Wilcoxon Matched-pairs Signed-rank Test Research Articles

Omadacycline drug susceptibility testing for non-tuberculous mycobacteria using oxyrase to overcome challenges with drug degradation

BackgroundDrug susceptibility testing (DST) protocol of omadacycline against non-tuberculous mycobacteria has not yet been established. We developed a method to accurately determine MIC omadacycline MIC against Mycobacterium abscessus (Mab), Mycobacterium avium-complex (MAC), and Mycobacterium kansasii (Mkn). MethodsFirst, we identified the oxyrase concentration not affecting Mab, MAC, and Mkn growth followed by omadacycline MIC experiments with and without oxyrase using reference and clinical strains. ResultsOxyrase 0.5 % (v/v) stabilized omadacycline in the culture medium. The median omadacycline MIC was 1 mg/L for Mab and 8 mg/L for Mkn. For MAC, the median omadacycline MIC was 2 mg/L for M. avium, 256 mg/L for M. intracellulare, and 4 mg/L for M. chimaera (p < 0.0001). Wilcoxon matched-pairs signed rank test revealed statistically lower MICs with oxyrase for all MAC subspecies (p < 0.0001), all Mab subspecies (p < 0.0001), and Mkn (p = 0.0002). The decrease in MICs with oxyrase was 17/18 of Mab, 14/19 of Mkn, 8/8 of M. avium, 4/5 M. chimera, but only 11/18 of M. intracellulare (p < 0.013). ConclusionUse of 0.5 % oxyrase could be a potential solution to reliable and reproducible omadacycline MIC of Mab. However, oxyrase demonstrated a variable effect in reducing MICs against MAC and Mkn.

The PocketPerio application significantly increases the accuracy of diagnosing periodontal conditions in didactic and chairside settings

The study aimed to determine the accuracy of diagnosing periodontal conditions using the developed web-based PocketPerio application and evaluate the user’s perspective on the use of PocketPerio. First, 22 third-year dental students (DS3) diagnosed ten cases without PocketPerio (control) and with PocketPerio (test) during a mock examination. Then, 105 DS3, 13 fourth-year dental students (DS4), and 32 senior second-year International Standing Program students (ISP2) used PocketPerio chairside. Statistical analysis was performed using a non-parametric paired two-tailed test of significance with the Wilcoxon matched-pairs signed rank test. The null hypothesis that PocketPerio did not increase the accuracy of periodontal diagnoses was rejected at α < 0.01. Periodontal diagnoses made using PocketPerio correlated with those made by periodontics faculty (“gold standard") in all cases. During the mock examination, PocketPerio significantly increased the accuracy of periodontal diagnoses compared to the control (52.73 vs. 13.18%, respectively). Chairside, PocketPerio significantly increased the accuracy of primary (100 vs. 40.0%) and secondary (100 vs. 14.25%) periodontal diagnoses compared to the respective controls. Students regardless of their training year felt more confident in diagnosing periodontal conditions using PocketPerio than their current tools, provided positive feedback on its features, and suggested avenues for its further development.

Abstract PO4-13-08: Mechanical conditioning (MeCo) score is higher in circulating tumor cells (CTCs) compared to primary tumors in early-stage breast cancer and even higher in metastases compared to CTCs in metastatic breast cancer

Abstract Background: The mechanical conditioning (MeCo) score is a gene expression signature that is acquired early by cancer cells in the primary breast tumor and is reflective of their responsiveness to matrix stiffness (fibrotic-like matrix rigidity). Further, chromatin remodeling in response to stiffness allows cancer cells to retain their aggressive features even in the absence of mechanical stimulation by the primary tumor microenvironment, for instance, during their dissemination through the circulation in metastasis. Importantly, patients who have high MeCo score tumors are at higher risk of developing metastatic breast cancer, compared to low MeCo scores (p&amp;lt; 0.0001; HR=2.2, 95%CI 1.7-2.7; Watson et al 2021, PMID: 34192535). Moreover, circulating tumor cells (CTCs) are associated with higher rate of metastatic dissemination, making CTC detection in the circulation of breast cancer patients a significant prognostic biomarker for breast cancer metastasis. Beyond their enumeration per blood volume units, specific prognostic features of CTCs are not fully explored. We sought to determine whether, compared to primary tumors, CTCs retain high MeCo scores and whether these scores are maintained during late-stage breast cancer in the metastatic sites. Methods: CTCs were isolated from peripheral blood of two patient cohorts: stage II-III breast cancer patients using immunomagnetic enrichment/FACS methodology (Lang et al 2018, PMID: 29868978) and of metastatic breast cancer patients using ANGLE Parsortix microfluidics system (Ring et al 2022, PMID: 35000083). Gene expression profiling using RNA-seq was performed in CTCs and in matching primary tumors (PT) and metastases (MET) for the early-stage and late-stage cohorts, respectively. A quantile normalization approach was used to allow comparison across cohorts. MeCo scores were computed for all samples as per Watson et al 2021. Wilcoxon matched-pairs signed rank test was performed for comparison of MeCo scores from matching samples within each cohort; Mann-Whitney unpaired test was used to compared MeCo scores of CTCs across cohorts. Results: In 12 pairs of early-stage breast cancer patient CTCs and PT, MeCo scores of CTCs were significantly higher than their matched PTs (p=0.026). Furthermore, in 26 pairs of metastatic patient’s CTCs and MET, MeCo scores of METs were significantly higher than matching CTCs (p=0.0004). MeCo scores of CTCs were similar between early- and late-stage breast cancer despite differing CTC isolation strategies (epitope-dependent and microfluidics size gradient). 98% of genes in the MeCo score were present in the evaluable CTC, MET and PT samples. Conclusions: Our results show that the MeCo score is higher in CTCs compared to PTs and in METs compared to CTCs in early- and late-stage breast cancer, respectively. Therefore, the MeCo score is progressively higher throughout the metastatic cascade in breast cancer. These findings demonstrate that mechanical conditioning is retained during metastatic progression, even as cancer cells transition through the circulation where the initial induction by matrix stiffness is lost. Further, these findings support that cancer cells with higher MeCo scores are more competent with–and potentially selected for by–metastatic progression. Importantly, these findings provide a novel feature of CTCs, mechanical conditioning (MeCo), which is associated with higher capacity for metastasis. Further, since the CTC MeCo score is elevated even in early-stage breast cancer, it could provide, in addition to CTC enumeration, a potential prognostic tool to predict metastatic risk in breast cancer patients. Citation Format: Gus Mouneimne, Adam Watson, Adam Grant, Daniel Campo, Alexander Ring, Pushpinder Bains, Julie Lang. Mechanical conditioning (MeCo) score is higher in circulating tumor cells (CTCs) compared to primary tumors in early-stage breast cancer and even higher in metastases compared to CTCs in metastatic breast cancer [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 PO4-13-08.

