Predicting Choroidal Nevus Transformation to Melanoma Using Machine Learning.

Purpose: To develop and validate machine learning (ML) models to predict choroidal nevus transformation to melanoma based on multimodal imaging at initial presentation. Design: Retrospective multicenter study. Participants: Patients diagnosed with choroidal nevus on the Ocular Oncology Service at Wills Eye Hospital (2007-2017) or Mayo Clinic Rochester (2015-2023). Methods: Multimodal imaging was obtained, including fundus photography, fundus autofluorescence, spectral domain OCT, and B-scan ultrasonography. Machine learning models were created (XGBoost, LGBM, Random Forest, Extra Tree) and optimized for area under receiver operating characteristic curve (AUROC). The Wills Eye Hospital cohort was used for training and testing (80% training-20% testing) with fivefold cross validation. The Mayo Clinic cohort provided external validation. Model performance was characterized by AUROC and area under precision-recall curve (AUPRC). Models were interrogated using SHapley Additive exPlanations (SHAP) to identify the features most predictive of conversion from nevus to melanoma. Differences in AUROC and AUPRC between models were tested using 10 000 bootstrap samples with replacement and results. Main Outcome Measures: Area under receiver operating curve and AUPRC for each ML model. Results: There were 2870 nevi included in the study, with conversion to melanoma confirmed in 128 cases. Simple AI Nevus Transformation System (SAINTS; XGBoost) was the top-performing model in the test cohort [pooled AUROC 0.864 (95% confidence interval (CI): 0.864-0.865), pooled AUPRC 0.244 (95% CI: 0.243-0.246)] and in the external validation cohort [pooled AUROC 0.931 (95% CI: 0.930-0.931), pooled AUPRC 0.533 (95% CI: 0.531-0.535)]. Other models also had good discriminative performance: LGBM (test set pooled AUROC 0.831, validation set pooled AUROC 0.815), Random Forest (test set pooled AUROC 0.812, validation set pooled AUROC 0.866), and Extra Tree (test set pooled AUROC 0.826, validation set pooled AUROC 0.915). A model including only nevi with at least 5 years of follow-up demonstrated the best performance in AUPRC (test: pooled 0.592 (95% CI: 0.590-0.594); validation: pooled 0.656 [95% CI: 0.655-0.657]). The top 5 features in SAINTS by SHAP values were: tumor thickness, largest tumor basal diameter, tumor shape, distance to optic nerve, and subretinal fluid extent. Conclusions: We demonstrate accuracy and generalizability of a ML model for predicting choroidal nevus transformation to melanoma based on multimodal imaging. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

REPRODUCTIVE AGEING: BGP-15 mitigates adverse impacts of aging on sperm quality, fertility, and offspring health in male mice.

In Brief: Aging in men is associated with diminished sperm quality and a higher incidence of altered fetal development and miscarriage in resultant pregnancies. This study in mice identifies a therapeutic compound that, when administered to aged males, improves sperm quality, subsequent embryo development and post-natal offspring health. Abstract: Aging in men is associated with diminished sperm quality and a higher incidence of altered fetal development and miscarriage in resultant pregnancies. We used a mouse model of advanced paternal age to characterize embryonic development in older male mice and tested whether pre-conception treatment with the mitochondrial activator BGP-15 improves reproductive outcomes in old males. Like older men, reproductively old male mice had higher levels of sperm DNA damage and delayed pre-implantation development, associated with a reduced fetal weight and placental weight. Analysis of neonatal outcomes of in vivo-conceived offspring found that pups sired by old males were smaller, had delayed locomotor development, and increased mortality. BGP-15 treatment for 5 days prior to conception reduced sperm DNA oxidation levels and improved on-time embryo development after IVF and pup survival. BGP-15 treatment for 3 weeks prior to conception improved on-time pre-implantation embryo development and fetal viability and increased fetal size in pregnancies sired by old males. These results validate that ageing negatively affects male fertility and offspring physiology and indicates that pre-conception treatment with BGP-15 has the potential to improve sperm quality as well as early embryo development and post-natal health.

