•The median effective dose (MED) of cognitive processing therapy was 8 sessions.•The MED of individual cognitive processing therapy was 3 sessions fewer than group.•MED can inform providers and ...patients about treatment course.
Cognitive Processing Therapy (CPT) has been disseminated in the Veterans Health Administration (VHA) to treat posttraumatic stress disorder (PTSD). Identifying the median effective dose (MED) of CPT, the number of sessions at which the probability of experiencing clinically meaningful improvement (CMI) is 50%, can assist with treatment.
From a cohort of Iraq and Afghanistan war veterans who received PTSD psychotherapy in VHA between 2001-2017, veterans who received CPT with available PTSD symptom outcomes (PTSD Checklist; PCL) were identified using natural language processing (n=26,189). Cox proportional hazards regression was used to examine how number of CPT sessions, together with covariates, influenced CMI (10-point PCL reduction). Kaplan-Meier curves were plotted to determine MED.
At eight sessions, there was a 50% probability of experiencing CMI. The Cox proportional hazard regression indicated a greater likelihood of CMI in fewer sessions for veterans who received individual-only CPT versus any group CPT (HR:1.31, 95%CI:1.23-1.39). Kaplan-Meier curves indicated a 50% probability of experiencing CMI at seven sessions for veterans who received individual-only CPT versus ten sessions for veterans receiving any group CPT.
PCL data was not available for all veterans who received CPT or at each potential assessment point. Not all veterans continued in CPT until CMI was observed.
The MED of CPT was eight sessions. Fewer sessions were needed to reach MED for veterans who received individual versus group CPT. These results may help those who treat, research, and are recovering from PTSD through accurately anchoring treatment expectations and providing a marker of initial treatment response.
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Unhealthy alcohol use is disproportionally experienced by individuals with minoritized sexual orientations. Unlike the general US population, for whom the burden of alcohol as it relates to mortality ...is consistently monitored across time with national survey data, the impact of unhealthy alcohol use among veterans with minoritized sexual orientations, for whom addressing substance use is a national priority, is largely unknown.
Using Alcohol Use Disorders Identification Test Consumption data from the Department of Veterans Affairs electronic health record and underlying cause of death from National Death Index from 2014 to 2018 we quantified alcohol consumption and related mortality among veterans with (n = 102,085) and without minoritized sexual orientations (n = 5300,521). Age adjusted rates of alcohol attributed deaths (AAD) per 100,000 persons and years of potential life lost (YPLL) were estimated by sexual orientation, sex, and sexual orientation stratified by sex.
Alcohol attributable deaths (n = 21,861) were higher among veterans with minoritized sexual orientations than veterans without after adjustment for age (486.5 deaths/100,000 versus 309.7 deaths/100,000, respectively). Veterans with minoritized sexual orientations also experienced more YPLL (13,772.8 years/100,000 versus 7618.9 years/100,000). Years of potential life lost per AAD was higher in women (33.2 years) than men (18.7 years).
Alcohol consumption results in substantial disability and death among veterans, particularly veterans with minoritized sexual orientations. Findings suggest need for increased alcohol-related services for all VA patients, and potential targeted approaches to for veterans with minoritized sexual orientations and women to offset risk for, and years of potential life lost from, alcohol attributable death.
•Drinking severity is higher among veterans with versus without minoritized sexual orientations.•Rates of deaths attributable to excessive drinking in veterans differs by sexual orientation.•Years of potential life lost per alcohol attributable death was higher in women than men.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Despite differences in prostate cancer risk across ancestry groups, relative performance of prostate cancer genetic risks scores (GRS) for positive biopsy prediction in different ancestry groups is ...unknown. This cross-sectional retrospective analysis examines the association between a polygenic hazard score (PHS290) and risk of prostate cancer diagnosis upon first biopsy in male veterans using 2-sided tests. Our analysis included 36 717 veterans (10 297 of African ancestry). Unadjusted rates of positive first prostate biopsy increased with higher genetic risk (low risk: 34%, high risk: 58%; P < .001). Among men of African ancestry, higher genetic risk was associated with increased prostate cancer detection on first biopsy (odds ratio = 2.18, 95% confidence interval = 1.93 to 2.47), but the effect was stronger among men of European descent (odds ratio = 3.89, 95% confidence interval = 3.62 to 4.18). These findings suggest that incorporating genetic risk into prediction models could better personalize biopsy decisions, although further study is needed to achieve equitable genetic risk stratification among ancestry groups.
