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1.
J Rheumatol ; 47(1): 82-88, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30877213

RESUMO

OBJECTIVE: Previously thought to involve primarily the microvasculature, systemic sclerosis (SSc) has been increasingly linked to macrovascular disease. Cardiovascular (CV) and cerebrovascular disease are responsible for 20-30% of mortality in SSc, but few studies have shown an independent association between SSc and stroke. We assessed whether SSc was an independent risk factor for ischemic stroke. METHODS: We conducted a retrospective cohort study using the national Veterans Affairs (VA) administrative database containing records from 1999 to 2014. We obtained data for all patients with a diagnosis of SSc as well as 2 controls per SSc patient matched on sex, race, smoking status, and VA site. All patients were followed until development of ischemic stroke, death, or last encounter. We used a Cox proportional hazard regression model to estimate risk of ischemic stroke, with adjustments for CV comorbidities (hypertension, diabetes, atrial fibrillation, non-cerebrovascular atherosclerotic disease, hyperlipidemia), baseline medication use (aspirin, nonsteroidal antiinflammatory drugs), and Medicare enrollment. RESULTS: Among 4545 individuals with SSc (83% male, mean age 60.9 yrs), the incidence rate of ischemic stroke was 15.3 per 1000 person-years (vs 12.2 in the control cohort), with an unadjusted HR 1.28 (95% CI 1.11-1.47). The adjusted HR was 1.21 (95% CI 1.05-1.40) after adjusting for baseline CV risk factors, medications, and Medicare enrollment. CONCLUSION: SSc is independently associated with a higher risk of ischemic stroke among US veterans. Patients with SSc represent a population likely to benefit from targeted stroke screening or prevention therapies.

2.
Arthritis Care Res (Hoboken) ; 72(2): 283-291, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30740931

RESUMO

OBJECTIVE: Applying treat-to-target strategies in the care of patients with rheumatoid arthritis (RA) is critical for improving outcomes, yet electronic health records (EHRs) have few features to facilitate this goal. We undertook this study to evaluate the effect of 3 health information technology (health-IT) initiatives on the performance of RA disease activity measures and outcomes in an academic rheumatology clinic. METHODS: We implemented the 3 following initiatives designed to facilitate performance of the Clinical Disease Activity Index (CDAI): an EHR flowsheet to input scores, peer performance reports, and an EHR SmartForm including a CDAI calculator. We performed an interrupted time-series trial to assess effects on the proportion of RA visits with a documented CDAI. Mean CDAI scores before and after the last initiative were compared using t-tests. Additionally, we measured physician satisfaction with the initiatives. RESULTS: We included data from 995 patients with 8,040 encounters between 2012 and 2017. Over this period, electronic capture of CDAI scores increased from 0% to 64%. Performance remained stable after peer reporting and the SmartForm were introduced. We observed no meaningful changes in disease activity levels. However, physician satisfaction increased after SmartForm implementation. CONCLUSION: Modifications to the EHR, provider culture, and clinical workflows effectively improved capture of RA disease activity scores and physician satisfaction, but parallel gains in disease activity levels were missing. This study illustrates how a series of health-IT initiatives can evolve to enable sustained changes in practice. However, capture of RA outcomes alone may not be sufficient to improve levels of disease activity without a comprehensive treat-to-target program.

