Collection Time Points Research Articles

Perinatal Depression and Breastfeeding Outcomes: A Systematic Review from South Asian Countries

Background: Breastfeeding is very beneficial to both mothers and infants. However, perinatal depression, encompassing both antenatal and postnatal depression, can significantly impact breastfeeding. Prior research suggests a link between postpartum depression and breastfeeding difficulties. This systematic review focuses on the duration of breastfeeding, the duration of exclusive breastfeeding (EBF), initiation, as well as the early cessation of breastfeeding among mothers in South Asian countries with unique sociocultural practices and mental health experiences. Methodology: The searched databases were PubMed, Ovid MEDLINE, ProQuest PsycINFO, EBSCOhost CINAHL, and Bielefeld Academic Search Engine (gray literature) for relevant records till February 2024. Studies conducted in South Asian countries with cross-sectional, cohort, or case–control designs were included, and all interventional studies, qualitative studies, case reports, and case series were excluded. The review examined breastfeeding duration among mothers with perinatal depression. Two reviewers independently screened and selected studies, extracted data, and used the Newcastle–Ottawa Scale for quality assessment. Results: This systematic review identified 109 records, of which 14 were eligible. Ten studies were cross-sectional and 4 were cohort studies. It involved 11,944 perinatal women, with sample sizes ranging from 100 to 8189 participants. Conclusion: Perinatal depression was associated with shorter breastfeeding duration, especially EBF and early cessation of all breastfeeding. However, any association between perinatal depression and the initiation of breastfeeding was unclear. Overall, supporting mothers suffering from perinatal depression is crucial for successful breastfeeding practice. Certain limitations of the review were data heterogeneity, risk of recall bias in breastfeeding practices, and different data collection time points. Future research could study the various sociocultural and economic factors and biological mechanisms in breastfeeding and maternal depression.

The changing association between pandemic-related stressors and child and adolescent mental health during the waning phase of the COVID-19 pandemic

This study examined the relation between pandemic-related stressors and mental health among young people (YP) in India during two time points in the waning phase of the pandemic. We use data from two cross-sectional waves of over 20,000 YP aged 5–19 in February 2022, during the peak of the Omicron wave, and October 2022, during a reduction in infections and easing of restrictions. COVID illness/death in the family’s social network, current lockdown stringency, and significant change in household income were examined in relation to adult respondents’ reports of YP internalizing symptoms. Internalizing symptoms declined slightly from February to October 2022. COVID-19 illness/death in the family’s network was generally associated with more internalizing symptoms. Higher lockdown stringency was associated with lower levels of internalizing symptoms. YP in households with increases in income tended to have more internalizing symptoms. Many associations were driven by older adolescents and were stronger during the earlier (Feb-2022) than later (Oct-2022) data collection time-points. The findings illustrate the importance of anchoring results within a study’s specific geographic context, including concurrent events during the study period. Importantly, findings that may initially seem counterintuitive ultimately illuminate the dynamic and complex processes underlying child and adolescent mental health.

First-in-Human Phase I Clinical Trial of the Adenosine A1R/A3R Agonist AST-004 in Healthy Subjects.

AST-004 is a small-molecule adenosine A1/A3 receptor agonist that has exhibited significant cerebroprotective efficacy in preclinical models of acute ischemic stroke and traumatic brain injury. The primary objectives of this clinical phase I first-in-human study were to evaluate the safety and tolerability profile of single ascending intravenous doses in healthy subjects. The secondary objectives were to characterize the single-dose pharmacokinetic profiles in plasma, cerebrospinal fluid (CSF), and urine. In part 1 of the study, AST-004 was administered in ascending dose cohorts of 5, 25, 50, 75, and 100 mg, with 6 subjects in each cohort receiving the study drug and 2 receiving placebo. In part 2, all 12 subjects received a 100 mg IV infusion of the study drug followed by a single CSF collection per subject via lumbar puncture at 20, 40, or 60 minutes after infusion. A total of 42 subjects received AST-004, with no severe or serious adverse events observed. Twelve of these subjects experienced a treatment-emergent adverse event, the most frequent across groups being headache. In part 2, pharmacokinetic analyses confirmed that AST-004 was distributed in the CSF, with the CSF-to-plasma ratio increasing over the 3 timepoints sampled. The mean half-life was 1.1 to 1.4 hours for doses of 25 to 100 mg, and the geometric mean maximum plasma concentration obtained in the highest dosing cohort (100 mg) was 2232±428 ng/mL. AST-004 was safe and well-tolerated at plasma concentrations 3 to 8× higher than those associated with significant efficacy in astrocyte's preclinical primate stroke efficacy studies, with CSF concentrations highest at the 60-minute collection timepoint, the last timepoint tested. This study supports additional clinical investigations, including evaluation of an extended infusion to support the phase 2 program in stroke and traumatic brain injury.

