocin concentrations did not differ across sessions (p > 0.05). Epinephrine concentrations tended (p = 0.0744) to decrease from week 1 to 4 of sessions. HAIS scores increased (p ≥ 0.0437) in week 3 and remained elevated as compared to week 1. Participant recruitment was the greatest challenge. These preliminary results agree with the literature suggesting that EAS can reduce symptoms of PTSD.

Total and H-specific growth/differentiation factor 15 levels are unaffected by liraglutide or naltrexone/bupropion administration.

To investigate growth/differentiation factor 15 (GDF-15) levels in response to antiobesity medications, namely, liraglutide (Lira) and naltrexone/bupropion (N/B), in individuals with overweight or obesity. This was a prospective, non-randomized clinical trial with a two-arm, parallel design. A total of 42 individuals with overweight or obesity without type 1 or type 2 diabetes mellitus were enrolled. The participants received either Lira 3 mg or N/B 32/360 mg, along with diet and exercise, according to comorbidities, cost and method of administration. Participants underwent clinical and laboratory measurements at baseline, as well as at the 3- and 6-month time points. Anthropometric measurements and body composition analysis via bioelectrical impendence analysis were performed. Total blood samples for GDF-15 and H-specific GDF-15 were collected in the fasting state and every 30 min for 3 h after the consumption of a standardized mixed meal. Overall, participants' weight was reduced by 9.29 ± 5.34 kg at Month 3 and 11.52 ± 7.52 kg at Month 6. Total and H-specific GDF-15 levels did not show significant changes during the mixed meal compared to values before the meal when all participants were examined at baseline, and at 3 and 6 month follow-ups. No statistical significance was found when participants were examined by subgroup (Lira vs. N/B). No significant differences between treatment groups in postprandial area under the curve (AUC) or incremental AUC values were found at baseline or in the follow-up months with regard to total and H-specific GDF-15 levels. Neither total nor H-specific GDF-15 levels are affected by Lira or N/B treatment in patients with overweight or obesity.

Time-Dependent Long-Term Effect of Memantine following Repetitive Mild Traumatic Brain Injury.

Repetitive mild traumatic brain injury (rmTBI, e.g., sports concussions) may be associated with both acute and chronic symptoms and neurological changes. Despite the common occurrence of these injuries, therapeutic strategies are limited. One potentially promising approach is N-methyl-D-aspartate receptor (NMDAR) blockade to alleviate the effects of post-injury glutamatergic excitotoxicity. Initial pre-clinical work using the NMDAR antagonist, memantine, suggests that immediate treatment following rmTBI improves a variety of acute outcomes. It remains unclear (1) whether acute memantine treatment has long-term benefits and (2) whether delayed treatment following rmTBI is beneficial, which are both clinically relevant concerns. To test this, animals were subjected to rmTBI via a weight drop model with rotational acceleration (five hits in 5 days) and randomized to memantine treatment immediately, 3 months, or 6 months post-injury, with a treatment duration of one month. Behavioral outcomes were assessed at 1, 4, and 7 months post-injury. Neuropathological outcomes were characterized at 7 months post-injury. We observed chronic changes in behavior (anxiety-like behavior, motor coordination, spatial learning, and memory), as well as neuroinflammation (microglia, astrocytes) and tau phosphorylation (T231). Memantine treatment, either immediately or 6 months post-injury, appears to confer greater rescue of neuroinflammatory changes (microglia) than vehicle or treatment at the 3-month time point. Although memantine is already being prescribed chronically to address persistent symptoms associated with rmTBI, this study represents the first evidence of which we are aware to suggest a small but durable effect of memantine treatment in mild, concussive injuries. This effect suggests that memantine, although potentially beneficial, is insufficient to treat all aspects of rmTBI alone and should be combined with other therapeutic agents in a multi-therapy approach, with attention given to the timing of treatment.

Low-Income Participants' Preference Between Financial Incentives for Behavioral Goals vs Weight Loss Targets and Associations With Behavioral Goal Adherence.