Response to analgesic therapy is influenced by several factors including genetics and drug-drug interactions. Pharmacogenetic (PGx) variants in the CYP2D6 gene modify response to opioids by altering ...drug metabolism. We sought to determine the potential impact of PGx testing on the care of Veterans with noncancer pain prescribed opioids metabolized by CYP2D6 (codeine, hydrocodone, or tramadol). A retrospective analysis was performed within the Veterans Health Administration evaluating prescription records for pain medications metabolized by CYP2D6 and interacting drugs from 2012 to 2017. Among 2,436,654 Veterans Health Administration pharmacy users with at least 1 opioid prescription, 34% met the definition of chronic use (longer than 90 days with more than 10 prescriptions or 120 days-supply). Opioids were commonly coprescribed with antidepressants interacting with CYP2D6 (28%). An estimated 21.6% (n = 526,905) of these patients are at an elevated risk of an undesirable response to their opioid medication based on predicted phenotypes and drug-drug interactions: 3.5% are predicted CYP2D6 ultrarapid metabolizers and at increased risk for toxicity, 5.4% are poor metabolizers at higher risk for nonresponse, and 12.8% are normal or intermediate metabolizers coprescribed a CYP2D6 inhibitor leading to phenoconversion into poor metabolizer. Despite the high rate of coprescription of opioids and interacting drugs, CYP2D6 testing was infrequent in the sample (0.02%), and chart review suggests that test results were used to optimize antidepressant treatments rather than pain medications. Using PGx testing combined with consideration of phenoconversion may allow for an enhanced precision medicine approach to pain management in Veterans.
•We identified a cohort receiving evidence-based psychotherapy (EBP) over 14 years.•Improvements in PTSD following EBP were associated with timing, dose and modality.•Modifiable factors like timing ...and modality can be used to improve EBP outcomes.
Despite availability of evidence-based psychotherapies (EBPs) for posttraumatic stress disorder (PTSD), not all veterans who initiate EBPs experience benefit. Better understanding factors associated with clinically significant improvement can help ameliorate care.
A cohort of Iraq and Afghanistan War veterans who initiated an EBP was identified (N = 32,780) with ≥1 post-deployment psychotherapy visit at the Veterans Health Administration from 10/2001-6/2017, a post-deployment PTSD diagnosis, and ≥2 PTSD symptom measures. We used random-effects logistic regression to assess whether patient-level, diagnostic, and treatment factors were associated with achieving symptom improvement.
Increased odds of PTSD symptom improvement were seen in women (OR = 1.19; 95% CI: 1.09--1.29), those who initiated EBP within a year of engaging in mental healthcare compared with the delayed EBP group (OR = 1.20; 95% CI: 1.14--1.28), those who completed at least 8 EBP sessions in 16 weeks (OR = 1.23; 95% CI:1.11--1.36), those who received PE only (vs. CPT or both; OR = 2.23; 95% CI: 1.86--2.68) or CPT individual therapy only (vs. CPT group or both; OR = 1.34; 95% CI: 1.22--1.48), and those with a drug dependence diagnosis (OR = 1.24; 95% CI: 1.11--1.39). Decreased odds of improvement were seen in Black veterans (OR=0.75; 95% CI: 0.69--0.81) and those with service-connected disability (OR = 0.61; 95% CI: 0.52--0.71).
Diagnoses were from medical charts and not confirmed with gold standard assessment tools; we only included veterans with at least two PTSD measurements, which may cause bias.
Modifiable factors associated with PTSD improvement (timing, dose, and modality) can be used to improve EBP outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Implementation of pharmacogenetic testing to guide drug prescribing has potential to improve drug response and prevent adverse events. Robust data exist for more than 30 gene-drug pairs linking ...genotype to drug response phenotypes; however, it is unclear which pharmacogenetic tests, if implemented, would provide the greatest utility for a given patient population.
