This paper presents simple weighted and fully augmented weighted estimators for the additive hazards model with missing covariates when they are missing at random. The additive hazards model estimates the difference in hazards and has an intuitive biological interpretation. The proposed weighted estimators for the additive hazards model use incomplete data nonparametrically and have close-form expressions. We show that they are consistent and asymptotically normal, and are more efficient than the simple weighted estimator which only uses the complete data. We illustrate their finite-sample performance through simulation studies and an application to study the progression from mild cognitive impairment to dementia using data from the Alzheimer's Disease Neuroimaging Initiative as well as an application to the mouse leukemia study.

Obesity is a rapidly growing public health threat in China. Improvement of dietary knowledge may potentially reduce the risk of obesity and being overweight. However, existing studies focus on measuring the mean effects of nutrition knowledge on body mass index (BMI). There is a lack of literature on the effect of dietary knowledge on BMI, and the potential heterogeneity of the effect across the whole BMI distribution and across socioeconomic status (SES) groups. This study aims to investigate the heterogeneous nature of the relationship between dietary knowledge, SES, and BMI, using data from the China Health and Nutrition Survey (CHNS) in 2015. We employed unconditional quantile regression (UQR) to assess how the relationship between dietary knowledge, SES, and BMI varies across the whole BMI distribution, and conducted subgroup analyses using different socio-economic subsamples. Results indicate that dietary knowledge had no statistically significant impact on BMI across the BMI distribution. There was a large degree of heterogeneity in the SES effect across the BMI distribution as well as a major gender difference in the SES effect on BMI. Education had a significant and inverse association with BMI across the BMI distribution, greater at higher BMI quantiles. Income growth had a larger effect on the 50th quantile of BMI for males in the middle-income group, but was not significant for females. As income increased, males without college educations had higher BMI while females with college or higher education generally had lower BMI. The findings of this study reveal the heterogeneous nature of the relationship between SES, gender, and obesity across the entire BMI distribution, suggesting that quantile regressions might offer a valuable framework for exploring the complex relationship of dietary knowledge, demographic, and socio-economic factors on obesity.

The inverse probability of treatment weighted (IPTW) estimator can be used to make causal inferences under two assumptions: (1) no unobserved confounders (ignorability) and (2) positive probability of treatment and of control at every level of the confounders (positivity), but is vulnerable to bias if by chance, the proportion of the sample assigned to treatment, or proportion of control, is zero at certain levels of the confounders. We propose to deal with this sampling zero problem, also known as practical violation of the positivity assumption, in a setting where the observed confounder is cluster identity, i.e., treatment assignment is ignorable within clusters. Specifically, based on a random coefficient model assumed for the potential outcome, we augment the IPTW estimating function with the estimated potential outcomes of treatment (or of control) for clusters that have no observation of treatment (or control). If the cluster-specific potential outcomes are estimated correctly, the augmented estimating function can be shown to converge in expectation to zero and therefore yield consistent causal estimates. The proposed method can be implemented in the existing software, and it performs well in simulated data as well as with real-world data from a teacher preparation evaluation study.

This article investigates the associations of violence and traumatic stress with changes in weight and waist circumference, hypothesizing that violence in midlife would be associated with increases or decreases in weight and waist circumference. The longitudinal cohort of the Study of Women's Health Across the Nation comprised the study sample, which included an ethnically/racially and socially diverse group of 2,870 women between the ages of 42 and 52 years at baseline. Women were followed annually for 10 years, and assessments included weight and waist circumference measures and data on violence, health outcomes, and confounders. At baseline, 8.6% Caucasian, 10.8% African American, 9.2% Chinese, and 5.0% Japanese women reported violence and traumatic stress. Reporting violence and traumatic stress during follow-up was significantly associated with weight gain (odds ratio [OR] = 2.39, 95% confidence interval [CI] = [1.28-4.47]), weight loss (OR = 3.54, 95% CI = [1.73-7.22]), and gain (OR = 2.44, 95% CI = [1.37-4.37]) or loss (OR = 2.66, 95% CI = [1.23-5.77]) in waist circumference, adjusting for age, race/ethnicity, education, marital status, and smoking. Violence and traumatic stress against midlife women were associated with gains or losses in weight and waist circumference.

