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2.
Lancet Digit Health ; 3(2): e98-e114, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33342753

RESUMO

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been postulated to affect susceptibility to COVID-19. Observational studies so far have lacked rigorous ascertainment adjustment and international generalisability. We aimed to determine whether use of ACEIs or ARBs is associated with an increased susceptibility to COVID-19 in patients with hypertension. METHODS: In this international, open science, cohort analysis, we used electronic health records from Spain (Information Systems for Research in Primary Care [SIDIAP]) and the USA (Columbia University Irving Medical Center data warehouse [CUIMC] and Department of Veterans Affairs Observational Medical Outcomes Partnership [VA-OMOP]) to identify patients aged 18 years or older with at least one prescription for ACEIs and ARBs (target cohort) or calcium channel blockers (CCBs) and thiazide or thiazide-like diuretics (THZs; comparator cohort) between Nov 1, 2019, and Jan 31, 2020. Users were defined separately as receiving either monotherapy with these four drug classes, or monotherapy or combination therapy (combination use) with other antihypertensive medications. We assessed four outcomes: COVID-19 diagnosis; hospital admission with COVID-19; hospital admission with pneumonia; and hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis. We built large-scale propensity score methods derived through a data-driven approach and negative control experiments across ten pairwise comparisons, with results meta-analysed to generate 1280 study effects. For each study effect, we did negative control outcome experiments using a possible 123 controls identified through a data-rich algorithm. This process used a set of predefined baseline patient characteristics to provide the most accurate prediction of treatment and balance among patient cohorts across characteristics. The study is registered with the EU Post-Authorisation Studies register, EUPAS35296. FINDINGS: Among 1 355 349 antihypertensive users (363 785 ACEI or ARB monotherapy users, 248 915 CCB or THZ monotherapy users, 711 799 ACEI or ARB combination users, and 473 076 CCB or THZ combination users) included in analyses, no association was observed between COVID-19 diagnosis and exposure to ACEI or ARB monotherapy versus CCB or THZ monotherapy (calibrated hazard ratio [HR] 0·98, 95% CI 0·84-1·14) or combination use exposure (1·01, 0·90-1·15). ACEIs alone similarly showed no relative risk difference when compared with CCB or THZ monotherapy (HR 0·91, 95% CI 0·68-1·21; with heterogeneity of >40%) or combination use (0·95, 0·83-1·07). Directly comparing ACEIs with ARBs demonstrated a moderately lower risk with ACEIs, which was significant with combination use (HR 0·88, 95% CI 0·79-0·99) and non-significant for monotherapy (0·85, 0·69-1·05). We observed no significant difference between drug classes for risk of hospital admission with COVID-19, hospital admission with pneumonia, or hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis across all comparisons. INTERPRETATION: No clinically significant increased risk of COVID-19 diagnosis or hospital admission-related outcomes associated with ACEI or ARB use was observed, suggesting users should not discontinue or change their treatment to decrease their risk of COVID-19. FUNDING: Wellcome Trust, UK National Institute for Health Research, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research & Development, IQVIA, South Korean Ministry of Health and Welfare Republic, Australian National Health and Medical Research Council, and European Health Data and Evidence Network.