Vision of the future: large language models in ophthalmology.

PURPOSE OF REVIEW: Large language models (LLMs) are rapidly entering the landscape of medicine in areas from patient interaction to clinical decision-making. This review discusses the evolving role of LLMs in ophthalmology, focusing on their current applications and future potential in enhancing ophthalmic care. RECENT FINDINGS: LLMs in ophthalmology have demonstrated potential in improving patient communication and aiding preliminary diagnostics because of their ability to process complex language and generate human-like domain-specific interactions. However, some studies have shown potential for harm and there have been no prospective real-world studies evaluating the safety and efficacy of LLMs in practice. SUMMARY: While current applications are largely theoretical and require rigorous safety testing before implementation, LLMs exhibit promise in augmenting patient care quality and efficiency. Challenges such as data privacy and user acceptance must be overcome before LLMs can be fully integrated into clinical practice.

Health Disparities in Young Adults: A Direct Comparison of Distress and Unmet Needs Across Cancer Centers.

PURPOSE: Information on concerns that young adults (YAs) with cancer face when receiving care outside of specialized treatment centers is needed to increase equitable care to YAs at greater risk of marginalization by the health care system. The current study compared distress and unmet needs at the time of clinic visit between YAs receiving care from three different cancer clinics: (1) a National Cancer Institute-designated center, (2) a community-based clinic, and (3) a county hospital outpatient clinic. METHODS: The Adolescent and Young Adult Psycho-Oncology Screening Tool (AYA-POST) was administered to measure distress and cancer-related concerns of YAs in active treatment. A one-way analysis of variance (ANOVA) compared distress scores by treatment site. A Fisher's exact test compared the number of participants endorsing each item on the Needs Assessment Checklist from each site. A simple linear regression determined the association between distress and number of items endorsed on the Needs Assessment Checklist. RESULTS: Ninety-seven participants completed the AYA-POST, endorsing, on average, 11 concerns. Fisher's exact test showed significant differences between sites in the proportion of participants endorsing eight items: boredom (P < .001), eating/appetite (P < .001), nausea/vomiting (P < .001), financial concern (P = .002), hopelessness/helplessness (P = .03), confidentiality (P = .04), sibling concern (P = .04), and insurance (P = .05). The simple linear regression model was significant (F(1, 94) = 39.772, P < .001, R2 = 0.297), indicating the number of unmet needs accounted for almost 30% of the variance in distress. The one-way ANOVA was not significant (F(2, 93) = 1.34, P = .267). CONCLUSION: Social determinants of health can influence the number and type of unmet needs experienced, affecting distress and other outcomes and underscoring the importance of timely, effective, age-appropriate screening and intervention for distress and unmet needs in YAs with cancer.

Pruritus in primary biliary cholangitis is under-recorded in patient medical records.

OBJECTIVE: Cholestatic pruritus in primary biliary cholangitis (PBC) reduces patients' health-related quality of life (HRQoL). Despite this, existing research suggests that pruritus is under-recorded in patients' health records. This study assessed the extent to which pruritus was recorded in medical records of patients with PBC as compared with patient-reported pruritus, and whether patients reporting mild itch were less likely to have pruritus recorded. We also evaluated clinico-demographic characteristics and HRQoL of patients with medical record-documented and patient-reported pruritus. DESIGN: This cross-sectional study used clinical information abstracted from medical records, together with patient-reported (PBC-40) data from patients with PBC in the USA enrolled in the PicnicHealth cohort. Medical record-documented pruritus was classified as 'recent' (at, or within 12 months prior to, enrolment) or 'ever' (at, or any point prior to, enrolment). Patient-reported pruritus (4-week recall) was assessed using the first PBC-40 questionnaire completed on/after enrolment; pruritus severity was classified by itch domain score (any severity: ≥1; clinically significant itch: ≥7). Patient clinico-demographic characteristics and PBC-40 domain scores were described in patients with medical record-documented and patient-reported pruritus; overlap between groups was evaluated. Descriptive statistics were reported. RESULTS: Pruritus of any severity was self-reported by 200/225 (88.9%) patients enrolled; however, only 88/225 (39.1%) had recent medical record-documented pruritus. Clinically significant pruritus was self-reported by 120/225 (53.3%) patients; of these, 64/120 (53.3%) had recent medical record-documented pruritus. Patients reporting clinically significant pruritus appeared to have higher mean scores across PBC-40 domains (indicating reduced HRQoL), versus patients with no/mild patient-reported pruritus or medical-record documented pruritus. CONCLUSION: Compared with patient-reported measures, pruritus in PBC is under-recorded in medical records and is associated with lower HRQoL. Research based only on medical records underestimates the true burden of pruritus, meaning physicians may be unaware of the extent and impact of pruritus, leading to potential undertreatment.