Examine associations between whether participants' were matched to their preferred financial incentive design and behavioral goal adherence in a weight management intervention. Secondary quantitative analysis incorporating qualitative survey data. Primary care clinics in socioeconomically disadvantaged communities in New York City and Los Angeles. 668 participants (mean age 47.7 years, 81.0% female, 72.6% Hispanic) with obesity were enrolled in the Financial Incentives foR Weight Reduction (FIReWoRk) intervention. We explored qualitatively participant's reasons for hypothetically choosing a behavioral goal-directed vs a weight loss outcome-based financial incentive program. Additionally, behavioral adherence to different goals was collected at the 6-month timepoint, categorized by match to preferred financial incentive design. Logistic regression was used to examine if participants with certain demographic and higher psychosocial factors were more likely to choose goal-directed over outcome-based incentives. Additionally, logistic regression was used to test for associations between preference and behavioral adherence, using incentive type as an interaction term. 60.2% of participants preferred the goal-directed incentive, with the majority stating that it was more structured. Married participants were more likely to prefer goal-directed incentives (OR = 1.57, CI = 1.06-2.33, P = .025). Moderation analysis revealed that participants who preferred goal-directed and were matched to goal-directed had greater rates of behavioral adherence for program attendance and self-weighing, but not dietary tracking and physical activity tracking, compared to those who preferred outcome-based and were matched to outcome-based. Receiving one's preferred incentive design may not play a strong role in behavioral goal adherence during financially incentivized weight loss interventions.

Assessment of Spillover of Antimicrobial Resistance to Untreated Children 7-12 Years Old After Mass Drug Administration of Azithromycin for Child Survival in Niger: A Secondary Analysis of the MORDOR Cluster-Randomized Trial.

The risk of antibiotic resistance is complicated by the potential for spillover effects from one treated population to another. Azithromycin mass drug administration programs report higher rates of antibiotic resistance among treatment arms in targeted groups. This study aimed to understand the risk of spillover of antibiotic resistance to nontarget groups in these programs. Data were used from a cluster-randomized trial comparing the effects of biannual azithromycin and placebo distribution to children 1-59 months old on child mortality rates. Nasopharyngeal samples from untreated children 7-12 years old were tested for genetic determinants of macrolide resistance (primary outcome) and resistance to other antibiotic classes (secondary outcomes). Linear regression was used to compare the community-level mean difference in prevalence by arm at the 24-month time point, adjusting for baseline prevalence. A total of 1103 children 7-12 years old in 30 communities were included in the analysis (15 azithromycin, 15 placebo). The adjusted mean differences in the prevalence of resistance determinants for macrolides, β-lactams, and tetracyclines were 3.4% (95% confidence interval, -4.1% to 10.8%; P = .37), -1.2% (-7.9% to 5.5%; P = .72), and -3.3% (-9.5% to 2.8%; P = .61), respectively. We were unable to demonstrate a statistically significant increase in macrolide resistance determinants in untreated groups in an azithromycin mass drug administration program. While the result might be consistent with a small spillover effect, this study was not powered to detect such a small difference. Larger studies are warranted to better quantify the potential for spillover effects within these programs.

Weight Changes after Ankle Fracture Surgery: A Retrospective Cohort Study

Background: Recovery from open reduction internal fixation of the ankle frequently involves a decrease in activity level and some limitations in weightbearing. The purpose of this study was to evaluate weight changes during the postoperative period following ankle fracture surgery. Methods: Hospital billing records were retrospectively reviewed to identify all patients who underwent open reduction internal fixation of bimalleolar and trimalleolar ankle fractures at our hospital system between January 1, 2018 and June 30, 2021. Weight data from outpatient encounters coinciding with the 3-month, 6-month, and 1-year postoperative time points were recorded and analyzed. Results: 56 patients had complete weight data. The mean age at surgery was 44.6±16.2 years. There were 27 women and 29 men. At time of surgery, the mean weight was 197.2.3±53.9 lbs and BMI was 30.3±7.1 kg/m2. At 1 year postoperative, the mean weight was 219.2±51.6 lbs and BMI was 33.8±7.0 kg/m2, representing statistically significant increases of 22.0 lbs and 3.4 BMI points compared to preoperative (p=0.0491 and 0.0330, respectively). On subgroup analysis of different preoperative BMI groups (&lt;25, 25-29, 30-34, and ≥35), only those patients with a pre-operative BMI of &lt;25 experienced statistically significant increases in weight and BMI, 27.9 lbs and 4.8 kg/m2 respectively (p=0.029 and p=0.001). Conclusion: This is the first study to evaluate weight changes following ankle fracture. This study showed that at 1 year patients recovering from ankle open reduction internal fixation gain an average of 22 lbs and 3.4 BMI points. Patients with a pre-operative BMI of &lt;25 are subject to statistically significant increases in weight. We recommend monitoring patients’ weight and counseling them on the risks of weight gain. Further research is necessary to better characterize the risk of weight gain following orthopedic surgery. Level of Evidence: 4 (retrospective cohort)

Change in clinical parameters after subgingival instrumentation for the treatment of periodontitis and timing of periodontal re-evaluation: A systematic review and meta-analysis.

