Baseline Measurements Research Articles

Pay Attention to Hypertension (PAtH): Findings from a cardiovascular health promotion intervention for adults with intellectual disabilities participating in Special Olympics programming.

Cardiovascular disease (CVD) affects adults globally. People with intellectual disabilities (PWID) may be at higher risk of CVD and associated risk factors (e.g. obesity, hypertension, and diabetes). We developed Pay Attention to Hypertension (PAtH), a cardiovascular health promotion intervention, and tested its impact on changes in blood pressure (BP), lifestyle behaviours and health-related empowerment among PWID. PAtH was developed with a Special Olympics community organisation that supports PWID in developing self-confidence and social skills through participation in sports. The 6-month intervention consisted of 1-h individualised virtual sessions delivered monthly by nursing students/novice nurses. Sessions covered specific themes, including monitoring BP, adopting healthy lifestyles and managing stress, and were individually tailored to the capacities and needs of participants. A single group pre-post-intervention design was used to assess the intervention's effects among participants who completed the intervention and data collection. Data included baseline and follow-up BP measurements from 7-day logbooks and questionnaires assessing lifestyle behaviours [physical activity (PA), screen time and diet], and health-related empowerment. Seventy-four participants were included in the analyses. Between baseline and follow-up, there were no changes in systolic and diastolic BP, PA or leisure screen time. The proportion of participants who reported adding salt when cooking decreased from baseline to follow-up (19.7% vs. 12.7%, P=0.034), and we found improvements for several items measuring health-related empowerment (P≤0.003). Improvements in health-related empowerment were found following PAtH. More intensive interventions may be needed to result in changes in lifestyle behaviours and BP. The integration of adapted cardiovascular health promotion initiatives within well-established community organisations such as Special Olympics is a promising avenue to contribute to cardiovascular health promotion among PWID.

A Fast 3D Range-Modulator Delivery Approach: Validation of the FLUKA Model on a Varian ProBeam System Including a Robustness Analysis

A 3D range-modulator (RM), optimized for a single energy and a specific target shape, is a promising and viable solution for the ultra-fast dose delivery in particle therapy. The aim of this work was to investigate the impact of potential beam and modulator misalignments on the dose distribution. Moreover, the FLUKA Monte Carlo model, capable of simulating 3D RMs, was adjusted and validated for the 250 MeV single-energy proton irradiation from a Varian ProBeam system. A 3D RM was designed for a cube target shape rotated 45° around two axes using a Varian-internal research version of the Eclipse treatment planning software, and the resulting dose distribution was simulated in a water phantom. Deviations from the ideal alignment were introduced, and the dose distributions from the modified simulations were compared to the original unmodified one. Finally, the FLUKA model and the workflow were validated with base-line data measurements and dose measurements of the manufactured modulator prototype at the HollandPTC facility in Delft. The adjusted FLUKA model, optimized particularly in the scope of a single-energy FLASH irradiation with a PMMA pre-absorber, demonstrated very good agreement with the measured dose distribution resulting from the 3D RM. Dose deviations resulting from modulator-beam axis misalignments depend on the specific 3D RM and its shape, pin aspect ratio, rotation angle, rotation point, etc. A minor modulator shift was found to be more relevant for the distal dose distribution than for the spread-out Bragg Peak (SOBP) homogeneity. On the other hand, a modulator tilt (rotation away from the beam axis) substantially affected not only the depth dose profile, transforming a flat SOBP into a broad, Gaussian-like distribution with increasing rotation angle, but also shifted the lateral dose distribution considerably. This work strives to increase awareness and highlight potential pitfalls as the 3D RM method progresses from a purely research concept to pre-clinical studies and human trials. Ensuring that gantry rotation and the combined weight of RM, PMMA, and aperture do not introduce alignment issues is critical. Given all the other range and positioning uncertainties, etc., not related to the modulator, the RM must be aligned with an accuracy below 1° in order to preserve a clinically acceptable total uncertainty budget. Careful consideration of critical parameters like the pin aspect ratio and possibly a novel robust modulator geometry optimization are potential additional strategies to mitigate the impact of positioning on the resulting dose. Finally, even the rotated cube 3D modulator with high aspect ratio pin structures (~80 mm height to 3 mm pin base width) was found to be relatively robust against a slight misalignment of 0.5° rotation or a 1.5 mm shift in one dimension perpendicular to the beam axis. Given a reliable positioning and QA concept, the additional uncertainties introduced by the 3D RM can be successfully managed adopting the concept into the clinical routine.

Is It Possible for Single-shade Composites to Mimic the Color, Lightness, Chroma, and Hue of Other Single-shade Composites? An In Vitro Study.

This study aimed to assess color matching post-repair using the same or different single-shade composites of three distinct composite resin materials (Omnichroma-OM, ZenChroma-ZC, and Charisma Topaz One-CTO) following aging in coffee solution and distilled water. Evaluation focused on color change parameters (ΔE00, ΔL00, ΔC00, and ΔH00). Specimens were prepared in disk shape with a diameter of 8 mm and a height of 2 mm (n=180). Half of each composite group was immersed in distilled water, while the other half was immersed in coffee solution for 12 days each (n=90). After aging, cylindrical cavities with a diameter of 4 mm and a depth of 1 mm were prepared at the center of the specimens. The cavities were repaired with both themselves and other composite resins (n=10). Color measurements of the specimens were performed using VITA Easyshade 5 (VITA Zahnfabrik, Bad Säckingen, Germany) at the following time points: baseline (T0), after aging (12 days) (T1), immediately after repair (T2), one day after repair (T3), one week after repair (T4), and one month after repair (T5). Statistically significant differences were found in the mean ΔE00 measurements among the study groups at all time points for each of the three composite resins (p<0.05). Similarly, statistically significant differences were found in the mean ΔE00 measurements over time for each of the three composite resins in each study group (p<0.05). The baseline measurements of materials repaired with themselves in the distilled water groups and the final measurements of materials repaired with themselves in the coffee groups were found to be within acceptable ΔE00limits. At the end of the study, only CTO repaired with OM showed acceptable color matching with different composites in both coffee and distilled water groups. Acceptable color matching was achieved when using the same material for repair in specimens aged in distilled water and coffee. However, variations in matching were observed when different materials were used for repair, indicating the need for ongoing monitoring. Contributions of ΔL00, ΔC00, and ΔH00 values to color differences vary depending on the resins and repair process and change over time.