Sucrose overconsumption impairs AgRP neuron dynamics and promotes palatable food intake.

Rapid gut-brain communication is critical to maintain energy balance and is disrupted in diet-induced obesity. In particular, the role of carbohydrate overconsumption in the regulation of interoceptive circuits in vivo requires further investigation. Here, we report that an obesogenic high-sucrose diet (HSD) selectively blunts silencing of hunger-promoting agouti-related protein (AgRP) neurons following intragastric delivery of glucose, whereas we previously showed that overconsumption of a high-fat diet (HFD) selectively attenuates lipid-induced neural silencing. By contrast, both HSD and HFD reversibly dampen rapid AgRP neuron inhibition following chow presentation and promote intake of more palatable foods. Our findings reveal that excess sugar and fat pathologically modulate feeding circuit activity in both macronutrient-dependent and -independent ways and thus may additively exacerbate obesity.

Maintenance of a host-specific minority mutation in the West Nile virus NS3.

West Nile virus (WNV), the most prevalent arthropod-borne virus (arbovirus) in the United States, is maintained in a cycle between Culex spp. mosquitoes and birds. Arboviruses exist within hosts and vectors as a diverse set of closely related genotypes. In theory, this genetic diversity can facilitate adaptation to distinct environments during host cycling, yet host-specific fitness of minority genotypes has not been assessed. Utilizing WNV deep-sequencing data, we previously identified a naturally occurring, mosquito-biased substitution, NS3 P319L. Using both cell culture and experimental infection in natural hosts, we demonstrated that this substitution confers attenuation in vertebrate hosts and increased transmissibility by mosquitoes. Biochemical assays demonstrated temperature-sensitive ATPase activity consistent with host-specific phenotypes. Together these data confirm the maintenance of host-specific minority variants in arbovirus mutant swarms, suggest a unique role for NS3 in viral fitness, and demonstrate that intrahost sequence data can inform mechanisms of host-specific adaptation.

MEPicides: α,ß-unsaturated Fosmidomycin N-Acyl Analogs as Efficient Inhibitors of Plasmodium falciparum 1-Deoxy-d-xylulose-5-phosphate reductoisomerase.

Malaria, a mosquito-borne disease caused by several parasites of the Plasmodium genus, remains a huge threat to global public health. There are an estimated 0.5 million malaria deaths each year, mostly among African children. Unlike humans, Plasmodium parasites and a number of important pathogenic bacteria employ the methyl erythritol phosphate (MEP) pathway for isoprenoid synthesis. Thus, the MEP pathway represents a promising set of drug targets for antimalarial and antibacterial compounds. Here, we present new unsaturated MEPicide inhibitors of 1-deoxy-d-xylulose-5-phosphate reductoisomerase (DXR), the second enzyme of the MEP pathway. A number of these compounds have demonstrated robust inhibition of Plasmodium falciparum DXR, potent antiparasitic activity, and low cytotoxicity against HepG2 cells. Parasites treated with active compounds are rescued by isopentenyl pyrophosphate, the product of the MEP pathway. With higher levels of DXR substrate, parasites acquire resistance to active compounds. These results further confirm the on-target inhibition of DXR in parasites by the inhibitors. Stability in mouse liver microsomes is high for the phosphonate salts, but remains a challenge for the prodrugs. Taken together, the potent activity and on-target mechanism of action of this series further validate DXR as an antimalarial drug target and the α,ß-unsaturation moiety as an important structural component.

