Child and adolescent benzodiazepine exposure and overdose in the United States: 16 years of poison center data.

Background: Recently, there has been an increase in prescription drug abuse and related fatalities. Although opioid analgesics are commonly implicated, there have been significant increases in the prevalence of benzodiazepine exposures and overdoses.Objective: To describe national trends in pediatric benzodiazepine exposures from 2000 to 2015.Methods: A retrospective database analysis was conducted. Data regarding benzodiazepine exposures in children ages 0 to <18 years reported to participating United States poison centers from January 2000 through December 2015 were obtained from the National Poison Data System. Population data were obtained from the US Census Bureau to determine annual population estimates. Data were analyzed using chi-square tests.Results: A total of 296,838 pediatric benzodiazepine exposures were identified during the study period. The rate of pediatric benzodiazepine exposure increased 54% between 2000 and 2015. The severity of medical outcomes also increased, as did the prevalence of co-ingestion of multiple drugs, especially in children ages 12 to <18 years. Nearly half of all reported exposures in 2015 were documented as intentional abuse, misuse, or attempted suicide, reflecting a change from prior years. The most commonly identified pediatric benzodiazepines of exposures were alprazolam, clonazepam, and lorazepam.Conclusions: The rate and severity of reported pediatric benzodiazepine exposure is increasing over time. Adolescent exposures are of specific concern, as co-ingestion and intentional abuse were found to be more common in this group. Medical providers and caretakers should be cognizant of this growing epidemic to avoid preventable harm to adolescents, young children, and infants.

Nonlinear Predictive Models for Multiple Mediation Analysis: With an Application to Explore Ethnic Disparities in Anxiety and Depression Among Cancer Survivors.

Mediation analysis allows the examination of effects of a third variable (mediator/confounder) in the causal pathway between an exposure and an outcome. The general multiple mediation analysis method (MMA), proposed by Yu et al., improves traditional methods (e.g., estimation of natural and controlled direct effects) to enable consideration of multiple mediators/confounders simultaneously and the use of linear and nonlinear predictive models for estimating mediation/confounding effects. Previous studies find that compared with non-Hispanic cancer survivors, Hispanic survivors are more likely to endure anxiety and depression after cancer diagnoses. In this paper, we applied MMA on MY-Health study to identify mediators/confounders and quantify the indirect effect of each identified mediator/confounder in explaining ethnic disparities in anxiety and depression among cancer survivors who enrolled in the study. We considered a number of socio-demographic variables, tumor characteristics, and treatment factors as potential mediators/confounders and found that most of the ethnic differences in anxiety or depression between Hispanic and non-Hispanic white cancer survivors were explained by younger diagnosis age, lower education level, lower proportions of employment, less likely of being born in the USA, less insurance, and less social support among Hispanic patients.

Outcomes in real-world practice are different than cooperative trial for elderly patients with early breast cancer treated with adjuvant radiation therapy.

BACKGROUND: The Cancer and Leukemia Group B 9,343 demonstrated that postoperative radiation can be safely omitted in women ≥70 years who underwent breast-conserving therapy for clinical stage I (T1N0M0) estrogen receptor positive breast cancer treated with antihormonal therapy. Whether such results are observed in real-world population is unknown. In this hospital-based data, we report the survival outcomes of patients who received adjuvant radiation therapy versus those who did not. METHODS: Using the National Cancer Data Base, we evaluated a cohort of 47,358 women with newly diagnosed breast cancer between 2004 and 2011 who underwent a lumpectomy and antihormonal therapy with the following criteria: age ≥70 years, clinical stage I, estrogen receptor positive, and negative margins. Patients were stratified into 2 groups: (1) radiation therapy and (2) no radiation therapy. Propensity score matching was used to compensate for differences in demographic and clinical characteristics of the patients. Univariate and multivariable survival analysis were employed to determine factors associated with overall survival. RESULTS: The 5-year overall survival after propensity score matching was 87.2% for radiation therapy and 79.4% for no radiation therapy (P < .0001). The median survival time was 113.7 months for radiation therapy and 105.2 months for no radiation therapy. After adjusting for sociodemographic and clinical factors, the risk of overall deaths was significantly higher for those not receiving radiation therapy (hazard ratio = 1.66; 95% confidence interval, 1.54-1.79). Other significant adjusted predictors (P < .05) of poor overall survival were, advanced age, comprehensive community cancer program, facility location, poorly differentiated tumor, and high comorbidity index. CONCLUSION: Patients who received radiation therapy had better survival outcomes than those who did not, revealing discordance between results of randomized trials and real-world setting.

Impact of CALGB 9343 Trial and Sociodemographic Variation on Patterns of Adjuvant Radiation Therapy Practice for Elderly Women (≥70 Years) with Stage I, Estrogen Receptor-positive Breast Cancer: Analysis of the National Cancer Data Base.

BACKGROUND: The Cancer and Leukemia Group B (CALGB) 9343 trial demonstrated that adjuvant radiation therapy (RT) can be omitted in women 70 years or older, with small (≤2 cm), negative lymph nodes, estrogen receptor (ER)-positive breast cancer. We examined whether RT usage following the CALGB publication had decreased over time and evaluated sociodemographic and clinical factors associated with RT omission. MATERIALS AND METHODS: From the National Cancer Data Base, we analyzed a cohort of 120,308 women aged 70 years or older with stage I, ER-positive breast cancer who underwent lumpectomy. Patients were classified into two groups based on the time of CALGB 9343 publication: (i) pre-CALGB (up to 2004), and (ii) post-CALGB (2005-2012). Clinicopathological and sociodemographic variables were compared between pre- and post-CALGB groups. Chi-square and multivariable logistic regression were employed, with the omission of adjuvant RT as the primary outcome in the regression analysis. RESULTS: Radiation therapy usage decreased by 4.1% after CALGB publication (on average 71.6% pre-CALGB vs. 67.5% post-CALGB; p<0.0001). Almost one-third of women aged ≥85 years received RT in the post-CALGB group. In a multivariable model, the variables significantly associated with increased odds for omission of RT in the post-CALGB group were: advanced age, African-American, increased great circle distance, therapy under academic research program, residents of East South-Central region, living in a rural population <2,500 not adjacent to a metropolitan area, low income level, Medicaid recipients, high comorbidity index, small tumor, well-differentiated histology, residual tumor, and lack of receipt of chemotherapy and anti-hormonal therapy. CONCLUSION: During the study period, the CALGB trial publication had a minimal impact on the rate of adjuvant RT use among elderly women with small, ER-positive breast cancers. Significant variation in RT usage existed across sociodemographic strata.

