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Dr. Elizabeth Brown Do

400 N Pepper Ave
Colton CA 92324
909 803-3362
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License #: 20A12407
NPI: 1215281019
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Estimating Efficacy in a Randomized Trial With Product Nonadherence: Application of Multiple Methods to a Trial of Preexposure Prophylaxis for HIV Prevention. - American journal of epidemiology
Antiretroviral preexposure prophylaxis (PrEP) for persons at high risk of human immunodeficiency virus infection is a promising new prevention strategy. Six randomized trials of oral PrEP were recently conducted and demonstrated efficacy estimates ranging from 75% to no effect, with nonadherence likely resulting in attenuated estimates of the protective effect of PrEP. In 1 of these trials, the Partners PrEP Study (Kenya and Uganda, 2008-2011), participants (4,747 serodiscordant heterosexual couples) were randomized to receipt of tenofovir (TDF), coformulated TDF/emtricitabine (FTC), or placebo. Intention-to-treat analyses found efficacy estimates of 67% for TDF and 75% for TDF/FTC. We applied multiple methods to data from that trial to estimate the efficacy of PrEP with high adherence, including principal stratification and inverse-probability-of-censoring (IPC) weights. Results were further from the null when correcting for nonadherence: 1) among the strata with an estimated 100% probability of high adherence (TDF hazard ratio (HR) = 0.19, 95% confidence interval (CI): 0.07, 0.56; TDF/FTC HR = 0.12, 95% CI: 0.03, 0.52); 2) with IPC weights used to approximate a continuously adherent population (TDF HR = 0.18, 95% CI: 0.06, 0.53; TDF/FTC HR = 0.15, 95% CI: 0.04, 0.52); and 3) in per-protocol analysis (TDF HR = 0.18, 95% CI: 0.06, 0.53; TDF/FTC HR = 0.16, 95% CI: 0.05, 0.53). Our results suggest that the efficacy of PrEP with high adherence is over 80%.© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail:
A pooled analysis of reproductive factors, exogenous hormone use and risk of multiple myeloma among women in the International Multiple Myeloma Consortium. - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Female sex hormones are known to have immunomodulatory effects. Therefore, reproductive factors and exogenous hormone use could influence the risk of multiple myeloma in women. However, the role of hormonal factors in multiple myeloma etiology remains unclear because previous investigations were underpowered to detect modest associations.We conducted a pooled analysis of seven case-control studies included in the International Multiple Myeloma Consortium, with individual data on reproductive factors and exogenous hormone use from 1,072 female cases and 3,541 female controls. Study-specific odd ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using logistic regression and pooled analyses were conducted using random effects meta-analyses.Multiple myeloma was not associated with reproductive factors, including ever parous (OR=0.92, 95%CI=0.68-1.25), or with hormonal contraception use (OR=1.04, 95%CI=0.80-1.36). Postmenopausal hormone therapy users had non-significantly reduced risks of multiple myeloma compared with never users, but this association differed across centers (OR=0.65, 95%CI=0.37-1.15, I2=76.0%, p-heterogeneity= 0.01).These data do not support a role for reproductive factors or exogenous hormones in myelomagenesis.Incidence rates of multiple myeloma are higher in men than in women, and sex hormones could influence this pattern. Associations with reproductive factors and exogenous hormone use were inconclusive despite our large sample size, suggesting that female sex hormones may not play a significant role in multiple myeloma etiology.Copyright © 2015, American Association for Cancer Research.
Quality of evidence revealing subtle gender biases in science is in the eye of the beholder. - Proceedings of the National Academy of Sciences of the United States of America
Scientists are trained to evaluate and interpret evidence without bias or subjectivity. Thus, growing evidence revealing a gender bias against women-or favoring men-within science, technology, engineering, and mathematics (STEM) settings is provocative and raises questions about the extent to which gender bias may contribute to women's underrepresentation within STEM fields. To the extent that research illustrating gender bias in STEM is viewed as convincing, the culture of science can begin to address the bias. However, are men and women equally receptive to this type of experimental evidence? This question was tested with three randomized, double-blind experiments-two involving samples from the general public (n = 205 and 303, respectively) and one involving a sample of university STEM and non-STEM faculty (n = 205). In all experiments, participants read an actual journal abstract reporting gender bias in a STEM context (or an altered abstract reporting no gender bias in experiment 3) and evaluated the overall quality of the research. Results across experiments showed that men evaluate the gender-bias research less favorably than women, and, of concern, this gender difference was especially prominent among STEM faculty (experiment 2). These results suggest a relative reluctance among men, especially faculty men within STEM, to accept evidence of gender biases in STEM. This finding is problematic because broadening the participation of underrepresented people in STEM, including women, necessarily requires a widespread willingness (particularly by those in the majority) to acknowledge that bias exists before transformation is possible.