To evaluate the changes in periodontal parameters (reduction in probing pocket depth [PPD], gain in clinical attachment level [CAL] and reduction in full-mouth bleeding on probing [BoP]) after subgingival instrumentation of periodontal pockets at different time points in systemically healthy patients suffering from periodontitis. Four databases were searched for RCTs that carried out subgingival instrumentation in periodontal pockets and evaluated PPD at a minimum of two consecutive time points other than baseline. The analysis was conducted for both all pocket depths and stratified for initially shallow (4-5 mm) and deep (≥6 mm) pockets and data were extracted for various time points, 1-2, 3-4 and 5-6 months. Weighted mean effects (WMEs) were calculated with 95% confidence interval (CI) and predictive intervals were calculated. Twenty-nine RCTs were identified, and all of them were included in the meta-analysis. The results showed that for both shallow and deep pockets there was a small though clinically meaningful change between 1- to 2-month and 3- to 4-month time points and between these and 5-6 months. In systemically healthy patients, the greater part of reduction in PPD and gain in CAL occurs within the first 1-2 months after subgingival instrumentation. However, additional benefits in terms of pocket depth reduction occur beyond these early time points.

Abstract PO5-14-01: Weight loss and omega-3 polyunsaturated fatty acid intervention in overweight and obese peri- and postmenopausal women with increased breast cancer risk modifies the gut microbiome and is associated with circulating biomarkers

Abstract Background: Obesity-associated gut microbiome dysbiosis is thought to increase risk for postmenopausal breast cancer through alteration of estrogen metabolism and an increase in pro-inflammatory microbe abundance. Many studies have reported an increase in the Firmicutes/Bacteroidetes phyla ratio as a biomarker of obesity and is associated with adverse metabolic outcomes. Marine omega-3 eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids are thought to have favorable metabolic and inflammation resolving properties resulting in reduced risk for several epithelial cancers. One possible mechanism is the effect of EPA and DHA on the gut microbiome. We assessed the effect of weight loss and/or omega-3 supplementation on the gut microbiome and circulating molecular breast cancer risk factors. Methods: 46 peri/postmenopausal overweight and obese women at increased risk for breast cancer were enrolled into a weight-loss intervention and after 2 weeks randomized to 3.25 g/day combined EPA and DHA or placebo (PMC8416797). Fecal samples were collected at 0, 2-weeks and 6-months, with matched fecal samples for all timepoints available for 26 patients. Fecal samples at 6-months were available for 34 patients. 12M read depth metagenomic sequencing was performed on DNA isolated from feces to determine shifts in the gut microbiome. Fasting and non-fasting blood was also collected for circulating biomarker analysis. Body composition by DXA scan were also performed at baseline and 6-month time points. Results: Mean baseline BMI was 32 kg/m2. There was no significant difference between arms in age, baseline BMI, % body fat, or baseline Firmicutes/Bacteroidetes ratio. We identified gut microbiota species (A. hadrus and P. faecium) that correlated with metabolic parameters (% body fat, adiponectin/leptin ratio, and fasting insulin), species (P. dorei and B. ovatus) that correlated with estradiol levels, and mucin-degrading species (D. formicigenerans and R. gnavus) whose abundance correlated with inflammation (as measured by circulating monocyte-chemoattractant protein 1 (MCP-1)). Median 6-month weight change for all randomized subjects was -10% from baseline. Favorable change in the Firmicutes/Bacteroidetes ratio was associated both with the degree of weight loss and with omega-3 supplementation, although significant species modification differed between weight loss and omega-3 PUFA groups. Women with both &amp;gt;10% weight loss and omega-3 supplementation had a significantly reduced Firmicutes abundance and lower Firmicute/Bacteroidetes ratio than other groups. Species abundance shifts appear to differ between weight loss and omega-3 supplementation with 3 species modified by weight loss and 12 species shifted by omega-3 PUFA administration. Omega-3 PUFA supplementation significantly reduced proportional abundance of Dorea formicigenerans, which was a microbe associated with inflammation. Conclusions: Omega-3 supplementation at 3.25 g/day compared to placebo had a greater net effect on changing the gut microbiome in overweight and obese women at increased risk for breast cancer undergoing a weight loss intervention. Change in the gut microbiome may serve as a useful response biomarker in Phase II prevention trials of omega-3 fatty acid and weight loss. Citation Format: Katherine L. Cook, Erin Giles, Amy Kreutzjans, Shahid Umar, Christie Befort, Bruce Kimler, Stephen Hursting, Carol Fabian. Weight loss and omega-3 polyunsaturated fatty acid intervention in overweight and obese peri- and postmenopausal women with increased breast cancer risk modifies the gut microbiome and is associated with circulating biomarkers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-14-01.