Changes in Auditory Performance Following a Virtual Reality Music Concert.

The purpose of this study was to evaluate threshold and suprathreshold auditory risk from a newly popular platform of music concert entertainment; virtual reality (VR) headsets. Recreational noise exposure to music is the primary source of hearing hazard in young-adults, with noise doses of in-person concert venues and music festivals well in excess of the recommended daily exposure recommendation from the National Institute for Occupational Safety and Health. While research on the relationship between personal music players and noise-induced hearing loss risk is abundant, no study has yet evaluated noise-induced hearing loss risk from VR headsets, which are newest to the commercial market at this time. Thirty-one young-adult participants (18 to 25 years) with normal-hearing sensitivity (0 to 16 dB HL) experienced a VR music concert and participated in three data collection timepoints: Session A preexposure, Session A post-exposure, and Session B post-exposure. Participants underwent baseline testing for audiometry (0.25 to 20 kHz), distortion product otoacoustic emission testing (1 to 10 kHz), and Words-in-Noise testing. Participants then wore a commercially available VR headset (Meta Quest 2) and experienced a freely available online VR music concert (via the video-sharing website "YouTube"). The VR music concert duration was 90 min set to maximum volume, which yielded an average sound level equivalent of 78.7 dBA, max sound level of 88.2 dBA, and LC peak sound level of 98.6 dBA. Post-exposure testing was conducted immediately at the conclusion of the VR concert, and again within 24 hr to 1 week after the exposure. Participants also answered a questionnaire that estimated noise exposure history (National Acoustics Laboratory "Noise Calculator"). Post-exposure deficit was not observed in DPOAEs or Words-in-Noise score (p's > 0.05). However, statistically significant temporary post-exposure deficit was observed in audiometry at 4, 8, and 12.5 kHz (p's < 0.05) (mean differences: 2 to 3 dB HL). Twenty-four hours and 1-week post-exposure measurements revealed no permanent changes from baseline measurements (p's > 0.05) aside from one spurious difference at 12.5 kHz. Males tended to exhibit a significantly higher noise history score on average than females. The primary, secondary, and tertiary sources of noise hazard history in this young-adult cohort included amplified music. These preliminary data suggest that VR music concerts-which are likely to produce a substantially lower noise dose than in-person music concerts-may still be capable of producing at least slight, temporary threshold shifts on the order of 2 to 3 dB HL. Future research should include VR headsets in personal music player risk assessment, as the VR music concert platform is increasing rapidly in popularity among young-adults.

7269 Interim Analysis of Gonadotropin-Releasing Hormone Agonist (GnRHa) Treatment in Children with Central Precocious Puberty: Focus on FMV Urinary LH Levels and Clinical Outcomes

Abstract Disclosure: X. Luo: Advisory Board Member; Self; Takeda. L. Hou: Advisory Board Member; Self; Takeda. Y. Li: Advisory Board Member; Self; Takeda. Y. Sun: Advisory Board Member; Self; Takeda. X.K. Jin: Employee; Self; Takeda. Background: Central precocious puberty (CPP) refers to early activation of the hypothalamic–pituitary–gonadal (HPG) axis in children. There is an urgent need to understand the treatment pattern and clinical outcomes among children suffering from CPP. Studies have reported that first morning voided (FMV) urinary Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) have substantial association with CPP tested in GnRH stimulation test and can be useful in diagnosis and management of CPP in children. Gonadotropin-releasing hormone agonists (GnRHa) such as Leuprolide acetate (LA) are the recommended treatment for children suffering from CPP. The current study aimed to provide the information on level of LH and FSH in FMV urine when CPP diagnosis at baseline and the present results may also revealed trend of FMV-LH and FMV-FSH change during LA intervention in children with CPP. Here we present interim results from this study. Methods: This is an open-label, multicentre, single arm, prospective study that enrolled 31 subjects with CPP. Individuals were administered LA depot 11.25 mg, subcutaneously every 12 weeks. The study comprises a screening period; a 6-month treatment period: 24 weeks; and a post-treatment follow-up period: 12 weeks. The FMV urinary LH and FSH were diagnosed by Clopper-Pearson method with a 95% confidence interval. Results: Due to the data collection time point for the interim analysis, only 8 female subjects reached the 12-week visit time point and had a 12-week visit for FMV urinary Gn testing. Therefore, for this interim analysis, only FMV Gn decline at week 12 of the 8 subjects who had a 12-week visit will be presented. At baseline, the mean value of FMV urinary LH and FSH is 0.58 IU/L and 2.27 IU/L respectively. The FMV Gn urinary LH was demonstrated a decrease in 87.5% (95% CI: 47.35,99.68) of the children after LA intervention. Additionally, urinary FSH value of FMV urinary Gn was found to decrease in 75.00% of the children (95% CI: 34.91,96.81) compared to baseline FSH value. Conclusion: The present study reveals a decreasing trend in FMV Gn urinary LH and FSH levels in CPP children treated with LA during interim analysis. LA was shown to be safe and effective in ameliorating the level of LH and FSH in children suffering from CPP. From the study, it can be concluded that urinary LH and FSH may act as a potential biomarker for diagnosis and management of CPP. Presentation: 6/3/2024

