Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 66
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
JCO Clin Cancer Inform ; 4: 171-183, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32134687

RESUMO

PURPOSE: Patients with cancer are predisposed to developing chronic, comorbid conditions that affect prognosis, quality of life, and mortality. While treatment guidelines and care variations for these comorbidities have been described for the general noncancer population, less is known about real-world treatment patterns in patients with cancer. We sought to characterize the prevalence and distribution of initial treatment patterns across a large-scale data network for depression, hypertension, and type II diabetes mellitus (T2DM) among patients with cancer. METHODS: We used the Observational Health Data Sciences and Informatics network, an international collaborative implementing the Observational Medical Outcomes Partnership Common Data Model to standardize more than 2 billion patient records. For this study, we used 8 databases across 3 countries-the United States, France, and Germany-with 295,529,655 patient records. We identified patients with cancer using SNOMED (Systematized Nomenclature of Medicine) codes validated via manual review. We then characterized the treatment patterns of these patients initiating treatment of depression, hypertension, or T2DM with persistent treatment and at least 365 days of observation. RESULTS: Across databases, wide variations exist in treatment patterns for depression (n = 1,145,510), hypertension (n = 3,178,944), and T2DM (n = 886,766). When limited to 6-node (6-drug) sequences, we identified 61,052 unique sequences for depression, 346,067 sequences for hypertension, and 40,629 sequences for T2DM. These variations persisted across sites, databases, countries, and conditions, with the exception of metformin (73.8%) being the most common initial T2DM treatment. The most common initial medications were sertraline (17.5%) and escitalopram (17.5%) for depression and hydrochlorothiazide (20.5%) and lisinopril (19.6%) for hypertension. CONCLUSION: We identified wide variations in the treatment of common comorbidities in patients with cancer, similar to the general population, and demonstrate the feasibility of conducting research on patients with cancer across a large-scale observational data network using a common data model.

2.
PLoS One ; 15(1): e0226718, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31910437

RESUMO

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) after cerebral infarction is a complex and multifactorial phenomenon in the acute stage of ischemic stroke, and often results in a poor prognosis. Thus, identifying risk factors and making an early prediction of HT in acute cerebral infarction contributes not only to the selections of therapeutic regimen but also, more importantly, to the improvement of prognosis of acute cerebral infarction. The purpose of this study was to develop and validate a model to predict a patient's risk of HT within 30 days of initial ischemic stroke. METHODS: We utilized a retrospective multicenter observational cohort study design to develop a Lasso Logistic Regression prediction model with a large, US Electronic Health Record dataset which structured to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). To examine clinical transportability, the model was externally validated across 10 additional real-world healthcare datasets include EHR records for patients from America, Europe and Asia. RESULTS: In the database the model was developed, the target population cohort contained 621,178 patients with ischemic stroke, of which 5,624 patients had HT within 30 days following initial ischemic stroke. 612 risk predictors, including the distance a patient travels in an ambulance to get to care for a HT, were identified. An area under the receiver operating characteristic curve (AUC) of 0.75 was achieved in the internal validation of the risk model. External validation was performed across 10 databases totaling 5,515,508 patients with ischemic stroke, of which 86,401 patients had HT within 30 days following initial ischemic stroke. The mean external AUC was 0.71 and ranged between 0.60-0.78. CONCLUSIONS: A HT prognostic predict model was developed with Lasso Logistic Regression based on routinely collected EMR data. This model can identify patients who have a higher risk of HT than the population average with an AUC of 0.78. It shows the OMOP CDM is an appropriate data standard for EMR secondary use in clinical multicenter research for prognostic prediction model development and validation. In the future, combining this model with clinical information systems will assist clinicians to make the right therapy decision for patients with acute ischemic stroke.

