This study aimed to describe severity-stratified early outcomes in pregnancies with prenatally suspected laterality spectrum disorders (LSD), defined as abnormalities of left-right body patterning affecting thoracoabdominal situs and associated cardiovascular and visceral structures, and to explore phenotype patterns associated with pregestational diabetes mellitus (PDM). Retrospective cohort study of pregnancies evaluated at a tertiary fetal care and fetal cardiology referral center (2010-2026). LSD subtype was assigned using a prespecified operational framework. Cardiac severity was classified as major versus nonmajor congenital heart disease (CHD). Outcomes included termination, intrauterine fetal demise (IUFD), neonatal survival (≤28 days), infant survival (28 days-1 year), cardiac surgery, and gastrointestinal morbidity. Seventy-eight pregnancies were included; 16/78 (20.5%) had PDM. Major CHD was present in 49/78 (62.8%). Pregnancy outcomes included live birth in 62/78 (79.5%), IUFD in 5/78 (6.4%), and termination in 11/78 (14.1%); all terminations occurred among major CHD cases. Among live births, neonatal survival was 59/62 (95.2%), and infant survival among neonatal survivors was 46/53 (86.8%). In major CHD live births (n = 33), neonatal survival was 30/33 (90.9%) and infant survival among neonatal survivors with available follow-up was 20/27 (74.1%). Cardiac surgery occurred in 22/62 (35.5%) and was more common in major versus nonmajor CHD (63.6 vs. 3.4%). Intestinal malrotation occurred in 18/62 (29.0%). Abdominal situs inversus was more frequent in PDM pregnancies (37.5 vs. 8.1%). In LSD, major CHD drives pregnancy termination, surgical intervention, and early mortality concentrated during infancy. PDM was associated with a higher frequency of abdominal situs phenotypes, supporting deliberate postnatal gastrointestinal surveillance planning. · In LSD, infant outcomes vary with CHD severity.. · Major CHD drives termination/surgery.. · PDM occurs across the LSD spectrum..

The UK Operational Research (OR) community has developed a good number of “soft” Operational Research approaches. Amongst those methodologies, Checkland’s Soft Systems Methodology (SSM) occupies a prominent place. This discussion paper examines SSM achievements and legacy in the UK, within the wider context of OR development. After outlining the main SSM features, the paper provides a 50-year span citation analysis to corroborate SSM’s prominent status. Three themes that SSM has brought to the fore exerting important effect in shaping the OR and systems thinking movements, are discussed: (i) SSM emphasis on the use of systems thinking as a means to tackle complexity and its insistence in transferring systemicity to the process of enquiry; (ii) SSM contribution to the emergence and development of the learning/interpretative view in OR practice; and (iii) SSM’s rational model for any research study, based on its constituent elements: Framework of ideas, Methodology and Area of interest. Reflecting on SSM trajectory and these themes, we advance the thesis that SSM has played a crucial role on shaping the soft end of the OR spectrum of approaches. Some initial conclusions are provided in the form of reflections to invite further discussing the legacy and impact of SSM.

Oral Roflumilast for Long-term Management of Behçet Spectrum Disorders: A Multicenter Observational Analysis.

