Functional Neurological Disorder Presenting After Concussion: A Retrospective Case Series.

OBJECTIVE: Although a majority of individuals recover from a concussion within weeks of the index injury, a substantial minority of patients report persistent postconcussion symptoms. Some of these symptoms may reflect a diagnosis of functional neurological disorder (FND). The authors evaluated the relationship between persistent postconcussion symptoms and FND symptoms. METHODS: In this retrospective chart review, the authors characterized demographic and clinical information from 50 patients with a confirmed diagnosis of FND whose functional neurological symptoms started after a concussion. RESULTS: Patients who developed FND after a concussion had high rates of baseline risk factors for both persistent postconcussion symptoms and FND. After the concussive event, functional neurological symptoms presented abruptly or developed insidiously over time. Functional neurological symptoms ranged widely and included gait symptoms, seizures, speech and language symptoms, weakness, sensory symptoms, tremors, and vision and oculomotor symptoms. CONCLUSIONS: Functional neurological symptoms can arise after a concussion. FND should be considered in the differential diagnosis of individuals presenting with neurological symptoms beginning after a concussion. By failing to recognize functional symptoms, clinicians may inadvertently reinforce negative health-related beliefs regarding a patient's injured brain.

Endoxifen Approval for Bipolar Disorder in India: A Premature or a Pragmatic Decision?

ABSTRACT: In this commentary, we critique the Indian government's decision to approve endoxifen for the treatment of acute mania among adults.

Proteomic Portraits Reveal Evolutionarily Conserved and Divergent Responses to Spinal Cord Injury.

Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of cerebrospinal fluid and serum samples from 111 patients with acute SCI and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at 6 months with an area under the receiver operating characteristic curve of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response and establish the cerebrospinal fluid abundance of glial fibrillary acidic protein as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.

How many people with type 2 diabetes fulfil the eligibility criteria for randomized, controlled trials of insulin glargine 300 U/mL in a real-world setting?

Randomized controlled trial (RCT) populations often do not reflect those typically seen in clinical practice. This retrospective, observational cohort study analysed the real-world data of people with type 2 diabetes (T2DM) prescribed basal insulin analogues from electronic medical records (EMRs) in the Explorys database, which includes data from 39 integrated healthcare systems in the United States, to determine how representative selected RCTs investigating insulin glargine 300 U/mL (Gla-300) are of T2DM populations in a real-world setting. Applying eligibility criteria derived from the EDITION 1, 2 and 3 (Gla-300 vs. insulin glargine 100 U/mL [Gla-100]) and BRIGHT (Gla-300 vs. insulin degludec) RCTs, we observed that only 17% (33 345/191 218) of people captured in the real-world database would have been eligible for such trials. Those who were ineligible tended to be older, had more comorbidities and a higher baseline hypoglycaemia rate than the eligible group. Using another large US EMR database (Optum Humedica) as corroboration, we found that 15% (36 285/235 697) would have been eligible to participate in the EDITION/BRIGHT RCTs. Furthermore, only 7% (1734/24 547) would have been eligible for the CONCLUDE (insulin degludec vs. Gla-300) RCT. Our findings remind us of the value of real-world data studies, complementing the results of RCTs, and providing additional insights into groups who would typically be excluded from RCTs.

A study of pathways to care among opioid dependent individuals seeking treatment at a community de-addiction clinic in India.

Drug use, including opioid use disorder, is one of the rapidly rising and serious problems affecting populations globally. There is a treatment gap and delay in presentation of drug users to treatment centers. The present study aimed at assessing the pathways to care among opioid-dependent individuals seeking treatment from a community-based treatment center in India. In a cross-sectional observational study conducted at a community clinic of the National Drug Dependence Treatment Centre (NDDTC), New Delhi, India, a total of 100 treatment-seeking drug users (age 18-60 years) fulfilling DSM IV TR criteria for opioid dependence were recruited. The data were collected using a semistructured pro forma based on patient self-report and the encounter form used in the World Health Organization (WHO) Pathway Study. All participants were male, were mostly married, were employed, and belonged to nuclear families. Ninety-eight percent of participants has ever used heroin in a dependent fashion and 20% were using it currently. Mean age of the participants was 40.83 years (SD 12.7). Median age of onset of heroin use was 22 years (IQR 12). Median duration of heroin use was 138 months (IQR 132). Only 21% of participants visited the community deaddiction clinic at the first contact with care. The median time for first treatment-seeking attempt was 9.5 years (IQR 7). The study findings suggest significant delay between onset of drug-related problems and first treatment contact. There is a need to increase the availability and accessibility of treatment services to reduce the delay in treatment seeking.