7128 Efficacy and Safety of Leuprolide Acetate 3M Depot in Chinese Children with Central Precocious Puberty: Interim Analysis of Multicenter, Single-Arm, Prospective Study

Abstract Disclosure: X. Luo: Advisory Board Member; Self; Takeda. L. Hou: Advisory Board Member; Self; Takeda. Y. Li: Advisory Board Member; Self; Takeda. Y. Sun: Advisory Board Member; Self; Takeda. X.K. Jin: Employee; Self; Takeda. Background: Central precocious puberty (CPP) due to early activation of the hypothalamic-pituitary-gonadal axis leads to early puberty. CPP has a negative impact on adult height. Leuprolide acetate (LA), a gonadotropin-releasing hormone agonist (GnRHa) is the standard treatment for CPP. As CPP requires prolonged treatment, a 3-month (3M) depot formulation would increase patient compliance and reduce the injection burden. This interim analysis presents the effect of LA 3M depot on the gonadotropic axis and assesses safety in children with CPP. Methods: In this open-label, multicenter, single-arm, and prospective study, 31 children with CPP were included. Key inclusion criteria were the appearance of secondary sexual characteristics below the age of eight years in girls and nine years in boys with a confirmed diagnosis of CPP. Children treated with prior GnRHa and/or having underlying medical conditions were excluded. Eligible children were treated with LA 11.25 mg subcutaneously every 12 weeks. The primary endpoint of this interim analysis was the proportion of children achieving inhibition of peak LH defined as peak LH ≤ 3.0 IU/L in the GnRH stimulation test at weeks 24. The secondary endpoint was safety analysis in the children receiving at least one dose of LA 3M depot. Results: At baseline, 30 girls and one boy were enrolled. The median (95% CI) chronological age (CA) of the girls was 8.0 (7.0, 9.0) years and the boy was 10 years old. Girls had a median height of 136.95 (131.5, 139.7) cm, weight of 30 (27, 34) kg, and BMI of 16.4 (15.1, 17.9) kg/m2. Baseline bone (BA) age was 11 (10, 11) years, and BA/CA was 1.24 (1.2, 1.3). Boy’s characteristics at baseline differed in CA (10 years), height (144 cm), and BMI (17.4 kg/m2) from girls of this cohort. Due to the data collection time points for the interim analysis, 8 out of the 31 enrolled subjects had a visit at week 24, and 30 subjects reached the week 12 visit time point and had a visit at week 12. The percentage of children achieving inhibition of peak LH (≤ 3.0 IU/L) in the GnRH stimulation test at week 12 was 100 (88.4, 100) %. At week 24, all of them achieved inhibition of LH in the GnRH stimulation test 100 (63, 100) %. Decreases in BA/CA from baseline at weeks 12 and 24 are 93 (77.9, 99.2) % and 50 (15.7, 84.3) % respectively. No progression of the Tanner stage was observed in 96.7 (82.8, 99.9) % and 100 (63, 100) % at weeks 12 and 24. At the data cut-off, 4 (13.33%) patients experienced a total of 5 treatment-emergent adverse events (TEAEs) in the safety population of 30 subjects. No grade ≥3 AE or serious AE was reported. The incidence of injection site reaction was 3.33%. Conclusion: LA at 11.25mg/3M depot effectively suppresses the gonadotropic axis at weeks 12 and 24, normalizing growth and reversibly slowing the early onset of puberty in children with CPP. LA in a 3-month injecting frequency is a safe and convenient treatment option to improve patient compliance. Presentation: 6/3/2024

Development and Application of a Liquid Sampling Device with Timing, Quantitative and Depth Determination

This thesis describes the development process of a liquid sampling device that can be timed, quantitative, and deep. The structural composition, working principle, and innovative features of the liquid sampling device are introduced, and the application prospects are analyzed. The device has the function of controllable and adjustable sampling point depth and sampling volume, and adopts quantitative collection and collection methods without contact with accessories. The device has a silent function in the sample body, which can realize pre-booking of collection time points and multi-point synchronous collection. Wireless remote control automatic mode is adopted for sending and stopping collection instructions, which can be sent one-to-one or one-to-many at the same time. It provides automation links for water quality monitoring projects and meets the requirements of modern scientific and technological development.