Robustness analysis of dynamic trajectory radiotherapy and volumetric modulated arc therapy plans for head and neck cancer

Background and purposeDynamic trajectory radiotherapy (DTRT) has been shown to improve healthy tissue sparing compared to volumetric arc therapy (VMAT). This study aimed to assess and compare the robustness of DTRT and VMAT treatment-plans for head and neck (H&N) cancer to patient-setup (PS) and machine-positioning uncertainties. Materials and methodsThe robustness of DTRT and VMAT plans previously created for 46H&N cases, prescribed 50–70 Gy to 95 % of the planning-target-volume, was assessed. For this purpose, dose distributions were recalculated using Monte Carlo, including uncertainties in PS (translation and rotation) and machine-positioning (gantry-, table-, collimator-rotation and multi-leaf collimator (MLC)). Plan robustness was evaluated by the uncertainties’ impact on normal tissue complication probabilities (NTCP) for xerostomia and dysphagia and on dose-volume endpoints. Differences between DTRT and VMAT plan robustness were compared using Wilcoxon matched-pair signed-rank test (α = 5 %). ResultsAverage NTCP for moderate-to-severe xerostomia and grade ≥ II dysphagia was lower for DTRT than VMAT in the nominal scenario (0.5 %, p = 0.01; 2.1 %, p < 0.01) and for all investigated uncertainties, except MLC positioning, where the difference was not significant. Average dosimetric differences compared to the nominal scenario were ≤ 3.5 Gy for rotational PS (≤ 3°) and machine-positioning (≤ 2°) uncertainties, <7 Gy for translational PS uncertainties (≤ 5 mm) and < 20 Gy for MLC-positioning uncertainties (≤ 5 mm). ConclusionsDTRT and VMAT plan robustness to the investigated uncertainties depended on uncertainty direction and location of the structure-of-interest to the target. NTCP remained on average lower for DTRT than VMAT even when considering uncertainties.

Building consensus on priority areas for Sub-Saharan Africa's ageing population research: An e-Delphi study protocol.

Improvement in medico-social services has increased life expectancy and population ageing in Sub-Saharan Africa (SSA). It was estimated that about 163 million people aged 65 and older will be resident in SSA by 2050. There is inadequate ageing research capacity in SSA which necessitates this study to (a) identify a decade-long ageing research opportunities, challenges, and solutions, and (b) prioritize critical ageing research areas and methodologies relevant to the SSA. We designed an e-Delphi protocol following the Reporting Guideline for Priority Setting of Health Research with Stakeholder. The stakeholders will be researchers, practitioners, older adults, and caregivers purposively selected through snowballing quota sampling to complete three rounds of e-Delphi surveys. Round 1 will involve open-ended questions derived from the study objectives. Responses from round 1 will be prepared as a checklist for stakeholders to rate during rounds 2 & 3, using a 9-point scale: low priority (1-3), moderate priority (4-6), and high priority (7-9). The criterion for reaching a consensus will be ≥ 70% of stakeholders rating an item "high priority" and ≤ 15% as "low priority." Quantitative data will be analysed using descriptive statistics, Wilcoxon matched-pairs signed-rank test will be used to assess the stability of stakeholders' responses, and qualitative comments will be analysed using content analysis. Setting aging research/practice priorities will help maximize the benefits of research investment and provide valuable direction for allocating public and private research funds to areas of strategic importance.