3.
J Biomed Inform ; 102: 103363, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31866433

RESUMO

Algorithms for identifying patients of interest from observational data must address missing and inaccurate data and are desired to achieve comparable performance on both administrative claims and electronic health records data. However, administrative claims data do not contain the necessary information to develop accurate algorithms for disorders that require laboratory results, and this omission can result in insensitive diagnostic code-based algorithms. In this paper, we tested our assertion that the performance of a diagnosis code-based algorithm for chronic kidney disorder (CKD) can be improved by adding other codes indirectly related to CKD (e.g., codes for dialysis, kidney transplant, suspicious kidney disorders). Following the best practices from Observational Health Data Sciences and Informatics (OHDSI), we adapted an electronic health record-based gold standard algorithm for CKD and then created algorithms that can be executed on administrative claims data and account for related data quality issues. We externally validated our algorithms on four electronic health record datasets in the OHDSI network. Compared to the algorithm that uses CKD diagnostic codes only, positive predictive value of the algorithms that use additional codes was slightly increased (47.4% vs. 47.9-48.5% respectively). The algorithms adapted from the gold standard algorithm can be used to infer chronic kidney disorder based on administrative claims data. We succeeded in improving the generalizability and consistency of the CKD phenotypes by using data and vocabulary standardized across the OHDSI network, although performance variability across datasets remains. We showed that identifying and addressing coding and data heterogeneity can improve the performance of the algorithms.

4.
Biomed Opt Express ; 10(11): 5905-5920, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31799054

RESUMO

Pedicle screw placement accuracy during spinal fixation surgery varies greatly and severe misplacement has been reported in 1-6.5% of screws. Diffuse reflectance (DR) spectroscopy has previously been shown to reliably discriminate between tissues in the human body. We postulate that it could be used to discriminate between cancellous and cortical bone. Therefore, the purpose of this study is to validate DR spectroscopy as a warning system to detect impending pedicle screw breach in a cadaveric surgical setting using typical clinical breach scenarios. DR spectroscopy was incorporated at the tip of an integrated pedicle screw and screw driver used for tissue probing during pedicle screw insertions on six cadavers. Measurements were collected in the wavelength range of 400-1600 nm and each insertion was planned to result in a breach. Measurements were labelled as cancellous, cortical or representing a pre-cortical zone (PCZ) in between, based on information from cone beam computed tomographies at corresponding positions. In addition, DR spectroscopy data was recorded after breach. Four typical pedicle breach types were performed, and a total of 45 pedicle breaches were recorded. For each breach direction, the technology was able to detect the transition of the screw tip from the cancellous bone to the PCZ (P < 0.001), to cortical bone (P < 0.001), and to a subsequent breach (P < 0.001). Using support vector machine (SVM) classification, breach could reliably be detected with a sensitivity of 98.3 % [94.3-100 %] and a specificity of 97.7 % [91.0-100 %]. We conclude that DR spectroscopy reliably identifies the area of transition from cancellous to cortical bone in typical breach scenarios and can warn the surgeon of impending pedicle breach, thereby resulting in safer spinal fixation surgeries.