3.
ACR Open Rheumatol ; 1(2): 113-118, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31777787

RESUMO

Objective: Research using electronic health records (EHRs) may offer advantages over observational prospective cohort studies, including lower costs and a more generalizable patient population; however, EHR data may be more biased because of the high prevalence of missing data. We took advantage of a unique clinical setting in which all patients with rheumatoid arthritis (RA) were asked to participate in a longitudinal cohort study that would examine potential biases of EHR vs. prospective cohort designs in assessment of disease outcomes, but only some chose to participate. Methods: For individuals both participating in the cohort ("cohort," n = 187) and not participating ("noncohort," n = 190), we retrieved data regarding RA disease activity and other sociodemographic and clinical factors from data recorded in the EHR between 2013 and 2017. We compared the prevalence of missing data between groups and studied differences in disease activity measures over time. Results: Disease activity measures were less likely to be missing for cohort participants compared with noncohort participants (0.2%-13% vs. 2%-22%, respectively). No significant differences were present at baseline with respect to race/ethnicity or disease activity measures between groups. However, black, non-Hispanic race/ethnicity was associated with worse longitudinal disease activity compared with white, non-Hispanic individuals in noncohort participants (ß = 6.47, P =0.03) but not in cohort participants (ß = -0.10, P = 0.97) (P interaction = 0.09). Conclusion: Findings suggest that data derived from the EHR were comparable to a cohort across some variables but captured racial/ethnic disparities in long-term outcomes not observed in the cohort study. Research utilizing EHR data in conjunction with cohort studies may provide new opportunities for studying health disparities.

4.
Nat Commun ; 10(1): 3902, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467281

RESUMO

Systemic lupus erythematous (SLE) is a heterogeneous autoimmune disease in which outcomes vary among different racial groups. Here, we aim to identify SLE subgroups within a multiethnic cohort using an unsupervised clustering approach based on the American College of Rheumatology (ACR) classification criteria. We identify three patient clusters that vary according to disease severity. Methylation association analysis identifies a set of 256 differentially methylated CpGs across clusters, including 101 CpGs in genes in the Type I Interferon pathway, and we validate these associations in an external cohort. A cis-methylation quantitative trait loci analysis identifies 744 significant CpG-SNP pairs. The methylation signature is enriched for ethnic-associated CpGs suggesting that genetic and non-genetic factors may drive outcomes and ethnic-associated methylation differences. Our computational approach highlights molecular differences associated with clusters rather than single outcome measures. This work demonstrates the utility of applying integrative methods to address clinical heterogeneity in multifactorial multi-ethnic disease settings.


Assuntos
Biologia Computacional , Grupos Étnicos/genética , Genômica , Lúpus Eritematoso Sistêmico/genética , Família Multigênica , Estudos de Coortes , Metilação de DNA , Epigenômica , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Locos de Características Quantitativas , Índice de Gravidade de Doença , Estados Unidos
6.
JAMA Netw Open ; 2(3): e190606, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30874779

RESUMO

Importance: Knowing the future condition of a patient would enable a physician to customize current therapeutic options to prevent disease worsening, but predicting that future condition requires sophisticated modeling and information. If artificial intelligence models were capable of forecasting future patient outcomes, they could be used to aid practitioners and patients in prognosticating outcomes or simulating potential outcomes under different treatment scenarios. Objective: To assess the ability of an artificial intelligence system to prognosticate the state of disease activity of patients with rheumatoid arthritis (RA) at their next clinical visit. Design, Setting, and Participants: This prognostic study included 820 patients with RA from rheumatology clinics at 2 distinct health care systems with different electronic health record platforms: a university hospital (UH) and a public safety-net hospital (SNH). The UH and SNH had substantially different patient populations and treatment patterns. The UH has records on approximately 1 million total patients starting in January 2012. The UH data for this study were accessed on July 1, 2017. The SNH has records on 65 000 unique individuals starting in January 2013. The SNH data for the study were collected on February 27, 2018. Exposures: Structured data were extracted from the electronic health record, including exposures (medications), patient demographics, laboratories, and prior measures of disease activity. A longitudinal deep learning model was used to predict disease activity for patients with RA at their next rheumatology clinic visit and to evaluate interhospital performance and model interoperability strategies. Main Outcomes and Measures: Model performance was quantified using the area under the receiver operating characteristic curve (AUROC). Disease activity in RA was measured using a composite index score. Results: A total of 578 UH patients (mean [SD] age, 57 [15] years; 477 [82.5%] female; 296 [51.2%] white) and 242 SNH patients (mean [SD] age, 60 [15] years; 195 [80.6%] female; 30 [12.4%] white) were included in the study. Patients at the UH compared with those at the SNH were seen more frequently (median time between visits, 100 vs 180 days) and were more frequently prescribed higher-class medications (biologics) (364 [63.0%] vs 70 [28.9%]). At the UH, the model reached an AUROC of 0.91 (95% CI, 0.86-0.96) in a test cohort of 116 patients. The UH-trained model had an AUROC of 0.74 (95% CI, 0.65-0.83) in the SNH test cohort (n = 117) despite marked differences in the patient populations. In both settings, baseline prediction using each patients' most recent disease activity score had statistically random performance. Conclusions and Relevance: The findings suggest that building accurate models to forecast complex disease outcomes using electronic health record data is possible and these models can be shared across hospitals with diverse patient populations.