Background

There are no epidemiologic data on the relation of depression before colorectal cancer diagnosis to colorectal cancer mortality among women with colorectal cancer, especially those who are postmenopausal. Our aim was to fill this research gap.

Methods

We analyzed data from a large prospective cohort in the US, the Women's Health Initiative (WHI). The study included 2,396 women with incident colorectal cancer, assessed for depressive symptoms and antidepressant use before cancer diagnosis at baseline (screening visit in the WHI study) during 1993-1998. Participants were followed up from cancer diagnosis till 2018. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) between depression (depressive symptoms or antidepressant use) at baseline, and all-cause mortality and colorectal cancer-specific mortality.

Results

Among women with colorectal cancer, there was no association between baseline depression and all-cause mortality or colorectal cancer-specific mortality after adjusting for age or multiple covariates.

Conclusion

Among women with colorectal cancer, there was no statistically significant association between depression before colorectal cancer diagnosis and all-cause mortality or colorectal cancer-specific mortality. Further studies are warranted to assess depressive symptoms and antidepressant use, measured at multiple points from baseline to diagnosis, and their interactions with specific types of colorectal cancer treatment on the risk of death from colorectal cancer.

Introduction/background

Second primary lung cancers (SPLC) are common following non-small cell lung cancer (NSCLC) treatment. Development of SPLC following stereotactic ablative radiation therapy (SABR) may differ as compared to surgical cohorts. We report incidence of and outcomes for SPLC detected by surveillance imaging in a cohort of patients treated with SABR.

Materials/methods

Patients treated with SABR for node-negative NSCLC between February, 2007 to May, 2019 were retrospectively identified. Patient characteristics, frequency of surveillance imaging, development of SPLC, recurrence patterns, and survival were reviewed. Surveillance CT was performed Q3-4 month year 1, Q3-6 month year 2, Q6-12 month year 3-5, and Q12 month thereafter. Actuarial estimates of development of SPLC and overall survival (OS) were generated with competing risk analysis.

Results

We identified 134 patients treated with SABR with ≥6 months follow up. Eighteen (13.4%) developed a total of 21 SPLC at a median of 28.5 months (range 3.0-84.7 months) following SABR, 19 (90.5%) biopsy-proven. Twenty (95.2%) SPLC were detected by surveillance imaging. Three patients developed 2 metachronous SPLC. Three and 5 year SPLC estimates were 11.7% and 13.1%. Eighteen (85.7%) SPLC were treated with curative intent. Two and 3 year estimate of OS following detection of SPLC was 79.8% and 54.7%.

Conclusion

SPLC were more common in our cohort than other published studies. Outcomes following surveillance detected SPLC are similar to those of de novo early stage lung cancers. The high frequency of SPLC in our cohort suggests further studies to refine overall surveillance in very high-risk populations are needed.

This article investigates the associations of violence and traumatic stress with changes in weight and waist circumference, hypothesizing that violence in midlife would be associated with increases or decreases in weight and waist circumference. The longitudinal cohort of the Study of Women's Health Across the Nation comprised the study sample, which included an ethnically/racially and socially diverse group of 2,870 women between the ages of 42 and 52 years at baseline. Women were followed annually for 10 years, and assessments included weight and waist circumference measures and data on violence, health outcomes, and confounders. At baseline, 8.6% Caucasian, 10.8% African American, 9.2% Chinese, and 5.0% Japanese women reported violence and traumatic stress. Reporting violence and traumatic stress during follow-up was significantly associated with weight gain (odds ratio [OR] = 2.39, 95% confidence interval [CI] = [1.28-4.47]), weight loss (OR = 3.54, 95% CI = [1.73-7.22]), and gain (OR = 2.44, 95% CI = [1.37-4.37]) or loss (OR = 2.66, 95% CI = [1.23-5.77]) in waist circumference, adjusting for age, race/ethnicity, education, marital status, and smoking. Violence and traumatic stress against midlife women were associated with gains or losses in weight and waist circumference.

Background

Few studies exist to inform the extrapolated practice of irradiating children for heterotopic ossification (HO) prevention. We report the incidence of HO formation following prophylactic preoperative compared with postoperative radiation therapy (RT) in children with neuromuscular hip dysplasia (NHD) following proximal femoral resection (PFR).