Patient-Led Urate Self-Monitoring to Improve Clinical Outcomes in People With Gout: A Feasibility Study.

Self-monitored point-of-care urate-measuring devices are an underexplored strategy to improve adherence to urate-lowering therapy and clinical outcomes in gout. This study observed patient-led urate self-monitoring practice and assessed its influence on allopurinol adherence, urate control, and health-related quality of life. People with gout (n = 31) and prescribed allopurinol self-monitored their urate concentrations (HumaSens2.0plus) at baseline and thereafter monthly for 12 months (3 months per quarter). Adherence to allopurinol was measured using medication event monitoring technology (Medication Event Monitoring System cap). Time spent below the target urate concentration (<0.36 mmol/L) was determined. Health-related quality of life was measured using a survey (EuroQoL EQ-5D-5L). Gout flares were recorded. Two-tailed Spearman correlation and the Wilcoxon matched-pairs signed-rank test (P < 0.05) were used for statistical comparisons. Most participants were male (94%) and had urate concentrations below the target (74%) at baseline. Overall, seven participants demonstrated repeated periods of "missed doses" (two or fewer allopurinol doses missed consecutively) and "drug holidays" (three or more missed doses). Most participants (94%) persisted with allopurinol. Time spent within the target urate concentration increased 1.3-fold (from 79% to 100%; P = 0.346), and the incidence of gout flares decreased 1.6-fold (from 8 to 5; P = 0.25) in the final quarter compared to that in the first quarter of the study. Health-related quality of life was reduced for participants reporting at least one gout flare (median utility values 0.9309 vs 0.9563, P = 0.04). Patient-led urate self-monitoring may support the maintenance of allopurinol adherence and improve urate control, thus reducing the incidence of gout flares. Further research on patient-led urate self-monitoring in a randomized controlled study is warranted.

Characterising vincristine-induced peripheral neuropathy in adults: symptom development and long-term persistent outcomes.

Decades following the introduction of vincristine as treatment for haematological malignancies, vincristine-induced peripheral neuropathy (VIPN) remains a pervasive, untreatable side-effect. However there remains a gap in understanding the characteristics of VIPN in adults. This study presents a comprehensive phenotyping of VIPN. Adult patients (n = 57; age = 59.8 ± 14.6) were assessed cross-sectionally following completion of vincristine (months post treatment = 16.3 ± 15.6, cumulative dose = 7.6 ± 4.4), with a subset of 20 patients assessed prospectively during treatment. Patient reported measures (EORTC-QLQ-CIPN20, R-ODS) were used to profile symptoms and disability. Neurological assessment was undertaken using the Total Neuropathy Score and nerve conduction studies. Sensory threshold and fine motor tasks were also undertaken. Comparisons of data between timepoints were calculated using paired-sample t tests or Wilcoxon matched-pairs signed-rank test. Comparisons between outcome measures were calculated with independent sample t tests or Mann-Whitney U tests for non-parametric data. The majority of patients developed VIPN by mid-treatment (77.8%, 7.0 ± 3.3weeks post baseline) with the prevalence remaining stable by end-of-treatment (75%, 8.1 ± 1.7weeks post mid-treatment). By 3months post-completion, 50% of patients still reported VIPN although there were significant improvements on neurological grading and functional assessment (P < 0.05). VIPN presented with sensorimotor involvement in upper and lower limbs and was associated with decreased sensory and motor nerve amplitudes, reduced fine-motor function and increased disability. VIPN in adults presents as a sensorimotor, upper- and lower-limb neuropathy that significantly impacts disability and function. Neuropathy recovery occurs in a proportion of patients; however, VIPN symptoms may persist and continue to affect long-term quality of life.

Abstract 778: Atorvastatin modulates serum biomarkers in women at increased risk for breast cancer