Acute ergogenic effects of repetitive maximal breath-holding maneuvers on hematological and physiological responses: a graded exercise test investigation.

Repetitive maximal breath-holds (BHs or apneas) have been noted to induce advantageous hematological and blood buffering changes. Building on this, the hypothesis was formulated that the execution of repeated maximal BH efforts might lead to subsequent enhancements in performance during a time-to-exhaustion test. This study investigated the acute effects of five static maximal breath-holding maneuvers conducted with face immersion in cold water (10°C) on subsequent graded exercise test (GET) performance. Seventeen well-trained participants completed a GET on a motorized treadmill under two randomized cross-over conditions: baseline measurement (CON) and after five repeated maximal breath-holding efforts (EXP). The GET protocol consists of incremental increases in speed until exhaustion. After the fifth breath-hold, participants in the EXP condition exhibited significant (P < 0.05) increases in hematocrit, hemoglobin concentration, red blood cell count, and muscle deoxygenation, accompanied by a reduction in blood lactate concentration (4.09 ± 2.21%, 3.9 ± 1.76%, 3.96 ± 2.1%, 81.48 ± 23.83%, and 15.22 ± 17.64%, respectively), compared to CON. During GET, the EXP condition showed a significantly (P < 0.05) delayed onset time of the second ventilatory threshold (3.14 ± 5.85%) and (P < 0.05) increased time to exhaustion (0.75 ± 1.02%). This evidence suggests that repeated maximal static breath-holding maneuvers enhance the oxygen delivery system by increasing the circulation of reserve red blood cells, heightened muscle oxygen deoxygenation, enhanced aerobic metabolism utilization, and postponing the transition from aerobic to anaerobic metabolism, implying a potential ergogenic effect. While pre-exercise breath-holding shows promise for improving time-to-exhaustion and optimizing subsequent distance running performance, further in-depth investigation is essential to fully elucidate the underlying mechanistic factors.

A randomised controlled trial to determine the effect of genotype-based personalised diet and physical activity advice for FTO genotype (rs9939609) delivered via email on healthy eating motivation in young adults.

The prevalence of obesity continues to rise, and public health dietary recommendations are not being adhered to. The transition to higher education is a period of risk for weight gain in young adults and has been demonstrated as a good time to initiate behaviour change. A genotype-based personalised approach to dietary recommendations may motivate young adults to maintain or adopt positive dietary behaviours. The aim of the present study was to determine the efficacy of genotype-based personalised dietary and physical activity advice on healthy eating motivation in young adults. Participants were young adults (n = 153), aged 18-25 years. Baseline measures (participant characteristics, height, weight, body mass index [BMI], body fat percentage [BF%], healthy eating motivation and physical activity) were collected. Participants were genotyped for a SNP in the FTO gene (rs99396090) and randomly allocated (stratified for genotype) to three different groups (1. Genotype-based personalised advice: dietary and physical activity advice based on genotype, BMI and reported physical activity; 2. Non-genotype-based personalised advice: dietary and physical activity advice based on BMI and reported physical activity; 3. Control: no advice). A week after receipt of advice delivered via email, participants completed the healthy eating motivation questionnaire for a second time. Genotype-based personalised dietary advice did not affect healthy eating motivation: when participants were analysed across the whole group (p = 0.417), when analysed according to those informed of a risk or non-risk-associated genotype (p = 0.287), or when analysed according to those with a BMI (>25 kg/m2; p = 0.336) or BF% (male >18%, female >31%; p = 0.387) outside the healthy range. There was also no significant difference in healthy eating motivation at 1-week in the control or non-genotype-based advice groups. Genotype-based personalised advice for the prevention of obesity did not affect healthy eating motivation in this group of healthy, young adults.

The Short-term Effect of Caffeine Consumption on Reading Performance

Objective: Caffeine, a widely consumed psychoactive substance, is recognized for its cognitive-enhancing effects, notably enhancing performance on tasks requiring narrative comprehension, where it has been shown to boost both acuity and speed. This study investigates the impact of caffeine intake on reading acuity and evaluates changes in reading speed post-caffeine consumption. Material and Methods: Employing a cross-sectional design, nineteen participants with distance best-corrected vision of 6/6 or better (equivalent to logMAR 0.00 or better) (mean age=22.5±1.00 years old) and near vision of 0.1 logMAR (N5) were recruited. Baseline measurements of reading acuity and speed were taken using the article sourced from Perpustakaan Tun Abdul Razak (PTAR) and Buari-Chen Malay Reading Chart (BCMRC) before coffee consumption, respectively. Participants consumed 200 mg of Nescafe Gold (caffeine) before the subsequent assessment. The time taken to read the reading materials was recorded, alongside any errors. Results: While reading speed significantly increased post-caffeine consumption (t=-7.536, p-value&lt;0.001), reading acuity remained unaffected (t=-0.378, p-value=0.705). These results suggest a moderate dose of 200 mg of caffeine can enhance reading speed without compromising acuity in young adults.Conclusion: This indicates that caffeine mainly affects the rate of reading, while it does not alter the reading acuity of individuals.

Effects of Exercise Training on Mitochondrial and Capillary Growth in Human Skeletal Muscle: A Systematic Review and Meta-Regression.