Glycaemic goal attainment and hypoglycaemia outcomes in type 2 diabetes patients initiating insulin glargine 300 units/mL or 100 units/mL: Real-world results from the DELIVER Naïve cohort study.

AIMS: To compare HbA1c and hypoglycaemia in insulin-naïve patients with type 2 diabetes (T2D) who initiated insulin glargine 300 units/mL (Gla-300) or 100 units/mL (Gla-100). MATERIALS AND METHODS: This retrospective cohort study examined electronic medical records of insulin-naïve adults with T2D who initiated Gla-300 or Gla-100 during March 2015 through to December 2016 with active records for ≥12 months before and ≥6 months after initiation, and ≥1 valid HbA1c value during 6-month baseline and 90-180-day follow-up. Outcomes included HbA1c and hypoglycaemia. Cohorts were propensity score-matched (1:2) on baseline demographic and clinical characteristics. Sensitivity analyses were conducted using broader inclusion criteria. RESULTS: The matched cohorts included 1004 Gla-300 and 2008 Gla-100 initiators (mean age 60.4 years; 53.2% male). During 6-month follow-up, Gla-300 versus Gla-100 initiators had a greater mean HbA1c decrease (-1.52 ± 2.08% vs. -1.30 ± 2.12%; P = 0.003) and more patients achieved HbA1c <7% (25.0% vs. 21.5%; P = 0.029) and <8% (55.0% vs. 49.2%; P = 0.002); and HbA1c <7% (21.9% vs. 17.4%; P = 0.003) and <8% (49.1% vs. 41.8%; P < 0.001) without hypoglycaemia. Gla-300 initiators were similarly or less likely to have any or inpatient/emergency department-associated hypoglycaemia during 3- and 6-month follow-up (e.g. any hypoglycaemia to 6 months: 9.7% vs. 12.5%; adjusted odds ratio 0.61; P = 0.057). CONCLUSIONS: Among insulin-naïve adults with T2D, Gla-300 was associated with significantly better HbA1c reductions (latest value during 90-180-day follow-up) and similar or improved hypoglycaemia outcomes (3- and 6-month follow-up) than Gla-100.

Comparable glycaemic control and hypoglycaemia in adults with type 2 diabetes after initiating insulin glargine 300 units/mL or insulin degludec: The DELIVER Naïve D real-world study.

AIM: To compare glycaemic control, hypoglycaemia and treatment discontinuation of insulin glargine 300 units/mL (Gla-300) and insulin degludec (IDeg) in a real-world study of insulin-naïve adults with type 2 diabetes (T2D). MATERIALS AND METHODS: DELIVER Naive D was a retrospective observational study that used electronic medical record data from the IBM Watson Health Explorys database. Insulin-naïve adults with T2D who started Gla-300 or IDeg between March 2015 and September 2017 were identified. Patients were active in the system for ≥12 months before and ≥6 months after starting Gla-300 or IDeg and had HbA1c measurements during 6-month baseline and 3- to 6-month follow-up. Outcomes were compared among 1:1 propensity score-matched cohorts. RESULTS: In the matched cohorts (n = 638 each), the mean age was 59 years, approximately 53% were male, and mean HbA1c was 9.67% (82 mmol/mol). Mean (SD) HbA1c decreases were comparable in the Gla-300 and IDeg cohorts (-1.67% [2.22] and -1.58% [2.20]; P = 0.51), as were HbA1c target attainment [<7% (53 mmol/mol): 23.8% and 27.4%; P = 0.20; <8% (64 mmol/mol): 55.0% and 57.1%; P = 0.63] and treatment discontinuation (29.2% and 32.6%; P = 0.14). Overall and inpatient/emergency department-associated hypoglycaemia incidences and event rates were similar in both cohorts using fixed 6-month or variable on-treatment follow-up. CONCLUSIONS: Among real-world insulin-naïve adults with T2D, initiation of Gla-300 or IDeg resulted in comparable improvements in glycaemic control and similar rates of hypoglycaemia. These real-world data complement and confirm a randomized trial and other real-world studies.

