Ecological drift during colonization drives within-host and between-host heterogeneity in an animal-associated symbiont.

Specialized host-microbe symbioses canonically show greater diversity than expected from simple models, both at the population level and within individual hosts. To understand how this heterogeneity arises, we utilize the squash bug, Anasa tristis, and its bacterial symbionts in the genus Caballeronia. We modulate symbiont bottleneck size and inoculum composition during colonization to demonstrate the significance of ecological drift, the noisy fluctuations in community composition due to demographic stochasticity. Consistent with predictions from the neutral theory of biodiversity, we found that ecological drift alone can account for heterogeneity in symbiont community composition between hosts, even when 2 strains are nearly genetically identical. When acting on competing strains, ecological drift can maintain symbiont genetic diversity among different hosts by stochastically determining the dominant strain within each host. Finally, ecological drift mediates heterogeneity in isogenic symbiont populations even within a single host, along a consistent gradient running the anterior-posterior axis of the symbiotic organ. Our results demonstrate that symbiont population structure across scales does not necessarily require host-mediated selection, as it can emerge as a result of ecological drift acting on both isogenic and unrelated competitors. Our findings illuminate the processes that might affect symbiont transmission, coinfection, and population structure in nature, which can drive the evolution of host-microbe symbioses and microbe-microbe interactions within host-associated microbiomes.

Enhancing cryo-EM structure prediction with DeepTracer and AlphaFold2 integration.

Understanding the protein structures is invaluable in various biomedical applications, such as vaccine development. Protein structure model building from experimental electron density maps is a time-consuming and labor-intensive task. To address the challenge, machine learning approaches have been proposed to automate this process. Currently, the majority of the experimental maps in the database lack atomic resolution features, making it challenging for machine learning-based methods to precisely determine protein structures from cryogenic electron microscopy density maps. On the other hand, protein structure prediction methods, such as AlphaFold2, leverage evolutionary information from protein sequences and have recently achieved groundbreaking accuracy. However, these methods often require manual refinement, which is labor intensive and time consuming. In this study, we present DeepTracer-Refine, an automated method that refines AlphaFold predicted structures by aligning them to DeepTracers modeled structure. Our method was evaluated on 39 multi-domain proteins and we improved the average residue coverage from 78.2 to 90.0% and average local Distance Difference Test score from 0.67 to 0.71. We also compared DeepTracer-Refine with Phenixs AlphaFold refinement and demonstrated that our method not only performs better when the initial AlphaFold model is less precise but also surpasses Phenix in run-time performance.

Observation of the Kondo screening cloud.

When a magnetic impurity exists in a metal, conduction electrons form a spin cloud that screens the impurity spin. This basic phenomenon is called the Kondo effect1,2. Unlike electric-charge screening, the spin-screening cloud3-6 occurs quantum coherently, forming spin-singlet entanglement with the impurity. Although the spins interact locally around the impurity, the Kondo cloud can theoretically spread out over several micrometres. The cloud has not so far been detected, and so its physical existence-a fundamental aspect of the Kondo effect-remains controversial7,8. Here we present experimental evidence of a Kondo cloud extending over a length of micrometres, comparable to the theoretical length ξK. In our device, a Kondo impurity is formed in a quantum dot2,9-11, coupling on one side to a quasi-one-dimensional channel12 that houses a Fabry-Pérot interferometer of various gate-defined lengths L exceeding one micrometre. When we sweep a voltage on the interferometer end gate-separated by L from the quantum dot-to induce Fabry-Pérot oscillations in conductance we observe oscillations in the measured Kondo temperature TK, which is a signature of the Kondo cloud at distance L. When L is less than ξK the TK oscillation amplitude becomes larger as L becomes smaller, obeying a scaling function of a single parameter L/ξK, whereas when L is greater than ξK the oscillation is much weaker. Our results reveal that ξK is the only length parameter associated with the Kondo effect, and that the cloud lies mostly within a length of ξK. Our experimental method offers a way of detecting the spatial distribution of exotic non-Fermi liquids formed by multiple magnetic impurities or multiple screening channels13-16 and of studying spin-correlated systems.

Convergent total synthesis of (+)-calcipotriol: A scalable, modular approach to vitamin D analogs.