Abstract Background Tamoxifen and Aromatase inhibitors have been shown to be highly effective at reducing the incidence of ER-positive breast cancers in women at increased risk, but there are no approved agents for the risk reduction of ER-negative cancers. Evidence from observational and preclinical studies supports the study of statins for breast cancer risk reduction. Objective This study aimed to investigate the effects of Atorvastatin treatment on serum and tissue biomarkers in women at increased risk for breast cancer. Methods Women at increased risk for breast cancer were accrued prospectively at UTMDACC, Breast Medical Oncology High-Risk Clinic. The study was approved by the IRB and all participants signed informed consent. High risk was defined as having a previous history of DCIS, LCIS, or atypical hyperplasia, 5-year projected Gail risk &amp;gt;1.67 %, or lifetime risk &amp;gt;20 % calculated by clinical models. Patients were randomized to no treatment (n=15) or daily 10mg (n=15), 20mg (n=14), or 40mg (n=16) Atorvastatin for 3 months. Fasting blood and breast tissue samples via fine needle aspiration (FNA) were collected at baseline and at study completion. Serum biomarkers were analyzed with ELISA (R&amp;D Systems). The IGF1/IGFBP3 molar ratio was calculated using [IGF1 (ng/mL) x 0.13]/[IGFBP-3 (ng/mL) x 0.035]. The Wilcoxon matched-pairs signed rank test was used to determine significance. Results Tissue biomarker evaluation was previously reported. Serum biomarker levels of IGF1 and its main binding proteins IGFBP1 and IGFBP3 were compared in baseline and post-intervention samples by ELISA analysis. The average change in serum IGF1 (ng/mL) levels between pre- and post-treatment samples (represented as average difference with interquartile range) was +3.5 (-16.8 to 8.7) p=0.98, -0.6 (-23.6 to 15.4) p=0.64, -1.76 (-27.7 to 28.6) p=0.81, and +2.6 (-14.5 to 32.2) p=0.67 in the 0, 10, 20, and 40mg groups respectively. The average change in serum IGFBP1 (pg/mL) was -23.2 (-2372 to 4487) p=0.33, -480 (-4567 to 3008) p=0.72, 429 (-1259 to 3039) p=0.54, and -250 (-3581 to 2492) p=0.94 in the 0, 10, 20, and 40mg groups. The average change in serum IGFBP3 (ng/mL) was -24 (-193 to 98) p=0.72, -119 (-353 to 111) p=0.17, -190 (-433 to 14) p=0.07, and -234 (-369 to -79) p=0.002 in the 0, 10, 20, and 40mg groups. Serum IGF1/IGFBP3 molar ratio was +0.012 (-0.018 to 0.026) p=,0.76, +0.0065 (-0.013, to 0.047) p=0.53, +.0073 (-0.036 to 0.045) p=0.86, and +.027 (-.011 to .062) p=0.058 in the 0, 10, 20, and 40mg groups. Conclusions Serum IGFBP3, which has been associated with breast cancer risk, was decreased in a dose-dependent manner in patients treated with Atorvastatin. The IGF1/IGFBP3 molar ratio was increased in the 40mg group, although not statistically significant (p=.0577). This shows that treatment with Atorvastatin induced changes in circulating biomarkers and that Atorvastatin could be further studied in larger prospective breast cancer prevention trials. Citation Format: Amanda L. Lanier, Johannes Fahrmann, Fatma N. Mustafayev, Angelica Gutierrez Barrera, Powel H. Brown, Banu Arun. Atorvastatin modulates serum biomarkers in women at increased risk for breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 778.

Abstract 6131: Increasing self efficacy, self confidence, and genetic knowledge via the Community Genetic Navigation Engagement Specialist Train-the-Trainer program

Abstract Background: Colorectal cancer (CRC) is the second and third leading cause of cancer deaths in US Hispanic/Latino (H/L) men and women, respectively. The Community Genetic Navigation Specialists (CoGENES) train-the-trainer program created a workforce of community health workers (CHWs) to educate H/L individuals about genetic testing, counseling, and research. Methods: The CoGENES three-week program, consisted of six in-person sessions, with a curriculum in both Spanish/English developed and delivered by experts, in Spanish, using presentations and hands-on activities. Acculturation, Latino values, self-efficacy, genetics and tumor testing knowledge, and self-confidence were assessed via pre- and post-training. Differences in scores were analyzed via Wilcoxon matched-pairs signed-rank tests with exact p-values. Results: Median age of the 12 participants was 50 (IQR = 12), 9 were female, 92% were Mexican-born, half completed 1-2 years of college, and 67% were very hispanic oriented. Self-efficacy increased after training, with pre- training median-score = 38.5 (IQR = 3) and post-training score = 39.5 (IQR =2.5) (p = 0.0547). Certainty about understanding tumor testing increased after training (p = 0.0039). The median number of correct answers on the 16-item genetic knowledge scale increased from 6.5 to 9.5 and the median number of “don’t know” responses decreased from 5 to 0 after training. Finally, self-confidence to train future CoGENES was significantly higher (p = 0.0098) at post-test. Conclusion: The CoGENES culturally tailored program led to improved self-efficacy, increased genetic knowledge, and self-confidence in a cohort of Hispanic community health educators. Findings will be shared within COPECC, and other NCI funded programs. Citation Format: Janet Rodriguez, Joel Sanchez Mendez, Yaneth L. Rodriguez, Lourdes Baezconde-Garbanati, Charité Ricker, Rosa Barahona, Bianca Rosales, Daisy Hernandez, Natalia Gutierrez, Julie Culver, Mariana Stern. Increasing self efficacy, self confidence, and genetic knowledge via the Community Genetic Navigation Engagement Specialist Train-the-Trainer program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6131.

Deciphering the Mysteries of Aromatic Incentive of Lemongrass Essential Oil Inhalation on Brain Activities in Healthy Adults

With the rapid advancement in brain science and imaging technology, there is a growing interest in investigating the connection between aromatherapy and its effects on the brain. This study employs Quantitative Electroencephalography (QEEG) to examine the impacts of exposure to the fragrance of lemongrass essential oil (LEO) on specific brain regions. The objective is to assess the influence of inhaling the scent of LEO on EEG patterns in awake, healthy adult females using power spectral analysis. In this experimental study, 30 healthy adult female participants were exposed to a water mist as a control after baseline recordings. Subsequently, participants inhaled LEO aromatic mist diffused into the room air, and their brain activity was recorded. Data from specific scalp electrode readings were analyzed using the Wilcoxon Matched-Pairs Signed Rank Test. The results revealed a significant increase in the relative power of alpha waves in the prefrontal, frontal and occipital regions, accompanied by heightened theta power and decreased beta power. These results suggests that the inhalation of LEO oil modulates brainwave activities, inducing relaxing effects on the brain.