Switching to insulin glargine 300 units/mL in real-world older patients with type 2 diabetes (DELIVER 3).

AIM: To compare the second-generation basal insulin glargine 300 units/mL (Gla-300) and first-generation basal insulins on glycaemic control and hypoglycaemia risk in older adults with type 2 diabetes (T2D). MATERIALS AND METHODS: DELIVER 3 was a retrospective observational cohort study of electronic medical records. A total of 1176 older adults (aged ≥ 65 years) with T2D and ≥1 HbA1c value during 6 month baseline and 3 to 6 month follow-up who switched from basal insulin to Gla-300 were propensity score-matched to 1176 older adults who switched to a first-generation basal insulin [insulin detemir (IDet) or insulin glargine 100 units/mL (Gla-100)]. Outcomes were follow-up HbA1c, achievement of HbA1c <7% and <8%, hypoglycaemia incidence and event rates, and healthcare resource utilization. RESULTS: Following basal insulin switching, HbA1c reductions were greater/similar with Gla-300 versus IDet/Gla-100 (variable follow-up: -0.45% ± 1.40% vs. -0.29% ± 1.57%; P = .021; fixed follow-up: -0.48% ± 1.49% vs. -0.38% ± 1.59%; P = .114), while HbA1c goal attainment was similar in both cohorts. Gla-300 was associated with less hypoglycaemia [event rate: adjusted rate ratio (aRR): 0.63, 95% CI: 0.53-0.75; P < .001] and inpatient/emergency department-associated hypoglycaemia (adjusted hazard ratio: 0.58, 95% CI: 0.37-0.90; P = .016; aRR: 0.43, 95% CI: 0.31-0.60; P < .001) by variable follow-up. By fixed follow-up, hypoglycaemia results significantly or numerically favoured Gla-300. CONCLUSION: Among older adults with T2D, switching to Gla-300 versus Gla-100/IDet was associated with greater/similar improvements in glycaemic control, and generally less hypoglycaemia.

Real-world evidence concerning clinical and economic outcomes of switching to insulin glargine 300 units/mL vs other basal insulins in patients with type 2 diabetes using basal insulin.

This retrospective cohort study compared real-world clinical and healthcare-resource utilization (HCRU) data in patients with type 2 diabetes using basal insulin (BI) who switched to insulin glargine 300 units/mL (Gla-300) or another BI. Data from the Predictive Health Intelligence Environment database 12 months before (baseline) and 6 months after (follow-up) the switch date (index date, March 1, 2015 to May 31, 2016) included glycated haemoglobin A1c (HbA1c), hypoglycaemia, HCRU and associated costs. Baseline characteristics were balanced using propensity score matching. Change in HbA1c from baseline was similar in both matched cohorts (n = 1819 in each). Hypoglycaemia incidence and adjusted event rate were significantly lower with Gla-300. Patients switching to Gla-300 had a significantly lower incidence of HCRU related to hypoglycaemia. All-cause and diabetes-related hospitalization and emergency-department HCRU were also favourable for Gla-300. Lower HCRU translated to lower costs in patients using Gla-300. In this real-world study, switching to Gla-300 reduced the risk of hypoglycaemia in patients with type 2 diabetes when compared with those switching to another BI, resulting in less HCRU and potential savings of associated costs.

Clinical outcomes in real-world patients with type 2 diabetes switching from first- to second-generation basal insulin analogues: Comparative effectiveness of insulin glargine 300 units/mL and insulin degludec in the DELIVER D+ cohort study.

