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This dissertation’s objective is to address methodological challenges in estimating the association of prepregnancy obesity with stillbirth and infant mortality. Our goal was to advance understanding of this topic of high public health importance to decrease the gap of high perinatal mortality between United States and other counties. Our focus was on the association of incident prepregnancy obesity with stillbirth and infant mortality. We constructed our analytic cohort of multiparous women who were non-obese in their first pregnancy from a population-based cohort study in Pennsylvania from 2003-2013 (n=1,551,919 singleton pregnancies). A visualization tool was developed for variable selection considering bias-variance tradeoff for inverse probability weights. Applying this tool to our study, we identified two high influential confounders which informed us to adjust for them carefully. Next, we examined the impact of parametric modeling assumptions on these associations by analytic methods with different reliance on parametric assumptions. Consistent, increased risk of stillbirth among women who became obese compared to those staying non-obese was observed with all methods. However, discrepancies in magnitude between methods were found: risk differences from semiparametric inverse probability weighting and nonparametric targeted minimum loss-based estimation (TMLE) were larger than those from parametric methods. Then, the analysis was constrained to those at normal first pregnancy weight, and we examined the effect of becoming overweight and obese on stillbirth and infant mortality in the second pregnancy. Nonparametric TMLE estimates showed that becoming overweight increased the risk of stillbirth (RD=1.4, 95% CI: 0.6, 2.2) while those becoming obese had increased risks of both stillbirth (RD=4.0, 95% CI: 1.4, 6.6) and neonatal mortality (RD=2.3, 95% CI: 0.1, 4.5) in the second pregnancy. A dose-response relationship was observed where increasing interpregnancy BM

This dissertation’s objective is to address methodological challenges in estimating the association of prepregnancy obesity with stillbirth and infant mortality. Our goal was to advance understanding of this topic of high public health importance to decrease the gap of high perinatal mortality between United States and other counties. Our focus was on the association of incident prepregnancy obesity with stillbirth and infant mortality. We constructed our analytic cohort of multiparous women who were non-obese in their first pregnancy from a population-based cohort study in Pennsylvania from 2003-2013 (n=1,551,919 singleton pregnancies). A visualization tool was developed for variable selection considering bias-variance tradeoff for inverse probability weights. Applying this tool to our study, we identified two high influential confounders which informed us to adjust for them carefully. Next, we examined the impact of parametric modeling assumptions on these associations by analytic methods with different reliance on parametric assumptions. Consistent, increased risk of stillbirth among women who became obese compared to those staying non-obese was observed with all methods. However, discrepancies in magnitude between methods were found: risk differences from semiparametric inverse probability weighting and nonparametric targeted minimum loss-based estimation (TMLE) were larger than those from parametric methods. Then, the analysis was constrained to those at normal first pregnancy weight, and we examined the effect of becoming overweight and obese on stillbirth and infant mortality in the second pregnancy. Nonparametric TMLE estimates showed that becoming overweight increased the risk of stillbirth (RD=1.4, 95% CI: 0.6, 2.2) while those becoming obese had increased risks of both stillbirth (RD=4.0, 95% CI: 1.4, 6.6) and neonatal mortality (RD=2.3, 95% CI: 0.1, 4.5) in the second pregnancy. A dose-response relationship was observed where increasing interpregnancy BM

Xing Lv,1,2,* Wei-Xiong Xia,1,2,* Liang-Ru Ke,1,2 Jing Yang,1,2 Wen-Zhe Qiu,1,2 Ya-Hui Yu,1,2 Hu Liang,1,2 Xin-Jun Huang,1,2 Guo-Yin Liu,1,2 Qi Zeng,1,2 Xiang Guo,1,2 Yan-Qun Xiang1,2 1Key Laboratory of Oncology in South China, 2Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally to this work Objective: Platinum-based chemotherapy in combination with radiotherapy is a standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma (NPC). This study aimed to investigate the long-term efficacy and tolerability of inductive chemotherapy with docetaxel plus carboplatin (TC) or 5-fluorouracil plus carboplatin (FC) followed by concurrent radiation therapy in patients with NPC. Methods: Patients (N=88) were randomized to receive TC or FC as inductive therapy followed by concurrent radiotherapy (60–70 Gy) with two cycles of carboplatin (area under the curve =5 mg·h/L). Patients were followed up for 8 years. Primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), toxicity, tumor response, distant metastasis-free survival, and local recurrence-free survival. Results: At the end of the follow-up period, 31 patients died, 32 had disease progression, eleven had cancer recurrence, and 25 had distant metastasis. Overall, there was no difference between treatment groups with regard to response or survival. We found that following induction and concurrent chemoradiotherapy, the majority of patients showed a complete response (~96%–98% for induction therapy and 82%–84% for comprehensive therapy) to both therapies. PFS and OS were also similar between groups. The rate of PFS was 63.6% for both FC and TC and that of OS was 65.9% and 63.5%, respectively. The overall incidence of grade 3–4 adverse events in the TC grou