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The most recent data on the labor force participation rate of individuals who identify as being blind or having vision loss in the United States indicate it is approximately 44%. In 2014, the Office of Federal Contract Compliance Programs promulgated regulations pertaining to Section 503 of the Rehabilitation Act of 1973 to address the continued lack of employment opportunities for individuals with disabilities. These reforms had the potential to expand individuals with disabilities' employment horizons as it was estimated that the number of employees who work directly under a federal contract number in the millions. Five years later, it is unclear how federal contractors are implementing these alterations to recruit and retain legally blind individuals. Using quantitative analysis of responses from 140 current/former legally blind employees and job applicants, this research measured the current employment outcomes of the legally blind community in relation to the Section 503 regulations update. Gaps in employment for legally blind individuals existed, especially in regards to the job classifications in which they found the most success and whether the position held was disability-oriented. These results will inform HR professionals, policymakers, and blind advocates on how to proceed in developing effective disability-conscious workplace laws and policies.

Abstract Pump-probe experiments investigate the strain sensitivity of crustal elastic properties, showing nonlinear variations during the strain cycle. In the laboratory, pre-seismic reductions in seismic velocity indicate that asperity contacts within the fault zone begin to fail before the macroscopic frictional sliding. The recognition of such effects in natural seismic-cycles has been challenging. Here we exploit seasonal hydrological strains, performing a natural analogue to a quasi-static laboratory pump-probe experiment to investigate the nonlinear strain sensitivity of crustal rocks and its role in seismic failure along the tectonically-active Irpinia Fault System (Southern Italy). By comparing 14-years-long series of spring discharge, strain, seismic velocity variations and earthquakes rate, we find that seismicity peaks during maximum hydrological forcing and minimum seismic velocity. Seasonal strains of ~10−6 are required for both earthquake triggering and significant nonlinearity effects arising from modulus reduction. We suggest that, for faults in a critical state, cyclical softening may lead to failure and seasonal seismicity.

Abstract Background Bidirectional crosstalk between HER2 and estrogen receptor (ER) pathways may influence outcomes and the efficacy of endocrine therapy (ET). Low HER2 expression levels (HER2-low) have emerged as a predictive biomarker in patients with breast cancer (BC). Methods PALLAS is an open, international, phase 3 study evaluating the addition of palbociclib for 2 years to adjuvant ET in patients with stage II-III ER-positive/HER2-negative BC. To assess the impact of HER2 expression on patient outcomes in the phase III PALLAS trial, we analyzed (1) the association between rate of HER2-low with demographic and clinicopathological parameters, (2) the prognostic value of HER2-low status on invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS) and (3) HER2 expression’s value as a predictive biomarker of response to palbociclib. HER2-low was defined as HER2 immunohistochemistry (IHC) 1 + or IHC 2 + with negative in situ hybridization (ISH). All pathologic evaluation was performed locally. Prognostic and predictive power of HER2 were assessed with Cox models. Results From the original PALLAS intention-to-treat population (N = 5753), 5304 patients (92.2%) were included in this analysis. Among these, 2254 patients (42.5%) were classified as having HER2 IHC 0 (HER2-0), and 3050 (57.5%) as having HER2-low disease (1838 with IHC 1 + and 1212 with IHC 2 +). Median follow-up was 59.8 months. HER2-low prevalence varied significantly across 21 participating countries (range 16.7% to 75.6%; p

Backgroundobjective: Post-oncological nasal reconstruction presents both aesthetic and functional challenges. While established methods exist for quantitatively evaluating functional results following surgery, equivalent systems for assessing aesthetic outcomes are lacking. Three-dimensional (3D) photogrammetry, already used in maxillofacial and orthodontic surgery for aesthetic evaluation, overcomes some limitations of traditional methods like direct anthropometry. However, its applicability in oncological facial reconstruction has not yet been explored. In our study, we applied the 3dMDtrio™ system for the quantitative analysis of line and surface modifications following nasal reconstruction. Methods: We conducted a prospective observational study enrolling patients with skin neoplasms located on the nose undergoing surgical excision and reconstruction. Using the 3dMDtrio™ system, we measured the dimensions and projections of nasal surfaces and the positions of specific landmarks before and after surgery. The surface measurements were then correlated with aesthetic evaluations performed by three plastic surgeons, not involved in the procedure, using a 5-point Likert scale. Results: We included 33 patients with a mean age of 71 years, ranging from 40 to 94. We obtained complete documentation of all postoperative measurements for 21 patients. We observed significant changes in the positions of the landmarks post-surgery, limited to the right ala and nasion. The average nasal surface area was 4674.41 mm2 ± 477.24 mm2 before surgery and 4667.95 mm2 ± 474.12 mm2 after surgery, with no significant discrepancies. The evaluation using the Likert scale revealed an average score of 3.04 ± 0.48, with a significant negative correlation to the measured surface changes. Conclusion: Our findings suggest that 3D photogrammetry can be considered a valid method for objectively assessing volumetric changes associated with post-oncological nasal reconstructive surgery.