Skeletal muscle mitochondria and capillaries are crucial for aerobic fitness, and suppressed levels are associated with chronic and age-related diseases. Currently, evidence-based exercise training recommendations to enhance these characteristics are limited. It is essential to explore how factors, such as fitness level, age, sex, and disease affect mitochondrial and capillary adaptations to different exercise stimuli. The main aim of this study was to compare the effects of low- or moderate intensity continuous endurance training (ET), high-intensity interval or continuous training (HIT), and sprint interval training (SIT) on changes in skeletal muscle mitochondrial content and capillarization. Secondarily, the effects on maximal oxygen consumption (VO2max), muscle fiber cross-sectional area, and fiber type proportion were investigated. A systematic literature search was conducted in PubMed, Web of Science, and SPORTDiscus databases, with no data restrictions, up to 2 February 2022. Exercise training intervention studies of ET, HIT, and SIT were included if they had baseline and follow-up measures of at least one marker of mitochondrial content or capillarization. In total, data from 5973 participants in 353 and 131 research articles were included for the mitochondrial and capillary quantitative synthesis of this review, respectively. Additionally, measures of VO2max, muscle fiber cross-sectional area, and fiber type proportion were extracted from these studies. After adjusting for relevant covariates, such as training frequency, number of intervention weeks, and initial fitness level, percentage increases in mitochondrial content in response to exercise training increased to a similar extent with ET (23 ± 5%), HIT (27 ± 5%), and SIT (27 ± 7%) (P > 0.138), and were not influenced by age, sex, menopause, disease, or the amount of muscle mass engaged. Higher training frequencies (6 > 4 > 2 sessions/week) were associated with larger increases in mitochondrial content. Per total hour of exercise, SIT was ~ 2.3 times more efficient in increasing mitochondrial content than HIT and ~ 3.9 times more efficient than ET, while HIT was ~ 1.7 times more efficient than ET. Capillaries per fiber increased similarly with ET (15 ± 3%), HIT (13 ± 4%) and SIT (10 ± 11%) (P = 0.556) after adjustments for number of intervention weeks and initial fitness level. Capillaries per mm2 only increased after ET (13 ± 3%) and HIT (7 ± 4%), with increases being larger after ET compared with HIT and SIT (P < 0.05). This difference coincided with increases in fiber cross-sectional area after ET (6.5 ± 3.5%), HIT (8.9 ± 4.9%), and SIT (11.9 ± 15.1%). Gains in capillarization occurred primarily in the early stages of training (< 4weeks) and were only observed in untrained to moderately trained participants. The proportion of type I muscle fibers remained unaltered by exercise training (P > 0.116), but ET and SIT exhibited opposing effects (P = 0.041). VO2max increased similarly with ET, HIT, and SIT, although HIT showed a tendency for greater improvement compared with both ET and SIT (P = 0.082), while SIT displayed the largest increase per hour of exercise. Higher training frequencies (6 > 4 > 2 sessions/week) were associated with larger increases in VO2max. Women displayed greater percentage gains in VO2max compared with men (P = 0.008). Generally, lower initial fitness levels were associated with greater percentage improvements in mitochondrial content, capillarization, and VO2max. SIT was particularly effective in improving mitochondrial content and VO2max in the early stages of training, while ET and HIT showed slower but steady improvements over a greater number of training weeks. The magnitude of change in mitochondrial content, capillarization, and VO2max to exercise training is largely determined by the initial fitness level, with greater changes observed in individuals with lower initial fitness. The ability to adapt to exercise training is maintained throughout life, irrespective of sex and presence of disease. While training load (volume × intensity) is a suitable predictor of changes in mitochondrial content and VO2max, this relationship is less clear for capillary adaptations.

Investigating the effects of artificial baroreflex stimulation on pain perception: A comparative study in no-pain and chronic low back pain individuals.

The autonomic nervous system (ANS) and pain exhibit a reciprocal relationship, where acute pain triggers ANS responses, whereas resting ANS activity can influence pain perception. Nociceptive signalling can also be altered by 'top-down' processes occurring in the brain, brainstem and spinal cord, known as 'descending modulation'. By employing the conditioned pain modulation (CPM) paradigm, we previously revealed a connection between reduced low-frequency heart rate variability and CPM. Individuals with chronic pain often experience both ANS dysregulation and impaired CPM. Baroreceptors, which contribute to blood pressure and heart rate variability regulation, may play a significant role in this relationship, although their involvement in pain perception and their functioning in chronic pain have not been sufficiently explored. In the present study, we combined artificial 'baroreceptor stimulation' in both pressure pain and CPM paradigms, seeking to explore the role of baroreceptors in pain perception and descending modulation. In total, 22 individuals with chronic low back pain (CLBP) and 29 individuals with no-pain (NP) took part in the present study. We identified a differential modulation of baroreceptor stimulation on pressure pain between the groups of NP and CLBP participants. Specifically, NP participants perceived less pain in response to baroreflex activation, whereas CLBP participants exhibited increased pain sensitivity. CPM scores were associated with baseline measures of baroreflex sensitivity in both CLBP and NP participants. Our data support the importance of the baroreflex in chronic pain and a possible mechanism of dysregulation involving the interaction between the ANS and descending pain modulation. KEY POINTS: Baroreflex stimulation has different effects on pressure pain in participants with chronic pain compared to matched individuals with no-pain. Baroreceptor activation decreases pain in participants with no-pain but increases pain perception in participants with chronic pain. Baroreflex sensitivity is associated with conditioned pain modulation in both groups of chronic pain and no-pain participants. The reactivity of the baroreflex during autonomic stress demonstrated a positive correlation with Pain Trait scores in participants with chronic back pain.

Translating theoretical insights into an emotion regulation flexibility intervention: assessing effectiveness

ABSTRACT Objective: Traditional research often categorizes emotion regulation strategies as adaptive or maladaptive, overlooking crucial situational and individual differences that dictate their efficacy. The literature highlights the need for a more nuanced approach, like the role of emotion regulation flexibility. Despite its importance, research on developing and testing interventions that promote this flexibility is scarce. Addressing this gap, our study designed and tested an “Emotion Regulation Flexibility Booster Program” (ERFBP). We aimed to assess its efficacy in improving emotion regulation flexibility (ERF) and its impact on various mental health indicators. Method: We recruited 153 participants with low emotion regulation flexibility, randomly assigning them to experimental, control, and no-treatment groups. The experimental group was provided with an intervention based on an ERF model. The control group received sessions on study habits, whereas no-treatment group received no training. Results: The analysis indicated that participants in the ERFBP group exhibited significant changes in ERF, subjective wellbeing, and emotion regulation goals and psychological distress compared to baseline measurements and post-intervention scores of other two groups. Conclusion: These findings support the effectiveness of the ERFBP in enhancing ERF and wellbeing. However, further research must confirm these findings across diverse contexts and populations.