Assuntos
Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Aprendizado Profundo , Diagnóstico por Computador/métodos , Registros Eletrônicos de Saúde/classificação , Adulto , Idoso , Estudos de Coortes , Feminino , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
7.
Jt Comm J Qual Patient Saf ; 45(5): 348-357, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30686706

RESUMO

OBJECTIVES: New specialty drugs such as biologics are now available in record numbers, presenting increased safety risks for people with immune-mediated diseases. However, comprehensive assessments of patient safety for these drugs are lacking. We examined performance on key patient safety measures, such as screening for latent tuberculosis (LTBI), hepatitis B virus (HBV), and hepatitis C virus (HCV), for new users of a broad group of specialty medications. METHODS: Data were extracted via electronic health record data warehouses of a large university health system using structured queries, and extensive chart review was performed to confirm measure elements. We included all new users of immunosuppressive specialty drugs between 2013 and 2017. We assessed screening for LTBI, HBV, and HCV from 12 months before through 60 days after medication initiation, and calculated performance on a composite measure that required screening for all three infections. Multivariable logistic regression was used to assess differences in screening across specialties, adjusting for patient race, sex, age, and comorbidities. RESULTS: Among 2027 patients, the most common drugs prescribed were adalimumab (32%), etanercept (24%), infliximab (19%), and ustekinumab (9%). Overall, 62% of patients were screened for LTBI, 42% for HBV, and 33% for HCV. Only 26% of patients were screened appropriately for all three infections. Screening patterns differed significantly according to treating specialty. CONCLUSIONS: We found gaps in ambulatory safety for patients treated with immunosuppressive specialty drugs for diverse inflammatory conditions across all relevant treating specialties. More robust safety protocols are urgently needed to prevent serious patient safety events in this high-risk population.

8.
J Rheumatol ; 46(4): 370-375, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30504507

RESUMO

OBJECTIVE: Prior studies around the relationship between smoking and rheumatoid arthritis (RA) disease activity have reported inconsistent findings, which may be ascribed to heterogeneous study designs or biases in statistical analyses. We examined the association between smoking and RA outcomes using statistical methods that account for time-varying confounding and loss to followup. METHODS: We included 282 individuals with an RA diagnosis using electronic health record data collected at a public hospital between 2013 and 2017. Current smoking status and disease activity were assessed at each visit; covariates included sex, race/ethnicity, age, obesity, and medication use. We used longitudinal targeted maximum likelihood estimation to estimate the causal effect of smoking on disease activity measures at 27 months, and compared results to conventional longitudinal methods. RESULTS: Smoking was associated with an increase of 0.64 units in the patient global score compared to nonsmoking (p = 0.01), and with 2.58 more swollen joints (p < 0.001). While smoking was associated with a higher clinical disease activity score (2.11), the difference was not statistically significant (p = 0.22). We found no association between smoking and physician global score, or C-reactive protein levels, and an inverse association between smoking and tender joint count (p = 0.05). Analyses using conventional methods showed a null relationship for all outcomes. CONCLUSION: Smoking is associated with higher levels of disease activity in RA. Causal methods may be useful for investigations of additional exposures on longitudinal outcome measures in rheumatologic disease.

