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Cancer Chemotherapy and Pharmacology - CC-486 is an oral formulation of azacitidine that allows for extended dosing schedules to prolong azacitidine exposure to malignant cells and maximize...  相似文献   
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Purpose

A hydrogel rectal spacer (HRS) is a medical device that is approved by the U.S. Food and Drug Administration to increase the separation between the prostate and rectum. We conducted a cost-effectiveness analysis of HRS use for reduction in radiation therapy (RT) toxicities in patients with prostate cancer (PC) undergoing external beam RT (EBRT).

Methods and Materials

A multistate Markov model was constructed from the U.S. payer perspective to examine the cost-effectiveness of HRS in men with localized PC receiving EBRT (EBRT alone vs EBRT + HRS). The subgroups analyzed included site of HRS placement (hospital outpatient, physician office, ambulatory surgery center) and proportion of patients with good baseline erectile function (EF). Data on EF, gastrointestinal and genitourinary toxicities incidence, and potential risks associated with HRS implantation were obtained from a recently published randomized clinical trial. Health utilities and costs were derived from the literature and the 2018 Physician Fee Schedule and were discounted 3% annually. Quality-adjusted life years (QALYs) and costs were modeled for a 5-year period from receipt of RT. Probabilistic sensitivity analysis and value-based threshold analyses were conducted.

Results

The per-patient 5-year incremental cost for spacers administered in a hospital outpatient setting was $3578, and the incremental effectiveness was 0.0371 QALYs. The incremental cost-effectiveness ratio was $96,440/QALY for patients with PC undergoing HRS insertion in a hospital and $39,286/QALY for patients undergoing HRS insertion in an ambulatory facility. For men with good baseline EF, the incremental cost-effectiveness ratio was $35,548/QALY and $9627/QALY in hospital outpatient and ambulatory facility settings, respectively.

Conclusions

Based on the current Medicare Physician Fee Schedule, HRS is cost-effective at a willingness to pay threshold of $100,000. These results contain substantial uncertainty, suggesting more evidence is needed to refine future decision-making.  相似文献   
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Introduction

The Advisory Committee on Immunization Practices (ACIP) has focused on maternal Tdap immunization as an important means to protect neonates from pertussis infections. There is little published data on provider and/or clinic characteristics as predictors of maternal Tdap uptake. This study examined differences in maternal Tdap coverage in women delivering at a single academic institution, but cared for prenatally in different clinical settings, in 2013, 2014, and 2015. Additionally, the accuracy and utilization of Vermont's immunization information system (IIS) was assessed.

Methods

This was a retrospective, multiple time-point cross-sectional analysis of annual maternal Tdap coverage in women delivering at a single academic institution in the 3?years following a fundamental change in national maternal Tdap vaccination guidelines. Tdap administration was examined across different obstetric groups using chart review and data from the state's IIS.

Results

All obstetric care groups except the resident-staffed clinic significantly increased maternal Tdap coverage in 2014, compared to 2013 coverage, with no further increase in 2015. In contrast, there was no increase in maternal Tdap coverage in 2014 in the resident-staffed clinics, but then a statistically significant increase in 2015. Overall Tdap coverage in 2014 was 80.4%, with variation in Tdap coverage between clinics types. In the subset of women who were cared for by the University-based groups, there was significant variation in Tdap coverage between clinics, despite racial homogeneity, which persisted after adjustment for maternal age and insurance type. The state's IIS was found to be highly accurate, using individual chart review as the “gold standard.”

Discussion

While we demonstrated high maternal Tdap coverage in women delivering at our institution, differences in clinic type and provider training appeared to impact immunization rates, as well as how quickly evolving national recommendations were adopted. Additionally, the fidelity of the state's IIS data was verified.  相似文献   
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Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.  相似文献   
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Lung and female breast cancers are highly prevalent worldwide. Although the association between exposure to ambient fine particulate matter (PM2.5) and lung cancer has been recognized, there is less evidence for associations with other common air pollutants such as nitrogen dioxide (NO2) and ozone (O3). Even less is known about potential associations between these pollutants and breast cancer. We conducted a population-based cohort study to investigate the associations of chronic exposure to PM2.5, NO2, O3 and redox-weighted average of NO2 and O3 (Ox) with incident lung and breast cancer, using the Ontario Population Health and Environment Cohort (ONPHEC), which includes all long-term residents aged 35–85 years who lived in Ontario, Canada, 2001–2015. Incident lung and breast cancers were ascertained using the Ontario Cancer Registry. Annual estimates of exposures were assigned to the residential postal codes of subjects for each year during follow-up. We used Cox proportional-hazards models adjusting for personal- and neighborhood-level covariates. Our cohorts for lung and breast cancer analyses included ~4.9 million individuals and ~2.5 million women, respectively. During follow-up, 100,146 incident cases of lung cancer and 91,146 incident cases of breast cancer were diagnosed. The fully adjusted analyses showed positive associations of lung cancer incidence with PM2.5 (hazard ratio [HR] = 1.02 [95% CI: 1.01–1.05] per 5.3 μg/m3) and NO2 (HR = 1.05 [95% CI: 1.03–1.07] per 14 ppb). No associations with lung cancer were observed for O3 or Ox. Relationships between PM2.5 and NO2 with lung cancer exhibited a sublinear shape. We did not find compelling evidence linking air pollution to breast cancer.  相似文献   
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