5.
Lancet ; 394(10211): 1816-1826, 2019 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-31668726

RESUMO

BACKGROUND: Uncertainty remains about the optimal monotherapy for hypertension, with current guidelines recommending any primary agent among the first-line drug classes thiazide or thiazide-like diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, dihydropyridine calcium channel blockers, and non-dihydropyridine calcium channel blockers, in the absence of comorbid indications. Randomised trials have not further refined this choice. METHODS: We developed a comprehensive framework for real-world evidence that enables comparative effectiveness and safety evaluation across many drugs and outcomes from observational data encompassing millions of patients, while minimising inherent bias. Using this framework, we did a systematic, large-scale study under a new-user cohort design to estimate the relative risks of three primary (acute myocardial infarction, hospitalisation for heart failure, and stroke) and six secondary effectiveness and 46 safety outcomes comparing all first-line classes across a global network of six administrative claims and three electronic health record databases. The framework addressed residual confounding, publication bias, and p-hacking using large-scale propensity adjustment, a large set of control outcomes, and full disclosure of hypotheses tested. FINDINGS: Using 4·9 million patients, we generated 22 000 calibrated, propensity-score-adjusted hazard ratios (HRs) comparing all classes and outcomes across databases. Most estimates revealed no effectiveness differences between classes; however, thiazide or thiazide-like diuretics showed better primary effectiveness than angiotensin-converting enzyme inhibitors: acute myocardial infarction (HR 0·84, 95% CI 0·75-0·95), hospitalisation for heart failure (0·83, 0·74-0·95), and stroke (0·83, 0·74-0·95) risk while on initial treatment. Safety profiles also favoured thiazide or thiazide-like diuretics over angiotensin-converting enzyme inhibitors. The non-dihydropyridine calcium channel blockers were significantly inferior to the other four classes. INTERPRETATION: This comprehensive framework introduces a new way of doing observational health-care science at scale. The approach supports equivalence between drug classes for initiating monotherapy for hypertension-in keeping with current guidelines, with the exception of thiazide or thiazide-like diuretics superiority to angiotensin-converting enzyme inhibitors and the inferiority of non-dihydropyridine calcium channel blockers. FUNDING: US National Science Foundation, US National Institutes of Health, Janssen Research & Development, IQVIA, South Korean Ministry of Health & Welfare, Australian National Health and Medical Research Council.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Adolescente , Adulto , Idoso , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Criança , Estudos de Coortes , Pesquisa Comparativa da Efetividade/métodos , Bases de Dados Factuais , Diuréticos/efeitos adversos , Diuréticos/uso terapêutico , Medicina Baseada em Evidências/métodos , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/prevenção & controle , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Adulto Jovem
6.
J Am Med Inform Assoc ; 26(11): 1237-1246, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31545380

RESUMO

OBJECTIVE: Electronic health records are increasingly utilized for observational and clinical research. Identification of cohorts using electronic health records is an important step in this process. Previous studies largely focused on the methods of cohort selection, but there is little evidence on the impact of underlying vocabularies and mappings between vocabularies used for cohort selection. We aim to compare the cohort selection performance using Australian Medicines Terminology to Anatomical Therapeutic Chemical (ATC) mappings from 2 different sources. These mappings were taken from the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM) and the Pharmaceutical Benefits Scheme (PBS) schedule. MATERIALS AND METHODS: We retrieved patients from the electronic Practice Based Research Network data repository using 3 ATC classification groups (A10, N02A, N06A). The retrieved patients were further verified manually and pooled to form a reference standard which was used to assess the accuracy of mappings using precision, recall, and F measure metrics. RESULTS: The OMOP-CDM mappings identified 2.6%, 15.2%, and 24.4% more drugs than the PBS mappings in the A10, N02A and N06A groups respectively. Despite this, the PBS mappings generally performed the same in cohort selection as OMOP-CDM mappings except for the N02A Opioids group, where a significantly greater number of patients were retrieved. Both mappings exhibited variable recall, but perfect precision, with all drugs found to be correctly identified. CONCLUSION: We found that 1 of the 3 ATC groups had a significant difference and this affected cohort selection performance. Our findings highlighted that underlying terminology mappings can greatly impact cohort selection accuracy. Clinical researchers should carefully evaluate vocabulary mapping sources including methodologies used to develop those mappings.

7.
Stud Health Technol Inform ; 264: 1831-1832, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438365

RESUMO

Observational research in cancer requires substantially more detail than most other therapeutic areas. Cancer conditions are defined through histology, affected anatomical structures, staging and grading, and biomarkers, and are treated with complex therapies. Here, we show a new cancer module as part of the OMOP CDM, allowing manual and automated abstraction and standardized analytics. We tested the model in EHR and registry data against a number of typical use cases.