Background: JAK2 V617F is a somatic mutation associated with myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). In MPNs, this mutation is associated with the germline GGCC (46/1) haplotype. Several studies associated JAK2 haplotype GGCC_46/1 with some MPNs clinical parameters, but not one explore the link between JAK2 haplotype GGCC_46/1 and onco-drug resistance. Thus, we assessed for the JAK2 46/1 haplotype’s correlation with therapy response in JAK2 V617F-positive patients. Methods: Patients with MPN, selected by the Hematology Laboratory of “V. Fazzi” Hospital (LE), were analyzed with RLFP-PCR assay with rs10974944 SNP. Results: Results show how the majority of patients had PV (63%) or PMF (61%) and that 58% of patients who developed drug resistance had the C/G genotype, while only 11% had the G/G allele. While no direct correlation between JAK2 46/1 haplotype variants and drug resistance was found, the G/G allele was associated with disease progression to myelofibrosis and certain resistance-related clinical parameters (p = 0.002449, odds ratio = 3.701209). Conclusions: Although other analyses are required, due to the narrow cardinality of sample, our findings suggest how the G/G allele could be useful for MPNs diagnosis and for the prediction of the disease outcome.

Abstract Systemic anticancer therapies (SACTs) are the leading cause of drug-induced interstitial lung disease (ILD). As more novel SACTs become approved, the incidence of this potentially life-threatening adverse event (AE) may increase. Early detection of SACT-related ILD allows for prompt implementation of drug-specific management recommendations, improving the likelihood of AE resolution and, in some instances, widening the patient’s eligibility for future cancer treatment options. ILD requires a diagnosis of exclusion through collaboration with the patient’s multidisciplinary team to rule out other possible etiologies of new or worsening respiratory signs and symptoms. At Grade 1, ILD is asymptomatic, and thus the radiologist is key to detecting the AE prior to the disease severity worsening. Planned computed tomography scans should be reviewed for the presence of ILD in addition to being assessed for tumor response to treatment, and when ILD is suspected, a high-resolution computed tomography (HRCT) scan should be requested immediately. An HRCT scan, with

Abstract Background Breast cancer presents diverse molecular subtypes affecting treatment strategies. Human epidermal growth factor receptor 2 (HER2)-low, hormone receptor-positive (HR+) breast cancer poses a challenge due to limited targeted therapies. Current neoadjuvant treatment primarily utilizes chemotherapy, with conflicting results regarding efficacy in patients with HER2-low breast cancer. Trastuzumab deruxtecan (T-DXd) shows promise in HER2-low metastatic disease, and preliminary evidence suggests synergy with endocrine therapy. Objective This editorial explores the hypothesis that neoadjuvant T-DXd with or without endocrine therapy offers efficacy in the clinical management of HR+/HER2-low breast cancer. Methods We propose a phase II study with two treatment arms: T-DXd + letrozole and T-DXd alone. The primary endpoint is the radiological complete response rate. Secondary endpoints include pathological complete response rate, safety, event-free survival, and overall survival. Exploratory analyses will compare the arms to identify potential for optimizing treatment efficacy and minimizing side effects. Conclusions This study design allows for initial assessment of T-DXd with or without endocrine therapy in the treatment of HER2-low breast cancer. The findings may pave the way for personalized treatment strategies and inform future research, potentially leading to a chemotherapy-sparing approach.

