Profound reduction in tamoxifen active metabolite endoxifen in a breast cancer patient treated with rifampin prior to initiation of an anti-TNFα biologic for ulcerative colitis: A case report

Background: Tamoxifen, a common anti-estrogen breast cancer medication, is a prodrug that undergoes bioactivation via cytochrome P450 enzymes, CYP2D6 and to a lesser degree, CYP3A4 to form the active metabolite endoxifen. With an increasing use of oral anti-cancer drugs, the risk for drug-drug interactions mediated by enzyme inhibitors and inducers may also be expected to increase. Here we report the first case demonstrating a potent drug-drug interaction in a real-world clinical setting between tamoxifen and rifampin in a breast cancer patient being treated concurrently for ulcerative colitis. Case presentation: We describe a patient on adjuvant tamoxifen therapy for breast cancer that was prescribed rifampin for TB prophylaxis prior to initiation of an anti-tumor necrosis factor (TNF)-α agent due to worsening ulcerative colitis. This 39 year old Caucasian woman had been followed by our personalized medicine clinic where CYP2D6 genotyping and therapeutic monitoring of tamoxifen and endoxifen levels had been carried out. The patient, known to be a CYP2D6 intermediate metabolizer, had a previous history of therapeutic endoxifen levels. Upon admission to hospital for a major flare of her ulcerative colitis a clinical decision was made to initiate an anti-TNFα biological agent. Due to concerns regarding latent TB, rifampin as an anti-mycobacterial agent was initiated which the patient was only able tolerate for 10 days. Interestingly, her plasma endoxifen concentration measured 2 weeks after cessation of rifampin was sub-therapeutic at 15.8 nM and well below her previous endoxifen levels which exceeded 40 nM. Conclusion: Rifampin should be avoided in patients on tamoxifen therapy for breast cancer unless continued tamoxifen efficacy can be assured through endoxifen monitoring. Drug-drug interactions can pose a significant risk of sub-therapeutic benefit in tamoxifen patients

Profound reduction in tamoxifen active metabolite endoxifen in a breast cancer patient treated with rifampin prior to initiation of an anti-TNFα biologic for ulcerative colitis: A case report

Background: Tamoxifen, a common anti-estrogen breast cancer medication, is a prodrug that undergoes bioactivation via cytochrome P450 enzymes, CYP2D6 and to a lesser degree, CYP3A4 to form the active metabolite endoxifen. With an increasing use of oral anti-cancer drugs, the risk for drug-drug interactions mediated by enzyme inhibitors and inducers may also be expected to increase. Here we report the first case demonstrating a potent drug-drug interaction in a real-world clinical setting between tamoxifen and rifampin in a breast cancer patient being treated concurrently for ulcerative colitis. Case presentation: We describe a patient on adjuvant tamoxifen therapy for breast cancer that was prescribed rifampin for TB prophylaxis prior to initiation of an anti-tumor necrosis factor (TNF)-α agent due to worsening ulcerative colitis. This 39 year old Caucasian woman had been followed by our personalized medicine clinic where CYP2D6 genotyping and therapeutic monitoring of tamoxifen and endoxifen levels had been carried out. The patient, known to be a CYP2D6 intermediate metabolizer, had a previous history of therapeutic endoxifen levels. Upon admission to hospital for a major flare of her ulcerative colitis a clinical decision was made to initiate an anti-TNFα biological agent. Due to concerns regarding latent TB, rifampin as an anti-mycobacterial agent was initiated which the patient was only able tolerate for 10 days. Interestingly, her plasma endoxifen concentration measured 2 weeks after cessation of rifampin was sub-therapeutic at 15.8 nM and well below her previous endoxifen levels which exceeded 40 nM. Conclusion: Rifampin should be avoided in patients on tamoxifen therapy for breast cancer unless continued tamoxifen efficacy can be assured through endoxifen monitoring. Drug-drug interactions can pose a significant risk of sub-therapeutic benefit in tamoxifen patients

Anti-Müllerian Hormone Levels and Urinary Cortisol in Women With Chronic Abdominal Pain