Tablet Versus Quick Response Code: Difference in Research Participation Rates?

Conducting research with immunocompromised populations, especially within the context of a global pandemic, warrants consideration of alternative research methods and modes of administration to keep participants safe. Digital and internet-based research methods have been utilized to minimize the risk of harm with cancer patients; however, adolescents and young adults with cancer (AYAs) remain an under served and understudied population with high levels of unmet needs. The purpose of the current study was to examine differences in AYA research participation rates based on two digital survey administration methods (tablet versus QR code). AYAs were randomly assigned to complete an online survey using either a tablet or quick response (QR) code, and participation rates in each group were compared. The total participation rate was 22.9%, with 75% of completed surveys from the tablet group and 25% from the QR code group. While the use of a QR code allows for reduced costs for in-clinic recruitment and may be the most sanitary option during COVID-19, eligible patients in the current study showed trends of increased engagement using a sanitized tablet. It is important to consider how psychosocial research and electronic surveys are administered, as the method may impact recruitment and/or information obtained.

Iatrogenic Calcinosis Cutis in the Pediatric Patient: Case Report and Literature Review.

Calcinosis cutis is the term used to describe the deposition of calcium compounds within the skin and subcutaneous tissue, which can occur after the administration of intravenous calcium compounds. Its etiology is broad, and the clinical presentation is variable, creating a diagnostic challenge. Although iatrogenic calcinosis cutis is extremely uncommon, awareness and early diagnosis of this entity can reduce the risks of severe complications, including soft tissue damage, restricted joint mobility, and even nerve compression. Clinical suspicion should prompt a thorough review of the medical history and appropriate radiographic studies. Evidence of extensive soft tissue calcification must be present on radiographic imaging to confirm the diagnosis. Iatrogenic calcinosis cutis is managed conservatively, and resolution of symptoms is expected within 2 months of symptom onset. Herein we report the case of an infant with DiGeorge syndrome who developed iatrogenic calcinosis cutis after receiving an intraoperative infusion of calcium gluconate. Our patient presented with right lower extremity swelling, erythema, and warmth over a broad area of the leg centered on the entry point of the venipuncture. This was initially mistaken and managed as cellulitis, but once an accurate diagnosis was made, the symptoms gradually resolved with conservative care and no functional sequelae. We also present the literature on iatrogenic and idiopathic calcinosis cutis in the pediatric population.

A single F153Sß3 mutation causes constitutive integrin αIIbß3 activation in a variant form of Glanzmann thrombasthenia.

This report identifies a novel variant form of the inherited bleeding disorder Glanzmann thrombasthenia, exhibiting only mild bleeding in a physically active individual. The platelets cannot aggregate ex vivo with physiologic agonists of activation, although microfluidic analysis with whole blood displays moderate ex vivo platelet adhesion and aggregation consistent with mild bleeding. Immunocytometry shows reduced expression of αIIbß3 on quiescent platelets that spontaneously bind/store fibrinogen, and activation-dependent antibodies (ligand-induced binding site-319.4 and PAC-1) report ß3 extension suggesting an intrinsic activation phenotype. Genetic analysis reveals a single F153Sß3 substitution within the ßI-domain from a heterozygous T556C nucleotide substitution of ITGB3 exon 4 in conjunction with a previously reported IVS5(+1)G>A splice site mutation with undetectable platelet messenger RNA accounting for hemizygous expression of S153ß3. F153 is completely conserved among ß3 of several species and all human ß-integrin subunits suggesting that it may play a vital role in integrin structure/function. Mutagenesis of αIIb-F153Sß3 also displays reduced levels of a constitutively activated αIIb-S153ß3 on HEK293T cells. The overall structural analysis suggests that a bulky aromatic, nonpolar amino acid (F,W)153ß3 is critical for maintaining the resting conformation of α2- and α1-helices of the ßI-domain because small amino acid substitutions (S,A) facilitate an unhindered inward movement of the α2- and α1-helices of the ßI-domain toward the constitutively active αIIbß3 conformation, while a bulky aromatic, polar amino acid (Y) hinders such movements and restrains αIIbß3 activation. The data collectively demonstrate that disruption of F153ß3 can significantly alter normal integrin/platelet function, although reduced expression of αIIb-S153ß3 may be compensated by a hyperactive conformation that promotes viable hemostasis.