A convergent approach for the total synthesis of calcipotriol (brand name: Dovonex), a proven vitamin D analog used for the treatment of psoriasis, and medicinally relevant synthetic analogs is described. A complete approach, not wedded to semisynthesis, toward both the A-ring and CD-ring is reported. From a retrosynthetic standpoint, hidden symmetry within the decorated A-ring is disclosed, which allowed for scalable quantities of this advanced intermediate. In addition, a radical retrosynthetic approach is described, which highlights an electrochemical reductive coupling as well as an intramolecular hydrogen atom transfer Giese addition to establish the 6,5-transcarbon skeleton found in the vitamin D family. Finally, a late-stage decarboxylative cross-coupling approach allowed for the facile preparation of various C20-arylated derivatives that show promising biological activity in an initial bioassay.

Impact of SARS-CoV-2 Infection on Long-Term Depression Symptoms among Veterans.

BACKGROUND: Prior research demonstrates that SARS-COV-2 infection can be associated with a broad range of mental health outcomes including depression symptoms. Veterans, in particular, may be at elevated risk of increased depression following SARS-COV-2 infection given their high rates of pre-existing mental and physical health comorbidities. However, few studies have tried to isolate SARS-COV-2 infection associations with long term, patient-reported depression symptoms from other factors (e.g., physical health comorbidities, pandemic-related stress). OBJECTIVE: To evaluate the association between SARS-COV-2 infection and subsequent depression symptoms among United States Military Veterans. DESIGN: Survey-based non-randomized cohort study with matched comparators. PARTICIPANTS: A matched-dyadic sample from a larger, stratified random sample of participants with and without known to SARS-COV-2 infection were invited to participate in a survey evaluating mental health and wellness 18-months after their index infection date. Sampled participants were stratified by infection severity of the participant infected with SARS-COV-2 (hospitalized or not) and by month of index date. A total of 186 participants in each group agreed to participate in the survey and had sufficient data for inclusion in analyses. Those in the uninfected group who were later infected were excluded from analyses. MAIN MEASURES: Participants were administered the Patient Health Questionnaire-9 as part of a phone interview survey. Demographics, physical and mental health comorbidities were extracted from VHA administrative data. KEY RESULTS: Veterans infected with SARS-COV-2 had significantly higher depression symptoms scores compared with those uninfected. In particular, psychological symptoms (e.g., low mood, suicidal ideation) scores were elevated relative to the comparator group (MInfected = 3.16, 95%CI: 2.5, 3.8; MUninfected = 1.96, 95%CI: 1.4, 2.5). Findings were similar regardless of history of depression. CONCLUSION: SARS-COV-2 infection was associated with more depression symptoms among Veterans at 18-months post-infection. Routine evaluation of depression symptoms over time following SARS-COV-2 infection is important to facilitate adequate assessment and treatment.

Risk of Suicide-Related Outcomes After SARS-COV-2 Infection: Results from a Nationwide Observational Matched Cohort of US Veterans.

BACKGROUND: Negative mental health-related effects of SARS-COV-2 infection are increasingly evident. However, the impact on suicide-related outcomes is poorly understood, especially among populations at elevated risk. OBJECTIVE: To determine risk of suicide attempts and other self-directed violence (SDV) after SARS-COV-2 infection in a high-risk population. DESIGN: We employed an observational design supported by comprehensive electronic health records from the Veterans Health Administration (VHA) to examine the association of SARS-COV-2 infection with suicide attempts and other SDV within one year of infection. Veterans with SARS-COV-2 infections were matched 1:5 with non-infected comparators each month. Three periods after index were evaluated: days 1-30, days 31-365, and days 1-365. PARTICIPANTS: VHA patients infected with SARS-COV-2 between March 1, 2020 and March 31, 2021 and matched non-infected Veteran comparators. MAIN MEASURES: Suicide attempt and other SDV events for the COVID-19 and non-infected comparator groups were analyzed using incidence rates per 100,000 person years and hazard ratios from Cox regressions modeling time from matched index date to first event. Subgroups were also examined. KEY RESULTS: 198,938 veterans with SARS-COV-2 (COVID-19 group) and 992,036 comparators were included. Unadjusted one-year incidence per 100,000 for suicide attempt and other SDV was higher among the COVID-19 group: 355 vs 250 and 327 vs 235, respectively. The COVID-19 group had higher risk than comparators for suicide attempts: days 1-30 hazard ratio (HR) = 2.54 (CI:2.05, 3.15), days 31-365 HR = 1.30 (CI:1.19, 1.43) and days 1-365 HR = 1.41 (CI:1.30, 1.54), and for other SDV: days 1-30 HR = 1.94 (CI:1.51, 2.49), days 31-365 HR = 1.32 (CI:1.20, 1.45) and days 1-365 HR = 1.38 (CI:1.26, 1.51). CONCLUSIONS: COVID-19 patients had higher risks of both suicide attempts and other forms of SDV compared to uninfected comparators, which persisted for at least one year after infection. Results support suicide risk screening of those infected with SARS-COV-2 to identify opportunities to prevent self-harm.