Moderators of the Effects of a Digital Parenting Intervention on Child Conduct and Emotional Problems Implemented During the COVID-19 Pandemic: Results From a Secondary Analysis of Data From the Supporting Parents and Kids Through Lockdown Experiences (SPARKLE) Randomized Controlled Trial.

A smartphone app, Parent Positive, was developed to help parents manage their children's conduct and emotional problems during the COVID-19 pandemic. A randomized controlled trial, Supporting Parents and Kids Through Lockdown Experiences (SPARKLE), found Parent Positive to be effective in reducing children's emotional problems. However, app effectiveness may be influenced by a range of child, family, socioeconomic, and pandemic-related factors. This study examined whether baseline factors related to the child, family, and socioeconomic status, as well as pandemic-related disruption circumstances, moderated Parent Positive's effects on child conduct and emotional problems at 1- and 2-month follow-up. This study was a secondary exploratory analysis of SPARKLE data. The data set included 646 children (4-10 years of age) with parents randomized to either Parent Positive (n=320) or follow-up as usual (n=326). Candidate baseline moderators included child age, gender, attention-deficit/hyperactivity disorder symptoms, parental psychological distress, family conflict, household income, employment status, household overcrowding, and pandemic-related disruption risk (ie, homeschooling, lockdown status, and isolation status). Child conduct and emotional problem outcomes measured at 1- (T2) and 2-months (T3) post randomization were analyzed using linear mixed-effects analysis of covariance models adjusting for baseline (T1) measure of outcome and including intervention and intervention by time point interaction terms allowing for different effects at the 2 time points. Moderation of intervention effects by baseline factors was assessed by replacing the intervention by time interaction terms with intervention by time point by baseline moderator interaction terms. Child gender was a significant moderator of the Parent Positive versus follow-up as usual effect on emotional problems (B=0.72, 95% CI 0.12-1.33; P=.02). Specifically, the effect of Parent Positive was close to significant (T2: B=-0.41, 95% CI -0.82 to 0.0004; P=.05) or significant (T3: B=-0.76, 95% CI -1.22 to -0.30; P<.001) in males only when compared with females, and males experienced a significantly larger reduction in emotional problems than females in the Parent Positive arm at the 2-month post randomization time point. None of the other investigated baseline factors moderated effects on emotional problems, and no factors moderated effects on conduct problems. This study highlights Parent Positive's potential for effectively reducing emotional problems in primary school-aged male children across a wide range of families. However, due to limited variability in the demographic background of the families, cautious interpretation is required, and replications are necessary in diverse samples with longer follow-up times. ClinicalTrials.gov NCT04786080; https://clinicaltrials.gov/ct2/show/NCT04786080.

8256 Early Life Stress and Pubertal Predictors of Youth Substance Use Initiation: Does Sex Moderate the Relationship Between ELS, Puberty, and Substance Use Initiation?

Abstract Disclosure: A. Donovan: None. S. Assari: None. M. Shaheen: None. C. Grella: None. L. Richter: None. T.C. Friedman: None. Background: Early life stress (ELS) is a construct composed of children’s experiences of abuse, neglect, and conflict. Approximately 20% of adolescents in the United States have experienced ELS at some point, and these experiences influence adolescent and adult health behavior outcomes. Adults with a history of ELS display higher rates of substance use disorders (SUD) and report earlier initiation of substance use. Additionally, ELS has been associated with early puberty, which in turn is linked to earlier substance use initiation. Our study examines the roles of pubertal status, sex hormones (estradiol, testosterone, and DHEA) and ELS as predictors of the initiation of substance use among a nationally representative sample of male and female adolescents in NIDA’s Adolescent Brain Cognitive Development (ABCD) database. Methods: Baseline measures from the ABCD database release 5.0 were used to generate an ELS score (0-60), puberty assessed via parental report on the Pubertal Development Scale (PDS, 1-4), and sex hormones (estradiol, testosterone, and DHEA) were analyzed via salivary samples. The relationship between these scores and time to first use of alcohol, nicotine, and marijuana was determined via survival analysis utilizing a cox regression. Age was tested as a covariate in the interaction of ELS and time to first use of alcohol, nicotine, and marijuana. Data were analyzed overall and for biological boys and girls separately (N=11,866, 52%M 48%F. ages 9-11 at baseline). Results: We observed additive effects of PDS score, estradiol measure, age, and ELS on time to first use of any substance (alcohol, nicotine, or marijuana) and found age (Exp β= 1.029, p&amp;lt;0.001) and ELS (Exp β= 1.017, p&amp;lt;0.05) to be significant predictors of time to first use. After separating by sex, ELS was no longer a significant predictor for males (Exp β= 1.014, p=0.054), but remained a predictor for females (Exp β= 1.019, p&amp;lt;0.05) indicating the overall effect was driven by females. Additionally, salivary estradiol was a significant predictor of first use for females (Exp β= 1.208, p&amp;lt;0.05), while salivary DHEA and testosterone were not predictors for males or females. Conclusions: Our results indicate sex does moderate the relationship between ELS and substance use initiation within our population, with females showing increased risk of initiation with increases in estradiol. Further findings from our study will help to describe sex differences among the factors that increase the risk of substance use initiation among ELS-exposed youth and explore how these vary by substance. ABCD provides an unprecedented opportunity to explore the mechanisms behind complex effects of ELS by sex on risk factors for adolescent substance use initiation. Presentation: 6/1/2024