RLC phosphorylation amplifies Ca2+ sensitivity of force in myocardium from cMyBP-C knockout mice.

Hypertrophic cardiomyopathy (HCM) is the leading genetic cause of heart disease. The heart comprises several proteins that work together to properly facilitate force production and pump blood throughout the body. Cardiac myosin binding protein-C (cMyBP-C) is a thick-filament protein, and mutations in cMyBP-C are frequently linked with clinical cases of HCM. Within the sarcomere, the N-terminus of cMyBP-C likely interacts with the myosin regulatory light chain (RLC); RLC is a subunit of myosin located within the myosin neck region that modulates contractile dynamics via its phosphorylation state. Phosphorylation of RLC is thought to influence myosin head position along the thick-filament backbone, making it more favorable to bind the thin filament of actin and facilitate force production. However, little is known about how these two proteins interact. We tested the effects of RLC phosphorylation on Ca2+-regulated contractility using biomechanical assays on skinned papillary muscle strips isolated from cMyBP-C KO mice and WT mice. RLC phosphorylation increased Ca2+ sensitivity of contraction (i.e., pCa50) from 5.80 ± 0.02 to 5.95 ± 0.03 in WT strips, whereas RLC phosphorylation increased Ca2+ sensitivity of contraction from 5.86 ± 0.02 to 6.15 ± 0.03 in cMyBP-C KO strips. These data suggest that the effects of RLC phosphorylation on Ca2+ sensitivity of contraction are amplified when cMyBP-C is absent from the sarcomere. This implies that cMyBP-C and RLC act in concert to regulate contractility in healthy hearts, and mutations to these proteins that lead to HCM (or a loss of phosphorylation with disease progression) may disrupt important interactions between these thick-filament regulatory proteins.

Quality Improvement Initiative to Improve Timing of Enteral Feeds in Pediatric Acute Pancreatitis.

BACKGROUND: Acute pancreatitis (AP) represents a significant disease burden in the pediatric population. The management of AP includes fluid resuscitation, pain management, and early enteral feeds. Contrary to old dogma, early enteral feeding has been shown to improve outcomes and reduce hospital length of stay (LOS), yet uptake of this approach has not been standardized. Our aim was to standardize the management of AP, increasing the percentage of patients receiving early enteral nutrition from 40% to 65% within 12 months. METHODS: Between January 2013 and September 2021, we conducted a quality improvement initiative among patients hospitalized with AP. Interventions included the development of a clinical care pathway, integration of an AP order set, and physician education. Our primary outcome was the percentage of patients receiving enteral nutrition within 48 hours of admission, and our secondary outcome was hospital LOS. Balancing measures included hospital readmission rates. RESULTS: A total of 652 patients were admitted for AP during the project, of which 322 (49%) were included after pathway implementation. Before pathway development, the percentage of patients receiving early enteral nutrition was 40%, which increased significantly to 84% after our interventions. This improvement remained stable. Median LOS decreased significantly from 5.5 to 4 days during this timeframe. Our balancing measure of readmission rates did not change during the project period. CONCLUSIONS: Through multiple interventions, including the implementation of an AP clinical pathway, we significantly increased the proportion of patients receiving early enteral nutrition and decreased hospital LOS without increasing hospital readmission rates.

Seeing Blue Dots After COVID-19 Infection.

A 12-year-old female individual receives a diagnosis of SARS-CoV-2 and reports bilateral blurry vision, large blue paracentral scotomata, and a migraine without a scintillating scotoma. What would you do next?

The AYA Care Plan: Initial Evaluation of a Web-Based Psychosocial Intervention.