Abstract Background/Aims Nailfold capillaroscopy is an important tool in the assessment of patients with Raynaud’s phenomenon (RP). Automated analysis of capillary morphology in nailfold images recorded using low-cost handheld microscopes has been shown to differentiate between normal capillaries, as found in primary RP, and capillaries from patients with a systemic sclerosis (SSc)-spectrum disorder. While fully automated analysis provides consistent, objective measures post-acquisition, the measures depend on the content and quality of the acquired images, which may vary with different operators. Our aim was to assess repeatability of automated analysis when imaging is performed by operators with varying levels of capillaroscopy experience. Methods 20 subjects (10 healthy controls, 10 patients with SSc) were recruited. Each subject had 4 nailfolds (left/right middle and ring fingers) imaged with a low-cost, handheld microscope, with imaging repeated by two experienced and one inexperienced operator. Acquisition was performed using in-house software to record video sequences, from which the 5 best frames for each nailfold were selected using an automated frame quality assessment model. A deep learning system then computed the following metrics for each nailfold: mean and maximum capillary widths (in µm), mean shape score (range [0,1]), and vessel density (per mm). These were averaged across all fingers to compute subject-level metrics for each operator. The repeatability of each metric was assessed using the intra-class coefficient (ICC). Results Table 1 shows group means for each user/metric combination. Mean and maximum capillary widths were significantly higher and mean shape scores and vessel densities significantly lower in the SSc group for all operators (all p < 0.05 using single-sided Mann-Whitney U-tests). The ICC values (95% CIs in brackets) for each metric were: mean width 0.98 (0.95 - 0.99); maximum width 0.94 (0.87 - 0.98); mean shape score 0.86 (0.73 - 0.92); vessel density 0.91 (0.81 - 0.95). Conclusion The excellent repeatability (ICC > 0.9) for capillary density and width measurements (with good agreement for shape score) between experienced and inexperienced operators provides further evidence that low-cost microscopes paired with automated analysis can provide consistent, objective measures of capillary morphology, aiding the early diagnosis of SSc in routine rheumatology out-patent clinics. Disclosure M. Berks: Shareholder/stock ownership; I am a joint shareholder and director of Capilytics Ltd, which has an interest in commercialising the application of AI to nailfold capillaroscopy images. M. Parkes: None. A. Murray: Shareholder/stock ownership; A.M is a joint shareholder and director of Capilytics Ltd, which has an interest in commercialising the application of AI to nailfold capillaroscopy images. G. Dinsdale: None. J. Manning: None. M. Mandzuk: None. C. Taylor: Shareholder/stock ownership; C.T is a joint shareholder and director of Capilytics Ltd, which has an interest in commercialising the application of AI to nailfold capillaroscopy images. A. Herrick: Shareholder/stock ownership; A.H is a joint shareholder and director of Capilytics Ltd, which has an interest in commercialising the application of AI to nailfold capillaroscopy images.

BackgroundParkinson's Spectrum Disorders are progressive conditions associated with motor, cognitive, and communication decline, making early advance care planning (ACP) essential. However, ACP discussions are often delayed, limiting patient involvement in decision-making. Group-based ACP interventions may offer a scalable and supportive format to facilitate ACP discussions, but their effectiveness in Parkinson's Spectrum Disorders remains unexamined. This study evaluates the impact of a group-based ACP workshop integrated into an outpatient education program for individuals with Parkinson's Spectrum Disorders. The primary outcome was change in participant understanding and engagement in ACP. Secondary and tertiary outcomes included workshop acceptability and perceived impact from the referring providers, respectively.MethodsA retrospective mixed-methods evaluation was conducted. Participants attended a single-session ACP workshop within a multidisciplinary outpatient rehabilitation program. Anonymous surveys were completed before, immediately after, and 3months post-workshop. Quantitative responses were analyzed using ordinal logistic regression. Free-text responses underwent qualitative analysis.ResultsForty survey responses were received across all time points. Participants reported greater comfort with ACP and improved understanding of substitute decision-making. Readiness to assign a power of attorney for personal care (POA-PC) increased significantly (P = 0.005) post-workshop. At 3-month follow-up, 70% of respondents had new ACP discussions with a healthcare provider, and 40% had newly appointed a POA-PC. Participants valued the relaxed, non-clinical group setting and requested more actionable resources.ConclusionsGroup-based ACP workshops represent a feasible and acceptable model for Parkinson's Spectrum Disorders. Observed improvements in ACP understanding and engagement, sustained at 3months, support further exploration of group-based formats for ACP in neurodegenerative conditions.

ABSTRACT Introduction Amyotrophic Lateral Sclerosis (ALS) is the most common adult motor neuron disease, now viewed as a spectrum disorder rather than a single entity. Because of the significant person-to-person variability in the disease’s biology, driven by both genetic and environmental interactions, finding a single “magic bullet” drug is unlikely. Despite decades of research, only a few ALS drugs have being developed. Drug discovery has a 95% failure rate due to genetic complexity, lack of sensitive biomarkers, diagnostic delays, inadequate animal models, and poor clinical trial design. Areas covered This article considers several aspects related to the prevalence of intrinsic disorder in ALS-related proteins and highlights how these features might hinder rational structure-based drug discovery. Expert opinion There is a common oversight in current drug discovery methodologies, which is the neglect of intrinsically disordered proteins (IDPs) playing several crucial roles in the pathology of neurodegeneration in general and ALS in particular. Therefore, it seems that the ‘one-size-fits-all’ approach to ALS is hitting a wall because these ‘shapeshifters’ of the cellular world are ignored. Consequently, to be more successful in finding drugs treating ALS, gears should be shifted from rational structure-based models to intrinsic disorder-centric approaches.