Assuntos
Registros Eletrônicos de Saúde , Modelos Teóricos , Neoplasias , Pesquisa , Bases de Dados Factuais , Sistema de Registros
8.
J Biomed Inform ; 96: 103239, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31238109

RESUMO

Systematic application of observational data to the understanding of impacts of cancer treatments requires detailed information models allowing meaningful comparisons between treatment regimens. Unfortunately, details of systemic therapies are scarce in registries and data warehouses, primarily due to the complex nature of the protocols and a lack of standardization. Since 2011, we have been creating a curated and semi-structured website of chemotherapy regimens, HemOnc.org. In coordination with the Observational Health Data Sciences and Informatics (OHDSI) Oncology Subgroup, we have transformed a substantial subset of this content into the OMOP common data model, with bindings to multiple external vocabularies, e.g., RxNorm and the National Cancer Institute Thesaurus. Currently, there are >73,000 concepts and >177,000 relationships in the full vocabulary. Content related to the definition and composition of chemotherapy regimens has been released within the ATHENA tool (athena.ohdsi.org) for widespread utilization by the OHDSI membership. Here, we describe the rationale, data model, and initial contents of the HemOnc vocabulary along with several use cases for which it may be valuable.

10.
J Med Internet Res ; 21(3): e13249, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30912749

RESUMO

BACKGROUND: Clinical sequencing data should be shared in order to achieve the sufficient scale and diversity required to provide strong evidence for improving patient care. A distributed research network allows researchers to share this evidence rather than the patient-level data across centers, thereby avoiding privacy issues. The Observational Medical Outcomes Partnership (OMOP) common data model (CDM) used in distributed research networks has low coverage of sequencing data and does not reflect the latest trends of precision medicine. OBJECTIVE: The aim of this study was to develop and evaluate the feasibility of a genomic CDM (G-CDM), as an extension of the OMOP-CDM, for application of genomic data in clinical practice. METHODS: Existing genomic data models and sequencing reports were reviewed to extend the OMOP-CDM to cover genomic data. The Human Genome Organisation Gene Nomenclature Committee and Human Genome Variation Society nomenclature were adopted to standardize the terminology in the model. Sequencing data of 114 and 1060 patients with lung cancer were obtained from the Ajou University School of Medicine database of Ajou University Hospital and The Cancer Genome Atlas, respectively, which were transformed to a format appropriate for the G-CDM. The data were compared with respect to gene name, variant type, and actionable mutations. RESULTS: The G-CDM was extended into four tables linked to tables of the OMOP-CDM. Upon comparison with The Cancer Genome Atlas data, a clinically actionable mutation, p.Leu858Arg, in the EGFR gene was 6.64 times more frequent in the Ajou University School of Medicine database, while the p.Gly12Xaa mutation in the KRAS gene was 2.02 times more frequent in The Cancer Genome Atlas dataset. The data-exploring tool GeneProfiler was further developed to conduct descriptive analyses automatically using the G-CDM, which provides the proportions of genes, variant types, and actionable mutations. GeneProfiler also allows for querying the specific gene name and Human Genome Variation Society nomenclature to calculate the proportion of patients with a given mutation. CONCLUSIONS: We developed the G-CDM for effective integration of genomic data with standardized clinical data, allowing for data sharing across institutes. The feasibility of the G-CDM was validated by assessing the differences in data characteristics between two different genomic databases through the proposed data-exploring tool GeneProfiler. The G-CDM may facilitate analyses of interoperating clinical and genomic datasets across multiple institutions, minimizing privacy issues and enabling researchers to better understand the characteristics of patients and promote personalized medicine in clinical practice.


Assuntos
Bases de Dados Factuais/normas , Genômica/métodos , Medicina de Precisão/métodos , Humanos , Estudos Retrospectivos
11.
Cancer Inform ; 18: 1176935119835538, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30906191

