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U.S. prevalence of endocrine therapy-naive locally advanced or metastatic breast cancerBackground: Variations in treatment choice, or late stage at first diagnosis, mean that, despite guideline recommendations, not all patients with hormone receptor (hr)-positive locally advanced or metastatic breast cancer (la/mbca) will have received endocrine therapy before disease progression. In the present study, we aimed to estimate the proportion of women with postmenopausal hr-positive la/mbca in the United States who are endocrine therapy-naive. Methods: Women in the Optum Electronic Health Record (ehr) database with a breast cancer (bca) diagnosis (January 2008-March 2015) were included. Patient and malignancy characteristics were identified using structured data fields and natural-language processing of free-text clinical notes. The proportion of women with postmenopausal hr-positive, human epidermal growth factor 2 (her2)-negative (or unknown) la/mbca who had not received prior endocrine therapy was determined. Results were extrapolated to the entire U.S. population using the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results database. Results are presented descriptively. Results: In the ehr database, 11,831 women with bca had discernible information on postmenopausal status, hr status, and disease stage. Of those women, 1923 (16.3%) had postmenopausal hr-positive, her2-negative (or unknown) la/mbca, and 70.7% of those 1923 patients (n = 1360) had not received prior endocrine therapy, accounting for 11.5% of the overall population. Extrapolating those estimates nationally suggests an annual incidence of 14,784 cases, and a 5-year limited duration prevalence of 50,638 cases. Conclusions: A substantial proportion of women with postmenopausal hr-positive la/mbca in the United States could be endocrine therapy-naive.
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Improved Methods of Sepsis Case Identification and the Effects of Treatment with Low Dose Steroids: A DissertationSepsis is the leading cause of death among critically ill patients and the 10th most common cause of death overall in the United States. The mortality rates increase with severity of the disease, ranging from 15% for sepsis to 60% for septic shock. Patient with sepsis can present varied clinical symptoms depending on the personal predisposition, causal microorganism, organ system involved, and disease severity. To facilitate sepsis diagnosis, the first sepsis consensus definitions was published in 1991 and then updated in 2001. Early recognition of a sepsis patient followed with timely and appropriate treatment and management strategies have been shown to significantly reduce sepsis-related mortality, and allows care to be provided at lower costs. Despite the rapid progress in the knowledge of pathophysiological mechanisms of sepsis and its treatment in the last two decades, identifying patient with sepsis and therapeutic approaches to sepsis and its complications remains challenging to critical care clinicians. Hence, the objectives of this thesis were to 1) evaluate the test characteristics of the two sepsis consensus definitions and delineate the differences in patient profile among patients meeting or not meeting sepsis definitions; 2) determine the relationship between the changes in several physiological parameters before sepsis onset and sepsis, and to determine whether these parameters could be used to identify sepsis in critically ill adults; 3) evaluate the effect of corticosteroids therapy on patient mortality. Data used in this thesis were prospectively collected from an electronic medical record system for all the adult patients admitted into the seven critical care units (ICUs) in a tertiary medical center. Besides analyzing data at the ICU stay level, we investigated patient information in various time frames, including 24-hour, 12-hour, and 6-hour time windows. In the first study of this thesis, the 1991 sepsis definition was found to have a high sensitivity of 94.6%, but a low specificity of 61.0%. The 2001 sepsis definition had a slightly increased sensitivity but a decreased specificity, which was 96.9% and 58.3%, respectively. The areas under the ROC curve for the two consensus definitions were similar, but less than optimal. The sensitivity and area under the ROC curve of both definitions were lower at the 24-hour time window level than those of the unit stay level, though the specificity increased slightly. At the time window level, the 1991 definitions performed slightly better than the 2001 definition. In the second study, minimum systolic blood pressure performed the best, followed by maximum respiratory rate in discriminating sepsis patients from SIRS patients. Maximum heart rate and maximum respiratory rate can differentiate sepsis patients from non-SIRS patients fairly well. The area under ROC of the combination of five physiological parameters was 0.74 and 0.90 for comparing sepsis to non-infectious SIRS patients and comparing sepsis to non-SIRS patients, respectively. Parameters typically performed better in 24-hour windows compared to 6-hour or 12-hour windows. In the third study, significantly increased hospital mortality and ICU mortality were observed in the group treated with low-dose corticosteroids than the control group based on the propensity score matched comparisons, and multivariate logistic regression analyses after adjustment for propensity score alone, covariates, or propensity score (in deciles) and covariates. This thesis advances the existing knowledge by systemically evaluating the test characteristics for the 1991 and 2001 sepsis consensus definitions, delineating physiological signs and symptoms of deterioration in the preceding 24 hours prior to sepsis onset, assessing the prediction performances of single or combined physiological parameters, and examining the use of corticosteroids treatment and survival among septic shock patients. In addition, this thesis sets an innovative example on how to use data from electronic medical records as these surveillance systems are becoming increasingly popular. The results of these studies suggest that a more parsimonious set of definitional criteria for sepsis diagnosis are needed to improve sepsis case identification. In addition, continuously monitored physiological parameters could help to identify patients who show signs of deterioration prior to developing sepsis. Last but not least, caution should be used when considering a recommendation on the use of low dose corticosteroids in clinical practice guidelines for the management of sepsis.
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Menopausal hormone therapy trends before versus after 2002: impact of the Women's Health Initiative Study ResultsOBJECTIVE: To better understand how to educate patients and providers about study findings relevant to treatment guidelines, we assessed pre- versus post-Women's Health Initiative (WHI) differences in menopausal hormone therapy (MHT) initiation and continuation and their correlates, and in women's reasons for initiation and discontinuation. METHODS: We analyzed survey data from up to 14 approximately annual visits over 17 years (1996-2013) from 3,018 participants in the Study of Women's Health Across the Nation, a prospective cohort study. We used logistic regression to compare pre- versus post-WHI associations of covariates with MHT initiation and continuation, and to compare pre- versus post-WHI reasons for initiation and continuation. RESULTS: MHT initiation dropped from 8.6% pre-WHI to 2.8% post-WHI (P < 0.0001), and the corresponding decrease in MHT continuation was 84.0% to 62.0% (P < 0.0001). Decreases in MHT initiation and continuation occurred across a range of participant subgroups, consistent with wide dissemination of post-WHI recommendations. However, contrary to current guidelines, we found large declines in MHT use in subgroups for whom MHT is often recommended, that is, younger women and those with more vasomotor symptoms. Post-WHI, women's reasons for MHT initiation and discontinuation reflected concerns highlighted by WHI results. The largest declines in initiation reasons were for reducing risks of osteoporosis and heart disease, whereas the largest increases in discontinuation reasons were for media reports and provider advice. CONCLUSIONS: Immediate post-WHI recommendations for MHT use were widely adopted. MHT risks documented in older women, however, may have led younger symptomatic women to forgo MHT for symptom relief.
