The 2010 i2b2/VA Workshop on Natural Language Processing Challenges for Clinical Records presented three tasks: a concept extraction task focused on the extraction of medical concepts from patient ...reports; an assertion classification task focused on assigning assertion types for medical problem concepts; and a relation classification task focused on assigning relation types that hold between medical problems, tests, and treatments. i2b2 and the VA provided an annotated reference standard corpus for the three tasks. Using this reference standard, 22 systems were developed for concept extraction, 21 for assertion classification, and 16 for relation classification. These systems showed that machine learning approaches could be augmented with rule-based systems to determine concepts, assertions, and relations. Depending on the task, the rule-based systems can either provide input for machine learning or post-process the output of machine learning. Ensembles of classifiers, information from unlabeled data, and external knowledge sources can help when the training data are inadequate.
We identified patients with non-tuberculous mycobacterial (NTM) disease in the US Veterans Health Administration (VHA), examined the distribution of diseases by NTM species, and explored the ...association between NTM disease and the frequency of clinic visits and mortality.
We combined mycobacterial isolate (from natural language processing) with ICD-9-CM diagnoses from VHA data between 2008 and 2012 and then applied modified ATS/IDSA guidelines for NTM diagnosis. We performed validation against a reference standard of chart review. Incidence rates were calculated. Two nested case-control studies (matched by age and location) were used to measure the association between NTM disease and each of 1) the frequency of outpatient clinic visits and 2) mortality, both adjusted by chronic obstructive pulmonary disease (COPD), other structural lung diseases, and immunomodulatory factors.
NTM cases were identified with a sensitivity of 94%, a specificity of >99%. The incidence of NTM was 12.6/100k patient-years. COPD was present in 68% of pulmonary NTM. NTM incidence was highest in the southeastern US. Extra-pulmonary NTM rates increased during the study period. The incidence rate ratio of clinic visits in the first year after diagnosis was 1.3 95%CI 1.34-1.35. NTM patients had a hazard ratio of mortality of 1.4 95%CI 1.1-1.9 in the 6 months after NTM identification compared to controls and 1.99 95%CI 1.8-2.3 thereafter.
In VHA, pulmonary NTM disease is commonly associated with COPD, with the highest rates in the southeastern US. After adjustment, NTM patients had more clinic visits and greater mortality compared to matched patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Peripheral artery disease (PAD) is a leading cause of cardiovascular morbidity and mortality; however, the extent to which genetic factors increase risk for PAD is largely unknown. Using electronic ...health record data, we performed a genome-wide association study in the Million Veteran Program testing ~32 million DNA sequence variants with PAD (31,307 cases and 211,753 controls) across veterans of European, African and Hispanic ancestry. The results were replicated in an independent sample of 5,117 PAD cases and 389,291 controls from the UK Biobank. We identified 19 PAD loci, 18 of which have not been previously reported. Eleven of the 19 loci were associated with disease in three vascular beds (coronary, cerebral, peripheral), including LDLR, LPL and LPA, suggesting that therapeutic modulation of low-density lipoprotein cholesterol, the lipoprotein lipase pathway or circulating lipoprotein(a) may be efficacious for multiple atherosclerotic disease phenotypes. Conversely, four of the variants appeared to be specific for PAD, including F5 p.R506Q, highlighting the pathogenic role of thrombosis in the peripheral vascular bed and providing genetic support for Factor Xa inhibition as a therapeutic strategy for PAD. Our results highlight mechanistic similarities and differences among coronary, cerebral and peripheral atherosclerosis and provide therapeutic insights.
Chronic kidney disease (CKD), defined by low estimated glomerular filtration rate (eGFR), contributes to global morbidity and mortality. Here we conduct a transethnic Genome-Wide Association Study of ...eGFR in 280,722 participants of the Million Veteran Program (MVP), with replication in 765,289 participants from the Chronic Kidney Disease Genetics (CKDGen) Consortium. We identify 82 previously unreported variants, confirm 54 loci, and report interesting findings including association of the sickle cell allele of betaglobin among non-Hispanic blacks. Our transcriptome-wide association study of kidney function in healthy kidney tissue identifies 36 previously unreported and nine known genes, and maps gene expression to renal cell types. In a Phenome-Wide Association Study in 192,868 MVP participants using a weighted genetic score we detect associations with CKD stages and complications and kidney stones. This investigation reinterprets the genetic architecture of kidney function to identify the gene, tissue, and anatomical context of renal homeostasis and the clinical consequences of dysregulation.