Background: Until recently, targeted therapies have failed to benefit patients with human epidermal growth factor receptor 2 (HER2)-low-expressing breast cancer (BC). Nevertheless, antibody–drug conjugates (ADCs) have reshaped their prognosis. Objectives: We performed a systematic review and meta-analysis to assess the effectiveness of ADCs in patients with HER2-low advanced/metastatic (a/m) BC. Design: This study is a systematic review and meta-analysis. Data sources: We searched PubMed, Embase, and Cochrane databases as well as the American Society of Clinical Oncology, European Society for Medical Oncology, and San Antonio Breast Cancer Symposium conference proceedings. Methods: Studies evaluating ADCs (trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), MRG002, and RC48-ADC) in patients with HER2-low a/mBC were included. We used R software (v.4.2.2) and random effects models for all analyses. Heterogeneity was assessed using the I 2 test. Results: Overall, 14 studies were included (five real-world studies and nine clinical trials (CTs)), with 2883 HER2-low a/mBC patients: 808 received treatment of physician’s choice (TPC), and 2075 ADCs. Most were treated with T-DXd ( n = 1691), followed by SG ( n = 310), MRG002 ( n = 56), and RC48-ADC ( n = 18). Patients treated with T-DXd achieved a significantly higher objective response rate (ORR), disease control rate (DCR), and clinical benefit rate (CBR) than those receiving other ADCs. In the pooled analysis of four randomized CTs, ADCs statistically prolonged progression-free survival ( n = 1828, hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.36–0.68, I 2 = 82%, p

Breast cancer remains a leading cause of brain metastases (BM), which carry a poor prognosis. The current approach to managing BMs in breast cancer patients involves a combination of local therapies (surgery, radiotherapy) and systemic treatments. Developing newer antibody–drug conjugates (ADCs) has sparked a revolution in metastatic breast cancer (MBC) care. ADCs such as ado-trastuzumab emtansine, trastuzumab deruxtecan, and sacituzumab govitecan have demonstrated significant improvement in patient outcomes and are standard of care in the treatment of MBC. Most of the ADC registration studies included patients with stable BMs but excluded individuals with active BM, making intracranial (IC) response assessment a challenge. Promising data has recently emerged, suggesting relevant IC activity for certain ADCs and ongoing studies in patients with active BM that will expand our knowledge. This review aims to summarize the effectiveness of approved ADCs as well as promising new ADCs in development for breast cancer with BM.

BackgroundVitamin B12 is essential for neurological function, red blood cell formation, and DNA synthesis. Deficiency can lead to diverse health conditions, including megaloblastic anemia and neurological issues. Oral supplementation is a standard treatment for B12 deficiency. The Sucrosomial® carrier system offers an innovative approach that enhances supplemental nutrient absorption and bioavailability.ObjectivesThis study aimed to compare the effectiveness of oral Sucrosomial® vitamin B12 formulation vs various conventional B12 supplements, randomly selected from local pharmacies, in increasing and maintaining circulatory B12 levels in healthy deficient adults (200–300 pg/mL).MethodsA randomized, double-blind clinical trial was conducted across three centers in Pakistan from April to July 2024. At KEMU, participants received either Sucrosomial® vitamin B12 or Mecogen SL B12; at LRH, Sucrosomial® B12 or B-SUB B12; and at LUMHS, Sucrosomial® B12, Evermin B12, or Neuromax B12. Participants took a daily single dose of 1,000 μg of the assigned B12 formulation for 7 days. Serum B12 levels were measured at baseline (day 0) and on days 1, 3, 5, and 7.ResultsSucrosomial® B12 was significantly more effective than conventional B12 formulations in increasing and maintaining higher serum B12 levels across all time points. At KEMU, it reached a peak concentration of 454 ± 3.9 pg/mL by day 5, compared to 274 ± 11.1 pg/mL with Mecogen SL B12. At LRH, it peaked at 496 ± 34.4 pg/mL by day 5 versus 304 ± 49.4 pg/mL for B-SUB B12. At LUMHS, it reached 592.7 ± 74.3 pg/mL by day 7, compared to 407.24 ± 41.6 pg/mL for Evermin B12 and 263.82 ± 23.8 pg/mL for Neuromax B12. Sucrosomial® B12 was the only formulation to surpass the deficiency-borderline threshold (200–300 pg/mL) within 24 h of the first dose and was well tolerated with no reported side effects.ConclusionSucrosomial® vitamin B12 demonstrated superior efficacy in rapidly and consistently elevating and maintaining higher circulatory B12 levels compared to conventional supplements. Its characteristic absorption mode and proven efficacy suggest it could effectively address B12 deficiency in a broad range of populations, including those with gastrointestinal conditions and pernicious anemia, thereby supporting overall health.Clinical trial registrationclinicaltrials.gov, NCT06376591.