Outcomes following allogeneic hematopoietic cell transplantation relapse in Philadelphia chromosome-positive acute lymphoblastic leukemia.

Improved first progression-free survival following allogeneic hematopoietic cell transplantation relapse with the use of immunotherapy.

Toxicities associated with tyrosine kinase inhibitor maintenance following allogeneic hematopoietic cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia.

Allogeneic hematopoietic cell transplantation (HCT) offers a potential cure in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL); nonetheless, relapses are common and the major cause of mortality. One strategy to prevent relapse is tyrosine kinase inhibitor (TKI) maintenance post-HCT, but published clinical experience is primarily with the first-generation TKI imatinib while data with newer generation TKIs are limited. We conducted a retrospective analysis of 185 Ph+ ALL patients who underwent HCT followed by TKI maintenance from 2003 to 2021 at City of Hope. Initially, 50 (27.0%) received imatinib, 118 (63.8%) received a second-generation TKI (2G-TKI), and 17 (9.2%) received ponatinib. A total of 77 patients (41.6%) required a dose reduction of their initial TKI due to toxicity. Sixty-six patients (35.7%) did not complete maintenance due to toxicity; 69 patients (37.3%) discontinued 1 TKI, and 11 (5.9%) discontinued 2 TKIs due to toxicity. Initial imatinib versus 2G-TKI versus ponatinib maintenance was discontinued in 19 (38.0%) versus 68 (57.6%) versus 3 (17.6%) patients due to toxicity (p = .003), respectively. Patients on ponatinib as their initial TKI had a longer duration of TKI maintenance versus 2G-TKI: 576.0 days (range, 72-921) versus 254.5 days (range, 3-2740; p = .02). The most common reasons for initial TKI discontinuation include gastrointestinal (GI) intolerance (15.1%), cytopenia (8.6%), and fluid retention (3.8%). The 5-year overall survival and progression-free survival for the total population were 78% and 71%, respectively. Our findings demonstrate the challenges of delivering post-HCT TKI maintenance in a large real-world cohort as toxicities leading to TKI interruptions, discontinuation, and dose reduction were common.

Building C(sp3)-rich complexity by combining cycloaddition and C-C cross-coupling reactions.

Prized for their ability to rapidly generate chemical complexity by building new ring systems and stereocentres1, cycloaddition reactions have featured in numerous total syntheses2 and are a key component in the education of chemistry students3. Similarly, carbon-carbon (C-C) cross-coupling methods are integral to synthesis because of their programmability, modularity and reliability4. Within the area of drug discovery, an overreliance on cross-coupling has led to a disproportionate representation of flat architectures that are rich in carbon atoms with orbitals hybridized in an sp2 manner5. Despite the ability of cycloadditions to introduce multiple carbon sp3 centres in a single step, they are less used6. This is probably because of their lack of modularity, stemming from the idiosyncratic steric and electronic rules for each specific type of cycloaddition. Here we demonstrate a strategy for combining the optimal features of these two chemical transformations into one simple sequence, to enable the modular, enantioselective, scalable and programmable preparation of useful building blocks, natural products and lead scaffolds for drug discovery.

Patterns of interventions for central venous catheter-associated deep vein thrombosis and outcomes in cancer patients.

PURPOSE: This letter evaluated the impact of different management strategies, specifically the presence or absence of therapeutic anticoagulation, on clinical outcomes for central venous catheter (CVC)-associated deep vein thrombosis (DVT) in cancer patients. METHODS: One-hundred ninety-eight adult cancer patients with a confirmed CVC-associated DVT diagnosis from February 2013 and February 2021 were included. RESULTS: Incidence of symptomatic recurrent venous thromboembolism (VTE) was similar between patients who received therapeutic anticoagulation and those who did not (14% vs 16%, p = 0.807). In addition, therapeutic anticoagulation did not significantly alter the incidence of grade 3 and above bleeding events despite most patients having hematologic malignancies (9% vs 8%, p = 0.826). CONCLUSION AND RELEVANCE: Therapeutic anticoagulation was not associated with a reduction in the incidence of recurrent VTE or increase the incidence of bleeding in adult cancer patients following a CVC-associated DVT diagnosis.