Acid-reducing agents (ARAs) are the most commonly prescribed medications in North America and Western Europe. There are currently no data describing the prevalence of their use among cancer patients. ...However, this is a paramount question due to the potential for significant drug–drug interactions (DDIs) between ARAs, most commonly proton pump inhibitors (PPIs), and orally administered cancer therapeutics that display pH-dependent solubility, which may lead to decreased drug absorption and decreased therapeutic benefit. Of recently approved orally administered cancer therapeutics, >50% are characterized as having pH-dependent solubility, but there are currently no data describing the potential for this ARA-DDI liability among targeted agents currently in clinical development. The objectives of this study were to (1) determine the prevalence of ARA use among different cancer populations and (2) investigate the prevalence of orally administered cancer therapeutics currently in development that may be liable for an ARA-DDI. To address the question of ARA use among cancer patients, a retrospective cross-sectional analysis was performed using two large healthcare databases: Thomson Reuters MarketScan (N = 1,776,443) and the U.S. Department of Veterans Affairs (VA, N = 1,171,833). Among all cancer patients, the total prevalence proportion of ARA use (no. of cancer patients receiving an ARA/total no. of cancer patients) was 20% and 33% for the MarketScan and VA databases, respectively. PPIs were the most commonly prescribed agent, comprising 79% and 65% of all cancer patients receiving a prescription for an ARA (no. of cancer patients receiving a PPI /no. of cancer patients receiving an ARA) for the MarketScan and VA databases, respectively. To estimate the ARA-DDI liability of orally administered molecular targeted cancer therapeutics currently in development, two publicly available databases, (1) Kinase SARfari and (2) canSAR, were examined. For those orally administered clinical candidates that had available structures, the pKa’s and corresponding relative solubilities were calculated for a normal fasting pH of 1.2 and an “ARA-hypochlorhydric” pH of 4. Taking calculated pKa’s and relative solubilities into consideration, clinical candidates were classified based on their risk for an ARA-DDI. More than one-quarter (28%) of the molecules investigated are at high risk for an ARA-DDI, and of those high risk molecules, nearly three-quarters (73%) are being clinically evaluated for at least one of five cancer types with the highest prevalence of ARA use (gastrointestinal, pancreatic, lung, glioblastoma multiforme, gastrointestinal stromal tumor (GIST)). These data strongly suggest that with the clinical development of ARA-DDI-susceptible cancer therapeutics will come continued challenges for drug-development scientists, oncologists, and regulatory agencies in ensuring that patients achieve safe and efficacious exposures of their cancer therapeutics and thus optimal patient outcomes.
The Million Veteran Program (MVP) was established in 2011 as a national research initiative to determine how genetic variation influences the health of US military veterans. Here we genotyped 312,571 ...MVP participants using a custom biobank array and linked the genetic data to laboratory and clinical phenotypes extracted from electronic health records covering a median of 10.0 years of follow-up. Among 297,626 veterans with at least one blood lipid measurement, including 57,332 black and 24,743 Hispanic participants, we tested up to around 32 million variants for association with lipid levels and identified 118 novel genome-wide significant loci after meta-analysis with data from the Global Lipids Genetics Consortium (total n > 600,000). Through a focus on mutations predicted to result in a loss of gene function and a phenome-wide association study, we propose novel indications for pharmaceutical inhibitors targeting PCSK9 (abdominal aortic aneurysm), ANGPTL4 (type 2 diabetes) and PDE3B (triglycerides and coronary disease).
•265,566 post-9/11 veterans with PTSD had >1 coded psychotherapy visit at the VA in 15 years.•While 22.8% initiated an evidence-based psychotherapy (EBP), only 9.1% completed treatment.•Veterans who ...completed EBP did so about 3 years after their initial mental health visit.•Factors associated with EBP completion included MST and combat/deployments.