To project the proportion of veterans in the US Veterans Health Administration (VHA) with actionable pharmacogenetic variants and evaluate how testing might be associated with prescribing decisions.
This cross-sectional study included veterans who used national VHA pharmacy services from October 1, 2011, to September 30, 2017. Data analyses began April 26, 2018, and were completed February 6, 2019.
Receipt of level A drugs based on VHA pharmacy dispensing records.
Projected prevalence of actionable pharmacogenetic variants among VHA pharmacy users based on variant frequencies from the 1000 Genomes Project and veteran demographic characteristics; incident number of level A prescriptions, and proportion of new level A drug recipients projected to carry an actionable pharmacogenetic variant.
During the study, 7 769 359 veterans (mean SD age, 58.1 17.8 years; 7 021 504 90.4% men) used VHA pharmacy services. It was projected that 99% of VHA pharmacy users would carry at least 1 actionable pharmacogenetic variant. Among VHA pharmacy users, 4 259 153 (54.8%) received at least 1 level A drug with 1 188 124 (15.3%) receiving 2 drugs, and 912 189 (11.7%) receiving 3 or more drugs. The most common incident prescriptions during the study were tramadol (923 671 new recipients), simvastatin (533 928 new recipients), citalopram (266 952 new recipients), and warfarin (205 177 new recipients). Gene-drug interactions projected to have substantial clinical impacts in the VHA population include the interaction of SLCO1B1 with simvastatin (1 988 956 veterans 25.6%), CYP2D6 with tramadol (318 544 veterans 4.1%), and CYP2C9 or VKORC1 with warfarin (7 163 349 veterans 92.2%).
Clinically important pharmacogenetic variants are highly prevalent in the VHA population. Almost all veterans would carry an actionable variant, and more than half of the population had been exposed to a drug affected by these variants. These results suggest that pharmacogenetic testing has the potential to affect pharmacotherapy decisions for commonly prescribed outpatient medications for many veterans.
Despite improvements in electronic medical record capability to collect data on sexual orientation, not all healthcare systems have adopted this practice. This can limit the usability of systemwide ...electronic medical record data for sexual minority research. One viable resource might be the documentation of sexual orientation within clinical notes. The authors developed an approach to identify sexual orientation documentation and subsequently derived a cohort of sexual minority patients using clinical notes from the Veterans Health Administration electronic medical record.
A hybrid natural language processing approach was developed and used to identify and categorize instances of terms and phrases related to sexual orientation in Veterans Health Administration clinical notes from 2000 to 2019. System performance was assessed with positive predictive value and sensitivity. Data were analyzed in 2019.
A total of 2,413,584 sexual minority terms/phrases were found within clinical notes, of which 439,039 (18%) were found to be related to patient sexual orientation with a positive predictive value of 85.9%. Documentation of sexual orientation was found for 115,312 patients. When compared with 2,262 patients with a record of administrative coding for homosexuality, the system found mentions of sexual orientation for 1,808 patients (79.9% sensitivity).
When systemwide structured data are unavailable or inconsistent, deriving a cohort of sexual minority patients in electronic medical records for research is possible and permits longitudinal analysis across multiple clinical domains. Although limitations and challenges to the approach were identified, this study makes an important step forward for the Veterans Health Administration sexual minority research, and the methodology can be applied in other healthcare organizations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Although Black men are more likely than non‐Hispanic White men to develop and die from prostate cancer, limited data exist to guide prostate‐specific antigen (PSA) screening protocols in ...Black men. This study investigated whether the risk for prostate cancer was higher than expected among self‐identified Black than White veterans based on prebiopsy PSA level.
Methods
Multivariable logistic regression models were estimated to predict the likelihood of prostate cancer diagnosis on first biopsy for 75,295 Black and 207,658 White male veterans. Self‐identified race, age at first PSA test, prebiopsy PSA, age at first biopsy, smoking status, statin use, and socioeconomic factors were used as predictors. The adjusted predicted probabilities of cancer detection on first prostate biopsy from the logistic models at different PSA levels were calculated.