Prognostic factors for multisystem inflammatory syndrome in children: A systematic review and meta-analysis.

AIM: Multisystem inflammatory syndrome in children (MIS-C) is a novel condition that can occur post-SARS-CoV-2 infection in children and adolescents. There is a paucity of evidence on the prognostic factors associated with MIS-C. The aim of this systematic review and meta-analysis was to summarise the prognostic factors for MIS-C development. METHODS: Five databases were systematically searched from January 2020 to May 2023 for studies reporting on prognostic factors for MIS-C using multivariable regression models. Random-effects meta-analyses were conducted to pool odds ratios for each prognostic factor. Risk of bias was rated using QUIPS and the GRADE framework was used to assess the certainty of evidence for each unique factor. RESULTS: Twelve observational studies (N = 18 024) were included, and 13 unique prognostic factors were amenable to meta-analysis. With moderate certainty, age <12 years, male sex and Black race probably increase the risk of MIS-C. Malignancy and underlying respiratory disease probably decrease the risk of MIS-C. Low-certainty evidence suggests that Asian race may increase the risk of MIS-C, and comorbidity may decrease the risk of MIS-C. CONCLUSION: Current literature presents several prognostic factors related to MIS-C following SARS-CoV-2 infection. Further research is necessary to elucidate the pathophysiologic mechanisms related to MIS-C.

A synthetic 5,3-cross-link in the cell wall of rod-shaped Gram-positive bacteria.

Gram-positive bacteria assemble a multilayered cell wall that provides tensile strength to the cell. The cell wall is composed of glycan strands cross-linked by nonribosomally synthesized peptide stems. Herein, we modify the peptide stems of the Gram-positive bacterium Bacillus subtilis with noncanonical electrophilic d-amino acids, which when in proximity to adjacent stem peptides form novel covalent 5,3-cross-links. Approximately 20% of canonical cell-wall cross-links can be replaced with synthetic cross-links. While a low level of synthetic cross-link formation does not affect B. subtilis growth and phenotype, at higher levels cell growth is perturbed and bacteria elongate. A comparison of the accumulation of synthetic cross-links over time in Gram-negative and Gram-positive bacteria highlights key differences between them. The ability to perturb cell-wall architecture with synthetic building blocks provides a novel approach to studying the adaptability, elasticity, and porosity of bacterial cell walls.

Selenomethionine as an expressible handle for bioconjugations.

Site-selective chemical bioconjugation reactions are enabling tools for the chemical biologist. Guided by a careful study of the selenomethionine (SeM) benzylation, we have refined the reaction to meet the requirements of practical protein bioconjugation. SeM is readily introduced through auxotrophic expression and exhibits unique nucleophilic properties that allow it to be selectively modified even in the presence of cysteine. The resulting benzylselenonium adduct is stable at physiological pH, is selectively labile to glutathione, and embodies a broadly tunable cleavage profile. Specifically, a 4-bromomethylphenylacetyl (BrMePAA) linker has been applied for efficient conjugation of complex organic molecules to SeM-containing proteins. This expansion of the bioconjugation toolkit has broad potential in the development of chemically enhanced proteins.

Suicide risk profiles among service members and veterans exposed to suicide.

OBJECTIVES: Rates of suicide exposure are high among service members and Veterans and are especially concerning given the link between suicide exposure and subsequent suicide risk. However, to date, it is unclear which individuals who are exposed to suicide are subsequently at high risk for suicide. Latent profile analysis (LPA) can provide information on unique risk profiles and subgroups of service members and Veterans who have higher suicide risk after suicide exposure, which has not yet been empirically studied. The purpose of this study was to utilize LPA to identify subgroups of service members and Veterans who are at the highest risk for suicidal thoughts and behaviors following suicide exposure. METHODS: We analyzed data using LPA from 2570 service members and Veterans (82.1% male, 69.5% White, and 12.1% Latino/a/x) who completed the Military Suicide Research Consortium's Common Data Elements, a battery of self-report suicide-related measures. Psychopathology, substance use, mental health service utilization, interpersonal theory of suicide, and suicide exposure variables were used to validate classes. RESULTS: Three latent classes emerged from analyses, one low-risk class and two-high risk classes with differing profile compositions (one primarily differentiated by anxiety symptoms and one differentiated by substance use). CONCLUSION: Class-specific recommendations for suicide prevention efforts will be discussed.