AIMS: To compare clinical outcomes in patients with type 2 diabetes (T2D) switching from insulin glargine 100 units/mL (Gla-100) or insulin detemir (IDet) to insulin glargine 300 units/mL (Gla-300) or insulin degludec (IDeg). MATERIALS AND METHODS: We conducted a retrospective, observational study of electronic medical records for Gla-300/IDeg adult switchers (March 1, 2015 to January 31, 2017) with active records for 12-month baseline (glycated haemoglobin [HbA1c] used a 6-month baseline period) and 6-month follow-up periods. Gla-300 and IDeg switchers were propensity score-matched using baseline demographic and clinical characteristics. Outcomes were HbA1c change and goal attainment (among patients with HbA1c captured at follow-up), and hypoglycaemia with fixed follow-up (intention-to-treat [ITT]; 6 months) and variable follow-up (on-treatment [OT]; to discontinuation or 6 months). RESULTS: Each matched cohort comprised 1592 patients. The mean decrease in HbA1c and HbA1c goal (<7.0% [53 mmol/mol] and <8.0% [64 mmol/mol]) attainment rates were similar for Gla-300 (n = 742) and IDeg (n = 727) switchers. Using fixed follow-up (ITT method), hypoglycaemia incidence decreased significantly from baseline with Gla-300 (all hypoglycaemia: 15.6% to 12.7%; P = .006; hypoglycaemia associated with inpatient/emergency department [ED] encounter: 5.3% to 3.5%; P = .007), but not with IDeg. After adjusting for baseline hypoglycaemia, no significant differences in hypoglycaemia incidence and event rate were found at follow-up (ITT) for Gla-300 vs IDeg. Using variable follow-up (OT), hypoglycaemia incidence was similar in both groups, but Gla-300 switchers had a lower inpatient/ED hypoglycaemia event rate at follow-up (adjusted rate ratio 0.56; P = .016). CONCLUSIONS: In a real-world setting, switching from Gla-100 or IDet to Gla-300 or IDeg was associated with similar improvements in glycaemic control and hypoglycaemia in adult patients with T2D.

Rationale and design of a cluster-randomized controlled trial to evaluate the effects of a community health worker-based program for cardiovascular risk factor control in India.

BACKGROUND: The increasing burden of cardiovascular disease (CVD) in low- and middle-income countries is largely driven by the increasing prevalence of hypertension, diabetes, and tobacco use. We hypothesize that the utilization of community health workers (CHWs) to screen for and manage these 3 determinants of CVD in an integrated manner would be an effective approach to favorably affecting public health. METHODS: We have designed and set up the infrastructure to implement a 2-year community-based cluster randomized controlled trial in an underserved region of West Bengal, India. Participants include around 1200 adults, aged between 35 and 70 years, with ≥1 cardiovascular risk factor. They are recruited through home-based screening into a total of 12 clusters, which are randomized to either a control or intervention arm before screening. After the screening, CHWs follow up with participants enrolled in the intervention arm for a period of 2 years through home visits. The control arm receives usual care in the community. The CHW arm follows a behavioral strategy focused on modifying the individual's lifestyle, increasing knowledge of CVD, promoting smoking cessation, increasing physician-seeking behavior, and promoting medication adherence. The main project office is based in Cleveland, OH, at University Hospitals/CWRU, and the local site office is located in Dalkhola, West Bengal, at a local nonprofit set up for the study. Institutional review board approval was obtained both in Cleveland as well as in India. OUTCOME EVALUATION: The 2-year primary outcome of the study is the absolute reduction in systolic blood pressure among hypertensive participants, absolute reduction in fasting blood glucose among diabetic participants, and absolute reduction in average number of cigarettes smoked per day among smokers. DISCUSSION: We believe that this study infrastructure serves as a useful model for international collaboration. It builds on unique local resources, attends to important domestic requirements, and will ultimately provide an evidence-based approach that will help manage the increasing burden of CVD worldwide.

Problematic Internet Use and Its Correlates Among Students from Three Medical Schools Across Three Countries.

OBJECTIVE: The authors aimed to assess and compare problematic internet use among medical students enrolled in a graduate degree course in one school each from Croatia, India, and Nigeria and to assess correlates of problematic use among these students. METHODS: The questionnaire included a sociodemographic profile of participants and Young's Internet Addiction Test. RESULTS: The final analysis included 842 subjects. Overall, 38.7 and 10.5 % of respondents scored in the mild and moderate categories. Only a small fraction (0.5 %) of students scored in the severe category. Being male and spending more time on the internet were correlated with problematic internet use. Moreover, a significantly higher proportion of participants who scored above the cutoff used the Internet for browsing, social networking, chatting, gaming, shopping, and viewing pornography. However, there was no difference between the two groups with regard to using the internet for e-mailing or academic activities. CONCLUSIONS: It is important to address problematic internet use among medical students. The correlates can help identify those at increased risk.