Results
After controlling for PSA and other covariates, Black veterans were 50% more likely to receive a prostate cancer diagnosis on their first prostate biopsy than White veterans (odds ratio OR, 1.50; 95% CI, 1.47‐1.53; p < .001). At a PSA level of 4.0 ng/mL, the probability of prostate cancer for a Black man was 49% compared with 39% for a White man. This model indicated that Black veterans with a PSA of 4.0 ng/mL have an equivalent risk of prostate cancer as White veterans with a PSA of 13.4 ng/mL.
Conclusions
The findings indicate that, at any given PSA level, Black men are more likely to harbor prostate cancer than White men. Prospective studies are needed to better evaluate risks and benefits of PSA screening in Black men and other high‐risk populations.
At any given prostate‐specific antigen level, Black men have substantially higher risk of prostate cancer detection on their first biopsy compared with White men after accounting for socioeconomic factors, age, and prebiopsy prostate‐specific antigen. This difference was more pronounced among younger men.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
To examine the association of serum lipids, inflammation and seropositivity on coronary heart disease (CHD) and stroke in patients with rheumatoid arthritis (RA).
The incidence of hospitalised ...myocardial infarction (MI) or stroke was calculated in a cohort of patients with RA receiving care within the national Veterans Health Administration from 1998 to 2011. Cox proportional hazard models were used to examine the association between these outcomes and low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as time-varying variables, divided into quintiles.
There were 37,568 patients with RA in the cohort with mean age of 63 years (SD 12.1); 90% were men. There was a no clear association between LDL-C and CHD/stroke. Compared with lower HDL-C (<34 mg/dL), higher HDL-C (≥54 mg/dL) was inversely associated with MI (hazard ratio (HR)=0.68, 95% CI 0.55 to 0.85) and stroke (HR=0.69, 95% CI 0.50 to 0.96). Higher CRP >2.17 mg/dL (vs CRP <0.26 mg/dL) was associated with increased risk (HR=2.43, 95% CI 1.77 to 3.33) for MI and 2.02 (95% CI 1.32 to 3.08) for stroke. ESR >47 mm/h compared with <8 mm/h had an HR 1.87 (95% CI 1.39 to 2.52) for MI and 2.00 (95% CI 1.26 to 3.18) for stroke. The association between MI was significant for RA seropositivity (HR=1.23, 95% CI 1.03 to 1.48).
In this predominantly older male RA cohort, there was no clear association between LDL-C and CHD, whereas higher HDL-C was inversely associated with MI and stroke. CRP and ESR were similarly associated with increase MI risk and stroke, reflecting the prominent role of inflammation in CHD risk in RA.
The US government considers veterans to have been exposed to Agent Orange if they served in Vietnam while the carcinogen was in use, and these veterans are often deemed at high risk of prostate ...cancer (PCa). Here, we assess whether presumed Agent Orange exposure is independently associated with increased risk of any metastatic or fatal PCa in a diverse Veteran cohort still alive in the modern era (at least 2011), when accounting for race/ethnicity, family history, and genetic risk.
Participants in the Million Veteran Program (MVP; enrollment began in 2011) who were on active duty during the Vietnam War era (August 1964-April 1975) were included (n = 301,470). Agent Orange exposure was determined using the US government definition. Genetic risk was assessed via a validated polygenic hazard score. Associations with age at diagnosis of any PCa, metastatic PCa, and death from PCa were assessed via Cox proportional hazards models.
On univariable analysis, exposure to Agent Orange was not associated with increased PCa (hazard ratio HR: 1.02, 95% confidence interval CI: 1.00-1.04, p = 0.06), metastatic PCa (HR: 0.98, 95% CI: 0.91-1.05, p = 0.55), or fatal PCa (HR: 0.94, 95% CI: 0.79-1.09, p = 0.41). When accounting for race/ethnicity and family history, Agent Orange exposure was independently associated with slightly increased risk of PCa (HR: 1.06, 95% CI: 1.04-1.09, <10-6) but not with metastatic PCa (HR: 1.07, 95% CI: 0.98-1.15, p = 0.10) or PCa death (HR: 1.02, 95% CI: 0.83-1.23, p = 0.09). Similar results were found when accounting for genetic risk. Agent Orange exposure history may not improve modern PCa risk stratification.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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