Psychotherapist perceptions of engagement-building behaviours with youth clients across developmental levels.

Building a positive therapeutic relationship is a challenging, yet critical, first step in conducting youth psychotherapy. A number of studies in the youth treatment literature have indicated that a positive therapeutic alliance is related to increased treatment attendance, participation, and outcome. Some research has examined therapist behaviours for engaging therapy clients; however, developmental differences in alliance formation have had limited exploration. The current study surveyed clinicians about their use of specific engagement strategies and the developmental stage of their youth clients. It was hypothesised that participants would differentially rate the importance of different aspects of therapeutic engagement based upon a youth client's developmental stage and that these would correspond with differences in specific engagement strategies. A total of 64 clinicians with experience treating youth completed the study. The participants completed a questionnaire administered online that asked them to rate the importance of developmental differences to forming a therapeutic relationship and provide example client behaviours from their clinical experience for each developmental stage. Results showed clinicians felt the relative importance of collaboration, advocacy, and trustworthiness increased with age. These differences were also evidenced in the specific strategies clinicians endorsed in relation to each engagement factor across developmental stages. This program of research will eventually aid in the development of new guidelines for engaging clients in youth psychotherapy. In addition, the results may be used to enhance psychotherapy training for those working with children and adolescents.

Septic arthritis of the cervical facet joint: Clinical report and review of the literature.

BACKGROUND: Facet joint septic arthritis (FJSA) is an uncommon cause of neck pain, most frequently occurring in the lumbosacral spine. Cervical facet joint septic arthritis is particularly rare. Symptoms typically include spinal or paraspinal pain and tenderness, with severe infections potentially causing neurological impairments. This condition can progress to discitis and osteomyelitis. High clinical suspicion is required for accurate diagnosis and timely treatment. OBJECTIVE: To present the first known case of cervical spine FJSA caused by Moraxella species and provide an updated narrative review of cervical spine FJSA. METHODS: A case study of a 66-year-old male with cervical spine FJSA caused by Moraxella osloensis is detailed. Additionally, a librarian-assisted literature search was conducted on MEDLINE Pubmed, filtering for adult human trials and including various study types, resulting in the inclusion of 9 relevant manuscripts. RESULTS: The patient's symptoms included neck, right upper thoracic, and periscapular pain, with episodes of numbness and tingling. MRI revealed septic arthritis at the C7-T1 facet joint and associated osteomyelitis. Cultures identified Moraxella osloensis as the causative agent. The patient was successfully treated with antibiotics and experienced significant symptom improvement. Literature review highlights that Staphylococcus aureus is the most common causative agent of cervical FJSA, with diagnosis typically involving MRI and culture tests. Treatment generally includes long-term antibiotics, with some cases requiring surgical intervention. CONCLUSIONS: This report underscores the need for high clinical suspicion in diagnosing FJSA and highlights the importance of early intervention. It documents the first known case of cervical spine FJSA caused by Moraxella osloensis, contributing valuable information to the limited literature on this rare condition.

Human Cytomegalovirus Hijacks WD Repeat Domain 11 for Virion Assembly Compartment Formation and Virion Morphogenesis.

Human cytomegalovirus (HCMV) has a large (∼235 kb) genome with more than 200 predicted open reading frames that exploits numerous cellular factors to facilitate its replication. A key feature of HCMV-infected cells is the emergence of a distinctive membranous cytoplasmic compartment termed the virion assembly compartment (vAC). Here, we report that host protein WD repeat domain 11 (WDR11) plays a key role in vAC formation and virion morphogenesis. We found that WDR11 was upregulated at both mRNA and protein levels during HCMV infection. At the late stage of HCMV replication, WDR11 relocated to the vAC and colocalized with markers of the trans-Golgi network (TGN) and vAC. Depletion of WDR11 hindered HCMV-induced membrane reorganization of the Golgi and TGN, altered vAC formation, and impaired HCMV secondary envelopment and virion morphogenesis. Further, motifs critical for the localization of WDR11 in TGN were identified by alanine-scanning mutagenesis. Mutation of these motifs led to WDR11 mislocation outside the TGN and loss of vAC formation. Taken together, these data indicate that host protein WDR11 is required for efficient viral replication at the stage of virion assembly, possibly by facilitating the remodeling of the endomembrane system for vAC formation and virion morphogenesis. IMPORTANCE During the late phase of human cytomegalovirus (HCMV) infection, the endomembrane system is dramatically reorganized, resulting in the formation of a unique structure termed the virion assembly compartment (vAC), which is critical for the assembly of infectious virions. The mechanism of HCMV-induced vAC formation is still not fully understood. In this report, we identified a host factor, WDR11, that plays an important role in vAC formation. Our findings argue that WDR11 contributes to the relocation of the Golgi and trans-Golgi network to the vAC, a membrane reorganization process that appears to be required for efficient virion maturation. The present work provides new insights into the vAC formation and HCMV virion morphogenesis and a potential novel target for antiviral treatment.