ABSTRACT To evaluate the impact of implementing a Developmental Outreach Clinic within a primary care practice, we implemented a Developmental Outreach Clinic that involved relocating 2 developmental pediatricians to a primary care practice for one half day per week to conduct developmental assessments and consultations on‐site. This care model included co‐location, sharing of: administrative booking process, electronic medical record messaging, and a charting system between the developmental pediatricians and the family physicians. To evaluate this clinic, a retrospective chart review cohort study was conducted. We compared patients who participated in the Developmental Outreach clinic with those who received standard care (i.e., pre‐implementation, family physician referred to the hospital‐affiliated developmental pediatrics clinic serving the same catchment). Health charts of all patients who were booked for a consultation with Developmental Pediatrics 23 months prior to the implementation of the Developmental Outreach Clinic and 23 months following were reviewed. Main outcome measures included changes in service usage (i.e., number of completed assessments/consultations, time from referral to consult) from pre‐ to post‐clinic implementation. A greater number of non‐Autism Spectrum Disorder (ASD) assessments/consultations were completed after implementation of the Developmental Outreach Clinic, with no change in the number of ASD assessments/consultations conducted pre‐ to post‐implementation. The wait time from referral to first appointment was significantly lower for the post‐compared to the pre‐implementation cohort. A Developmental Outreach Clinic within a primary care practice may help improve access to developmental pediatricians through co‐location, including sharing of administrative processes and an Electronic Medical Record. This represents a relatively low‐cost way to reduce administrative inefficiencies while enabling specialists to support a greater number of families alongside family physicians.

People with intellectual disabilities (ID) are known to have a higher risk for a wide range of health conditions compared to the general population. However, there is little research comparing a more comprehensive range of diseases and conditions at different ages. Therefore, the aim of this study was to explore the overall age-specific diagnostic pattern among people with ID compared to the general population. Of all people living in Skåne, the southernmost part of Sweden (n = 1 274 727), those with a diagnosis indicating ID (F70-F79 or Q90 according to ICD-10) and/or service and support for people with ID/Autism spectrum disorders (ASD) constituted the ID cohort (n = 14 716). After excluding those in the same family/household as someone in the ID cohort, the remaining people comprised the general population cohort (gPop; n = 1 226 955). The main outcome was diagnoses by body system (i.e., ICD-10 chapters) during 2014-2021. Differences between the cohorts were investigated using Poisson regression, thereby estimating relative risks for the ID cohort vs. the gPop cohort. Four different diagnostic patterns among people with ID compared to the general population were identified: (1) increased risks with an age-related decline (ICD-10 Chapters III, IV, V, VI, VII, VIII, IX, XI, XII and XIV), (2) increased risk for higher ages but overall similar risks at younger ages (Chapters I and X) and (3) similar or decreased risk across age groups (Chapters II and XIII). For most body systems, there was an increased risk of diagnosis for people with ID, although in some cases, it declined with age. Although there are some potential explanations for this age-related decline, further investigations are needed to understand the pathways behind this phenomenon. Cancer diagnoses stood out in that a decreased risk was found for the ID cohort. This needs further attention. One reason may be due to lower rates of cancer screening in this group. The need for screening interventions tailored for people with ID has been highlighted for at least two decades, but few seem to have been developed, tested or implemented, which means that such interventions are still urgently warranted.

Cartilage hair hypoplasia-anauxetic dysplasia (CHH-AD) spectrum disorders are rare skeletal dysplasias caused by pathogenic variants in RMRP, associated with immune dysfunction and cancer predisposition. While non-Hodgkin lymphoma is more commonly seen, Hodgkin lymphoma (HL) is rarely reported, and its management in this setting remains unclear. We describe 2 siblings with genetically confirmed CHH-AD who developed relapsed/refractory EBV-positive classic HL. Both presented with short stature, atopy, recurrent infections, and elevated IgE. The brother was diagnosed with stage IV disease, and the sister with stage IIB. Despite receiving frontline chemotherapy, both relapsed within a year. Salvage therapy with gemcitabine/vinorelbine induced metabolic responses, followed by radiotherapy and consolidation with brentuximab vedotin. Autologous transplant was considered but declined by the family due to perceived risks. At 30 months follow-up, both remain in complete remission. Genetic testing confirmed a shared homozygous pathogenic RMRP variant. These cases expand the oncologic spectrum of CHH-AD to include HL, highlight the risk of aggressive disease and early relapse, and demonstrate that durable remission may be achieved without transplantation when consolidation with targeted therapy is feasible. Early recognition of CHH-AD features in HL patients may allow risk-adapted therapy and informed genetic counseling.