RESUMO

In diffuse large B-cell lymphoma (DLBCL), predictive modeling may contribute to targeted drug development by enrichment of the study populations enrolled in clinical trials of DLBCL investigational drugs to include patients with lower likelihood of responding to standard of care. In clinical practice, predictive modeling has the potential to optimize therapy choices in DLBCL. The objectives of this study were to create a model for predicting health outcomes in patients with DLBCL treated with standard of care and determine informative predictors of health outcomes for patients with DLBCL. This was a retrospective observational study using data extracted from the IMS Health Database between September 2007 and April 2015. Patients were ⩾18 years of age with a DLBCL diagnosis. The index date was the date of the first DLBCL diagnosis. Patients were followed until outcome occurrence, defined as progression to a later line of therapy after ⩾60 days from the end of a previous therapy or stem cell transplantation. Patients were categorized into three cohorts depending on the post-index observation period: ⩽1 year, ⩽3 years, or ⩽5 years. Lasso logistic regression (LASSO), Naive Bayes, gradient-boosting machine (GBM), random forest (RF), and neural network models were performed for each cohort. The best-performing algorithms were predictive models based on GBM and observation periods ⩽1 and ⩽3 years after index date. Informative predictors included myocardial imaging, DLBCL stage IV, bronchiolar and renal disease, a chemotherapy regimen, and exposure to diphenhydramine and vasoprotectives on or before the first DLBCL diagnosis. These predictive models may be applied to targeted drug development and have the potential to optimize therapy choices in DLBCL. They were generated efficiently using a large number of independent variables readily available in standard insurance claims or electronic health record data systems.

12.
J Biomed Opt ; 24(1): 1-11, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30701722

RESUMO

Safe and accurate placement of screws remains a critical issue in open and minimally invasive spine surgery. We propose to use diffuse reflectance (DR) spectroscopy as a sensing technology at the tip of a surgical instrument to ensure a safe path of the instrument through the cancellous bone of the vertebrae. This approach could potentially reduce the rate of cortical bone breaches, thereby resulting in fewer neural and vascular injuries during spinal fusion surgery. In our study, DR spectra in the wavelength ranges of 400 to 1600 nm were acquired from cancellous and cortical bone from three human cadavers. First, it was investigated whether these spectra can be used to distinguish between the two bone types based on fat, water, and blood content along with photon scattering. Subsequently, the penetration of the bone by an optical probe was simulated using the Monte-Carlo (MC) method, to study if the changes in fat content along the probe path would still enable distinction between the bone types. Finally, the simulation findings were validated via an experimental insertion of an optical screw probe into the vertebra aided by x-ray image guidance. The DR spectra indicate that the amount of fat, blood, and photon scattering is significantly higher in cancellous bone than in cortical bone (p < 0.01), which allows distinction between the bone types. The MC simulations showed a change in fat content more than 1 mm before the optical probe came in contact with the cortical bone. The experimental insertion of the optical screw probe gave similar results. This study shows that spectral tissue sensing, based on DR spectroscopy at the instrument tip, is a promising technology to identify the transition zone from cancellous to cortical vertebral bone. The technology therefore has the potential to improve the safety and accuracy of spinal screw placement procedures.

14.
Nat Rev Drug Discov ; 17(5): 317-332, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29472638

RESUMO

A large proportion of biomedical research and the development of therapeutics is focused on a small fraction of the human genome. In a strategic effort to map the knowledge gaps around proteins encoded by the human genome and to promote the exploration of currently understudied, but potentially druggable, proteins, the US National Institutes of Health launched the Illuminating the Druggable Genome (IDG) initiative in 2014. In this article, we discuss how the systematic collection and processing of a wide array of genomic, proteomic, chemical and disease-related resource data by the IDG Knowledge Management Center have enabled the development of evidence-based criteria for tracking the target development level (TDL) of human proteins, which indicates a substantial knowledge deficit for approximately one out of three proteins in the human proteome. We then present spotlights on the TDL categories as well as key drug target classes, including G protein-coupled receptors, protein kinases and ion channels, which illustrate the nature of the unexplored opportunities for biomedical research and therapeutic development.