3.
medRxiv ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33269355

RESUMO

Objective: Patients with autoimmune diseases were advised to shield to avoid COVID-19, but information on their prognosis is lacking. We characterised 30-day outcomes and mortality after hospitalisation with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza. Design: Multinational network cohort study. Setting: Electronic health records data from Columbia University Irving Medical Center (CUIMC) (NYC, United States [US]), Optum [US], Department of Veterans Affairs (VA) (US), Information System for Research in Primary Care-Hospitalisation Linked Data (SIDIAP-H) (Spain), and claims data from IQVIA Open Claims (US) and Health Insurance and Review Assessment (HIRA) (South Korea). Participants: All patients with prevalent autoimmune diseases, diagnosed and/or hospitalised between January and June 2020 with COVID-19, and similar patients hospitalised with influenza in 2017-2018 were included. Main outcome measures: 30-day complications during hospitalisation and death. Results: We studied 133,589 patients diagnosed and 48,418 hospitalised with COVID-19 with prevalent autoimmune diseases. The majority of participants were female (60.5% to 65.9%) and aged ≥50 years. The most prevalent autoimmune conditions were psoriasis (3.5 to 32.5%), rheumatoid arthritis (3.9 to 18.9%), and vasculitis (3.3 to 17.6%). Amongst hospitalised patients, Type 1 diabetes was the most common autoimmune condition (4.8% to 7.5%) in US databases, rheumatoid arthritis in HIRA (18.9%), and psoriasis in SIDIAP-H (26.4%).Compared to 70,660 hospitalised with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2% to 4.3% versus 6.3% to 24.6%). Conclusions: Patients with autoimmune diseases had high rates of respiratory complications and 30-day mortality following a hospitalization with COVID-19. Compared to influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality. Future studies should investigate predictors of poor outcomes in COVID-19 patients with autoimmune diseases. What is already known about this topic: Patients with autoimmune conditions may be at increased risk of COVID-19 infection andcomplications.There is a paucity of evidence characterising the outcomes of hospitalised COVID-19 patients with prevalent autoimmune conditions. What this study adds: Most people with autoimmune diseases who required hospitalisation for COVID-19 were women, aged 50 years or older, and had substantial previous comorbidities.Patients who were hospitalised with COVID-19 and had prevalent autoimmune diseases had higher prevalence of hypertension, chronic kidney disease, heart disease, and Type 2 diabetes as compared to those with prevalent autoimmune diseases who were diagnosed with COVID-19.A variable proportion of 6% to 25% across data sources died within one month of hospitalisation with COVID-19 and prevalent autoimmune diseases.For people with autoimmune diseases, COVID-19 hospitalisation was associated with worse outcomes and 30-day mortality compared to admission with influenza in the 2017-2018 season.

4.
Contemp Clin Trials ; 101: 106247, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33316457

RESUMO

Genomic testing has the potential to improve patient outcomes and reduce patient care costs by personalizing medication selection. Commercial pharmacogenetic (PGx) testing for psychotropic and other medications is widely available and promoted as a means to implement "precision medicine." Despite evidence that genetic variation affects the metabolism of psychotropic medications, the clinical utility of these test results has not been established. Moreover, implementing such testing in routine clinical care is complex, requiring informatics support and a systematic approach to patient and provider education. The PRIME Care program is designed to bridge this gap, applying both clinical trials and implementation science methods to conduct a program of research. It is centered on a large, pragmatic randomized clinical trial (RCT) in which 2000 Veterans with a major depressive disorder (MDD) and their health care providers are randomized together to receive PGx test results at the beginning of an episode of care or 6 months later. We hypothesize that providers who receive the PGx test results will prescribe an antidepressant guided by the PGx findings and Veterans whose care is guided by PGx testing will experience higher rates of remission from MDD. If the results of the trial replicate those of prior PGx studies, which provided preliminary evidence of the utility of PGx guided prescribing, it would strongly support using a precision medicine approach to treat MDD. This program of research is also evaluating dissemination influencers, other biomarkers (e.g., genetic variation associated with depression response), and the health care cost implications of PGx testing. ClinicalTrials.gov Identifier: NCT03170362.