Plasma ctDNA as a Treatment Response Biomarker in Metastatic Cancers: Evaluation by the RECIST Working Group.

Early indicators of metastatic cancer response to therapy are important for evaluating new drugs and stopping ineffective treatment. The RECIST guidelines based on repeat cancer imaging are widely adopted in clinical trials, are used to identify active regimens that may change practice, and contribute to regulatory approvals. However, these criteria do not provide insight before 6 to 12 weeks of treatment and typically require that patients have measurable disease. Recent data suggest that measuring on-treatment changes in the amount or proportion of ctDNA in peripheral blood plasma may accurately identify responding and nonresponding cancers at earlier time points. Over the past year, the RECIST working group has evaluated current evidence for plasma ctDNA kinetics as a treatment response biomarker in metastatic cancers and early endpoint in clinical trials to identify areas of focus for future research and validation. Here, we outline the requirement for large standardized trial datasets, greater scrutiny of optimal ctDNA collection time points and assay thresholds, and consideration of regulatory body guidelines and patient opinions. In particular, clinically meaningful changes in plasma ctDNA abundance are likely to differ by cancer type and therapy class and must be assessed before ctDNA can be considered a potential pan-cancer response evaluation biomarker. Despite the need for additional data, minimally invasive on-treatment ctDNA measurements hold promise to build upon existing response assessments such as RECIST and offer opportunities for developing novel early endpoints for modern clinical trials.

B - 25 Documenting the Prevalence of Sleep Disturbances among TBI Survivors: a FITBIR Study

Abstract Objective The objective of this study is to utilize data from the Federal Interagency Traumatic Brain Injury Research (FITBIR) database to document the short-term prevalence of sleep disorders among a sample of mild Traumatic Brain Injury (mTBI) survivors. Method Data was extracted from the FITBIR website. Adult individuals who sustained an mTBI (Rivermead Post Concussion Symptoms Questionnaire; RPQ6) and had a data collection timepoint within 10 days of the injury were included. Measures of demographic characteristics and sleep problems (Pittsburgh Sleep Quality Index; PSQI) were utilized. A total of 74 participants (97% male, 73% white, mean age = 22.49 SD = 11.25) were included. Descriptive analysis were conducted to document the prevalence of sleep problems among this sample. Results Across our sample, broad sleep difficulties were common (PSQI Mean = 7.014, Median = 5, SD = 7.56). 47.29% of participants reported severe sleep difficulties (PSQI &amp;gt;5). 14(23.3%) individuals met criteria for insomnia based on their component 5 scores. Among individuals with a bed partner, only 3(7%) endorsed long breathing pauses, suggestive of Central Sleep Apnea (CSA), 16(40%) endorsed snoring, suggestive of Obstructive Sleep Apnea, and 16(22%) endorsed leg twitching, possibly indicative of Restless Leg Syndrome. Conclusion This study highlights the prevalence of sleep problems as a salient issue among mTBI patients. The FITBIR is a valuable tool to further TBI research. Future studies should examine the temporal trajectory of sleep problems and its relationship to other outcomes and include more diverse samples.

Efficacy and Safety of Shi Cervical Rotational Manipulation in Patients With Atlantoaxial Joint Subluxation: Protocol for a Randomized Controlled Trial.

The clinical diagnosis of atlantoaxial joint subluxation (AJS) in traditional Chinese medicine (TCM) is characterized by an unequal distance between the lateral mass of the atlas and the odontoid process on imaging, resulting in neck pain accompanied by symptoms such as dizziness, headache, and limited cervical mobility. In Shanghai, Shi cervical rotational manipulation (SCRM) is a commonly employed TCM manual therapy for treating this condition. Nevertheless, there is a lack of evidence-based medical information regarding the clinical efficacy and safety of this technique. The principal aim of this study is to evaluate the efficacy and safety of SCRM in patients diagnosed with AJS. This study is a prospective randomized controlled clinical trial that will be conducted at a single center and that has a follow-up period of 24 weeks. A total of 96 patients diagnosed with AJS will be recruited from outpatient and inpatient clinics at Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine. These patients will be randomly assigned to either the experimental group (SCRM) or the comparison group (basic cervical manipulation [BCM]). Treatment sessions consisting of SCRM or BCM will be administered twice a week for a duration of 4 weeks. Clinical monitoring indicators include the presence or absence of clinical symptoms as recorded on a symptom recording form, cervical imaging examination findings using cervical computed tomography, degree of neck pain measured by a visual analog scale (VAS), cervical range of motion assessed through cervical mobility measurement, degree of vertigo evaluated using the Vertigo Symptoms Scale-Chinese Version (VSS-C), and adverse events that may occur during the follow-up period. The time points for data collection and follow-up are baseline and postintervention (weeks 4, 8, 12, 16, 20, and 24). This paper presents an overview of the reasoning and structure of a prospective randomized controlled trial with the objective of investigating the clinical efficacy and safety of SCRM in patients with AJS by assessing improvements in clinical symptoms, neck pain severity, and vertigo severity and evaluating changes in cervical imaging findings. Recruitment was started in March 2023. By the end of May 2024, 76 patients were included in this project. The last follow-up data are predicted to be collected by the end of February 2025. This investigation will yield dependable evidence regarding the efficacy and safety of SCRM in patients with AJS. Chinese Clinical Trial Registry ChiCTR2300068510; https://www.chictr.org.cn/showprojEN.html?proj=186883. DERR1-10.2196/57865.