7490 Comparative Clinical Analysis of DPP-4 inhibitors and SGLT2 inhibitors; Switch Study in Real-World Setting

Abstract Disclosure: H. Choe: None. M. Kwak: None. J. Lee: None. Y. Choi: None. E. Hong: None. Objective: Dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) represent two distinct pharmacological pathways in the management of type 2 diabetes, both aiming to improve glycemic control without risk of hypoglycemia. Metabolic implications and glycemic control associated with the interchange between SGLT2i and DPP-4i are scarce. This study aimed to evaluate the effect of switching between SGLT2i and DPP4i on various clinical parameters in Korean patients with type 2 diabetes. Methods: We conducted a retrospective cohort study at Hallym University Dongtan Sacred Heart Hospital, using clinical data warehouse. Baseline measurements and follow-up data at 3 months were collected for parameters including hemoglobin A1c (HbA1c), blood pressure, lipid profile, liver enzymes, renal function, and other metabolic markers. Results: Between 2015 and 2023, 104 participants switched from SGLT2 inhibitors to DPP4 inhibitors, while 321 switched in the opposite direction. Initially, those who switched from SGLT2 inhibitors to DPP4 inhibitors presented with lower baseline HbA1c levels (7.22 ± 0.73% versus 7.42 ± 0.76%, P = 0.017) and higher estimated glomerular filtration rates (eGFR) (95.2 ± 23.1 versus 85.9 ± 23.7 mL/min/1.73m², P = 0.001) compared to those who switched from DPP4 inhibitors to SGLT2 inhibitors. At three months of follow-up, the SGLT2 inhibitors to DPP4 inhibitors group exhibited a more significant reduction in HbA1c (adjusted β 0.22, 95% CI 0.03 to 0.40, P = 0.023), especially in patients with reduced eGFR (&amp;lt;60 mL/min/1.73 m²) (β 1.2, 95% CI 0.30 to 2.11, P = 0.013; P for interaction = 0.005). On the other hand, the DPP4 inhibitors to SGLT2 inhibitors group showed a greater decrease in fasting glucose levels (β -9.73, 95% CI -17.6 to -1.86, P = 0.016), along with more pronounced reductions in liver enzymes AST (β -4.15, 95% CI -6.49 to -1.81, P &amp;lt; 0.001) and ALT (β -6.42, 95% CI -9.58 to -3.27, P &amp;lt; 0.001), and a significant increase in hematocrit (β 3.31, 95% CI 2.36 to 4.26, P &amp;lt; 0.001) compared to the initial group. Conclusions: The study concludes that in Korean patients with type 2 diabetes, switching from SGLT2 inhibitors to DPP4 inhibitors is associated with a greater reduction in HbA1c, particularly in those with reduced renal function. Conversely, switching from DPP4 inhibitors to SGLT2 inhibitors results in more substantial improvements in fasting glucose and liver enzyme levels, suggesting differential benefits depending on the direction of the medication switch. Presentation: 6/3/2024

9240 Role Of Genetics In The Age-Related Testosterone Decline In Men: A UK Biobank Study

Abstract Disclosure: L. Ogoniak: None. S. Sandmann: None. J. Varghese: None. A.S. Busch: None. Background: Age-related decline in circulating serum testosterone concentrations is a well-established phenomenon in men. While the decline is partially linked to comorbidities such as obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD), healthy ageing men present with rather stable levels. Recent genetic mapping studies demonstrated a large influence of common genetic variation on testosterone levels in men. However, increasing incidence rates of comorbidities in the ageing population are posing a challenge for the disentanglement of effects. Objective: Our study aims to investigate the genetic component of age-dependent testosterone decline in men. We hypothesize that the decline in testosterone levels in ageing men is primarily influenced by comorbidities, without significant alterations in the genetic architecture of testosterone levels. Material and Methods: We included 6,406 men with baseline and follow-up measurements of circulating serum concentrations of total testosterone (T), bioavailable testosterone (BAT) and sex hormone-binding globulin (SHBG) representing an independent sub-cohort of the UK Biobank study. We 1) assessed the association of baseline levels with the decline in sex steroids and 2) developed and verified polygenic risk score (PRS) models for T, BAT and SHBG based on 183,909 men from the UK Biobank (sub cohorts: 70% base, 15% target and 15% validation, follow-up cohort excluded for PRS development). Results: In the follow-up sub cohort, mean age (SD) at baseline was 58.2 yrs ( 7.5) and mean (SD) follow-up period was 4.3 (1.0) yrs. Mean (SD) BAT at baseline were 5.2 (1.32) nmol/L with a mean (SD) decline of 1.6 (24.4) % at follow-up. Baseline BAT, T and SHBG levels were significantly associated with the relative change of the respective biomarker at follow-up (-7.8, -2.9 and -0.4% per nmol/L, respectively, all p &amp;lt;0.001). After correcting for age at baseline, follow-up period and principal components 1-10, PGSTestosterone and PGSBAT were not associated with relative decline of the respective biomarker (both p = n.s.). Conclusion: Our study did not find evidence supporting a genetic component in the age-related decline of circulating serum T or BAT concentrations. Instead, in accordance to previous observational studies, our results suggest that rather non-genetic factors, e.g. increasing incidence rates of comorbidities, drive the age-related decline in sex steroid levels in men. Our study contributes to understanding the intricate relationship between genetic and non-genetic factors with age-related testosterone decline in men and offers valuable insights for potential interventions targeting age-related hormonal changes and associated health outcomes. Presentation: 6/2/2024