9.
Semin Arthritis Rheum ; 48(6): 1087-1092, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30449650

RESUMO

INTRODUCTION/OBJECTIVES: Pneumocystis jirovecii pneumonia (PJP) is a rare but potentially fatal opportunistic infection; however, consensus varies around which conditions or medications confer a level of risk sufficient to justify antibiotic prophylaxis for PJP. We used electronic health record (EHR) data to assess the current patterns of PJP prophylaxis, PJP outcomes, and prophylaxis-related adverse events among patients with rheumatic diseases who were receiving high-risk immunosuppressant drugs. METHODS: Data derive from the EHR of a large health system. We included new immunosuppressant users with diagnoses of vasculitis, myositis, or systemic lupus erythematosus. We calculated the proportion of patients who received PJP prophylaxis for each diagnosis and drug combination. We also calculated the number of PJP infections and the number of antibiotic adverse drug events (ADEs) per patient-year of exposure. RESULTS: We followed 316 patients for 23.2 + /- 14.2 months. Overall, 124 (39%) of patients received prophylactic antibiotics for PJP. At least 25% of patients with the highest risk conditions (e.g. vasculitis) or highest risk immunosuppressants (e.g. cyclophosphamide) did not receive PJP prophylaxis. We found no cases of PJP infection over 640 patient-years of follow up, including among those not receiving prophylaxis, and an overall incidence rate of ADEs of 2.2% per patient-year. CONCLUSIONS: PJP prophylaxis for patients with rheumatic conditions is inconsistent, with one quarter of patients who have high risk conditions or high risk immunosuppressants not receiving prophylaxis. However, given extremely low rates of PJP infection, but detectable ADEs to prophylactic antibiotics, our findings suggest that evidence to guide more personalized risk assessments are needed to inform PJP prophylaxis.

10.
Arthritis Care Res (Hoboken) ; 71(7): 925-935, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30099861

RESUMO

OBJECTIVE: Most studies that have evaluated patient-reported outcomes, such as those utilizing the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Short Form 10a (PF10a) in rheumatoid arthritis (RA), have been performed in white and English-speaking populations. The aim of our study was to assess the measurement properties of the PF10a in a racially/ethnically diverse population with RA and to determine the effect of non-English language proficiency, insurance status, and race/ethnicity on the validity and responsiveness of the PF10a. METHODS: Data were abstracted from electronic health records for all RA patients seen in a university-based rheumatology clinic between 2013 and 2017. We evaluated the use of the PF10a, floor and ceiling effects, and construct validity across categories of language preference, insurance, and race/ethnicity. We used standardized response means and linear mixed-effects models to evaluate the responsiveness of the PF10a to longitudinal changes in the Clinical Disease Activity Index (CDAI) across population subgroups. RESULTS: We included 595 patients in a cross-sectional analysis of validity and 341 patients in longitudinal responsiveness analyses of the PF10a. The PF10a had acceptable floor and ceiling effects and was successfully implemented. We observed good construct validity and responsiveness to changes in CDAI among white subjects, English speakers, and privately insured patients. However, constructs evaluated by the PF10a were less correlated with clinical measures among Chinese speakers and Hispanic subjects, and less sensitive to clinical improvements among Medicaid patients and Spanish speakers. CONCLUSION: While the PF10a has good measurement properties and is both practical and acceptable for implementation in routine clinical practice, we also found important differences across racial/ethnic groups and those with limited English proficiency that warrant further investigation.

11.
JAMA Intern Med ; 178(11): 1544-1547, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30128552

RESUMO

A promise of machine learning in health care is the avoidance of biases in diagnosis and treatment; a computer algorithm could objectively synthesize and interpret the data in the medical record. Integration of machine learning with clinical decision support tools, such as computerized alerts or diagnostic support, may offer physicians and others who provide health care targeted and timely information that can improve clinical decisions. Machine learning algorithms, however, may also be subject to biases. The biases include those related to missing data and patients not identified by algorithms, sample size and underestimation, and misclassification and measurement error. There is concern that biases and deficiencies in the data used by machine learning algorithms may contribute to socioeconomic disparities in health care. This Special Communication outlines the potential biases that may be introduced into machine learning-based clinical decision support tools that use electronic health record data and proposes potential solutions to the problems of overreliance on automation, algorithms based on biased data, and algorithms that do not provide information that is clinically meaningful. Existing health care disparities should not be amplified by thoughtless or excessive reliance on machines.