Non-suicidal self-injury trajectories among adolescents during the COVID-19 pandemic: The role of parenting dimensions and stress reactions

BackgroundThe literature on the trajectories of NSSI behavior during the pandemic is scarce and mainly short-term. Furthermore, studies have not explored the buffering mechanisms that may have altered risk trajectories during this vulnerable period. This study aims to analyze the univariate change of NSSI during adolescence and to examine the alteration of the univariate growth due to the time-varying effect of COVID-19-related stress, parenting dimensions (i.e., positive and negative parenting), and their interaction. MethodsParticipants included 830 Italian adolescents (44.2 % females; Mage = 14.52; SD = 0.80), who participated in at least one time point of data collection, from a three-wave longitudinal study (T1: from December 2019 to January 2020; T2: December 2020; T3: December 2021). ResultsThe Latent Growth Curve Analyses show a linear increase in NSSI over time. In regards to time-varying, at T1, the results highlight that higher levels of negative parenting are associated with higher levels of NSSI at the same time point. Instead, at T2, results show that pandemic stress is associated with higher levels of NSSI at T2. Regarding the interaction effect, positive parenting significantly buffered the effect of COVID-19 stress on NSSI at both T2 and T3. LimitationsOnly some dimensions of parenting style (i.e., positive and negative parenting) are included. ConclusionsThis study attempts to deepen the trajectory of NSSI behavior during the two years of the pandemic and examine the changes caused by the time-varying effects, thus providing suggestions for designing programs to prevent engagement in NSSI.

Tailored approach to participant recruitment and retention to maximize health equity in pediatric cancer research

BackgroundLack of diversity in participants throughout the research process limits the generalizability of findings and may contribute to health disparities. There are unique challenges to recruitment of families to pediatric cancer research studies, especially for those from disadvantaged backgrounds. Thus, there is a need to evaluate the most effective recruitment and retention strategies to optimize equitable recruitment of diverse participants.MethodsThe present study adapted and implemented methods outlined previously in the literature. These previous efforts were developed to address barriers to pediatric research, behavioral health intervention research and research with Black adolescents. Recruitment and retention strategies are described across four different time points: pre-approach, initial connection, building connection and follow-up. Eligible families of children with a pediatric cancer diagnosis were approached during a routine oncology visit. Once consented, enrollment and retention rates over three timepoints of data collection were recorded and evaluated.ResultsResults indicated high rates of enrollment (86%) and retention (95%) for eligible participants. There were no trends in heightened attrition for any specific subgroup.ConclusionsThe findings of this study are promising and suggest these recruitment and retention strategies may be useful in recruiting individuals from disadvantaged backgrounds.

Sustained gut dysbiosis and intestinal inflammation show correlation with weight gain in person with chronic HIV infection on antiretroviral therapy