5.
JAMA Netw Open ; 3(12): e2031357, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33369662

RESUMO

Importance: Identification of subgroups at greatest risk for suicide mortality is essential for prevention efforts and targeting interventions. Sexual minority individuals may have an increased risk for suicide compared with heterosexual individuals, but a lack of sufficiently powered studies with rigorous methods for determining sexual orientation has limited the knowledge on this potential health disparity. Objective: To investigate suicide mortality among sexual minority veterans using Veterans Health Administration (VHA) electronic health record data. Design, Setting, and Participants: This retrospective population-based cohort study used data on 8.1 million US veterans enrolled in the VHA after fiscal year 1999 that were obtained from VHA electronic health records from October 1, 1999 to September 30, 2017. Data analysis was carried out from March 1, 2020 to October 31, 2020. Exposure: Veterans with documentation of a minority sexual orientation. Documentation of sexual minority status was obtained through natural language processing of clinical notes and extraction of structured administrative data for sexual orientation in VHA electronic health records. Main Outcomes and Measures: Suicide mortality rate using data on the underlying cause of death obtained from the National Death Index. Crude and age-adjusted mortality rates were calculated for all-cause death and death from suicide among sexual minority veterans compared with the general US population and the general population of veterans. Results: Among the 96 893 veterans with at least 1 sexual minority documentation in the electronic health record, the mean (SD) age was 46 (16) years, 68% were male, and 70% were White. Of the 12 591 total deaths, 3.5% were from suicide. Veterans had a significantly higher rate of mortality from suicide (standardized mortality ratio, 4.50; 95% CI, 4.13-4.99) compared with the general US population. Suicide was the fifth leading cause of death in 2017 among sexual minority veterans (3.8% of deaths) and the tenth leading cause of death in the general US population (1.7% of deaths). The crude suicide rate among sexual minority veterans (82.5 per 100 000 person-years) was higher than the rate in the general veteran population (37.7 per 100 000 person-years). Conclusions and Relevance: The results of this population-based cohort study suggest that sexual minority veterans have a greater risk for suicide than the general US population and the general veteran population. Further research is needed to determine whether and how suicide prevention efforts reach sexual minority veterans.


Assuntos
Minorias Sexuais e de Gênero/estatística & dados numéricos , Suicídio/estatística & dados numéricos , Veteranos/estatística & dados numéricos , Adulto , Feminino , Disparidades nos Níveis de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Minorias Sexuais e de Gênero/psicologia , Suicídio/psicologia , Estados Unidos/epidemiologia , United States Department of Veterans Affairs , Veteranos/psicologia
6.
Behav Res Ther ; 135: 103756, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33157475

RESUMO

Prolonged exposure therapy (PE) is an effective treatment for posttraumatic stress disorder (PTSD). Identifying metrics of treatment response can guide treatment delivery. The median effective dose represents the number of sessions at which there is a 50% probability of clinically meaningful improvement (i.e., 10-point reduction in PTSD checklist). The goal of the current study was to investigate the median effective dose of PE. We identified a cohort of Iraq and Afghanistan war veterans who received psychotherapy for PTSD in the Veterans Health Administration between 2001 and 2017. From this cohort, 10,234 veterans who received PE (as identified using natural language processing) and had ≥2 PTSD symptom measures were included in analyses. To determine how the number of PE sessions and covariates affected clinically meaningful improvement, we utilized a Cox proportional hazards regression, followed by Kaplan-Meier curves to determine the median effective dose. The median effective dose of PE was four sessions. Although some covariates were found to be statistically significant predictors of clinically meaningful improvement (e.g., age, gender, PTSD medications, and depressive disorder comorbidity), these effects were small. Clinicians and patients should consider evaluating treatment response after four sessions to determine preliminary effectiveness of PE.

7.
medRxiv ; 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33140068

RESUMO

Early identification of symptoms and comorbidities most predictive of COVID-19 is critical to identify infection, guide policies to effectively contain the pandemic, and improve health systems' response. Here, we characterised socio-demographics and comorbidity in 3,316,107persons tested and 219,072 persons tested positive for SARS-CoV-2 since January 2020, and their key health outcomes in the month following the first positive test. Routine care data from primary care electronic health records (EHR) from Spain, hospital EHR from the United States (US), and claims data from South Korea and the US were used. The majority of study participants were women aged 18-65 years old. Positive/tested ratio varied greatly geographically (2.2:100 to 31.2:100) and over time (from 50:100 in February-April to 6.8:100 in May-June). Fever, cough and dyspnoea were the most common symptoms at presentation. Between 4%-38% required admission and 1-10.5% died within a month from their first positive test. Observed disparity in testing practices led to variable baseline characteristics and outcomes, both nationally (US) and internationally. Our findings highlight the importance of large scale characterization of COVID-19 international cohorts to inform planning and resource allocation including testing as countries face a second wave.