Assuntos
Algoritmos , Registros Eletrônicos de Saúde , Aprendizado de Máquina , Disparidades em Assistência à Saúde , Humanos , Fatores Socioeconômicos
12.
Mult Scler Relat Disord ; 24: 135-141, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30005356

RESUMO

BACKGROUND: Multiple sclerosis (MS) incidence has increased recently, particularly in women, suggesting a possible role of one or more environmental exposures in MS risk. The study objective was to determine if animal, dietary, recreational, or occupational exposures are associated with MS risk. METHODS: Least absolute shrinkage and selection operator (LASSO) regression was used to identify a subset of exposures with potential relevance to disease in a large population-based (Kaiser Permanente Northern California [KPNC]) case-control study. Variables with non-zero coefficients were analyzed in matched conditional logistic regression analyses, adjusted for established environmental risk factors and socioeconomic status (if relevant in univariate screening),± genetic risk factors, in the KPNC cohort and, for purposes of replication, separately in the Swedish Epidemiological Investigation of MS cohort. These variables were also assessed in models stratified by HLA-DRB1*15:01 status since interactions between risk factors and that haplotype have been described. RESULTS: There was a suggestive association of pesticide exposure with having MS among men, but only in those who were positive for HLA-DRB1*15:01 (OR pooled = 3.11, 95% CI 0.87, 11.16, p = 0.08). CONCLUSIONS: While this finding requires confirmation, it is interesting given the association between pesticide exposure and other neurological diseases. The study also demonstrates the application of LASSO to identify environmental exposures with reduced multiple statistical testing penalty. Machine learning approaches may be useful for future investigations of concomitant MS risk or prognostic factors.


Assuntos
Exposição Ambiental , Esclerose Múltipla/epidemiologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Interação Gene-Ambiente , Cadeias HLA-DRB1/genética , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/genética , Praguicidas/toxicidade , Fatores de Risco , Fatores Sexuais , Adulto Jovem
13.
JMIR Med Inform ; 6(2): e31, 2018 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-29743158

RESUMO

BACKGROUND: Despite significant interest in the collection of patient-reported outcomes to make care more patient-centered, few studies have evaluated implementation efforts to collect patient-reported outcomes from diverse patient populations. OBJECTIVE: We assessed the collection of patient-reported outcomes from rheumatoid arthritis patients in an academic rheumatology clinic, using a paper and an online form through the electronic health record patient portal. METHODS: We identified patients seen between 2012-2016 with ≥2 face-to-face encounters with a rheumatology provider and International Classification of Diseases codes for RA, ≥30 days apart. In 2013, our clinic implemented a paper version of the Patient Reported Outcome Measurement Information System (PROMIS) physical function form that was administered to patients upon their check-in at the clinic. In 2015, an online version of the form became available by way of the electronic health record patient portal to patients with active portal accounts. We compared the proportion of visits with documented PROMIS scores across age, race and ethnicity, and language and examined trends over time using a control chart. RESULTS: We included 1078 patients with rheumatoid arthritis with 7049 in-person encounters at the rheumatology clinic over 4 years, with an average of 168 visits per month. Of the included patients, 80.4% of patients (867/1078) were female and the mean age was 58 (SD 16) years. The overall PROMIS physical function score documentation increased from 60.4% (1081/1791) of visits in 2013 to 74.4% (905/1217) of visits in 2016. Online score documentation increased from 10.0% (148/1473) in 2015 to 19.3% (235/1217) in 2016. African American patients were least likely to have a PROMIS physical function score recorded (55/88, 62.5% compared to 792/990, 80.0% for other racial or ethnic groups; P<.001). Compared with white patients, both African American and Hispanic patients were less likely to have active online electronic health record portal accounts (44/88, 50% and 90/157, 57.3% respectively, compared to 437/521, 83.9% of white patients; P<.001) and, once activated, less likely to use the online survey (6/44, 13.6% and 16/90, 17.8% respectively, compared to 135/437, 30.9% of white patients; P=.02). There was no significant difference in the proportion of any PROMIS physical function forms recorded between non-English vs English preferred patients. No significant differences were found across age or gender. CONCLUSIONS: PROMIS physical function form completion improved overall from 2012-2016 but lagged among racial and ethnic minorities and non-English preferred patients. Future studies should address issues of portal access, enrollment, satisfaction, and persistence and focus on developing PRO implementation strategies that accommodate the needs and preferences of diverse populations.