BackgroundSchizophrenia spectrum disorders (SSDs) and autism spectrum disorder (ASD) share social‐cognitive deficits, genetic architecture, and overlapping animal models, yet the neurochemical signatures that differentiate them remain unclear. This protocol describes a systematic review and meta‐analysis of proton magnetic resonance spectroscopy (1H‐MRS) studies examining glutamate, glutamine, and their combined signals. The primary aim is to establish a human neurochemical benchmark to guide translational research.MethodsEligible studies will be those measuring 1H‐MRS glutamatergic metabolites at ≥3 T field strength in at least one of five brain regions: anterior cingulate cortex, dorsolateral prefrontal cortex, hippocampus, striatum, or thalamus. Adults (≥18 years) with SSD (stratified as ultra‐high risk, first‐episode psychosis, and treatment‐resistant schizophrenia) and ASD diagnosed using standardized criteria will be compared to healthy controls. Systematic searches will be conducted in databases. Two independent reviewers will assess the risk of bias using the AXIS (Appraisal Tool for Cross‐Sectional Studies) and MRS‐Q (Magnetic Resonance Spectroscopy Quality Assessment Tool). Primary outcomes will be regional differences in metabolite concentrations. We will conduct random‐effects meta‐analyses integrating direct and indirect comparisons, with subgroup analyses by illness stage and medication status.ResultsWe expect to identify both shared and distinct glutamatergic alterations across SSD subgroups and ASD, with potential stage‐specific patterns in cortical and subcortical regions.ConclusionsThis comprehensive analysis aims to identify regional brain glutamatergic biomarkers differentiating SSD and ASD. These neurochemical signatures will provide an essential reference framework for validating and guiding reverse‐translational research.PROSPERO Registration NumberCRD420251003550.

Numerous observational studies are available to asymptomatic individuals at risk to carry or known carriers of pathogenic variations associated with amyotrophic lateral sclerosis and frontotemporal degeneration (ALS-FTD) spectrum disorders. Little is known about such individuals' motivations for participation or the impact on their emotional well-being. Asymptomatic at-risk adults, with or without genetic status known, were recruited through social media advocacy groups and by National Society of Genetic Counselors ALS-FTD special interest group members. Interviews were conducted through secure videoconferencing. Two coders independently analyzed interview transcripts, followed by thematic content analysis. Twelve participants (9 status-aware and 3 status-unaware) were interviewed, representing experience with 11 observational studies. Some motivations for participation aligned with previous literature, including altruism, health focus, and intellectual interest. Motivations unique to this population stemmed from the hereditary nature of the disease, including fear of future disease onset and the desire to establish a relationship with a specialized clinical care team, reflecting individual, familial, and societal factors. Benefits of participation included meeting these motivational goals, social connection and support, psychological well-being, and practical benefits. Challenges to participation fell into research-related (e.g., struggles with the observational nature of research), disease-related (e.g., anxiety about disease risk), and logistical (e.g., travel and study procedures) categories. Compared with status-unaware participants, status-aware participants more frequently cited individual motivators for research participation and encountered more research-related challenges when their participation did not align with their anticipated personal health benefits. Interviewees found relationships with providers through research to be rewarding but noted confusion between research and clinical care as a significant challenge. Participation in observational research helps address unmet emotional and medical needs for asymptomatic individuals who are at risk of ALS-FTD spectrum disorders. However, some of these needs are beyond the scope of research, highlighting the need for new models of clinical care for at-risk individuals.

Developmental and epileptic encephalopathy with spike-wave activation in sleep (D/EE-SWAS): Clinical and treatment insights from a cohort of 50 children.