8039 Role Of Genetics In The Age-Related Testosterone Decline In Men: A UK Biobank Study

Abstract Disclosure: L. Ogoniak: None. S. Sandmann: None. J. Varghese: None. A.S. Busch: None. Background: Age-related decline in circulating serum testosterone concentrations is a well-established phenomenon in men. While the decline is partially linked to comorbidities such as obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD), healthy ageing men present with rather stable levels. Recent genetic mapping studies demonstrated a large influence of common genetic variation on testosterone levels in men. However, increasing incidence rates of comorbidities in the ageing population are posing a challenge for the disentanglement of effects. Objective: Our study aims to investigate the genetic component of age-dependent testosterone decline in men. We hypothesize that the decline in testosterone levels in ageing men is primarily influenced by comorbidities, without significant alterations in the genetic architecture of testosterone levels. Material and Methods: We included 6,406 men with baseline and follow-up measurements of circulating serum concentrations of total testosterone (T), bioavailable testosterone (BAT) and sex hormone-binding globulin (SHBG) representing an independent sub-cohort of the UK Biobank study. We 1) assessed the association of baseline levels with the decline in sex steroids and 2) developed and verified polygenic risk score (PRS) models for T, BAT and SHBG based on 183,909 men from the UK Biobank (sub cohorts: 70% base, 15% target and 15% validation, follow-up cohort excluded for PRS development). Results: In the follow-up sub cohort, mean age (SD) at baseline was 58.2 yrs ( 7.5) and mean (SD) follow-up period was 4.3 (1.0) yrs. Mean (SD) BAT at baseline were 5.2 (1.32) nmol/L with a mean (SD) decline of 1.6 (24.4) % at follow-up. Baseline BAT, T and SHBG levels were significantly associated with the relative change of the respective biomarker at follow-up (-7.8, -2.9 and -0.4% per nmol/L, respectively, all p &amp;lt;0.001). After correcting for age at baseline, follow-up period and principal components 1-10, PGSTestosterone and PGSBAT were not associated with relative decline of the respective biomarker (both p = n.s.). Conclusion: Our study did not find evidence supporting a genetic component in the age-related decline of circulating serum T or BAT concentrations. Instead, in accordance to previous observational studies, our results suggest that rather non-genetic factors, e.g. increasing incidence rates of comorbidities, drive the age-related decline in sex steroid levels in men. Our study contributes to understanding the intricate relationship between genetic and non-genetic factors with age-related testosterone decline in men and offers valuable insights for potential interventions targeting age-related hormonal changes and associated health outcomes. Presentation: 6/2/2024

9240 Role Of Genetics In The Age-Related Testosterone Decline In Men: A UK Biobank Study

Abstract Disclosure: L. Ogoniak: None. S. Sandmann: None. J. Varghese: None. A.S. Busch: None. Background: Age-related decline in circulating serum testosterone concentrations is a well-established phenomenon in men. While the decline is partially linked to comorbidities such as obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD), healthy ageing men present with rather stable levels. Recent genetic mapping studies demonstrated a large influence of common genetic variation on testosterone levels in men. However, increasing incidence rates of comorbidities in the ageing population are posing a challenge for the disentanglement of effects. Objective: Our study aims to investigate the genetic component of age-dependent testosterone decline in men. We hypothesize that the decline in testosterone levels in ageing men is primarily influenced by comorbidities, without significant alterations in the genetic architecture of testosterone levels. Material and Methods: We included 6,406 men with baseline and follow-up measurements of circulating serum concentrations of total testosterone (T), bioavailable testosterone (BAT) and sex hormone-binding globulin (SHBG) representing an independent sub-cohort of the UK Biobank study. We 1) assessed the association of baseline levels with the decline in sex steroids and 2) developed and verified polygenic risk score (PRS) models for T, BAT and SHBG based on 183,909 men from the UK Biobank (sub cohorts: 70% base, 15% target and 15% validation, follow-up cohort excluded for PRS development). Results: In the follow-up sub cohort, mean age (SD) at baseline was 58.2 yrs ( 7.5) and mean (SD) follow-up period was 4.3 (1.0) yrs. Mean (SD) BAT at baseline were 5.2 (1.32) nmol/L with a mean (SD) decline of 1.6 (24.4) % at follow-up. Baseline BAT, T and SHBG levels were significantly associated with the relative change of the respective biomarker at follow-up (-7.8, -2.9 and -0.4% per nmol/L, respectively, all p &amp;lt;0.001). After correcting for age at baseline, follow-up period and principal components 1-10, PGSTestosterone and PGSBAT were not associated with relative decline of the respective biomarker (both p = n.s.). Conclusion: Our study did not find evidence supporting a genetic component in the age-related decline of circulating serum T or BAT concentrations. Instead, in accordance to previous observational studies, our results suggest that rather non-genetic factors, e.g. increasing incidence rates of comorbidities, drive the age-related decline in sex steroid levels in men. Our study contributes to understanding the intricate relationship between genetic and non-genetic factors with age-related testosterone decline in men and offers valuable insights for potential interventions targeting age-related hormonal changes and associated health outcomes. Presentation: 6/2/2024

8039 Role Of Genetics In The Age-Related Testosterone Decline In Men: A UK Biobank Study

Abstract Disclosure: L. Ogoniak: None. S. Sandmann: None. J. Varghese: None. A.S. Busch: None. Background: Age-related decline in circulating serum testosterone concentrations is a well-established phenomenon in men. While the decline is partially linked to comorbidities such as obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD), healthy ageing men present with rather stable levels. Recent genetic mapping studies demonstrated a large influence of common genetic variation on testosterone levels in men. However, increasing incidence rates of comorbidities in the ageing population are posing a challenge for the disentanglement of effects. Objective: Our study aims to investigate the genetic component of age-dependent testosterone decline in men. We hypothesize that the decline in testosterone levels in ageing men is primarily influenced by comorbidities, without significant alterations in the genetic architecture of testosterone levels. Material and Methods: We included 6,406 men with baseline and follow-up measurements of circulating serum concentrations of total testosterone (T), bioavailable testosterone (BAT) and sex hormone-binding globulin (SHBG) representing an independent sub-cohort of the UK Biobank study. We 1) assessed the association of baseline levels with the decline in sex steroids and 2) developed and verified polygenic risk score (PRS) models for T, BAT and SHBG based on 183,909 men from the UK Biobank (sub cohorts: 70% base, 15% target and 15% validation, follow-up cohort excluded for PRS development). Results: In the follow-up sub cohort, mean age (SD) at baseline was 58.2 yrs ( 7.5) and mean (SD) follow-up period was 4.3 (1.0) yrs. Mean (SD) BAT at baseline were 5.2 (1.32) nmol/L with a mean (SD) decline of 1.6 (24.4) % at follow-up. Baseline BAT, T and SHBG levels were significantly associated with the relative change of the respective biomarker at follow-up (-7.8, -2.9 and -0.4% per nmol/L, respectively, all p &amp;lt;0.001). After correcting for age at baseline, follow-up period and principal components 1-10, PGSTestosterone and PGSBAT were not associated with relative decline of the respective biomarker (both p = n.s.). Conclusion: Our study did not find evidence supporting a genetic component in the age-related decline of circulating serum T or BAT concentrations. Instead, in accordance to previous observational studies, our results suggest that rather non-genetic factors, e.g. increasing incidence rates of comorbidities, drive the age-related decline in sex steroid levels in men. Our study contributes to understanding the intricate relationship between genetic and non-genetic factors with age-related testosterone decline in men and offers valuable insights for potential interventions targeting age-related hormonal changes and associated health outcomes. Presentation: 6/2/2024