BackgroundPerson with human immunodeficiency virus type-1 (PWH) are prone to chronic inflammation due to residual viral production, even with antiretroviral therapy (ART), which increases the risk of age-related diseases. There is also limited information on changes in the intestinal environment of PWH during ART. In this longitudinal study, we investigated changes in the gut microbiota, persistence of chronic inflammation, interactions between the gut environment and inflammation, and metabolic changes in PWH using long-term ART.ResultsWe analyzed changes in clinical parameters and gut microbiota in 46 PWH over a mean period of 4 years to understand the influence of gut dysbiosis on inflammation. Overall, changes in the gut microbiota included a decrease in some bacteria, mainly involved in short-chain fatty acid (SCFA) production, and an increase in certain opportunistic bacteria. Throughout the study period, an increase in bacterial-specific metabolic activity was observed in the intestinal environment. Continued decline in certain bacteria belonging to the Clostridia class and metabolic changes in gut bacteria involved in glucose metabolism. Additionally, patients with a low abundance of Parabacteroides exhibited low bacterial alpha diversity and a significant increase in body mass index (BMI) during the study period. Monocyte chemoattractant protein 1, a marker of macrophage activation in the plasma, continued to increase from baseline (first stool collection timepoint) to follow-up (second stool collection timepoint), demonstrating a mild correlation with BMI. Elevated BMI was mild to moderately correlated with elevated levels of plasma interleukin 16 and chemokine ligand 13, both of which may play a role in intestinal inflammation and bacterial translocation within the gut microbiota. The rate of BMI increase correlated with the rate of decrease in certain SCFA-producing bacteria, such as Anaerostipes and Coprococcus 3.ConclusionOur data suggest that despite effective ART, PWH with chronic inflammation exhibit persistent dysbiosis associated with gut inflammation, resulting in a transition to an intestinal environment with metabolic consequences. Moreover, the loss of certain bacteria such as Parabacteroides in PWH correlates with weight gain and may contribute to the development of metabolic diseases.

Mechanical characterization and cytocompatibility of linoleic acid modified bone cement for percutaneous cement discoplasty

Minimally invasive spine treatments have been sought after for elderly patients with comorbidities suffering from advanced degenerative disc disease. Percutaneous cement discoplasty (PCD) is one such technique where cement is injected into a degenerated disc with a vacuum phenomenon to relieve patients from pain. Adjacent vertebral fractures (AVFs) are however an inherent risk, particularly for osteoporotic patients, due to the high stiffness of the used cements. While low-modulus cements have been developed for vertebroplasty through the addition of linoleic acid, there are no such variations with a high-viscosity base cement, which is likely needed for the discoplasty application.Therefore, a low-modulus polymethyl methacrylate was developed by the addition of 12%vol. linoleic acid to a high-viscosity bone cement (hv-LA-PMMA). Initial experimental validation of the cement was performed by mechanical testing under compression over a period of 24 weeks, after storage in 37 °C phosphate buffer saline (PBS) solution. Furthermore, cement extracts were used to evaluate residual monomer release and the cytotoxicity of hv-LA-PMMA using fibroblastic cells.Relative to the base commercial cement, a significant reduction of Young’s modulus and compressive strength of 36% and 42% was observed, respectively. Compression-tension fatigue tests at 5 MPa gave an average fatigue limit of 31,078 cycles. This was higher than another low-modulus cement and comparable to the fatigue properties of the disc annulus tissue. Monomer release tests showed that hv-LA-PMMA had a significantly higher release between 24 h and 7 days compared to the original bone cement, similarly to other low-modulus cements. Also, the control cement showed cytocompatibility at all time points of extract collection for 20-fold dilution, while hv-LA-PMMA only showed the same for extract collections at day 7. However, the 20-fold dilution was needed for both the control and the hv-LA-PMMA extracts to demonstrate more than 70% fibroblast viability at day 7.In conclusion, the mechanical testing showed promise in the use of linoleic acid in combination with a high-viscosity PMMA cement to achieve properties adequate to the application. Further testing and in vivo studies are however required to fully evaluate the mechanical performance and biocompatibility of hv-LA-PMMA for possible future clinical application.

P-513 Non-invasive PGT (niPGT) of vitrified blastocysts cultured for 24 hours after thawing