Genetic associations of leptin-related polymorphisms with systemic lupus erythematosus. - Clinical immunology (Orlando, Fla.)
Leptin is abnormally elevated in the plasma of patients with systemic lupus erythematosus (SLE), where it is thought to promote and/or sustain pro-inflammatory responses. Whether this association could reflect an increased genetic susceptibility to develop SLE is not known, and studies of genetic associations with leptin-related polymorphisms in SLE patients have been so far inconclusive. Here we genotyped DNA samples from 15,706 SLE patients and healthy matched controls from four different ancestral groups, to correlate polymorphisms of genes of the leptin pathway to risk for SLE. It was found that although several SNPs showed weak associations, those associations did not remain significant after correction for multiple testing. These data do not support associations between defined leptin-related polymorphisms and increased susceptibility to develop SLE.Copyright © 2015 Elsevier Inc. All rights reserved.
New evidence in the treatment of overactive bladder. - Current opinion in obstetrics & gynecology
Overactive bladder (OAB) in women is highly prevalent. It can be very bothersome and affect quality of life. Treatment differs significantly depending on the clinical presentation, and includes behavioural modification, medicinal therapies and surgical procedures. New treatment options have become available in recent years, and can offer great benefit to patients with persistent, bothersome OAB.First-line management for OAB consists of lifestyle and behavioural therapy, followed by antimuscarinic therapy or oral beta-3 agonists. Sacral neuromodulation, onabotulinumtoxinA and posterior tibial nerve stimulation are additional well tolerated and efficacious treatment options that should be considered in carefully selected, refractory OAB patients. These recent advances in OAB therapy are discussed in this review.The treatment of OAB is often complex, and can require trials of multiple different treatment modalities. Although the treatment advances discussed in this review have augmented treatment of OAB, the condition continues to negatively impact quality of life for our ageing female population. Clinical trials and development of novel therapies continue to be paramount.
Evaluation of a performance appraisal framework for radiation therapists in planning and simulation. - Journal of medical radiation sciences
Constantly evolving technology and techniques within radiation therapy require practitioners to maintain a continuous approach to professional development and training. Systems of performance appraisal and adoption of regular feedback mechanisms are vital to support this development yet frequently lack structure and rely on informal peer support.A Radiation Therapy Performance Appraisal Framework (RT-PAF) for radiation therapists in planning and simulation was developed to define expectations of practice and promote a supportive and objective culture of performance and skills appraisal. Evaluation of the framework was conducted via an anonymous online survey tool. Nine peer reviewers and fourteen recipients provided feedback on its effectiveness and the challenges and limitations of the approach.Findings from the evaluation were positive and suggested that both groups gained benefit from and expressed a strong interest in embedding the approach more routinely. Respondents identified common challenges related to the limited ability to implement suggested development strategies; this was strongly associated with time and rostering issues.This framework successfully defined expectations for practice and provided a fair and objective feedback process that focussed on skills development. It empowered staff to maintain their skills and reach their professional potential. Management support, particularly in regard to provision of protected time was highlighted as critical to the framework's ongoing success. The demonstrated benefits arising in terms of staff satisfaction and development highlight the importance of this commitment to the modern radiation therapy workforce.