PURPOSE: Adolescents and young adults (AYA) with cancer do not fit neatly into pediatric or older adult oncology care settings. Recent efforts have led to the development of psychosocial interventions for AYAs, but studies show AYAs demonstrate low levels of engagement in psychosocial services. The AYA Care Plan is one of the only web-based tools providing a personalized, psychosocial resource that addresses unmet needs for AYAs in active treatment and post-treatment survivorship. The current study aims to assess the usability and utility of the AYA Care Plan and identify opportunities for improvement. METHODS: Clinic staff administered an online distress and needs assessment to AYA patients with cancer at outpatient oncology clinics. Personalized care plans were sent to participants on the basis of their responses. A total of 11 AYAs between the ages 18 and 39 years, with a mean age of 31.64 years, then completed qualitative interviews about their experiences. Thematic analysis was used to identify themes on the AYA Care Plan. RESULTS: A majority of participants reported positive usability features. Half of the participants reported using their care plan to make health care decisions. One person indicated not finding the resources helpful, and the other half of participants reported not engaging with the care plan. Participants also offered suggestions for improvement. CONCLUSION: The AYA Care Plan appears to be a useful psychosocial intervention for some AYAs with cancer. Future research should continue to examine the AYA Care Plan's usability and utility, and specify when, how, and for whom the AYA Care Plan is useful.

Biopsychosocial Experiences of Elite Athletes Retiring From Sport for Career-Ending Injuries: A Critically Appraised Topic.

CLINICAL SCENARIO: Injuries cause individuals varying amounts of time loss from participation, which may depend on injury and sport-specific factors such as level of participation. Athletes who never return to sport either choose or are forced to retire due to numerous factors. At elite levels of play, when an athlete chooses retirement, they have the opportunity to create and execute a retirement plan; however, if unexpected (eg, due to career-ending injury), athletes may struggle to transition out of sport effectively, impacting physical, mental, and social health. The biopsychosocial model looks at the relationship between biology, psychology, and socio-environmental factors. Therefore, the purpose of this study was to better understand the biopsychosocial experiences elite athletes face after a career-ending injury so that sport stakeholders can develop and implement strategies to support a healthy transition. CLINICAL QUESTION: How does suffering a career-ending injury affect elite athletes' biopsychosocial experiences during retirement from sport? SUMMARY OF KEY FINDINGS: All studies found that a career-ending injury negatively impacted athlete's biopsychosocial health during the transition period. In addition, social support was identified as a positive coping mechanism and research highlighted the role of education in promoting successful transitions. Sport stakeholders should educate athletes regarding the importance of creating secondary plans. By creating a culture of athletic and nonathletic identity, athletes can feel empowered to navigate different phases of their life despite transition being forced upon them due to injury. CLINICAL BOTTOM LINE: Career-ending injuries negatively impact the biopsychosocial experiences of elite athletes as they transition out of sport. Athletes may face many transitional challenges including a loss of identity, a lack of external support, and/or mental health decline; those more closely identifying with their role as an athlete tend to have a harder transition. Therefore, it is important for all athletes to be adequately prepared for sport retirement, especially given the uncertainty about when and how retirement may occur. STRENGTH OF RECOMMENDATION: Collectively, the body of evidence included to answer the clinical question aligns with the strength of recommendation of C.

The Role of the Flavivirus Replicase in Viral Diversity and Adaptation.

Flaviviruses include several emerging and re-emerging arboviruses which cause millions of infections each year. Although relatively well-studied, much remains unknown regarding the mechanisms and means by which these viruses readily alternate and adapt to different hosts and environments. Here, we review a subset of the different aspects of flaviviral biology which impact host switching and viral fitness. These include the mechanism of replication and structural biology of the NS3 and NS5 proteins, which reproduce the viral genome; rates of mutation resulting from this replication and the role of mutational frequency in viral fitness; and the theory of quasispecies evolution and how it contributes to our understanding of genetic and phenotypic plasticity.

Feasibility of an Opioid Sparing Discharge Protocol Following Laparoscopic Bariatric Surgery.