8.
Am J Prev Med ; 59(5): 755-763, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33011005

RESUMO

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

9.
Lancet Rheumatol ; 2(11): e698-e711, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32864627

RESUMO

Background: Hydroxychloroquine, a drug commonly used in the treatment of rheumatoid arthritis, has received much negative publicity for adverse events associated with its authorisation for emergency use to treat patients with COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin, to determine the risk associated with its use in routine care in patients with rheumatoid arthritis. Methods: In this multinational, retrospective study, new user cohort studies in patients with rheumatoid arthritis aged 18 years or older and initiating hydroxychloroquine were compared with those initiating sulfasalazine and followed up over 30 days, with 16 severe adverse events studied. Self-controlled case series were done to further establish safety in wider populations, and included all users of hydroxychloroquine regardless of rheumatoid arthritis status or indication. Separately, severe adverse events associated with hydroxychloroquine plus azithromycin (compared with hydroxychloroquine plus amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, the Netherlands, Spain, the UK, and the USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (HRs) according to drug use. Estimates were pooled where the I 2 value was less than 0·4. Findings: The study included 956 374 users of hydroxychloroquine, 310 350 users of sulfasalazine, 323 122 users of hydroxychloroquine plus azithromycin, and 351 956 users of hydroxychloroquine plus amoxicillin. No excess risk of severe adverse events was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. Self-controlled case series confirmed these findings. However, long-term use of hydroxychloroquine appeared to be associated with increased cardiovascular mortality (calibrated HR 1·65 [95% CI 1·12-2·44]). Addition of azithromycin appeared to be associated with an increased risk of 30-day cardiovascular mortality (calibrated HR 2·19 [95% CI 1·22-3·95]), chest pain or angina (1·15 [1·05-1·26]), and heart failure (1·22 [1·02-1·45]). Interpretation: Hydroxychloroquine treatment appears to have no increased risk in the short term among patients with rheumatoid arthritis, but in the long term it appears to be associated with excess cardiovascular mortality. The addition of azithromycin increases the risk of heart failure and cardiovascular mortality even in the short term. We call for careful consideration of the benefit-risk trade-off when counselling those on hydroxychloroquine treatment. Funding: National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, NIHR Senior Research Fellowship programme, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research and Development, IQVIA, Korea Health Industry Development Institute through the Ministry of Health and Welfare Republic of Korea, Versus Arthritis, UK Medical Research Council Doctoral Training Partnership, Foundation Alfonso Martin Escudero, Innovation Fund Denmark, Novo Nordisk Foundation, Singapore Ministry of Health's National Medical Research Council Open Fund Large Collaborative Grant, VINCI, Innovative Medicines Initiative 2 Joint Undertaking, EU's Horizon 2020 research and innovation programme, and European Federation of Pharmaceutical Industries and Associations.

10.
Circulation ; 142(17): 1633-1646, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-32981348

RESUMO

BACKGROUND: Abdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality; however, its genetic determinants remain incompletely defined. In total, 10 previously identified risk loci explain a small fraction of AAA heritability. METHODS: We performed a genome-wide association study in the Million Veteran Program testing ≈18 million DNA sequence variants with AAA (7642 cases and 172 172 controls) in veterans of European ancestry with independent replication in up to 4972 cases and 99 858 controls. We then used mendelian randomization to examine the causal effects of blood pressure on AAA. We examined the association of AAA risk variants with aneurysms in the lower extremity, cerebral, and iliac arterial beds, and derived a genome-wide polygenic risk score (PRS) to identify a subset of the population at greater risk for disease. RESULTS: Through a genome-wide association study, we identified 14 novel loci, bringing the total number of known significant AAA loci to 24. In our mendelian randomization analysis, we demonstrate that a genetic increase of 10 mm Hg in diastolic blood pressure (odds ratio, 1.43 [95% CI, 1.24-1.66]; P=1.6×10-6), as opposed to systolic blood pressure (odds ratio, 1.06 [95% CI, 0.97-1.15]; P=0.2), likely has a causal relationship with AAA development. We observed that 19 of 24 AAA risk variants associate with aneurysms in at least 1 other vascular territory. A 29-variant PRS was strongly associated with AAA (odds ratioPRS, 1.26 [95% CI, 1.18-1.36]; PPRS=2.7×10-11 per SD increase in PRS), independent of family history and smoking risk factors (odds ratioPRS+family history+smoking, 1.24 [95% CI, 1.14-1.35]; PPRS=1.27×10-6). Using this PRS, we identified a subset of the population with AAA prevalence greater than that observed in screening trials informing current guidelines. CONCLUSIONS: We identify novel AAA genetic associations with therapeutic implications and identify a subset of the population at significantly increased genetic risk of AAA independent of family history. Our data suggest that extending current screening guidelines to include testing to identify those with high polygenic AAA risk, once the cost of genotyping becomes comparable with that of screening ultrasound, would significantly increase the yield of current screening at reasonable cost.