15.
Eur J Anaesthesiol ; 35(7): 527-533, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29389819

RESUMO

BACKGROUND: Beginners in residency programmes in anaesthesia are challenged because working environment is complex, and they cannot rely on experience to meet challenges. During this early stage, residents need rules and structures to guide their actions and ensure patient safety. OBJECTIVE: We investigated whether self-training with an electronic audiovisual checklist app on a mobile phone would produce a long-term improvement in the safety-relevant actions during induction of general anaesthesia. DESIGN, SETTING AND PARTICIPANTS: During the first month of their anaesthesia residency, we randomised 26 residents to the intervention and control groups. The study was performed between August 2013 and December 2014 in two university hospitals in Germany. INTERVENTION: In addition to normal training, the residents of the intervention group trained themselves on well tolerated induction using the electronic checklist for at least 60 consecutive general anaesthesia inductions. MAIN OUTCOME MEASURES: After an initial learning phase, all residents were observed during one induction of general anaesthesia. The primary outcome was the number of safety items completed during this anaesthesia induction. Secondary outcomes were similar observations 4 and 8 weeks later. RESULTS: Immediately, and 4 weeks after the first learning phase, residents in the intervention group completed a significantly greater number of safety checks than residents in the control group 2.8 [95% confidence interval (CI) 0.4 to 5.1, P = 0.021, Cohen's d = 0.47] and 3.7 (95% CI 1.3 to 6.1, P = 0.003, Cohen's d = 0.61), respectively. The difference between the groups had disappeared by 8 weeks: mean difference in the number of safety checks at 8 weeks was 0.4, 95% CI -2.0 to 2.8, P = 0.736, Cohen's d = 0.07). CONCLUSION: The use of an audiovisual self-training checklists improves safety-relevant behaviour in the early stages of a residency training programme in anaesthesia.


Assuntos
Anestesia/métodos , Anestesiologia/educação , Lista de Checagem , Educação de Pós-Graduação em Medicina/métodos , Internato e Residência/métodos , Adulto , Recursos Audiovisuais , Feminino , Alemanha , Humanos , Masculino , Segurança do Paciente
16.
Stress ; 21(2): 169-178, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29307250

RESUMO

Psychosocial stress is linked to the etiology of several neuropsychiatric disorders, including Major Depressive Disorder and Post-Traumatic-Stress-Disorder. Adolescence is a critical neurobehavioral developmental period wherein the maturing nervous system is sensitive to stress-related psychosocial events. The effects of social defeat stress, an animal model of psychosocial stress, on adolescent neurobehavioral phenomena are not well explored. Using the standard Resident-Intruder-Paradigm (RIP), adolescent Long-Evans (LE, residents, n = 100) and Sprague-Dawley (SD, intruders, n = 100) rats interacted for five days to invoke chronic social stress. Tests of depressive behavior (forced-swim-test (FST)), fear conditioning, and long-term synaptic plasticity are affected in various adult rodent chronic stress models, thus we hypothesized that these phenomena would be similarly affected in adolescent rats. Serendipitously, we observed the Intruders became the dominant rats and the Residents were the defeated/submissive rats. This robust and reliable role-reversal resulted in defeated LE-Residents showing a depressive-like state (increased time spent immobile in the FST), enhanced fear conditioning in both hippocampal-dependent and hippocampal-independent fear paradigms and altered hippocampal long-term synaptic plasticity, measured electrophysiologically in vitro in hippocampal slices. Importantly, SD-Intruders, SD and LE controls did not significantly differ from each other in any of these assessments. This reverse-Resident-Intruder-Paradigm (rRIP) represents a novel animal model to study the effects of stress on adolescent neurobehavioral phenomenon.