Predicting disease onset from electronic health records for population health management: a scalable and explainable Deep Learning approach.

Introduction: The move from a reactive model of care which treats conditions when they arise to a proactive model which intervenes early to prevent adverse healthcare events will benefit from advances in the predictive capabilities of Artificial Intelligence and Machine Learning. This paper investigates the ability of a Deep Learning (DL) approach to predict future disease diagnosis from Electronic Health Records (EHR) for the purposes of Population Health Management. Methods: In this study, embeddings were created using a Word2Vec algorithm from structured vocabulary commonly used in EHRs e.g., Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) codes. This study is based on longitudinal medical data from ~50 m patients in the USA. We introduced a novel method of including binned observation values into an embeddings model. We also included novel features associated with wider determinants of health. Patient records comprising these embeddings were then fed to a Bidirectional Gated Recurrent Unit (GRU) model to predict the likelihood of patients developing Type 2 Diabetes Mellitus, Chronic Obstructive Pulmonary Disorder (COPD), Hypertension or experiencing an Acute Myocardial Infarction (MI) in the next 3 years. SHapley Additive exPlanations (SHAP) values were calculated to achieve model explainability. Results: Increasing the data scope to include binned observations and wider determinants of health was found to improve predictive performance. We achieved an area under the Receiver Operating Characteristic curve value of 0.92 for Diabetes prediction, 0.94 for COPD, 0.92 for Hypertension and 0.94 for MI. The SHAP values showed that the models had learned features known to be associated with these outcomes. Discussion: The DL approach outlined in this study can identify clinically-relevant features from large-scale EHR data and use these to predict future disease outcomes. This study highlights the promise of DL solutions for identifying patients at future risk of disease and providing clinicians with the means to understand and evaluate the drivers of those predictions.

Meditation-induced psychosis: a narrative review and individual patient data analysis.

BACKGROUND: Meditation is associated with health benefits; however, there are reports that it may trigger or exacerbate psychotic states. In this review, we aim to collate case reports of psychotic disorders occurring in association with meditative practice and to discuss the relationship between psychosis and meditation. METHODOLOGY: We performed case-based analysis of all the existing studies published in English language using PubMed, PsycINFO, Cochrane, Scopus, EMBASE, CINAHL and Google Scholar with the search terms; 'Psychosis' OR 'Psychotic Symptoms' OR 'Schizophrenia' AND 'Meditation.' RESULTS: A total of 19 studies and 28 cases were included in the review. The patients described had an age range of 18-57 years; there was equal distribution of males and females. The diagnoses included acute psychosis in 14 cases, schizophrenia in 7 cases, mania with psychotic symptoms in 3 cases, and schizoaffective disorder in 1 case. The types of meditation described were Transcendent, Mindfulness, Buddhist Meditation like Qigong, Zen, and Theraveda, and others like Bikram yoga, Pranic Healing, and Hindustan Type meditation. Of the 28 cases reported, 14 patients had certain precipitating factors like insomnia, lack of food intake, history of mental illness, stress, and psychoactive substance use. CONCLUSION: There are case reports of psychotic disorder arising in association with meditative practice; however, it is difficult to attribute a causal relationship between the two. At the same time, there is a body of research describing the beneficial effect of meditative practice in clinical settings for patients with psychotic disorders. Appropriately designed studies are needed to further investigate the relationship between meditative practice and psychosis.

Clinical outcomes in high-hypoglycaemia-risk patients with type 2 diabetes switching to insulin glargine 300 U/mL versus a first-generation basal insulin analogue in the United States : Results from the DELIVER High Risk real-world study.