11.
PLoS One ; 15(8): e0237430, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32841307

RESUMO

BACKGROUND & AIMS: Given ongoing challenges in non-invasive non-alcoholic liver disease (NAFLD) diagnosis, we sought to validate an ALT-based NAFLD phenotype using measures readily available in electronic health records (EHRs) and population-based studies by leveraging the clinical and genetic data in the Million Veteran Program (MVP), a multi-ethnic mega-biobank of US Veterans. METHODS: MVP participants with alanine aminotransferases (ALT) >40 units/L for men and >30 units/L for women without other causes of liver disease were compared to controls with normal ALT. Genetic variants spanning eight NAFLD risk or ALT-associated loci (LYPLAL1, GCKR, HSD17B13, TRIB1, PPP1R3B, ERLIN1, TM6SF2, PNPLA3) were tested for NAFLD associations with sensitivity analyses adjusting for metabolic risk factors and alcohol consumption. A manual EHR review assessed performance characteristics of the NAFLD phenotype with imaging and biopsy data as gold standards. Genetic associations with advanced fibrosis were explored using FIB4, NAFLD Fibrosis Score and platelet counts. RESULTS: Among 322,259 MVP participants, 19% met non-invasive criteria for NAFLD. Trans-ethnic meta-analysis replicated associations with previously reported genetic variants in all but LYPLAL1 and GCKR loci (P<6x10-3), without attenuation when adjusted for metabolic risk factors and alcohol consumption. At the previously reported LYPLAL1 locus, the established genetic variant did not appear to be associated with NAFLD, however the regional association plot showed a significant association with NAFLD 279kb downstream. In the EHR validation, the ALT-based NAFLD phenotype yielded a positive predictive value 0.89 and 0.84 for liver biopsy and abdominal imaging, respectively (inter-rater reliability (Cohen's kappa = 0.98)). HSD17B13 and PNPLA3 loci were associated with advanced fibrosis. CONCLUSIONS: We validate a simple, non-invasive ALT-based NAFLD phenotype using EHR data by leveraging previously established NAFLD risk-associated genetic polymorphisms.


Assuntos
Alanina Transaminase/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , 17-Hidroxiesteroide Desidrogenases/genética , Abdome/diagnóstico por imagem , Proteínas Adaptadoras de Transdução de Sinal/genética , Idoso , Alanina Transaminase/genética , Registros Eletrônicos de Saúde , Feminino , Loci Gênicos , Predisposição Genética para Doença , Variação Genética , Humanos , Lipase/genética , Fígado/patologia , Lisofosfolipase/genética , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/etnologia , Hepatopatia Gordurosa não Alcoólica/genética , Fenótipo , Fatores de Risco , Veteranos
12.
medRxiv ; 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32587982

RESUMO

INTRODUCTION: Angiotensin converting enzyme inhibitors (ACEs) and angiotensin receptor blockers (ARBs) could influence infection risk of coronavirus disease (COVID-19). Observational studies to date lack pre-specification, transparency, rigorous ascertainment adjustment and international generalizability, with contradictory results. METHODS: Using electronic health records from Spain (SIDIAP) and the United States (Columbia University Irving Medical Center and Department of Veterans Affairs), we conducted a systematic cohort study with prevalent ACE, ARB, calcium channel blocker (CCB) and thiazide diuretic (THZ) use to determine relative risk of COVID-19 diagnosis and related hospitalization outcomes. The study addressed confounding through large-scale propensity score adjustment and negative control experiments. RESULTS: Following over 1.1 million antihypertensive users identified between November 2019 and January 2020, we observed no significant difference in relative COVID-19 diagnosis risk comparing ACE/ARB vs CCB/THZ monotherapy (hazard ratio: 0.98; 95% CI 0.84 - 1.14), nor any difference for mono/combination use (1.01; 0.90 - 1.15). ACE alone and ARB alone similarly showed no relative risk difference when compared to CCB/THZ monotherapy or mono/combination use. Directly comparing ACE vs. ARB demonstrated a moderately lower risk with ACE, non-significant for monotherapy (0.85; 0.69 - 1.05) and marginally significant for mono/combination users (0.88; 0.79 - 0.99). We observed, however, no significant difference between drug- classes for COVID-19 hospitalization or pneumonia risk across all comparisons. CONCLUSION: There is no clinically significant increased risk of COVID-19 diagnosis or hospitalization with ACE or ARB use. Users should not discontinue or change their treatment to avoid COVID-19.

