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Background: Prediction of high-risk events in mental disorder patients is crucial. In our previous study, we developed a deep learning model: DeepBiomarker by using electronic medical records (EMR) to predict suicide related event (SRE) risk in post-traumatic stress disorder (PTSD) patients., Methods: We applied DeepBiomarker2 through data integration of multimodal information: lab test, medication, co-morbidities, and social determinants of health. We analyzed EMRs of 5,565 patients from University of Pittsburgh Medical Center with a diagnosis of PTSD and alcohol use disorder (AUD) on risk of developing an adverse event (opioid use disorder, SREs, depression and death)., Results: DeepBiomarker2 predicted whether a PTSD + AUD patient will have a diagnosis of any adverse events (SREs, opioid use disorder, depression, death) within 3 months with area under the receiver operator curve (AUROC) of 0.94. We found piroxicam, vilazodone, dronabinol, tenofovir, suvorexant, empagliflozin, famciclovir, veramyst, amantadine, sulfasalazine, and lamivudine to have potential to reduce risk., Conclusions: DeepBiomarker2 can predict multiple adverse event risk with high accuracy and identify potential risk and beneficial factors. Our results offer suggestions for personalized interventions in a variety of clinical and diverse populations.

Introduction: Prediction of high-risk events amongst patients with mental disorders is critical for personalized interventions. In our previous study, we developed a deep learning-based model, DeepBiomarker by utilizing electronic medical records (EMR) to predict the outcomes of patients with suicide-related events in post-traumatic stress disorder (PTSD) patients., Methods: We improved our deep learning model to develop DeepBiomarker2 through data integration of multimodal information: lab tests, medication use, diagnosis, and social determinants of health (SDoH) parameters (both individual and neighborhood level) from EMR data for outcome prediction. We further refined our contribution analysis for identifying key factors. We applied DeepBiomarker2 to analyze EMR data of 38,807 patients from University of Pittsburgh Medical Center diagnosed with PTSD to determine their risk of developing alcohol and substance use disorder (ASUD)., Results: DeepBiomarker2 predicted whether a PTSD patient will have a diagnosis of ASUD within the following 3 months with a c-statistic (receiver operating characteristic AUC) of 0·93. We used contribution analysis technology to identify key lab tests, medication use and diagnosis for ASUD prediction. These identified factors imply that the regulation of the energy metabolism, blood circulation, inflammation, and microbiome is involved in shaping the pathophysiological pathways promoting ASUD risks in PTSD patients. Our study found protective medications such as oxybutynin, magnesium oxide, clindamycin, cetirizine, montelukast and venlafaxine all have a potential to reduce risk of ASUDs., Discussion: DeepBiomarker2 can predict ASUD risk with high accuracy and can further identify potential risk factors along with medications with beneficial effects. We believe that our approach will help in personalized interventions of PTSD for a variety of clinical scenarios., Competing Interests: Declaration of Interests: Neal David Ryan is the Treasurer, of the American Academy of Child and Adolescent Psychiatry and also a member of the Scientific Advisory Board of the Child Mind Institute. He reported financial honorarium from the Scientific Advisory Board of the Child Mind Institute. Thomas R Kosten reports funding from the Department of Defense. LiRong Wang reports sub-award from Pharmacotherapies for Alcohol and Substance Use Disorders Alliance (PASA) funded by the Department of Defense. No other disclosures were reported.

Background: Psychotic symptoms are reported as one of the most common complications of Alzheimer's disease (AD), affecting approximately half of AD patients, in whom they are associated with more rapid deterioration and increased mortality. Empiric treatments, namely first and second-generation antipsychotics, confer modest efficacy in AD patients with psychosis (AD+P) and themselves increase mortality. A recent genome-wide meta-analysis and early clinical trials suggest the use and beneficial effects of antidepressants among AD+P patients. This motivates our rationale for exploring their potential as a novel combination therapy option amongst these patients., Methods: We included University of Pittsburgh Medical Center (UPMC) electronic medical records (EMRs) of 10,260 AD patients from January 2004 and October 2019 in our study. Survival analysis was performed to assess the effects of the combination of antipsychotics and antidepressants on the mortality of these patients. To provide more valuable insights on the hidden mechanisms of the combinatorial therapy, a protein-protein interaction (PPI) network representing AD+P was built, and network analysis methods were used to quantify the efficacy of these drugs on AD+P. An indicator score combining the measurements on the separation between drugs and the proximity between the drugs and AD+P was used to measure the effect of an antipsychotic-antidepressant drug pair against AD+P., Results: Our survival analyses replicated that antipsychotic usage is strongly associated with increased mortality in AD patients while the co-administration of antidepressants with antipsychotics showed a significant beneficial effect in reducing mortality. Our network analysis showed that the targets of antipsychotics and antidepressants are well-separated, and antipsychotics and antidepressants have similar proximity scores to AD+P. Eight drug pairs, including some popular recommendations like Aripiprazole/Sertraline and other pairs not reported previously like Iloperidone/Maprotiline showed higher than average indicator scores which suggest their potential in treating AD+P via strong synergetic effects as seen in our study., Conclusion: Our proposed combinations of antipsychotics and antidepressants therapy showed a strong superiority over current antipsychotics treatment for AD+P. The observed beneficial effects can be further strengthened by optimizing drug-pair selection based on our systems pharmacology analysis.