Dose planning objectives in anal canal cancer IMRT: the TROG ANROTAT experience. - Journal of medical radiation sciences
Intensity modulated radiotherapy (IMRT) is ideal for anal canal cancer (ACC), delivering high doses to irregular tumour volumes whilst minimising dose to surrounding normal tissues. Establishing achievable dose objectives is a challenge. The purpose of this paper was to utilise data collected in the Assessment of New Radiation Oncology Treatments and Technologies (ANROTAT) project to evaluate the feasibility of ACC IMRT dose planning objectives employed in the Australian situation.Ten Australian centres were randomly allocated three data sets from 15 non-identifiable computed tomography data sets representing a range of disease stages and gender. Each data set was planned by two different centres, producing 30 plans. All tumour and organ at risk (OAR) contours, prescription and dose constraint details were provided. Dose-volume histograms (DVHs) for each plan were analysed to evaluate the feasibility of dose planning objectives provided.All dose planning objectives for the bone marrow (BM) and femoral heads were achieved. Median planned doses exceeded one or more objectives for bowel, external genitalia and bladder. This reached statistical significance for bowel V30 (P = 0.04), V45 (P < 0.001), V50 (P < 0.001), external genitalia V20 (P < 0.001) and bladder V35 (P < 0.001), V40 (P = 0.01). Gender was found to be the only significant factor in the likelihood of achieving the bowel V50 (P = 0.03) and BM V30 constraints (P = 0.04).The dose planning objectives used in the ANROTAT project provide a good starting point for ACC IMRT planning. To facilitate clinical implementation, it is important to prioritise OAR objectives and recognise factors that affect the achievability of these objectives.
A phospholipid uptake system in the model plant Arabidopsis thaliana. - Nature communications
Plants use solar energy to produce lipids directly from inorganic elements and are not thought to require molecular systems for lipid uptake from the environment. Here we show that Arabidopsis thaliana Aminophospholipid ATPase10 (ALA10) is a P4-type ATPase flippase that internalizes exogenous phospholipids across the plasma membrane, after which they are rapidly metabolized. ALA10 expression and phospholipid uptake are high in the epidermal cells of the root tip and in guard cells, the latter of which regulate the size of stomatal apertures to modulate gas exchange. ALA10-knockout mutants exhibit reduced phospholipid uptake at the root tips and guard cells and are affected in growth and transpiration. The presence of a phospholipid uptake system in plants is surprising. Our results suggest that one possible physiological role of this system is to internalize lysophosphatidylcholine, a signalling lipid involved in root development and stomatal control.
Exploring the Patient and Staff Experience With the Process of Primary Care. - Annals of family medicine
Previous studies suggest that the highest-risk patients value accessible, coordinated primary care that they perceive to be of high technical quality. We have limited understanding, however, of how low-income, chronically ill patients and the staff who care for them experience each individual step in the primary care process.We conducted qualitative interviews with uninsured or Medicaid patients with chronic illnesses, as well as with primary care staff. We interviewed 21 patients and 30 staff members with a variety of job titles from 3 primary care practices (1 federally qualified health center and 2 academically affiliated clinics).]The interviews revealed 3 major issues that were present at all stages of a primary care episode: (1) information flow throughout an episode of care is a frequent challenge, despite systems that are intended to improve communication; (2) misaligned goals and expectations among patients, clinicians, and staff members are often an impediment to providing and obtaining care; and (3) personal relationships are highly valued by both patients and staff.Vulnerable populations and the primary care staff who work with them perceive some of the same challenges throughout the primary care process. Improving information flow, aligning goals and expectations, and developing personal relationships may improve the experience of both patients and staff.© 2015 Annals of Family Medicine, Inc.
Predicting the need for adaptive radiotherapy in head and neck cancer. - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
Adaptive radiotherapy (ART) can account for the dosimetric impact of anatomical change in head and neck cancer patients; however it can be resource intensive. Consequently, it is imperative that patients likely to require ART are identified. The purpose of this study was to find predictive factors that identify oropharyngeal squamous cell carcinoma (OPC) and nasopharyngeal carcinoma (NPC) patients more likely to need ART.One hundred and ten patients with OPC or NPC were analysed. Patient demographics and tumour characteristics were compared between patients who were replanned and those that were not. Factors found to be significant were included in logistic regression models. Risk profiles were developed from these models. A dosimetric analysis was performed.Nodal disease stage, pre-treatment largest involved node size, diagnosis and initial weight (categorised in 2 groups) were identified as significant for inclusion in the model. Two models were found to be significant (p=0.001), correctly classifying 98.2% and 96.1% of patients respectively. Three ART risk profiles were developed.Predictive factors identifying OPC or NPC patients more likely to require ART were reported. A risk profile approach could facilitate the effective implementation of ART into radiotherapy departments through forward planning and appropriate resource allocation.Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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