Assuntos
Depressão/fisiopatologia , Dominação-Subordinação , Plasticidade Neuronal/fisiologia , Estresse Psicológico/fisiopatologia , Animais , Comportamento Animal/fisiologia , Modelos Animais de Doenças , Medo , Hipocampo/fisiopatologia , Masculino , Ratos , Ratos Long-Evans , Ratos Sprague-Dawley
17.
JAMA Netw Open ; 1(4): e181755, 2018 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-30646124

RESUMO

Importance: Consensus around an efficient second-line treatment option for type 2 diabetes (T2D) remains ambiguous. The availability of electronic medical records and insurance claims data, which capture routine medical practice, accessed via the Observational Health Data Sciences and Informatics network presents an opportunity to generate evidence for the effectiveness of second-line treatments. Objective: To identify which drug classes among sulfonylureas, dipeptidyl peptidase 4 (DPP-4) inhibitors, and thiazolidinediones are associated with reduced hemoglobin A1c (HbA1c) levels and lower risk of myocardial infarction, kidney disorders, and eye disorders in patients with T2D treated with metformin as a first-line therapy. Design, Setting, and Participants: Three retrospective, propensity-matched, new-user cohort studies with replication across 8 sites were performed from 1975 to 2017. Medical data of 246 558 805 patients from multiple countries from the Observational Health Data Sciences and Informatics (OHDSI) initiative were included and medical data sets were transformed into a unified common data model, with analysis done using open-source analytical tools. Participants included patients with T2D receiving metformin with at least 1 prior HbA1c laboratory test who were then prescribed either sulfonylureas, DPP-4 inhibitors, or thiazolidinediones. Data analysis was conducted from 2015 to 2018. Exposures: Treatment with sulfonylureas, DPP-4 inhibitors, or thiazolidinediones starting at least 90 days after the initial prescription of metformin. Main Outcomes and Measures: The primary outcome is the first observation of the reduction of HbA1c level to 7% of total hemoglobin or less after prescription of a second-line drug. Secondary outcomes are myocardial infarction, kidney disorder, and eye disorder after prescription of a second-line drug. Results: A total of 246 558 805 patients (126 977 785 women [51.5%]) were analyzed. Effectiveness of sulfonylureas, DPP-4 inhibitors, and thiazolidinediones prescribed after metformin to lower HbA1c level to 7% or less of total hemoglobin remained indistinguishable in patients with T2D. Patients treated with sulfonylureas compared with DPP-4 inhibitors had a small increased consensus hazard ratio of myocardial infarction (1.12; 95% CI, 1.02-1.24) and eye disorders (1.15; 95% CI, 1.11-1.19) in the meta-analysis. Hazard of observing kidney disorders after treatment with sulfonylureas, DPP-4 inhibitors, or thiazolidinediones was equally likely. Conclusions and Relevance: The examined drug classes did not differ in lowering HbA1c and in hazards of kidney disorders in patients with T2D treated with metformin as a first-line therapy. Sulfonylureas had a small, higher observed hazard of myocardial infarction and eye disorders compared with DPP-4 inhibitors in the meta-analysis. The OHDSI collaborative network can be used to conduct a large international study examining the effectiveness of second-line treatment choices made in clinical management of T2D.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hemoglobina A Glicada/análise , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Tiazolidinedionas/uso terapêutico , Estudos de Coortes , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Feminino , Humanos , Masculino , Compostos de Sulfonilureia/efeitos adversos , Tiazolidinedionas/efeitos adversos
18.
Epilepsia ; 58(8): e101-e106, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28681416

RESUMO

Recent adverse event reports have raised the question of increased angioedema risk associated with exposure to levetiracetam. To help address this question, the Observational Health Data Sciences and Informatics research network conducted a retrospective observational new-user cohort study of seizure patients exposed to levetiracetam (n = 276,665) across 10 databases. With phenytoin users (n = 74,682) as a comparator group, propensity score-matching was conducted and hazard ratios computed for angioedema events by per-protocol and intent-to-treat analyses. Angioedema events were rare in both the levetiracetam and phenytoin groups (54 vs. 71 in per-protocol and 248 vs. 435 in intent-to-treat). No significant increase in angioedema risk with levetiracetam was seen in any individual database (hazard ratios ranging from 0.43 to 1.31). Meta-analysis showed a summary hazard ratio of 0.72 (95% confidence interval [CI] 0.39-1.31) and 0.64 (95% CI 0.52-0.79) for the per-protocol and intent-to-treat analyses, respectively. The results suggest that levetiracetam has the same or lower risk for angioedema than phenytoin, which does not currently carry a labeled warning for angioedema. Further studies are warranted to evaluate angioedema risk across all antiepileptic drugs.


