Comparative survival between neoadjuvant chemotherapy and adjuvant chemotherapy for patients with cT2-4N0-1M0 non–small cell lung cancer has not been extensively studied.
Methods
Patients with cT2-4N0-1M0 non–small cell lung cancer who received platinum-based chemotherapy were retrospectively identified. Exclusion criteria included stage IV disease, induction radiotherapy, and targeted therapy. The primary end point was disease-free survival. Secondary end points were overall survival, chemotherapy tolerance, and ability of Response Evaluation Criteria In Solid Tumors response to predict survival. Survival was estimated using the Kaplan–Meier method, compared using the log-rank test and Cox proportional hazards models, and stratified using matched pairs after propensity score matching.
Results
In total, 330 patients met the inclusion criteria (n = 92/group after propensity-score matching; median follow-up, 42 months). Five-year disease-free survival was 49% (95% confidence interval, 39-61) for neoadjuvant chemotherapy versus 48% (95% confidence interval, 38-61) for adjuvant chemotherapy (P = .70). On multivariable analysis, disease-free survival was not associated with neoadjuvant chemotherapy or adjuvant chemotherapy (hazard ratio, 1.1; 95% confidence interval, 0.64-1.90; P = .737), nor was overall survival (hazard ratio, 1.21; 95% confidence interval, 0.63-2.30; P = .572). The neoadjuvant chemotherapy group was more likely to receive full doses and cycles of chemotherapy (P = .014/0.005) and had fewer grade 3 or greater toxicities (P = .001). Response Evaluation Criteria In Solid Tumors response to neoadjuvant chemotherapy was associated with disease-free survival (P = .035); 15% of patients receiving neoadjuvant chemotherapy (14/92) had a major pathologic response.
Conclusions
Timing of chemotherapy, before or after surgery, is not associated with an improvement in overall or disease-free survival among patients with cT2-4N0-1M0 non–small cell lung cancer who undergo complete surgical resection. 相似文献
ContextIt is especially important that patients are well informed when making high-stakes, preference-sensitive decisions like those on the Physician Orders for Life-Sustaining Treatment (POLST) form. However, there is currently no way to easily evaluate whether patients understand key concepts when making these important decisions.ObjectivesTo develop a POLST knowledge survey.MethodsExpert (n = 62) ratings of key POLST facts were used to select items for a POLST knowledge survey. The survey was administered to nursing facility residents (n = 97) and surrogate decision-makers (n = 112). A subset (n = 135) were re-administered the survey after a standardized advance care planning discussion to assess the scale's responsiveness to change.ResultsThe 19-item survey demonstrated adequate reliability (α = 0.72.). Residents' scores (x = 11.4, standard deviation 3.3) were significantly lower than surrogate scores (x = 14.7, standard deviation 2.5) (P < 0.001). Scores for both groups increased significantly after administration of a standardized advance care planning discussion (P < 0.001). Although being a surrogate, age, race, education, cognitive functioning, and health literacy were significantly associated with higher POLST Knowledge Survey scores in univariate analyses, only being a surrogate (P < 0.001) and being white (P = 0.028) remained significantly associated with higher scores in multivariate analyses.ConclusionThe 19-item POLST Knowledge Survey demonstrated adequate reliability and responsiveness to change. Findings suggest the survey could be used to identify knowledge deficits and provide targeted education to ensure adequate understanding of key clinical decisions when completing POLST. 相似文献
Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance. 相似文献
Payers frequently rely on budget impact model (BIM) results to help determine drug coverage policy and its effect on their bottom line. It is unclear whether BIMs typically overestimate or underestimate real-world budget impact.
Objective
We examined how different modeling assumptions influenced the results of 6 BIMs from the Institute for Clinical and Economic Review (ICER).
Study Design
Retrospective analysis of pharmaceutical sales data.
Methods
From ICER reports issued before 2016, we collected estimates of 3 BIM outputs: aggregate therapy cost (ie, cost to treat the patient population with a particular therapy), therapy uptake, and price. We compared these against real-world estimates that we generated using drug sales data. We considered 2 classes of BIM estimates: those forecasting future uptake of new agents, which assumed “unmanaged uptake,” and those describing the contemporaneous market state (ie, estimates of current, managed uptake and budget impact for compounds already on the market).
Results
Differences between ICER's estimates and our own were largest for forecasted studies. Here, ICER's uptake estimates exceeded real-world estimates by factors ranging from 7.4 (sacubitril/valsartan) to 54 (hepatitis C treatments). The “unmanaged uptake” assumption (removed from ICER's approach in 2017) yields large deviations between BIM estimates and real-world consumption. Nevertheless, in some cases, ICER's BIMs that relied on current market estimates also deviated substantially from real-world sales data.
Conclusions
This study highlights challenges with forecasting budget impact. In particular, assumptions about uptake and data source selection can greatly influence the accuracy of results. 相似文献
Physician communication impacts patient outcomes. However, communication skills, especially around difficult conversations, remain suboptimal, and there is no clear way to determine the validity of entrustment decisions. The aims of this study were to 1) describe the development of a simulation-based mastery learning (SBML) curriculum for breaking bad news (BBN) conversation skills and 2) set a defensible minimum passing standard (MPS) to ensure uniform skill acquisition among learners.
Innovation
An SBML BBN curriculum was developed for fourth-year medical students. An assessment tool was created to evaluate the acquisition of skills involved in a BBN conversation. Pilot testing was completed to confirm improvement in skill acquisition and set the MPS.
Outcomes
A BBN assessment tool containing a 15-item checklist and six scaled items was developed. Students' checklist performance improved significantly at post-test compared to baseline (mean 65.33%, SD = 12.09% vs mean 88.67%, SD = 9.45%, P < 0.001). Students were also significantly more likely to have at least a score of 4 (on a five-point scale) for the six scaled questions at post-test. The MPS was set at 80%, requiring a score of 12 items on the checklist and at least 4 of 5 for each scaled item. Using the MPS, 30% of students would require additional training after post-testing.
Comments
We developed a SBML curriculum with a comprehensive assessment of BBN skills and a defensible competency standard. Future efforts will expand the mastery model to larger cohorts and assess the impact of rigorous education on patient care outcomes. 相似文献
Introduction: Major Depressive Disorder (MDD) and General Anxiety Disorder (GAD) significantly contribute to the global burden of disease. Vilazodone, a combined serotonin reuptake inhibitor and 5-HT1A partial agonist, is an approved therapy for the treatment of MDD and which has been further investigated for GAD.
Areas covered: This article covers the pharmacokinetics and pharmacodynamics of vilazodone and provides an evaluation of the clinical usefulness of vilazodone for the treatment of MDD and anxiety disorders. A literature search was performed using PubMed/MEDLINE, Web of Science and the Cochrane Library.
Expert opinion: Studies have shown that vilazodone is significantly superior to placebo. However, vilazodone cannot as yet be recommended as a first-line treatment option for MDD as it is unclear whether the drug’s dual mechanism of action provides greater efficacy than prevailing treatment options. Moreover, more phase IV studies are needed to establish its efficacy and long-term safety in larger and more diverse populations. Although vilazodone may have an additional advantage for the treatment of anxiety symptoms in MDD, here also additional studies are required to confirm its efficacy over and above SSRI alternatives and other antidepressant treatments. Therefore, presently, vilazodone should be considered as a second- or third-line treatment option for MDD and GAD. 相似文献