Recent studies have revealed increasingly worse and more complex mental health conditions in young people, which is reflected in a growing trend in emergency room (ER) visits for acute psychopathological symptoms (APSs). This phenomenon has become exacerbated in recent decades, with a peak in the post-pandemic period. To better characterize the phenomenon, we investigated the change in the rate and type of ER counseling requests provided at the Child Neuropsychiatry Unit of the University Hospital of Bari, Italy over the period between 2019 and 2023 for subjects younger than 18 years old. For this purpose, we retrospectively analyzed a total number of 1073 urgent consultation reports retrieved through the reporting computerized operating system of our hospital. The distribution of the counseling requests provided for APSs and, among these, the distribution of the numbers of APSs and of the male: female ratio were significantly different over the years, with an increasing linear trend identified for APSs (p = 3.095 × 10−7), the average number of APSs (p = 3.598 × 10−7), and female gender prevalence (p = 0.03908), as well as for the patients with a history of psychotropic drug assumption (p = 0.0006319). A significant change in the number of urgent counseling requests received for eating disorders (p = 0.0007408), depression (p = 7.92 × 10−8), somatization (p = 4.03 × 10−6), self-harm (SA) (p = 1.358 × 10−6), and non-suicidal self-injury (NSSI) (p = 8.965 × 10−6) was found, with a significant increasing trend for anxiety (p = 0.0444), depression (p = 8.06 × 10−6), somatization (p = 0.004616), SA (p = 3.998 × 10−8), and NSSI (p = 5.074 × 10−7). The findings of our study support the hypothesis of an alarming progressive worsening of the mental health of children and adolescents, with an overlapping effect of the pandemic exacerbating the process.

Abstract Background Chronic migraine (CM) negatively impacts the quality of life of 2 to 4% of pediatric patients. In adults, CM is frequently linked to medication overuse headache (MOH), but there is a much lower prevalence of MOH in children. A suboptimal response to acute therapies may lead to their reduced use, thus preventing MOH development in children and adolescents. The frequency of patients with CM who do not respond to acute therapies was examined in the present study. We investigated whether the prevalence of MOH was different between responders and non-responders. We also examined whether patients receiving prophylactic therapy had an improved response to acute therapy. Finally, we investigated if there was a difference in the frequency of psychiatric comorbidities between responders and non-responders. Methods We retrospectively analysed clinical data of all chronic pediatric migraineurs under the age of 18 referred to the Headache Centre at Bambino Gesù Children Hospital in June 2021 and February 2023. ICHD3 criteria were used to diagnose CM and MOH. We collected demographic data, including the age at onset of migraine and the age of the CM course. At baseline and after 3 months of preventive treatment, we evaluated the response to acute medications. Neuropsychiatric comorbidities were referred by the children’s parents during the first attendance evaluation. Results Seventy patients with CM were assessed during the chosen period. Paracetamol was tried by 41 patients (58.5%), NSAIDs by 56 patients (80.0%), and triptans by 1 patient (1.4%). Fifty-one participants (73%) were non-responder to the abortive treatment. The presence of MOH was detected in 27.1% of the whole populations. Regarding our primary aim, MOH was diagnosed in 29% of non-responder patients and 22% of responders (p > 0.05). All patients received preventative treatment. After 3 months of preventive pharmacological therapy, 65.4% of patients who did not respond to acute medications achieved a response, while 34.6% of patients who were non-responder remain non-responder (p