Effect of Phone-based Counseling on Physical Activity and Fatigue in Postpartum Women

Objectives: Research shows that physical activity during postpartum affects maternal physical and mental health. In this study, we examined the associations of a phone-based physical activity intervention on objectively measured physical activity and self-reported fatigue. Methods: Participants (N=450) were randomly assigned to either a phone-based physical activity group (N=150), a wellness group (N=150), or a control group (N=150). Participants were on average 4.35 weeks postpartum at the time of the study. Physical activity was measured via accelerometer, and fatigue was measured via self-reported survey. We used a series of one-way analyses of variance (ANOVAs) to examine differences between study groups at the 6-month timepoint. Results: The physical activity group was significantly more active than the control group at 6 months, F(2, 243) = 4.27, p &lt; .05. The control group had significantly higher levels of reduced motivation at 6 months F(2,372) = 3.534, p &lt; .05. Other subscales of the fatigue measure were not significantly different by group. Conclusions: Phone-based counseling may be a useful tool to increase physical activity among postpartum women, but more research is needed to see if those benefits are sustained.

Healthy rural hearts: The feasibility of a telehealth nutrition randomised controlled trial for rural people at risk of cardiovascular disease.

Improving dietary patterns using medical nutrition therapy delivered via telehealth could make an effective contribution to reducing cardiovascular disease burden in rural Australia. However, it is important that medical nutrition therapy programmes are developed in collaboration with rural stakeholders, to increase feasibility for the rural context and the likelihood of successful implementation. The aim of this study was to evaluate the preliminary feasibility outcomes of integration (implementation), practicality, acceptability, demand, and preliminary effectiveness at the 3-month timepoint of the Healthy Rural Hearts randomised control trial. Feasibility measures were collected from participants in the Healthy Rural Hearts medical nutrition therapy trial. Study participants were patients from eligible primary care practices who had been assessed by their general practitioner as being at moderate to high risk of developing cardiovascular disease in the next five years. The sample in this analysis includes those who had completed the first 3-months of the study. Feasibility outcomes were measured over the first 3-months of the trial intervention. A process evaluation survey was used to collect measures relating to intervention implementation, practicality, acceptability, and demand. Completion rates of the Australian Eating Survey Heart version, Personalised Nutrition Questionnaire, pathology tests and telehealth medical nutrition therapy consultations delivered by Accredited Practising Dietitians were also used to measure intervention practicality. Preliminary effectiveness was evaluated by comparing the intervention group's dietary change, measured using Australian Eating Survey Heart with data from the control group. A total of 105 participants (75 intervention, 30 control participants) were eligible for inclusion in analysis. Attendance rates at the first 3-months of dietitian consultations ranged from 94.7% to 89.3% between the first and 3-month consultations, and most participants were able to complete the Australian Eating Survey Heart and Personalised Nutrition Questionnaire prior to their initial consultation [Australian Eating Survey Heart (n = 57, 76%) and Personalised Nutrition Questionnaire (n = 61, 81.3%)] and the Australian Eating Survey Heart prior to their 3-month consultation (n = 52, 69.3%). Of the participants who completed a pathology test at the 3-month time-point (n = 54, 72%), less than half were able to do so prior to their dietitian consultation (n = 35, 46.7%). Of the 75 intervention participants, 28 (37.3%) completed the process evaluation survey. Intervention participants ranked acceptability of the Healthy Rural Hearts intervention highly (mean rank out of 10 = 9.5, SD 1.9), but provided mixed responses on whether they would access the intervention outside of the study (mean rank out of 10 = 6.0, SD 3.5). There were statistically significant increases in percentage total energy intake derived from nutrient-dense core foods compared to the control group (p ≤ 0.05). The positive findings related to acceptability and implementation outcomes suggest that the Healthy Rural Hearts intervention was acceptable, practical, and able to be implemented within this population living in rural NSW. This, combined with the small to medium effect size in the proportion of total energy derived from nutrient-dense core foods compared to the control group indicates that long-term intervention effectiveness on other cardiovascular disease outcomes is important to evaluate in the future.