13.
J Affect Disord ; 273: 425-433, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32560937

RESUMO

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. LIMITATIONS: 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. CONCLUSIONS: 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.

14.
Nat Genet ; 52(7): 680-691, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32541925

RESUMO

We investigated type 2 diabetes (T2D) genetic susceptibility via multi-ancestry meta-analysis of 228,499 cases and 1,178,783 controls in the Million Veteran Program (MVP), DIAMANTE, Biobank Japan and other studies. We report 568 associations, including 286 autosomal, 7 X-chromosomal and 25 identified in ancestry-specific analyses that were previously unreported. Transcriptome-wide association analysis detected 3,568 T2D associations with genetically predicted gene expression in 687 novel genes; of these, 54 are known to interact with FDA-approved drugs. A polygenic risk score (PRS) was strongly associated with increased risk of T2D-related retinopathy and modestly associated with chronic kidney disease (CKD), peripheral artery disease (PAD) and neuropathy. We investigated the genetic etiology of T2D-related vascular outcomes in the MVP and observed statistical SNP-T2D interactions at 13 variants, including coronary heart disease (CHD), CKD, PAD and neuropathy. These findings may help to identify potential therapeutic targets for T2D and genomic pathways that link T2D to vascular outcomes.


Assuntos
Complicações do Diabetes/genética , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Afro-Americanos , Cromossomos Humanos X , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/etnologia , Angiopatias Diabéticas/genética , Europa (Continente) , Feminino , Estudos de Associação Genética , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Polimorfismo de Nucleotídeo Único , Medição de Risco
15.
J Am Med Inform Assoc ; 27(9): 1437-1442, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32569358

RESUMO

Large observational data networks that leverage routine clinical practice data in electronic health records (EHRs) are critical resources for research on coronavirus disease 2019 (COVID-19). Data normalization is a key challenge for the secondary use of EHRs for COVID-19 research across institutions. In this study, we addressed the challenge of automating the normalization of COVID-19 diagnostic tests, which are critical data elements, but for which controlled terminology terms were published after clinical implementation. We developed a simple but effective rule-based tool called COVID-19 TestNorm to automatically normalize local COVID-19 testing names to standard LOINC (Logical Observation Identifiers Names and Codes) codes. COVID-19 TestNorm was developed and evaluated using 568 test names collected from 8 healthcare systems. Our results show that it could achieve an accuracy of 97.4% on an independent test set. COVID-19 TestNorm is available as an open-source package for developers and as an online Web application for end users (https://clamp.uth.edu/covid/loinc.php). We believe that it will be a useful tool to support secondary use of EHRs for research on COVID-19.


Assuntos
Betacoronavirus , Técnicas de Laboratório Clínico/classificação , Infecções por Coronavirus/diagnóstico , Logical Observation Identifiers Names and Codes , Pneumonia Viral/diagnóstico , Terminologia como Assunto , Infecções por Coronavirus/classificação , Registros Eletrônicos de Saúde , Humanos , Pandemias
16.
J Affect Disord ; 273: 1-7, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32421589

RESUMO

BACKGROUND: 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. METHODS: 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. RESULTS: 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). LIMITATIONS: 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. CONCLUSION: Modifiable factors associated with PTSD improvement (timing, dose, and modality) can be used to improve EBP outcomes.