8483 Changes in kidney hemodynamics during gender-affirming hormone therapy in transgender individuals - findings from the KNIGHT pilot study

Abstract Disclosure: S.A. van Eeghen: None. C. Wiepjes: None. L.L. Pyle: None. M. den Heijer: Research Investigator; Self; Kyowa Kirin. Other; Self; Novartis Pharmaceuticals. P. Bjornstad: Advisory Board Member; Self; AstraZeneca, Bayer, Inc., Boehringer Ingelheim, Novo Nordisk, XORTX. Consulting Fee; Self; AstraZeneca, Bayer, Inc., Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly &amp; Company, LG Chemistry, Horizon Pharma, Novo Nordisk, Sanofi. Research Investigator; Self; AstraZeneca, Merck, Horizon Pharma. Other; Self; Bayer, Inc. D. van Raalte: Consulting Fee; Self; AstraZeneca, Bayer, Inc., Boehringer Ingelheim, Eli Lilly &amp; Company, Merck, Sanofi, MSD. Research Investigator; Self; AstraZeneca, Boehringer Ingelheim, Eli Lilly &amp; Company, Merck, Sanofi, MSD. N.J. Nokoff: Consulting Fee; Self; Neurocrine Biosciences, Inc, Ionis Pharmaceuticals Inc.. Research Investigator; Self; Neurocrine Biosciences, Inc. Other; Self; World Athletics. Background: Studies in transgender individuals have shown that gender-affirming hormone therapy (GAHT) impacts estimated glomerular filtration rate (eGFR). Masculinizing hormone therapy decreases, while feminizing hormone therapy increases eGFR, based on changes in serum creatinine and cystatin C. These substantial changes suggest an effect of sex hormones on kidney hemodynamics. To investigate this, we studied kidney hemodynamic changes before and after 3 months of gender-affirming hormone therapy (GAHT) in transgender individuals. Methods: This prospective observational pilot study assessed kidney hemodynamics in 23 transgender individuals assigned male at birth receiving feminizing hormone therapy and 21 transgender individuals assigned female at birth receiving masculinizing hormone therapy. Feminizing therapy included transdermal (n=16), sublingual (n=5), or oral estradiol (n=2), in combination with an anti-androgen (n=22); intramuscular triptorelin (n=16), spironolactone (n=5) or finasteride (n=1). Masculinizing therapy involved transdermal (n=17) or injected testosterone (n=4). Measures included glomerular filtration rate (GFR; Iohexol clearance), effective renal plasma flow (ERPF; p-aminohippurate clearance), and renal vascular resistance (RVR; mean arterial pressure/renal blood flow). Glomerular hydraulic pressure (PGLO), and afferent/efferent vascular resistance (RA/RE) were estimated by Gomez equations. Linear mixed models compared baseline and three-month measurements. Results: Individuals undergoing feminizing hormone therapy [median age 21 (IQR 19-29) years, BMI median 22.9 (IQR 18.9-30.7) kg/m²] had increased GFR by 2.8 mL/min per 1.73m² (95% CI, 0.01 to 5.6) and a nonsignificant increase in ERPF (+42 mL/min per 1.73m²; 95% CI, -5 to 90). RVR and RA significantly decreased [RVR: -0.007 mmHg/L/min (95% CI, -0.015 to -0.0003), RA: -294 dyn/s per cm5 (5% CI, -568 to -21)], indicating afferent vasodilation. In contrast, individuals receiving masculinizing therapy (median age median 20 (IQR 18-23) years, BMI median 24.2 (IQR 21.1-27.3) kg/m²) showed a slight, nonsignificant decrease in GFR (-2.1 mL/min per 1.73m²; 95% CI, -4.9 to 0.8), with no changes in other kidney hemodynamic parameters. Conclusions: In this cohort of transgender individuals, GFR increased during feminizing hormone therapy, likely due to afferent vasodilatation, while during masculinizing hormone therapy GFR tended to decrease. These findings suggest an influence of sex hormones on kidney hemodynamics, especially during feminizing hormone therapy. Presentation: 6/3/2024

12424 A Feasibility Trial Of A Co-created Digital Self-management Programme For Adults With Polycystic Ovary Syndrome (Hope PCOS)