External validation of the SI2NCAL2C score for outcomes following cerebral venous thrombosis

ObjectivesPrognostication for cerebral venous thrombosis (CVT) remains difficult. We sought to validate the SI2NCAL2C score in an international cohort. Materials and methodsThe SI2NCAL2C score was originally developed to predict poor outcome (modified Rankin Scale (mRS) 3-6) at 6 months, and mortality at 30 days and 1 year using data from the International CVT Consortium. The SI2NCAL2C score uses 9 variables: the absence of any female-sex-specific risk factors, intracerebral hemorrhage, central nervous system infection, focal neurological deficits, coma, age, lower level of hemoglobin, higher level of glucose, and cancer. The ACTION-CVT study was an international retrospective study that enrolled consecutive patients across 27 centers. The poor outcome score was validated using 90-day mRS due to lack of follow-up at the 6-month time-point in the ACTION-CVT cohort. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Missing data were imputed using the additive regression and predictive mean matching methods. Bootstrapping was performed with 1000 iterations. ResultsMortality data were available for 950 patients and poor outcome data were available for 587 of 1,025 patients enrolled in ACTION-CVT. Compared to the International CVT Consortium, the ACTION-CVT cohort was older, less often female, and with milder clinical presentation. Mortality was 2.5% by 30 days and 6.0% by one year. At 90-days, 16.7% had a poor outcome. The SI2NCAL2C score had an AUC of 0.74 [95% CI 0.69-0.79] for 90-day poor outcome, 0.72 [0.60-0.82] for mortality by 30 days, and 0.82 [0.76-0.88] for mortality by one year. ConclusionsThe SI2NCAL2C score had acceptable to good performance in an international external validation cohort. The SI2NCAL2C score warrants additional validation studies in diverse populations and clinical implementation studies.

Predicting the risk of neurocognitive decline after brain irradiation in adult patients with a primary brain tumor.

Deterioration of neurocognitive function in adult patients with a primary brain tumor is the most concerning side effect of radiotherapy. This study aimed to develop and evaluate normal-tissue complication probability (NTCP) models using clinical and dose-volume measures for 6-month, 1-year, and 2-year Neurocognitive Decline (ND) postradiotherapy. A total of 219 patients with a primary brain tumor treated with radical photon and/or proton radiotherapy (RT) between 2019 and 2022 were included. Controlled oral word association test, Hopkins verbal learning test-revised, and trail making test were used to objectively measure ND. A comprehensive set of potential clinical and dose-volume measures on several brain structures were considered for statistical modeling. Clinical, dose-volume and combined models were constructed and internally tested in terms of discrimination (area under the curve, AUC), calibration (mean absolute error, MAE), and net benefit. Fifty percent, 44.5%, and 42.7% of the patients developed ND at 6-month, 1-year, and 2-year time points, respectively. The following predictors were included in the combined model for 6-month ND: age at radiotherapy > 56 years (OR = 5.71), overweight (OR = 0.49), obesity (OR = 0.35), chemotherapy (OR = 2.23), brain V20 Gy ≥ 20% (OR = 3.53), brainstem volume ≥ 26 cc (OR = 0.39), and hypothalamus volume ≥ 0.5 cc (OR = 0.4). Decision curve analysis showed that the combined models had the highest net benefits at 6-month (AUC = 0.79, MAE = 0.021), 1-year (AUC = 0.72, MAE = 0.027), and 2-year (AUC = 0.69, MAE = 0.038) time points. The proposed NTCP models use easy-to-obtain predictors to identify patients at high risk of ND after brain RT. These models can potentially provide a base for RT-related decisions and post-therapy neurocognitive rehabilitation interventions.