Abstract Study question Is niPGT on culture medium exposed for 24 hours to vitrified-thawed blastocysts useful? Summary answer niPGT using a culture medium from vitrified blastocysts cultured for 24hours after thawing showed a high concordance rate with the PGTa results. What is known already Conventional PGTa, which is widely practiced around the world, requires specialized techniques and involves embryonic trophectoderm (TE) biopsy. Recently, niPGT using cell free DNA released from embryos into culture medium has been reported as an alternative to conventional PGT, and has been found to correlate well with TE-biopsy analysis results (Carmen. Rubio, 2020). Although there have been numerous reports of niPGT accuracy based on the timing of culture medium collection, there have been few comparisons of its accuracy based on different time points of medium collection from the same embryo. Study design, size, duration From March to April 2023, 128 vitrified pronuclear stage embryos from 33 patients with consent for research use, were thawed and cultured, and from Day 4, they were individually cultured for over 40 hours. 60 embryos that reached blastocyst by Day 6 were vitrified, and the spent culture medium (SCM1) was collected. The vitrified blastocysts were later thawed and cultured individually for 24 hours, and then the embryos and spent culture medium (SCM2) were collected. Participants/materials, setting, methods Embryos were cultured in a 30 μl droplet until Day 4 and a 10 μl droplet for individual culture. Culture medium was collected and embryos were subjected to chromosomal analysis by NGS. We compared the results of niPGT taken from the same embryos on days 4- 6 (SCM1) and after thawing of vitrified blastocysts (SCM2), with PGTa analysis of the embryos. Main results and the role of chance Among all media samples analyzed, results were obtained for 80.0% (48/60) SCM1 and 96.7% (58/60) SCM2 samples. The ploidy concordance rate was 81.3% (39/48) for SCM1 and 98.3% (57/58) for SCM2. The overall concordance rate, defined as the combined rate of the total concordance for all chromosomes and the partial concordance for some chromosomes was 72.9% (35/48) for SCM1 and 94.8% (55/58) for SCM2 respectively. Significant differences were identified in the informative sample rate, the ploidy concordance rate, and the overall concordance rate(p &amp;lt; 0.05) between SCM1 and SCM2. Fisher’s exact test was used for statistical analysis. Limitations, reasons for caution In this study, embryo culture was continued to day 6, regardless of morphology of the embryo at day 5, which differs from the usual clinical culture process. Additionally, the timing of sample collection differed between the day 4-6 culture medium sample and that for a blastocyst. Wider implications of the findings The results demonstrated that accuracy of ploidy status was higher in the SCM2 compared to the SCM1 sample, suggesting that analysis of thawed vitrified blastocyst medium maybe a more precise predictor and therefore a non-invasive alternative to conventional PGTa. Trial registration number not applicable

Responsive Complementary Feeding Practices in Rural Muhanga District of Rwanda: A Mixed Methods Study

ABSTRACTBackgroundResponsive feeding among infants and young children (IYC) determines their food acceptance and adequate dietary intake, which enhances growth and developmental opportunities. However, little is known about responsive feeding practices among IYC in Rwanda. This study explored the status and barriers of responsive feeding practices among mothers from rural areas of Muhanga District in Rwanda.MethodThis descriptive longitudinal and exploratory mixed methods study was conducted among 29 mothers from 2 rural health centers in Muhanga District. Mothers were interviewed, and their interactions with children during lunch meals at 6, 9, and 12 months were observed. The interviews were recorded, transcribed, and thematically analyzed using Atlas.ti software.ResultsThe study shows that the number of mothers who reported to verbally encourage their children to eat during feeding increased with the child's age. Less than half of mothers, at all three time points of data collection (at 6, 9, and 12 months), reported and were observed allowing their children to self‐feed, smiling and talking to them during feeding. The perceived major barriers to mother–child interaction during feeding were lack of time due to the burden of other responsibilities, and poverty. In addition, fear of messing up and food waste were barriers to child self‐feeding opportunities.ConclusionFindings indicate that responsive feeding was less practiced among study mothers due to lack of time, poverty, and fear of food waste during child self‐feeding. Nutrition interventions in this community should consider raising awareness of responsive feeding practices through education and encouraging mothers to devote sufficient time to interact with their children during feeding episodes.

Role of HDAC5 Epigenetics in Chronic Craniofacial Neuropathic Pain.

The information provided from the papers reviewed here about the role of epigenetics in chronic craniofacial neuropathic pain is critically important because epigenetic dysregulation during the development and maintenance of chronic neuropathic pain is not yet well characterized, particularly for craniofacial pain. We have noted that gene expression changes reported vary depending on the nerve injury model and the reported sample collection time point. At a truly chronic timepoint of 10 weeks in our model of chronic neuropathic pain, functional groupings of genes examined include those potentially contributing to anti-inflammation, nerve repair/regeneration, and nociception. Genes altered after treatment with the epigenetic modulator LMK235 are discussed. All of these differentials are key in working toward the development of diagnosis-targeted therapeutics and likely for the timing of when the treatment is provided. The emphasis on the relevance of time post-injury is reiterated here.

BIOM-09. TOWARDS CLINICAL IMPLEMENTATION OF LIQUID BIOPSY ANALYSIS FOR PAEDIATRIC BRAIN TUMOUR PATIENTS – A PAN-EUROPEAN EFFORT FOR STANDARDIZATION