Novel use of contrast enhanced ultrasonography with urodynamics in children: A comparison study to fluoroscopy.

Video urodynamics (UDS) has classically been performed using fluoroscopy (fluoro). Contrast enhanced voiding ultrasonography (ceVUS) has rarely been reported for use with UDS. This is the first study to compare the imaging characteristics of ceVUS versus fluoro UDS. Children were enrolled for ceVUS UDS who previously underwent fluoro UDS. Demographics, imaging data for ceVUS and fluoro UDS, time between studies, and clinical data between studies were recorded. Changes in clinical status included implantation/cessation of catheterization or anticholinergic medications, leakage between, urinary tract infections, hydronephrosis and neurologic changes. Comparison testing was performed using McNemar's Chi-Squared and Wilcoxon matched-pairs signed rank test. Seventy-five children were recruited. Median time between studies was 1.3 years (IQR 0.9-2.9). There were no differences for bladder shape (p = 0.59), vesicoureteral reflux (p = 0.10), bladder neck (p = 0.59) or urethra (p = 1.0) between studies. In 5 cases, the bladder neck could not be visualized adequately due to layering of the microbubble contrast against urine. Benefits to ceVUS included ability to visualize the exact moment the bladder neck opened. Following exclusion of patients with clinical changes that might affect imaging findings, an analysis of 28 patients demonstrated no differences between the two studies. CeVUS can be used adequately in conjunction with UDS. Limitations to ceVUS include more granular imaging for bladder shape versus fluoro and inability to visualize bladder neck if residual urine is in the bladder, mitigated by bladder emptying. Benefits include ability to visualize the dynamic activity of the bladder neck due to constant imaging with ceVUS.

520 - Evaluating the expression of OX40 and OX40 ligand in lesional skin versus non-lesional skin in volunteers with atopic dermatitis and in healthy control skin

Abstract Introduction/Background Growing evidence suggests that blocking the OX40 ligand (OX40L)/OX40 costimulatory pathway could have therapeutic effects in inflammatory diseases such as atopic dermatitis (AD). Amlitelimab (SAR445229; KY1005) is a potential first-in-class, fully human, non-depleting anti-OX40L monoclonal antibody that blocks OX40L-OX40 interactions. We report OX40L and OX40 expression from skin biopsies collected in two studies: an amlitelimab Phase 2a (Ph2a) study in patients with moderate-to-severe AD, and a small-scale study of patients with mild AD and healthy volunteers. Objectives Assess OX40L and OX40 expression in AD skin (lesional and non-lesional) and healthy control skin. Methods As part of a Ph2a randomized, double-blind, placebo-controlled study (NCT03754309) of amlitelimab in moderate-to-severe AD, 174 baseline-paired lesional/non-lesional skin biopsies were collected from all patients (n=87). In a separate small-scale study, 24 skin biopsies were collected, including healthy control skin from healthy volunteers (n=6) and paired lesional/non-lesional skin from patients with mild AD (n=9). Each biopsy underwent immunohistochemical (IHC; formalin-fixed paraffin-embedded) analyses using various antibodies (OX40L: rabbit IgG antibody from Cell Signaling Technology for Ph2a biopsies, proprietary mouse IgG2a KY1005 for small-scale study biopsies; OX40: clone Ber-ACT35 from BioLegend for all biopsies). A trained pathologist assessed IHC staining in the dermis and/or epidermis using semi-quantitative scoring (0 [no stained cells] to 10 [all cells stained]) or quantitative methods (cells/mm2, Tissue Studio 4.0, and HALO link image analysis software). Wilcoxon matched-pairs signed-rank test was used to assess IHC staining of Ph2a biopsies. Ph2a biopsies also underwent transcriptomic analyses (stored in RNALater) for OX40L (TNFSF4) and OX40 (TNFRSF4) on sequenced RNA using a linear mixed model with Benjamini-Hochberg adjustment. Results In baseline Ph2a biopsies, IHC analysis revealed elevated OX40L and OX40 staining in lesional versus non-lesional AD skin (P &amp;lt;0.0001 for both markers). For OX40L, the median score was 3 (lesional) versus 1 (non-lesional) and the Wilcoxon matched-pairs signed-rank test found P&amp;lt;0.0001. For OX40+ cells, the median expression was 179.8 cells/mm2 in lesional AD skin versus 54.45 cells/mm2 in non-­lesional AD skin (P&amp;lt;0.0001 using the Wilcoxon matched-pairs signed-rank test). These findings were confirmed by RNA sequencing analysis, with TNFSF4 (OX40L) and TNFRSF4 (OX40) differentially expressed in lesional and non-lesional AD skin (P&amp;lt;0.01 and P&amp;lt;0.0001, respectively). A larger scale study is ongoing that may further support this finding. In the small-scale study including patients with mild AD and healthy volunteers, there was a trend for an increase of mean OX40L+ and OX40+ cells/mm2 in lesional skin versus non-lesional skin and healthy control skin in the dermis and epidermis (OX40L+ dermal lesional, non-lesional, healthy, respectively: 17.6, 11.2, 11.5; OX40L+ epidermal: 5.8, 2.1, 1.9; OX40+ dermal: 5.7, 2.1, 0.4; OX40+ epidermal: 10.9, 9.0, 1.8); the increase was significant for lesional versus healthy control skin for dermal OX40+ cells/mm2 (P&amp;lt;0.001). Conclusions We confirm with IHC and RNA sequencing that OX40L and OX40 expression is elevated in skin lesions of patients with moderate-to-severe AD. We also demonstrate a trend to elevated OX40L and elevated OX40 in mild AD skin versus healthy volunteers. A potential explanation for the lower levels of OX40L and OX40 in patients with mild AD in this study may be their lower disease severity versus Ph2a study patients. These findings support the OX40L/OX40 pathway as a relevant target in T cell immune dysregulation; its blockade may represent a novel treatment approach for moderate-to-severe AD.