Abstract Background Capacitively coupling electric fields (CCEF) is a method of non-invasive biophysical stimulation that enhances fracture repair and spinal fusion. This multicentre randomized controlled trial aimed to further examine the roles of CCEF in (1) the resolution of vertebral bone marrow oedema (VBME) using a follow-up MRI study and (2) pain relief, analgesic drug consumption and quality of life improvement in stimulated patients who were referred with acute vertebral fragility fractures (VFFs) compared to non-stimulated patients. Methods Between September 2016 and December 2019, patients who were referred to the spine centres that participated in this multicentre randomized clinical study with acute VFFs of type OF1 or OF2 were included in the present study. All the VFFs were conservatively managed according to Good Clinical Practice. Moreover, the patients were randomized into two groups: the CCEF group received, as an adjunct to the clinical study protocol, biophysical stimulation with a CCEF device (Osteospine, IGEA) for 8 h per day for 60 days, whereas the control group was treated according to the clinical study protocol. At baseline (T0), the 30-day follow-up (T1), the 60-day follow-up (T2), and the 6-month follow-up (T3), each patient underwent clinical evaluation using the Visual Analogue Scale (VAS) for Pain and the Oswestry Disability Index (ODI). Analgesic therapy with paracetamol 1000 mg tablets for 7 days—or longer, depending on the pain intensity—was performed; patients were required to report their paracetamol consumption on a specific sheet between study day 8 to 180 days of follow-up. MRI studies of the thoracolumbar spine were performed at 0 (T0), 30 (T1) and 60 days of follow-up (T2) using a 1.5-T MRI system in all of the centres that took part in the study. For each VBME area examined via MRI, the vertebral body geometry (i.e. anterior wall height/posterior wall height and vertebral kyphosis) were assessed. Results A total of 66 patients (male: 9, 13.63%; mean age: 73.15 years old) with 69 VFFs were included in the present study and randomized as follows: 33 patients were included in the control group and the remaining 33 patients were randomized into the CCEF group. In the CCEF group, good compliance with CCEF therapy was observed (adherence = 94%), and no adverse effects were recorded. In the stimulated patients, faster VBME resolution and significantly less vertebral body collapse during follow-up were observed compared to the control patients. Moreover, in the active group, faster pain reduction and improvement in the ODI mean score were observed. Stimulated patients also reported a significantly lower paracetamol consumption rate from the third follow-up after treatment until the 6-month follow-up. In terms of sex-related differences, in the CCEF group, VBME showed a faster resolution in male patients compared with females. Conclusion Biophysical stimulation with CCEF, as an adjunct to traditional conservative treatment, is a useful tool to hasten the VBME resolution process and prevent vertebral body deformation. These MRI findings also correlate with faster back pain resolution and quality of life improvement. From the third follow-up after treatment until the 6-month follow-up, stimulated patients reported a significantly lower paracetamol consumption than control patients, even though back pain and quality of life showed no significant differences between the two groups. Level of evidence II. Trial Registration Register: ClinicalTrials.gov, number: NCT05803681.

Abstract To evaluate the role of chemotherapy in stage IA triple-negative breast cancer, we conducted a retrospective population-based study including 8601 patients. The use of chemotherapy significantly increased from 2010 to 2019 in patients with T1b and T1c tumors (p = 0.001 and p

Jin G Choi,1,2 Pathik Amin,3 Alaina Tarantino,4 Mary Qiu3 1Pritzker School of Medicine, University of Chicago, Chicago, IL, USA; 2Department of Ophthalmology, California Pacific Medical Center, San Francisco, CA, USA; 3Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL, USA; 4Ambulatory Pharmacy Services, University of Chicago, Chicago, IL, USACorrespondence: Mary Qiu, Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL, USA, Tel +1 (773) 702-3937, Email mary.qiu@gmail.comPurpose: A major barrier to glaucoma medication adherence is the patient’s out-of-pocket costs. At the University of Chicago Medical Center (UCMC), the institutional pharmacy piloted a program to query out-of-pocket costs for each patient’s medication list based on their insurance coverage. This study aims to describe the impact of this collaboration between the glaucoma service and the outpatient pharmacy service.Methods: This study is a single institution, retrospective chart review of glaucoma patients with a formulary inquiry placed by a single glaucoma specialist between 4/1/2020 and 2/28/2022. Main outcome measures included medications before and after formulary inquiries, additional steps required to access the medications (ie, formulary exceptions, prior authorizations, tier exceptions), and out-of-pocket costs.Results: A total of 343 formulary inquiries, representing 568 individual medication inquiries, were conducted. Out of the 568 medication inquiries, only 78 could be filled for an affordable price without any additional steps. For 45 inquiries, additional steps were required for the medication to become covered at an affordable price. The remaining 445 inquires required additional steps with subsequent denial or prohibitive out-of-pocket costs.Conclusion: The UCMC workflow provided transparent out-of-pocket costs for patients to access glaucoma medications. This workflow may be cost-effective as it minimizes the burden on the overall system by reducing the number of patients who are unable to fill a prescription at the pharmacy due to issues with coverage or affordability. This model of physician-pharmacy collaboration can guide other institutions to implement similar workflows which directly mitigate costs and improve quality of care.Keywords: medication, access, cost