Little is known about predictors of initiation and completion of evidence-based psychotherapy (EBP) for posttraumatic stress disorder (PTSD), with most data coming from small cohort studies and post-hoc analyses of clinical trials. We examined patient and treatment factors associated with initiation and completion of EBP for PTSD in a large longitudinal cohort. We conducted a national, retrospective cohort study of all Iraq and Afghanistan War veterans who had a post-deployment PTSD diagnosis from 10/01–9/15 at a Veterans Health Administration facility and had at least one coded post-deployment psychotherapy visit. We examined utilization of PE and CPT (individual or group) during any 24-week period. We used ordered logistic, logistic, and Cox proportional hazards regressions to examine variables associated with EBP initiation, early termination, and completion, and time to completion. Over a 15-year period, of 265,566 veterans with PTSD, 22.8% initiated an EBP, and only 9.1% completed treatment. Completers did so about three years after their initial mental health visit. Factors positively associated with EBP completion included military sexual trauma, older age, race/ethnicity (i.e., African-American race for PE), combat, and multiple deployments. The VHA has become timelier in delivering EBP for PTSD, and several subgroups are more likely to complete EBP.
Objective: Questionnaire studies show people with minoritized sexual orientations (MSOs) face increased risk for conditions including posttraumatic stress disorder (PTSD). This study replicated ...Harrington et al.'s (2019) electronic health record probabilistic algorithm to evaluate lifetime PTSD prevalence in Veterans Health Administration (VHA)-using veterans. Method: In 115,853 MSO veterans and a 1:3 matched (on sex assigned at birth, and age at and year of first VHA visit) sample of non-MSO veterans. Each veteran was given a probability of "likely PTSD" (0.0-1.0) and thresholds (e.g., 0.7) applied to minimize false positive classifications. Results: Veterans with MSO were 2.35 times, CI 2.33, 2.38, more likely to have "likely PTSD" than veterans with non-MSO. The prevalence of "likely PTSD" using the rule-based International Classification of Diseases (ICD) approach was 40.8% among the MSO group compared to 22.0% among the non-MSO group after excluding those with bipolar or schizophrenia diagnoses and those with limited VHA engagement. Without those exclusions, prevalence was slightly higher in both groups (46.1% vs. 24.3%, respectively; prevalence ratio: 1.90). Despite increased prevalence of exposure to military sexual trauma (MST; MSO = 20.7%; non-MSO = 8.3%) and double "likely PTSD" among MSO veterans, they were less likely to have a service-connected PTSD disability than their matched non-MSO (MSO = 78.1%; non-MSO = 87.6%) comparators. Conclusions: VHA-using veterans with MSO were twice as likely to have "likely PTSD" and exposure to MST than veterans with non-MSO. Veterans with MSO were less likely to be service connected for PTSD than non-MSO counterparts.
What is the public health significance of this article?
Gay, lesbian, and bisexual veterans who use VA healthcare are more likely to have posttraumatic stress disorder (PTSD) and have had military sexual trauma than straight veterans who use VA healthcare. However, gay, lesbian, and bisexual veterans are less likely to get disability payments for PTSD than straight veterans.
While evidence-based psychotherapy (EBP) for posttraumatic stress disorder (PTSD) is a first-line treatment, its real-world effectiveness is unknown. We compared cognitive processing therapy (CPT) ...and prolonged exposure (PE) each to an individual psychotherapy comparator group, and CPT to PE in a large national healthcare system.
We utilized effectiveness and comparative effectiveness emulated trials using retrospective cohort data from electronic medical records. Participants were veterans with PTSD initiating mental healthcare (
= 265 566). The primary outcome was PTSD symptoms measured by the PTSD Checklist (PCL) at baseline and 24-week follow-up. Emulated trials were comprised of 'person-trials,' representing 112 discrete 24-week periods of care (10/07-6/17) for each patient. Treatment group comparisons were made with generalized linear models, utilizing propensity score matching and inverse probability weights to account for confounding, selection, and non-adherence bias.
There were 636 CPT person-trials matched to 636 non-EBP person-trials. Completing ⩾8 CPT sessions was associated with a 6.4-point greater improvement on the PCL (95% CI 3.1-10.0). There were 272 PE person-trials matched to 272 non-EBP person-trials. Completing ⩾8 PE sessions was associated with a 9.7-point greater improvement on the PCL (95% CI 5.4-13.8). There were 232 PE person-trials matched to 232 CPT person-trials. Those completing ⩾8 PE sessions had slightly greater, but not statistically significant, improvement on the PCL (8.3-points; 95% CI 5.9-10.6) than those completing ⩾8 CPT sessions (7.0-points; 95% CI 5.5-8.5).
PTSD symptom improvement was similar and modest for both EBPs. Although EBPs are helpful, research to further improve PTSD care is critical.
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