17.
Psychol Trauma ; 12(3): 260-271, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31343206

RESUMO

OBJECTIVE: Cognitive processing therapy (CPT) and prolonged exposure therapy (PE) were widely disseminated to treat posttraumatic stress disorder (PTSD) in the Veterans Health Administration (VHA). However, few Iraq and Afghanistan war veterans (Operation Enduring Freedom [OEF], Operation Iraqi Freedom [OIF], Operation New Dawn [OND]) diagnosed with PTSD have received CPT/PE and many initiate CPT/PE after substantial delay. Veterans who do not initiate CPT/PE or initiate CPT/PE after delay may have poorer treatment outcomes. This study aimed to identify predictors of CPT/PE initiation and timing. METHODS: Participants included OEF/OIF/OND veterans diagnosed with PTSD who received psychotherapy between 2001 and 2017 in the VHA (n = 265,566). Logistic regression analysis was utilized to predict initiating CPT/PE (vs. no CPT/PE). Multinomial logistic regression analysis was utilized to predict not initiating or initiating delayed CPT/PE versus "early CPT/PE" (< 1 year after first mental health visit). Analyzed predictors included demographic, military, and clinical complexity variables (e.g., comorbidities, reported military sexual trauma [MST] history). RESULTS: Seventy-Seven percent of veterans did not initiate CPT/PE, with 7.4% initiating early and 15.4% initiating delayed CPT/PE. Reported MST history (odds ratio [OR] = 1.45, 95% CI [1.39, 1.51]) and history of suicidal ideation/attempt (OR = 1.42, 95% CI [1.38, 1.46]) were strong predictors of CPT/PE initiation versus no CPT/PE. Comorbid pain (relative risk ratio [RRR] = 1.35, 95% CI [1.30, 1.42]) and depressive disorders (RRR = 1.37, 95% CI [1.32, 1.43]) were associated with increased likelihood of delayed versus early CPT/PE. CONCLUSIONS: Most veterans in our study did not initiate CPT/PE. Generally, clinical complexity variables increased likelihood of initiating CPT/PE and initiating CPT/PE more than 1 year after first mental health visit. Additional research is needed to understand whether CPT/PE delay results from receipt of alternative intervention due to clinical complexity variables. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


Assuntos
Prática Clínica Baseada em Evidências , Psicoterapia/métodos , Transtornos de Estresse Pós-Traumáticos/terapia , Veteranos/psicologia , Adolescente , Adulto , Campanha Afegã de 2001- , Idoso , Feminino , Humanos , Guerra do Iraque 2003-2011 , Masculino , Saúde Mental , Pessoa de Meia-Idade , Transtornos de Estresse Pós-Traumáticos/psicologia , Fatores de Tempo , Estados Unidos , United States Department of Veterans Affairs , Saúde dos Veteranos , Adulto Jovem
18.
Depress Anxiety ; 37(4): 356-364, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31850650

RESUMO

BACKGROUND: Although evidence-based psychotherapies (EBPs) for posttraumatic stress disorder (PTSD) were implemented starting in 2005 in the veterans health administration (VHA), the largest national healthcare system in the U.S., the rate of initiation (uptake) and prevalence of these treatments in each calendar year have not been determined. We aimed to elucidate two metrics of EBP utilization, uptake and prevalence, following implementation. METHODS: Cohort study of Iraq and Afghanistan veterans in VHA (N = 181,620) with a PTSD diagnosis and ≥1 psychotherapy-coded outpatient visit from 2001 to 2014. Using natural language processing techniques, annual and cumulative uptake and prevalence rates from 2001 to 2014 were calculated for each of the two EBPs for PTSD, cognitive processing therapy (CPT) and prolonged exposure (PE) therapy. RESULTS: Annual uptake of CPT increased during most years, reaching a maximum of 11.1%. Annual uptake of PE showed little change until 2008 and then increased, reaching a maximum of 4.4%. The annual prevalence of CPT increased throughout the study, reaching a maximum of 14.6%. The annual prevalence of PE increased to a maximum of 5.0% in 2010, but then flattened and declined. Annual uptake of minimally adequate CPT increased a to maximum of 5% in 2014. Annual uptake of minimally adequate PE increased to a maximum of 1.2% in 2010. The cumulative prevalence of CPT was 19.9% and cumulative prevalence for PE was 7.5%. CONCLUSIONS: Access to EBPs for PTSD modestly increased for Iraq and Afghanistan veterans after nationwide implementation efforts. Further expanding the reach to veterans is critical, given low rates of minimally adequate EBPs for PTSD.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Veteranos , Afeganistão , Estudos de Coortes , Humanos , Iraque , Psicoterapia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/terapia , Estados Unidos/epidemiologia , United States Department of Veterans Affairs
19.
Womens Health Issues ; 30(2): 128-135, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31870696