AIMS: To compare 12-month clinical effectiveness of insulin glargine 300 units/mL (Gla-300) versus first-generation basal insulin analogues (BIAs) (insulin glargine 100 units/mL [Gla-100] or insulin detemir [IDet]) in patients with type 2 diabetes (T2D) who were at high risk of hypoglycaemia and switched from one BIA to a different one (Gla-300 or Gla-100/IDet) in a real-world setting. METHODS: DELIVER High Risk was a retrospective observational cohort study of 2550 patients with T2D who switched BIA to Gla-300 (Gla-300 switchers) and were propensity score-matched (1:1) to patients who switched to Gla-100 or IDet (Gla-100/IDet switchers). Outcomes were change in glycated haemoglobin A1c (HbA1c), attainment of HbA1c goals (<7% and <8%), and incidence and event rates of hypoglycaemia (all-hypoglycaemia and hypoglycaemia associated with an inpatient/emergency department [ED] contact). RESULTS: HbA1c reductions were similar following switching to Gla-300 or Gla-100/IDet (-0.51% vs. -0.53%; p = .67), and patients showed similar attainment of HbA1c goals. Patients in both cohorts had comparable all-hypoglycaemia incidence and event rates. However, the Gla-300 switcher cohort had a significantly lower risk of inpatient/ED-associated hypoglycaemia (adjusted odds ratio: 0.73, 95% confidence interval: 0.60-0.89; p = .002) and experienced significantly fewer inpatient/ED-associated hypoglycaemic events (0.21 vs. 0.33 events per patient per year; p < .001). CONCLUSION: In patients with T2D at high risk of hypoglycaemia, switching to Gla-300 or Gla-100/IDet achieved similar HbA1c reductions and glycaemic goal attainment, but Gla-300 switchers had a significantly lower risk of hypoglycaemia associated with an inpatient/ED contact during 12 months after switching.

Penetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia, Bipolar Disorder, and Depression Among Adults in the US Veterans Affairs Health Care System.

Importance: Serious mental illnesses, including schizophrenia, bipolar disorder, and depression, are heritable, highly multifactorial disorders and major causes of disability worldwide. Objective: To benchmark the penetrance of current neuropsychiatric polygenic risk scores (PRSs) in the Veterans Health Administration health care system and to explore associations between PRS and broad categories of human disease via phenome-wide association studies. Design, Setting, and Participants: Extensive Veterans Health Administration's electronic health records were assessed from October 1999 to January 2021, and an embedded cohort of 9378 individuals with confirmed diagnoses of schizophrenia or bipolar 1 disorder were found. The performance of schizophrenia, bipolar disorder, and major depression PRSs were compared in participants of African or European ancestry in the Million Veteran Program (approximately 400 000 individuals), and associations between PRSs and 1650 disease categories based on ICD-9/10 billing codes were explored. Last, genomic structural equation modeling was applied to derive novel PRSs indexing common and disorder-specific genetic factors. Analysis took place from January 2021 to January 2022. Main Outcomes and Measures: Diagnoses based on in-person structured clinical interviews were compared with ICD-9/10 billing codes. PRSs were constructed using summary statistics from genome-wide association studies of schizophrenia, bipolar disorder, and major depression. Results: Of 707 299 enrolled study participants, 459 667 were genotyped at the time of writing; 84 806 were of broadly African ancestry (mean [SD] age, 58 [12.1] years) and 314 909 were of broadly European ancestry (mean [SD] age, 66.4 [13.5] years). Among 9378 individuals with confirmed diagnoses of schizophrenia or bipolar 1 disorder, 8962 (95.6%) were correctly identified using ICD-9/10 codes (2 or more). Among those of European ancestry, PRSs were robustly associated with having received a diagnosis of schizophrenia (odds ratio [OR], 1.81 [95% CI, 1.76-1.87]; P < 10-257) or bipolar disorder (OR, 1.42 [95% CI, 1.39-1.44]; P < 10-295). Corresponding effect sizes in participants of African ancestry were considerably smaller for schizophrenia (OR, 1.35 [95% CI, 1.29-1.42]; P < 10-38) and bipolar disorder (OR, 1.16 [95% CI, 1.11-1.12]; P < 10-10). Neuropsychiatric PRSs were associated with increased risk for a range of psychiatric and physical health problems. Conclusions and Relevance: Using diagnoses confirmed by in-person structured clinical interviews and current neuropsychiatric PRSs, the validity of an electronic health records-based phenotyping approach in US veterans was demonstrated, highlighting the potential of PRSs for disentangling biological and mediated pleiotropy.