Determining Adherence to Inhaled Corticosteroids From the Epic Electronic Medical Record

OBJECTIVE Often we call the patient’s pharmacy to obtain a refill history to assess inhaled corticosteroid (ICS) adherence. The purpose of this project was to determine the accuracy of refill histories for ICS (with or without long-acting beta agonist) listed in Epic’s Medication Dispense History. METHODS We evaluated 61 patients and used data from 38 who met the following criteria: 1) under the care of the UF Pediatric Severe Asthma Clinic; 2) taking the same dose of the same ICS product for 6 months before the patient’s last clinic visit; and 3) having data available from the pharmacy where the last ICS prescription was electronically sent. We called the pharmacies to obtain a verbal report of their refill record. Then, we compared the number of refills reported to the number listed in Epic’s records using a Wilcoxon matched-pairs signed-ranks test. RESULTS Of the 293 refill dates listed in Epic, 157 were duplicates, giving a 54% error. After deleting duplicates, the mean (SD) number of refills listed in Epic was 3.6 (2.0) compared with 3.3 (2.0) in pharmacies over a period of 6 months (p &amp;lt; 0.0001). After removing duplicates Epic correctly reported the total number of refills for 30 of the 38 patients (78.9%). Seven of the remaining patients had more refills listed in Epic while 1 patient had more refills dispensed. CONCLUSION This study indicates that our version of Epic over-reports refills thus limiting assessment of adherence. In contrast, absence of refills in Epic is a clear indication of poor adherence.

Safe Fall Recovery Education for Older Adults.

High fall rates among older adults in combination with prolonged time on the floor after a fall have created an urgent need to preventatively address fall recovery strategies. The purpose of this study is to describe the outcomes of a novel safe fall recovery (SFR) educational module provided by physical therapists to older adults in their homes. A pre- and post-test descriptive study used a convenience sample to recruit 30 adults (≥65 years). A baseline assessment and SFR in-home education were provided. Pre- and post-education measures included the Steps for Safe Fall Recovery (Steps for SFR) tool, the Activity Specific Balance Confidence (ABC) scale, and a fall confidence survey. The Wilcoxon matched-pairs signed-rank test determined significance (P < .05). Participants were age 77.2 (6.8) years and 20 females. Eight reported a fall during the prior year. Statistically significant improvements were identified in the Steps to SFR tool (P = .001), the ABC scale (P = .004), and the fall recovery confidence survey (P = .001). Integration of an SFR educational intervention delivered to an older adult population in their home demonstrated improved safety and confidence to recover from a fall.

Feasibility of frozen soft tissues to simulate fresh soft tissue conditions in cone beam CT scans.

To evaluate the feasibility of frozen soft tissues in simulating fresh soft tissues of pig mandibles using cone beam CT (CBCT). Two fresh pig mandibles with soft tissues containing 2 tubes filled with a radiopaque homogeneous solution were scanned using 4 CBCT units and 2 field-of-view (FOV) sizes each. The pig mandibles were deep-frozen and scanned again. Three cross-sections were exported from each CBCT volume and grouped into pairs, with one cross-section representing a fresh and one a frozen mandible. Three radiologists compared the pairs and attributed a score to assess the relative image quality using a 5-point scale. Mean grey values and standard deviation were obtained from homogeneous areas in the tubes, compared using the Wilcoxon matched-pair signed-rank test and subjected to Pearson correlation analysis between fresh and frozen physical states (α = .05). Subjective evaluation revealed similarity of the CBCT image quality between fresh and frozen states. The distribution of mean grey values was similar between fresh and frozen states. Mean grey values of the frozen state in the small FOV were significantly greater than those of the fresh state (P = .037), and noise values of the frozen state in the large FOV were significantly greater than those of the fresh state (P = 0.007). Both mean grey values and noise exhibited significant and positive correlations between fresh and frozen states (P < 0.01). The freezing of pig mandibles with soft tissues may serve as a method to prolong their usability and working time when CBCT imaging is planned.