Veteran suicide and associated community characteristics in Oregon.

Developing a public health approach to suicide prevention among United States (US) military veterans requires additional data and guidance on where, when, for whom, and what prevention resources should be deployed. This study examines veteran suicide mortality across one US state (Oregon) to identify county-level "hotspots" for veteran suicide, identify community characteristics associated with increased suicide among veterans, and examine excess spatial risk after accounting for space, time, and community characteristics. We linked Oregon mortality data with VA databases to identify veterans who had resided in Oregon and died by suicide between January 1, 2009 and December 31, 2018 (n = 1727). Community characteristic data were gathered at the county level from publicly available datasets on social determinants of health known to be associated with poor health outcomes, including suicide risk. We estimated spatial generalized linear mixed models for the full 10-year period and for each 5-year period using integrated nested Laplace approximation with county as the higher hierarchy. Smoothed standardized mortality ratios were used to identify counties with higher risk of veteran suicide. We found a small clustering of counties in the southwestern corner of Oregon that held the highest risk for veteran suicide across the ten years studied. In multivariable models, higher prevalence of unmarried persons was the only community measure significantly associated with increased veteran suicide risk. However, social contextual factors as a group, along with geographic space, explained most risk for suicide among veterans at the population level.

Syndrome of anterior neural stalk, vertebral abnormality, enteric duplication cyst, and diaphragmatic hernia related to persistent ventral neurenteric canal: report of two cases.

PURPOSE: Abnormalities in notochordal development can cause a range of developmental malformations, including the split notochord syndrome and split cord malformations. We describe two cases that appear related to unusual notochordal malformations, in a female and a male infant diagnosed in the early postnatal and prenatal periods, which were treated at our institution. These cases were unusual from prior cases given a shared constellation of an anterior cervicothoracic meningocele with a prominent "neural stalk," which coursed ventrally from the spinal cord into the thorax in proximity to a foregut duplication cyst. METHODS: Two patients with this unusual spinal cord anomaly were assessed clinically, and with neuroimaging and genetics studies. RESULTS: We describe common anatomical features (anterior neural stalk arising from the spinal cord, vertebral abnormality, enteric duplication cyst, and diaphragmatic hernia) that support a common etiopathogenesis and distinguish these cases. In both cases, we opted for conservative neurosurgical management in regards to the spinal cord anomaly. We proposed a preliminary theory of the embryogenesis that explains these findings related to a persistence of the ventral portion of the neurenteric canal. CONCLUSION: These cases may represent a form of spinal cord malformation due to a persistent neurenteric canal and affecting notochord development that has rarely been described. Over more than 1 year of follow-up while managed conservatively, there was no evidence of neurologic dysfunction, so far supporting a treatment strategy of observation.

Self-Directed Violence Surveillance in the Veterans Health Administration: A National Examination of Factors Associated with Undetermined Versus Suicide Attempt Classification.

This national, observational study examined factors associated with undetermined self-directed violence (SDV) classification among Veterans with a SDV event classified as either "suicide attempt" or "undetermined SDV" in in the Veterans Health Administration (VHA) between 2013 and 2018 (N = 55,878). Generalized estimating equations were used to examine associations of patient and SDV event factors with likelihood of an undetermined SDV classification. Veterans who used poisoning or other methods had 1.52 (95%CI: 1.38, 1.66) and 2.33 (95%CI: 2.16, 2.50) increased odds of having their SDV classified as undetermined, respectively. Veterans with a prior year substance use disorder diagnosis had 1.19 (95%CI: 1.14, 1.24) increased odds of having their SDV classified as undetermined. In sex-stratified analyses, associations of poisoning and substance use disorders held only among males. Additional clinical evaluation of patients with histories of substance use disorders or who use poisoning as method of SDV may be warranted when making SDV determinations.