Abstract Chemotherapy and immune checkpoint inhibitors have a role in the post-neoadjuvant setting in patients with triple-negative breast cancer (TNBC). However, the effects of nivolumab, a checkpoint inhibitor, capecitabine, or the combination in changing peripheral immunoscore (PIS) remains unclear. This open-label randomized phase II OXEL study (NCT03487666) aimed to assess the immunologic effects of nivolumab, capecitabine, or the combination in terms of the change in PIS (primary endpoint). Secondary endpoints included the presence of ctDNA, toxicity, clinical outcomes at 2-years and association of ctDNA and PIS with clinical outcomes. Forty-five women with TNBC and residual invasive disease after standard neoadjuvant chemotherapy were randomized to nivolumab, capecitabine, or the combination. Here we show that treatment with immunotherapy containing arms (nivolumab or a combination of nivolumab plus capecitabine) leads to an increase in PIS from baseline to week 6 compared with capecitabine alone, meeting the pre-specified primary endpoint. In addition, the presence of circulating tumor DNA (ctDNA) is associated with disease recurrence, with no new safety signals in the combination arm. Our results provide efficacy and safety data on this combination in TNBC and support further development of PIS and ctDNA analyses to identify patients at high risk of recurrence.

Objective To estimate the cost-effectiveness of craniotomy, compared with decompressive craniectomy (DC) in UK patients undergoing evacuation of acute subdural haematoma (ASDH).Design Economic evaluation undertaken using health resource use and outcome data from the 12-month multicentre, pragmatic, parallel-group, randomised, Randomised Evaluation of Surgery with Craniectomy for Patients Undergoing Evacuation-ASDH trial.Setting UK secondary care.Participants 248 UK patients undergoing surgery for traumatic ASDH were randomised to craniotomy (N=126) or DC (N=122).Interventions Surgical evacuation via craniotomy (bone flap replaced) or DC (bone flap left out with a view to replace later: cranioplasty surgery).Main outcome measures In the base-case analysis, costs were estimated from a National Health Service and Personal Social Services perspective. Outcomes were assessed via the quality-adjusted life-years (QALY) derived from the EuroQoL 5-Dimension 5-Level questionnaire (cost-utility analysis) and the Extended Glasgow Outcome Scale (GOSE) (cost-effectiveness analysis). Multiple imputation and regression analyses were conducted to estimate the mean incremental cost and effect of craniotomy compared with DC. The most cost-effective option was selected, irrespective of the level of statistical significance as is argued by economists.Results In the cost-utility analysis, the mean incremental cost of craniotomy compared with DC was estimated to be −£5520 (95% CI −£18 060 to £7020) with a mean QALY gain of 0.093 (95% CI 0.029 to 0.156). In the cost-effectiveness analysis, the mean incremental cost was estimated to be −£4536 (95% CI −£17 374 to £8301) with an OR of 1.682 (95% CI 0.995 to 2.842) for a favourable outcome on the GOSE.Conclusions In a UK population with traumatic ASDH, craniotomy was estimated to be cost-effective compared with DC: craniotomy was estimated to have a lower mean cost, higher mean QALY gain and higher probability of a more favourable outcome on the GOSE (though not all estimated differences between the two approaches were statistically significant).Ethics Ethical approval for the trial was obtained from the North West—Haydock Research Ethics Committee in the UK on 17 July 2014 (14/NW/1076).Trial registration number ISRCTN87370545.

Transgender and gender diverse youth and young adults (TGDY) experience higher mental health morbidity, including self-harm, suicide ideation, and suicide attempts, as compared to cisgender peers. Support from family members is associated with improved mental health outcomes for TGDY. However, little is known about the process that caregivers who consider themselves supportive undergo and how caregiver-youth relationships evolve through a TGDY's gender journey. Through a reflexive thematic analysis of 14 interviews conducted with caregivers of TGDY from April–July 2022, we sought to understand how caregivers who considered themselves supportive of TGDY navigated shifting relationships with themselves, their children, and their communities. Applying theories of Ambiguous Loss and Thriving Through Relationships, findings coalesced around several themes including reflecting on change, re-negotiating interpersonal relationships, and educating through relationships. The gender journeys of TGDY required caregivers to navigate relationships with self (feeling loss and wrestling with worry for their child), negotiate relationships with others (disclosing to extended family and social networks), and educate themselves and others through relationships (connecting through personal narratives from other families, parents supporting parents, learning to advocate for their child). The process of caregivers learning to support their children was facilitated through profound intrapersonal and interpersonal reflection, connection, and community. Understanding this process is important to inform educational interventions and programs that help caregivers learn to support and advocate effectively for TGDY.