AbstractObjectiveTo explore the association of hypothalamic–pituitary–adrenal activity with ovarian functioning in women with and without chronic abdominal pain (CAP).Design and SettingA secondary data analysis was performed with data from female participants in a natural history protocol at the National Institutes of Health.ParticipantsA total of 36 women (age range = 19–39 years, mean = 27.11 years) were included in the study.MethodsThis pilot study was conducted with a subset of participants enrolled in a natural history protocol conducted in the Hatfield Clinical Research Center at the National Institutes of Health. The parent study included participants with and without CAP who provided a 5-hour urine sample for determination of cortisol levels and serum samples for determination of circulating levels of cortisol, luteinizing hormone, and follicle-stimulating hormone. CAP was defined as presence or absence of chronic pain for at least 6 months and was determined via self-report.ResultsAnti-Müllerian hormone (AMH) concentrations declined significantly with age as expected. When AMH levels were dichotomized as normal or abnormal (defined as higher or lower than age-specific normative ranges, respectively), there were significant associations between abnormal AMH levels and CAP and urine cortisol levels. Participants with CAP or low urine cortisol levels were significantly more likely to have abnormal AMH levels.ConclusionResults suggest that chronic abdominal pain and hypothalamic–pituitary–adrenal dysregulation may be associated with abnormal AMH levels

Symptom Status Predicts Patient Outcomes in Persons with HIV and Comorbid Liver Disease

Persons living with human immunodeficiency virus (HIV) are living longer; therefore, they are more likely to suffer significant morbidity due to potentially treatable liver diseases. Clinical evidence suggests that the growing number of individuals living with HIV and liver disease may have a poorer health-related quality of life (HRQOL) than persons living with HIV who do not have comorbid liver disease. Thus, this study examined the multiple components of HRQOL by testing Wilson and Cleary’s model in a sample of 532 individuals (305 persons with HIV and 227 persons living with HIV and liver disease) using structural equation modeling. The model components include biological/physiological factors (HIV viral load, CD4 counts), symptom status (Beck Depression Inventory II and the Medical Outcomes Study HIV Health Survey (MOS-HIV) mental function), functional status (missed appointments and MOS-HIV physical function), general health perceptions (perceived burden visual analogue scale and MOS-HIV health transition), and overall quality of life (QOL) (Satisfaction with Life Scale and MOS-HIV overall QOL). The Wilson and Cleary model was found to be useful in linking clinical indicators to patient-related outcomes. The findings provide the foundation for development and future testing of targeted biobehavioral nursing interventions to improve HRQOL in persons living with HIV and liver disease

Psychometric testing of the breastfeeding self-efficacy scale to measure exclusive breastfeeding in African American women: a cross-sectional study

BackgroundIn United States, African American women are the least likely group to breastfeed exclusively compared with Hispanic and non-Hispanic white women. It is crucial to examine the perceived confidence of African American women towards practicing exclusive breastfeeding. Previous studies have examined breastfeeding self-efficacy and other factors influencing exclusive breastfeeding. However, there is no research on exclusive breastfeeding self-efficacy of this population. The purpose of this study was to examine the validity and reliability of the breastfeeding self-efficacy scale to measure exclusive breastfeeding, and the relationship between exclusive breastfeeding self-efficacy and general self-efficacy and demographic variables in African American women.MethodsDescriptive cross-sectional design was used. A convenience sample of 53 pregnant African American women completed an online survey. Construct and criterion-related validity were assessed and reliability of the breastfeeding self-efficacy scale to measure exclusive breastfeeding (BSES-EBF) was examined using Cronbach’s reliability. The general self-efficacy scale measured general self-efficacy. Descriptive statistics, bivariate correlation and non-parametric analyses were performed using statistical package for social sciences (v.28).ResultsThe breastfeeding self-efficacy to measure exclusive breastfeeding scale had a Cronbach’s alpha score of 0.907. One principal component was extracted from the BSES-EBF scale, with an Eigenvalue of 5.271 and which explained 58.57% of the variance in the instrument. The mean prenatal exclusive breastfeeding self-efficacy of participants was 35.15 (±7.41) from a range of 9 to 45. Exclusive breastfeeding was significantly associated with general self-efficacy (r = 0.503, p ≤ 0.001) and exclusive breastfeeding intention (p = 0.034).ConclusionBreastfeeding self-efficacy scale to measure exclusive breastfeeding is a valid and reliable tool to measure exclusive breastfeeding self-efficacy in African American women. African American women had high exclusive breastfeeding self-efficacy (internal motivation). Hence, there is a need to address breastfeeding barriers and provide access to culturally sensitive support (external motivation) to increase exclusive breastfeeding in African American women

Factors Associated with Preoperative Magnetic Resonance Imaging Use among Medicare Beneficiaries with Nonmetastatic Breast Cancer

Preoperative breast magnetic resonance imaging (MRI) use among Medicare beneficiaries with breast cancer has substantially increased from 2005 to 2009. We sought to identify factors associated with preoperative breast MRI use among women diagnosed with ductal carcinoma in situ (DCIS) or stage I-III invasive breast cancer (IBC)

Control of center of mass motion during walking correlates with gait and balance in people with incomplete spinal cord injury

