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Aims

Concomitant chemoradiation is the standard of care in patients with inoperable non-small cell lung cancer. The purpose of this study was to analyse the survival outcome and toxicity data of using hypofractionated chemoradiation.

Materials and methods

One hundred patients were treated from June 2011 to November 2016. Treatment consisted of 55 Gy in 20 daily fractions concurrently with split-dose cisplatin vinorelbine chemotherapy over 4 weeks followed by two cycles of cisplatin vinorelbine only. Survival was estimated using Kaplan–Meier and Cox regression was carried out for known prognostic factors. A systematic search of literature was conducted using Medline, Embase and Cochrane databases and relevant references included.

Results

In total, 97% of patients completed radiotherapy and 73% of patients completed all four cycles of chemotherapy. One patient died of a cardiac event during consolidative chemotherapy. There were two cases of grade 4 toxicities (one sepsis, one renal impairment). Grade 3 toxicities included nausea/vomiting (17%), oesophagitis (15%), infection with neutropenia (12%) and pneumonitis (4%). Clinical benefit was seen in 86%. Two-year progression-free survival and overall survival rates were 49% and 58%, respectively. The median progression-free survival and overall survival were 23.4 and 43.4 months, respectively. The only significant prognostic factor was the number of chemotherapy cycles received (P = 0.02). The systematic review identified 13 relevant studies; a variety of regimens were assessed with variable reporting of outcomes and toxicity but with overall an improvement in survival over time.

Conclusion

Our experience compared with the original phase II trial showed improved treatment completion rates and survival with acceptable morbidity. With appropriate patient selection this regimen is an effective treatment option for locally advanced non-small cell lung cancer. This study helps to benchmark efficacy and toxicity rates while considering the addition of new agents to hypofractionated concurrent chemoradiotherapy. The agreement of a standard regimen for assessment in future trials would be beneficial.  相似文献   
106.

Objective

The gene therapy voretigene neparvovec (VN) is the first Food and Drug Administration–approved treatment for vision loss owing to the ultra-rare RPE65-mediated inherited retinal disorders. We modeled the cost-utility of VN compared with standard of care (SoC).

Study Design

A 2-state Markov model, alive and dead, with a lifetime horizon.

Methods

Visual acuity (VA) and visual field (VF) were tracked to model quality-adjusted life-years (QALYs). VN led to an improvement in VA and VF that we assumed was maintained for 10 years followed by a 10-year waning period. The cost of VN was $850 000, and other direct medical costs for depression and trauma were included for a US healthcare system perspective. A modified societal perspective also included direct nonmedical costs and indirect costs.

Results

VN provided an additional 1.3 QALYs over the remaining lifetime of an individual. The average total lifetime direct medical cost for individuals treated with VN was $1 039 000 compared with $213 400 for SoC, leading to an incremental cost-effectiveness ratio (ICER) of $643 800/QALY from the US healthcare system perspective. Direct nonmedical costs totalled $1 070 900 for VN and $1 203 300 for SoC, and indirect costs totalled $405 400 for VN and $482 900 for SoC, leading to an ICER of $480 100/QALY from the modified societal perspective.

Conclusions

At the current price, VN was unlikely to reach traditional cost-effectiveness standards compared with SoC. VN has important implications for both development and pricing of future gene therapies; therefore clinical and economic analyses must be carefully considered.  相似文献   
107.
IntroductionPrenatal exposure to di(2-ethylhexyl) phthalate (DEHP) has been reported to be associated with adverse effects on neurodevelopment that yield behavior syndromes in young children with an estimated median exposure lower than the currently recommended tolerable daily intake (TDI) and reference dose (RfD).ObjectivesOur aim was to derive the benchmark dose for prenatal exposure to DEHP for the neurodevelopmental health in children.MethodsA total of 122 mother-child pairs from the Taiwan Maternal and Infant Cohort Study were analyzed for the dose-response relationship between maternal exposure to DEHP and children's behavioral syndromes evaluated at 8 years (n = 122, 2009), 11 years (n = 96, 2012), and 14 years (n = 78, 2015) of age. We employed a multivariate regression model to assess the statistical associations between the estimated maternal average daily intake of DEHP and child's individual CBCL scores for boys and girls at each separate age, followed by a mixed model for all the children across three ages accounting for individual variations. We then employed structural equation models by combining the children's specific behavioral problem scores at different ages and obtained a simulated overall latent score in relation to maternal exposure. Based on the established dose-response relationship, we derived the benchmark dose (BMD) and the lower limit (BMDL).ResultsAssociations of maternal DEHP exposure (median 4.54μg/kg_bw/day) with the Child Behavior Checklist (CBCL) scores were all significant, except for somatic complaints, adjusting for child's age, gender, IQ, and family income. The BMDL, given a benchmark response of 0.10 (0.05) and a background response of 0.05, was 6.01 (2.16) μg/kg_bw/dayfor an integrated CBCL score.ConclusionsThe current TDI (RfD) of 50 (20) μg/kg_bw/day for DEHP might not protect pregnant women for their children from behavioral problems. There remains the lack of comparable toxicological data. Further investigations are needed.  相似文献   
108.

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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The human microbiome comprises a diverse set of microorganisms, which play a mostly cooperative role in processes such as metabolism and host defense. Next-generation genomic sequencing of bacterial nucleic acids now can contribute a much broader understanding of the diverse organisms composing the microbiome. Emerging evidence has suggested several roles of the microbiome in pediatric hematology/oncology, including susceptibility to infectious diseases, immune response to neoplasia, and contributions to the tumor microenvironment as well as changes to the microbiome from chemotherapy and antibiotics with unclear consequences. In this review, the authors have examined the evidence of the role of the microbiome in pediatric hematology/oncology, discussed how the microbiome may be modulated, and suggested key questions in need of further exploration.  相似文献   
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