Abstract Disclosure: C.A. Percy: None. A. Turner: None. L. Aphramor: None. D. Broom: None. C. Clark: None. F. Martin: None. P. Wark: None. Introduction: Polycystic ovary syndrome (PCOS) has significant impact on depression, anxiety, psychological wellbeing and health-related quality of life. We co-created a theory-led, evidence-based, 6-week, digital self-management and positive wellbeing intervention (Hope PCOS), delivered to UK adults. We tested the intervention’s potential to improve mental health and wellbeing outcomes and its acceptability and usability for adults living with PCOS. Methods: This was a mixed methods feasibility randomised controlled trial conducted online, with a pre-post, waitlist-controlled design. Primary outcomes were recruitment, completion (≥ 3 intervention sessions) and follow-up rates. At baseline, participants reported demographic information, PCOS symptoms, depression (Patient Health Questionnaire (PHQ-9)), anxiety ((Generalised Anxiety Disorder Assessment (GAD-7)), polycystic ovary syndrome health-related quality of life (PCOSQ-50), psychological wellbeing (Warwick-Edinburgh Mental Wellbeing Scale, WEMWBS) and self-efficacy (Self-Efficacy to Manage Chronic Disease Scale (SEMCD6)) before randomisation to an intervention group (IG) receiving the intervention immediately or a waitlist control group (CG) receiving the intervention 12 weeks later. PHQ-9, GAD-7, PCOSQ-50, WEMWBS and SEMDC6 were reassessed at 6 and 12 weeks. IG participants reported the usability of the digital intervention (system usability scale (SUS)) and acceptability via qualitative exit interviews. Results: Of 131 eligible, consented participants, 83% (N=109, age M=37.1, SD=8.6 years) completed baseline measures and were randomised to the IG (n=54) or the CG (n=55). Baseline clinical caseness was high for depression (n=77, 70.6%) and anxiety (n=78, 71.6 %). Twenty-one participants (39%) in the IG completed ≥3 intervention sessions. At 6-week follow-up, completion of secondary outcomes was n=32 (59%) for IG and n= 38 (69%) for CG; at 12 weeks, n=31 (57%) for IG and n= 38 (69%) for CG. Twelve IG participants took part in the exit interviews. Exploratory descriptive statistics suggest there were greater improvements in depression, anxiety, psychological wellbeing, self-efficacy and quality of life for the intervention group completers compared to the waitlist control group. SUS data and thematic analysis suggest the intervention was usable, acceptable, relevant and interesting. Participants reported experiences including feeling seen and valued, having the difficulties of lifestyle change acknowledged, and learning valuable lessons, particularly how to monitor and manage emotions, prioritise self-care and complete personal goals. Conclusions: This novel intervention was rated as usable and acceptable, with potential for improving mental health and wellbeing outcomes. More research is needed to identify for whom the intervention is beneficial and on implementation in practice. Presentation: 6/1/2024

8570 Association Between Preconception Lifestyle and Anthropometric Modifications and Fertility outcomes in Women with Infertility and Obesity

Abstract Disclosure: A. Thibodeau: None. C. Richer dit Laflèche: None. G. Ngueta: None. M. Belan: None. F. Jean-Denis: None. M. Langlois: None. M. Pesant: None. B. Carranza Mamane: None. J. Baillargeon: Grant Recipient; Self; Ferring Pharmaceuticals. Introduction: Infertility is a common problem that is affected by many lifestyle behaviors, and preconception lifestyle modifications are recommended in women with infertility and obesity. This study thus aims to explore whether preconception lifestyle or anthropometric changes are associated with a viable pregnancy or a live birth in this population. Methods: This prospective cohort study, nested within a randomized controlled trial that recruited 127 women with infertility and obesity at an academic fertility clinic, reports on 70 women who had at least one research visit during their follow-up until the onset of pregnancy or a maximum of 18 months. Lifestyles were assessed using a questionnaire. Logistic regression was used to examine the association between changes in lifestyle or anthropometry and the occurrence of a viable pregnancy or live birth. Changes were defined by the incremental area under the curve (divided by follow-up time; iAUC) and the difference between baseline and the minimum or maximum measure achieved during follow-up. Regressions were corrected for baseline measures of the age of both partners, waist circumference, multiparity, socioeconomic status and multivitamin use. Results: The odds of a pregnancy and live birth were higher among women who had a greater minimum change (improvement) in their weekly consumption of fruits (p=.028/.014) or dairy products (p=.005/.003), in their reduction of tobacco use (p=.038/NS), in their sleep duration (p=.044/NS), or in their loss of weight, waist circumference or fat mass (p=.007/.007; .006/.006; .045/.019). Unexpectedly, a higher maximum change in energy expenditure was associated with lower odds of pregnancy (p=.013). Multivariate analyses showed that a higher minimum change in fruit consumption (p=.008), in tobacco use reduction (p=.033), and waist circumference loss (p=.002), and a lower maximum change in energy expenditure (p=.008) were all independently associated with the occurrence of pregnancy, after adjustment for the abovementioned potential confounders. For live birth, a higher minimum change in dairy products consumption (p=.012), in tobacco use reduction (p=.017), and in weight loss (p=.003) were all independently associated with a live birth. Conclusion: Our exploratory analyses are among the first to show that preconception lifestyle improvements are associated with the occurrence of a viable pregnancy and live birth in women with infertility and obesity, particularly higher minimal and sustained changes in fruit and dairy product intake and tobacco reduction. Higher minimal and sustained weight or waist circumference losses also contributed to improve their fertility, as expected. However, the negative association between higher energy expenditure and pregnancy was unexpected and requires further evaluation. Presentation: 6/1/2024

”I am now on ‘speaking terms’ with my migraine monster” – patient experiences in acceptance-based cognitive behavioral therapy delivered via the internet for migraine: a randomized controlled pilot study using a mixed-method approach

ABSTRACT Migraine is a common neurological disorder globally. Migraines, with or without aura, are episodic and recurring with symptom-free periods. Frequent and prolonged attacks can lead to chronic migraine. This pilot randomized controlled trial (RCT) aimed to evaluate feasibility of therapist-guided, acceptance-based internet cognitive behavioral therapy (iCBT) as an adjunct to standard medical care for migraine patients in Swedish primary healthcare settings using a mixed methods approach. Participants (treatment n = 15, control n = 14) underwent qualitative and quantitative assessments to evaluate feasibility, acceptance, and initial treatment effects. Interviews with participants (n = 7) indicate that most participants had struggled with migraines for decades and expressed dissatisfaction with the limited medical care. They found the flexible, digital format particularly helpful, praising its accessibility and structured learning. While they appreciated the comprehensive content, some faced challenges with the psychological language and the program pace. Post-treatment, participants reported emotional and behavioral changes, and better migraine management. Seventy-two percent of the 29 participants completed both baseline and 3-month follow-up measures. On average, participants completed 7.7 modules, with 60% completing all 10 modules. Promising effect size indicated a reduction in migraine days during the three-month follow-up. Both qualitative and quantitative data support the feasibility and acceptability of the intervention in primary care settings.