Methods

A retrospective, 2-institution chart review was performed. Eligibility was limited to patients with at least 1 year of follow-up. Evaluation included radiographic HO grading by a combined severity scale, assessment of synchronous symptoms of pain or decreased range of motion, and stratification by preoperative versus postoperative reception of RT. A control cohort included 4 nonirradiated hips with NHD after PFR.

Results

Twenty-five hips in 20 children met eligibility criteria. Eleven hips were irradiated preoperatively and 14 postoperatively. Radiographic evidence of post-RT development of radiographic evidence of heterotopic ossification (rHO) was found in all 25 hips and earlier in patients irradiated preoperatively (median time to rHO was 4.0 vs. 15.7 mo, P=0.03, 95% confidence interval, 0.24-21.5). There was no statistically significant difference in the development of symptomatic HO (P=0.62) between the preoperative (45.5%) and postoperative (35.7%) groups, nor in HO grade (P=0.34). Seven (28%) of the 25 hips (5 preoperative and 2 postoperative) had documentation of rHO-free intervals after surgery, with an average duration of 5.6 months, while the remaining presented with rHO at first follow-up visit. All eligible control hips (100%) developed rHO and symptomatic heterotopic ossification.

Conclusions

Perioperative RT did not prevent the formation of HO in any child with NHD after PFR. Extrapolation of evidence of the efficacy of RT for HO prevention in ambulatory adults after traumatic hip injury to a population of children with central nervous system injury and NHD may be premature. Additional studies are needed to clarify optimal prevention of HO in this population.

Level of evidence

Level III-therapeutic retrospective comparative study.

Purpose

We investigate the use and impact of a vaginal brachytherapy boost (VBB) after pelvic radiotherapy for stage III endometrial adenocarcinoma on vaginal and pelvic control.

Material and methods

One hundred patients treated from 1998-2011 with surgery and adjuvant therapy with or without a VBB were included. Variables examined were grade, stage, lymphovascular space invasion (LVSI), vaginal involvement (VI), cervical stromal involvement (CSI), myometrial invasion (MI), and a VBB. Failure was scored as vaginal, or pelvic. Fisher's exact test assessed association between variables with vaginal and pelvic control.

Results

With a median follow up of 43 months, 31% were stage IIIA, 6% stage IIIB, and 63% stage IIIC. Thirty-eight (38%) received pelvic radiotherapy alone, and 62% received adjuvant chemotherapy. Of the 100 patients, 82 were treated with a VBB, 10 were not treated with a VBB, and 8 were not treated with RT. Of the 82 patients who received a VBB, 5 failed in the vagina with vaginal and pelvic control rates of 94% and 92%. The impact of VB reached borderline significance with its impact on pelvic control, 92% vs. 70% (p = 0.056), and did not affect vaginal control, 94% and 90% (p = 0.50). Neither tumor grade, LVSI, CSI, stage, nor LVSI (p > 0.05) statistically significantly impacted vaginal control.

Conclusions

There are no clinical guidelines for the use of a VBB in stage III endometrial cancer. The majority of our patients were treated with a VBB and experienced excellent pelvic and vaginal control. The presence of traditional adverse features did not negatively impact control in our patient cohort. However, the role of a VBB needs further investigation to understand the incremental benefit beyond pelvic RT.

Background

The aims of this study are to investigate the impact of pre-existing diabetes and diabetes treatments on lung cancer prognosis.

Methods

A total of 2484 women with confirmed incident lung cancer from the Women's Health Initiative were followed for an average of 2.9 years through the date of death or 29 August 2014.

Results

Compared with women with lung cancer but without diabetes, women with lung cancer and diabetes had significantly increased risk of overall mortality (HR=1.27, 95% CI: 1.07-1.50). Women with diabetes receiving insulin or metformin or women who had long duration of diabetes also had increased risk of overall mortality.

Conclusions

Our large prospective study provides evidence that pre-existing diabetes is associated with poor overall survival among women with lung cancer, but do not support the hypothesis that metformin use may have a protective effect in women with lung cancer and diabetes.