BACKGROUND: Opioids are commonly prescribed after laparoscopic bariatric surgery but have untoward effects including dependence and diversion. Prior investigation revealed that over three-fourths of discharge opioids prescribed to our patients went unused. OBJECTIVES: To determine the feasibility of an opioid sparing discharge protocol following laparoscopic bariatric surgery. METHODS: A total of 212 opioid-naïve patients undergoing laparoscopic bariatric surgery were examined and divided into two groups; 106 prior to (Cohort A) and 106 after implementation of an opioid sparing discharge protocol (Cohort B). Opioids were converted to morphine milligram equivalents (MME) and post-operative consumption was examined. Data was described as mean ± standard deviation. RESULTS: No patients in Cohort B and 54.7% (58) in Cohort A received an opioid discharge prescription (37.5 MME). Of the 154 patients that remained, only 1.3% (2) received one after discharge. Cohort A took greater amounts of opioids than Cohort B after discharge (4.74 ± 11 vs. 0.21 ± 2 MME; p < 0.001). During hospitalization, Cohort A took greater amounts of opioids (6.92 ± 11 vs. 2.74 ± 5 MME; p < 0.001) but lower amounts of methocarbamol (759 ± 590 vs. 966 ± 585 mg; p = 0.011). No patient requested an opioid prescription refill or presented to the emergency room secondary to pain. CONCLUSION: Following laparoscopic bariatric surgery, an opioid sparing discharge protocol is feasible with < 2% of patients receiving opioids after discharge and no increase in emergency room visits. Education regarding these protocols may impact the amount of opioids taken during hospitalization.

Weight gain and comorbidities associated with oral second-generation antipsychotics: analysis of real-world data for patients with schizophrenia or bipolar I disorder.

BACKGROUND: Many second-generation antipsychotics (SGAs) are associated with weight gain and cardiometabolic effects. Antipsychotic-associated weight gain is linked to treatment interruptions, potentially increasing risk of relapse and hospitalization. This retrospective study assessed clinically significant weight gain (CSWG), treatment interruptions, and development of cardiometabolic conditions in patients with schizophrenia (SZ) or bipolar I disorder (BD-I) following initiation of oral SGAs with moderate to high weight gain risk. METHODS: Patients with no prior use of moderate to high weight gain risk oral SGAs were identified from patient-level medical/pharmacy claims and electronic medical records (January 2013-February 2020; OM1 Real-World Data Cloud). Those with ≥ 1 weight measurement in both the 12 months preceding and 3 months after SGA initiation (index date) were analyzed for continuous changes in weight, CSWG (≥ 7% and ≥ 10% increases from baseline), treatment interruptions (switches/discontinuations), and development of cardiometabolic conditions. RESULTS: Median follow-up times in the SZ (n = 8174) and BD-I (n = 9142) cohorts were 153.4 and 159.4 weeks, respectively; 45.5% and 50.7% were obese at baseline. Mean (SD) percent weight increase during treatment was 3.3% (7.2) and 3.7% (7.0) for patients with SZ and BD-I, respectively, and was highest for underweight/normal weight patients (SZ: 4.8% [8.1]; BD-I: 5.5% [8.7]). More than 96% had treatment interruptions during follow-up, primarily discontinuations. CSWG and treatment interruptions occurred within a median of 13 and 14 weeks after treatment initiation, respectively. Of patients with CSWG and treatment interruptions, approximately 75% did not return to baseline weight during follow-up. Among those without baseline cardiometabolic conditions, 14.7% and 11.3% of patients with SZ or BD-I, respectively, developed ≥ 1 condition over 12 months post-index. Incidence was generally highest among those who were overweight/obese at baseline and those who experienced CSWG. CONCLUSIONS: In this analysis of real-world data, both weight gain and treatment interruptions occurred early in treatment for patients with SZ or BD-I. Treatment-associated weight gain persisted despite switching or discontinuing index treatment. Additionally, cardiometabolic morbidity increased within 12 months of treatment initiation. Patients with SZ or BD-I are at greater risk than the general population for cardiometabolic conditions; weight gain associated with SGAs may exacerbate these health risks.