RESUMO

BACKGROUND: Longer time intervals from presentation with hematuria to bladder cancer diagnosis have been reported among women compared with men. Despite women being the fastest growing cohort within the Department of Veterans Affairs, little is known about women veterans with bladder cancer. Our objectives were to quantify the time from hematuria to bladder cancer diagnosis in Department of Veterans Affairs and assess differences between sexes. METHODS: This was a retrospective cohort study of patients diagnosed with bladder cancer from 2001 to 2016. Included were patients with hematuria for fewer than 365 days before a bladder cancer diagnosis and who had a record of diagnostic cystoscopy after hematuria but before diagnosis. We evaluated the number of days from hematuria to diagnostic cystoscopy (clinical appraisal), cystoscopy to bladder cancer diagnosis (surgical appraisal), and hematuria to bladder cancer diagnosis (total diagnostic appraisal). We used quantile regression models to separately evaluate the effect of sex on the three appraisal intervals. RESULTS: Data from 213 women and 24,295 men were analyzed. The median clinical appraisal time was 78 days for women and 72 for men (p = .49). The median surgical appraisal time was 32 days for women and 33 for men (p = .74). The median total diagnostic appraisal time was 135 days for women and 130 for men (p = .71). Multivariable analyses showed no differences between men and women for any of the three appraisal intervals. CONCLUSIONS: The majority of time from hematuria to bladder cancer diagnosis is spent in clinical appraisal, but little difference was observed between men and women in Department of Veterans Affairs.


Assuntos
Cistoscopia/métodos , Diagnóstico Tardio/estatística & dados numéricos , Hematúria/etiologia , Neoplasias da Bexiga Urinária/diagnóstico , Veteranos/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Hematúria/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Distribuição por Sexo , Fatores de Tempo , Tempo para o Tratamento , Estados Unidos/epidemiologia , United States Department of Veterans Affairs , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/epidemiologia
20.
Appl Clin Inform ; 10(5): 794-803, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31645076

RESUMO

BACKGROUND: The development and adoption of health care common data models (CDMs) has addressed some of the logistical challenges of performing research on data generated from disparate health care systems by standardizing data representations and leveraging standardized terminology to express clinical information consistently. However, transforming a data system into a CDM is not a trivial task, and maintaining an operational, enterprise capable CDM that is incrementally updated within a data warehouse is challenging. OBJECTIVES: To develop a quality assurance (QA) process and code base to accompany our incremental transformation of the Department of Veterans Affairs Corporate Data Warehouse health care database into the Observational Medical Outcomes Partnership (OMOP) CDM to prevent incremental load errors. METHODS: We designed and implemented a multistage QA) approach centered on completeness, value conformance, and relational conformance data-quality elements. For each element we describe key incremental load challenges, our extract, transform, and load (ETL) solution of data to overcome those challenges, and potential impacts of incremental load failure. RESULTS: Completeness and value conformance data-quality elements are most affected by incremental changes to the CDW, while updates to source identifiers impact relational conformance. ETL failures surrounding these elements lead to incomplete and inaccurate capture of clinical concepts as well as data fragmentation across patients, providers, and locations. CONCLUSION: Development of robust QA processes supporting accurate transformation of OMOP and other CDMs from source data is still in evolution, and opportunities exist to extend the existing QA framework and tools used for incremental ETL QA processes.


Assuntos
Registros Eletrônicos de Saúde/estatística & dados numéricos , Modelos Estatísticos , Garantia da Qualidade dos Cuidados de Saúde , Assistência à Saúde
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