Tuberous sclerosis complex (TSC) is a rare genetic disorder resulting in hamartomas in multiple organs, causing varied manifestations with a substantial burden of illness (BOI) for patients and caregivers. A significant component of the BOI is the high prevalence of TSC-associated epilepsy. The objective of this systematic literature review is to provide an overview of the BOI in TSC-associated epilepsy, a focus not reported in the recent review by Zöllner et al. (2020). Following a search of major databases and congress sites to April 2023, published studies covering epidemiology, quality of life (QOL) of patients and their caregivers, direct and indirect costs, resource use and treatment patterns in children and/or adults with TSC were included. Studies on efficacy and safety, and non-neurological TSC manifestations, were excluded. Relevant studies were manually reviewed, double screened and summarised/synthesised. No statistical analyses or bias assessments were conducted. Relevant articles (n = 241) included 182 reporting global epidemiology data, revealing a wide range of TSC incidence per 100,000 live births (0.153-17.24) and prevalence per 100,000 general population (0.6-12.7). TSC-associated seizures were reported in a mean of 64.1% and 79.8% of adults and children, respectively. Patient-reported outcome (PRO) tools indicated that cognitive impairment and neuropsychiatric disorders (e.g.autism spectrum disorder) frequently occur with TSC-associated epilepsy. The reported BOI is substantial, impacting the QOL of patients, caregivers and the wider family. Additionally, TSC-associated seizures negatively impact QOL, elevate indirect and healthcare costs (e.g. £14,335 vs £4,448), resource use (e.g. hospital admissions, physician visits and impact on patients' and caregivers' careers) and risk of mortality (7.53% vs 3.68%) compared with the healthy population or patients with TSC without seizures. This review summarises the BOI caused by the early onset and refractory nature of TSC-associated epilepsy. Limitations include a lack of recent prevalence data (> 2016), standardised PROs, formal statistical analysis, BOI data in adults and impact on wider family QOL. More robust epidemiological data are needed. Nevertheless, this review supports the importance of early identification and effective seizure management to improve the BOI of TSC-associated epilepsy for patients, caregivers and the wider family, and society.

Abstract Background Enlarged Vestibular Aqueduct (EVA) presents diagnostic challenges owing to varied clinical manifestations and significant variation in hearing loss (HL) progression, which makes it difficult for clinicians to provide timely advice on HL surveillance, surgical interventions, and lifestyle modifications. EVA is often identified incidentally after head trauma or through unrelated symptoms. Aim This case report details an uncommon presentation of EVA in an adolescent, drawing attention to its diverse clinical expression and stressing the need for reliable prognostic tools to guide clinical decision-making and patient support. An adolescent with atypical EVA highlights clinical variability and emphasizes the importance of developing prognostic criteria for better management and counseling. Case presentation A 17-year-old male patient was seen in the Hearing and Balance Clinic at Dubai Hospital in August 2024 with a chief complaint of a constant left ear tinnitus of a few months’ duration. The patient was asymptomatic and did not present with any vestibular symptoms (such as dizziness or vertigo) or systemic comorbidities. On initial examination and audiological assessment, Pure-tone audiometry (PTA) revealed normal right ear thresholds up to 4 kHz, with moderate, sloping sensorineural hearing loss (SNHL) at higher frequencies. The left ear had normal thresholds up to 1 kHz, with moderate to severe SNHL at higher frequencies. Bilateral Type A tympanograms with asymmetrical acoustic reflexes matched the PTA findings. Subsequent evaluations showed stable right ear thresholds but progressive moderate to severe SNHL in the left ear, possibly linked to noise exposure during national service. Despite a 15-day tapered corticosteroid regimen, a limited improvement was noted at low frequencies during follow-up. MRI and CT scans showed significant dilatation of the left vestibular aqueduct and enlargement of the endolymphatic sac. This case suggests that noise exposure may act as an aggravating factor in EVA-associated asymmetric SNHL. Conclusion This case report illustrates an atypical presentation of EVA, which was incidentally discovered and suggested as a potential cause of progressive SNHL. EVA should be included in the differential diagnoses of unilateral SNHL. EVA's clinical variability supports its consideration as a spectrum disorder, emphasizing the need for standardized prognostic criteria to predict the progression course of hearing loss, improve management, and counseling.