An Investigation of Inter-Rater and Intra-Proxy Agreement in Measuring Quality of Life of Children in the Community Using the EQ-5D-Y-3L.

Self-reporting of health-related quality of life (HRQoL) in children is not always feasible. To date, proxy perspectives (Proxy versions 1 and 2) using the EQ-5D-Y-3L have not been explored for its impact on agreement with child self-report. Proxy version 1 requires the proxy to consider their own view of the child's HRQoL (proxy-proxy), while with Proxy version 2, the proxy is asked to respond as they believe their child would self-report their HRQoL (proxy-child). This study compared the inter-rater and intra-proxy agreement (overall and dimension level) using the EQ-5D-Y-3L self, proxy-proxy, and proxy-child reports. A community-based sample of child (aged 6-12 years) and parent dyads were invited to participate in a semi-structured interview. The child self-completed the EQ-5D-Y-3L independently of the parent who completed the EQ-5D-Y-3L from proxy-proxy and proxy-child perspectives. Agreement was determined using Concordance Correlation Coefficients (CCCs) for the overall (preference-weighted) HRQoL, while agreement at the dimension level was evaluated using Gwet's agreement coefficient (AC1). To assess the differences between the self and the two proxy reports, the Wilcoxon matched-pair signed-rank test was used. This study involved 85 child-parent dyads. The agreement between self and proxy overall HRQoL was low (fair) with both proxy-proxy (CCC=0.28) and proxy-child (CCC=0.26) reports. The largest discrepancy in the child-proxy agreement at dimension level with both the proxy versions was observed for 'feeling worried, sad or unhappy'. Within this dimension, the proxy-child perspective resulted in a stronger agreement (AC1=0.7, good) with child self-report compared with the traditional proxy-proxy perspective (AC1=0.58, moderate). Although the preference-weighted HRQoL was consistent across both the proxy perspectives, a significant difference was observed in the EQ VAS scores (p=0.02). This study demonstrates that choice of proxy perspective may have an impact on the problems reported on HRQoL dimensions and EQ VAS scores. However, in this community-based sample of generally healthy children, no significant difference was observed in the inter-rater agreement for child-self and proxy preference-weighted EQ-5D-Y-3L values based on proxy perspectives. While this suggests that preference-weighted data are not sensitive to the choice of perspective, these findings may differ for different HRQoL instruments and for alternative value sets with different properties.

The effectiveness of community-based interprofessional education for undergraduate medical and health promotion students

BackgroundCommunity-based interprofessional education (CBIPE) has been proven effective in enhancing the interprofessional competencies of medical and health professional students. However, there is a lack of evaluation on the impact of experiential CBIPE among undergraduate medical and health promotion students in Thailand. Therefore, the objective of this study is to assess the influence of CBIPE learning on the collaborative competencies of these students.MethodsA one-group pre-posttest design in 193 (152 medical students and 41 health promotion) students were involved in the CBIPE program, later divided into 12 groups. Data was collected by direct observations of mentors using the Interprofessional Collaborative Competencies Attainment Survey (ICCAS). The Wilcoxon matched-pairs signed-rank test was conducted to evaluate the effectiveness of the CBIPE program.ResultsA total of 175 (90.67%) completed ICCAS and satisfaction questions before and after the CBIPE program. The mean age of respondents was 20.29 ± 1.63 years; 60.57% were women and 39.43% were men. The results showed a significant increase in collaborative competencies before and after the 2-week course. Gender-stratified analysis showed an improvement after CBIPE training for all subscales in women, while the communication, collaboration, conflict management, and functioning team skills segment score was significantly higher in the post-assessment among men.ConclusionThe implementation of CBIPE learning was successful in enhancing collaborative competencies among both medical and health promotion students. These findings will provide valuable insights for the design and improvement of CBIPE learning programs in other universities.

P1072 Upadacitinib appears effective in inducing clinical, biochemical, endoscopic and histologic improvements in previously treatment refractory Ulcerative Colitis