14.
Clin Rheumatol ; 37(2): 467-474, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28993952

RESUMO

Despite the increasing use of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cardiovascular (CV) risk score in clinical practice, few studies have compared this score to the Framingham risk score among rheumatologic patients. We calculated Framingham and 2013 ACC/AHA risk scores in subjects with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and assessed demographic, CV, and rheumatologic characteristics associated with discordant scores (high-risk ACC/AHA scores but low-risk Framingham scores). SLE and RA subjects drawn from two population-based cohort studies were assessed during in-person study visits. We used chi-squared tests and t tests to examine the association of discordant CV risk scores with baseline characteristics. Eleven (7.0%) of 157 SLE subjects and 11 (11.5%) of 96 RA subjects had discordant CV risk scores with high ACC/AHA scores and low Framingham scores. These findings did not significantly change when a 1.5 multiplier was applied to the Framingham score. Rheumatologic disease duration, high-sensitivity CRP levels, African-American race, diabetes, current use of anti-hypertensive medication, higher age, and higher systolic blood pressure were each significantly associated with discordant risk scores. Approximately 10% of SLE and RA subjects had discordant 10-year CV risk scores. Our findings suggest that the use of the 2013 ACC/AHA risk score could result in changes to lipid-lowering therapy recommendations in a significant number of rheumatologic patients. Prospective studies are needed to compare which score better predicts CV events in rheumatologic patients, especially those with risk factors associated with discordant risk scores.


Assuntos
Artrite Reumatoide/complicações , Doenças Cardiovasculares/etiologia , Lúpus Eritematoso Sistêmico/complicações , Adulto , Idoso , American Heart Association , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Estados Unidos
15.
Rheumatol Int ; 38(2): 313-314, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29209792

RESUMO

In a recent publication, Quintana-Dunque et al. studied patients with early onset rheumatoid arthritis (RA) and showed that baseline smoking status was inversely associated with disease activity and disability at 36 months. The authors conclude that smoking may not be as deleterious as previously considered in RA disease course. However, the authors fail to highlight several limitations of study design and analysis, including time-varying confounding, which may have a direct impact on results and corresponding conclusions.


Assuntos
Artrite Reumatoide , Fumar , Pessoas com Deficiência , Progressão da Doença , Humanos , Projetos de Pesquisa
16.
Rheumatol Int ; 38(2): 319, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29273937

RESUMO

The given and family name of a co-author R. Adams Dudley was swapped in the published article. The correct given name is R. Adams and the family name is Dudley.

17.
Per Med ; 14(3): 203-211, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28993792

RESUMO

AIM: Since whole-genome sequencing (WGS) information can have positive and negative personal utility for individuals, we examined predictors of willingness to pay (WTP) for WGS. PATIENTS & METHODS: We surveyed two independent populations: adult patients (n = 203) and college seniors (n = 980). Ordinal logistic regression models were used to characterize the relationship between predictors and WTP. RESULTS: Sex, age, education, income, genomic knowledge and knowing someone who had genetic testing or having had genetic testing done personally were associated with significantly higher WTP for WGS. After controlling for income and education, males were willing to pay more for WGS than females. CONCLUSION: Differences in WTP may impact equity, coverage, affordability and access, and should be anticipated by public dialog about related health policy.