Abstract BACKGROUND Liquid biopsies (LBs) allow for analysis of tumour-derived molecules, such as cell-free DNA (cfDNA) and microRNAs (miRNAs), complementing cancer diagnostics, therapy monitoring, and minimal residual disease detection. While circulation-based LB has benefit for extracranial tumour entities, peripheral blood has not historically been a reliable source for diagnosis and disease-monitoring in brain tumours. For these tumours, cerebrospinal fluid (CSF) analysis is better suited for detection despite being a more invasive procedure. However, standardized protocols for sample collection and pre-analytical parameters for these LBs currently are limited. AIM We aim to establish an evidence-based gold standard protocol for cfDNA and miRNA analyses from CSF in paediatric brain tumour patients. In addition to higher compliance in trial-related CSF sampling, this initiative seeks to facilitate identification of clinically relevant indications and time-points for collection, thereby paving the way for well-informed, routine CSF molecular diagnostics. METHODS AND RESULTS We have initiated the Liquid Biopsy Working Group within the framework of the International Society of Paediatric Oncology Europe Brain Tumour Group (SIOPE-BTG). Available literature on LB in brain tumours was critically assessed regarding pre-analytical parameters, downstream analyses and LB assay performance. To directly evaluate confounding by pre-analytical factors, we experimentally compared the impact of CSF sampling sites, storage conditions, and different pre-processing protocols. cfDNA and miRNA yields, purity, and the fraction of tumour-derived material were selected as read-outs and correlated with tumour tissue information. To prepare for clinical translation, we consulted clinical paediatric brain tumour trial coordinators to identify major bottlenecks for CSF sampling in routine clinical practice. In addition, clinical practitioners and patient/ parent representatives have been consulted to comprehensively represent the perspectives and needs of all stakeholders. Together, results of this collaborative effort will be fundamental to the successful clinical integration of LBs to improve the future management of paediatric brain tumour patients.

International trends in shoulder replacement: a meta-analysis from 11 public joint registers.

International variation exists in the types of shoulder replacement used for treatment of specific diseases. Implant choice continues to evolve without high-quality evidence. Our aim was to evaluate trends in incidence rates of shoulder replacement and assess any recent changes in practice between countries by using registry data. Patient characteristics, indication and year of surgery, type of replacement, and collection methods of patient-reported outcomes (PROMs) was extracted from 11 public joint registries. Meta-analyses examined use of reverse total shoulder replacement (RTSR) for osteoarthritis, cuff tear arthropathy, and acute fracture; use of anatomical total shoulder replacement (TSR) for osteoarthritis; and use of humeral hemiarthroplasty for fracture. The annual growth rate of shoulder replacements performed is 6-15% (2011-2019). The use of RTSR has almost doubled (93%). RTSR is now universally performed for cuff tear arthropathy (97.3%, 95% confidence interval [CI] 96.0-98.1). Its use for avascular necrosis, trauma, and inflammatory arthropathy is increasing. The use of RTSR was similar (43.1%, CI 30.0-57.2) versus TSR (44.7%, CI 31.1-59.1) for osteoarthritis. The types of PROMs used, collection time points, and response rates lack standardization. COVID-19 had a varying inter-registry impact on incidence rates. The incidence of shoulder replacements has grown. Use of RTSR has increased for all disease indications despite limited high-quality evidence driving this change in indications outside of cuff arthropathy. Consequently, less variation is observed in international practice. Existing differences now relate to use of newer implant types and methodology of PROMs collection, which prevents international comparison and outcome analysis.

Advanced Ovarian Cancer Patients’ Experiences of Surgical Treatment: A Qualitative Analysis

ObjectivesRecommended treatment for advanced ovarian cancer involves a combination of debulking surgery and chemotherapy. Surgery places a significant burden on a patient's physical, social, sexual, and emotional wellbeing. Existing research exploring the impact of surgery is often limited to questionnaire administration with large gaps between data collection time points, missing key aspects of the perioperative period. Little is known of the experience of ovarian cancer surgical treatment from a patient perspective. This research aims to qualitatively explore advanced ovarian cancer patients’ experience of surgery and identify areas in which quality of life may be impacted. MethodsSemi-structured telephone or face-to-face interviews were conducted with patients who had undergone combined surgical and chemotherapy treatment. Interviews were audio-recorded and transcribed verbatim. Transcripts were analyzed using an inductive approach to thematic analysis. ResultsTwenty ovarian cancer patients who had undergone debulking surgery participated in interviews lasting between 33 and 68 minutes. Qualitative analysis generated five key themes: (1) care services; (2) experiences of a stoma; (3) preoperative experience; (4) impact of surgery; and (5) coping mechanisms. ConclusionsUnderstanding the patient experience of surgical treatment for advanced ovarian cancer can help inform and improve future care. This research explored the ways in which a patient's quality of life is impacted by surgery and highlights areas in which further support may be needed. Knowledge of the patient experience may also aid decision-making for both clinicians and patients when considering different treatment pathways. Implications for Nursing PracticeResults highlighted two crucial points in the surgical pathway where patients' need for emotional support was significant: during pre-op and recovering from surgery as an inpatient. Nursing staff are key to providing reassurance during this time. Specialized stoma nurses were also essential for supporting patients to adapt to their stomas both physically and psychologically.