Abstract Background Upadacitinib is a novel, oral agent which acts by inhibition of JAK signaling. It has proven efficacy in large-scale, randomised trials for the treatment of UC. We report our real-world experience of upadacitinib as induction therapy in a single centre study of UC patients, including patients who were refractory or intolerant of other advanced therapies. Methods We performed a retrospective analysis of outcomes in patients who were commenced on upadacitinib for UC at a tertiary IBD centre between October 2022 to October 2023. The parameters used to assess disease activity were the Simple Clinical Colitis Activity Index (SCCAI), faecal calprotectin (FCP), Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and Nancy Histological Index (NHI). Clinical response was defined as a reduction of SCCAI of ≥3 points, clinical remission as SCCAI of ≤2, biochemical remission as FC&amp;lt;150ug/g. Endoscopic remission was defined as UCEIS 0-1 and histological remission as NHI 0-1. Medical records were reviewed for patient-reported adverse events. Wilcoxon matched-pairs signed rank test was used to compare pre- and post-treatment continuous variables. Results 42 patients were started on 45mg once daily upadacitinib over this period. 20 were female, the mean age was 39. 31 had left sided disease, 8 had pancolitis. 39 (93%) patients had prior experience of advanced therapy and 22 (52%) had ≥2 prior therapies. At baseline, mean SCCAI was 7 (1-15), and mean FCP 1328 (42-6810) μg/g. Baseline endoscopy demonstrated a mean UCEIS of 5 (3-7) and baseline histology a mean NHI of 3 (1-4). At the 6-week follow up, paired data on clinical and biochemical responses were available in 23 and 27 patients respectively, showing an improvement to a mean SCCAI of 3 (p=0.0004) and mean FCP of 491 μg/g (p=0.002). 16 (70%) achieved clinical response, 14 (61%) were in clinical remission. 15 (56%) had a reduction in FCP to &amp;lt;150 μg/g. Endoscopic reevaluation took place after a minimum of 12 weeks on treatment. Paired endoscopic outcomes in 20 patients demonstrated an improvement of UCEIS to a mean of 1 (p&amp;lt;0.0001), with 16 (80%) patients in endoscopic remission. Week 12 histology showed improvement to a mean NHI of 2 (p&amp;lt;0.0001, n=19), with 9 (47%) patients achieving histological remission. 6 (14%) patients were non-responders. 3 required a colectomy, 2 necessitated a switch in medical therapy, 1 remained on extended induction. 3 patients (7%) reported facial acne as an adverse event, no others were reported. Conclusion Upadacitinib appears effective at inducing significant clinical, biochemical, endoscopic and histological improvements within 12 weeks, amongst a real-world cohort of patients with moderate-to-severe UC that has proved refractory to other advanced therapies.

Do the Various Indirect Bonding Techniques Provide the Same Accuracy for Orthodontic Bracket Placement? (Randomized Clinical Trial).

For orthodontic treatment to be effective, bracket placement must be precise to make the finishing stage easier, leading to an ideal occlusion with minimal intervention. This study aimed to evaluate the accuracy of manual and digital bracket positioning techniques utilizing computer-aided design and computer-aided manufacturing (CAD/CAM) jigs, 3D-printed indirect bonding trays (IBT), and double-layer vacuum-formed thermoplastic IBT. This study was done by scanning the dental arch of 30 orthodontic patients. The virtual setup and bracket positioning were performed with the Insignia™ system for ten patients, and 3D Maestro® software was used for the virtual setup of the remaining 20 patients. At the same time, the bracket positioning of 10 patients was done digitally by the 3D Maestro® software and the remaining 10 patients manually through the Ray Set® device. IBT were fabricated by CAD/CAM system, 3D printer, and vacuum-formed thermoplastic machine. A virtual bracket position was compared to the actual bracket position using the best-fit method of 3D digital superimposition in Geomagic® Control X™ (CX) software to determine how accurate it was in terms of linear and angular accuracy. Statistical analyses using SPSS 26.0 including Bland-Altman plots were used to assess the intra-examiner reproducibility. Shapiro-Wilk test was used to measure normality distribution. Wilcoxon matched-pairs signed rank test was used to analyze the differences between bracket positions within each group. Although there were obvious positional discrepancies between several readings, they were still within clinically acceptable ranges. All types of IBT would translate the planned position of the bracket from the digital and manual techniques to the teeth of patients with accepted precision in both linear and angular measurements; in addition, the error rate is about the same for all types of IBT. This trial is registered with NCT05549089.

Mental health dynamics of adolescents: A one-year longitudinal study in Harari, eastern Ethiopia.

This study aims to assess the dynamics of in-school adolescents' mental health problems in Harari regional state, eastern Ethiopia for a year. Using multistage sampling technique, we conducted a year-long longitudinal study at three public high schools between March 2020 and 2021. Three hundred fifty-eight in-school adolescents were chosen by systematic random sampling for the baseline assessment, and 328 completed the follow-up assessment. We used self-administered, adolescent version of SDQ-25 Questionnaire to collect the data. Wilcoxon matched-pairs signed-rank test and McNemara's Chi-squared tests were used to examine the median difference and distribution of mental health problems between times one and two. Random-effects logistic regressions on panel data was used to identify factors associated with mental health problems. A p-value < 0.05 was considered as statistically significant. The magnitude of overall mental health problems at baseline assessment was 20.11% (95% CI: 16-25), with internalizing problems accounting for 27.14% (95% CI: 23-32) and externalizing problems accounting for 7.01% (95% CI: 4.6-10.3). At the follow-up assessment, these proportions rose to 22.56% (95% CI, 18-27) for overall problems and 10.3% (95% CI, 7.7-14.45) for externalizing problems. On other hand, internalizing problems decreased unexpectedly to 22.86% (95% CI, 18.6-27.7) at follow-up assessment. Internalizing problem scores at time two were significantly lower than baseline among older adolescents, girls and those with average wealth index in our study cohort. The prevalence of mental health problems were high among the study cohort. The proportion of overall problems and externalizing problems has increased over time, indicating a deterioration in the mental health of the study cohort. However, the decrease in internalizing problems among older adolescents, girls, and those with an average wealth index is a positive sign. The findings highlight that tailored interventions are required to reduce externalizing problems and maintain the decrease in internalizing problems. These interventions should target middle-aged and male adolescents from low-income families.