18.
Mult Scler ; : 1352458517733551, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28980494

RESUMO

BACKGROUND: Strong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology. OBJECTIVE: We comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to POMS. METHODS: Cases with onset <18 years ( n = 569) and controls ( n = 16,251) were included from the United States and Sweden. Adjusted logistic regression and meta-analyses were performed for individual risk variants and a weighted genetic risk score (wGRS) for non-MHC variants. Results were compared to adult MS cases ( n = 7588). RESULTS: HLA-DRB1*15:01 was strongly associated with POMS (odds ratio (OR)meta = 2.95, p < 2.0 × 10-16). Furthermore, 28 of 104 non-MHC variants studied (23%) were associated ( p < 0.05); POMS cases carried, on average, a higher burden of these 28 variants compared to adults (ORavg = 1.24 vs 1.13, respectively), though the difference was not significant. The wGRS was strongly associated with POMS (ORmeta = 2.77, 95% confidence interval: 2.33, 3.32, p < 2.0 × 10-16) and higher, on average, when compared to adult cases. Additional class III risk variants in the MHC region associated with POMS were revealed after accounting for HLA-DRB1*15:01 and HLA-A*02. CONCLUSION: Pediatric and adult MS share many genetic variants suggesting similar biological processes are present. MHC variants beyond HLA-DRB1*15:01 and HLA-A*02 are also associated with POMS.

19.
Rheumatol Int ; 37(10): 1611-1618, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28748425

RESUMO

Evidence suggests that hydroxychloroquine (HCQ) retinal toxicity is more common than previously thought. Adhering to careful weight-based dosing can significantly reduce the risk of this adverse event and is recommended in recent guidelines. We used electronic health record data from a large health system to examine HCQ dosing over a 5-year period and identify risk factors associated with higher dosage of HCQ. We constructed a longitudinal, retrospective cohort of patients with HCQ prescriptions (1681 patients with 3490 prescribing events) between 2012 and 2016. We measured HCQ dosing patterns relative to guidelines (<6.5 and <5.0 mg/kg) over time and used longitudinal multivariate mixed effects logistic regression to identify sociodemographic, clinical and health system factors associated with receiving higher than recommended doses of HCQ. The proportion of patients receiving doses above 6.5 mg/kg decreased from 12% in 2012 to 7% by 2016. Similarly, the proportion of patients with doses above 5.0 mg/kg fell from 38% in 2012 to 30% in 2016. Low body weight (<68 kg) was strongly associated with receiving doses of HCQ above 6.5 mg/kg across all time points, even after adjusting for other factors (odds ratios ranging from 13.2 to 21.0). Although the proportion of patients receiving higher than recommended HCQ doses has declined over a period of 5 years, a substantial number of individuals remain at increased risk for toxicity. Given the widespread use of HCQ in immune-mediated diseases, our study suggests that interventions aimed to ensure appropriate dosing are warranted to improve patient safety.


Assuntos
Antirreumáticos/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Dermatopatias/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
20.
Eur J Epidemiol ; 32(10): 909-919, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28597127

RESUMO

Interactions between environment and genetics may contribute to multiple sclerosis (MS) development. We investigated whether the previously observed interaction between smoking and HLA genotype in the Swedish population could be replicated, refined and extended to include other populations. We used six independent case-control studies from five different countries (Sweden, Denmark, Norway, Serbia, United States). A pooled analysis was performed for replication of previous observations (7190 cases, 8876 controls). Refined detailed analyses were carried out by combining the genetically similar populations from the Nordic studies (6265 cases, 8401 controls). In both the pooled analyses and in the combined Nordic material, interactions were observed between HLA-DRB*15 and absence of HLA-A*02 and between smoking and each of the genetic risk factors. Two way interactions were observed between each combination of the three variables, invariant over categories of the third. Further, there was also a three way interaction between the risk factors. The difference in MS risk between the extremes was considerable; smokers carrying HLA-DRB1*15 and lacking HLA-A*02 had a 13-fold increased risk compared with never smokers without these genetic risk factors (OR 12.7, 95% CI 10.8-14.9). The risk of MS associated with HLA genotypes is strongly influenced by smoking status and vice versa. Since the function of HLA molecules is to present peptide antigens to T cells, the demonstrated interactions strongly suggest that smoking alters MS risk through actions on adaptive immunity.


Assuntos
Predisposição Genética para Doença , Antígenos HLA-A/genética , Cadeias HLA-DRB1/genética , Esclerose Múltipla/epidemiologia , Fumar/efeitos adversos , Estudos de Casos e Controles , Feminino , Interação Gene-Ambiente , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Fatores de Risco , Fumar/imunologia , Suécia/epidemiologia
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