Influence of facility type on survival outcomes after pancreatectomy for pancreatic adenocarcinoma.

INTRODUCTION: Although a volume-outcome relationship has been well established for pancreatectomy, little is known about differences in mortality by facility type. The objective of this study is to evaluate the impact of facility type on short-term and long-term survival outcomes for patients with pancreatic adenocarcinoma who underwent pancreatectomy and identify determinants of overall survival (OS). METHODS: A cohort of 33,382 patients with Stage I-III pancreatic adenocarcinoma diagnosed between 1998 and 2011 were evaluated from the National Cancer Data Base. Clinicopathological, sociodemographic and treatment variables were compared among three facility types where patients received resection: (i) community cancer program (CCP), (ii) comprehensive community cancer program (CCCP), and (iii) academic research program (ARP). 5-year OS was calculated using the Kaplan-Meier method. RESULTS: Despite ARP having significantly higher percentage of poorly differentiated tumors, higher T-stage tumors, more positive lymph nodes, and greater circle distance compared to the other facilities, it had the highest 5-yr OS. The 5-yr OS for CCP, CCCP, and ARP was 11.2%, 13.2%, and 16.6%, respectively (P < 0.0001) and the median survival time (months) was 12.4, 15.6 and 19.1, respectively. CONCLUSION: Patients receiving pancreatic resection at an ARP yielded a higher 5-year OS compared to CCP or CCCP.

Poor survival in stage IIB/C (T4N0) compared to stage IIIA (T1-2 N1, T1N2a) colon cancer persists even after adjusting for adequate lymph nodes retrieved and receipt of adjuvant chemotherapy.

BACKGROUND: A survival paradox between Stage IIB/C and Stage IIIA colon cancers exists. It is unclear how adequate lymph nodes dissection (LN) and post-surgery chemotherapy contribute to the survival paradox. We intended to assess the impact of these two factors on the survival paradox. RESULTS: We evaluated 34,999 patients diagnosed with stage IIIA or stage IIB/C colon cancer in 2003-2012 from the National Cancer Data Base. The 5-year overall survival (OS) was 73.5 % for stage IIIA and 51.1 % for stage IIB/C (P < 0.0001). The 5-year OS was 84.1 % for stage IIIA with post-surgery chemotherapy, 70.8 % for stage IIB/C with ≥ 12 LNs retrieved with chemotherapy, 53.9 % for stage IIB/C < 12 LNs with chemotherapy, 49.5 % for stage IIIA without chemotherapy, 43.7 % for stage IIB/C ≥ 12 LNs retrieved without chemotherapy, to 27.7 % for stage IIB/C < 12 LNs without chemotherapy. Even among stage IIB/C who had optimal treatment (≥12 LNs retrieved, received chemotherapy), OS remains lower than stage IIIA with chemotherapy. After adjusting LN dissection and chemotherapy in addition to the adjustment of other clinical factors, the survival paradox was reduced from HR = 1.76 (95 % CI: 1.68-1.85) to HR 1.51 (95 % CI: 1.44-1.59). CONCLUSIONS: LN dissection and post-surgery chemotherapy partially explained the survival paradox. More research is warranted to identify other factors that contribute to this paradox. Future iteration of TNM staging system should take this into consideration.

RETRACTED: Impact of Cooperative Trial and Sociodemographic Variation on Adjuvant Radiation Therapy Usage in Elderly Women (≥70 Years) with Stage I, Estrogen Receptor-Positive Breast Cancer: Analysis of the National Cancer Data Base.

BACKGROUND: The Cancer and Leukemia Group B (CALGB) 9343 trial demonstrated that adjuvant radiation therapy (RT) can be omitted in women aged 70 years or older, with small, estrogen receptor (ER)+ breast cancer. We postulated that RT usage after CALGB's publication should have decreased over time. STUDY DESIGN: We evaluated a cohort of 205,860 women aged 70 years or older, with stage I, ER+/progesterone receptor (PR)+ breast cancer with lumpectomy, diagnosed between 1998 and 2012, in the National Cancer Data Base. Clinicopathologic and sociodemographic variables were compared between pre-CALGB and post-CALGB publication (circa 2004). Univariate and multivariate analysis were used. RESULTS: Radiation therapy usage decreased by only 2.95% after CALGB publication (68.71% vs 65.76%; p < 0.0001). Almost one-third of women with short life expectancy (≥85 years) received RT in the post-CALGB group. Significant predictors (p < 0.01) of lowest RT use include advanced age, increased great circle distance, academic research program, East South Central region, rural population < 2,500 not adjacent to a metropolitan area, low income level, high comorbidity index, small tumor, well-differentiated histology, residual tumor, and lack of receipt of anti-hormonal therapy. CONCLUSIONS: The CALGB trial had a minimal impact on the rate of adjuvant RT use among elderly women with small, hormone positive breast cancers. Significant variation in RT usage exists across sociodemographic strata.