Natural-cause mortality and C-reactive protein levels in patients with schizophrenia spectrum disorders: A prospective total cohort study

ABSTRACTSchizophrenia spectrum disorders (SSD) are marked by cognitive deficits and clinical symptoms linked to disrupted neural oscillations. While changes in spectral power are well documented in SSD, many studies have not clearly separated rhythmic (periodic) from the nonrhythmic (aperiodic) brain activity. This study examined both periodic and aperiodic resting‐state EEG components in SSD, recorded from 152 healthy controls and 97 SSD participants. EEG features (periodic power, bandwidth, center frequency; aperiodic exponent and offset) were extracted from global scalp averages and frontoinsular regions, including the dorsal anterior cingulate cortex (dACC), right anterior insula (R‐INS), and left anterior insula (L‐INS). At the scalp level, SSD individuals exhibited a global increase in theta power, along with a decreased alpha center frequency. Aperiodic activity showed increased exponent and offset in SSD. In frontoinsular regions, increased theta power was observed in the dACC, R‐INS, and L‐INS, along with lower alpha center frequency in L‐INS. No significant differences were found for aperiodic activity in these regions. Increased frontoinsular theta power, especially in the dACC, was associated with worse cognitive performance, particularly global cognition and working memory. These findings highlight the importance of separating periodic and aperiodic EEG activity in SSD, suggesting that periodic alterations, particularly in frontoinsular theta oscillations, may underlie cognitive dysfunction in SSD.

Branchio-Oto-Renal Spectrum Disorder: Progressive Genetic Nephropathy with Expanded Phenotypic Presentation in a Nephrology Population

Background: Overfilled Face Syndrome (OFS) is an emerging aesthetic concern resulting from excessive or inappropriate use of dermal fillers. Despite growing recognition of its clinical and psychological consequences, no universally accepted classification or pathophysiological framework currently exists to guide the diagnosis or management of this condition. Methods: This narrative review synthesises current literature on anatomical, procedural and patient-related contributors to OFS. Expert insights, clinical observations and anatomical analysis were incorporated to develop a new classification system based on filler depth, anatomical layer involvement, and etiological mechanisms. The review was structured according to SANRA (Scale for the Assessment of Narrative Review Articles) guidelines to ensure scientific rigour and clarity. Results: A five-type anatomical classification of OFS is proposed to support clinical recognition and staging. Type I represents focal superficial overfill; Type II involves global superficial overfill; Type III denotes deep volumetric overfill; Type IV describes myomodulatory overfill due to interference with mimetic muscles; and Type V includes chronic layered overfill associated with fibrosis and pseudo-ageing. This anatomy-based, aetiology-driven classification is likely to enhance the understanding of filler-induced facial distortions and support more targeted reversal and prevention strategies. Conclusion: A structured classification of OFS can provide a clinically relevant foundation for diagnosis and management. Recognising OFS as a spectrum disorder allows for a personalised, layer-specific and aetiology-informed corrective approach in aesthetic practice.

445PPLXND1: further evidence for the role of PLXND1 in Poland-Möbius spectrum disorder

BackgroundSchizophrenia spectrum disorders (SSD) are chronic psychiatric conditions with high rates of medication nonadherence, relapse, and hospitalization. Long-acting injectable antipsychotics (LAIs) aim to improve adherence; their real-world use in inpatient settings is not yet well understood.ObjectiveTo investigate prescription patterns of LAI antipsychotics in a real-life setting among psychiatric inpatients with SSD in Australia.MethodsThis retrospective cross-sectional study was conducted at a major Australian tertiary center. It investigated prescription trends, demographics, hospitalization outcomes, and substance use among inpatients with SSD who received oral, LAI, or combined oral–LAI treatment. Readmission rates were also analyzed in patients with a history of medication nonadherence.ResultsAmong the total of 510 inpatients with SSD, 26.6% received LAIs, 40% were treated with combined oral–LAI therapy, and 33.3% were prescribed oral antipsychotics alone. Second-generation LAIs were most prevalent (87.5%), with paliperidone being the most frequently used (53.7%). The combined oral–LAI therapy group had the highest rates of nonadherence (83.8%) and substance use (82.8%). Among patients with a history of medication nonadherence, those receiving LAIs had lower 30-day readmission rates compared with the oral antipsychotic treatment group.ConclusionsFindings align with global trends favoring second-generation LAIs and highlight the rising yet understudied use of combined oral–LAI therapy. High nonadherence and substance use in the combined oral–LAI therapy group call for targeted interventions. While LAIs may reduce readmissions in nonadherent patients, further research is needed to assess combined therapy’s effectiveness and optimize prescribing. These insights reinforce the role of LAIs in relapse prevention and the need for tailored adherence strategies.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-025-00511-z.