BackgroundThere is evidence that ambulatory people with incomplete spinal cord injury (iSCI) have an impaired ability to control lateral motion of their whole-body center of mass (COM) during walking. This impairment is believed to contribute to functional deficits in gait and balance, however that relationship is unclear. Thus, this cross-sectional study examines the relationship between the ability to control lateral COM motion during walking and functional measures of gait and balance in people with iSCI.MethodsWe assessed the ability to control lateral COM motion during walking and conducted clinical gait and balance outcome measures on 20 ambulatory adults with chronic iSCI (C1-T10 injury, American Spinal Injury Association Impairment Scale C or D). To assess their ability to control lateral COM motion, participants performed three treadmill walking trials. During each trial, real-time lateral COM position and a target lane were projected on the treadmill. Participants were instructed to keep their lateral COM position within the lane. If successful, an automated control algorithm progressively reduced the lane width, making the task more challenging. If unsuccessful, the lane width increased. The adaptive lane width was designed to challenge each participant’s maximum capacity to control lateral COM motion during walking. To quantify control of lateral COM motion, we calculated lateral COM excursion during each gait cycle and then identified the minimum lateral COM excursion occurring during five consecutive gait cycles. Our clinical outcome measures were Berg Balance Scale (BBS), Timed Up and Go test (TUG), 10-Meter Walk Test (10MWT) and Functional Gait Assessment (FGA). We used a Spearman correlation analysis (ρ) to examine the relationship between minimum lateral COM excursion and clinical measures.ResultsMinimum lateral COM excursion had significant moderate correlations with BBS (ρ = −0.54, p = 0.014), TUG (ρ = 0.59, p = 0.007), FGA (ρ = −0.59, p = 0.007), 10MWT-preferred (ρ = −0.59, p = 0.006) and 10MWT-fast (ρ = −0.68, p = 0.001).ConclusionControl of lateral COM motion during walking is associated with a wide range of clinical gait and balance measures in people with iSCI. This finding suggests the ability to control lateral COM motion during walking could be a contributing factor to gait and balance in people with iSCI

Breast MRI in the Diagnostic and Preoperative Workup Among Medicare Beneficiaries With Breast Cancer

We compared the frequency and sequence of breast imaging and biopsy use for the diagnostic and preoperative workup of breast cancer according to breast MRI use among older women

The Holy Grail: A road map for unlocking the climate record stored within Mars' polar layered deposits

In its polar layered deposits (PLD), Mars possesses a record of its recent climate, analogous to terrestrial ice sheets containing climate records on Earth. Each PLD is greater than 2 ​km thick and contains thousands of layers, each containing information on the climatic and atmospheric state during its deposition, creating a climate archive. With detailed measurements of layer composition, it may be possible to extract age, accumulation rates, atmospheric conditions, and surface activity at the time of deposition, among other important parameters; gaining the information would allow us to “read” the climate record. Because Mars has fewer complicating factors than Earth (e.g. oceans, biology, and human-modified climate), the planet offers a unique opportunity to study the history of a terrestrial planet’s climate, which in turn can teach us about our own planet and the thousands of terrestrial exoplanets waiting to be discovered. During a two-part workshop, the Keck Institute for Space Studies (KISS) hosted 38 Mars scientists and engineers who focused on determining the measurements needed to extract the climate record contained in the PLD. The group converged on four fundamental questions that must be answered with the goal of interpreting the climate record and finding its history based on the climate drivers. The group then proposed numerous measurements in order to answer these questions and detailed a sequence of missions and architecture to complete the measurements. In all, several missions are required, including an orbiter that can characterize the present climate and volatile reservoirs; a static reconnaissance lander capable of characterizing near surface atmospheric processes, annual accumulation, surface properties, and layer formation mechanism in the upper 50 ​cm of the PLD; a network of SmallSat landers focused on meteorology for ground truth of the low-altitude orbiter data; and finally, a second landed platform to access ~500 ​m of layers to measure layer variability through time. This mission architecture, with two landers, would meet the science goals and is designed to save costs compared to a single very capable landed mission. The rationale for this plan is presented below. In this paper we discuss numerous aspects, including our motivation, background of polar science, the climate science that drives polar layer formation, modeling of the atmosphere and climate to create hypotheses for what the layers mean, and terrestrial analogs to climatological studies. Finally, we present a list of measurements and missions required to answer the four major questions and read the climate record. 1. What are present and past fluxes of volatiles, dust, and other materials into and out of the polar regions? 2. How do orbital forcing and exchange with other reservoirs affect those fluxes? 3. What chemical and physical processes form and modify layers? 4. What is the timespan, completeness, and temporal resolution of the climate history recorded in the PLD