Assuntos
Angioedema/induzido quimicamente , Angioedema/epidemiologia , Epilepsia/tratamento farmacológico , Fenitoína/efeitos adversos , Piracetam/análogos & derivados , Redes Comunitárias/estatística & dados numéricos , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Levetiracetam , Masculino , Piracetam/efeitos adversos
19.
Pharmacoepidemiol Drug Saf ; 25(9): 973-81, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27418432

RESUMO

BACKGROUND: We reviewed the results of the Observational Medical Outcomes Research Partnership (OMOP) 2010 Experiment in hopes of finding examples where apparently well-designed drug studies repeatedly produce anomalous findings. OMOP had applied thousands of designs and design parameters to 53 drug-outcome pairs across 10 electronic data resources. Our intent was to use this repository to elucidate some sources of error in observational studies. METHOD: From the 2010 OMOP Experiment, we sought drug-outcome-method combinations (DOMCs) that met consensus design criteria, yet repeatedly produced results contrary to expectation. We set aside DOMCs for which we could not agree on the suitability of the designs, then selected for an in-depth scrutiny one drug-outcome pair analyzed by a seemingly plausible methodological approach, whose results consistently disagreed with the a priori expectation. RESULTS: The OMOP "all-by-all" assessment of possible DOMCs yielded many combinations that would not be chosen by researchers as actual study options. Among those that passed a first level of scrutiny, two of seven drug-outcome pairs for which there were plausible research designs had anomalous results. The use of benzodiazepines was unexpectedly associated with acute renal failure and upper gastrointestinal bleeding. We chose the latter as an example for in-depth study. The factitious appearance of a bleeding risk may have been partly driven by an excess of procedures on the first day of treatment. A risk window definition that excluded the first day largely removed the spurious association. CONCLUSION: One cause of reproducible "error" may be repeated failure to tie design choices closely enough to the research question at hand. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Estudos Observacionais como Assunto/métodos , Vigilância de Produtos Comercializados/métodos , Projetos de Pesquisa , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Humanos , Estudos Observacionais como Assunto/normas , Reprodutibilidade dos Testes
20.
Proc Natl Acad Sci U S A ; 113(27): 7329-36, 2016 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-27274072

RESUMO

Observational research promises to complement experimental research by providing large, diverse populations that would be infeasible for an experiment. Observational research can test its own clinical hypotheses, and observational studies also can contribute to the design of experiments and inform the generalizability of experimental research. Understanding the diversity of populations and the variance in care is one component. In this study, the Observational Health Data Sciences and Informatics (OHDSI) collaboration created an international data network with 11 data sources from four countries, including electronic health records and administrative claims data on 250 million patients. All data were mapped to common data standards, patient privacy was maintained by using a distributed model, and results were aggregated centrally. Treatment pathways were elucidated for type 2 diabetes mellitus, hypertension, and depression. The pathways revealed that the world is moving toward more consistent therapy over time across diseases and across locations, but significant heterogeneity remains among sources, pointing to challenges in generalizing clinical trial results. Diabetes favored a single first-line medication, metformin, to a much greater extent than hypertension or depression. About 10% of diabetes and depression patients and almost 25% of hypertension patients followed a treatment pathway that was unique within the cohort. Aside from factors such as sample size and underlying population (academic medical center versus general population), electronic health records data and administrative claims data revealed similar results. Large-scale international observational research is feasible.


Assuntos
Padrões de Prática Médica/estatística & dados numéricos , Antidepressivos/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bases de Dados Factuais , Depressão/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Registros Eletrônicos de Saúde , Humanos , Hipertensão/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Internacionalidade , Informática Médica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA